Search results for: drug toxicity

Authors: D. Velayadum, P. Sthandiwe , N. Maharaj, T. Munien, S. Ndamase, G. Zulu, S. Xulu, F. Oosthuizen

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Introduction and aims of the study: It is the responsibility of the pharmacist to manage drug-related problems in order to ensure the greatest benefit to the patient. In order to prevent drug-related morbidity, pharmacists should be aware of medicines that may contribute to certain drug-related problems due to their pharmacological action. In an attempt to assist healthcare practitioners to prevent drug-related morbidity (PDRM), indicators for prevention have been designed. There are currently no indicators available for primary health care in developing countries like South Africa, where the majority of the population access primary health care. There is, therefore, a need to develop such indicators, specifically with the aim of assisting healthcare practitioners in primary health care. Methods: A literature study was conducted to compile a comprehensive list of PDRM indicators as developed internationally using the search engines Google Scholar and PubMed. MESH term used to retrieve suitable articles was 'preventable drug-related morbidity indicators'. The comprehensive list of PDRM indicators obtained from the literature study was further evaluated for face validity. Face validity was done in duplicate by 2 sets of independent researchers to ensure 1) no duplication of indicators when compiling a single list, 2) inclusion of only medication available in primary healthcare, and 3) inclusion of medication currently available in South Africa. Results: The list of indicators, compiled from PDRM indicators in the USA, UK, Portugal, Australia, India, and Canada contained 324 PDRM. 184 of these indicators were found to be duplicates, and the duplications were omitted, leaving a final list of 140. The 140 PDRM indicators were evaluated for face-validity, and 97 were accepted as relevant to primary health care in South Africa. 43 indicators did not comply with the criteria and were omitted from the final list. Conclusion: This study is a first step in compiling a list of PDRM indicators for South Africa. It is important to take cognizance to the fact the health systems differ vastly internationally, and it is, therefore, important to develop country-specific indicators.

Keywords: drug-related morbidity, primary healthcare, South Africa, developing countries

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Authors: Abdu Zakari, Sai’d Jibril, Adoum A. Omar

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The leaves of Combretum molle was selected on the basis of its uses in folk medicine as insecticides. The leave extracts of Combretum molle was tested against the larvae of Artemia salina, i.e. Brine Shrimp Lethality Test (BST), Culex quinquefasciatus Say (Filaria disease vector) i.e. Larvicidal Test, using crude ethanol, n-hexane, chloroform, ethyl acetate, and methanol extracts. The methanolic extract proved to be the most effective in inducing complete lethality at minimum doses both in the BST and the Larvicidal activity test. The LC50¬ values obtained are 24.85 µg/ml and 0.4µg/ml respectively. The bioactivity-guided column chromatography afforded the pure compound ACM–3. ACM-3 was not active in the BST with LC50 value >1000µg/ml, but was active in the Larvicidal activity test with LC50 value 4.0µg/ml. ACM-3 was proposed to have the structure I, (Cholesta-β-D-Glucopyranoside).

Keywords: toxicity, larvicidal, Combretum molle, Artemia salina, Culex quinquefasciatus Say.

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Authors: Masoumeh Haghbin Nazarpak, Hamidreza Tolabi, Aryan Ekhlasi

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Bone defects are mentioned as one of the most challenging clinical conditions, affecting millions of people each year. A fracture, osteoporosis, tumor, or infection usually causes these defects. At present, autologous and allogeneic grafts are used to correct bone defects, but these grafts have some difficulties, such as limited access, infection, disease transmission, and immune rejection. Bone tissue engineering is considered a new strategy for repairing bone defects. However, problems with scaffolds’ design with unique structures limit their clinical applications. In addition, numerous in-vitro studies have been performed on the behavior of bone cells in two-dimensional environments. Still, cells grow in physiological situations in the human body in a three-dimensional environment. As a result, the controlled design of porous structures with high structural complexity and providing the necessary flexibility to meet specific needs in bone tissue repair is beneficial. For this purpose, a three-dimensional composite scaffold based on gelatin and sodium alginate hydrogels is used in this research. In addition, the antibacterial drug-loaded halloysite nanotubes were introduced into the hydrogel scaffold structure to provide a suitable substrate for controlled drug release. The presence of halloysite nanotubes improved hydrogel’s properties, while the drug eliminated infection and disease transmission. Finally, it can be acknowledged that the composite scaffold prepared in this study for bone tissue engineering seems promising.

Keywords: halloysite nanotubes, bone tissue engineering, composite scaffold, controlled drug release

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Authors: Mehdi Shahmoradi Moghadam, Saba Kavian, Mehdi Zabihzadeh, Amir Mohammad Alborzi, Reza Sadeghi

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Cypermethrin is one of the most widely used synthetic insecticides to control pests in veterinary, industrial and agricultural environments. In the present study, the mortalities of Lucilia Cuprina as the key pest of meat were studied after being exposed to HICIDE VD-9 (a ready-to-use disinfectant/insecticide containing cypermethrin, polyhexanide and quaternary ammonium compounds produced by Dana pharmed lotus Co., Iran) within 15 minutes. The experimental results showed that moralities percentage of egg, larvae and adults of Lucilia Cuprina were 48%, 81% and 70%, respectively. Based on the obtained results, it can be predicted that in addition to controlling the insect pests of blow flies, HICIDE VD-9, as a cost-effective and environmentally friendly disinfectant/insecticide, can be effective against other insects, e.g., biting flies, fleas, midges, mosquitoes and ticks.

Keywords: cypermethrin, HICIDE VD-9, Lucilia cuprina, mortality, toxicity

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Authors: Abdoon A.S., El Ashkar E.A., Kandil O.M., Wael H. Eisa, Shaban A.M., Khaled H.M., El Ashkar M.R., El Shaer M., Hussein H., Shaalan A.H., El Sayed M.

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Cancer is a major obstacle to human health and development worldwide. Conventional strategies for cancer intervention include surgery, chemotherapy, and radiation therapy. Recently, plasmon photothermal therapy (PPTT) was introduced as a promising treatment for the management of cancer and several non-cancerous diseases that are generally characterized by overgrowth of abnormal cells. The present work was conducted to evaluate the cytotoxic efficacy and toxicity of gold nanorods (AuNRs) in dogs and cats suffering from spontaneous mammary gland. AuNRs was injected intratumoral (IT, n=10, dose of 75 p.p.m/kg body weight) or by using spray method after surgical removal of cancer tissue (n=2) in dogs and cats. Then exposed to laser light after 60 min. Treated animals were observed every 2 days and the morphological changes in tumor size and shape were recorded. Blood samples were collected before and after treatment for checking CBC, liver and kidney functions. Results revealed that AuNRs successfully treat mammary gland tumor in dogs and cats (adenocarcinoma type 1 to IV). AuNRs induced sloughing of carcinogenic tissue within 5 to 15 days. AuNRs have no toxic effect on blood profile and the toxicity studies still under evaluation. Conclusion, AuNRs can be used for treatment of mammary gland carcinoma in dogs and cats.

Keywords: pet animals, mammary gland tumor, AuNRs, photothermal therapy, toxicity studies

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Authors: Sophio Kobauri, Tengiz Kantaria, Temur Kantaria, David Tugushi, Nina Kulikova, Ramaz Katsarava

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Nanosized environmentally responsive materials are of special interest for various applications, including targeted drug to a considerable potential for treatment of many human diseases. The important technological advantages of nanoparticles (NPs) usage as drug carriers (nanocontainers) are their high stability, high carrier capacity, feasibility of encapsulation of both hydrophilic or hydrophobic substances, as well as a high variety of possible administration routes, including oral application and inhalation. NPs can also be designed to allow controlled (sustained) drug release from the matrix. These properties of NPs enable improvement of drug bioavailability and might allow drug dosage decrease. The targeted and controlled administration of drugs using NPs might also help to overcome drug resistance, which is one of the major obstacles in the control of epidemics. Various degradable and non-degradable polymers of both natural and synthetic origin have been used for NPs construction. One of the most promising for the design of NPs are amino acid-based biodegradable polymers (AABBPs) which can clear from the body after the fulfillment of their function. The AABBPs are composed of naturally occurring and non-toxic building blocks such as α-amino acids, fatty diols and dicarboxylic acids. The particles designed from these polymers are expected to have an improved bioavailability along with a high biocompatibility. The present work deals with a systematic study of the preparation of NPs by cost-effective polymer deposition/solvent displacement method using AABBPs. The influence of the nature and concentration of surfactants, concentration of organic phase (polymer solution), and the ratio organic phase/inorganic (water) phase, as well as of some other factors on the size of the fabricated NPs have been studied. It was established that depending on the used conditions the NPs size could be tuned within 40-330 nm. As the next step of this research an evaluation of biocompatibility and bioavailability of the synthesized NPs has been performed, using two stable human cell culture lines – HeLa and A549. This part of study is still in progress now.

Keywords: amino acids, biodegradable polymers, nanoparticles (NPs), non-toxic building blocks

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Authors: Firman Riyudha, Endrik Mifta Shaiful

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The spread of drug users is one kind of behavioral epidemiology that becomes a threat to every country in the world. This problem caused various crisis simultaneously, including financial or economic crisis, social, health, until human crisis. Most drug users are teenagers at school age. A new deterministic model would be constructed to determine the dynamics of the spread of drug users by considering level of education in a susceptible population. Based on the analytical model, two equilibria points were obtained; there were E₀ (zero user) and E₁ (endemic equilibrium). Existence of equilibrium and local stability of equilibria depended on the Basic Reproduction Ratio (R₀). This parameter was defined as the expected rate of secondary prevalence and primary prevalence in virgin population along spreading primary prevalence. The zero-victim equilibrium would be locally asymptotically stable if R₀ < 1 while if R₀ > 1 the endemic equilibrium would be locally asymptotically stable. The result showed that R₀ was proportional to the rate of interaction of each susceptible population based on educational level with the users' population. It is concluded that there was a need to be given a control in interaction, so that drug users population could be minimized. Numerical simulations were also provided to support analytical results.

Keywords: drugs users, level education, mathematical model, stability

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Authors: Tahammal Hussain, Khuram Zia, Mumammad Jalal Arif, Megha Parajulee, Abdul Hakeem

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The Bioassay on neonate, 2nd and 3rd instar larvae of Helicoverpa armigera (Hubner) were conducted against Bacillus thuringiensis proteins Cry1Ac. Cry1Ac was incorporated into an artificial diet and was serially diluted with distilled water and then mixed with diet at an appropriate temperature of diet. Toxins incorporated prepared diet was poured into Petri-dishes. For controls, distilled water was mixed with the diet. Five toxin doses 0.25, 0.5, 1, 2, and 4 ug / ml and one control were used for each instars of H. armigera 20 larvae were used in each replication and each treatment is replicated four times. LC50 of Cry1Ac against neonate, 2nd and 3rd instar larvae of H. armigera were 0.34, 0.81 and 1.46 ug / ml. So Cry1Ac is more effective against neonate larvae of H .armigera as compared to 2nd and 3rd instar larvae under laboratory conditions.

Keywords: B. thuringiensis, Cry1Ac, H. armigera, toxicity

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Authors: Prakash Singh

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Many schools throughout the world are facing constant pressure to cope with the violence and drug abuse of learners who show little or no respect for acceptable and desirable social norms. These delinquent learners tend to harbour feelings of being beyond reproach because they strongly believe that it is well within their rights to engage in violent and destructive behaviour. Knives, guns, and other weapons appear to be more readily used by them on the school premises than before. It is known that learners smoke, drink alcohol, and use drugs during school hours, hence, their ability to concentrate, work, and learn, is affected. They become violent and display disruptive behaviour in their classrooms as well as on the school premises, and this atrocious behaviour makes it possible for drug dealers and gangsters to gain access onto the school premises. The primary purpose of this exploratory quantitative study was therefore to establish how tobephobia (TBP), caused by school violence and drug abuse, affects teaching and learning in schools. The findings of this study affirmed that poor discipline resulted in producing poor quality education. Most of the teachers in this study agreed that educating learners who consumed alcohol and other drugs on the school premises resulted in them suffering from TBP. These learners are frequently abusive and disrespectful, and resort to violence to seek attention. As a result, teachers feel extremely demotivated and suffer from high levels of anxiety and stress. The word TBP will surely be regarded as a blessing by many teachers throughout the world because finally, there is a word that will make people sit up and listen to their problems that cause real fear and anxiety in schools.

Keywords: aims and objectives of quality education, debilitating effects of tobephobia, fear of failure associated with education, learners' violent behaviour and drug abuse

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Authors: Ting Wang, Pierre Marle, Vera I. Slaveykova, Kristin Schirmer, Wei Liu

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Metal-based nanoparticles (NPs) are considered detrimental to aquatic organisms due to their potential accumulation. However, little is known about the mechanisms underlying these effects and their species-specificity. Here, we used stable silver (Ag) NPs (20 nm, from 10 to 500 μg/L) with a low dissolution rate (≤2.4%) to study the bioaccumulation and biological impacts in two freshwater gastropods: Lymnaea stagnalis and Planorbarius corneus. No mortality was detected during the experiments. Ag bioaccumulation showed a dose-related increase with an enhanced concentration in both species after 7d exposure. L. stagnalis displayed a higher accumulation for AgNPs than P. corneus (e.g., up to 18- and 15-fold in hepatopancreas and hemolymph, respectively), which could be due to the more active L. stagnalis having greater contact with suspended AgNPs. Furthermore, the hepatopancreas and stomach were preferred organs for bioaccumulation compared to the kidney, mantle and foot. Regarding biological responses, the hemolymph rather than hepatopancreas appeared more susceptible to oxidative stress elicited by AgNPs, as shown by significantly increasing lipid peroxidation (i.e., formation of malondialdehyde). Neurotoxicity was detected in L. stagnalis when exposed to high concentrations (500 μg/L). Comparison with impacts elicited by dissolved Ag revealed that the effects observed on AgNPs exposure were mainly attributable to NPs. These results highlighted the relationship between the physiological traits, bioaccumulation, and toxicity responses of these two species to AgNPs and demonstrated the necessity of species-specificity considerations when assessing the toxicity of NPs.

Keywords: nanotoxicity, freshwater gastropods, species-specificity, metals, physiological traits

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Authors: Sunil Kamboj, Suman Bala, Vipin Saini

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Niosomes were formulated with an aim of enhancing the oral bioavailability of losartan potassium and formulated in different molar ratios of surfactant, cholesterol and dicetyl phosphate. The formulated niosomes were found in range of 54.98 µm to 107.85 µm in size. Formulations with 1:1 ratio of surfactant and cholesterol have shown maximum entrapment efficiencies. Niosomes with sorbitan monostearate showed maximum drug release and zero order release kinetics, at the end of 24 hours. The in vivo study has shown the significant enhancement in oral bioavailability of losartan potassium in rats, after a dose of 10 mg/kg. The average relative bioavailability in relation with pure drug solution was found 2.56, indicates more than two fold increase in oral bioavailability. A significant increment in MRT reflects the release retarding ability of the vesicles. In conclusion, niosomes could be a promising delivery of losartan potassium with improved oral bioavailability and prolonged release profiles.

Keywords: non-ionic surfactant vesicles, losartan potassium, oral bioavailability, controlled release

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Authors: Eman M. Sarhan, Doaa A. Ghareeb, Gabriella Ortore, Amr A. Amara, Mohamed M. El-Sayed

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Drug salting and nanoparticle-based drug delivery formulations are considered to be an effective means for rendering the hydrophobic drugs’ nano-scale dispersion in aqueous media, and thus circumventing the pitfalls of their poor solubility as well as enhancing their membrane permeability. The current study aims to increase the bioavailability of quaternary ammonium berberine through acid salting and biodegradable bovine serum albumin (BSA)-based nanoparticulate drug formulation. Berberine hydroxide (BBR-OH) that was chemically synthesized by alkalization of the commercially available berberine hydrochloride (BBR-HCl) was then acidified to get Di-berberine sulfate (BBR)₂SO₄. The purified crystals were spectrally characterized. The desolvation technique was optimized for the preparation of size-controlled BSA-BBR-HCl, BSA-BBR-OH, and BSA-(BBR)₂SO₄ nanoparticles. Particle size, zeta potential, drug release, encapsulation efficiency, Fourier transform infrared spectroscopy (FTIR), tandem MS-MS spectroscopy, energy-dispersive X-ray spectroscopy (EDX), scanning and transmitting electron microscopic examination (SEM, TEM), in vitro bioactivity, and in silico drug-polymer interaction were determined. BSA (PDB ID; 4OR0) protonation state at different pH values was predicted using Amber12 molecular dynamic simulation. Then blind docking was performed using Lamarkian genetic algorithm (LGA) through AutoDock4.2 software. Results proved the purity and the size-controlled synthesis of berberine-BSA-nanoparticles. The possible binding poses, hydrophobic and hydrophilic interactions of berberine on BSA at different pH values were predicted. Antioxidant, anti-hemolytic, and cell differentiated ability of tested drugs and their nano-formulations were evaluated. Thus, drug salting and the potentially effective albumin berberine nanoparticle formulations can be successfully developed using a well-optimized desolvation technique and exhibiting better in vitro cellular bioavailability.

Keywords: berberine, BSA, BBR-OH, BBR-HCl, BSA-BBR-HCl, BSA-BBR-OH, (BBR)₂SO₄, BSA-(BBR)₂SO₄, FTIR, AutoDock4.2 Software, Lamarkian genetic algorithm, SEM, TEM, EDX

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Authors: Ravi Sheshala, Annie Lee, Ai Lin Ong, Ling Ling Cheu, Thiagarajan Madheswaran, Thankur R. R. Singh

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The objectives of the present research work were to develop and characterize biodegradable controlled release photo cross-linked implants of Triamcinolone Acetonide (TA) for the treatment of chronic ocular diseases. The photo cross-linked implants were prepared using film casting technique by mixing TA (2.5%) polyethylene glycol diacrylate (PEGDA 700), pore formers (mannitol, maltose, and gelatin) and the photoinitiator (Irgacure 2959). The resulting mixture was injected into moulds using 21 G and subjected to photocrosslinking at 365 nm. Scanning electron microscopy results demonstrated that more pores were formed in the films with the increase in the concentration of pore formers from 2%-10%. The maximum force required to break the films containing 2-10% of pore formers were determined in both dry and wet conditions using texture analyzer and found that films in a dry condition required a higher force to break compared to wet condition and blank films. In vitro drug release from photo cross-linked films were determined by incubating samples in 50 ml PBS pH 7.4 at 37 C and the samples were analyzed for drug release by HPLC. The films demonstrated a biphasic release profile i.e. an initial burst release (<20%) on the first day followed by a constant and continuous drug release in a controlled manner for 42 days. The drug release from all formulations followed the first-order release pattern and the combination of diffusion and erosion release mechanism. In conclusion, the developed formulations were able to provide controlled drug delivery to treat the chronic ocular diseases.

Keywords: controlled release, ophthalmic, PEGDA, photocrosslinking, pore formers

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Authors: Saleh N. Maodaa

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Background: Lead (Pb) is an environmental pollutant causing serious health problems, including impairment of reproduction. Visnagin (VIS) is a furanochromone with promising antioxidant and anti-inflammatory effects; however, its protective efficacy against Pb toxicity has not been investigated. Objective: This study evaluated the protective effect of VIS on Pb reproductive toxicity, impaired steroidogenesis and spermatogenesis, oxidative stress and inflammation. Methods: Rats received VIS (30 or 60 mg/kg) and 50 mg/kg lead acetate for 3 weeks, and blood and testes samples were collected. Results: Pb intoxication impaired the pituitary-testicular axis (PTA), manifested by the decreased serum levels of gonadotropins and testosterone. Pb decreased sperm count, motility and viability, increased sperm abnormalities, and downregulated the steroidogenesis markers StAR, CYP17A1, 3β-HSD and 17β-HSD in the testis of rats. VIS significantly increased serum gonadotropins and testosterone, alleviated sperm parameters and upregulated steroidogenesis. In addition, VIS decreased pro-inflammatory cytokines, testicular lipid peroxidation and DNA fragmentation, downregulated Bax, and enhanced antioxidants and Bcl-2 Conclusion: These results demonstrate the protective effect of VIS against Pb reproductive toxicity in rats. VIS improved serum gonadotropins and testosterone, enhanced steroidogenesis and spermatogenesis, and attenuated oxidative injury, inflammation and apoptosis. Therefore, VIS is a promising candidate for the protection against Pb-induced reproduction impairment.

Keywords: pituitary-gonadal axis, cytokines, DNA damage, apoptosis

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Authors: Lichung Jen, Yi Chun Liu, Kuan-Wei Lee

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Fruitful data has been accumulated in database nowadays and is commonly used as support for decision-making. In the healthcare industry, hospital, for instance, ordering pharmacy inventory is one of the key decision. With large drug inventory, the current cost increases and its expiration dates might lead to future issue, such as drug disposal and recycle. In contrast, underestimating demand of the pharmacy inventory, particularly standing drugs, affects the medical treatment and possibly hospital reputation. Prescription behaviour of hospital physicians is one of the critical factor influencing this decision, particularly irregular prescription behaviour. If a drug’s usage amount in the month is irregular and less than the regular usage, it may cause the trend of subsequent stockpiling. On the contrary, if a drug has been prescribed often than expected, it may result in insufficient inventory. We proposed a hierarchical Bayesian mixture model with two components to identify physicians’ regular/irregular prescription patterns with probabilities. Heterogeneity of hospital is considered in our proposed hierarchical Bayes model. The result suggested that modeling the prescription patterns of physician is beneficial for estimating the order quantity of medication and pharmacy inventory management of the hospital. Managerial implication and future research are discussed.

Keywords: hierarchical Bayesian model, poission mixture model, medicines prescription behavior, irregular behavior

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Authors: Amanda C. Q. M. Vieira, Cybelly M. Melo, Camila B. M. Figueirêdo, Giovanna C. R. M. Schver, Salvana P. M. Costa, Magaly A. M. de Lyra, Ping I. Lee, José L. Soares-Sobrinho, Pedro J. Rolim-Neto, Mônica F. R. Soares

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Epiisopiloturine (EPI) is a drug candidate that is extracted from Pilocarpus microphyllus and isolated from the waste of Pilocarpine. EPI has demonstrated promising schistosomicidal, leishmanicide, anti-inflammatory and antinociceptive activities, according to in vitro studies that have been carried out since 2009. However, this molecule shows poor aqueous solubility, which represents a problem for the release of the drug candidate and its absorption by the organism. The purpose of the present study is to investigate the extent of enhancement of kinetic solubility of a solid solution (SS) of EPI in hipromellose phthalate HP-55 (HPMCP), an enteric polymer carrier. SS was obtained by the solvent evaporation methodology, using acetone/methanol (60:40) as solvent system. Both EPI and polymer (drug loading 10%) were dissolved in this solvent until a clear solution was obtained, and then dried in oven at 60ºC during 12 hours, followed by drying in a vacuum oven for 4 h. The results show a considerable modification in the crystalline structure of the drug candidate. For instance, X-ray diffraction (XRD) shows a crystalline behavior for the EPI, which becomes amorphous for the SS. Polarized light microscopy, a more sensitive technique than XRD, also shows completely absence of crystals in SS sample. Differential Scanning Calorimetric (DSC) curves show no signal of EPI melting point in SS curve, indicating, once more, no presence of crystal in this system. Interaction between the drug candidate and the polymer were found in Infrared microscopy, which shows a carbonyl 43.3 cm-1 band shift, indicating a moderate-strong interaction between them, probably one of the reasons to the SS formation. Under sink conditions (pH 6.8), EPI SS had its dissolution performance increased in 2.8 times when compared with the isolated drug candidate. EPI SS sample provided a release of more than 95% of the drug candidate in 15 min, whereas only 45% of EPI (alone) could be dissolved in 15 min and 70% in 90 min. Thus, HPMCP demonstrates to have a good potential to enhance the kinetic solubility profile of EPI. Future studies to evaluate the stability of SS are required to conclude the benefits of this system.

Keywords: epiisopiloturine, hipromellose phthalate HP-55, pharmaceuticaltechnology, solubility

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Authors: Gabrielle Peck, Ryan Hayes

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Polyurethane (PU) foam is typically sold as acoustic foam that is often used as sound insulation in settings such as night clubs and bars. As a construction product, PU is tested by being glued to the walls and ceiling of the ISO 9705 room corner test room. However, when heat is applied to PU foam, it melts and burns as a pool fire due to it being a thermoplastic. The current test layout is unable to accurately measure mass loss and doesn’t allow for the material to burn as a pool fire without seeping out of the test room floor. The lack of mass loss measurement means gas yields pertaining to smoke toxicity analysis can’t be calculated, which makes data comparisons from any other material or test method difficult. Additionally, the heat release measurements are not representative of the actual measurements taken as a lot of the material seeps through the floor (when a tray to catch the melted material is not used). This research aimed to modify the ISO 9705 test to provide the ability to measure mass loss to allow for better calculation of gas yields and understanding of decomposition. It also aimed to accurately measure smoke toxicity in both the doorway and duct and enable dilution factors to be calculated. Finally, the study aimed to examine if doubling the fuel loading would force under-ventilated flaming. The test layout was modified to be a combination of the SBI (single burning item) test set up inside oof the ISO 9705 test room. Polyurethane was tested in two different ways with the aim of altering the ventilation condition of the tests. Test one was conducted using 1 x SBI test rig aiming for well-ventilated flaming. Test two was conducted using 2 x SBI rigs (facing each other inside the test room) (doubling the fuel loading) aiming for under-ventilated flaming. The two different configurations used were successful in achieving both well-ventilated flaming and under-ventilated flaming, shown by the measured equivalence ratios (measured using a phi meter designed and created for these experiments). The findings show that doubling the fuel loading will successfully force under-ventilated flaming conditions to be achieved. This method can therefore be used when trying to replicate post-flashover conditions in future ISO 9705 room corner tests. The radiative heat generated by the two SBI rigs facing each other facilitated a much higher overall heat release resulting in a more severe fire. The method successfully allowed for accurate measurement of smoke toxicity produced from the PU foam in terms of simple gases such as oxygen depletion, CO and CO2. Overall, the proposed test modifications improve the ability to measure the smoke toxicity of materials in different fire conditions on a large-scale.

Keywords: flammability, ISO9705, large-scale testing, polyurethane, smoke toxicity

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Authors: A. Gharaei, R. Karami

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Rutilus frisii Kutum was exposed to various concentrations of mercuric chloride in water to determine its acute toxicity and bioaccumulation. We carried out ten treatments with three replicates and one control for each of the chemicals using the static O. E. C. D. method in 55-liter-tanks each containing 14 fingerlings. During the experiments, the average pH was recorded as 7.8, total hardness was measured to be 255 mg/l, the average water temperature was 27±1 degrees centigrade and dissolved oxygen was 7.2 mg/l. Mean LC50 values of Hgcl2 for juvenile R. frisii kutum with mean weight 1±0.2 gr were 0.102 and 0.86 mgHg/l at 24h and 96h, respectively. The bioaccumulation values during 24h in tissue, kidney, and gill were 1.55, 16.1, and 22.7 mgHg/l, respectively. So, these values during 96h were 2.8, 16.8, and 26.65 mgHg/l, respectively. The bioconcentration factors in tissue, kidney, and gill during 24h were 14.75, 153.39, and 216.11 and so during 96h were 33.8, 198.1, and 313.5 times. These results show that bioaccumulation was highest in the gill and then kidney and tissue, respectively. This study suggested that between mercury concentrations of water with bioaccumulation in tissue more than kidney and gill.

Keywords: HgCl2, LC5096h, bioaccumulation, Rutilus frisii Kutum, Caspian Sea

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Authors: Tadesse Melaku Abegaz

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Background: there was paucity of data on the self-reported adverse drug reactions (ADRs), level of adherence and clinical outcomes with antidepressants among major depressive disorder (MDD) patients in Ethiopia. Hence, the present study sought to determine the level of adherence for and clinical outcome with antidepressants and the magnitude of ADRs. Methods: A prospective cross-sectional study was employed on MDD patients from September 2016 to January 2017 at Gondar university hospital psychiatry clinic. All patients who were available during the study period were included under the study population. The Naranjo adverse drug reaction probability scale was employed to assess the adverse drug reaction. The rate of medication adherence was determined using morisky medication adherence measurement scale eight. Clinical Outcome of patients was measured by using patient health questionnaire. Multivariable logistic carried out to determine factors for adherence and patient outcome. Results: two hundred seventy patients were participated in the study. More than half of the respondents were males 122(56.2%). The mean age of the participants was 30.94 ± 8.853. More than one-half of the subjects had low adherence to their medications 124(57.1%). About 186(85.7%) of patients encountered ADR. The most common ADR was weight gain 29(13.2). Around 198(92.2%) ADRs were probable and 19(8.8%) were possible. Patients with long standing MDD had high risk of non-adherence COR: 2.458[4.413-4.227], AOR: 2.424[1.185-4.961]. More than one-half 125(57.6) of respondents showed improved outcome. Optimal level of medication adherence was found to be associated with reduced risk of progression of the diseases COR: 0.37[0.110-5.379] and AOR: 0.432[0.201-0.909]. Conclusion: Patient reported adverse drug reactions were more prevalent in major depressive disorder patients. Adherence to medications was very poor in the setup. However, the clinical outcome was relatively higher. Long standing depression was associated with non-adherence. In addition, clinical outcome of patients were affected by non-adherence. Therefore, adherence enhancing interventions should be provided to improve medication adherence and patient outcome.

Keywords: adverse drug reactions, clinical outcomes, Ethiopia, prospective study, medication adherence

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Authors: Palwinder Singh, Baljit Kaur, Sukhmeet Kaur

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Amongst a library of rationally designed small peptides, (H)Gly-Gly-Phe-Leu(OMe) was identified, reducing prostaglandin production of COX-2 with IC50 60 nM vs. 6000 nM for COX-1. The 5 mg Kg-1 dose of this compound rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of the compound for targeting COX-2, iNOS, and VGSC was investigated by using substances P, L-arginine, and veratrine, respectively, as the biomarkers. The interactions of the potent compound with COX-2 were supported by the isothermal calorimetry experiments showing Ka 6.10±1.10x104 mol-1 and ΔG -100.3 k J mol-1 in comparison to Ka 0.41x103 ±0.09 mol-1 and ΔG -19.2±0.06 k J mol-1 for COX-1. This compound did not show toxicity up to 2000 mg Kg-1 dose. Furthermore, beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, COX-2 was provided with a peptide-based alternate substrate. Proline-centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin-induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Hence, we suggest small peptides as highly potent and promising candidates for their further development into an anti-inflammatory drug.

Keywords: small peptides, cyclooxygenase, inflammation, substrate

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Authors: Jinfeng Zhang, Chun-Sing Lee

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Pure nanodrugs (PNDs) – nanoparticles consisting entirely of drug molecules, have been considered as promising candidates for the next-generation nanodrugs. However, the traditional preparation method via reprecipitation faces critical challenges including low production rates, relatively large particle sizes and batch-to-batch variations. Here, for the first time, we successfully developed a novel, versatile and controllable strategy for preparing PNDs via an anodized aluminium oxide (AAO) template-assisted method. With this approach, we prepared PNDs of an anti-cancer drug (VM-26) with precisely controlled sizes reaching the sub-20 nm range. This template-assisted approach has much higher feasibility for mass production comparing to the conventional reprecipitation method and is beneficial for future clinical translation. The present method is further demonstrated to be easily applicable for a wide range of hydrophobic biomolecules without the need of custom molecular modifications and can be extended for preparing all-in-one nanostructures with different functional agents.

Keywords: drug delivery, pure nanodrugs, size control, template

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Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, C. V. Rao

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Elvitegravir is the mainstay of anti-HIV combination therapy in most endemic countries presently. However, it cannot be used alone owing to its long onset time of action. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one (Quercetin: QU) is a polyphenolic compound obtained from Argeria speciosa Linn (Family: Convolvulaceae), an anti-HIV candidate. In the present study, a sensitive, simple and rapid high-performance liquid chromatography coupled with positive ion electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the simultaneous determination elvitegravir and Quercetin, in rat plasma. The method was linear over a range of 0.2–500 ng/ml. All validation parameters met the acceptance criteria according to regulatory guidelines. LC–MS/MS method for determination of Elvitegravir and Quercetin was developed and validated. Results show the potential of drug–drug interaction upon co-administration this marketed drugs and plant derived secondary metabolite.

Keywords: anti-HIV resistance, extraction, HPLC-ESI-MS-MS, validation

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Authors: Uchenna Nkiruka Umeononihu, Adenike Kuku, Oludele Odekanyin, Olubunmi Babalola, Femi Agboola, Rapheal Okonji

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In this study, a lectin from the bulb of Dioscorea bulbifera was purified, characterised, and its acute and sub-acute toxicity was investigated with a view to evaluate its toxic effects in mice. The protein from the bulb was extracted by homogenising 50 g of the bulb in 500 ml of phosphate buffered saline (0.025 M) of pH 7.2, stirred for 3 hr, and centrifuged at the speed of 3000 rpm. Blood group and sugar specificity assays of the crude extract were determined. The lectin was purified in a two-step procedure- gel filtration on Sephadex G-75 and affinity chromatography on Sepharose 4-B arabinose. The degree of purity of the purified lectin was ascertained by SDS-polyacrylamide gel electrophoresis. Detection of covalently bound carbohydrate was carried out with Periodic Acid-Schiffs (PAS) reagent staining technique. Effects of temperature, pH, and EDTA on the lectin were carried out using standard methods. This was followed by acute toxicity studies via oral and subcutaneous routes using mice. The animals were monitored for mortality and signs of toxicity. The sub-acute toxicity studies were carried out using rats. Different concentrations of the lectin were administered twice daily for 5 days via the subcutaneous route. The animals were sacrificed on the sixth day; blood samples and liver tissues were collected. Biochemical assays (determination of total protein, direct bilirubin, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), catalase (CAT), and superoxide dismutase (SOD)) were carried out on the serum and liver homogenates. The collected organs (heart, liver, kidney, and spleen) were subjected to histopathological analysis. The results showed that lectin from the bulbs of Dioscorea bulbifera agglutinated non-specifically the erythrocytes of the human ABO system as well as rabbit erythrocytes. The haemagglutinating activity was strongly inhibited by arabinose and dulcitol with minimum inhibitory concentrations of 0.781 and 6.25, respectively. The lectin was purified to homogeneity with native and subunit molecular weights of 56,273 and 29,373 Daltons, respectively. The lectin was thermostable up to 30 0C and lost 25 %, 33.3 %, and 100 % of its heamagglutinating activity at 40°C, 50°C, and 60°C, respectively. The lectin was maximally active at pH 4 and 5 but lost its total activity at pH eight, while EDTA (10 mM) had no effect on its haemagglutinating activity. PAS reagent staining showed that the lectin was not a glycoprotein. The sub-acute studies on rats showed elevated levels of ALT, AST, serum bilirubin, total protein in serum and liver homogenates suggesting damage to liver and spleen. The study concluded that the aerial bulb of D. bulbifera lectin was non-specific in its heamagglutinating activity and dimeric in its structure. The lectin shared some physicochemical characteristics with lectins from other Dioscorecea species and was moderately toxic to the liver and spleen of treated animals.

Keywords: Dioscorea bulbifera, heamagglutinin, lectin, toxicity

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

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Authors: Huafeng Wei

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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: Ava Faridi, Pouya Faridi, Aleksandr Kakinen, Ibrahim Javed, Thomas P. Davis, Pu Chun Ke

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Human islet amyloid polypeptide (IAPP) is a hormone associated with glycemic control and type 2 diabetes. Biophysically, the chirality of IAPP fibrils has been little explored with respect to the aggregation and toxicity of the peptide. Biochemically, it remains unclear as for how protein expression in pancreatic beta cells may be altered by cell exposure to the peptide, and how such changes may be mitigated by nanoparticle inhibitors for IAPP aggregation. In this study, we first demonstrated the elimination of the IAPP nucleation phase and shortening of its elongation phase by silica nanoribbons. This accelerated IAPP fibrillization translated to reduced toxicity, especially for the right-handed silica nanoribbons, as revealed by cell viability, helium ion microscopy, as well as zebrafish embryo survival, developmental and behavioral assays. We then examined the proteomes of βTC6 pancreatic beta cells exposed to the three main aggregation states of monomeric, oligomeric and amyloid fibrillar IAPP, and compared that with cellular protein expression modulated by graphene quantum dots (GQDs). A total of 29 proteins were significantly regulated by different forms of IAPP, and the majority of these proteins were nucleotide-binding proteins. A regulatory capacity of GQDs against aberrant protein expression was confirmed. These studies have demonstrated the great potential of employing nanomaterials targeting the mesoscopic enantioselectivity and protein expression dysregulation in pancreatic beta cells.

Keywords: graphene quantum dots, IAPP, silica nanoribbons, protein expression, toxicity

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Authors: Zhi Hao Chow, Cian Mulligan, Jack Walsh, Antonio Garzon Vico, Dimitar Krastev

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Drug development is resource-intensive, time-consuming, and increasingly expensive with each developmental stage. The success rates of drug development are also relatively low, and the resources committed are wasted with each failed candidate. As such, a reliable method of predicting the success of drug development is in demand. The hypothesis was that some examples of failed drug candidates are pushed through developmental pipelines based on false confidence and may possess common linguistic features identifiable through sentiment analysis. Here, the concept of using text analysis to discover such features in research publications and investor reports as predictors of success was explored. R studios were used to perform text mining and lexicon-based sentiment analysis to identify affective phrases and determine their frequency in each document, then using SPSS to determine the relationship between our defined variables and the accuracy of predicting outcomes. A total of 161 publications were collected and categorised into 4 groups: (i) Cancer treatment, (ii) Neurodegenerative disease treatment, (iii) Vaccines, and (iv) Others (containing all other drugs that do not fit into the 3 categories). Text analysis was then performed on each document using 2 separate datasets (BING and AFINN) in R within the category of drugs to determine the frequency of positive or negative phrases in each document. A relative positivity and negativity value were then calculated by dividing the frequency of phrases with the word count of each document. Regression analysis was then performed with SPSS statistical software on each dataset (values from using BING or AFINN dataset during text analysis) using a random selection of 61 documents to construct a model. The remaining documents were then used to determine the predictive power of the models. Model constructed from BING predicts the outcome of drug performance in clinical trials with an overall percentage of 65.3%. AFINN model had a lower accuracy at predicting outcomes compared to the BING model at 62.5% but was not effective at predicting the failure of drugs in clinical trials. Overall, the study did not show significant efficacy of the model at predicting outcomes of drugs in development. Many improvements may need to be made to later iterations of the model to sufficiently increase the accuracy.

Keywords: data analysis, drug development, sentiment analysis, text-mining

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Authors: Bouchiha Hanene, Rouabhi Rachid, Bouchama Khaled, Djebar Berrebbah Houraya, Djebar Mohamed Reda

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Recently, some natural products such as essentials oils (EOs) have been used in the fields as alternative to synthetic compounds, to minimize the negative impacts to the environment. This fact has led to questions about the possible impact of EOs on ecosystems. Currently in toxicology, the use of alternative models can help to understand the mechanisms of toxic action, at different levels of organization of ecosystems. Algae, protozoa and bacteria form the base of the food chain and protozoan cells are used as bioindicators often of pollution in environment. Unicellular organisms offer the possibility of direct study of independent cells with specific characteristics of individual cells and whole organisms at the same time. This unicellular facilitates the study of physiological processes, and effects of pollutants at the cellular level, which makes it widely used to assess the toxic effects of various xenobiotics. This study aimed to verify the effects of EOs of one famous plant used tremendously in our folk medicine, namely Artemisia herba alba in causing acute toxicity (24 hours) and chronic (15 days) toxicity for model cellular (Paramecium sp). To this end, cellular’s of paramecium were exposed to various concentrations (Three doses were chosen) of EOs extracted from plant (Artemisia herba alba). In the first experiment, the cellular s cultures were exposed for 48 hours to different concentrations to determine the median lethal concentration (DL50). We followed the evolution of physiological parameters (growth), biochemical (total proteins, respiratory metabolism), as well as the variations of a bio marker the GSH. Our results highlighted a light inhibition of the growth of the protozoa as well as a disturbance of the contents of total proteins and a reduction in the reduced rate of glutathione. The polarographic study revealed a stimulation of the consumption of O2 and this at the treated cells.

Keywords: essential oils, protozoa, bio indicators, toxicity, Growth, bio marker, proteins, polarographic

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Authors: Minh-Phuong Ngoc Bui, Abdennour Abbas

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Microbial spoilage of food/drug has been a constant nuisance and an unavoidable problem throughout history that affects food/drug quality and safety in a variety of ways. A simple and rapid test of fungi and bacteria in food/drugs and environmental clinical samples is essential for proper management of contamination. A number of different techniques have been developed for detection and enumeration of foodborne microorganism including plate counting, enzyme-linked immunosorbent assay (ELISA), polymer chain reaction (PCR), nucleic acid sensor, electrical and microscopy methods. However, the significant drawbacks of these techniques are highly demand of operation skills and the time and cost involved. In this report, we introduce a rapid method for detection of bacteria and fungi in food/drug products using a specific interaction between a reducing agent (tris(2-carboxylethyl)phosphine (TCEP)) and the microbial surface proteins. The chemical reaction was transferred to a transduction system using gold nanoplates-enhanced chemiluminescence. We have optimized our nanoplates synthetic conditions, characterized the chemiluminescence parameters and optimized conditions for the microbial assay. The new detection method was applied for rapid detection of bacteria (E.coli sp. and Lactobacillus sp.) and fungi (Mucor sp.), with limit of detection as low as single digit cells per mL within 10 min using a portable luminometer. We expect our simple and rapid detection method to be a powerful alternative to the conventional plate counting and immunoassay methods for rapid screening of microorganisms in food/drug products.

Keywords: microorganism testing, gold nanoplates, chemiluminescence, reducing agents, luminol

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Authors: Francis Angelo A. Sta. Ana

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Heavy metal pollutants are a major environmental concern in built-up areas in the Philippines. It causes negative effects on aquatic organisms and human health. Heavy metals concentrations of chromium, mercury, lead, copper, arsenic, zinc, cadmium, and nickel were investigated in Sta. Maria river, in Laguna. A total of 16 sediment samples were collected from the river at four stations. Atomic absorption spectroscopy (AAS) was used for element detection. It is found that copper is associated with chromium based on statistical analysis using principal component analysis (PCA). Conduct of Sediment Quality Guideline (SQG) revealed that chromium has high toxicity due to values higher than Sediment Quality Guidelines Probable Effect Level (SQG’s PEL). Copper, Nickel, and Pb fall on average toxicity while others are below PEL and effect range low (ERL).

Keywords: heavy metals, pollutants, sediment quality guidelines, atomic absorption spectroscopy

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