Search results for: drug promiscuity

Authors: Marc Polo, Núria Arbonés Arán

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Amsterdam is considered one of the great European capitals, which concentrates the headquarters of various multinational companies and which, in addition, enjoys a huge tourist attraction. Its typical residential buildings next to the canals, the museums, or its striking "Red Light District" are a great focus of attraction. In 2019 almost 9 million tourists visited it, but few of them traveled to the farthest neighborhood in the city: Amsterdam-Zuidoost (Amsterdam-Southeast). This neighborhood is geographically separated from the urban core, which makes it an exclave of Amsterdam as it does not border any of the other boroughs. Bijlmermeer neighborhood is the largest of the Amsterdam-Zuidoost, and it was born in the 1960s with the expectations of becoming the city of the future. Its main architect, Siegfried Nassuth, was inspired by the Swiss Le Corbusier to design nearly 18,000 homes, most of which were in high-rise tower blocks and built together, forming a recognizable "honeycombed" pattern. For more than 40 years, a series of infrastructure and social vicissitudes have made the neighborhood outline quite different as it was expected to be. It helped also varied elements such as ethnicity, demolitions, or unoccupied apartments. The called “city of the future” became home to immigrants, drug addicts, and vandals, and the conflicts denigrated the Amsterdam-Zuidoost. This work analyzes the evolution of the Bijlmermeer from its origins and illustrates relevant international referents able to help the area. The purpose of the work is to show how different variations along the recent history didn't help enough, but how there are positive perspectives for the future taking advantage of the food as a creative issue. The research, based on academic literature, existing material in different stadiums, plus the analysis of the city imaginaries, will help to concrete relevant elements in terms of innovation, creativity, and disruption. Despite of radical renewal that is taking place, the research will demonstrate that there are still new opportunities for the old Bijlmermeer.

Keywords: amsterdam, bijlmermeer, creativity, food

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Authors: Alireza Rafieerad, Bushroa Abd Razak, Bahman Nasiri Tabrizi, Jamunarani Vadivelu

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Recently, reports on the fabrication of nanotubular arrays have generated considerable scientific interest, owing to the broad range of applications of the oxide nanotubes in solar cells, orthopedic and dental implants, photocatalytic devices as well as lithium-ion batteries. A more attractive approach for the fabrication of oxide nanotubes with controllable morphology is the electrochemical anodization of substrate in a fluoride-containing electrolyte. Consequently, titanium dioxide nanotubes (TiO2 NTs) have been highly considered as an applicable material particularly in the district of artificial implants. In addition, regarding long-term efficacy and reasons of failing and infection after surgery of currently used dental implants required to enhance the cytocompatibility properties of Ti-based bone-like tissue. As well, graphene oxide (GO) with relevant biocompatibility features in tissue sites, osseointegration and drug delivery functionalization was fully understood. Besides, the boasting antibacterial ability of silver (Ag) remarkably provided for implantable devices without infection symptoms. Here, surface modification of Ti–6Al–7Nb implants (Ti67IMP) by the development of Ag/GO co-decorated TiO2 NTs was examined. Initially, the anodic TiO2 nanotubes obtained at a constant potential of 60 V were annealed at 600 degree centigrade for 2 h to improve the adhesion of the coating. Afterward, the Ag/GO co-decorated TiO2 NTs were developed by spin coating on Ti67IM. The microstructural features, phase composition and wettability behavior of the nanostructured coating were characterized comparably. In a nutshell, the results of the present study may contribute to the development of the nanostructured Ti67IMP with improved surface properties.

Keywords: anodic tio2 nanotube, biomedical applications, graphene oxide, silver, spin coating

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Authors: Norhan H. Mahdally, Bathini Thissera Riham A. ElShiekh, Noha M. Elhosseiny, Mona T. Kashef, Ali M. El Halawany, Mostafa E. Rateb, Ahmed S. Attia

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Multidrug-resistant (MDR) pathogens pose a global threat to healthcare settings. The exhaustion of the current antibiotic arsenal and the scarcity of new antimicrobials in the pipeline aggravate this threat and necessitate a prompt and effective response. This study focused on two major pathogens that can cause serious infections: carbapenem-resistant Acinetobacter baumannii (CRAB) and methicillin-resistant Staphylococcus aureus (MRSA). Multiple soil isolates were collected from several locations throughout Egypt and screened for their conventional and non-conventional antimicrobial activities against MDR pathogens. One isolate exhibited potent antimicrobial activity and was subjected to multiple rounds of fractionation. After fermentation and bio-guided fractionation, we identified pure microbial secondary metabolites with two scaffolds that exhibited promising effects against CRAB and MRSA. Scaling up and chemical synthesis of derivatives of the identified metabolite resulted in obtaining a more potent derivative, which we designated as 2HP. Cytotoxicity studies indicated that 2HP is well-tolerated by human cells. Ongoing work is focusing on formulating the new compound into a nano-formulation to enhance its delivery. Also, to have a better idea about how this compound works, a proteomic approach is currently underway. Our findings suggest that 2HP is a potential new broad-spectrum antimicrobial agent. Further studies are needed to confirm these findings and to develop 2HP into a safe and effective treatment for MDR infections.

Keywords: broad-spectrum antimicrobials, carbapenem-resistant acinetobacter baumannii, drug discovery, methicillin-resistant staphylococcus aureus, multidrug-resistant, natural products

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Authors: Lubna M. Zakaryia Mahmoud, Mohammed A. Dawood, Doaa A. Heiba

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A prospective double-blind placebo controlled trial carried out on 60 children known to be asthmatic who presented to the emergency department at Alexandria University of Children’s Hospital at El-Shatby with acute asthma exacerbations to assess the efficacy of adding inhaled magnesium sulfate to β-agonist, compared with β-agonist in saline, in the management of acute asthma exacerbations in children. The participants in the study were divided in two groups; Group A (study group) received inhaled salbutamol solution (0.15 ml/kg) plus isotonic magnesium sulfate 2 ml in a nebulizer chamber. Group B (control group): received nebulized salbutamol solution (0.15 ml/kg) diluted with placebo (2 ml normal saline). Both groups received inhaled solution every 20 minutes that was repeated for three doses. They were evaluated using the Pediatric Asthma Severity Score (PASS), oxygen saturation using portable pulse oximetry and peak expiratory flow rate using a portable peak expiratory flow meter at initially recorded as zero-minute assessment and every 20 minutes from the end of each nebulization (nebulization lasts 5-10 minutes) recorded as 20, 40 and 60-minute assessments. Regarding PASS, comparison showed non-significant difference with p-value 0.463, 0.472, 0.0766 at 20, 40 and 60 minutes. Regarding oxygen saturation, improvement was more significant towards group A starting from 40 min with significant p-value=0.000. At 60 min p-value=0.000. Although mean PEFR significantly improved from zero-min in both groups; however, improvement was more significant in group A with significant p-value = 0.015, 0.001, 0.001 at 20 min, 40 min and 60 min, respectively. The conclusion this study suggests is that inhaled magnesium sulfate is an efficient add on drug to standard β- agonist inhalation used in the treatment of moderate to severe asthma exacerbations.

Keywords: nebulized, magnesium sulfate, acute asthma , pediatric

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Authors: F. A. Gberindyer, M. O.Abatan, A. B. Saba

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Background: Gentamicin is an aminoglycoside antibiotic used in the treatment of infections caused by Gram-negative aerobic bacteria organisms in human and animals. In Nigeria, there are arrays of multisource generic versions of injectable gentamicin sulphate in the drug markets. There is a high prevalence of counterfeit and substandard drugs in the third world countries with consequent effect on their therapeutic efficacy and safety. Aim: The aim of this study was to investigate pharmaceutical equivalence of some of these generics used in veterinary practice in Nigeria. Methodology: About 20 generics of injectable gentamicin sulphate were sampled randomly across Nigeria but 15 were analyzed for identity and potency. Identity test was done using Fourier transform infra red spectroscopy and the spectral for each product compared with that of the USP reference standard for similarity. Microbiological assay using agar diffusion method with E. coli as a test organism on nutrient agar was employed and the respective diameters of bacterial inhibition zones obtained after 24 hour incubation at 37°C. The percent potency for each product was thereafter calculated and compared with the official specification. Result And Discussion: None of the generics is produced in any African country. About 75 % of the products are imported from China whereas 60 % of the veterinary generics are manufactured in Holland. Absorption spectra for the reference and test samples were similar. Percent potencies of all test products were within the official specification of 95-115 %. Nigeria relies solely on imported injectable gentamicin sulphate products. All sampled generic versions passed both identity and potency tests. Clinicians should ensure that drugs are used rationally since the converse could be contributing to the therapeutic failures reported for most of these generics. Bioequivalence study is recommended to ascertain their interchangeability when parenteral extra venous routes are indicated.

Keywords: generics, gentamicin, identity, multisource, potency

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Authors: Selina Schwaabe

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Community pharmacies deliver high-quality health care and are responsible for medication safety. During the pandemic, accessibility to the nearest pharmacy became more essential to get vaccinated against Covid-19 and to get medical aid. The government's goal is to ensure nationwide, reachable, and affordable medical health care services by pharmacies. Therefore, the density of community pharmacies matters. Overall, the density of community pharmacies is fluctuating, with slightly decreasing tendencies in some countries. So far, the literature has shown that changes in the system affect prices and density. However, a European overview of the development of the density of community pharmacies and its triggers is still missing. This research is essential to counteract against decreasing density consulting in a lack of professional health care through pharmacies. The analysis focuses on liberal versus regulated market structures, mail-order prescription drug regulation, and third-party ownership consequences. In a panel analysis, the relative influence of the measures is examined across 27 European countries over the last 21 years. In addition, the paper examines seven selected countries in depth, selected for the substantial variance in their pharmacy system: Germany, Austria, Portugal, Denmark, Sweden, Finland and Poland. Overall, the results show that regulated pharmacy markets have over 10.75 pharmacies/100.000 inhabitants more than liberal markets. Further, mail-order prescription drugs decrease the density by -17.98 pharmacies/100.000 inhabitants. Countries allowing third-party ownership have 7.67 pharmacies/100.000 inhabitants more. The results are statistically significant at a 0.001 level. The output of this analysis recommends regulated pharmacy markets, with a ban on mail-order prescription drugs allowing third-party ownership to support nationwide medical health care through community pharmacies.

Keywords: community pharmacy, market conditions, pharmacy, pharmacy market, pharmacy lobby, prescription, e-prescription, ownership structures

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Authors: Ana Paula Mousinho, Ronaldo D. Mansano, Nelson Ordonez

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Carbon nanotubes are one of the main elements in nanotechnologies; their applications are in microelectronics, nano-electronics devices (photonics, spintronic), chemical sensors, structural material and currently in clean energy devices (supercapacitors and fuel cells). The use of magnetic particle decorated carbon nanotubes increases the applications in magnetic devices, magnetic memory, and magnetic oriented drug delivery. In this work, single-walled carbon nanotubes (CNTs) forest decorated with chromium were deposited at room temperature by high-density plasma chemical vapor deposition (HDPCVD) system. The CNTs forest was obtained using pure methane plasmas and chromium, as precursor material (seed) and for decorating the CNTs. Magnetron sputtering deposited the chromium on silicon wafers before the CNTs' growth. Scanning electron microscopy, atomic force microscopy, micro-Raman spectroscopy, and X-ray diffraction characterized the single-walled CNTs forest decorated with chromium. In general, the CNTs' spectra show a unique emission band, but due to the presence of the chromium, the spectra obtained in this work showed many bands that are related to the CNTs with different diameters. The CNTs obtained by the HDPCVD system are highly aligned and showed metallic features, and they can be used as photonic material, due to the unique structural and electrical properties. The results of this work proved the possibility of obtaining the controlled deposition of aligned single-walled CNTs forest films decorated with chromium by high-density plasma chemical vapor deposition system.

Keywords: CNTs forest, high density plasma deposition, high-aligned CNTs, nanomaterials

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Authors: A. D. Zikiryahodjaev, L. V. Bolotina, A. S. Sukhotko

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Purpose. To evaluate the expediency and timeliness of performance of surgical treatment as a component of multi-therapy treatment of patients with stage IV breast cancers. Materials and Methods. This investigation comparatively analyzed the results of complex treatment with or without surgery in patients with metastatic breast cancer. We analyzed retrospectively treatment experience of 196 patients with generalized breast cancer in the department of oncology and breast reconstructive surgery of P.A. Herzen Moscow Cancer Research Institute from 2000 to 2012. The average age was (58±1,1) years. Invasive ductul carcinoma was verified in128 patients (65,3%), invasive lobular carcinoma-33 (16,8%), complex form - 19 (9,7%). Complex palliative care involving drug and radiation therapies was performed in two patient groups. The first group includes 124 patients who underwent surgical intervention as complex treatment, the second group includes 72 patients with only medical therapy. Standard systemic therapy was given to all patients. Results. Overall, 3-and 5-year survival in fist group was 43,8 and 21%, in second - 15,1 and 9,3% respectively [p=0,00002 log-rank]. Median survival in patients with surgical treatment composed 32 months, in patients with only systemic therapy-21. The factors having influencing an influence on the prognosis and the quality of life outcomes for of patients with generalized breast cancer were are also studied: hormone-dependent tumor, Her2/neu hyper-expression, reproductive function status (age, menopause existence). Conclusion.Removing primary breast tumor in patients with generalized breast cancer improve long-term outcomes. Three- and five-year survival increased by 28,7 and 16,3% respectively, and median survival–for 11 months. These patients may benefit from resection of the breast tumor. One explanation for the effect of this resection is that reducing the tumor load influences metastatic growth.

Keywords: breast cancer, combination therapy, factors of prognosis, primary tumor

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Authors: Nelya Babynets

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Shakespeare and Mexican theatregoers have enjoyed quite a complex relationship. Shakespearean plays have appeared on the Mexican stage with remarkable perseverance, yet with mixed success. Although Shakespeare has long been a part of the global cultural marketplace and his works are celebrated all around the world, the adaptation of his plays on the contemporary Mexican stage is always an adventure, since the works of this early modern author are frequently seen as the legacy of a ‘high’, but obsolete, culture, one that is quite distant from the present-day viewers’ daily experiences and concerns. Moreover, Mexican productions of Shakespeare are presented mostly in Peninsular Spanish, a language similar yet alien to the language spoken in Mexico, one that does not wholly fit into the viewers’ cultural praxis. This is the reason why Mexican dramatic adaptations of Shakespearean plays tend to replace the cultural references of the original piece with ones that are more significant and innate to Latin American spectators. This paper analyses the new Mexican production of Richard III adapted and directed by Mauricio Garcia Lozano, which employs onstage violence - a cultural force that is inherent to all human beings regardless of their beliefs, ethnic background or nationality - as the means to make this play more relevant to a present-day audience. Thus, this paper addresses how the bloody bombast of staged murders helps to avoid the tyranny of a rigid framework of fixed meanings that denies the possibility of an intercultural appropriation of this European play written over four hundred years ago. The impact of violence displayed in Garcia Lozano’s adaptation of Richard III on Mexican audiences will also be examined. This study is particularly relevant in Mexico where the term ‘tragedy’ has become a commonplace and where drug wars and state-sanctioned violence have already taken the lives of many people.

Keywords: audience, dramatic adaptation, Shakespeare, viewer

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Authors: Rachmat Mauludin, Novita R. Kusuma, Diky Mudhakir

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Famotidine (FMT) is one of used substances in the treatment of hiperacidity and peptic ulcer, administered orally and parenterally via intravenous injection. Oral administration, which is more favorable, has been reported to have many obstacles in the process of the treatment, includes decreasing the bioavailability of FMT. This research was aimed to prepare FMT in form of solid lipid nanoparticles (SLN) with size ranging between 100-200 nm. The research was carried out also by optimizing factors that may affect physical stability of SLN. Formulation of Famotidine SLN was carried out by optimizing factors, such as duration of homogenization and sonication, lipid concentration, stabilizer composition and stabilizer concentration. SLN physical stability was evaluated (particle size distribution) for 42 days in 3 diferent temperatures. Entrapment efficiency and drug loading was determined indirectly and directly. The morphology of SLN was visualized by transmission electron microscope (TEM). In vitro release study of FMT was conducted in 2 mediums, at pH of 1.2 and 7.4. Chemical stability of FMT was determined by quantifying the concentration of FMT within 42 days. Famotidin SLN consisted of GMS as lipid and poloxamer 188, lecithin, and polysorbate 80 as stabilizers. Homogenization and sonication was performed for 5 minutes and 10 minutes. Physyical stability of nanoparticles at 3 different temperatures was no significant difference. The best formula was physically stable until 42 days with mean particle size below 200 nm. Nanoparticles produced was able to entrap FMT until 86.6%. Evaluation by TEM showed that nanoparticles was spherical and solid. In medium pH of 1.2, FMT was released only 30% during 4 hour. On the other hand, within 4 hours SLN could release FMT completely in medium pH of 7.4. The FMT concentration in nanoparticles dispersion was maintained until 95% in 42 days (40oC, RH 75%). Famotidine SLN was able to be produced with mean particle size ranging between 100-200 nm and physically stable for 42 days. SLN could be loaded by 86,6% of FMT. Morphologically, obtained SLN was spheric and solid. During 4 hours in medium pH of 1.2 and 7.4, FMT was released until 30% and 100%, respectively.

Keywords: solid lipid nanoparticle (SLN), famotidine (FMT), physicochemical properties, release study

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Authors: Masaaki Ii, Takashi Saito, Yasuhiko Tabata, Shintaro Nemoto

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Background: Clinical trials of autologous adipose-derived stem cell (AdSC) therapy for ischemic heart diseases (IHD) are now on-going. We have investigated the hypothesis that combination of AdSCs and statin, an agent with pleiotropic effects, could augment the therapeutic effect on myocardial infarction (MI). Methods and Results: Human AdSC functions with different doses of simvastatin-conjugated nanoparticle (STNP) uptake were evaluated by in vitro assays. STNP promoted the migration activity without changing the proliferation activity, and also up-regulated growth factors. Next, MI was induced by LAD ligation in nude mice, and the mice were assigned in the following groups 3 days after MI: 1) PBS (control), 2) NP-AdSCs (50000 cells), 3) STNP, and 4) STNP-AdSCs (50000 cells). Cardiac functional recovery assessed by echocardiography was improved at 4 weeks after surgery in STNP-AdSC group. Masson’s trichrome-stained sections revealed that LV fibrosis length was reduced, and the number of TUNEL-positive cardiomyocytes was less in STNP-AdSC group. Surprisingly, a number of de novo endogenous Nkx-2.5/GATA4 positive immature cardiomyocytes as well as massive vascular formation were observed in outer layer of infarcted myocardium despite of a few recruited/retained transfused STNP-AdSCs 4 weeks after MI in STNP-AdSC group. Finally, massive myocardial regeneration was observed 8 weeks after MI. Conclusions: Intravenously injected small number of statin nanoparticle-loaded hAdSCs exhibited a potent therapeutic effect inducing endogenous cardiac tissue regeneration.

Keywords: statin, drug delivery system, stem cells, cardiac regeneration

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Authors: Svitlana Antonenko, Gennady Telegeev

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Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.

Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell

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Authors: Tanyaporn Chairoch

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Introduction: Cannabis is a drug to treat patients with many diseases such as Multiple sclerosis, Alzheimer’s disease, and Epilepsy, where theycontain many active compounds such as delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Especially, THC is the primary psychoactive ingredient in cannabis and binds to cannabinoid 1 (CB1) receptors. Moreover, CB1 is located on the neocortex, hippocampus, basal ganglia, cerebellum, and brainstem. In previous study, we found the association between the variant of CB1recptors gene (rs2023239) and decreased effect of nicotine reinforcement in patients. However, there are no data describing whether the distribution of CB1 receptor gene is a genetic marker for Thai patients who are treated with cannabis. Objective: Thus, the aim of this study we want to investigate the frequency of the CB1 receptor gene in Thai patients. Materials and Methods: All of sixty Thai patients received the medical cannabis for treatment who were recruited in this study. DNA will be extracted from EDTA whole blood by Genomic DNA Mini Kit. The genotyping of CNR1 gene (rs 2023239) was genotyped by the TaqMan real time PCR assay (ABI, Foster City, CA, USA).and using the real-time PCR ViiA7 (ABI, Foster City, CA, USA). Results: We found thirty-eight (63.3%) Thai patients were female, and twenty-two (36.70%) were male in this study with median age of 45.8 (range19 – 87 ) years. Especially, thirty-two (53.30%) medical cannabis tolerant controls were female ( 55%) and median age of52.1 (range 27 – 79 ) years. The most adverse effects for medical cannabis treatment was tachycardia. Furthermore, the number of rs 2023239 (TT) carriers was 26 of 27 (96.29%) in medical cannabis-induced adverse effects and 32 of 33 (96.96%) in tolerant controls. Additionally, rs 2023239 (CT) variant was found just only one of twenty-seven (3.7%) in medical cannabis-induced adverse effects and 1 of 33 (3.03%) in tolerant controls. Conclusions: The distribution of genetic variant in CNR1 gene might serve as a pharmacogenetics markers for screening before initiating the therapy with medical cannabis in Thai patients.

Keywords: cannabis, pharmacogenetics, CNR1 gene, thai patient

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Authors: C. Puangsawat, C. Limotai, P. Srikhachin

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Bio-psycho-social caring was required for promoting the quality of life of the patients with epilepsy (PWE), despite controlled seizures. Multifaceted issues emerge at the epilepsy clinic. Unpredicted seizures, antiepileptic drug compliance problems/adverse effects, psychiatric, and social problems are all needed to be explored and managed. The Nursing Service System (NSS) at the tertiary epilepsy clinic (TEC) was consequently developed for improving the clinical care for PWE. Case manager concept was integrated as the framework guiding the processes and strategies used for developing the NSS as well as the roles of the multidisciplinary team at the clinic. This study aimed to report the outcomes of the developed NSS integrated case manager concept. The processes of our developed NSS program included 1) screening for patient’s problems using questionnaire prior to seeing epileptologists i.e., assessing the patient’s risk to develop acute seizures at the clinic, issues related to medication use, and uncovered psychiatric and social problems; and 2) assigning the patients at risk to be evaluated and managed by appropriate team. Nurses specializing in epilepsy in coordination with the multidisciplinary team implemented the NSS to promote coordinated work among the team which consists of epileptologists, nurses, pharmacists, psychologists, and social workers. Determination of the role of each person and their responsibilities along with joint care plan were clearly established. One year after implementation, the rate of acute seizure occurrence at the clinic was decreased, and satisfactory feedback from the patients was received. In order to achieve an optimal goal to promote self-management behaviors in PWE, continuing the NSS and systematic assessment of its effectiveness is required.

Keywords: case manager concept, nursing service system, patients with epilepsy, quality of life

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Authors: Ismail I. Abo-Ghanema, Faheim E. Wehaish, Rasha M. Saleh , Walaa F. Awadin, Mohamed F. Elshal

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The antidiabetic activity of myrrh and ginseng ethanolic extracts were investigated in streptozotocin (STZ)-induced diabetic rats. Thirty male albino rats were divided into five groups, each consisted of six rats. The first group (G1) is the negative control that was fed basal diet, the second group (G2) was injected with STZ and received no treatment, the third group (G3) injected with STZ and received metformin (50 mg/kg, b.wt) as standard anti-diabetic drug, the fourth group (G4) injected with STZ and ginseng (50 mg/kg, b.wt), the fifth group (G5) injected with STZ and received myrrh (500 mg/kg, b.wt). As compared with G1-group, STZ injection increased blood concentrations of glucose (6.2 fold), glycated hemoglobin (HbA1c) (2.51 fold), aspartateaminotransferase (AST), and alanine aminotransferase (ALT) (2.64, 4.60 fold respectively), creatinine (2.91 fold), cholesterol (1.79 fold), triglycerides (2.06 fold), low density lipoprotein-cholesterol (LDL) (2.92 fold), nitric oxide (NO) (20.18 fold), and malondialdehyde (MDA) (2.25 fold), whereas it decreased blood insulin (0.40 fold), albumin (0.60 fold), high density lipoprotein-cholesterol (HDL) (0.33 fold), and reduced glutathione (GSH) (0.49 fold). Vascular permeability index (VPI as measured by Evan's Blue; EB extravasations test) was significantly increased in the skin of diabetic animals (9.6 fold) when compared with the G1-group. In addition, histological alterations in liver, pancreas, kidneys and heart were observed. After 4 weeks of treatment, rats in G4 and G5 showed significant corrections in the all measured parameters and indices. In conclusions, the ethanolic extracts of ginseng and myrrh exhibited promising and safe anti-diabetic activity especially on peripheral circulation as manifested by decreased vascular permeability and improved histopathological alterations of examined organs and insulin secretion. Hence, it may be pursued for their clinical usefulness in the management of diabetes mellitus (DM) and associated vascular complications.

Keywords: diabetic rats, peripheral circulation, natural plants, myrrh, ginseng

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Authors: Maria Bercea, Monica Diana Olteanu

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Investigation of polymer systems able to change inside of the body into networks represent an attractive approach, especially when there is a minimally invasive and patient friendly administration. Pharmaceutical formulations based on Pluronic F127 [poly (oxyethylene) (PEO) blocks (70%) and poly(oxypropylene) (PPO) blocks (30%)] present an excellent potential as drug delivery systems. The use of Pluronic F127 alone as gel-forming solution is limited by some characteristics, such as poor mechanical properties, short residence time, high permeability, etc. Investigation of the interactions between the natural and synthetic polymers and surfactants in solution is a subject of great interest from both scientific and practical point of view. As for example, formulations based on Pluronics and chitosan could be used to obtain dual phase transition hydrogels responsive to temperature and pH changes. In this study, different materials were prepared by using poly(vinyl alcohol), chitosan solutions mixed with aqueous solutions of Pluronic F127. The rheological properties of different formulations were investigated in temperature sweep experiments as well as at a constant temperature of 37oC for exploring in-situ gel formation in the human body conditions. In addition, some viscometric investigations were carried out in order to understand the interactions which determine the complex behaviour of these systems. Correlation between the thermodynamic and rheological parameters and phase separation phenomena observed for the investigated systems allowed the dissemination the constitutive response of polymeric materials at different external stimuli, such as temperature and pH. The rheological investigation demonstrated that the viscoelastic moduli of the hydrogels can be tuned depending on concentration of different components as well as pH and temperature conditions and cumulative contributions can be obtained.

Keywords: hydrogel, polymer mixture, stimuli responsive, biomedical applications

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Authors: Feras Darwish Elhajji, Alberto Berardi, Manal Ayyash, Iman Basheti

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The concept of the use of probiotics for humans now has been known for decades however, their intake by the Jordanian population seems to be less common when compared to population in the developed countries. Community pharmacy is the main supplier of probiotics, however, after conducting an extensive literature review, not any published research article could be found talking about the role, knowledge, and practice of the pharmacists in the area of probiotics. The main aim of this study was to evaluate the level of knowledge about probiotics and their dispensing practice in community pharmacies in Jordan. Community pharmacy staff (pharmacists and technicians) in Amman and north of Jordan were randomly selected to complete an anonymous questionnaire that had been pre-tested and validated. Ethical approval was obtained from the university ethics committee. The questionnaire included the following sections: demographics, knowledge and perceptions about probiotics, and role of the pharmacist Pharmacists and technicians were visited and interviewed in 281 community pharmacies. Asking about probiotics, 90.4% of them said that they know what probiotics are, although only 29.5% agreed that pharmacy staff in Jordan have good knowledge about probiotics, and 88.3% agreed that pharmacy staff in Jordan need more training and knowledge about probiotics. Variables that were significantly related to knowledge about probiotics were being a pharmacist (ρ= 0.012), area of the community pharmacy (ρ= 0.019), and female staff (ρ= 0.031) after conducting logistic regression statistical analysis. More than two-thirds of the participants thought that probiotics are classified as dietary supplements by Jordan Food and Drug Administration (JFDA). Of those who knew probiotics, the majority of them – 76.8% and 91.7% – agreed that probiotics are effective and safe, respectively. Believing in efficacy of the probiotics was significantly associated with answering their use to be with or after antibiotic administration and to increase normal flora gut population (ρ= 0.007). Efficacy was also significantly associated with recommending probiotics to consumers by the pharmacist (ρ< 0.001) and by the doctor (ρ= 0.041). At the same time, the concept of safety was mainly associated with their use for flatulence and gases (ρ= 0.048). Level of knowledge about probiotics and their uses, efficacy and safety amongst community pharmacy staff in Jordan is found to be good. However, this level can be raised in the future, especially knowledge about uses of probiotics.

Keywords: community pharmacy, Jordan, prebiotics, probiotics

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Authors: Zahra Dehghani, Hoda Dehghani, Elham Zarenezhad

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1,2,3-Triazole derivatives are important compounds in medicinal chemistry owing to their wide applications in drug discovery. They can readily associate with biologically targets through the hydrogen bonding and dipole interactions. The 1,2,3-triazole core is a key structural motif in many bioactive compounds, exhibiting a broad spectrum of biological activities, such as antiviral, anticancer, anti-HIV, antibiotic, antibacterial, and antimicrobial. Additionally, they have found significant industrial applications as dyes, agrochemicals, corrosion inhibitors, photo stabilizers, and photographic materials. we disclose the synthesis and characterization of 1-azido-3-(aryl-2-yloxy)propan-2-ol drivatives. The chemistry works well with various ß-azido alcohols involving aryloxy, alkoxy and alkyl residues, and also tolerates a wide spectrum of electron-donating and electron-withdrawing functional groups in both alkyne and azide molecules. Most of ß-azidoalcohols used in these experiments were pre-synthesized by the regioselective ring opening reaction of corresponded epoxides with sodium azide, whereas the majority of terminal alkynes were prepared via SN2-type reaction of propargyl bromide and corresponded nucleophiles. To evaluate the bioactivity of title compounds, the in vitro antifungal activity of all compound was investigated against several pathogenic fungi including Candida albicans, Candida krusei, Aspergillus niger, and Trichophyton rubrum , clotrimazole and fluconazole was used as standard antifungal drugs, also To understand the antibacterial activity of synthesized compounds, they were in vitro screened against E. coli and S. aureus as Gram-negative and Gram-positive bacteria, respectively. The in vitro tests have shown the promising antifungal but marginal antibacterial activity against tested fungi and bacteria.

Keywords: biological activities, antibacterial, antifungal, 1, 2, 3-Triazole

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Authors: Tadesse Eguale, Ephrem Engdawork, Wondwossen Gebreyes, Dainel Asrat, Hile Alemayehu, John Gunn

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Salmonella is one of the major zoonotic pathogens affecting wide range of vertebrates and humans worldwide. Consumption of contaminated dairy products and contact with dairy cattle represent the common sources of non-typhoidal Salmonella infection in humans. Fecal samples were collected from 132 dairy herds in central Ethiopia and cultured for Salmonella to determine the prevalence, serotype distribution and antimicrobial susceptibility. Salmonella was recovered from the feces of at least one cattle in 10(7.6%) of the dairy farms. Out of 1193 fecal samples 30(2.5%) were positive for Salmonella. Large farm size, detection of diarrhea in one or more animals during sampling and keeping animals completely indoor compared to occasional grazing outside were associated with Salmonella positivity of the farms. Farm level prevalence of Salmonella was significantly higher in young animals below 6 months of age compared to other age groups(X2=10.24; p=0.04). Nine different serotypes were isolated. The four most frequently recovered serotypes were S. Typhimurium (23.3%),S. Saintpaul (20%) and S. Kentucky and S. Virchow (16.7%) each. All isolates were resistant or intermediately resistant to at least one of the 18 drugs tested. Twenty-six (86.7%), 20(66.7%), 18(60%), 16(53.3%) of the isolates were resistant to streptomycin, nitrofurantoin, sulfisoxazole and tetracycline respectively. Resistance to 2 drugs was detected in 93.3% of the isolates. Resistance to 3 or more drugs were detected in 21(70%) of the total isolates while multi-drug resistance (MDR) to 7 or more drugs were detected in 12 (40%) of the isolates. The rate of occurrence of MDR in Salmonella strains isolated from dairy farms in Addis Ababa was significantly higher than those isolated from farms outside of Addis Ababa((p= 0.009). The detection of high MDR in Salmonella isolates originating from dairy farms warrants the need for strict pathogen reduction strategy in dairy cattle and spread of these MDR strains to human population.

Keywords: salmonella, antimicrobial resistance, fecal prevalence

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Authors: Ronel Solis, Leonardo Collado

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Migration law in the Republic of Panama has been regulated mainly by the executive branch. This has created a crisis not only institutional but also social because the evolution of these norms has rested greatly from the discretion of the government in office. This has created instability in immigration regulation and more now, with the migration crisis of which Panama is also part. Different migration policies have been established. The most recent is that of the controlled migration flow, in which, for humanitarian reasons, migrants move from the border with Colombia to the border with Costa Rica. Unfortunately, such control is not enough, and in some cases, unprotected migrants have been confined for months, their passports have been withheld, and no recognition of their rights is offered. The Inter-American Court of Human Rights has condemned Panama for the unfair detention of an irregular migrant, who was detained for two years in Panamanian prisons, without having committed a crime and without accessing a just defense. This is the case Vélez Loor vs. the Republic of Panama. Uncontrollable migration has been putting pressure on Panamanian public health services. The recent denunciation of HIV-related NGOs that warns that there are hundreds of foreigners who receive expensive antiretroviral therapy in Panama is serious, and several of them are irregular migrants. On the other hand, there are no border control posts with the Republic of Colombia, because it is a jungle area and migrants are exposed to arms and drug trafficking, and unfortunately, also to prostitution. Government entities such as the border police service have provided humanitarian support to migrants on the border with Colombia, although it is not their administrative function, and various entities discuss who should address this crisis. However, few economic resources are allocated by the government to solve this problem, especially with the recent mass migration of Venezuelans who have fled their country. The establishment of a migratory normative code is necessary to establish uniformity in the recognition and application of migratory rights. In this way, dependence on the changing migration policies of the different Panamanian governments would be eliminated, and the rights of migrants and nationals would be guaranteed.

Keywords: executive branch, irregular migration, migration code, Republic of Panama

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Authors: Naveeda Akhtar Qureshi, Wajiha

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Coccidiosis is a protozoan parasitic disease of genus Eimeria. It is an avian infection causing a great economic loss of 3 billion USD per year globally. A number of anticoccidial drugs are in use however many of them have side effects and cost effective. With increase in poultry demand throughout the world there is a need of more drugs and vaccines against coccidiosis. The present study is based upon the use of F. racemosa a medicinal plant to be a potential source of anticoccidial agents. The methanolic leaves extract was fractionated by column and thin layer chromatography and got nineteen fractions. Each fraction different concentrations was evaluated for its anticoccidial properties in an invitro experiment against E. tenella, E. necatrix and E. mitis. The anticoccidial active fractions were further characterized by spectroscopy (UV-Vis, FTIR) and GC-MS analysis. The in silico molecular docking of active fractions identified compounds were carried out. Among all fractions significantly maximum sporulation inhibition efficacy was shown by F-19 (67.11±2.18) followed by F-15 (65.21±1.34) at concentration of 30mg/ml against E. tenella. The significantly highest sporozoites viability inhibition was shown by F-19 (69.23±2.11) followed by F-15 (67.14±1.52) against E. necatrix at concentration 30mg/ml. Anticoccidial active fractions 15 and 19 showed peak spectrum at 207 and 202nm respectively by UV analysis. Their FTIR analysis confirmed the presence of carboxylic acid, amines, phenols, etc. Anticoccidial active compounds like Cyclododecane methanol, oleic acid, Octadecanoic acid, etc were identified by GC-MS analysis. Identified compounds in silico molecular docking study showed that cyclododecane methanol of F-19 and oleic acid of F-15 showed highest binding affinity with target S-Adenosylmethionine synthase. Hence for further authentication in vivo anticoccidial studies are recommended.

Keywords: ficus racemosa, cluster fig, column chromatography, anticoccidial fractions, GC-MS, molecular docking., s-adenosylmethionine synthase

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Authors: Abbas Pourreza

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MicroRNAs (miRNAs) are small single-stranded non-coding RNAs. They are almost 18-25 nucleotides long and very conservative through evolution. They are involved in adjusting the expression of numerous genes due to the existence of a complementary region, generally in the 3' untranslated regions (UTR) of target genes, against particular mRNAs in the cell. Also, miRNAs have been proven to be involved in cell development, differentiation, proliferation, and apoptosis. More than 2000 miRNAs have been recognized in human cells, and these miRNAs adjust approximately one-third of all genes in human cells. Dysregulation of miRNA originated from abnormal DNA methylation patterns of the locus, cause to down-regulated or overexpression of miRNAs, and it may affect tumor formation or development of it. Breast cancer (BC) is the most commonly identified cancer, the most prevalent cancer (23%), and the second-leading (14%) mortality in all types of cancer in females. BC can be classified based on the status (+/−) of the hormone receptors, including estrogen receptor (ER), progesterone receptor (PR), and the Receptor tyrosine-protein kinase erbB-2 (ERBB2 or HER2). Currently, there are four main molecular subtypes of BC: luminal A, approximately 50–60 % of BCs; luminal B, 10–20 %; HER2 positive, 15–20 %, and 10–20 % considered Basal (triple-negative breast cancer (TNBC)) subtype. Aberrant expression of miR-145, miR-21, miR-10b, miR-125a, and miR-206 was detected by Stem-loop real-time RT-PCR in BC cases. Breast tumor formation and development may result from down-regulation of a tumor suppressor miRNA such as miR-145, miR-125a, and miR-206 and/or overexpression of an oncogenic miRNA such as miR-21 and miR-10b. MiR-125a, miR-206, miR-145, miR-21, and miR-10b are hugely predicted to be new tumor markers for the diagnosis and prognosis of BC. MiR-21 and miR-125a could play a part in the treatment of HER-2-positive breast cancer cells, while miR-145 and miR-206 could speed up the evolution of cure techniques for TNBC. To conclude, miRNAs will be presented as hopeful molecules to be used in the primary diagnosis, prognosis, and treatment of BC and battle as opposed to its developed drug resistance.

Keywords: breast cancer, HER2 positive, miRNA, TNBC

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Authors: Oluyomi Stephen Adeyemi, Kentaro Kato

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Toxoplasma gondii is the etiological agent of toxoplasmosis, a common parasitic disease capable of infecting a range of hosts, including nearly one-third of the human population. Current treatment options for toxoplasmosis patients are limited. In consequence, toxoplasmosis represents a large global burden that is further enhanced by the shortcomings of the current therapeutic options. These factors underscore the need for better anti-T. gondii agents and/or new treatment approach. In the present study, we sought to find out whether preparing and capping nanoparticles (NPs) in amino acids, would enhance specificity toward the parasite versus the host cell. The selection of amino acids was premised on the fact that T. gondii is auxotrophic for some amino acids. The amino acid-nanoparticles (amino-NPs) were synthesized, purified and characterized following established protocols. Next, we tested to determine the anti-T. gondii activity of the amino-NPs using in vitro experimental model of infection. Overall, our data show evidence that supports enhanced and excellent selective action against the parasite versus the host cells by amino-NPs. The findings are promising and provide additional support that warrants exploring the prospects of NPs as alternative anti-parasite agents. In addition, the anti-parasite action by amino-NPs indicates that nutritional requirement of parasite may represent a viable target in the development of better alternative anti-parasite agents. Furthermore, data suggest the anti-parasite mechanism of the amino-NPs involves multiple cellular processes including the production of reactive oxygen species (ROS), modulation of hypoxia-inducing factor-1 alpha (HIF-1α) as well as the activation of kynurenine pathway. Taken together, findings highlight further, the prospects of NPs as alternative source of anti-parasite agents.

Keywords: drug discovery, infectious diseases, mode of action, nanomedicine

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Authors: Kang-Hyun Leem, Myung-Gyou Kim, Hye Kyung Kim

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Deer antler, traditionally used as a tonic and valuable drug in oriental medicine, has been considered to possess bone-strengthening activity. The upper section, mid section, and base of the antler has been known to exhibit different biological properties. Present study was performed to examine the effects of different parts of deer antler extract (DH) on osteogenic gene expressions in MG-63 cells and longitudinal bone growth in adolescent male rats. The expressions of osteogenic genes, collagen, alkaline phosphatase, osteocalcin, and osteopontin, were measured by quantitative real-time PCR. Longitudinal bone growth was measured in 3-week-old male Sprague-Dawley rats using fluorescence microscopy. To examine the effects on the growth plate metabolism, the total height of growth plate and bone morphogenetic protein-2 (BMP-2) were measured. Collagen and osteocalcin mRNA expressions were increased by all three parts of the DH treatment while osteopontin gene expression was not affected by any of the DH treatment. Alkaline phosphatase gene expression was increased by upper and mid part of DH while base part of DH fails to affect alkaline phosphatase gene expression. The upper and mid parts of the DH treatment enhanced longitudinal bone growth and total height of growth plate. The induction of BMP-2 protein expression in growth plate assessed by immunostaining was also promoted by upper and mid parts of the DH treatment. These results suggest that DH, especially upper and mid parts, stimulate osteogenic gene expressions and have the effect on bone growth in adolescent rats and might be used for the growth delayed adolescent and inherent growth failure patient.

Keywords: bone morphogenetic protein-2, deer antler, longitudinal bone growth, osteogenic genes

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Authors: Faisal A. Salih

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Vinpocetine (Vin) is an ethyl ester of apovincamic acid and is a semisynthetic derivative of vincamine, an alkaloid from plants of the genus Periwinkle (plant) vinca minor. It was found that this compound stimulates cerebral metabolism: it increases the uptake of glucose and oxygen, as well as the consumption of these substances by the brain tissue. Vinpocetine enhances the flow of blood in the brain and has a vasodilating, antihypertensive, and antiplatelet effect. Vinpocetine seems to improve the human ability to acquire new memories and restore memories that have been lost. This drug has been clinically used for the treatment of cerebrovascular disorders such as stroke and dementia memory disorders, as well as in ophthalmology and otorhinolaryngology. It has no side effects, and no toxicity has been reported when using vinpocetine for a long time. For the quantitative determination of Vin in dosage forms, the HPLC methods are generally used. A promising alternative is potentiometry with Vin- selective electrode, which does not require expensive equipment and materials. Another advantage of the potentiometric method is that the pills and solutions for injections can be used directly without separation from matrix components, which reduces both analysis time and cost. In this study, it was found that the choice of a good plasticizer an electrode with the following membrane composition: PVC (32.8 wt.%), ortho-nitrophenyl octyl ether (66.6 wt.%), tetrakis-4-chlorophenyl borate (0.6 wt.%) exhibits excellent analytical performance: lower detection limit (LDL) 1.2•10⁻⁷ M, linear response range (LRR) 1∙10⁻³–3.9∙10⁻⁶ M, the slope of the electrode function 56.2±0.2 mV/decade). Vin masses per average tablet weight determined by direct potentiometry (DP) and potentiometric titration (PT) methods for the two different sets of 10 tablets were (100.35±0.2–100.36±0.1) mg for two sets of blister packs. The mass fraction of Vin in individual tablets, determined using DP, was (9.87 ± 0.02–10.16 ±0.02) mg, while the RSD was (0.13–0.35%). The procedure has very good reproducibility, and excellent compliance with the declared amounts was observed.

Keywords: vinpocetine, potentiometry, ion selective electrode, pharmaceutical analysis

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Authors: Amira Abdelrasoul

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This study aimed to ascertain the controlled permeability of biomimetic cellulose triacetate (CTA) membranes by investigating the electrical oscillatory behavior across impregnated membranes (IM). The biomimetic CTA membranes were infused with a fatty acid to induce electrical oscillatory behavior and, hence, to ensure controlled permeability. In situ synchrotron radiation micro-computed tomography (SR-μCT) at the BioMedical Imaging and Therapy (BMIT) Beamline at the Canadian Light Source (CLS) was used to evaluate the main morphology of IMs compared to neat CTA membranes to ensure fatty acid impregnation inside the pores of the membrane matrices. A monochromatic beam at 20 keV was used for the visualization of the morphology of the membrane. The X-ray radiographs were recorded by means of a beam monitor AA-40 (500 μm LuAG scintillator, Hamamatsu, Japan) coupled with a high-resolution camera, providing a pixel size of 5.5 μm and a field of view (FOV) of 4.4 mm × 2.2 mm. Changes were evident in the phase transition temperatures of the impregnated CTA membrane at the melting temperature of the fatty acid. The pulsations of measured voltages were related to changes in the salt concentration of KCl in the vicinity of the electrode. Amplitudes and frequencies of voltage pulsations were dependent on the temperature and concentration of the KCl solution, which controlled the permeability of the biomimetic membranes. The presented smart biomimetic membrane successfully combined porous polymer support and impregnating liquid not only imitate the main barrier properties of the biological membranes but could be easily modified to achieve some new properties, such as facilitated and active transport, regulation by chemical, physical and pharmaceutical factors. These results open new frontiers for the facilitation and regulation of active transport and permeability through biomimetic smart membranes for a variety of biomedical and drug delivery applications.

Keywords: biomimetic, membrane, synchrotron, permeability, morphology

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Authors: Nassima Elyebdri, Asma Boumediou, Soumia Addoun

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Traditional medicine has been part of the Algerian culture for decades. In particular, the city of Tlemcen still retains practices based on phytotherapy to the present day, as this kind of medicine fulfills the needs of its followers among the local population. The toxic plants contain diverse natural substances which supplied a lot of medicine in the pharmaceutical industry. In order to explore new medicinal sources among toxic plants, an ethnobotanical study was carried out on the use of these plants by the population, at Emir Abdelkader Square of the city of Tlemcen, a rather busy place with a high number of traditional health practitioners and herbalists. This is a descriptive and transversal study aimed at estimating the frequency of using toxic plants among the studied population, for a period of 4 months. The information was collected, using self-anonymous questionnaires, and analyzed by the IBM SPSS Statistics software used for statistical analysis. A sample of 200 people, including 120 women and 80 men, were interviewed. The mean age was 41 ± 16 years. Among those questioned, 83.5% used plants; 8% of them used toxic plants and 35% used plants that can be toxic under certain conditions. Some improvements were observed in 88% of the cases where toxic plants were used. 80 medicinal plants, belonging to 36 botanical families, were listed, identified and classified. The most frequent indications for these plants were for respiratory diseases in 64.7% of cases, and for digestive disorders in 51.5% of cases. 11% of these plants are toxic, 26% could be toxic under certain conditions. Among toxics plants, the most common ones are Berberis vulgaris with 5.4%, indicated in the treatment of uterine fibroids and thyroid, Rhamnus alaternus with 4.8% for hepatic jaundice, Nerium oleander with 3% for hemorrhoids, Ruta chalepensis with 1.2%, indicated for digestive disorders and dysmenorrhea, and Viscum album with 1.2%, indicated for respiratory diseases. The most common plants that could be toxic are Mentha pulegium (15.6%), Eucalyptus globulus (11.4%), and Pimpinella anisum (10.2%). This study revealed interesting results on the use of toxic plants, which are likely to serve as a basis for further ethno-pharmacological investigations in order to get new drug sources.

Keywords: ethnobotany, phytotherapy, Tlemcen, toxic plants

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Authors: Scholastic Nangila Adeli, Francisca Mbutitia Ngithi

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Stigma is commonly associated with mental health patients and may act as a barrier to individuals who may seek or engage in treatment services. Stigmatization among university students is common whether they know someone with a mental health problem, or have a good knowledge and experience of mental health issues. The objective of this study was to establish the various barriers that prevent university students who have mental health challenges from seeking treatment and care. The study was a descriptive in nature where 320 respondents helped to establish the barriers to treatment or participation in mental health care among university students. A questionnaire was used to help establish the barriers and attitude towards mental illness among the respondents. Results from this study revealed that mental illnesses are common among university students and they are manifested in different forms like; anxiety and panic attacks, mood and eating disorders, Impulse control leading to gambling, alcohol and drug addictions, anger and depression leading to loneliness. Mental stigma (both social and self) was the major barrier with 62% of the respondents stating that social stigma was worse than self-stigma. This is because of the social discrimination towards the victim of mental challenges. On issues of attitude, 71% of the respondents said that they can never admit that they have a mental issue and would rather secretly seek clinical or psychological help for fear of being discriminated or excluded by peers. This view is informed by the societal belief that people with mental health challenges were dangerous (associating them with criminal behavior) and hard to socialize with or help. From the findings of this study, it is concluded that mental health problems are real among university students in Kenya and it is important for the university environment to minimize or eradicate stigma within the social circles. Stigma can be minimized or eradicated by creating awareness among university students and fostering social inclusion so that the students who have mental health challenges can experience a sense of belonging and acceptance hence build their self-esteem.

Keywords: disorders, impulse control, mental health problems, stigma

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Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

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Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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Authors: Fitsumbrhan Tajebe, Fadil Murad, Mitikie Tigabie, Mareye Abebaw, Tadele Alemu, Sefanit Abate, Rezika Mohammedw, Arega Yeshanew, Elias Shiferaw

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Background: Visceral leshimaniasis is a parasitic disease characterized by a systemic infection of phagocytic cells. Hematological parameters of these patients may be affected by the progress of the disease or treatment. Thus, the current study aimed to assess the hematological profiles of visceral leishmaniasis patients before and after treatment. Method: An institutional based retrospective cohort study was conducted among visceral leishmaniasis patients at University of Gondar Comprehensive Specialized Referral Hospital Leishmaniasis Research and Treatment Center from 2013 to 2018. Hematological profiles before initiation and after completion of treatment were extracted from registration book. Descriptive statics was presented using frequency and percentage. Paired t-test and Wilcoxon Signed rank test were used for comparing mean difference for normally and non- normally distributed data, respectively. Spearman and Pearson correlation analysis was used to describe the correlation of hematological parameters with different variables. P value < 0.05 was considered as statistically significant. Result: Except absolute nerutrophil count, post treatment hematological parameters show a significant increment compared to pretreatment one. The prevalence of anemia, leucopenia and thrombocytopenia was 85.5%, 83.4% and 75.8% prior to treatment and it was 58.3%, 38.2% and 19.2% after treatment, respectively. Moreover, parasite load of the disease showed statistically significant negative correlation with hematological profiles mainly with white blood cell and red blood cell. Conclusion: Majority of hematological profiles of patients with active VL have been restored after treatment, which might be associated with treatment effect on parasite proliferation and concentration of parasite in visceral organ, which directly affect hematological profiles.

Keywords: visceral leshimaniasis, hematological profile, anti-leshimanial drug, Gondar

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