Search results for: drug releasing

Authors: Jeena Gupta

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In the today’s world of pharmaceutical products, one should not forget the healing properties of inexpensive food materials especially spices. They are known to possess hidden pharmaceutical ingredients, imparting them the qualities of being anti-microbial, anti-oxidant, anti-inflammatory and anti-carcinogenic. Further aberrant epigenetic regulatory mechanisms like DNA methylation, histone modifications or altered microRNA expression patterns, which regulates gene expression without changing DNA sequence, contribute significantly in the development of various diseases. Changing lifestyles and diets exert their effect by influencing these epigenetic mechanisms which are thus the target of dietary phytochemicals. Bioactive components of plants have been in use since ages but their potential to reverse epigenetic alterations and prevention against diseases is yet to be explored. Spices being rich repositories of many bioactive constituents are responsible for providing them unique aroma and taste. Some spices like curcuma and garlic have been well evaluated for their epigenetic regulatory potential, but for others, it is largely unknown. We have evaluated the biological activity of phyto-active components of Fennel, Cardamom and Fenugreek by in silico molecular modeling, in vitro and in vivo studies. Ligand-based similarity studies were conducted to identify structurally similar compounds to understand their biological phenomenon. The database searching has been done by using Fenchone from fennel, Sabinene from cardamom and protodioscin from fenugreek as a query molecule in the different small molecule databases. Moreover, the results of the database searching exhibited that these compounds are having potential binding with the different targets found in the Protein Data Bank. Further in addition to being epigenetic modifiers, in vitro study had demonstrated the antimicrobial, antifungal, antioxidant and cytotoxicity protective effects of Fenchone, Sabinene and Protodioscin. To best of our knowledge, such type of studies facilitate the target fishing as well as making the roadmap in drug design and discovery process for identification of novel therapeutics.

Keywords: epigenetics, spices, phytochemicals, fenchone

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Authors: Mohammed E. Ibrahim, Baraa A. Taha, Kamil M. A. Shabban

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Background: Epilepsy is a common but widely misunderstood illness. Consequently, patients with epilepsy suffer from considerable stigmatization in society. This social stigma and discrimination often cause more suffering for the patients than the disease itself. Since very few studies have explored the misperceptions about epilepsy among university students in Sudan, it is not possible to provide focused intervention aimed at eliminating this discrimination. Methods: A cross-sectional study was applied among the first-year medical students at the University of Khartoum between December (2020) and February (2021). A 29-item standardized questionnaire was self-administered by 198 students (out of 320) who agreed to participate in this study. Google form was the tool used to collect the data. The data were analyzed using the Statistical Package for Social Science software version 26. Result: Overall, the results indicate a negative trend in knowledge and attitude toward epilepsy. The vast majority of the respondents (84.8%) have read or heard about epilepsy, while 43.9% had seen someone with epilepsy. Only 7.5% of the participants reported that epilepsy is contagious, whereas 43.4% of them think that epilepsy is a psychological disorder. About 62.2% of students think head/birth trauma is a cause of epilepsy. On the other side, about 15.7% and 5.1% believed that evil spirits and punishment from god can also be a possible cause of epilepsy; we found these false beliefs are more common in participants from rural areas (p-value < 0.05). In regard to attitude, 19.7% of students thought that it is inappropriate for a patient with epilepsy to have a child. This attitude correlates with the mother’s education as the percentage is higher for those who have lower mother’s education (through secondary school education and below) (p < 0.05). The majority of Our participant knew that some people with epilepsy need life-long drug treatment; this belief was found to be more common in females than their counterparts(p < 0.05). . Finally, most of the respondents (93.9%) thought that a child with epilepsy Can be successful in a normal class. This belief is four-time as common in participants whose mothers have higher education (through university education and above) compared with corresponding respondents (p < 0.05). Conclusion: This study concludes that students' knowledge about epilepsy is limited and requires immediate intervention through educational campaigns to develop a well-informed and tolerant community.

Keywords: epilepsy, awareness, attitude, university students, Sudan

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Authors: Indranil Chakraborty, Kalyan Mandal

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Three new α-hydroxy carboxylate group functionalized MnFe₂O₄ nanoparticles (NPs) have been developed to explore the microscopic origin of ligand modified fluorescence and magnetic properties of nearly monodispersed MnFe₂O₄ NPs. The surface functionalization has been carried out with three small organic ligands (tartrate, malate, and citrate) having different number of α-hydroxy carboxylate functional group along with steric effect. Detailed study unveils that α-hydroxy carboxylate moiety of the ligands plays key role to generate intrinsic fluorescence in functionalized MnFe₂O₄ NPs through the activation of ligand to metal charge transfer transitions, associated with ligand-Mn²⁺/Fe³⁺ interactions along with d-d transition corresponding to d-orbital energy level splitting of Fe³⁺ ions on NP surface. Further, MnFe₂O₄ NPs show a maximum 140.88% increase in coercivity and 97.95% decrease in magnetization compared to its bare one upon functionalization. The ligands that induce smallest crystal field splitting of d-orbital energy level of transition metal ions are found to result in strongest ferromagnetic activation of the NPs. Finally, our developed tartrate functionalized MnFe₂O₄ (T-MnFe₂O₄) NPs have been utilized for studying DNA binding interaction and nuclease activity for stimulating their beneficial activities toward diverse biomedical applications. The spectroscopic measurements indicate that T-MnFe₂O₄ NPs bind calf thymus DNA by intercalative mode. The ability of T-MnFe₂O₄ NPs to induce DNA cleavage was studied by gel electrophoresis technique where the complex is found to promote the cleavage of pBR322 plasmid DNA from the super coiled form I to linear coiled form II and nicked coiled form III with good efficiency. This may be taken into account for designing new biomolecular detection agents and anti-cancer drug which can open up a new door toward diverse non-invasive biomedical applications.

Keywords: MnFe₂O₄ nanoparticle, α-hydroxy carboxylic acid, comparative fluorescence, magnetism study, DNA interaction, nuclease activity

Procedia PDF Downloads 139

Authors: Alami Ilyass, Loubna Kharchoufa, Elachouri Mostafa

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The two great realms of living diversity are cultural and biological. Today, both are being lost at an alarming rate. Of all the Earth’s biological diversity, plant kingdom is of high significance, and most essential to human welfare, in fact, medicinal plants are extensively exploited for countless purposes. Among these multiple uses, medicinal plants are the most important source of medicine for humankind healthcare and well being. In recent years there has been a great surge of public interest in the use of herbs and plants. Some scientists have viewed this phenomenon as a modern “herbal renaissance”. The importance of plants as medicines in developed and developing countries has recently been acknowledged by the United Nations (UN). However, to date fewer than 5% of the approximately 250,000 species of higher plants have been exhaustively studied for their potential pharmacological activity. A number of drugs from ethnobotanical leads have provided significant milestones in Western medicine. Despite this success, pharmacognosy research on Moroccan flora needs more studies aimed at the exploration of their therapeutic potential. A major weakness is the absence of strong funding agencies in the country, and a real national drug discovery program. Moreover, the lack of the coordination between different universities and research institutions leads, in most cases, to a waste of time, money and efforts of many researchers. In this work, we focus our attention on research into traditional indigenous medicinal plants in Morocco. Three parts constitute the head lines of this work: In the first one, we take up Moroccan biodiversity matter, the second part is devoted principally to the state of research into medicinal plants by Moroccan scholars and the last one is consecrated to the debate of factors which handicap the progress of research on phytomedicine in Morocco. The objectives of the present study are twofold: first, to highlight the state of the medicinal plants researches in Morocco. Second goal is to assess and correlate the levels of knowledge of the local flora to the research on medicinal plants to attempt to build capacity for research within Moroccan Scientific community at rate of developing country.

Keywords: Morocco, medicinal plants, ethnobotanical, pharmacognosy, phytomedicine

Procedia PDF Downloads 190

Authors: Laura Bravo-García, Gotzone Barandika, Begoña Bazán, M. Karmele Urtiaga, Luis M. Lezama, María I. Arriortua

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Solid coordination networks (SCNs) are materials consisting of metal ions or clusters that are linked by polyfunctional organic ligands and can be designed to form tridimensional frameworks. Their structural features, as for example high surface areas, thermal stability, and in other cases large cavities, have opened a wide range of applications in fields like drug delivery, host-guest chemistry, biomedical imaging, chemical sensing, heterogeneous catalysis and others referred to greenhouse gases storage or even separation. In this sense, the use of polycarboxylate anions and dipyridyl ligands is an effective strategy to produce extended structures with the needed characteristics for these applications. In this context, a novel compound, [Cu4(m-BDC)4(bpa)2DMF]•DMF has been obtained by microwave synthesis, where m-BDC is 1,3-benzenedicarboxylate and bpa 1,2-bis(4-pyridyl)ethane. The crystal structure can be described as a three dimensional framework formed by two equal, interpenetrated networks. Each network consists of two different CuII dimers. Dimer 1 have two coppers with a square pyramidal coordination, and dimer 2 have one with a square pyramidal coordination and other with octahedral one, the last dimer is unique in literature. Therefore, the combination of both type of dimers is unprecedented. Thus, benzenedicarboxylate ligands form sinusoidal chains between the same type of dimers, and also connect both chains forming these layers in the (100) plane. These layers are connected along the [100] direction through the bpa ligand, giving rise to a 3D network with 10 Å2 voids in average. However, the fact that there are two interpenetrated networks results in a significant reduction of the available volume. Structural analysis was carried out by means of single crystal X-ray diffraction and IR spectroscopy. Thermal and magnetic properties have been measured by means of thermogravimetry (TG), X-ray thermodiffractometry (TDX), and electron paramagnetic resonance (EPR). Additionally, CO2 and CH4 high pressure adsorption measurements have been carried out for this compound.

Keywords: gas adsorption, interpenetrated networks, magnetic measurements, solid coordination network (SCN), thermal stability

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Authors: Fatemeh Haghiralsadat, Mohadese Hashemi, Elham Akhoundi Kharanaghi, Mojgan Yazdani, Mahboobe Sharafodini, Omid Javani

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Niosomes are colloidal particles formed from the self-assembly of non-ionic surfactants in aqueous medium resulting in closed bilayer structures. As a consequence of this hydrophilic and hydrophobic structure, niosomes have the capacity to entrap compounds of different solubilities. Niosomes are promising vehicle for drug delivery which protect sensitive drugs and improve the therapeutic index of drugs by restricting their action to target cells. Essential oils are complex mixtures of volatile compounds such as terpenoids, phenol-derived aromatic components that have been used for many biological properties including bactericidal, fungicidal, insecticidal, antioxidant, anti-tyrosinase and other medicinal properties. Encapsulation of essential oils in niosomes can be an attractive method to overcome their limitation such as volatility, easily decomposition by heat, humidity, light, or oxygen. Cuminum cyminum L. (Cumin) is an aromatic plant included in the Apiaceae family and is used to flavor foods, added to fragrances, and for medical preparations which is indigenous to Egypt, the Mediterranean region, Iran and India. The major components of the Cumin oil were reported as cuminaldehyde, γ -terpinene, β-pinene, p-cymene, p-mentha-1, 3-dien-7-al, and p-mentha-1, 4-dien-7-al which provide the antimicrobial and antioxidant activity. The aim of this work was to formulate Cumin essential oil-loaded niosomes to improve water solubility of natural product and evaluate its physico-chemical features and stability. Cumin oil was obtained through steam distillation using a clevenger-type apparatus and GC/MS was applied to identify the main components of the essential oil. Niosomes were prepared by using thin film hydration method and nanoparticles were characterized for particle size, dispersity index, zeta potential, encapsulation efficiency, in vitro release, and morphology.

Keywords: Cuminum cyminum L., Cumin, niosome, essential oil, encapsulation

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Authors: Abdul Mutalib Md Jani, Abdul Hadi Mahmud, Mohd Tajuddin Mohd Ali

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The rapid growth of interest in surface modification of nanostructures materials that exhibit improved structural and functional properties is attracting more researchers. The unique properties of highly ordered nanoporous anodic aluminium oxide (NAAO) membrane have been proposed as a platform for biosensing applications. They exhibit excellent physical and chemical properties with high porosity, high surface area, tunable pore sizes and excellent chemical resistance. In this study, NAAO was functionalized with 3-aminopropyltriethoxysilane (APTES) to prepared silane-modified NAAO. Amine functional groups are formed on the surface of NAAO during silanization and were characterized using Fourier Transform Infrared spectroscopy (FTIR). The synthesis of multi segment of peptide on NAAO surfaces can be realized by changing the surface chemistry of the NAAO membrane via click chemistry. By click reactions, utilizing alkyne terminated with amino group, various peptides tagged on NAAO can be envisioned from chiral natural or unnatural amino acids using standard coupling methods (HOBt, EDCI and HBTU). This strategy seemly versatile since coupling strategy of dipeptide with another amino acids, leading to tripeptide, tetrapeptide or pentapeptide, can be synthesized without purification. When an appropriate terminus is selected, multiple segments of amino acids can be successfully synthesized on the surfaces. The immobilized NAAO should be easily separated from the reaction medium by conventional filtration, thus avoiding complicated purification methods. Herein, we proposed to synthesize multi fragment peptide as a model for capturing and attaching various small biomolecules on NAAO surfaces and can be also applied as biosensing device, drug delivery systems and biocatalyst.

Keywords: nanoporous anodic aluminium oxide, silanization, peptide synthesise, click chemistry

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Authors: Moulay Driss Mellaoui, Khadija Zaki, Khalid Abbiche, Abdallah Imjjad, Rachid Boutiddar, Abdelouahid Sbai, Aaziz Jmiai, Souad El Issami, Al Mokhtar Lamsabhi, Hanane Zejli

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This study presents a comprehensive analysis of six isoxazolidine and isoxazoline derivatives, leveraging a multifaceted approach that combines Density Functional Theory (DFT), AdmetSAR analysis, and molecular docking simulations to explore their electronic, pharmacokinetic, and anticancer properties. Through DFT analysis, using the B3LYP-D3BJ functional and the 6-311++G(d,p) basis set, we optimized molecular geometries, analyzed vibrational frequencies, and mapped Molecular Electrostatic Potentials (MEP), identifying key sites for electrophilic attacks and hydrogen bonding. Frontier Molecular Orbital (FMO) analysis and Density of States (DOS) plots revealed varying stability levels among the compounds, with 1b, 2b, and 3b showing slightly higher stability. Chemical potential assessments indicated differences in binding affinities, suggesting stronger potential interactions for compounds 1b and 2b. AdmetSAR analysis predicted favorable human intestinal absorption (HIA) rates for all compounds, highlighting compound 3b superior oral effectiveness. Molecular docking and molecular dynamics simulations were conducted on isoxazolidine and 4-isoxazoline derivatives targeting the EGFR receptor (PDB: 1JU6). Molecular docking simulations confirmed the high affinity of these compounds towards the target protein 1JU6, particularly compound 3b, among the isoxazolidine derivatives, compound 3b exhibited the most favorable binding energy, with a g score of -8.50 kcal/mol. Molecular dynamics simulations over 100 nanoseconds demonstrated the stability and potential of compound 3b as a superior candidate for anticancer applications, further supported by structural analyses including RMSD, RMSF, Rg, and SASA values. This study underscores the promising role of compound 3b in anticancer treatments, providing a solid foundation for future drug development and optimization efforts.

Keywords: isoxazolines, DFT, molecular docking, molecular dynamic, ADMET, drugs.

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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Authors: Rizoyeva Marjona Rustam Qizi

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Transnational organized crime (TOC) represents one of the most significant threats to global security and social stability in the 21st century. Criminal networks operating across borders engage in activities such as drug trafficking, human trafficking, arms smuggling, and cybercrime, exploiting legal loopholes and jurisdictional challenges. In response, criminal law has evolved to address the complexities of TOC through enhanced international cooperation, harmonization of legal standards, and stronger enforcement mechanisms. This abstract explores the role of criminal law in combating TOC, focusing on three key areas: legislative frameworks, international collaboration, and enforcement practices. First, the development of international legal instruments such as the United Nations Convention against Transnational Organized Crime (UNTOC) has facilitated the standardization of legal definitions and procedures. Countries have adopted these frameworks to ensure a coordinated response to TOC, closing jurisdictional gaps and simplifying extradition processes. Second, international collaboration among law enforcement agencies, facilitated by organizations like INTERPOL and Europol, has enhanced information sharing and joint operations, making it more difficult for criminal organizations to evade detection. Finally, advancements in technology have improved investigative techniques, enabling law enforcement to track and dismantle criminal networks more effectively. However, despite these achievements, challenges remain. Issues such as corruption, insufficient resources, and differing legal systems continue to hinder the global fight against TOC. In conclusion, criminal law plays a pivotal role in the global effort to combat transnational organized crime by providing a legal framework for prosecution and fostering international cooperation. Ongoing reforms and technological innovations are essential for overcoming existing challenges and ensuring a more secure future. This abstract highlights the need for continuous adaptation of criminal law to address the evolving nature of TOC and underscores the importance of a unified international approach in achieving long-term success.

Keywords: transnational organized crime, criminal law, international cooperation, legal frameworks

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Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

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Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

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Authors: Nyimas Annissa Mutiara Andini

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There are 325,000 children younger than age 15 in the U.S. have epilepsy. In Indonesia, 40% of 3,5 millions cases of epilepsy happens in children. The most common type of epilepsy, which affects 6 out of 10 people with the disorder, is called idiopathic epilepsy and which has no identifiable cause. One of the most commonly used medications in the treatment of this childhood epilepsy is sodium valproate. Administration of sodium valproat in children has a problem to fail. Nearly 60% of pediatric patients known were mildly, moderately, or severely non-adherent with therapy during the first six months of treatment. Many parents or caregiver took far less medication than prescribed, and the treatment-adherence pattern for the majority of patients was established during the first month of treatment. 42% of the patients were almost always given their medications as prescribed but 13% had very poor adherence even in the early weeks and months of treatment. About 7% of patients initially gave the medication correctly 90% of the time, but adherence dropped to around 20% within six months of starting treatment. Over the six months of observation, the total missing of administration is about four out of 14 doses in any given week. This fail can cause the epilepsy to relapse. Whereas, current reported epilepsy disorder were significantly more likely than those never diagnosed to experience depression (8% vs 2%), anxiety (17% vs 3%), attention-deficit/hyperactivity disorder (23% vs 6%), developmental delay (51% vs 3%), autism/autism spectrum disorder (16% vs 1%), and headaches (14% vs 5%) (all P< 0.05). They had a greater risk of limitation in the ability to do things (relative risk: 9.22; 95% CI: 7.56–11.24), repeating a school grade (relative risk: 2.59; CI: 1.52–4.40), and potentially having unmet medical and mental health needs. In the other side, technology can help to make our life easier. One of the technology, that we can use is a mobile application. A mobile app is a software program we can download and access directly using our phone. Indonesians are highly mobile centric. They use, on average, 6.7 applications over a 30 day period. This paper is aimed to describe an application that could help to control a sodium valproat administration in children; we call it as D-Epi app. D-Epi app is a downloadable application that can help parents or caregiver alert by a timer-related application to warn whether it is the time to administer the sodium valproat. It works not only as a standard alarm, but also inform important information about the drug and emergency stuffs to do to children with epilepsy. This application could help parents and caregiver to take care a child with epilepsy in Indonesia.

Keywords: application, children, D-Epi, epilepsy

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Authors: Simon Nyarko

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This study examined the microbial flora contamination of the Ghanaian paper currency notes and antibiotic resistance in Ejura Municipal, Ashanti Region, Ghana. This is a descriptive cross-sectional study designed to assess the profile of microflora contamination of the Ghanaian paper currency notes and antibiotic-resistant in the Ejura Municipality. The research was conducted in Ejura, a town in the Ejura Sekyeredumase Municipal of the Ashanti region of Ghana. 70 paper currency notes which were freshly collected from the bank, consisting of 15 pieces of GH ¢1, GH ¢2, and GH ¢5, 10 pieces of GH ¢10 and GH ¢20, and 5 pieces of GH ¢50, were randomly sampled from people by exchanging their money in usage with those freshly secured from the bank. The surfaces of each GH¢ note were gently swabbed and sent to the lab immediately in sterile Zip Bags and sealed, and tenfold serial dilution was inoculated on plate count agar (PCA), MacConkey agar (MCA), mannitol salt agar (MSA), and deoxycholate citrate agar (DCA). For bacterial identification, the study used appropriate laboratory and biochemical tests. The data was analyzed using SPSS-IBM version 20.0. It was found that 95.2 % of the 70 GH¢ notes tested positive for one or more bacterial isolates. On each GH¢ note, mean counts on PCA ranged from 3.0 cfu/ml ×105 to 4.8 cfu/ml ×105. Of 124 bacteria isolated. 36 (29.03 %), 32 (25.81%), 16 (12.90 %), 20 (16.13%), 13 (10.48 %), and 7 (5.66 %) were from GH¢1, GH¢2, GH¢10, GH¢5, GH¢20, and GH¢50, respectively. Bacterial isolates were Escherichia coli (25.81%), Staphylococcus aureus (18.55%), coagulase-negative Staphylococcus (15.32%), Klebsiella species (12.10%), Salmonella species (9.68%), Shigella species (8.06%), Pseudomonas aeruginosa (7.26%), and Proteus species (3.23%). Meat shops, commercial drivers, canteens, grocery stores, and vegetable shops contributed 25.81 %, 20.16 %, 19.35 %, 17.74 %, and 16.94 % of GH¢ notes, respectively. There was 100% resistance of the isolates to Erythromycin (ERY), and Cotrimoxazole (COT). Amikacin (AMK) was the most effective among the antibiotics as 75% of the isolates were susceptible to it. This study has demonstrated that the Ghanaian paper currency notes are heavily contaminated with potentially pathogenic bacteria that are highly resistant to the most widely used antibiotics and are a threat to public health.

Keywords: microflora, antibiotic resistance, staphylococcus aureus, culture media, multi-drug resistance

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Authors: Dong-Gi Lee, Suyeon Cha, Yong-Sun Bahn

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Sterol lipid is essential for cell membrane structure in eukaryotic cells. In mammalian cells, sterol regulatory element binding proteins (SREBPs) act as principal regulators of cellular cholesterol which is essential for proper cell membrane fluidity and structure. SREBP and sterol regulation are related to levels of cellular oxygen because it is a major substrate for sterol synthesis. Upon cellular sterol and oxygen levels are depleted, SREBP is translocated to the Golgi where it undergoes proteolytic cleavage of N terminus, then it travels to the nucleus to play a role as transcription factor. In yeast cells, synthesis of ergosterol is also highly oxygen consumptive, and Sre1 is a transcription factor known to play a central role in adaptation to growth under low oxygen condition and sterol homeostasis in Cryptococcus neoformans. In this study, we observed phenotypes in other strains of Cryptococcus species by constructing hob1Δ and sre1Δ mutants to confirm whether the functions of both genes are conserved in most serotypes. As a result, hob1Δ showed no noticeable phenotype under treatment of antifungal drugs and most environmental stresses in R265 (C. gattii) and XL280 (C. neoformans), suggesting that Hob1 is related to sterol regulation only in H99 (serotype A). On the other hand, the function of Sre1 was found to be conserved in most serotypes. Furthermore, mating experiment of hob1Δ or sre1Δ showed dramatic defects in serotype A (H99) and D (XL280). It revealed that Hob1 and Sre1 related to mating ability in Cryptococcus species, especially cell fusion efficiency. In conclusion, HOB1 and SRE1 play crucial role in regulating sterol-homeostasis and differentiation in C. neoformans, moreover, Hob1 is specific gene in Cryptococcus neoformans. It suggests that Hob1 is considered as potent factor-targeted new safety antifungal drug.

Keywords: cryptococcus neoformans, Hob1, Sre1, sterol regulatory element binding proteins

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Authors: Nasrin Amirrajab, Yasaman Razavi Ghahfarokhi, Zahra Tootak, Maryam Hadian, Fatemeh Abooali Shamshiri

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Urinary tract infections (UTIs) have been reported in children with nephrotic syndrome. However, the only causes for the infection reported to date are bacteria, but not many prior reported occurrences of fungi or yeast as causative organisms. Hence, the present study aimed to describe the epidemiology of urinary tract fungal infections in a tertiary care pediatric. A single-center cross-sectional study was conducted at the nephrology ward of Aboozar Pediatric Hospital between March 21, 2021, and April 28, 2022. Urine was collected aseptically from children, inoculated onto culture media, and incubated at 37 °C for 18–48 hours. Yeast was identified following standard procedures. Antifungal susceptibility testing was determined by the disk diffusion method according to the CLSI guideline. Descriptive statistics and logistical regressions were used to estimate the crude ratio with a 95% confidence interval. P-value < 0.05 was considered significant. Among 68 individuals referred to the mycology lab, the result of direct examination and culture of all patients approved for C.albicans. Of these, 38 individuals (55.8%) were male, and 30 (44.2%) were female. The patients' age ranges were between one month and an 18-year-old. In the study of infection intensity, the patients were classified into three levels such as few (73.5%), moderate (20.6%), and many (5.9%). In the present study, all the patients were sensitive to Posaconazole. Also, the eagle effect was found in Amphotericin B, Voriconazole, and Fluconazole with frequencies of 91.7%, 91.7%, and 83%, respectively. In addition, just 8.3% of isolates were resistant to Itraconazole. It has not shown resistance in other mentioned medicine. The patients showed an intermediate response to Itraconazole (91.7%), Fluconazole (17%), Voriconazole (8.3%), and Amphotericin B (8.3%). There is a high prevalence of yeast infections in children with suspected UTIs. Also, boys are more likely to get yeast infections, and the severity of the infection is higher than girls. The present study demonstrated the importance of diagnosing and selecting the appropriate drug for urinary tract fungal infections in hospitalized children.

Keywords: urinary tract infections, children, fungal infections, yeast, antifungal susceptibility

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Authors: Grace McCambridge, Alanna Keady, Madhur Agrawal, Dequina Nicholas Alvarado, Barbara Nikolajczyk, Leena Panneerseelan-Bharath

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Age is a non-modifiable risk factor for the inflammation that underlies pathologies such as type 2 diabetes mellitus (T2DM). Inflammation, as indicated by circulating cytokines, rises in aging, but mechanisms that promote this ‘inflammaging’ remain poorly defined. Furthermore, downstream consequences of inflammaging, including the development of an inflammatory profile that predicts comorbidities like T2DM, remain speculative. We tested the possibility that natural aging-associated changes in autophagy, a process that is compromised in both aging and T2DM, regulates inflammatory profiles in older subjects. Our data showed that circulating CD4⁺ T cells from older compared to younger subjects have (i) defects in autophagy; (ii) higher mitochondria accumulation; (iii) a failure to metabolically shift from oxidative phosphorylation to anaerobic glycolysis upon αCD3/CD28 activation; (iv) more reactive oxygen species (ROS) accumulation; and (v) a cytokine profile that recapitulates the Th17 profile that predicts T2DM. ROS scavenging in cells from older subjects restored mitochondrial mass and membrane potential (indicators of improved autophagy) and reduced Th17 cytokines to amounts made by T cells from younger subjects. Knock-down of the autophagy protein Atg3 in T cells from younger subjects increased mitochondrial accumulation and Th17 cytokines. To begin translating these findings to clinical practice, we showed that physiological concentrations of the diabetes drug metformin (100 µM) added in vitro enhanced autophagy, prevented mitochondria and ROS accumulation, increased anaerobic glycolysis, and decreased Th17 cytokines in activated CD4⁺ T cells from older subjects. Metformin therefore improves autophagy and multiple downstream pro-inflammatory mechanisms CD4⁺ T cells from older subjects. We conclude that autophagy improvement ameliorates the development of a T2DM-predictive Th17 profile in aging, and thus holds promise for delay or prevention of aging-associated metabolic decline.

Keywords: autophagy, mitochondrial turnover, ROS, glycolysis

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Authors: Abdullah Faqihi, John Hedley

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Biosensors play a significant role in the healthcare sectors, scientific and technological progress. Developing electrodes that are easy to manufacture and deliver better electrochemical performance is advantageous for diagnostics and biosensing. They can be implemented extensively in various analytical tasks such as drug discovery, food safety, medical diagnostics, process controls, security and defence, in addition to environmental monitoring. Development of biosensors aims to create high-performance electrochemical electrodes for diagnostics and biosensing. A biosensor is a device that inspects the biological and chemical reactions generated by the biological sample. A biosensor carries out biological detection via a linked transducer and transmits the biological response into an electrical signal; stability, selectivity, and sensitivity are the dynamic and static characteristics that affect and dictate the quality and performance of biosensors. In this research, a developed experimental study for laser scribing technique for graphene oxide inside a vacuum chamber for processing of graphene oxide is presented. The processing of graphene oxide (GO) was achieved using the laser scribing technique. The effect of the laser scribing on the reduction of GO was investigated under two conditions: atmosphere and vacuum. GO solvent was coated onto a LightScribe DVD. The laser scribing technique was applied to reduce GO layers to generate rGO. The micro-details for the morphological structures of rGO and GO were visualised using scanning electron microscopy (SEM) and Raman spectroscopy so that they could be examined. The first electrode was a traditional graphene-based electrode model, made under normal atmospheric conditions, whereas the second model was a developed graphene electrode fabricated under a vacuum state using a vacuum chamber. The purpose was to control the vacuum conditions, such as the air pressure and the temperature during the fabrication process. The parameters to be assessed include the layer thickness and the continuous environment. Results presented show high accuracy and repeatability achieving low cost productivity.

Keywords: laser scribing, lightscribe DVD, graphene oxide, scanning electron microscopy

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Authors: Sohan Sengupta, Arnab Pramanik, Abhrajyoti Ghosh, Maitree Bhattacharyya

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Newly emerged phyto-pathogens and multi drug resistance have been threating the world for last few decades. Actinomycetes, the most endowed group of microorganisms isolated from unexplored regions of the world may be the ultimate solution to these problems. Thus the aim of this study was to isolate several bioactive actinomycetes strains capable of producing antimicrobial secondary metabolite from Sundarbans, the only mangrove tiger land of the world. Fifty four actinomycetes were isolated and analyzed for antimicrobial activity against fifteen test organisms including three phytopathogens. Nine morphologically distinct and biologically active isolates were subjected to polyphasic identification study. 16s rDNA sequencing indicated eight isolates to reveal maximum similarity to the genus streptomyces, whereas one isolate presented only 93.57% similarity with Streptomyces albogriseolus NRRL B-1305T. Seventy-one carbon sources and twenty-three chemical sources utilization assay revealed their metabolic relatedness. Among these nine isolates three specific strains were found to have notably higher degree of antimicrobial potential effective in a broader range including phyto-pathogenic fungus. PCR base whole genome screen for PKS and NRPS genes, confirmed the occurrence of bio-synthetic gene cluster in some of the isolates for novel antibiotic production. Finally the strain SMS_SU21, which showed antimicrobial activity with MIC value of 0.05 mg ml-1and antioxidant activity with IC50 value of 0.242±0.33 mg ml-1 was detected to be the most potential one. True prospective of this strain was evaluated utilizing GC-MS and the bioactive compound responsible for antimicrobial activity was purified and characterized. Rare bioactive actinomycetes were isolated from unexplored heritage site. Diversity of the biosynthetic gene cluster for antimicrobial compound production has also been evaluated. Antimicrobial compound SU21-C has been identified and purified which is active against a broad range of pathogens.

Keywords: actinomycetes, sundarbans, antimicrobial, pks nrps, phyto-pathogens, GC-MS

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Authors: Marina Arino Martin, John McEvoy, Eakalak Khan

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Endoxifen is an active metabolite responsible for the effectiveness of tamoxifen, a chemotherapeutic drug widely used for endocrine responsive breast cancer and chemo-preventive long-term treatment. Tamoxifen and endoxifen are not completely metabolized in human body and are actively excreted. As a result, they are released to the water environment via wastewater treatment plants (WWTPs). The presence of tamoxifen in the environment produces negative effects on aquatic lives due to its antiestrogenic activity. Because endoxifen is 30-100 times more potent than tamoxifen itself and also presents antiestrogenic activity, its presence in the water environment could result in even more toxic effects on aquatic lives compared to tamoxifen. Data on actual concentrations of endoxifen in the environment is limited due to recent discovery of endoxifen pharmaceutical activity. However, endoxifen has been detected in hospital and municipal wastewater effluents. The detection of endoxifen in wastewater effluents questions the treatment efficiency of WWTPs. Studies reporting information about endoxifen removal in WWTPs are also scarce. There was a study that used chlorination to eliminate endoxifen in wastewater. However, an inefficient degradation of endoxifen by chlorination and the production of hazardous disinfection by-products were observed. Therefore, there is a need to remove endoxifen from wastewater prior to chlorination in order to reduce the potential release of endoxifen into the environment and its possible effects. The aim of this research is to isolate and identify bacteria strain(s) capable of degrading endoxifen into less hazardous compound(s). For this purpose, bacteria strains from WWTPs were exposed to endoxifen as a sole carbon and nitrogen source for 40 days. Bacteria presenting positive growth were isolated and tested for endoxifen biodegradation. Endoxifen concentration and by-product formation were monitored. The Monod kinetic model was used to determine endoxifen biodegradation rate. Preliminary results of the study suggest that isolated bacteria from WWTPs are able to growth in presence of endoxifen as a sole carbon and nitrogen source. Ongoing work includes identification of these bacteria strains and by-product(s) of endoxifen biodegradation.

Keywords: biodegradation, bacterial degraders, endoxifen, wastewater

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Authors: Rolivhuwa Bishop Ramagoma1*, Lynn Cairncross1, , Saartjie Roux1

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According to the world health organisation, colon cancer is among the most common cancers diagnosed in both men and women. Specifically, it is the second leading cause of cancer related deaths accounting for over 860 000 deaths worldwide in 2018. Currently, chemotherapy has become an essential component of most cancer treatments. Despite progress in cancer drug development over the previous years, traditional chemotherapeutic drugs still have low selectivity for targeting tumour tissues and are frequently constrained by dose-limiting toxicity. The creation of nanoscale delivery vehicles capable of directly directing treatment into cancer cells has recently caught the interest of researchers. Herein, the development of peptide-functionalized polyethylene glycol gold nanoparticles (Peptide-PEG-AuNPs) as a cellular probe and delivery agent is described, with the higher aim to develop a specific diagnostic prototype and assess their specificity not only against cell lines but primary human cells as well. Gold nanoparticles (AuNPs) were synthesized and stabilized through chemical conjugation. The synthesized AuNPs were characterized, stability in physiological solutions was assessed, their cytotoxicity against colon carcinoma and non-carcinoma skin fibroblasts was also studied. Furthermore, genetic effect through real-time polymerase chain reaction (RT-PCR), localization and uptake, peptide specificity were also determined. In this study, different peptide-AuNPs were found to have preferential toxicity at higher concentrations, as revealed by cell viability assays, however, all AuNPs presented immaculate stability for over 3 months following the method of synthesis. The final obtained peptide-PEG-AuNP conjugates showed good biocompatibility in the presence of high ionic solutions and biological media and good cellular uptake. Formulation of colon cancer specific targeting peptide was successful, additionally, the genes/pathways affected by the treatments were determined through RT-PCR. Primary cells study is still on going with promising results thus far.

Keywords: nanotechnology, cancer, diagnosis, therapeutics, gold nanoparticles.

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Authors: Ben Main Piotr Ozieranski

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State government spending on pharmaceuticals stands at 1 trillion USD globally, promoting criticism of the pharmaceutical industry's monetization of drug efficacy, product cost overvaluation, and health injustice. This paper elucidates the mechanisms behind a state-institutional response to this problem through the sociological lens of the strategic relational approach to state power. To do so, 30 expert interviews, legal and policy documents are drawn on to explain how state elites in New Zealand have successfully contested a 30-year “pharmaceutical spending containment policy”. Proceeding from Jessop's notion of strategic “selectivity”, encompassing analyses of the enabling features of state actors' ability to harness state structures, a theoretical explanation is advanced. First, a strategic context is described that consists of dynamics around pharmaceutical dealmaking between the state bureaucracy, pharmaceutical pricing strategies (and their effects), and the industry. Centrally, the pricing strategy of "bundling" -deals for packages of drugs that combine older and newer patented products- reflect how state managers have instigated an “incentivization game” that is played by state and industry actors, including HTA professionals, over pharmaceutical products (both current and in development). Second, a protective context is described that is comprised of successive legislative-judicial responses to the strategic context and characterized by the regulation and the societalisation of commercial law. Third, within the policy, the achievement of increased pharmaceutical coverage (pharmaceutical “mix”) alongside contained spending is conceptualized as a state defence of a "social profit". As such, in contrast to scholarly expectations that political and economic cultures of neo-liberalism drive pharmaceutical policy-making processes, New Zealand's state elites' approach is shown to be antipathetic to neo-liberals within an overall capitalist economy. The paper contributes an analysis of state pricing strategies and how they are embedded in state regulatory structures. Additionally, through an analysis of the interconnections of state power and pharmaceutical value Abrahams's neo-liberal corporate bias model for pharmaceutical policy analysis is problematised.

Keywords: pharmaceutical governance, pharmaceutical bureaucracy, pricing strategies, state power, value theory

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Authors: Ammar Asma, Bouafia Nabiha, Ghammam Rim, Ezzi Olfa, Ben Cheikh Asma, Mahjoub Mohamed, Helali Radhia, Sma Nesrine, Chouchène Imed, Boussarsar Hamadi, Njah Mansour

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Background: Central venous catheter associated infections (CVC-AI) are among the serious hospital-acquired infections. The aims of this study are to determine the incidence of CVC-AI, and their risk factors among patients followed in a Tunisian medical intensive care unit (ICU). Materials / Methods: A prospective cohort study conducted between September 15th, 2015 and November 15th, 2016 in an 8-bed medical ICU including all patients admitted for more than 48h. CVC-AI were defined according to CDC of ATLANTA criteria. The enrollment was based on clinical and laboratory diagnosis of CVC-AI. For all subjects, age, sex, underlying diseases, SAPS II score, ICU length of stay, exposure to CVC (number of CVC placed, site of insertion and duration catheterization) were recorded. Risk factors were analyzed by conditional stepwise logistic regression. The p-value of < 0.05 was considered significant. Results: Among 192 eligible patients, 144 patients (75%) had a central venous catheter. Twenty-eight patients (19.4%) had developed CVC-AI with density rate incidence 20.02/1000 CVC-days. Among these infections, 60.7% (n=17) were systemic CVC-AI (with negative blood culture), and 35.7% (n=10) were bloodstream CVC-AI. The mean SAPS II of patients with CVC-AI was 32.76 14.48; their mean Charlson index was 1.77 1.55, their mean duration of catheterization was 15.46 10.81 days and the mean duration of one central line was 5.8+/-3.72 days. Gram-negative bacteria was determined in 53.5 % of CVC-AI (n= 15) dominated by multi-drug resistant Acinetobacter baumani (n=7). Staphylococci were isolated in 3 CVC-AI. Fourteen (50%) patients with CVC-AI died. Univariate analysis identified men (p=0.034), the referral from another hospital department (p=0.03), tobacco (p=0.006), duration of sedation (p=0.003) and the duration of catheterization (p=0), as possible risk factors of CVC-AI. Multivariate analysis showed that independent factors of CVC-AI were, male sex; OR= 5.73, IC 95% [2; 16.46], p=0.001, Ramsay score; OR= 1.57, IC 95% [1.036; 2.38], p=0.033, and duration of catheterization; OR=1.093, IC 95% [1.035; 1.15], p=0.001. Conclusion: In a monocenter cohort, CVC-AI had a high density and is associated with poor outcome. Identifying the risk factors is necessary to find solutions for this major health problem.

Keywords: central venous catheter associated infection, intensive care unit, prospective cohort studies, risk factors

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Authors: Simone F. Medeiros, Jessica M. Fonseca, Gizelda M. Alves, Danilo M. Santos, Sérgio P. Campana-Filho, Amilton M. Santos

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Stimuli responsive and biocompatible hydrogel nanoparticles have gained special attention as systems for potential applications in controlled release of drugs to improve their therapeutic efficacy while minimizing side effects. In this work, novel solid dispersions based on thermo- and pH-responsive poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate) hydrogel nanoparticles embedded in chitosan matrices were prepared via spray drying for controlled release of ketoprofen. Firstly, the hydrogel nanoparticles containing ketoprofen were prepared via precipitation polymerization and their stimuli-responsive behavior, thermal properties, chemical composition, encapsulation efficiency and morphology were characterized. Then, hydrogel nanoparticles with different particles size were embedded into chitosan matrices via spray-drying. Scanning electron microscopy (SEM) analyses were performed to investigate the particles size, dispersity and morphology. Finally, ketoprofen release profiles were studied as a function of pH and temperature. Chitosan/poly(NVCL-co-IA-co-EGDMA)-ketoprofen microparticles presented spherical shape, rough surface and pronounced agglomeration, indicating that hydrogels nanoparticles loaded with ketoprofen modified the surface of chitosan matrix. The maximum encapsulation efficiency of ketoprofen into hydrogel nanoparticles was 57.8% and the electrostatic interactions between amino groups from chitosan and carboxylic groups from hydrogel nanoparticles were able to control ketoprofen release. The hydrogel nanoparticles themselves were capable to retard the release of ketoprofen-loaded until 48h of in vitro release tests, while their incorporation into chitosan matrix achieved a maximum percentage of drug release of 45%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 10:7, and 69%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 5:2.

Keywords: hydrogel nanoparticles, poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate), chitosan, ketoprofen, spray-drying

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Authors: Adepeju Simon-Oke, Olatunji Odeyemi, Mobolanle Oniya

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Urinary tract infection has become the most common bacterial infections in humans, both at the community and hospital settings; it has been reported in all age groups and in both sexes. This study was carried out in order to determine and evaluate the prevalence, current drug susceptibility pattern of the isolated organisms and identify the associated risk factors of UTIs among the pregnant women in Akure, Ondo State, Nigeria. A cross-sectional study was conducted on the urine of pregnant women, and socio-demographic information of the women was collected. A total of 300 clean midstream urine samples were collected, and a general urine microscopic examination and culture were carried out, the Microbact identification system was used to identify gram-negative bacteria. Out of the 300 urine samples cultured, 183(61.0%) yielded significant growth of urinary pathogens while 117(39.0%) yielded either insignificant growth or no growth of any urinary pathogen. Prevalence of UTI was significantly associated with the type of toilet used, symptoms of UTI, and previous history of urinary tract infection (p<0.05). Escherichia coli 58(31.7%) was the dominant pathogen isolated, and the least isolated uropathogens were Citrobacter freudii and Providencia retgerri 2(1.1%) respectively. Gram-negative bacteria showed 77.6%, 67.9%, and 61.2% susceptibility to ciprofloxacin, augmentin, and chloramphenicol, respectively. Resistance against septrin, chloramphenicol, sparfloxacin, amoxicillin, augmentin, gentamycin, pefloxacin, trivid, and streptomycin was observed in the range of 23.1 to 70.1%. Gram-positive uropathogens isolated showed high resistance to amoxicillin (68.4%) and high susceptibility to the remaining nine antibiotics in the range 65.8% to 89.5%. This study justifies that pregnant women are at high risk of UTI. Therefore screening of pregnant women during antenatal clinics should be considered very important to avoid complications. Health education with regular antenatal and personal hygiene is recommended as precautionary measures to UTI.

Keywords: pregnant women, prevalence, risk factor, UTIs

Procedia PDF Downloads 147

Authors: Djebbar Atmani, Aghiles Karim Aissat, Nadjet Debbache-Benaida, Nassima Chaher-Bazizi, Dina Atmani-Kilani, Meriem Rahmani-Berboucha, Naima Saidene, Malika Benloukil, Lila Azib

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Medicinal plants are believed to be an important source for the discovery of potential antioxidant, anti-inflammatory and anti-diabetic substances. The present study was designed to investigate the neuroprotective, anti-inflammatory, anti-diabetic and anti-hyperuricemic potential of Pistacia lentiscus, as well as the identification of active compounds. The antioxidant potential of plant extracts against known radicals was measured using various standard in vitro methods. Anti-inflammatory activity was determined using the paw edema model in mice and by measuring the secretion of the pro-inflammatory cytokine, whereas the anti-diabetic effect was assessed in vivo on streptozotocin-induced diabetic rats and in vitro by inhibition of alpha-amylase. The anti-hyperuricemic activity was evaluated using the xanthine oxidase assay, whereas neuroprotective activity was investigated using an Aluminum-induced toxicity test. Pistacia lentiscus extracts and fractions exhibited high scavenging capacity against DPPH, NO. and ABTS+ radicals in a dose-dependent manner and restored blood glucose levels, in vivo, to normal values, in agreement with the in vitro anti-diabetic effect. Oral administration of plant extracts significantly decreased carrageenan-induced mice paw oedema, similar to the standard drug, diclofenac, was effective in reducing IL-1β levels in cell culture and induced a significant increase in urinary volume in mice, associated to a promising anti-hyperuricemic activity. Plant extracts showed good neuroprotection and restoration of cognitive functions in mice. HPLC-MS and NMR analyses allowed the identification of known and new phenolic compounds that could be responsible for the observed activities. Therefore, Pistacia lentiscus could be beneficial in the treatment of inflammatory conditions and diabetes complications and the enhancement of cognitive functions.

Keywords: Pistacia lentiscus, anti-inflammatory, antidiabetic, flavanols, neuroprotective

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Authors: S. Sreeja, Radhakrishnan R. Nair, Noble Gracious, Sreeja S. Nair, M. Radhakrishna Pillai

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Background: Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients though dose optimization is poorly managed. However, So far no study has been carried out on the South Indian kidney transplant patients. The objective of this study is to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Materials and Methods: Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of Tacrolimus were observed. All patients were on standard immunosuppressive regime of Tacrolimus-Mycophenolate mofetil along with steroids on a starting dose of Tac 0.1 mg/kg/day. CYP3A5 genotyping was performed by PCR followed with RFLP. Conformation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated generic analyzer. Results: A significant association was found between tacrolimus per dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1, *1/*3 and *3/*3 genotypes were detected in 5 (20 %), 5 (20 %) and 15 (60 %) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Concentration/Dose ratio in kidney transplant recipients. Significantly higher L/D was observed among non-expressors 9.483 ng/mL(4.5- 14.1) as compared with the expressors 5.154 ng/mL (4.42-6.5 ) of CYP3A5. Acute rejection episodes were significantly higher for CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40 % versus 20 % and 13 %, respectively ). The dose normalized TAC concentration (ng/ml/mg/kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. Conclusion: This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients and also shows that majority of our patients carry mutant allele A6986G in CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus for each patient.

Keywords: kidney transplant patients, CYP3A5 genotype, tacrolimus, RFLP

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Authors: Ahilya Singh, Brad Carte, Ramesh Subramani, William Aalbersberg

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A total of 37 actinomycete strains were purified from 25 Solomon Islands marine sediments using four different types of isolation media. Among them, 54% of the strains had obligate requirement of seawater for growth. The ethyl acetate extract of 100 ml fermentation product of each strain was screened for antimicrobial activity against multidrug resistant human pathogens and cytotoxic activity against brine shrimps. A total of 67% of the ethyl acetate extracts showed antimicrobial and/or cytotoxic activities. A strain F-1915 was selected for isolation and evaluation of bioactive compound(s) based on its bioactive properties and chemical profile analysis using the LC-MS. The strain F-1915 was identified to have 96% sequence similarity to Streptomyces violaceusniger on the basis of 16S rDNA sequences using BLAST analysis. The 16S rDNA revealed that the strain F-1915 is a new member of MAR4 clade of actinomycetes. The MAR4 clade is an interesting clade of actinomycetes known for the production of pharmaceutically important hybrid isoprenoid compounds. The ethyl acetate extract of the fermentation product of this strain was purified by silica gel column chromatography and afforded the isolation of one bioactive pure compound. Based on the 1D and 2D NMR spectral data of compound 1 it was identified as a new mono-brominated phenazinone, Marinophenazimycin A, a structure which has already been studied by external collaborators at Scripps Institution of Oceanography but is yet to be published. Compound 1 displayed significant antimicrobial activity against drug resistant human pathogens. The minimum inhibitory concentration (MIC) of compound 1 was against Methicillin Resistant Staphylococcus aureus (MRSA) was about 1.9 μg/ml and MIC recorded against Amphotericin Resistant Candida albicans (ARCA) was about 0.24 μg/ml. The bioactivity of compound 1 against ARCA was found to be better than the standard antifungal agent amphotericin B. Compound 1 however did not show any cytotoxic activity against brine shrimps.

Keywords: actinomycetes, antimicrobial activity, brominated phenazine, MAR4 clade, marine natural products, multidrug resistent, 1D and 2D NMR

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Authors: Anna M. N. Shifotoka, Richard Walker, Katie Haighton, Richard McNally

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An analysis of trends in Case Notification Rates (CNR) can be used to monitor the impact of Tuberculosis (TB) control interventions over time in order to inform the implementation of current and future TB interventions. A retrospective analysis of trends in TB CNR for two urban regions in Namibia, namely Khomas and Erongo regions, was conducted. TB case notification data were obtained from annual TB reports of the national TB programme, Ministry of Health and Social Services, covering the period from 1997 to 2015. Joinpoint regression was used to analyse trends in CNR for different types of TB groups. A trend was considered to be statistically significant when a p-value was less than 0.05. During the period under review, the crude CNR for all forms of TB declined from 808 to 400 per 100 000 population in Khomas, and from 1051 to 611 per 100 000 population in Erongo. In both regions, significant change points in trends were observed for all types of TB groups examined. In Khomas region, the trend for new smear positive pulmonary TB increased significantly by an annual rate of 4.1% (95% Confidence Interval (CI): 0.3% to 8.2%) during the period 1997 to 2004, and thereafter declined significantly by -6.2% (95%CI: -7.7% to -4.3%) per year until 2015. Similarly, the trend for smear negative pulmonary TB increased significantly by 23.7% (95%CI: 9.7 to 39.5) per year from 1997 to 2004 and thereafter declined significantly by an annual change of -26.4% (95%CI: -33.1% to -19.8%). The trend for all forms of TB CNR in Khomas region increased significantly by 8.1% (95%CI: 3.7 to 12.7) per year from 1997 to 2004 and thereafter declined significantly a rate of -8.7% (95%CI: -10.6 to -6.8). In Erongo region, the trend for smear positive pulmonary TB increased at a rate of 1.2% (95%CI: -1.2% to 3.6%) annually during the earlier years (1997 to 2008), and thereafter declined significantly by -9.3% (95%CI: -13.3% to -5.0%) per year from 2008 to 2015. Also in Erongo, the trend for all forms of TB CNR increased significantly by an annual rate of 4.0% (95%CI: 1.4% to 6.6%) during the years between 1997 to 2006 and thereafter declined significantly by -10.4% (95%CI: -12.7% to -8.0%) per year during 2006 to 2015. The trend for extra-pulmonary TB CNR declined but did not reach statistical significance in both regions. In conclusion, CNRs declined for all types of TB examined in both regions. Further research is needed to study trends for other TB dimensions such as treatment outcomes and notification of drug resistant TB cases.

Keywords: epidemiology, Namibia, temporal trends, tuberculosis

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Authors: Misty Attwood, Helgi Schioth

Abstract:

Transmembrane proteins are important components in many essential cell processes such as signal transduction, cell-cell signalling, transport of solutes, structural adhesion activities, and protein trafficking. Due to their involvement in diverse critical activities, transmembrane proteins are implicated in different disease pathways and hence are the focus of intense interest in understanding functional activities, their pathogenesis in disease, and their potential as pharmaceutical targets. Further, as the structure and function of proteins are correlated, investigating a group of proteins with the same tertiary structure, i.e., the same number of transmembrane regions, may give understanding about their functional roles and potential as therapeutic targets. In this in silico bioinformatics analysis, we identify and comprehensively characterize the previously unstudied group of proteins with five transmembrane-spanning regions (5TM). We classify nearly 60 5TM proteins in which 31 are members of ten families that contain two or more family members and all members are predicted to contain the 5TM architecture. Furthermore, nine singlet proteins that contain the 5TM architecture without paralogues detected in humans were also identifying, indicating the evolution of single unique proteins with the 5TM structure. Interestingly, more than half of these proteins function in localization activities through movement or tethering of cell components and more than one-third are involved in transport activities, particularly in the mitochondria. Surprisingly, no receptor activity was identified within this family in sharp contrast with other TM families. Three major 5TM families were identified and include the Tweety family, which are pore-forming subunits of the swelling-dependent volume regulated anion channel in astrocytes; the sidoreflexin family that acts as mitochondrial amino acid transporters; and the Yip1 domain family engaged in vesicle budding and intra-Golgi transport. About 30% of the proteins have enhanced expression in the brain, liver, or testis. Importantly, 60% of these proteins are identified as cancer prognostic markers, where they are associated with clinical outcomes of various tumour types, indicating further investigation into the function and expression of these proteins is important. This study provides the first comprehensive analysis of proteins with 5TM regions and provides details of the unique characteristics and application in pharmaceutical development.

Keywords: 5TM, cancer prognostic marker, drug targets, transmembrane protein

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Authors: Vaibhav D. Bhatt, Anju P. Kunjadia, D. S. Nauriyal, Bhumika J. Joshi, Chaitanya G. Joshi

Abstract:

Metagenomic analysis of milk samples collected from local cattle breed, kankrej (Bos indicus), Gir (Bos indicus) and Crossbred (Bos indicus X Bos taurus) cattle harbouring subclinical mastitis was carried out by next-generation sequencing (NGS) 454 GS-FLX technology. Around 56 different species including members of Enterobacteriales, Pseudomonadales, Bacillales and Lactobacillales with varying abundance were detected in infected milk. The interesting presence of bacteriophages against Staphylococcus aureus, Escherichia coli, Enterobacter and Yersinia species were observed, especially Enterobacteria and E. coli phages (0∙32%) in Kankrej, Enterobacteria and Staphylococcus phages (1∙05%) in Gir and Staphylococcus phages (2∙32%) in crossbred cattle. NGS findings suggest that phages may be involved in imparting natural resistance of the cattle against pathogens. Further infected milk samples were subjected for bacterial isolation. Fourteen different isolates were identified, and DNA was extracted. Genes (Tet-K, Msr-A, and Mec-A) providing antibiotic resistance to the bacteria were screened by Polymerase Chain Reaction and results were validated with traditional antibiotic assay. Total 3 bacteriophages were isolated from nearby environment of the cattle farm. The efficacy of phages was checked against multi-drug resistant bacteria, identified by PCR. In-vivo study was carried out for phage therapy in mammary glands of female rats “Wister albino”. Mammary glands were infused with MDR isolates for 3 consecutive days. Recovery was observed in infected rats after intramammary infusion of sterile phage suspension. From day 4th onwards, level of C-reactive protein was significant increases up to day 12th . However, significant reduction was observed between days 12th to 18th post treatment. Bacteriophages have significant potential as antibacterial agents and their ability to replicate exponentially within their hosts and their specificity, make them ideal candidates for more sustainable mastitis control.

Keywords: bacteriophages, c-reactive protein, mastitis, metagenomic analysis

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