Search results for: orphan drug production

Authors: Bounoua Nadia, Rebizi Mohamed Nadjib

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Chiral molecules in relation to particular biological roles are stereoselective. Enantiomers differ significantly in their biochemical responses in a biological environment. Despite the current advancement in drug discovery and pharmaceutical biotechnology, the chiral separation of some racemic mixtures continues to be one of the greatest challenges because the available techniques are too costly and time-consuming for the assessment of therapeutic drugs in the early stages of development worldwide. Various nanoparticles became one of the most investigated and explored nanotechnology-derived nanostructures, especially in chirality, where several studies are reported to improve the enantiomeric separation of different racemic mixtures. The production of surface-modified nanoparticles has contributed to these limitations in terms of sensitivity, accuracy, and enantioselectivity that can be optimized and therefore makes these surface-modified nanoparticles convenient for enantiomeric identification and separation.

Keywords: chirality, enantiomeric recognition, selectors, analysis, surface-modified nanoparticles

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Authors: Gail Louw, Helena Boshoff, Taeksun Song, Clifton Barry

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Drug resistance in Mycobacterium tuberculosis is primarily attributed to mutations in target genes. These mutations incur a fitness cost and result in bacterial generations that are less fit, which subsequently acquire compensatory mutations to restore fitness. We hypothesize that mutations in specific drug target genes influence bacterial metabolism and cellular function, which affects its ability to develop subsequent resistance to additional agents. We aim to determine whether the sequential acquisition of drug resistance and specific mutations in a well-defined clinical M. tuberculosis strain promotes or limits the development of additional resistance. In vitro mutants resistant to pretomanid, linezolid, moxifloxacin, rifampicin and kanamycin were generated from a pan-susceptible clinical strain from the Beijing lineage. The resistant phenotypes to the anti-TB agents were confirmed by the broth microdilution assay and genetic mutations were identified by targeted gene sequencing. Growth of mono-resistant mutants was done in enriched medium for 14 days to assess in vitro fitness. Double resistant mutants were generated against anti-TB drug combinations at concentrations 5x and 10x the minimum inhibitory concentration. Subsequently, mutation frequencies for these anti-TB drugs in the different mono-resistant backgrounds were determined. The initial level of resistance and the mutation frequencies observed for the mono-resistant mutants were comparable to those previously reported. Targeted gene sequencing revealed the presence of known and clinically relevant mutations in the mutants resistant to linezolid, rifampicin, kanamycin and moxifloxacin. Significant growth defects were observed for mutants grown under in vitro conditions compared to the sensitive progenitor. Mutation frequencies determination in the mono-resistant mutants revealed a significant increase in mutation frequency against rifampicin and kanamycin, but a significant decrease in mutation frequency against linezolid and sutezolid. This suggests that these mono-resistant mutants are more prone to develop resistance to rifampicin and kanamycin, but less prone to develop resistance against linezolid and sutezolid. Even though kanamycin and linezolid both inhibit protein synthesis, these compounds target different subunits of the ribosome, thereby leading to different outcomes in terms of fitness in the mutants with impaired cellular function. These observations showed that oxazolidinone treatment is instrumental in limiting the development of multi-drug resistance in M. tuberculosis in vitro.

Keywords: oxazolidinones, mutations, resistance, tuberculosis

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Authors: Bhumika Wadhwa, Fayaz Malik

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The serine/threonine protein kinase B (PKB) also known as Akt, is one of the multifaceted kinase in human kinome, existing in three isoforms. Akt plays a vital role in phosphoinositide 3-kinase (PI3K) mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. The functional significance of an individual isoform of Akt is not redundant in cancer cell proliferation and metastasis instead Akt isoforms play distinct roles during metastasis; thereby regulating EMT. This study aims to determine isoform specific functions of Akt in cancer. The results obtained suggest that Akt1 restrict tumor invasion, whereas Akt2 promotes cell migration and invasion by various techniques like MTT, wound healing and invasion assay. Similarly, qRT-PCR also revealed that Akt3 has shown promising results in promoting cancer cell migration. Contrary to pro-oncogenic properties attributed to Akt, it is to be understood how various isoforms of Akt compensates each other in the regulation of common pathways during cancer progression and drug resistance. In conclusion, this study aims to target selective isoforms which is essential to inhibit cancer. However, the question now is whether, and how much, Akt inhibition will be tolerated in the clinic remains to be answered and the experiments will have to address the question of which combinations of newly devised Akt isoform specific inhibitors exert a favourable therapeutic effect in in vivo models of cancer to provide the therapeutic window with minimal toxicity.

Keywords: Akt isoforms, cancer, drug resistance, epithelial mesenchymal transition

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Authors: Kwanputtha Arunprasert, Chaiyakarn Pornpitchanarong, Praneet Opanasopit, , Prasopchai Patrojanasophon

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Capsaicin, a recently FDA-approved drug for the topical treatment of neuropathic pain, is associated with several side effects like burning sensation and erythema leading to severe skin irritation and poor patient compliance. These unwanted side effects are due to the rapid penetration of capsaicin into the epidermis and low permeation to the dermis layer. The purpose of this study was to develop nanostructured lipid carriers (NLCs) that entrapped capsaicin for reducing dermal irritation. Solid lipid (glyceryl monostearate (GM), cetyl palmitate (CP), cetyl alcohol (COH), stearic acid (SA), and stearyl alcohol (SOH)) and surfactant (Tween®80, Tween®20, and Span®20) were varied to obtained optimal capsaicin-loaded NLCs. The formulation using CP as solid lipid and Tween®80 as a surfactant (F2) demonstrated the smallest size, excellent colloidal stability, and narrow range distribution of the particles as being analyzed using Zetasizer. The obtained capsaicin-loaded NLCs were then characterized by entrapment efficiency (EE) and loading capacity (LC). The release characteristics followed Higuchi kinetics, and the prolonged capsaicin release may result in the reduction in skin irritation. These results could demonstrate the potentials of capsaicinloaded lipid-based nanoparticles for topical drug delivery.

Keywords: capsaicin, lipid-based nanoparticles, nanostructured lipid carriers, topical drug delivery system

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Authors: Melkamu Tadesse Getachew

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Intelligent control systems have revolutionized biomedical engineering, advancing research and enhancing medical practice. This review paper examines the impact of intelligent control on various aspects of biomedical engineering. It analyzes how these systems enhance precision and accuracy in biomedical instrumentation, improving diagnostics, monitoring, and treatment. Integration challenges are addressed, and potential solutions are proposed. The paper also investigates the optimization of drug delivery systems through intelligent control. It explores how intelligent systems contribute to precise dosing, targeted drug release, and personalized medicine. Challenges related to controlled drug release and patient variability are discussed, along with potential avenues for overcoming them. The comparison of algorithms used in intelligent control systems in biomedical control is also reviewed. The implications of intelligent control in computational and systems biology are explored, showcasing how these systems enable enhanced analysis and prediction of complex biological processes. Challenges such as interpretability, human-machine interaction, and machine reliability are examined, along with potential solutions. Intelligent control in biomedical engineering also plays a crucial role in risk management during surgical operations. This section demonstrates how intelligent systems improve patient safety and surgical outcomes when integrated into surgical robots, augmented reality, and preoperative planning. The challenges associated with these implementations and potential solutions are discussed in detail. In summary, this review paper comprehensively explores the widespread impact of intelligent control on biomedical engineering, showing the future of human health issues promising. It discusses application areas, challenges, and potential solutions, highlighting the transformative potential of these systems in advancing research and improving medical practice.

Keywords: Intelligent control systems, biomedical instrumentation, drug delivery systems, robotic surgical instruments, Computational monitoring and modeling

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Authors: Stanley Ibuchukwu Onwukwe

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Most reservoir in mature oil fields are vulnerable to challenges of water and/or gas coning as the size of their oil column reduces due to long period of oil production. These often result to low oil production and excessive water and/or gas production. Since over 50 years of oil production in the Niger delta, it is apparent that most of the oil fields in the region have reached their mature stages, thereby susceptible to coning tendencies. As a result of these, a good number of wells have been shut-in and abandoned, with significant amount of oil left unproduced. Analysis of the movement of fluid contacts in the reservoir is a significant aspect of reservoir studies and can assist in the management of coning tendencies and production performance of reservoirs in a mature field. This study, therefore, seeks to evaluate the occurrence of coning through the movement of fluid contacts (GOC and OWC) and determine the critical rate for controlling coning tendencies in mature oil field. This study applies the principle of Nodal analysis to calibrate the thin oil column of a reservoir of a mature field, and was graphically evaluated using the Joshi’s equation of critical rate for gas-oil system and oil-water system respectively. A representative Proxy equation was developed and sensitivity analysis carried out to determine the trend of critical rate as the oil column is been depleted. The result shows the trend in the movement of the GOC and OWC, and the critical rate, beyond which will result in excessive water and gas production, resulting to decreasing oil production from the reservoir. This result of this study can be used as a first pass assessment in the development of mature oil field reservoirs anticipated to experience water and/or gas coning during production.

Keywords: coning, fluid contact movement, mature oil field, oil production

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Authors: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant

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Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.

Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment

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Authors: E. Al-Essa, R. Bello-Mendoza, D. G. Wareham

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Anaerobic batch experiments were conducted to investigate the effect of magnetite-supplementation (7 mM) on methane production from digested sludge undergoing two different microbial growth phases, namely fresh sludge (exponential growth phase) and degassed sludge (endogenous decay phase). Three different particle sizes were assessed: small (50 - 150 nm), medium (168 – 490 nm) and large (800 nm - 4.5 µm) particles. Results show that, in the case of the fresh sludge, magnetite significantly enhanced the methane production rate (up to 32%) and reduced the lag phase (by 15% - 41%) as compared to the control, regardless of the particle size used. However, the cumulative methane produced at the end of the incubation was comparable in all treatment and control bottles. In the case of the degassed sludge, only the medium-sized magnetite particles increased significantly the methane production rate (12% higher) as compared to the control. Small and large particles had little effect on the methane production rate but did result in an extended lag phase which led to significantly lower cumulative methane production at the end of the incubation period. These results suggest that magnetite produces a clear and positive effect on methane production only when an active and balanced microbial community is present in the anaerobic digester. It is concluded that, (i) the effect of magnetite particle size on increasing the methane production rate and reducing lag phase duration is strongly influenced by the initial metabolic state of the microbial consortium, and (ii) the particle size would positively affect the methane production if it is provided within the nanometer size range.

Keywords: anaerobic digestion, iron oxide, methanogenesis, nanoparticle

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Authors: Akwu N. A., Naidoo Y., Salau V. F., Olofinsan K. A.

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Grewia lasiocarpa E. Mey. ex Harv. (Malvaceae) is a Southern African medicinal plant indigenously used with other plants for birthing problems. The anti-diabetic properties of the hexane, chloroform, and methanol extracts of Grewia lasiocarpa stem bark were assessed using in vitro α-glucosidase enzyme inhibition assay. The predictive in silico drug-likeness and toxicity properties of the phytocompounds were conducted using the pKCSM, ADMElab, and SwissADME computer-aided online tools. The highest α-glucosidase percentage inhibition was observed in the hexane extract (86.76%, IC50= 0.24 mg/mL), followed by chloroform (63.08%, IC50= 4.87 mg/mL) and methanol (53.22%, IC50= 9.41 mg/mL); while acarbose, the standard anti-diabetic drug was (84.54%, IC50= 1.96 mg/mL). The α-glucosidase assay revealed that the hexane extract exhibited the strongest carbohydrate inhibiting capacity and is a better inhibitor than the standard reference drug-acarbose. The computational studies also affirm the results observed in the in vitroα-glucosidaseassay. Thus, the extracts of G. lasiocarpa may be considered a potential plant-sourced compound for treating type 2 diabetes mellitus. This is the first study on the anti-diabetic properties of Grewia lasiocarpa hexane, chloroform, and methanol extracts using in vitro and in silico models.

Keywords: grewia lasiocarpa, α-glucosidase inhibition, anti-diabetes, ADMET

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Authors: Germán Díaz Flórez, Carlos Alberto Olvera Olvera, Domingo José Gómez Meléndez, Francisco Eneldo López Monteagudo

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In recent decades, population growth has exerted great pressure on natural resources. Two of the most scarce and difficult to obtain resources, arable land, and water, are closely interrelated, to the satisfaction of the demand for food production. In Mexico, the agricultural sector uses more than 70% of water consumption. Therefore, maximize the efficiency of current production systems is inescapable. It is essential to utilize techniques and tools that will enable us to the significant savings of water, labor and fertilizer. In this study, we present a production module of hydroponic green forage (HGF), which is a viable alternative in the production of livestock feed in the semi-arid and arid zones. The equipment in addition to having a forage production module, has a climate and irrigation control system that operated with photovoltaics. The climate control, irrigation and power management is based on fuzzy control techniques. The fuzzy control provides an accurate method in the design of controllers for nonlinear dynamic physical phenomena such as temperature and humidity, besides other as lighting level, aeration and irrigation control using heuristic information. In this working, firstly refers to the production of the hydroponic green forage, suitable weather conditions and fertigation subsequently presents the design of the production module and the design of the controller. A simulation of the behavior of the production module and the end results of actual operation of the equipment are presented, demonstrating its easy design, flexibility, robustness and low cost that represents this equipment in the primary sector.

Keywords: fuzzy, climate control system, hydroponic green forage, forage production module

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Authors: Tunjo Perić, Franjo Bratić

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In this paper the goal programming methodology for solving multiple objective problem of the technological variants and production plan optimization has been applied. The optimization criteria are determined and the multiple objective linear programming model for solving a problem of the technological variants and production plan optimization is formed and solved. Then the obtained results are analysed. The obtained results point out to the possibility of efficient application of the goal programming methodology in solving the problem of the technological variants and production plan optimization. The paper points out on the advantages of the application of the goal programming methodolohy compare to the Surrogat Worth Trade-off method in solving this problem.

Keywords: goal programming, multi objective programming, production plan, SWT method, technological variants

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Authors: Ilaria Manca, Ilaria Manca, Francesca Pettinau, Ignazia Mocci, Elisabetta M. Usai, Barbara Pittau

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Lamotrigine is a phenyltriazine used in the treatment of epilepsy and bipolar disorder type I. The purpose of this study was to test and compare various solid forms of immediate release (IR) lamotrigine products, at different strenghts, in order to study their disaggregation and dissolution behavior. IR products are designed to release their active substance promptly after administration. Concentration of hydrochloric acid in gastric juice is about 0.1-0.001 M, so FDA (Food and Drug Administration) recommends, for lamotrigine regular tablets, dissolution tests in HCl 0.1 M.Toinvestigate the pH dependency of drug release in the entire gastrointestinal tract, we worked at two additional media with different pH values (4.5 and 6.8), that reflect conditions in it. To afford acceptable dissolution rates, tablets must disintegrate. Disaggregation of constituent particles increases the surface area and substantially increases the dissolution rate. For this reason availability of an active substance from tablets depends on its ability to disintegrate fast in dissolution media. pH of gastrointestinal fluid affects drug absorption by conditioning its solubility and dissolution, but also tablet disintegration may be influenced by it. To obtain information about the quantitative relationship between different mixture components, Nuclear Magnetic Resonance (NMR) spectroscopy was used. We also investigate tablet hardness. The investigation carried out confirms pH 1.2 as the ideal environment for the immediate availability of the active substance.

Keywords: dissolution, disaggregation, Lamotrigine, bioequivalence

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Authors: Hari Bezwada, Michelle Cheon, Ryan Divan, Hannah Escritor, Michelle Kagramian, Isha Korgaonkar, Maya MacAdams, Udgita Pamidigantam, Richard Pilny, Eleanor Race, Angadh Singh, Nathan Zhang, LeeAnn Nguyen, Fina Liotta

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Malaria is a deadly disease caused by the Plasmodium parasite, which continues to develop resistance to current antimalarial drugs. In this research project, the effectiveness of numerous thiazole derivatives was explored in inhibiting the PfPKG, a crucial part of the Plasmodium life cycle. This study involved the synthesis of six thiazole-derived amides to inhibit the PfPKG pathway. Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy were used to characterize these compounds. Furthermore, AutoDocking software was used to predict binding affinities of these thiazole-derived amides in silico. In silico, compound 6 exhibited the highest predicted binding affinity to PfPKG, while compound 5 had the lowest affinity. Compounds 1-4 displayed varying degrees of predicted binding affinity. In-vitro, it was found that compound 4 had the best percent inhibition, while compound 5 had the worst percent inhibition. Overall, all six compounds had weak inhibition (approximately 30-39% at 10 μM), but these results provide a foundation for future drug discovery experiments.

Keywords: Medicinal Chemistry, Malaria, drug discovery, PfPKG, Thiazole, Plasmodium

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Authors: Armin Shirbazo, Mohammad Vahab, Hamed Lamei Ramandi, Jalal Fahimpour

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One of the most effective ways for increasing production in wells that are faced with problems such as pressure depletion and low rate is hydraulic fracturing. Hydraulic fracturing is creating a high permeable path through the reservoir and simulated area around the wellbore. This is very important for low permeability reservoirs, which their production is uneconomical. In this study, the influence of the fracturing pattern in multi-stage fractured horizontal wells is analyzed for a tight, heavy oil reservoir to explore the impact of fracturing patterns on improving oil recovery. The horizontal well has five transverse fractures with the same fracture length, width, height, and conductivity properties. The fracture patterns are divided into four distinct shapes: uniform shape, diamond shape, U shape, and W shape. The results show that different fracturing patterns produce various cumulative production after ten years, and the best pattern can be selected based on the most cumulative production. The result also illustrates that optimum design in fracturing can boost the production up to 3% through the permeability distribution around the wellbore and reservoir.

Keywords: multi-stage fracturing, horizontal well, fracture patterns, fracture length, number of stages

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Authors: Chaimongkol Limpianchob

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This work addresses the problem of production planning that arises in the production of aromatic coconuts from Samudsakhorn province in Thailand. The planning involves the forwarding of aromatic coconuts from the harvest areas to the factory, which is classified into two groups; self-owned areas and contracted areas, the decisions of aromatic coconuts flow in the plant, and addressing a question of which warehouse will be in use. The problem is formulated as a mixed-integer linear programming model within supply chain management framework. The objective function seeks to minimize the total cost including the harvesting, labor and inventory costs. Constraints on the system include the production activities in the company and demand requirements. Numerical results are presented to demonstrate the feasibility of coconuts supply chain model compared with base case.

Keywords: aromatic coconut, supply chain management, production planning, mixed-integer linear programming

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Authors: A. V. Shrirao, N. I. Kochar, A. V. Chandewar

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The flower extract of Butea monosperma herb has been used traditionally in India for medicinal purposes. The plant has been reported to treat hyperglycemia and associated hyperlipidemia. Hyperlipidemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. The present work was undertaken to investigate the possible antihyperlipidemic and antioxidative effect of Butea monosperma flowers on hyperlipidemic rats. Hyperlipidemia was induced in rats by a single intraperitonial (i.p.) injection of Triton WR 1339 (400 mg/kg) and it showed sustained elevated levels of serum cholesterol and triglyceride. Ethanolic extract of Butea monosperma flowers (Et-BM) (250 and 500 mg/kg/day) was administered to normal and hyperlipidemic rats for 14 days. Serum and liver tissue were analyzed at three different time intervals for lipid profile and antioxidants enzymes and the activity were compared to the cholesterol-lowering drug, Atorvastatin (10 mg/kg). Parameters were altered during hyperlipidemia and reverted back to near normal values after Et-BM treatment or standard drug Atorvastatin. Lipid peroxidation decreased whereas the activities of superoxide dismutase, glutathione peroxidase and catalase increased in Et-BM treated rats. Pronounced changes were observed at 500 mg/kg of Et-BM for 2 weeks and it was comparable to the standard drug Atorvastatin. The current study provides strong evidence that Et-BM has a remarkable beneficial effect in treating hyperlipidemia and ROS without any side effects at the dosage and duration studied.

Keywords: antioxidant, butea monopserma, hyperlipidemia, triton WR 1339

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Authors: Geetakshi Arora, Danish Malhotra

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Diabetic wounds are serious health issues and often fail to heal, leading to limb amputation that makes the life of the patient miserable. Delayed wound healing has been characterized by an increase in matrix metalloproteinase-9 (MMP-9). Thus research throughout the world has been going on to develop selective MMP-9 inhibitors for aiding diabetic wound healing. Bioactive constituents from natural sources always served as potential leads in drug development with high rates of success. Considering the need for novel selective MMP-9 inhibitors and the importance of natural bioactive compounds in drug development, we have screened a library of bioactive constituents from plant sources that were effective in diabetic wound healing on human MMP-9 (hMMP-9) using molecular docking studies. Screened constituents are ranked according to their dock score, ∆G value (binding affinity), and Ligand efficiency evaluated from FleXX docking and Hyde scoring modules available with drug designing platform LeadIT. Rhamnocitrin showed the highest correlation between dock score, ∆G value (binding affinity), and Ligand efficiency was further explored for binding interactions with hMMP-9. The overall study suggest that Rhamnocitrin is sufficiently decorated with both hydrophilic and hydrophobic substitutions that perfectly block hMMP-9 and act as a potential lead in the design and development of selective hMMP-9 inhibitors.

Keywords: MMP-9, diabetic wound, molecular docking, phytoconstituents

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Authors: Mengying Wang, Xiaohui Wang, Chun Deng, Bei Liu, Changyu Sun, Guangjin Chen, Mahmoud El-Halwagi

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Significant amounts of natural gas hydrates (NGHs) are considered potential new sustainable energy resources in the future. However, common used methods for methane gas recovery from hydrate sediments require high investment but with low gas production efficiency, and may cause potential environment and security problems. Therefore, there is a need for effective gas production from hydrates. The natural gas hydrate production method by CO₂/H₂ replacement coupling steam methane reforming can improve the replacement effect and reduce the cost of gas separation. This paper develops a simulation model of the gas production process integrated with steam reforming and membrane separation. The process parameters (i.e., reactor temperature, pressure, H₂O/CH₄ ratio) and the composition of CO₂ and H₂ in the feed gas are analyzed. Energy analysis is also conducted. Two design scenarios with different composition of CO₂ and H₂ in the feed gas are proposed and evaluated to assess the energy efficiency of the novel system. Results show that when the composition of CO₂ in the feed gas is between 43 % and 72 %, there is a certain composition that can meet the requirement that the flow rate of recycled gas is equal to that of feed gas, so as to ensure that the subsequent production process does not need to add feed gas or discharge recycled gas. The energy efficiency of the CO₂ in feed gas at 43 % and 72 % is greater than 1, and the energy efficiency is relatively higher when the CO₂ mole fraction in feed gas is 72 %.

Keywords: Gas production, hydrate, process integration, steam reforming

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Authors: Nihar Ranjan, Derrick Watkins, Dev P. Arya

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Current methods in the study of antibiotic activity of ribosome targeted antibiotics are dependent on cell based bacterial inhibition assays or various forms of ribosomal binding assays. These assays are typically independent of each other and little direct correlation between the ribosomal binding and bacterial inhibition is established with the complementary assay. We have developed novel high-throughput capable assays for ribosome targeted drug discovery. One such assay examines the compounds ability to bind to a model ribosomal RNA A-site. We have also coupled this assay to other functional orthogonal assays. Such analysis can provide valuable understanding of the relationships between two complementary drug screening methods and could be used as standard analysis to correlate the affinity of a compound for its target and the effect the compound has on a cell.

Keywords: bacterial resistance, aminoglycosides, screening, drugs

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Authors: Arragaw Alemayehu, Woldeamlak Bewket

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The aim of this study was to understand the influence of current climate variability on crop production in the central highlands of Ethiopia. We used monthly rainfall and temperature data from 132 points each representing a pixel of 10×10 km. The data are reconstructions based on station records and meteorological satellite observations. Production data of the five major crops in the area were collected from the Central Statistical Agency for the period 2004-2013 and for the main cropping season, locally known as Meher. The production data are at the Enumeration Area (EA ) level and hence the best available dataset on crop production. The results show statistically significant decreasing trends in March–May (Belg) rainfall in the area. However, June – September (Kiremt) rainfall showed increasing trends in Efratana Gidim and Menz Gera Meder which the latter is statistically significant. Annual rainfall also showed positive trends in the area except Basona Werana where significant negative trends were observed. On the other hand, maximum and minimum temperatures showed warming trends in the study area. Correlation results have shown that crop production and area of cultivation have positive correlation with rainfall, and negative with temperature. When the trends in crop production are investigated, most crops showed negative trends and below average production was observed. Regression results have shown that rainfall was the most important determinant of crop production in the area. It is concluded that current climate variability has a significant influence on crop production in the area and any unfavorable change in the local climate in the future will have serious implications for household level food security. Efforts to adapt to the ongoing climate change should begin from tackling the current climate variability and take a climate risk management approach.

Keywords: central highlands, climate variability, crop production, Ethiopia, regression, trend

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Authors: Jwan J. Abdullah, Greetham Darren, Gregory A, Tucker, Chenyu Du

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Solid-state fermentation (SSF) is an alternative to liquid fermentations for the production of commercially important products such as antibiotics, single cell proteins, enzymes, organic acids, or biofuels from lignocellulosic material. This paper describes the optimisation of SSF on municipal solid waste (MSW) for the production of cellulase enzyme. Production of cellulase enzymes was optimised by Trichoderma reesei or Aspergillus niger for temperature, moisture content, inoculation, and period of incubation. Also, presence of minerals, and alternative carbon and nitrogen sources. Optimisation revealed that production of cellulolytic enzymes was optimal when using Trichoderma spp at 30°C with an incubation period of 168 hours with a 60% moisture content. Crude enzymes produced from MSW, by Trichoderma were evaluated for the saccharification of MSW and compared with activity of a commercially available enzyme, results demonstrated that MSW can be used as inexpensive lignocellulosic material for the production of cellulase enzymes using Trichoderma reesei.

Keywords: SSF, enzyme hydrolysis, municipal solid waste (MSW), optimizing conditions, enzyme hydrolysis

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Authors: Matej Buzgo, Erico Himawan, Ksenija JašIna, Aiva Simaite

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Electrospinning is a versatile and efficient technology for producing nanofibers for biomedical applications. One of the most common polymers used for the preparation of nanofibers for regenerative medicine and drug delivery applications is polycaprolactone (PCL). PCL is a biocompatible and bioabsorbable material that can be used to stimulate the regeneration of various tissues. It is also a common material used for the development of drug delivery systems by blending the polymer with small active molecules. However, for many drug delivery applications, e.g. cancer immunotherapy, PCL biodegradation rate that may exceed 9 months is too long, and faster nanofiber dissolution is needed. In this paper, we investigate the dissolution and small molecule release rates of PCL blends with two hydrophilic polymers: polyethylene oxide (PEO) or polyvinylpyrrolidone (PVP). We show that adding hydrophilic polymer to the PCL reduces the water contact angle, increases the dissolution rate, and strengthens the interactions between the hydrophilic drug and polymer matrix that further sustain its release. Finally using this method, we were also able to increase the nanofiber degradation rate when PCL-PEO and PCL-PVP were used as a shell in the electrospun core-shell nanofibers and spread up the release of active proteins from their core. Electrospinning can be used for the preparation of the core-shell nanofibers, where active ingredients are encapsulated in the core and their release rate is regulated by the shell. However, such fibers are usually prepared by coaxial electrospinning that is an extremely low-throughput technique. An alternative is emulsion electrospinning that could be upscaled using needleless blades. In this work, we investigate the possibility of using emulsion electrospinning for encapsulation and sustained release of the growth factors for the development of the organotypic skin models. The core-shell nanofibers were prepared using the optimized formulation and the release rate of proteins from the fibers was investigated for 2 weeks – typical cell culture conditions.

Keywords: electrospinning, polycaprolactone (PCL), polyethylene oxide (PEO), polyvinylpyrrolidone (PVP)

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Authors: R. M. Noah, N. M. Nasir, M. R. Jais, M. S. S. Wahab, M. H. Abdullah, A. S. S. Raj

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Infectious diseases are getting more difficult to treat due to the resistant strains of bacteria. Current generations of antibiotics are most likely ineffective against multi-drug resistant strains bacteria. Thus, there is an urgent need in search of natural antibiotics in particular from medicinal plants. One of the common medicinal plants, Melaleuca cajuputi, has been reported to possess antibacterial properties. The study was conducted to evaluate and justify the presence of antibacterial activity of Melaleuca cajuputi essential oil (EO) against the multi-drug resistant bacteria. Clinical isolates obtained from the teaching hospital were re-assessed to confirm the exact identity of the bacteria to be tested, namely methicillin-resistant staphylococcus aureus (MRSA), carbapenem-resistant enterobacteriaceae (CRE), and extended-spectrum beta-lactamases producer (ESBLs). A well diffusion method was done to observe the inhibition zones of the essential oil against the bacteria. Minimum inhibitory concentration (MIC) was determined using the microdilution method in 96-well flat microplate. The absorbance was measured using a microplate reader. Minimum bactericidal concentration (MBC) was performed using the agar medium method. The zones of inhibition produced by the EO against MRSA, CRE, and ESBL were comparable to that of generic antibiotics used, gentamicin and augmentin. The MIC and MBC results highlighted the antimicrobial efficacy of the EO. The outcome of this study indicated that the EO of Melaleuca cajuputi had antibacterial activity on the multi-drug resistant bacteria. This finding was eventually substantiated by electron microscopy work.

Keywords: melaleuca cajuputi, antibacterial, resistant bacteria, essential oil

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Authors: Smruti Mahapatra, Dipankar Biswas, Richard Um, Michael Meggyesy, Riccardo Serra, Noah Gorelick, Steven Marra, Amir Manbachi, Mark G. Luciano

Abstract:

Intracranial pressure (ICP) is profoundly regulated by the effects of cardiac pulsation and the volume of the incoming blood. Furthermore, these effects on ICP are incremented by the presence of a rigid skull that does not allow for changes in total volume during the cardiac cycle. These factors play a pivotal role in cerebrospinal fluid (CSF) dynamics and distribution, with consequences that are not well understood to this date and that may have a deep effect on the Central Nervous System (CNS) functioning. We designed this study with two specific aims: (a) To study how pulsatility influences local CSF flow, and (b) To study how modulating intracranial pressure affects drug distribution throughout the SAS globally. In order to achieve these aims, we built an elaborate in-vitro model of the SAS closely mimicking the dimensions and flow rates of physiological systems. To modulate intracranial pressure, we used an intracranially implanted, cardiac-gated, volume-oscillating balloon (CADENCE device). Commercially available dye was used to visualize changes in CSF flow. We first implemented two control cases, seeing how the tracer behaves in the presence of pulsations from the brain phantom and the balloon individually. After establishing the controls, we tested 2 cases, having the brain and the balloon pulsate together in sync and out of sync. We then analyzed the distribution area using image processing software. The in-sync case produced a significant increase, 5x times, in the tracer distribution area relative to the out-of-sync case. Assuming that the tracer fluid would mimic blood flow movement, a drug introduced in the SAS with such a system in place would enhance drug distribution and increase the bioavailability of therapeutic drugs to a wider spectrum of brain tissue.

Keywords: blood-brain barrier, cardiac-gated, cerebrospinal fluid, drug delivery, neurosurgery

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Authors: Peter Yamoah, Frasia Oosthuizen

Abstract:

Introduction: Reporting of Adverse Events Following Immunization continues to be a challenge. Pharmacovigilance centers throughout the world are mandated by the WHO to submit AEFI reports from various countries to a large pool of adverse drug reaction electronic database called Vigibase. Despite the relevant information of AEFI in Vigibase, it is unavailable to the general public. However, the WHO has an alternative website called VigiAccess which is an open access website serving as a repository of reported adverse drug reactions and AEFIs. The aim of the study was to ascertain the reporting pattern of a number of commonly used vaccines in VigiAccess. Methods: VigiAccess was thoroughly searched on the 5th of February 2018 for AEFI reports of measles vaccine, oral polio vaccine (OPV), yellow fever vaccine, pneumococcal vaccine, rotavirus vaccine, meningococcal vaccine, tetanus vaccine and tuberculosis (BCG) vaccine. These were reports from all pharmacovigilance centers in the world from the time they joined the WHO drug monitoring program. Results: After a thorough search in VigiAccess, there were 9,062 measles vaccine AEFIs, 185,829 OPV AEFIs, 24,577 yellow fever vaccine AEFIs, 317,208 pneumococcal vaccine AEFIs, 73,513 rotavirus vaccine AEFIs, 145,447 meningococcal vaccine AEFIs, 22,781 tetanus vaccine AEFIs and 35,556 BCG vaccine AEFIs. Conclusion: The study revealed that out of the eight vaccines studied, pneumococcal vaccines are associated with the highest number of AEFIs whilst measles vaccines were associated with the least AEFIs.

Keywords: vaccines, adverse reactions, VigiAccess, adverse event reporting

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Authors: Noora Al Muftah, Reda Rawi, Richard Thompson, Halima Bensmail

Abstract:

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. There is an urgent need to identify biomarkers that predict which patients with are most likely to respond to treatment. Systematic efforts to correlate tumor mutational data with biologic dependencies may facilitate the translation of somatic mutation catalogs into meaningful biomarkers for patient stratification. To identify genomic features associated with drug sensitivity and uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we have screened and integrated a panel of several hundred cancer cell lines from different databases, mutation, DNA copy number, and gene expression data for hundreds of cell lines with their responses to targeted and cytotoxic therapies with drugs under clinical and preclinical investigation. We found mutated cancer genes were associated with cellular response to most currently available Glioma cancer drugs and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Keywords: cancer, gene network, Lasso, penalized regression, P-values, unbiased estimator

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Authors: Abdelatif Gadoum, Djilali Benyoucef, Mouloudj Hadj, Alla Eddine Toubal Maamar, Mohamed Habib Allah Lahoual

Abstract:

Hydrogen occurs naturally in the form of chemical compounds, most often in water and hydrocarbons. The main objective of this study is 2D modeling of hydrogen production in inductively coupled plasma in methane at low pressure. In the present model, we include the motions and the collisions of both neutral and charged particles by considering 19 species (i.e in total ; neutrals, radicals, ions, and electrons), and more than 120 reactions (electron impact with methane, neutral-neutral, neutral-ions and surface reactions). The results show that the rate conversion of methane reach 90% and the hydrogen production is about 30%.

Keywords: hydrogen production, inductively coupled plasma, fluid model, methane plasma

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Authors: Hanife Merve Öztürk, Sıdıka Dalgan

Abstract:

In this project, a capacity analysis study is done at TAT A. Ş. Maret Plant. Production capacity of products which generate 80% of sales amount are determined. Obtained data entered the LEKIN Scheduling Program and we get production schedules by using heuristic methods. Besides heuristic methods, as mathematical model, disjunctive programming formulation is adapted to flexible job shop problems by adding a new constraint to find optimal schedule solution.

Keywords: scheduling, flexible job shop problem, shifting bottleneck heuristic, mathematical modelling

Procedia PDF Downloads 401

Authors: Ikrima Zaleda Zia, Devi Fitri Kumalasari, Rosita Khusna, Farah Hidayati, Ilham Fajrul Haq, Amin Yusuf Efendi

Abstract:

Fertilizer is one of the production factors that are important to agriculture. Fertilizers contribution to the agricultural sector improvement is quite high. Fertilizers scarcity on the society are giving effect to agricultural sector, that is decreasing farmers production. Through a system called Kemal Propuri, society will be taught how to be independent, especially in terms of supplying the fertilizer and how to earn extra income besides of relying on the agriculture production. This research aims to determine implementation measures of Kemal Propuri in realizing farmers independence. This research was designed to use descriptive research with a qualitative approach. In this case, writers are trying to make an illustration of the increasing role of KUD (rural unit cooperative) through Kemal Propuri system (Independence System Through Individual Fertilizer Production) towards farmer independence. It can be concluded that Kemal Propuri system can contribute in order to achieve farmers independence. Independence fertilizer production will overcome farmers dependence of the subsidized fertilizer from the government.

Keywords: Kemal Propuri, KUD (Rural Unit Cooperative), independence farmers, fertilizer production

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Authors: Rajesh S. Mony, Vaidyaratnam Oushadhasala

Abstract:

An attempt is made in this study to evolve a drug development modality based on classical Ayurvedic knowledge base as well as on modern scientific methodology. The present study involves (a) identification of a specific ailment condition, (b) the selection of a polyherbal formulation, (c) deciding suitable extraction procedure, (d) confirming the efficacy of the combination by in-vitro trials and (e) fixing up the recommended dose. The ailment segment selected is arthritic condition. The selected herbal combination is Kunturushka, Vibhitaki, Guggulu, Haridra, Maricha and Nirgundi. They were selected as per Classical Ayurvedic references, Authentified as per API (Ayurvedic Pharmacopeia of India), Extraction of each drug was done by different ratios of Hydroalcoholic menstrums, Invitro assessment of each extract after removing residual solvent for anti-Inflammatory, anti-arthritic activities (by UV-Vis. Spectrophotometer with positive control), Invitro assessment of each extract for COX enzyme inhibition (by UV-Vis. Spectrophotometer with positive control), Selection of the extracts was made having good in-vitro activity, Performed the QC testing of each selected extract including HPTLC, that is the in process QC specifications, h. Decision of the single dose with mixtures of selected extracts was made as per the level of in-vitro activity and available toxicology data, Quantification of major groups like Phenolics, Flavonoids, Alkaloids and Bitters was done with both standard Spectrophotometric and Gravimetric methods, Method for Marker assay was developed and validated by HPTLC and a good resolved HPTLC finger print was developed for the single dosage API (Active Pharmaceutical Ingredient mixture of extracts), Three batches was prepared to fix the in process and API (Active Pharmaceutical Ingredient) QC specifications.

Keywords: drug development, antiinflammatory, quality stardardisation, planar chromatography

Procedia PDF Downloads 99