Search results for: kinetic inhibitors

Authors: Reem Al-Shidhani, Isabelle S. R. Storer, Michael J. Bromley, Lydia Tabernero

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Invasive fungal diseases are an increasing global health concern that contributes to the high mortality rates in immunocompromised patients. The rising of antifungal resistance severely lowers the efficacy of the limited antifungal agents available. New antifungal drugs that target new mechanisms are necessary to tackle the current shortfalls. Amongst post- modifications, phosphorylation is a predominant and an outstanding protein alteration in all eukaryotes. In fungi, protein phosphorylation plays a vital role in many signal transduction pathways, including cell cycle, cell growth, metabolism, transcription, differentiation, proliferation, and virulence. The investigation of Aspergillus fumigatus phosphatases revealed seven genes essential for viability. Inhibiting one of these phosphatases is a new interesting route to develop novel antifungal drugs. In this study, we carried out an early drug discovery process targeting oneessential phosphatase, GlcA. Here, we report the identification of new GlcA inhibitors that show antifungal activity. These important finding open a new avenue to the development of novel antifungals to expand the current narrow arsenal of clinical candidates.

Keywords: invasive fungal diseases, phosphatases, GlcA, competitive inhibitors

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Authors: C. Iitake, K. Iitake

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Background and Aims: The number of diabetic patients based on obesity is increasing drastically in Asia. Since most patients have multiple complications, if one medicine can treat those at the same time, it would contribute to financial savings and patients’ compliance. A Japanese-made DPP-4 inhibitor, Anagliptin is only sold in Japan and South Korea. It is said to have its unique aspect of lowering LDL-cholesterol (LDL-C) levels together with lowering blood glucose. We have assessed 63 patients in our faculty to investigate this fact clinically and statistically. Method: Patients with type 2 diabetes who has been treated with Anagliptin for the first time was investigated changes in HbA1c, fasting and random blood glucose and LDL-C levels from the baseline at 1 month, 6 months and 1 year. Results: 29 patients (46.1%) were given DPP-4 inhibitors for the first time (original group), and 34 patients (53.9%) were using other DPP-4 inhibitors before Anagliptin (exchanged group). The change in HbA1c and fasting glucose from the baseline were -2.0% (P < 0.001) and -38.3mg/dl (P < 0.01) respectively with original group, -0.5% (P < 0.01) and -29.4mg/dl (P < 0.01) respectively with exchanged group. 23 patients (36.5%) were using statins or fibrates and 28 patients (44.4%) were using none, and its LDL-C change were -8.1mg/dl (P = 0.2582) and -10.1mg/dl(P < 0.05) respectively. 16 patients(25%) with LDL-C level ≥ 140mg/dl, change were -21.7mg/dl(P < 0.05). LDL-C change did not have a correlation coefficient (=-0.03238) with change in HbA1c and was not affected by other diabetic drugs. Conclusion: These findings indicate that Anagliptin is a potential treatment option for type 2 diabetes complicated by hyperlipidemia.

Keywords: DPP-4 inhibitors, anagliptin, LDL-cholesterol, type 2 diabetes

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Authors: Alireza Bahramian

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High-purity TiO₂ nanoparticles (NPs) with size ranging between 50 nm and 100 nm are synthesized from titanium slag through sulphate route under sonochemical procedure. The effect of dissolution parameters such as the sulfuric acid/slag weight ratio, caustic soda concentration, digestion temperature and time, and initial particle size of the dried slag on the extraction efficiency of TiO₂ and removal of iron are examined. By optimizing the digestion conditions, a rutile TiO₂ powder with surface area of 42 m²/g and mean pore diameter of 22.4 nm were prepared. A thermo-kinetic analysis showed that the digestion temperature has an important effect, while the acid/slag weight ratio and initial size of the slag has a moderate effect on the dissolution rate. The shrinking-core model including both chemical surface reaction and surface diffusion is used to describe the leaching process. A low value of activation energy, 38.12 kJ/mol, indicates the surface chemical reaction model is a rate-controlling step. The kinetic analysis suggested a first order reaction mechanism with respect to the acid concentrations.

Keywords: TiO₂ nanoparticles, titanium slag, dissolution rate, sonochemical method, thermo-kinetic study

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Authors: Rhoda Afriyie Mensah, Lin Jiang, Solomon Asante-Okyere, Xu Qiang, Cong Jin

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Flammability analysis of extruded polystyrene (XPS) has become crucial due to its utilization as insulation material for energy efficient buildings. Using the Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa methods, the degradation kinetics of two pure XPS from the local market, red and grey ones, were obtained from the results of thermogravity analysis (TG) and microscale combustion calorimetry (MCC) experiments performed under the same heating rates. From the experiments, it was discovered that red XPS released more heat than grey XPS and both materials showed two mass loss stages. Consequently, the kinetic parameters for red XPS were higher than grey XPS. A comparative evaluation of activation energies from MCC and TG showed an insignificant degree of deviation signifying an equivalent apparent activation energy from both methods. However, different activation energy profiles as a result of the different chemical pathways were presented when the dependencies of the activation energies on extent of conversion for TG and MCC were compared.

Keywords: flammability, microscale combustion calorimetry, thermogravity analysis, thermal degradation, kinetic analysis

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Authors: Aid Asma, Dahdouh Nadjib, Amokrane Samira, Ladjali Samir, Nibou Djamel

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The present work has for main objective the elimination of the textile dye Maxilon Red (MR) by two processes, adsorption on activated clay followed by photocatalysis in presence of ZnO as a photocatalyst. The influence of the physical parameters like the initial pH, adsorbent dose of the activated clay, the MR concentration and temperature has been studied. The best adsorption yield occurs at neutral pH ~ 7 within 60 min with an uptake percentage of 97% for a concentration of 25 mg L⁻¹ and a dose of 0.5 g L⁻¹. The adsorption data were suitably fitted by the Langmuir model with a maximum capacity of 176 mg g⁻¹. The MR adsorption is well described by the pseudo second order kinetic. The second part of this work was dedicated to the photocatalytic degradation onto ZnO under solar irradiation of the residual MR concentration, remained after adsorption. The effect of ZnO dose and MR concentration has also been investigated. The parametric study showed that the elimination is very effective by this process, based essentially on the in situ generation of free radicals *OH which are non-selective and very reactive. The photodegradation process follows a first order kinetic model according to the Langmuir-Hinshelwood model.

Keywords: maxilon red, adsorption, photodegradation, ZnO, coupling

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Authors: Miroslaw Wendeker, Piotr Kacejko, Marcin Szlachetka, Mariusz Duk

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This paper discusses a model of fuel economy in a city bus driving in a dynamic urban environment. Rapid changes in speed result in a constantly changing kinetic energy accumulated in a bus mass and an increased fuel consumption due to hardly recuperated kinetic energy. The model is based on the bench test results achieved from chassis dynamometer, airport and city street researches. The verified model was applied to simulate the behavior of a bus during the Japanese JE05 Emission Test Cycle. The fuel consumption was calculated for three separate research stages, i.e. urban, downtown and motorway. The simulations were performed for several values of vehicle mass and electrical load applied to on-board devices. The research results show fuel consumption is impacted by driving dynamics.

Keywords: city bus, heavy duty vehicle, Japanese JE05 test cycle, kinetic energy

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Authors: Amir Zeb, Shailima Rampogu, Minky Son, Ayoung Baek, Sang H. Yoon, Keun W. Lee

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Neurotoxic insults activate calpain, which in turn produces truncated p25 from p35. p25 forms hyperactivated Cdk5/p25 complex, and thereby induces severe neuropathological aberrations including hyperphosphorylated tau, neuroinflammation, apoptosis, and neuronal death. Inhibition of Cdk5/p25 complex alleviates aberrant phosphorylation of tau to mitigate AD pathology. PHA-793887 and Roscovitine have been investigated as selective inhibitors of Cdk5/p25 with IC50 values 5nM and 160nM, respectively, but their mechanistic studies remain unknown. Herein, computational simulations have explored the binding mode and interaction mechanism of PHA-793887 and Roscovitine with Cdk5/p25. Docking results suggested that PHA-793887 and Rsocovitine have occupied the ATP-binding site of Cdk5 and obtained highest docking (GOLD) score of 66.54 and 84.03, respectively. Furthermore, molecular dynamics (MD) simulation demonstrated that PHA-793887 and Roscovitine established stable RMSD of 1.09 Å and 1.48 Å with Cdk5/p25, respectively. Profiling of polar interactions suggested that each inhibitor formed hydrogen bonds (H-bond) with catalytic residues of Cdk5 and could remain stable throughout the molecular dynamics simulation. Additionally, binding free energy calculation by molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) suggested that PHA-793887 and Roscovitine had lowest binding free energies of -150.05 kJ/mol and -113.14 kJ/mol, respectively with Cdk5/p25. Free energy decomposition demonstrated that polar energy by H-bond between the Glu81 of Cdk5 and PHA-793887 is the essential factor to make PHA-793887 highly selective towards Cdk5/p25. Overall, this study provided substantial evidences to explore mechanistic interactions of the selective inhibitors of Cdk5/p25 and could be used as fundamental considerations in the development of structure-based selective inhibitors of Cdk5/p25.

Keywords: Cdk5/p25 inhibition, molecular modeling of Cdk5/p25, PHA-793887 and roscovitine, selective inhibition of Cdk5/p25

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Authors: Ragy Raafat Gaber Attaalla

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For cardiovascular illness, oral P2Y12 inhibitors including clopidogrel, prasugrel, and ticagrelor are frequently recommended. Each of these medications has advantages and disadvantages. In the absence of genotyping, it has been demonstrated that the stronger platelet aggregation inhibitors prasugrel and ticagrelor are superior than clopidogrel at preventing significant adverse cardiovascular events following an acute coronary syndrome and percutaneous coronary intervention (PCI). Both, nevertheless, come with a higher risk of bleeding unrelated to a coronary artery bypass. As a prodrug, clopidogrel needs to be bioactivated, principally by the CYP2C19 enzyme. A CYP2C19 no function allele and diminished or absent CYP2C19 enzyme activity are present in about 30% of people. The reduced exposure to the active metabolite of clopidogrel and reduced inhibition of platelet aggregation among clopidogrel-treated carriers of a CYP2C19 no function allele likely contributed to the reduced efficacy of clopidogrel in clinical trials. Clopidogrel's pharmacogenetic results are strongest when used in conjunction with PCI, but evidence for other indications is growing. One of the most typical examples of clinical pharmacogenetic application is CYP2C19 genotype-guided antiplatelet medication following PCI. Guidance is available from expert consensus groups and regulatory bodies to assist with incorporating genetic information into P2Y12 inhibitor prescribing decisions. Here, we examine the data supporting genotype-guided P2Y12 inhibitor selection's effects on clopidogrel response and outcomes and discuss tips for pharmacogenetic implementation. We also discuss procedures for using genotype data to choose P2Y12 inhibitor therapies as well as any unmet research needs. Finally, choosing a P2Y12 inhibitor medication that optimally balances the atherothrombotic and bleeding risks may be influenced by both clinical and genetic factors.

Keywords: inhibitors, cardiovascular events, coronary intervention, pharmacogenetic implementation

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Authors: Onur Karaman, Ceren Karaman

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In this study, the adsorption of Methylene Blue (MB), a cationic dye, onto Orange Peel Derived Activated Carbon (OPAC) and chitosan(OPAC/Chitosan composite) composite (a low-cost absorbent) was carried out using a batch system. The composite was characterised using IR spectra, XRD, FESEM and Pore size studies. The effects of initial pH, adsorbent dose rate and initial dye concentration on the initial adsorption rate, capacity and dye removal efficiency were investigated. The Langmuir and Freundlich adsorption models were used to define the adsorption equilibrium of dye-adsorbent system mathematically and it was decided that the Langmuir model was more suitable to describe the adsorption equilibrium for the system. In addition, first order, second order and saturation type kinetic models were applied to kinetic data of adsorption and kinetic constants were calculated. It was concluded that the second order and the saturation type kinetic models defined the adsorption data more accurately. Finally, the evaluated thermodynamic parameters of adsorption show a spontaneous and exothermic behavior. Overall, this study indicates OPAC/Chitosan composite as an effective and low-cost adsorbent for the removal of MB dye from aqueous solutions.

Keywords: activated carbon, adsorption, chitosan, methylene blue, orange peel

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Authors: Driouiche Ali, Karmal Ilham

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The Agadir region is characterized by a dry climate, ranging from arid attenuated by oceanic influences to hyper-arid. The water mobilized in the agricultural sector of greater Agadir is 95% of underground origin and comes from the water table of Chtouka. The rest represents the surface waters of the Youssef Ben Tachfine dam. These waters are intended for the irrigation of 26880 hectares of modern agriculture. More than 120 boreholes and wells are currently exploited. Their depth varies between 10 m and 200 m and the unit flow rates of the boreholes are 5 to 50 l/s. A drop in the level of the water table of about 1.5 m/year, on average, has been observed during the last five years. Farmers are thus called upon to improve irrigation methods. Thus, localized or drip irrigation is adopted to allow rational use of water. The importance of this irrigation system is due to the fact that water is applied directly to the root zone and its compatibility with fertilization. However, this irrigation system faces a thorny problem which is the clogging of pipes and drippers. This leads to a lack of uniformity of irrigation over time. This so-called scaling phenomenon, the consequences of which are harmful (cleaning or replacement of pipes), leads to considerable unproductive expenditure. The objective set by this work is the search for green inhibitors likely to prevent this phenomenon of scaling. This study requires a better knowledge of these waters, their physico-chemical characteristics and their scaling power. Thus, using the "LCGE" controlled degassing technique, we initially evaluated, on pure calco-carbonic water at 30°F, the scaling-inhibiting power of some available plant extracts in our region of Souss-Massa. We then carried out a comparative study of the efficacy of these green inhibitors. The action of the most effective green inhibitor on real agricultural waters was then studied.

Keywords: green inhibitors, localized irrigation, plant extracts, scaling inhibition

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Authors: Gokhan Zengin, Abdurrahman Aktumsek

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The key enzyme inhibitory theory is one of the most accepted strategies in the treatment of global health problems including Alzheimer’s Disease and Diabetes mellitus. For this reason, the enzyme inhibitory potentials of different solvent extracts from Linaria genistifolia subsp. genistifolia were investigated against cholinesterase, and tyrosinase. The in vitro enzyme inhibitory potentials were measured with a microplate reader. The acetone and methanol extracts exhibited the strongest enzyme inhibitory effects on cholinesterase. However, the water extract was only active on tyrosinase. The results suggested that Linaria genistifolia subsp. genistifolia could be considered as a source of natural enzyme inhibitors for the treatment of major health problems.

Keywords: enzyme inhibitors, cholinesterase, tyrosinase, linaria, Turkey

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Authors: Owamah Hilary, O. C. Izinyon

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Many existing biogas kinetic models are difficult to apply to substrates they were not developed for, as they are substrate specific. Biodegradability kinetic (BIK) model and maximum biogas production potential and stability assessment (MBPPSA) model were therefore developed in this study for the anaerobic co-digestion of food waste and maize husk. Biodegradability constant (k) was estimated as 0.11d-1 using the BIK model. The results of maximum biogas production potential (A) obtained using the MBPPSA model corresponded well with the results obtained using the popular but complex modified Gompertz model for digesters B-1, B-2, B-3, B-4, and B-5. The (If) value of MBPPSA model also showed that digesters B-3, B-4, and B-5 were stable, while B-1 and B-2 were unstable. Similar stability observation was also obtained using the modified Gompertz model. The MBPPSA model can therefore be used as alternative model for anaerobic digestion feasibility studies and plant design.

Keywords: biogas, inoculum, model development, stability assessment

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Authors: Mohamed El Hattab

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The Supercritical carbon dioxide (SFE) and the focused microwave-assisted hydrodistillation (FMAHD) were employed to isolate the volatile fraction of the brown alga Dictyopteris membranacea from the crude extract. The volatiles fractions obtained were analyzed by GC/MS. The major compounds in this case: dictyopterene A, 6-butylcyclohepta-1,4-diene, Undec-1-en-3-one, Undeca-1,4-dien-3-one, (3-oxoundec-4-enyl) sulphur, tetradecanoic acid, hexadecanoic acid, 3-hexyl-4,5-dithia-cycloheptanone and albicanol (this later is present only in the FMAHD oil) are identified by comparing their mass spectra with those reported on the commercial MS data base and also on our previously work. A kinetic study realized on both extraction processes and followed by an external standard quantification has allowed the study of the mass percent evolution of the major compounds in the two oils, an empirical mathematical modelling was used to describe their kinetic extraction.

Keywords: dictyopteris membranacea, extraction techniques, mathematical modeling, volatile oils

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Authors: M. Hakami, A. Jammaly, I. Attafi, M. Oraiby, M. Jeraiby

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We reviewed an unusual case of a 65-year-old male taking an herbal mixture containing compounds with anticholinesterase activity for a long period of time, presented with acute my myocardial infarction and multiple organ dysfunction syndrome followed by death. Clinically, there are findings correlated with anticholinesterase activity, such as bilateral miosis, diaphoresis, vomiting and fasciculation without a history of any toxic ingestion or exposure. Gas chromatography–mass spectrometry screening studies identified the presence of thymol, anethole in the herbal extract and butylated hydroxytoluene in the blood sample. Hence, with this case report, we intend to highlight the necessity of evaluating the long-term use of the herbal mixture.

Keywords: cholinesterase inhibitors, thymole, anethole, butylatedhydroxytoluene, cardiac toxicity, myocardial infarction

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Authors: Rachid Kacem

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Excessive recruitment of Neutrophils into the lungs is a hallmark of several chronic inflammatory disorders such as emphysema and COPD. The resulting of this recruitment is the pathogenesis of lungs which is characterized by an imbalance between leukocyte serine proteinases mainly neutrophil elastase and the physiological inhibitors. The development of emphysema and remodeling of airway tissue occurred when neutrophil migrate into the lungs with more release of elastase and other proteolytic enzymes. Many reports have demonstrated that the extracts from medicinal plants such as Nigella sativa (L.) seeds extracts have anti-elastase activity; this is mainly due to the enrichment of the extracts with many bioactive molecules mainly phenolic compounds. Neutrophil serine proteases including human neutrophil elastase are involved in many inflammatory diseases, such as chronic obstructive pulmonary disease and emphysema. Since the current therapies for these diseases are inadequate and have numerous adverse effects, there is an acute need of potential alternative therapies. The natural protease inhibitors have received increasing attention as useful tools for potential utilization in pharmacology. This work is elucidating the most important natural phenolic substances that have been reported recently for their effectiveness as natural anti-elastase molecules, and hence, to the possibility of their use in the field of pharmaceuticals.

Keywords: medicinal plants, phenols, elastase, anti-elastase, chronic obstructive pulmonary disease, COPD, emphysema

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Authors: M. S. Yalfani, J. Kohzadi, P. Ghadimi, S. Sobhani, M. Ghadimi

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The use of oil and water-soluble corrosion inhibitors has been established in Iranian oil and gas production systems for a long time. Imidazoline and its derivatives are being extensively used which are known as conventional corrosion inhibitors. This type of product has shown significant performance and low side effects, so that could monopolize the market of inhibitors in this region. However, the price growth of imidazolines, as well as the development of new lower-cost components with similar or even higher performance than imidazoline, have influenced the exclusive market of imidazoline-based products. During the latest years, pyridine and its derivatives have challenged imidazoline due to their remarkable anticorrosive properties and lower prices as well. Recently, we presented a formulated water-soluble inhibitor based on pyridine - an alkyl pyridine quaternary salt (APQS) - which could successfully pass all lab tests and eventually succeeded in being applied in an offshore sweet oil pipeline. The product was able to achieve high corrosion protection (> 90 %) with the LPR technique at low dosages of 15-25 ppm under severe corrosion conditions. Moreover, the lab test results showed that the APQS molecule is able to form a strong and persistent bond with the metal surface. The product was later nominated to be evaluated through a field trial in an offshore sweet oil pipeline where PH2S < 0.05 psi and CO2 is 6.4 mol%. The three-month trial - extended to six months- resulted in remarkable internal protection obtained by continuous injection of 10 ppm inhibitor, which was as low as 1 mpy measured by both weight loss corrosion coupons and online ER probes. In addition, no side effects, such as tight emulsion and stable foaming, were observed. The residual of the corrosion inhibitor was measured at the end of the pipeline to ensure the full coverage of the inhibitor throughout the pipeline. Eventually, these promising results were able to convince the end user to consider pyridine-based inhibitors as a reliable alternative to imidazoline.

Keywords: corrosion inhibitor, pyridine, sweet oil, pipeline, offshore

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Authors: Gabriela D. Silva, Rodrigo L. O. R. Cunha, Mauricio D. Coutinho-Neto

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In the last four decades the biological activities of selenium compounds has received great attention, particularly for hypervalent derivates from selenium (IV) used as enzyme inhibitors. The unregulated activity of cysteine proteases are related to the development of several pathologies, such as neurological disorders, cardiovascular diseases, obesity, rheumatoid arthritis, cancer and parasitic infections. These enzymes are therefore a valuable target for designing new small molecule inhibitors such as selenuranes. Even tough there has been advances in the synthesis and design of new selenuranes based inhibitors, little is known about their mechanism of action. It is a given that inhibition occurs through the reaction between the thiol group of the enzyme and the chalcogen atom. However, several open questions remain about the nature of the mechanism (associative vs. dissociative) and about the nature of the reactive species in solution under physiological conditions. In this work we performed a theoretical investigation on model systems to study the possible routes of substitution reactions. Nucleophiles may be present in biological systems, our interest is centered in the thiol groups from the cysteine proteases and the hydroxyls from the aqueous environment. We therefore expect this study to clarify the possibility of a route reaction in two stages, the first consisting of the substitution of chloro atoms by hydroxyl groups and then replacing these hydroxyl groups per thiol groups in selenuranes. The structures of selenuranes and nucleophiles were optimized using density function theory along the B3LYP functional and a 6-311+G(d) basis set. Solvent was treated using the IEFPCM method as implemented in the Gaussian 09 code. Our results indicate that hydrolysis from water react preferably with selenuranes, and then, they are replaced by the thiol group. It show the energy values of -106,0730423 kcal/mol for dople substituition by hydroxyl group and 96,63078511 kcal/mol for thiol group. The solvatation and pH reduction promotes this route, increasing the energy value for reaction with hydroxil group to -50,75637672 kcal/mol and decreasing the energy value for thiol to 7,917767189 kcal/mol. Alternative ways were analyzed for monosubstitution (considering the competition between Cl, OH and SH groups) and they suggest the same route. Similar results were obtained for aliphatic and aromatic selenuranes studied.

Keywords: chalcogenes, computational study, cysteine proteases, enzyme inhibitors

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Authors: Harish Rajak, Preeti Patel

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HDAC inhibitors can reactivate gene expression and inhibit the growth and survival of cancer cells. The 3D-QSAR and Pharmacophore modeling studies were performed to identify important pharmacophoric features and correlate 3D-chemical structure with biological activity. The pharmacophore hypotheses were developed using e-pharmacophore script and phase module. Pharmacophore hypothesis represents the 3D arrangement of molecular features necessary for activity. A series of 55 compounds with well-assigned HDAC inhibitory activity was used for 3D-QSAR model development. Best 3D-QSAR model, which is a five PLS factor model with good statistics and predictive ability, acquired Q2 (0.7293), R2 (0.9811) and standard deviation (0.0952). Molecular docking were performed using Histone Deacetylase protein (PDB ID: 1t69) and prepared series of hydroxamic acid based HDAC inhibitors. Docking study of compound 43 show significant binding interactions Ser 276 and oxygen atom of dioxine cap region, Gly 151 and amino group and Asp 267 with carboxyl group of CONHOH, which are essential for anticancer activity. On docking, most of the compounds exhibited better glide score values between -8 to -10.5. We have established structure activity correlation using docking, energetic based pharmacophore modelling, pharmacophore and atom based 3D QSAR model. The results of these studies were further used for the design and testing of new HDAC analogs.

Keywords: Docking, e-pharmacophore, HDACIs, QSAR, Suberoylanilidehydroxamic acid.

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Authors: Ceren Efe, Hale Sütçü

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In this study, the pyrolysis of bituminous coal, peat and their blends formed by mixing various ratios of them were examined by thermogravimetric analysis method. Thermogravimetric analyses of peat, bituminous coal and their blends in the proportions of 25 %, 50 % and 75 % were performed at heating rate of 10 °C/min and from the room temperature until to 800 °C temperature, in a nitrogen atmosphere of 100 ml/min. Kinetic parameters for the pyrolysis process were calculated using Coats&Redfern kinetic model.

Keywords: bituminous coal, peat, pyrolysis, thermogravimetric analysis, Coats&Redfern

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Authors: M. A. Munteanu, A. M. Lungu, A. I. Chivescu, V. Teodorescu, E. Tufanoiu, C. Nicolae, T. I. Nanea

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Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i), which were first developed as antidiabetic medications, have demonstrated numerous positive benefits on the cardiovascular system, especially in the prevention of heart failure (HF). HF is a challenging, multifaceted disease that needs all-encompassing therapy. It should not be viewed as a limited form of heart illness but rather as a systemic disease that leads to multiple organ failure and death. SGLT2i is an extremely effective tool for treating HF by using its pleiotropic effects. In addition to its use in patients with diabetes mellitus who are at high cardiovascular risk or who have already experienced a cardiovascular event, SGLT2i administration has been shown to have positive effects on a variety of HF manifestations and stages, regardless of the patient's presence of diabetes mellitus. Material and Methods: According to the guide, 110 patients (83 males and 27 females) with heart failure with mildly reduced ejection fraction (HFmrEF), with T2D and neoplasia, were enrolled in the prospective study. The structural and functional state of the left ventricle myocardium and ejection fraction was assessed through echocardiography. Patients were randomized to receive once-daily dapagliflozin 10 mg. Results: Patients with HFmrEF were divided into 3 subgroups according to age. 7% (8) patients aged < 45 years, 35% (28) patients aged between 46-59 years, and 58% (74) patients aged> 60 years. The most prevalent comorbidities were hypertension (43.1%), coronary heart disease (40%), and obesity (33.2%). Study drug discontinuation and serious adverse events were not frequent in the subgroups, in either men or women, until now. Conclusions: SGLT-2 inhibitors are a novel class of antidiabetic agents that have demonstrated positive efficacy and safety outcomes in the setting of HFmrEF. Until now, in our study, dapagliflozin was safe and well-tolerated irrespective of sex.

Keywords: diabetes mellitus type 2, Sodium-glucose co-transporters-2 inhibitors, heart failure, neoplasia

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Authors: M. Ouassaf, S. Belaidi

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Aromatase is an estrogen biosynthetic enzyme belonging to the cytochrome P450 family, which catalyzes the limiting step in the conversion of androgens to estrogens. As it is relevant for the promotion of tumor cell growth. A set of thirty 1,2,3-triazole derivatives was used in the quantitative structure activity relationship (QSAR) study using regression multiple linear (MLR), We divided the data into two training and testing groups. The results showed a good predictive ability of the MLR model, the models were statistically robust internally (R² = 0.982) and the predictability of the model was tested by several parameters. including external criteria (R²pred = 0.851, CCC = 0.946). The knowledge gained in this study should provide relevant information that contributes to the origins of aromatase inhibitory activity and, therefore, facilitates our ongoing quest for aromatase inhibitors with robust properties.

Keywords: aromatase inhibitors, QSAR, MLR, 1, 2, 3-triazole

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Authors: Li-Kai Kuo, Shyh-Hau Wang

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The kinetic trajectory of the median nerve (MN) in the wrist has shown to be capable of being applied to assess the carpal tunnel syndrome (CTS), and was found able to be detected by high-frequency ultrasound image via motion tracking technique. Yet, previous study may not quickly perform the measurement due to the use of a single element transducer for ultrasound image scanning. Therefore, previous system is not appropriate for being applied to clinical application. In the present study, B-mode ultrasound images of the wrist corresponding to movements of fingers from flexion to extension were acquired by clinical applicable real-time scanner. The kinetic trajectories of MN were off-line estimated utilizing two dimensional Baysian speckle tracking (TDBST) technique. The experiments were carried out from ten volunteers by ultrasound scanner at 12 MHz frequency. Results verified from phantom experiments have demonstrated that TDBST technique is able to detect the movement of MN based on signals of the past and present information and then to reduce the computational complications associated with the effect of such image quality as the resolution and contrast variations. Moreover, TDBST technique tended to be more accurate than that of the normalized cross correlation tracking (NCCT) technique used in previous study to detect movements of the MN in the wrist. In response to fingers’ flexion movement, the kinetic trajectory of the MN moved toward the ulnar-palmar direction, and then toward the radial-dorsal direction corresponding to the extensional movement. TDBST technique and the employed ultrasound image scanner have verified to be feasible to sensitively detect the kinetic trajectory and displacement of the MN. It thus could be further applied to diagnose CTS clinically and to improve the measurements to assess 3D trajectory of the MN.

Keywords: baysian speckle tracking, carpal tunnel syndrome, median nerve, motion tracking

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Authors: Mohammad Reza Ghaani, Michele Catti

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The reduction of CoO/Fe₂O₃ oxides supported on carbon xerogels was studied to elucidate the effect of nano-size distribution of the catalyst in carbon matrices. Resorcinol formaldehyde xerogels were synthesized, impregnated with iron and cobalt nitrates, and subsequently heated to obtain the oxides. The mechanism of oxide reduction to metal was investigated by in-situ synchrotron X-ray diffraction in dynamic, non-isothermal conditions. Kinetic profiles of the reactions were obtained by plotting the diffraction intensities of selected Bragg peaks vs. temperature. The extracted Temperature-Programmed-Reduction (TPR) diagrams were analyzed by appropriate kinetic models, leading to best results with the Avrami-Erofeev model for all reduction reactions considered. The activation energies for the two-step reduction of iron oxide were 65 and 37 kJmol⁻¹, respectively. The average value for the reduction of CoO to Co was found to be around 21 kJ mol⁻¹. Such results may contribute to develop efficient and inexpensive non-noble metal-based catalysts in element form, e.g., Fe, Co, via heterogenization of metal complexes on mesoporous supports.

Keywords: non-isothermal kinetics, carbon aerogel, in-situ synchrotron X-ray diffraction, reduction mechanisms

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Authors: Marina Borgert Moraes, Wesley Francisco, Filipe Vargas, Gilmar Patrocínio Thim

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In recent years, carbon nanotubes (CNT) and graphene oxide (GO), especially the functionalized ones, have been added to epoxy resin in order to increase the mechanical, electrical and thermal properties of nanocomposites. However, it's still unknown how the presence of these nanoparticles influences the curing process and the final mechanical properties as well. In this work, kinetic and mechanical properties of the nanocomposites were analyzed, where the kinetic process was followed by DSC and the mechanical properties by DMA. Initially, CNT was annealed at high temperature (1800 °C) under vacuum atmosphere, followed by a chemical treatment using acids and ethylenediamine. GO was synthesized through chemical route, washed clean, dried and ground to #200. The presence of functional groups on CNT and GO surface was confirmed by XPS spectra and FT-IR. Then, epoxy resin, nanoparticles and acetone were mixed by sonication in order to obtain the composites. DSC analyses were performed on samples with different curing cycles (1h 80°C + 2h 120°C; 3h 80°C + 2h 120°C; 5h 80°C) and samples with different times at constant temperature (120°C). Results showed that the kinetic process and the mechanical strength are very dependent on the presence of graphene and functionalized-CNT in the nanocomposites.

Keywords: carbon nanotube, epoxy resin, Graphene oxide, nanocomposite

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Authors: N. Q. Bau, N. V. Nghia

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The acoustomagnetoelectric (AME) field in a rectangular quantum wire with an infinite potential (RQWIP) is calculated in the presence of an external magnetic field (EMF) by using the quantum kinetic equation for the distribution function of electrons system interacting with external phonons and electrons scattering with internal acoustic phonon in a RQWIP. We obtained ananalytic expression for the AME field in the RQWIP in the presence of the EMF. The dependence of AME field on the frequency of external acoustic wave, the temperature T of system, the cyclotron frequency of the EMF and the intensity of the EMF is obtained. Theoretical results for the AME field are numerically evaluated, plotted and discussed for a specific RQWIP GaAs/GaAsAl. This result has shown that the dependence of the AME field on intensity of the EMF is nonlinearly and it is many distinct maxima in the quantized magnetic region. We also compared received fields with those for normal bulk semiconductors, quantum well and quantum wire to show the difference. The influence of an EMF on AME field in a RQWIP is newly developed.

Keywords: rectangular quantum wire, acoustomagnetoelectric field, electron-phonon interaction, kinetic equation method

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Authors: Christine Fräulin, Daniela Schurr, Hamed Shahidi Rad, Gerrit Waters, Günter Rinke, Roland Dittmeyer, Michael Nilles

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The reaction mechanisms of many liquid-phase reactions in organic chemistry have not yet been sufficiently clarified. Process conditions of several hundred degrees celsius and pressures to ten megapascals complicate the sampling and the determination of kinetic data. Space resolved in-situ measurements promises new insights. A non-invasive in-situ measurement technique has the advantages that no sample preparation is necessary, there is no change in sample mixture before analysis and the sampling do no lead to interventions in the flow. Thus, the goal of our research was the development of a contact-free spatially resolved measurement technique for kinetic studies of liquid phase reaction under process conditions. Therefore we used laser Raman spectroscopy combined with an optical transparent microchannel reactor. To show the performance of the system we choose the oxidation of cyclohexane as sample reaction. Cyclohexane oxidation is an economically important process. The products are intermediates for caprolactam and adipic acid, which are starting materials for polyamide 6 and 6.6 production. To maintain high selectivities of 70 to 90 %, the reaction is performed in industry at a low conversion of about six percent. As Raman spectroscopy is usually very selective but not very sensitive the detection of the small product concentration in cyclohexane oxidation is quite challenging. To meet these requirements, an optical experimental setup was optimized to determine the concentrations by laser Raman spectroscopy with respect to good detection sensitivity. With this measurement technique space resolved kinetic studies of uncatalysed and homogeneous catalyzed cyclohexane oxidation were carried out to obtain details about the reaction mechanism.

Keywords: in-situ laser raman spectroscopy, space resolved kinetic measurements, homogeneous catalysis, chemistry

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Authors: R. Frikha, H. Kamoun

Abstract:

Background:Chronicmyeloidleukemia (CML), a hematologicaldisease, ischaracterized by t (9; 22) and relatedoncogene BCR-ABL formation. Although Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML, resistanceoccurs and possibly médiates by mutation in severalgenesindependently of the bcr-abl1 kinase mechanism. it has been reportedthat JAK2V617F/BCR-ABL double positivitymaybe a potential marker of resistance in CML. Aims: This studywasinvestigated the JAK2V617F mutation in TKI-resistant CML patients. Methods: A retrospectivestudywasconducted in the Hospital University of Sfax, south of Tunisia, including all CML TKI-resistant patients. A Sanger sequencingwasperformedusing a high-fidelity DNA polymerase. Results:Nineresistant CP-CML patients wereenrolled in thisstudy. The JAK2V617F mutation wasdetectedin 3 patients with TKI resistance. Conclusion:Despite the limit of ourstudy, ourfinding highlights the high frequency of JAK2V617F/BCR-ABL double positivity as an important marker of resistance. So; the combination of JAK and TKI inhibitorsmightbe effective and potentiallybeguided by molecular monitoring of minimal residual disease1.

Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, resistance, JAK2V617F, BCR-ABL

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Authors: Shazia Mannan, Zunera Khalid, Hammad-Ul-Mubeen

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Wingless type Mouse mammary tumor virus (MMTV) Integration site-10B (Wnt10B) is an important member of the Wnt protein family that functions as cellular messenger in paracrine manner. Aberrant Wnt10B activity is the cause of several abnormalities including cancers of breast, cervix, liver, gastric tract, esophagus, pancreas as well as physiological problems like obesity, and osteoporosis. The objective of this study was to determine the possible inhibitors against aberrant expression of Wnt10B in order to prevent and treat the physiological disorders associated with it. Wnt10B3D structure was predicted by using comparative modeling and then analyzed by PROCHECK, Verify3D, and Errat. The model having 84.54% quality value was selected and acylated to satisfy the hydrophobic nature of Wnt10B. For search of inhibitors, virtual screening was performed on Natural Products (NP) database. The compounds were filtered and ligand-based screening was performed using the antagonist for mouse Wnt-3A. This resulted in a library of 272 unique compounds having most potent drug like activities for Wnt-4. Out of the 271 molecules analyzed three small molecules ZINC35442871, ZINC85876388, and ZINC00754234 having activity against Wnt4 abbarent expression were found common through docking experiment of Wnt10B. It is concluded that the three molecules ZINC35442871, ZINC85876388, and ZINC00754234 can be considered as lead compounds for performing further drug designing experiments against aberrant Wnt expressions.

Keywords: Wnt10B inhibitors, comparative computational studies, proto-oncogene, molecular docking

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Authors: Ali Driouiche, Abdallah Hadfi

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During this work on scaling phenomenon observed in the irrigation water pipes in the agricultural region of Greater Agadir, a follow-up was carried out during a year of the physico-chemical quality of these waters. Sampling was conducted from 120 sampling points, well distributed in the study area and involved 120 water samples. The parameters measured for each sample are temperature, pH, conductivity, total hardness and the concentrations of the ions HCO₃₋, Ca²⁺, Mg²⁺, Na⁺, K⁺, SO₄₋, NO₃₋, Cl₋ and OH₋. Indeed, the monitoring of the physico-chemical quality shows that the total hardness varies between 20 and 65 °F and the complete alkalimetric title varies from 14 °F to 42 °F. For the kinetic study of the scaling power, an object of this work, 6 samples which have high hardness were selected from the 120 samples analyzed. This study was carried out using the controlled degassing method Laboratoire de Chimie et de Génie de l’Environnement (LCGE) where it was developed) and showed that the studied waters are calcifying. The germination time Tg varies between 16 and 34 minutes. The highlighting of new scale inhibitors to prevent the formation of scale in the pipelines of the agricultural sector of Greater Agadir will also be discussed.

Keywords: agadir, clogging pipes, localized irrigation, scaling power

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Authors: Chusak Thanawattano, Roongroj Bhidayasiri

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This paper proposes a novel feature set utilized for classifying the Parkinson tremor and essential tremor. Ten ET and ten PD subjects are asked to perform kinetic, postural and resting tests. The empirical mode decomposition (EMD) is used to decompose collected tremor signal to a set of intrinsic mode functions (IMF). The IMFs are used for reconstructing representative signals. The feature set is composed of peak frequencies of IMFs and reconstructed signals. Hypothesize that the dominant frequency components of subjects with PD and ET change in different directions for different tests, difference of peak frequencies of IMFs and reconstructed signals of pairwise based tests (kinetic-resting, kinetic-postural and postural-resting) are considered as potential features. Sets of features are used to train and test by classifier including the quadratic discriminant classifier (QLC) and the support vector machine (SVM). The best accuracy, the best sensitivity and the best specificity are 90%, 87.5%, and 92.86%, respectively.

Keywords: tremor, Parkinson, essential tremor, empirical mode decomposition, quadratic discriminant, support vector machine, peak frequency, auto-regressive, spectrum estimation

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