Search results for: drug carriers

Authors: K. Veluraja

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Glycan of glycolipids and glycoproteins is playing a significant role in living systems particularly in molecular recognition processes. Molecular recognition processes are attributed to their occurrence on the surface of the cell, sequential arrangement and type of sugar molecules present in the oligosaccharide structure and glyosidic linkage diversity (glycoinformatics) and conformational diversity (glycoconformatics). Molecular Dynamics Simulation study is a theoretical-cum-computational tool successfully utilized to establish glycoconformatics of glycan. The study on various oligosaccharides of glycan clearly indicates that oligosaccharides do exist in multiple conformational states and these conformational states arise due to the flexibility associated with a glycosidic torsional angle (φ,ψ) . As an example: a single disaccharide structure NeuNacα(2-3) Gal exists in three different conformational states due to the differences in the preferential value of glycosidic torsional angles (φ,ψ). Hence establishing three dimensional structural and conformational models for glycan (cartesian coordinates of every individual atoms of an oligosaccharide structure in a preferred conformation) is quite crucial to understand various molecular recognition processes such as glycan-toxin interaction and glycan-virus interaction. The gycoconformatics models obtained for various glycan through Molecular Dynamics Simulation stored in our 3DSDSCAR (3DSDSCAR.ORG) a public domain database and its utility value in understanding the molecular recognition processes and in drug design venture will be discussed.

Keywords: glycan, glycoconformatics, molecular dynamics simulation, oligosaccharide

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Authors: Ikram Mohamed Eltayeb Elsiddig, Abdel Khalig Muddather, Hiba Abdel Rahman Ali, Saad Mohamed Hussein Ayoub

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Anogeissusleiocarpus (Combretaceae) is well known for its medicinal uses in African traditional medicine, for treating many human diseases mainly skin diseases and infections.Mycetoma disease is a fungal and/ or bacterial skin infection, mainly cause by Madurella mycetomatis fungus.This study was carried out in vitro to investigate the antifungal activity of Anogeissusleiocarpus leaf extracts against the isolated pathogenicMadurellamycetomatis, by using the NCCLS modified method compared to Ketoconazole standard drug and MTT assay. The bioactive fraction was subjected to chemical analysis implementing different chromatographic analytical methods (TLC, HPLC, and LC-MS/MS). The results showed significance antifungal activity of A. leiocarpus leaf extractsagainst the isolated pathogenicM. mycetomatis, compared to negative and positive controls. The chloroform fraction showed the highest antifungal activity.The chromatographic analysis of the chloroform fraction with the highest activity showed the presence of important bioactive compounds such as ellagic and flavellagic acids derivatives, flavonoids and stilbenoid, which are well known for their antifungal activity.

Keywords: Anogeissus leiocarpus, crude extracts and fractions of Anogeissus leiocarpus, in vitrosusceptibility of Madurella mycetomatis, Madurella mycetomatis

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Authors: Sankha Chakrabortty, Biswajit Ruj, Parimal Pal

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Methanol is one of the most important chemical products and intermediates. It can be used as a solvent, intermediate or raw material for a number of higher valued products, fuels or additives. From the last one decay, the total global demand of methanol has increased drastically which forces the scientists to produce a large amount of methanol from a renewable source to meet the global demand with a sustainable way. Different types of non-renewable based raw materials have been used for the synthesis of methanol on a large scale which makes the process unsustainable. In this circumstances, photocatalytic conversion of CO₂ into methanol under solar/UV excitation becomes a viable approach to give a sustainable production approach which not only meets the environmental crisis by recycling CO₂ to fuels but also reduces CO₂ amount from the atmosphere. Development of such sustainable production approach for CO₂ conversion into methanol still remains a major challenge in the current research comparing with conventional energy expensive processes. In this backdrop, the development of environmentally friendly materials, like photocatalyst has taken a great perspective for methanol synthesis. Scientists in this field are always concerned about finding an improved photocatalyst to enhance the photocatalytic performance. Graphene-based hybrid and composite materials with improved properties could be a better nanomaterial for the selective conversion of CO₂ to methanol under visible light (solar energy) or UV light. The present invention relates to synthesis an improved heterogeneous graphene-based photocatalyst with improved catalytic activity and surface area. Graphene with enhanced surface area is used as coupled material of copper-loaded titanium oxide to improve the electron capture and transport properties which substantially increase the photoinduced charge transfer and extend the lifetime of photogenerated charge carriers. A fast reduction method through H₂ purging has been adopted to synthesis improved graphene whereas ultrasonication based sol-gel method has been applied for the preparation of graphene coupled copper loaded titanium oxide with some enhanced properties. Prepared photocatalysts were exhaustively characterized using different characterization techniques. Effects of catalyst dose, CO₂ flow rate, reaction temperature and stirring time on the efficacy of the system in terms of methanol yield and productivity have been studied in the present study. The study shown that the newly synthesized photocatalyst with an enhanced surface resulting in a sustained productivity and yield of methanol 0.14 g/Lh, and 0.04 g/gcat respectively, after 3 h of illumination under UV (250W) at an optimum catalyst dosage of 10 g/L having 1:2:3 (Graphene: TiO₂: Cu) weight ratio.

Keywords: renewable energy, CO₂ capture, photocatalytic conversion, methanol

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Authors: Salma Ainine, Colin Ritchie, Tracey McFee

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Background: The societal impact of antibiotic resistance is a major public health concern. The increase in the incidence of resistant bacteria can ultimately be fatal. Objective: To analyse the appropriateness of antibiotic prescribing in Dundee Dental Hospital, ultimately improving the safety and quality of patient care. Methods: Two examiners independently cross-checked approximately fifty consecutive prescriptions, and corresponding patient case notes, for three data collection cycles between August 2014–September 2015. The Scottish Dental Clinical Effectiveness Program (SDCEP) Drug Prescribing for Dentistry guidelines was the standard utilised. The criteria: clinical justification, regime justification, and review arrangements was measured, and compared to the standard. Results: Cycle one revealed 42% of antibiotic prescriptions were appropriate. Interventions included: multiple staff meetings, an introduction of a checklist attached to the prescription pack, and production of patient leaflets explaining indications for antibiotics. Cycle two and three revealed 44%, and 30% compliance, respectively. Conclusion: The results of the audit have yet to meet target standards set out in prescribing guidelines. However, steps are being taken and change has occurred on a cultural level.

Keywords: antibiotic resistance, antibiotic stewardship, dental infection, hygiene standards

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Authors: Joseph Carl Macalintal, Erlinda Armovit

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Magnesium sulfate has been a mainstay in the management of preeclampsia and is associated with a decreased incidence of morbidity and mortality. The syndrome has an unpredictable course, sometimes rapidly evolving to full-blown disease. In patients with deteriorating status, it is indicated to terminate the pregnancy via cesarean section. The anesthesiologists would prefer to have the procedure done under regional anesthesia; however, there may be cases when neuraxial anesthesia is contraindicated, or a general anesthesia would permit prompt delivery of the fetus. A patient with severe preeclampsia was given magnesium sulfate intrapartum, wherein a primary cesarean section was indicated for arrest in cervical dilatation, and was performed under general anesthesia. The patient developed acute respiratory failure and the causes of this occurrence were investigated in this report. It was later found out that neither the hypermagnesemia nor the muscle relaxant alone caused the patient’s condition but the interaction between the two. The patient was managed expectantly at the intensive care unit (ICU) and was eventually extubated during the 1st post-operative day. Knowledge of this drug interaction would allow obstetricians to advise their patients and their family about the possibility of prolonged intubation and ICU admission. This would also bring to the anesthesiologists’ attention the need to decrease the dose of muscle relaxant and to prepare drugs for immediate decurarisation.

Keywords: eclampsia, magnesium sulfate, preeclampsia, rocuronium bromide

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Authors: J. Punj, R. K. Pandey, V. Darlong, K. Thangavel

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Background: Dural puncture epidural (DPE) technique has been introduced recently for labour analgesia however, no study has compared ropivacaine and levobupivacaine for the same. Methods: The primary aim of the study was to compare time to onset of the Numerical Pain Rating Score (NPRS) ≤ 1 in labour analgesia with both drugs. After obtaining ethics and patient consent, ASA I and ASA II parturient with single foetus in vertex presentation and cervical dilatation <5.0 cm were included. DPE was performed with 16/ 26 G combined spinal epidural (CSE) technique, and parturients randomized into two groups. In Group R ( Ropivacaine) 20 ml 0.125% ropivacaine+ fentanyl 2µg/ml was injected to a maximum of 20 ml in 20 minutes and in Group L (Levobupivacaine), 20 ml 0.125% levobupivacaine + fentanyl 2µg/ml was injected. Outcomes were assessed at 0.5,2,4,6,8,10,12,14,16,18,20 and 30 minutes, then every 90 minutes until delivery. Appropriate statistical analysis was done, and p value of <0.05 was considered statistically significant. Results: The median time to onset of NPRS ≤1 in both groups was comparable (group R= 16 minutes vs group L= 18 minutes (p = 0.076). Volume of drug for NPR ≤1 in both groups was also comparable (Group R 15.95± 2.03 ml vs Group L 16.35 ± 1.34 ml (p=0.47). Conclusion: DPE with 16 G epidural needle and 26 gauge spinal needle with both 0.125% ropivacaine and 0.125% levobupivacaine results in similar efficacy of labour analgesia.

Keywords: dural puncture epidural, labour analgesia, obstetric analgesia, hypotension

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Authors: Sena Su, Burak Ozbek, Yesim M. Sahin, Sevil Yucel, Dilek Kazan, Faik N. Oktar, Nazmi Ekren, Oguzhan Gunduz

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In recent years, protein, lipid or polysaccharide-based polymers have been used in order to develop biodegradable materials and their chemical nature determines the physical properties of the resulting films. Among these polymers, proteins from different sources have been extensively employed because of their relative abundance, film forming ability, and nutritional qualities. In this study, the biodegradable composite nanofiber films based on fish sarcoplasmic protein (FSP) were prepared via electrospinning technique. Biodegradable polycaprolactone (PCL) was blended with the FSP to obtain hybrid FSP/PCL nanofiber mats with desirable physical properties. Mixture solutions of FSP and PCL were produced at different concentrations and their density, viscosity, electrical conductivity and surface tension were measured. Mechanical properties of electrospun nanofibers were evaluated. Morphology of composite nanofibers was observed using scanning electron microscopy (SEM). Moreover, Fourier transform infrared spectrometer (FTIR) studies were used for analysis chemical composition of composite nanofibers. This study revealed that the FSP based nanofibers have the potential to be used for different applications such as biodegradable packaging, drug delivery, and wound dressing, etc.

Keywords: edible film, electrospinning, fish sarcoplasmic protein, nanofiber

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Authors: Vipin Kumar, Girish S. Setlur

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Graphene has been recognized as a promising 2D material with many new properties. However, pristine graphene is gapless which hinders its direct application towards graphene-based semiconducting devices. Graphene is a zero-gapp and linearly dispersing semiconductor. Massless charge carriers (quasi-particles) in graphene obey the relativistic Dirac equation. These Dirac fermions show very unusual physical properties such as electronic, optical and transport. Graphene is analogous to two-level atomic systems and conventional semiconductors. We may expect that graphene-based systems will also exhibit phenomena that are well-known in two-level atomic systems and in conventional semiconductors. Rabi oscillation is a nonlinear optical phenomenon well-known in the context of two-level atomic systems and also in conventional semiconductors. It is the periodic exchange of energy between the system of interest and the electromagnetic field. The present work describes the phenomenon of Rabi oscillations in graphene based systems. Rabi oscillations have already been described theoretically and experimentally in the extensive literature available on this topic. To describe Rabi oscillations they use an approximation known as rotating wave approximation (RWA) well-known in studies of two-level systems. RWA is valid only near conventional resonance (small detuning)- when the frequency of the external field is nearly equal to the particle-hole excitation frequency. The Rabi frequency goes through a minimum close to conventional resonance as a function of detuning. Far from conventional resonance, the RWA becomes rather less useful and we need some other technique to describe the phenomenon of Rabi oscillation. In conventional systems, there is no second minimum - the only minimum is at conventional resonance. But in graphene we find anomalous Rabi oscillations far from conventional resonance where the Rabi frequency goes through a minimum that is much smaller than the conventional Rabi frequency. This is known as anomalous Rabi frequency and is unique to graphene systems. We have shown that this is attributable to the pseudo-spin degree of freedom in graphene systems. A new technique, which is an alternative to RWA called asymptotic RWA (ARWA), has been invoked by our group to discuss the phenomenon of Rabi oscillation. Experimentally accessible current density shows different types of threshold behaviour in frequency domain close to the anomalous Rabi frequency depending on the system chosen. For single layer graphene, the exponent at threshold is equal to 1/2 while in case of bilayer graphene, it is computed to be equal to 1. Bilayer graphene shows harmonic (anomalous) resonances absent in single layer graphene. The effect of asymmetry and trigonal warping (a weak direct inter-layer hopping in bilayer graphene) on these oscillations is also studied in graphene systems. Asymmetry has a remarkable effect only on anomalous Rabi oscillations whereas the Rabi frequency near conventional resonance is not significantly affected by the asymmetry parameter. In presence of asymmetry, these graphene systems show Rabi-like oscillations (offset oscillations) even for vanishingly small applied field strengths (less than the gap parameter). The frequency of offset oscillations may be identified with the asymmetry parameter.

Keywords: graphene, Bilayer graphene, Rabi oscillations, Dirac fermion systems

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Authors: Madhu Gupta, G. P. Agrawa, Suresh P. Vyas

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Certain tumor cells overexpress a membrane-spanning molecule aminopeptidase N (CD13) isoform, which is the receptor for peptides containing the NGR motif. NGR-modified Docetaxel (DTX)-loaded PEG-b-PLGA polymeric nanoparticles (cNGR-DNB-NPs) were developed and evaluated for their in vitro potential in HT-1080 cell line. The cNGR-DNB-NPs containing particles were about 148 nm in diameter with spherical shape and high encapsulation efficiency. Cellular uptake was confirmed both qualitatively and quantitatively by Confocal Laser Scanning Microscopy (CLSM) and flow cytometry. Both quantitatively and qualitatively results confirmed the NGR conjugated nanoparticles revealed the higher uptake of nanoparticles by CD13-overexpressed tumor cells. Free NGR inhibited the cellular uptake of cNGR-DNB-NPs, revealing the mechanism of receptor mediated endocytosis. In vitro cytotoxicity studies demonstrated that cNGR-DNB-NPs, formulation was more cytotoxic than unconjugated one, which were consistent well with the observation of cellular uptake. Hence, the selective delivery of cNGR-DNB-NPs formulation in CD13-overexpressing tumors represents a potential approach for the design of nanocarrier-based dual targeted delivery systems for targeting the tumor cells and vasculature.

Keywords: solid Tumor, docetaxel, targeting, NGR ligand

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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: Darma Putra Sitepu, Dewi Larasati, Yohanes Wolter Hendrik George

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Sepsis is a life-threatening medical emergency frequently observed in intensive care unit (ICU). Surviving Sepsis Campaign in 2018 has recommended the administration of early vasopressor in the first hour of sepsis or septic shock but has not yet included de-resuscitation protocol. De-resuscitation in acute management of septic shock is where patient received active removal of accumulated fluid. It has been proposed by some studies and ongoing clinical trials. Here we present a case with early vasopressor and de-resuscitation. Male, 27 years old presenting to the emergency room with shortness of breath, altered mental status, and widespread blisters on his body and lips started a few hours prior, after receiving non-steroidal anti-inflammatory drug through intravenous injection. Patient was hypotensive, tachycardic, and tachypneic at admission, diagnosed with Steven Johnson Syndrome with Septic Shock. Patient received fluid resuscitation, early vasopressor, and diuresis agent aimed to actively remove fluid after the initial phase of resuscitation. Patient was admitted to ICU and progressively recovering. At day-10, patient was stabilized and was transferred to general ward. Early vasopressor and de-resuscitation are beneficial for the patient.

Keywords: sepsis, shock, de-resuscitation, vasopressor, fluid, case report

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Authors: Mohamed N. Al-Arifi, Hessa Othman Al-Husein, Mostafa Q. Al Shamiri, Ragab Said, Syed Wajid, Salmeen D. Babelghaith

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Polypharmacy was defined as a taking more than 4 medications per single patients (minor polypharmacy), patients who are taking more than 10 medications we considered as a major polypharmacy. This study was aimed to evaluate the prevalence of polypharmacy in elderly Saudi cardiac patient. A retrospective observational study was carried out at the department of CCU and cardiology unit of the King Fahad cardiac centre (KFCC) in King Khalid university hospital from May 2012 to October 2012. All Parameters was analyzed by using Statistical Packages for Social Science (SPSS) to conclude the result; tests of association were performed using the chi-square statistic. The mean age of patients was 70.1 ± 7.75 years, more than half 83 (51.6%) were males. The highest frequency of chronic diseases found were hypertension (91.0%) followed by, dyslipidemia (74.9%), and diabetes mellitus. Results showed that 82% had polypharmacy (>4 drugs) during the study period, and 47.9% had major polypharmacy. The incidence of inappropriate drug use was found to be higher with men than female (p = 0.984). In conclusion, this study revealed that high prevalence of polypharmacy and potentially inappropriate medications in elderly Saudi cardiac inpatients.

Keywords: cardiac inpatients, medications, polypharmacy, prevalence

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Authors: Kedar S. Prabhavalkar, Nimmy Baby Poovanpallil

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Lamotrigine is approved for maintenance treatment of bipolar I disorder. However, its role in the treatment of acute bipolar depression is not well clear. Its efficacy in the treatment of major depressive disorders including refractory unipolar depression suggested the use of lamotrigine as an augmentation drug for acute bipolar depression. The present study aims to evaluate and perform a comparative analysis of the therapeutic effects of lamotrigine, an epileptic mood stabilizer, when used alone and in combination with duloxetine in treating acute bipolar depression at different doses of lamotrigine. Male swiss albino mice were used. For evaluation of efficacy of combination, immobility period was analyzed 30 min after the treatment from forced swim and tail suspension tests. Further amount of sucrose consumed in sucrose preference test was estimated. The combination of duloxetine and lamotrigine showed potentiation of antidepressant activity in acute models. Decrease in immobility time and increase in the amount of sucrose consumption in stressed mice were higher in combined group compared to lamotrigine monotherapy group. Brain monoamine levels were also attenuated more with combination compared to monotherapy. Results of the present study suggest potential role of lamotrigine and duloxetine combination in the treatment of acute bipolar depression.

Keywords: lamotrigine, duloxetine, acute bipolar depression, augmentation

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Authors: T. Mdzinarashvili, M. Khvedelidze, E. Shekiladze, S. Chinchaladze, M. Mdzinarashvili

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The study of the possible interaction between calcium ions and lipids is of great importance for the studies of complexes of calcium drug-carrying nanoparticles. We prepared calcium-containing complex liposomes from Dipalmitoylphosphatidylcholine (DPPC) lipids and studied their thermodynamic properties. In calorimetric studies, we determined that the phase transition temperature of these complexes is close to 420 C. It was shown that both hydrophobic and hydrophilic connections take part in the formation of calcium nanoparticles. We were interested in hydrophilic bonds represented by hydrogen bonds. We have shown that these hydrogen bonds are formed between the phospholipid heads, and the main contributor is the oxygen atoms in the phosphoric acid residues. In addition, based on the amount of heat absorbed during the breaking of hydrogen bonds formed between calcium-containing nanoparticle complexes, it can be concluded that the hydrogen atoms in the head of DPPC lipids form hydrogen bonds between P=O and P-O groups of phosphate. The energy of heat absorption measured by the calorimeter is of the order obtained by breaking the hydrogen bonds we have specified. Thus, we conclude that our approach to the model of liposome formation from lipids is correct. As for calcium atoms - due to the fact that it is present in the form of positive ions in the liposome, they will connect only with negatively charged phosphorus ions.

Keywords: DPPC, liposomes, calcium, complex nanoparticles

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Authors: S. Pradhan, D. Pradhan, G. Tripathy, T. Dasmohapatra

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Suppressors of cytokine signalling (SOCS3), a newly indentified anti-apoptotic molecule is a downstream effecter of the receptor tyrosine kinase-Ras signalling pathway. Current study has uncovered that SOCS3 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS3 on MDR, we analyzed the expression of P-gp and SOCS3 by immune-histochemistry and found there was positive correlation between them. At that point we effectively interfered with RNA translation by the contamination of siRNA of SOCS3 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flowcytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS3 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: SOCS3gene, breast cancer, multidrug resistance, MDR1 gene, RNA interference

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Authors: Yasser Gaber, Mohamed Ismail, Serena Bisagni, Mohamad Takwa, Rajni Hatti-Kaul

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Enzymes are safe and selective catalysts. They skillfully catalyze chemical reactions; however, the native form is not usually suitable for industrial applications. Enzymes are therefore engineered by several techniques to meet the required catalytic task. Clopidogrel is recorded among the five best selling pharmaceutical in 2010 under the brand name Plavix. The commonly used route for production of the drug on an industrial scale is the synthesis of the racemic mixture followed by diastereomeric resolution to obtain the pure S isomer. The process consumes a lot of solvents and chemicals. We have evaluated a biocatalytic cleaner approach for asymmetric hydrolysis of racemic clopidogrel. Initial screening of a selected number of hydrolases showed only one enzyme EST to exhibit activity and selectivity towards the desired stereoisomer. As the crude EST is a mixture of several isoenzymes, a homology model of EST-1 was used in molecular dynamic simulations to study the interaction of the enzyme with R and S isomers of clopidogrel. Analysis of the geometric hindrances of the tetrahedral intermediates revealed a potential site for mutagenesis in order to improve the activity and the selectivity. Single point mutation showed dramatic increase in activity and inversion of the enantioselectivity (400 fold change in E value).

Keywords: biocatalysis, biotechnology, enzyme, protein engineering, molecular modeling

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Authors: Sakshi Tomar, Renu Chadha

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Cocrystallization comprises a selective route to the intensive design of pharmaceutical products with desired physiochemical and pharmacokinetic properties. The present study is focused on the preparation, characterization, and evaluation of etodolac (ET) co-crystals with coformers nicotinamide (ETNI) and Glutaric acid (ETGA), using cocrystallization approach. Preliminarily examination of the prepared co-crystal was done by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD). DSC thermographs of ETNI and ETGA cocrystals showed single sharp melting endotherms at 144°C and 135°C, respectively, which were different from the melting of drugs and coformers. FT-IR study points towards carbonyl-acid interaction sandwiched between the involving molecules. The emergence of new peaks in the PXRD pattern confirms the formation of new crystalline solid forms. Both the cocrystals exhibited better apparent solubility, and 3.8-5.0 folds increase in IDR were established, as compared to pure etodolac. Evaluations of these solid forms were done using anti-osteoarthritic activities. All the results indicate that etodolac cocrystals possess better anti-osteoarthritic efficacy than free drug. Thus loom of cocrystallization has been found to be a viable approach to resolve the solubility and bioavailability issues that circumvent the use of potential antiosteoarthritic molecules.

Keywords: bioavailability, etodolac, nicotinamide, osteoarthritis

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Authors: Ghazanfar Ali, Fahad N Almajhdi

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This study provides data on the viral diagnosis and molecular epidemiology of influenza A(H3N2) virus isolated in Riyadh, Saudi Arabia. Nasopharyngeal aspirates from 80 clinically infected patients in the peak of the 2010-2011 winter seasons were processed for viral diagnosis by RT-PCR. Sequencing of entire HA and NA genes of representative isolates and molecular epidemiological analysis were performed. A total of 06 patients were positive for influenza A, B and respiratory syncytial viruses by RT-PCR assays; out of these only one sample was positive for influenza A(H3N2) by RT-PCR. Phylogenetic analysis of the HA and NA gene sequences showed identities higher than 99-98.8 % in both genes. They were also similar to reference isolates in HA sequences (99 % identity) and in NA sequences (99 % identity). Amino acid sequences predicted for the HA gene were highly identical to reference strains. The NA amino acid substitutions identified did not include the oseltamivir-resistant H275Y substitution. Conclusion: Viral isolation and RT-PCR together were useful for diagnosis of the influenza A (H3N2) virus. Variations in HA and NA sequences are similar to those identified in worldwide reference isolates and no drug resistance was found.

Keywords: influenza A (H3N2), genetic characterization, viral isolation, RT-PCR, Saudi Arabia

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Authors: Sourabh Jain, Vikas Jain, Dharmendar Kumar

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The present study investigated the antidiabetic potential of Cedrus deodara heart wood aqueous extract. Aqueous extract of Cedrus deodara was found to reduce blood sugar level in alloxan induced diabetic rats. Reduction in blood sugar could be seen from 5th day after continuous administration of the extract and on 21st day sugar levels were found to be reduced by 40.20%. Oxidative stress produced by alloxan was found to be significantly lowered by the administration of Cedrus deodara aqueous extract (500 mg/kg). This was evident from a significant decrease in lipid per oxidation level in liver induced by alloxan. The level of Glutathione, Catalase, Superoxide dismutase and Glutathione-S-Transferase in liver, kidney and pancreas tissue were found to be increased significantly after drug administration. The results obtained in the present study suggest that the Cedrus deodara aqueous extract effectively and significantly reduced the oxidative stress induced by alloxan and produced a reduction in blood sugar level.

Keywords: Cedrus deodara, heartwood, antioxidant, anti-diabetic, anti-inflammatory

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Authors: Murat Mert, Yusuf Ozer, Fatih Kolay

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Behaviour of giving harm to the body in literature has been named as “self-injury”, “self-mutilation” ve “self-harm”. “Self-injury”, or “self-mutilation” is generally used for the same meaning and mentioned as an action which is committed to the body itself directly. As is seen that alcohol and drug users have injured their bodies because of deprivation, whereas behaviour of self-injury in some societies is accepted as religious and cultural, it has nevertheless been diagnosed in people who have a borderline personality disorder, histrionic personality disorder, psychotic personality disorder and mood disorder. There has not been any direct self-murder tendency in people having self-harmed. However, death cases can be seen together with loss of consciousness depending on loss of blood by exceeding the limit in the course of injury action. 34- year old – male person who was alcohol addicted, having had a psycological treatment beforehand, had mutilated his small intestine together with fatty tissue by cutting his body with a razor-blade at the thought of insects strolling around the body (delirium tremens) due to deprivation attack and had died in the result of various cuts. In this study, crime scene investigation and death mechanism of the person having had self-harmed in a result of abstinence syndrome will be explained. Relevant criteria which differentiate this case from homicide will be examined.

Keywords: self-injury, autopsy, abstinence syndrome, CSI

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Authors: Seyedeh Zeinab Peighambarzadeh, Mehdi Tavana

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Cataract is the most common cause of blindness worldwide and its incidence will increase as the World’s population ages. Even in modern ophthalmology, there is no effective medical treatment for cataract except surgery. Development of a drug which could prevent or delay the onset of cataract will lessen this burden and reduce the number of blind patients waiting for cataract surgery. This study was undertaken to evaluate the protective effect of vitamin E on Selenite-induced Cataract in Sprague-dawely rats. Cataracts were induced in rats by administration of sodium selenite. On postpartum day ten, in group I, saline was injected subcutaneously. Group II rat pups received subcutaneous injection of vitamin E (60mg/kg B.W.) at day 8 postpartum and every other day thereafter. Group III and IV rat pups received a subcutaneous injection of sodium selenite (13mg/kg B.W.) at day 10 postpartum. Group IV also received subcutaneous injection of vitamin E (60mg/kg B.W.) at day 8 postpartum and every other day thereafter. The development of cataract in rats was assessed clinically by slit-lamp biomicroscope from day 14 up to postpartum day 28. After sacrifice, extricated pup lenses were analyzed for total and soluble protein concentrations and eletrophoretic pattern (SDS-PAGE). There was no opacification of lens in Group I and II. There was mature cataract in 95% of Group III. In group IV, 55% of rats developed sub capsular or cortical cataract. Cataractous and biochemical changes of the crystalline lens proteins due to selenite can be retard or prevented by vitamin E.

Keywords: preventive effect, selenite-induced cataract, vitamin E, rat

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Authors: Olphiara Rodolpheza Alexandre, Carla David, Rafael Guerra Lund, Nadia Ferreira

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Due to the increasing demand for biomaterials in the dental field, especially in endodontics, calcium silicate-based cements (CSCs) have gained prominence because of their biocompatibility and tissue regeneration capabilities. Originating from Mineral Trioxide Aggregate (MTA), the first bioceramic in endodontics derived from Portland cement, these materials are becoming increasingly prevalent in the market. For any drug released to the market, pharmacovigilance must ensure the absence of adverse health effects on consumers through rigorous toxicological testing. Although these materials have undergone in vitro and in vivo testing, such tests have typically been conducted over a limited period. Some effects may only become apparent after several years, and these studies are generally carried out on a non-specific population. However, the variety of calcium silicate-based products, including cement and sealers, raises questions about their toxicity, particularly considering potential long-term effects not addressed in existing studies. While the scientific literature includes comparative studies on the toxicity of these materials, the consistency of their conclusions is often controversial. Therefore, this project aims to map the scientific evidence from in vitro biocompatibility studies, including those investigating the toxicity of calcium silicate-based bioceramics.

Keywords: toxicity, toxicity test, bioceramics, calcium silicate, genotoxicity

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Authors: Wafa Al Jabri

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Background: In Middle Eastern Countries (MECs), there is a high prevalence of genetic blood disorders (GBDs), particularly sickle cell disease and thalassemia. The GBDs are considered a major public health concern that place a huge burden to individuals, families, communities, and health care systems. The high rates of consanguineous marriages, along with the unacceptable termination of at-risk pregnancy in MECs, reduce the possible solutions to control the high prevalence of GBDs. Since the early 1970s, most of MECs have started introducing premarital screening services (PSS) as a preventive measure to identify the asymptomatic carriers of GBDs and to provide genetic counseling to help couples plan for healthy families; yet, the success rate of PSS is very low. Purpose: This paper aims to highlight the factors that affect the success of PSS in MECs. Methods: An integrative review of articles located in CINAHL, PubMed, SCOPUS, and MedLine was carried out using the following terms: “premarital screening,” “success,” “effectiveness,” and “ genetic blood disorders”. Second, a hand search of the reference lists and Google searches were conducted to find studies that did not exist in the primary database searches. Only studies which are conducted in MECs and published after 2010 were included. Studies that were not published in English were excluded. Results: Eighteen articles were included in the review. The results showed that PSS in most of the MECs was successful in achieving its objective of identifying high-risk marriages; however, the service failed to meet its ultimate goal of reducing the prevalence of GBDs. Various factors seem to hinder the success of PSS, including poor public awareness, late timing of the screening, culture and social stigma, lack of prenatal diagnosis services and therapeutic abortion, emotional factors, religious beliefs, and lack of genetic counseling services. However, poor public awareness, late timing of the screening, religious misbeliefs, and the lack of adequate counseling services were the most common barriers identified. Conclusion and Implications: The review help in providing a framework for an effective preventive measure to reduce the prevalence of GBDs in MECS. This framework focuses primarily in overcoming the identified barriers by providing effective health education programs in collaboration with religious leaders, offering the screening test to young adults at an earlier stage, and tailoring the genetic counseling to consider people’s values, beliefs, and preferences.

Keywords: premarital screening, middle east, genetic blood disorders, factors

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Authors: Zahra Tolou-Ghamari

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Introduction: After allogeneic organ transplantation, in order to lower the rate of rejectiontacrolimus is given. In fact, infection is reported as the most complication of tacrolimus that might be associated with higher susceptibility by its’ long term use. Aim: This study aims to review the association between the occurrence of infections after organ transplantation following the administration of tacrolims. Materials and Methods: Scientific literature on the pharmacotherapy of tacrolimus after organ transplantation and infections were searched using PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/), Web of Science, and Scopus. Results: In order to prevent acute and chronic rejection, the potent immunosuppressive drug tacrolimus administered as a calcineurin inhibitor after organ transplantation. Its’ most frequent infectious complication is reported as urinary tract infection. Virulent strain of recombinant Literiamonocytogenes, in addition to an increase in bacterial burden in the liver and spleen tissues, was reported in the animal experimental study. The consequence of aggressive events and recipients total area under the cureve exposure to immunosuppressive could be as considered as surrogate markers for individual infection’s risk evaluation. Conclusion: Transplant surgery and duration of hospital stay could determinate the risk of infection during the first month of organ transplantation. Despite administration of antiviral drugs, opportunistic infection such as cytomegalovirus could increase the risk of infection during month 1 to year after transplantation.

Keywords: transplant, infection, tacrolimus, kidney

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Authors: Vishal Kumar Singh

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Bioprocess development is a time-constrained activity aimed at harnessing the full potential of culture performance in an ambience that is not natural to cells. Even with the use of chemically defined media and feeds, a significant amount of time is devoted in identifying the apt operating parameters. In addition, the scale-up of these processes is often accompanied by loss of antibody titer and product quality, which further delays the commercialization of the drug product. In such a scenario, the investigation of this disparity of culture performance is done by further experimentation at a smaller scale that is representative of at-scale production bioreactors. These scale-down model developments are also time-intensive. In this study, a computation fluid dynamics-based multi-objective scaling approach has been illustrated to speed up the process transfer. For the implementation of this approach, a transient multiphase water-air system has been studied in Ansys CFX to visualize the air bubble distribution and volumetric mass transfer coefficient (kLa) profiles, followed by the design of experiment based parametric optimization approach to define the operational space. The proposed approach is completely in silico and requires minimum experimentation, thereby rendering a high throughput to the overall process development.

Keywords: bioprocess development, scale up, scale down, computation fluid dynamics, multi-objective, Ansys CFX, design of experiment

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Authors: Yomna T. Abdou, Hala F. Zaki, Sanaa A. Kenawy

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Naringenin is a flavanone, a type of flavonoid, found in fruits such as grapefruit, oranges, and tomatoes, was found to possess antioxidant, anti-inflammatory and antitumor effects. The present study was conducted to investigate the protective effect of naringenin on iodoacetamide-induced ulcerative colitis (UC) in rats. Male Wistar rats were pretreated with sulfasalazine (300 mg/kg, p.o.) as standard anti-inflammatory drug or naringenin (50 mg/kg, p.o.) for 7 consecutive days then UC was induced by intracolon administration of 0.1 ml (2%) iodoacetamide dissolved in 1% methylcelluose. One week later, animals were scarificed and the colonic tissues were dissected. Colon inflammation was evident by elevation in colon tumor necrosis factor alpha (TNFα) and interleukin-8 (IL-8) as well as inducible nitric oxide synthase (iNOS) enzyme, prostaglandin- E2 (PG-E2) and myeloperoxidase (MPO) activities. Additionally, oxidative stress was manifested by increased colon lipoperoxidation (MDA), glutathione (GSH) depletion, elevated nitric oxide (NO) content and glutathione peroxidase (GPx) activity. Pretreatment with naringenin largely mitigated these alterations. The present study reinforces the hypothetical use of naringenin as an anti-inflammatory complement to conventional UC treatment and could be considered in the dietary prevention of intestinal inflammation and related disorders.

Keywords: iodoacetamide, naringenin, sulfasalazine, ulcerative colitis

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Authors: Richard Ssempala, Francis Kintu, Christine K. Tashobya

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Funding for health remains a key constraint facing many developing countries, Uganda inclusive. Uganda’s health sector budget to the national budgetary allocation has stagnated between 8.2% to 10% over the years. Using data collected from different government documents, we sought to establish the implications of the budget allocation over the period (FY2010/11-2018/19) on health services delivery in Uganda to inform policymakers specifically Members of Parliament who are critical in making sectorial allocation on the steps they can adapt to change the terrain of health financing in Uganda. Findings revealed that the contribution of public funding to the health sector is low (15.7%) with private sources (42.6%) and donors contributing much more, with the bulk of private funds, are out of pocket. The study further revealed that low budget allocation had been manifested in inadequate and poorly motivated health workers, essential drug stock-outs that ultimately contribute to poor access to services, catastrophic health expenditures, and high morbidity rates. We recommend for a substantial and sustained increase in the government health budget, optimizing the available resources by addressing wastages, prioritizing health promotion, prevention and finally, institutionalizing the National Health Insurance Scheme.

Keywords: budget allocations, universal health coverage, health service delivery, Uganda

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Authors: Sonam Kumari

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Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, possesses a remarkable feature of entering into and emerging from a persistent state. The mechanism by which Mtb switches from the dormant state to the replicative form is still poorly characterized. Proteome studies have given us an insight into the role of certain proteins in giving stupendous virulence to Mtb, but numerous dotsremain unconnected and unaccounted. The WhiB family of proteins is one such protein that is associated with developmental processes in actinomycetes.Mtb has seven such proteins (WhiB1 to WhiB7).WhiB proteins are transcriptional regulators; their conserved C-terminal HTH motif is involved in DNA binding. They regulate various essential genes of Mtbby binding to their promoter DNA. Biophysical Analysis of the effect of DNA binding on WhiB proteins has not yet been appropriately characterized. Interaction with DNA induces conformational changes in the WhiB proteins, confirmed by steady-state fluorescence and circular dichroism spectroscopy. ITC has deduced thermodynamic parameters and the binding affinity of the interaction. Since these transcription factors are highly unstable in vitro, their stability and solubility were enhanced by the co-expression of molecular chaperones. The present study findings help determine the conditions under which the WhiB proteins interact with their interacting partner and the factors that influence their binding affinity. This is crucial in understanding their role in regulating gene expression in Mtbandin targeting WhiB proteins as a drug target to cure TB.

Keywords: tuberculosis, WhiB proteins, mycobacterium tuberculosis, nucleic acid binding

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Authors: H. Boucheloukh, S. Rouissa, N. Aoun, M. Beloucifa, T. Sehili, F. Parrino, V. Loddo

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To optimize water purification and wastewater treatment by heterogeneous photocatalysis, we used NiFe₂O₄ as a catalyst and solar irradiation as a source of energy. In this concept, an organic substance present in many industrial effluents was chosen: naproxen ((S)-6-methoxy-α-methyl-2-naphthaleneacetic acid or 2-(6-methoxynaphthalenyl) propanoic), a non-steroidal anti-inflammatory drug. The main objective of this study is to degrade naproxen by an iron and nickel catalyst, the degradation of this organic pollutant by nickel ferrite has been studied in a heterogeneous aqueous medium, with the study of the various factors influencing photocatalysis such as the concentration of matter and the acidity of the medium. The photocatalytic activity was followed by HPLC-UV andUV-Vis spectroscopy. A first-order kinetic model appropriately fitted the experimental data. The degradation of naproxen was also studied in the presence of H₂O₂ as well as in an aqueous solution. The new hetero-system NiFe₂O₄/oxalic acid is also discussed. The fastest naproxen degradation was obtained with NiFe₂O₄/H₂O₂. In a first-place, we detailed the characteristics of the material NiFe₂O₄, which was synthesized by the sol-gel methods, using various analytical techniques: visible UV spectrophotometry, X-ray diffraction, FTIR, cyclic voltammetry, luminescent discharge optical emission spectroscopy.

Keywords: naproxen, nickelate, photocatalysis, oxalic acid

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Authors: Friday Godwin Okibe, Christian Chinweuba Onoyima, Edith Bolanle Agbaji, Victor Olatunji Ajibola

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Polymer-inorganic nanocomposites are presently impacting diverse areas, specifically in biomedical sciences. In this research, hydroxyapatite-sodium alginate has been prepared, and characterized, with emphasis on the influence of sodium alginate on its characteristics. In situ wet chemical precipitation method was used in the preparation. The prepared nanocomposite was characterized with Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), with image analysis, and X-Ray Diffraction (XRD). The FTIR study shows peaks characteristics of hydroxyapatite and confirmed formation of the nanocomposite via chemical interaction between sodium alginate and hydroxyapatite. Image analysis shows the nanocomposites to be of irregular morphologies which did not show significant change with increasing sodium alginate addition, while particle size decreased with increase in sodium alginate addition (359.46 nm to 109.98 nm). From the XRD data, both the crystallite size and degree of crystallinity also decreased with increasing sodium alginate composition (32.36 nm to 9.47 nm and 72.87% to 1.82% respectively), while the specific surface area and microstrain increased with increasing sodium alginate composition (0.0041 to 0.0139 and 58.99 m²/g to 201.58 m²/g respectively). The results show that the formulation with 50%wt of sodium alginate (HASA-50%wt), possess exceptional characteristics for biomedical applications such as drug delivery.

Keywords: nanocomposite, sodium alginate, hydroxyapatite, biomedical, FTIR, XRD, SEM

Procedia PDF Downloads 330