Search results for: non steridol anti inlfammatory agents

Authors: Monalisa Pradhan, Ajana Dutta, Irshad Kariyattuparamb Abbas, Boby Joseph, T. N. Guru Row, Diptikanta Swain, Gopal K. Pradhan

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Compounds with the Vanthoffite crystal structure having general formula Na6M(SO₄)₄ (M= Mg, Mn, Ni , Co, Fe, Cu and Zn) display a variety of intriguing physical properties intimately related to their structural arrangements. The compound Na6Mn(SO4)4 shows antiferromagnetic ordering at low temperature where the in-plane Mn-O•••O-Mn interactions facilitates antiferromagnetic ordering via a super-exchange interaction between the Mn atoms through the oxygen atoms . The inter-atomic bond distances and angles can easily be tuned by applying external pressure and can be probed using high resolution X-ray diffraction. Moreover, because the magnetic interaction among the Mn atoms are super-exchange type via Mn-O•••O-Mn path, the variation of the Mn-O•••O-Mn dihedral angle and Mn-O bond distances under high pressure inevitably affects the magnetic properties. Therefore, it is evident that high pressure studies on the magnetically ordered materials would shed light on the interplay between their structural properties and magnetic ordering. This will indeed confirm the role of buckling of the Mn-O polyhedral in understanding the origin of anti-ferromagnetism. In this context, we carried out the pressure dependent X-ray diffraction measurement in a diamond anvil cell (DAC) up to a maximum pressure of 17 GPa to study the phase transition and determine equation of state from the volume compression data. Upon increasing the pressure, we didn’t observe any new diffraction peaks or sudden discontinuity in the pressure dependences of the d values up to the maximum achieved pressure of ~17 GPa. However, it is noticed that beyond 12 GPa the a and b lattice parameters become identical while there is a discontinuity in the β value around the same pressure. This indicates a subtle transition to a pseudo-monoclinic phase. Using the third order Birch-Murnaghan equation of state (EOS) to fit the volume compression data for the entire range, we found the bulk modulus (B0) to be 44 GPa. If we consider the subtle transition at 12 GPa, we tried to fit another equation state for the volume beyond 12 GPa using the second order Birch-Murnaghan EOS. This gives a bulk modulus of ~ 34 GPa for this phase.

Keywords: mineral, structural phase transition, high pressure XRD, spectroscopy

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Authors: Ahmed El-Fiqi, Hae-Won Kim

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Incorporation of therapeutic elements such as Sr, Cu and Co into bioglass structure and their release as ions is considered as one of the promising approaches to enhance cellular responses, e.g., osteogenesis and angiogenesis. Here, cobalt as angiogenesis promoter has been incorporated (at 0, 1 and 4 mol%) into sol-gel derived calcium silicate mesoporous bioglass nanoparticles. The composition and structure of cobalt-free (CFN) and cobalt-doped (CDN) mesoporous bioglass nanoparticles have been analyzed by X-ray fluorescence (XRF), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier-Transform Infra-red spectroscopy (FT-IR). The physicochemical properties of CFN and CDN have been investigated using high-resolution transmission electron microscopy (HR-TEM), Selected area electron diffraction (SAED), and Energy-dispersive X-ray (EDX). Furthermore, the textural properties, including specific surface area, pore-volume, and pore size, have been analyzed from N²⁻sorption analyses. Surface charges of CFN and CDN were also determined from surface zeta potential measurements. The release of ions, including Co²⁺, Ca²⁺, and SiO₄⁴⁻ has been analyzed using inductively coupled plasma atomic emission spectrometry (ICP-AES). Loading and release of diclofenac as an anti-inflammatory drug model were explored in vitro using Ultraviolet-visible spectroscopy (UV-Vis). XRD results ensured the amorphous state of CFN and CDN whereas, XRF further confirmed that their chemical compositions are very close to the designed compositions. HR-TEM analyses unveiled nanoparticles with spherical morphologies, highly mesoporous textures, and sizes in the range of 90 - 100 nm. Moreover, N²⁻ sorption analyses revealed that the nanoparticles have pores with sizes of 3.2 - 2.6 nm, pore volumes of 0.41 - 0.35 cc/g and highly surface areas in the range of 716 - 830 m²/g. High-resolution XPS analysis of Co 2p core level provided structural information about Co atomic environment and it confirmed the electronic state of Co in the glass matrix. ICP-AES analysis showed the release of therapeutic doses of Co²⁺ ions from 4% CDN up to 100 ppm within 14 days. Finally, diclofenac loading and release have ensured the drug/ion co-delivery capability of 4% CDN.

Keywords: mesoporous bioactive glass, nanoparticles, cobalt ions, release

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Authors: Debamitra Chakravorty, Pratap K. Parida

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Cold-adapted proteases enhance wash performance in low-temperature laundry resulting in a reduction in energy consumption and wear of textiles and are also used in the dehairing process in leather industries. Unfortunately, the possible drawbacks of using cold-adapted proteases are their instability at higher temperatures. Therefore, proteases with broad temperature stability are required. Unfortunately, wild-type cold-adapted proteases exhibit instability at higher temperatures and thus have low shelf lives. Therefore, attempts to engineer cold-adapted proteases by protein engineering were made previously by directed evolution and random mutagenesis. The lacuna is the time, capital, and labour involved to obtain these variants are very demanding and challenging. Therefore, rational engineering for cold stability without compromising an enzyme's optimum pH and temperature for activity is the current requirement. In this work, mutations were rationally designed with the aid of high throughput computational methodology of network analysis, evolutionary conservation scores, and molecular dynamics simulations for Savinase from Bacillus lentus with the intention of rendering the mutants cold stable without affecting their temperature and pH optimum for activity. Further, an attempt was made to incorporate a mutation in the most stable mutant rationally obtained by this method to introduce oxidative stability in the mutant. Such enzymes are desired in detergents with bleaching agents. In silico analysis by performing 300 ns molecular dynamics simulations at 5 different temperatures revealed that these three mutants were found to be better in cold stability compared to the wild type Savinase from Bacillus lentus. Conclusively, this work shows that cold adaptation without losing optimum temperature and pH stability and additionally stability from oxidative damage can be rationally designed by in silico enzyme engineering. The key findings of this work were first, the in silico data of H5 (cold stable savinase) used as a control in this work, corroborated with its reported wet lab temperature stability data. Secondly, three cold stable mutants of Savinase from Bacillus lentus were rationally identified. Lastly, a mutation which will stabilize savinase against oxidative damage was additionally identified.

Keywords: cold stability, molecular dynamics simulations, protein engineering, rational design

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Authors: Ilona Ivova Anachkova

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The analogy between the artist and the shaman as both being practitioners that more easily recognize and explore spiritual matters, and thus contribute to the society in a unique way has been implied in both Modernity and Postmodernity. The Romantic conception of the shaman as a great artist who helps common men see and understand messages of a higher consciousness has been employed throughout Modernity and is active even now. This paper deconstructs the term ‘shaman’ in the metaphorical analogy ‘artist – shaman’ that was developed more fully in Modernity in different artistic and scientific discourses. The shaman is a figure that to a certain extent adequately reflects the late modern and postmodern holistic views on the world. Such views aim at distancing from traditional religious and overly rationalistic discourses. However, the term ‘shaman’ can be well substituted by other concepts such as the priest, for example. The concept ‘shaman’ is based on modern ethnographic and historical investigations. Its later philosophical, psychological and artistic appropriations designate the role of the artist as a spiritual and cultural leader. However, the artist and the shaman are not fully interchangeable terms. The figure of the shaman in ‘primitive’ societies has performed many social functions that are now delegated to different institutions and positions. The shaman incorporates the functions of a judge, a healer. He is a link to divine entities. He is the creative, aspiring human being that has heightened sensitivity to the world in both its spiritual and material aspects. Building the metaphorical analogy between the shaman and the artist comes in many ways. Both are seen as healers of the society, having propensity towards connection to spiritual entities, or being more inclined to creativity than others. The ‘shaman’ however is a fashionable word for a spiritual person used perhaps because of the anti-traditionalist religious modern and postmodern views. The figure of the priest is associated with a too rational, theoretical and detached attitude towards spiritual matters, while the practices of the shaman and the artist are considered engaged with spirituality on a deeper existential level. The term ‘shaman’ however does not have priority of other words/figures that can explore and deploy spiritual aspects of reality. Having substituted the term ‘shaman’ in the pair ‘artist as a shaman’ with ‘the priest’ or literally ‘anybody,' we witness destruction of spiritual hierarchies and come to the view that everybody is responsible for their own spiritual and creative evolution.

Keywords: artist as a shaman, creativity, extended theory of art, functions of art, priest as an artist

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Authors: Zhala Ahmad, Zainab Lazim, Haider Hamzah

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Bacterial resistance is a pressing global health issue, with multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) strains to pose a serious threat. In this context, researchers are investigating effective, safe, and affordable metabolites to combat these pathogens. This study focuses on gum essential oil (GEO) extracted from Pistacia atlantica and its activity and the mechanism of action against XDR Gram-negative Acinetobacter baumannii. GEO was extracted by hydrodistillation and analyzed using GC-MS. Eleven A. baumannii isolates were collected from the ward environment of Burn and Plastic Surgery Hospital in Al Sulaymaniyah City, Iraq. They were identified using the VITEK 2 system, 16S rRNA gene, and confirmed with the blaₒₓₐ₋₅₁ gene; A. baumannii ATCC 19606 was used as a reference strain. The isolates were identified as resistant to twelve different antibiotics spanning six distinct antibiotic classes while showing susceptibility to tetracycline and trimethoprim. Over 40 chemical constituents were detected in the gum's essential oils, with α-pinene being the most abundant. GEO was found to inhibit the growth of A. baumannii isolates; the minimum inhibitory concentration (MIC) of GEO was 2.5 µl/ml. GEO induced protein leakage, phosphate, and potassium ion efflux, distorted cell morphology, and cell death in the tested bacteria. GEO exhibited bacterial clearance and anti-adhesion activity using Band-Aids. This study's findings suggest that GEO could be used as a potential alternative treatment for infectious diseases caused by XRD pathogens, shedding further light on the importance of GEO in biomedical applications. Future studies must focus on generating clinically feasible sources of GEO for testing in small animal models before proceeding to human trials, ensuring safe and effective translation from the laboratory to the clinic.

Keywords: antibiotic resistance, Acinetobacter baumannii, essential oils, Pistacia atlantica, alpha-pinene

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Authors: Leixuri Aguirre, Iñaki Milton-Laskibar, Elizabeth Hijona, Luis Bujanda, Agnes M. Rimando, Maria P. Portillo

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Introduction: In recent years great attention has been paid by scientific community to phenolic compounds as active biomolecules naturally present in foodstuffs due to their beneficial effects on health. Pterostilbene is a resveratrol dimethylether derivative which shows higher biodisponibility. Objective. To analyze the effects of two doses of pterostilbene on several markers of thermogenic capacity in a model of genetic obesity, which shows reduced thermogenesis. Methods: The experiment was conducted with thirty Zucker (fa/fa) rats that were distributed in 3 experimental groups, the control group and two groups orally administered with pterostilbene at 15 and 30 mg/kg body weight/day for 6 weeks. Gene expression of Ucp1, Pgc-1α, Cpt1b, Pparα, Nfr1, Tfam and Cox-2 were assessed by RT-PCR, protein expression of UCP1 and GLUT4 by western blot and enzyme activity of carnitine palmitoyl transferase 1b and citrate synthase by spectrophotometry in interscapular brown adipose tissue (iBAT). Statistical analysis was performed by using one way ANOVA and Newman-Keuls as post-hoc test. Results: Pterostilbene did not change gene expression of Pgc-1α. However, significant increases were found in the expression of Ucp1, Pparα, Nfr-1 and Cox-2. Protein expression of UCP1 and GLUT4 was increased in animals treated with pterostilbene, as well as the activities of CPT-1b and CS. These effects were observed with both doses of pterostilbene, without differences between them. Conclusions: These results show that pterostilbene increases thermogenic and oxidative capacity of brown adipose tissue in obese rats. Whether these effects effectively contribute to the anti-obesity properties of these compound needs further research. Acknowledgments: MINECO-FEDER (AGL2015-65719-R), Basque Government (IT-572-13), University of the Basque Country (ELDUNANOTEK UFI11/32), Institut of Health Carlos III (CIBERobn). Iñaki Milton is a fellowship from the Basque Government.

Keywords: brown adipose tissue, pterostilbene, thermogenesis, uncoupling protein 1

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Authors: Victoria I. Michailova, Denitsa B. Momekova, Hristiana A. Velichkova, Evgeni H. Ivanov

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The aim of this work is to design and develop thermo-responsive nanosized drug delivery systems based on poly(N-isopropylacrylamide)-g-poly(ethylene oxide) (PNIPAM-g-PEO) double hydrophilic graft copolymers. The PNIPAM-g-PEO copolymers are able to self-assemble in water into nanoparticles above the LCST of the thermo-responsive PNIPAM backbone and to disassemble and rapidly release the entrapped drugs upon cooling. However, their drug delivery applications are often hindered by their low loading capacity as the drugs to be encapsulated do not dissolve in water. In order to overcome this limitation, here we applied a low-temperature procedure with ethanol as an alternative route to the formation and loading a model hydrophobic drug, Indomethacin (IMC), into PNIPAM-g-PEO nanoparticles. The rationale for this approach was that ethanol dissolves both IMC and the copolymer and its mixing with water may induce micellization of PNIPAM-g-PEO at temperatures lower than the LCST. The influence of the volume fraction of ethanol and the temperature on the aggregation characteristics of PNIPAM-g-PEO copolymers (2.7 mol% PEO) was investigated by means of DLS, TEM and rheological dynamic oscillatory tests. The studies showed rich phase behavior at T < LCST, incl. the formation of highly solvated 500-1000 nm complex structures, 30-70 nm micelles and polymersomes as well as giant polymersomes, as the fraction of added ethanol increased. We believe that the PNIPAM-g-PEO self-assembly is favored due to the different solvation of its constituting blocks in ethanol-water mixtures. The incorporation of IMC led to alteration of the physicochemical and morphological characteristics of the blank nanoparticles. In this case, only monodisperse polymersomes and micelles were observed in the solutions with an average diameter less than 65 nm and substantial drug loading (DLC ~117 – 146 wt%). Indomethacin release from the nanoparticles was responsive to temperature changes, being much faster at a temperature of 42oC compared to that of 37oC under otherwise the same conditions. The results obtained suggest that these PNIPAM-g-PEO nanoparticles could be potential in mild hyper-thermic delivery of nonsteroidal anti-inflammatory drugs.

Keywords: drug delivery, nanoparticles, poly(N-isopropylacryl amide)-g-poly(ethylene oxide), thermo-responsive

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Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour

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Significant number of studies and preclinical research in formulation of cancer nano-pharmaceutics have led to an improvement in cancer care. Nonetheless, the antineoplastic agents have ‘failed to live up to its promise’ since their clinical performance is moderately low. For almost ninety years, iron oxide nanoparticles (IONPS) have managed to keep its reputation in clinical application due to their low toxicity, versatility and multi-modal capabilities. Drug Administration approved utilization of IONPs for diagnosis of cancer as contrast media in magnetic resonance imaging, as heat mediator in magnetic hyperthermia and for the treatment of iron deficiency. Furthermore, IONPs have high drug-loading capacity, which makes them good candidates as therapeutic agent transporters. There are yet challenges to overcome for successful clinical application of IONPs, including stability of drug and poor delivery, which might lead to (i) drug resistance, (ii) shorter blood circulation time, and (iii) rapid elimination and adverse side effects from the system. In this study, highly stable and super paramagnetic IONPs were prepared for efficient and targeted drug delivery in cancer treatment. The synthesis procedure was briefly involved the production of IONPs via co-precipitation followed by coating with tetraethyl orthosilicate and 3-aminopropylethoxysilane and grafting with folic acid for stability targeted purposes and controlled drug release. Physiochemical and morphological properties of modified IONPs were characterised using different analytical techniques. The resultant IONPs exhibited clusters of 10 nm spherical shape crystals with less than 100 nm size suitable for drug delivery. The functionalized IONP showed mesoporous features, high stability, dispersibility and crystallinity. Subsequently, the functionalized IONPs were successfully loaded with oxaliplatin, a chemotherapeutic agent, for a controlled drug release in an actively targeting cancer cells. FT-IR observations confirmed presence of oxaliplatin functional groups, while ICP-MS results verified the drug loading was ~ 1.3%.

Keywords: cancer treatment, chemotherapeutic agent, drug delivery, iron oxide, multi-functional nanoparticle

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Authors: Kulwinder Singh

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Punjab is one of the major labour exporting states of India. Every year more than 20,000 youths from Punjab attempt irregular migration. About 84 irregular migrants are from rural areas and 16 per cent from urban areas. Irregular migration could only be achieved if be organized through highly efficient international networks with the countries of origin, transit, and destination. A good number of Punjabis continue to immigrate into the UK for work through unauthorized means entering the country on visit visas and overstaying or getting ‘smuggled into’ the country with the help of transnational networks of agents. Although, the efforts are being made by the government to curb irregular migration through The Punjab Prevention of Human Smuggling Rules (2012, 2014) and Punjab Travel Regulation Act (2012), but yet it exists parallel to regular migration. Despite unprecedented miseries of irregular migrants and strict laws implemented by the state government to check this phenomenon, ‘why do Punjabis migrate abroad irregularly’ is the important question to answer. This study addresses this question through the comparison of irregular migration with regular one. In other words, this analysis reveals major causes, specifically economic ones, of irregular migration from rural Punjab. This study is unique by presenting economics of irregular migration, given previous studies emphasize the role of sociological and psychological factors. Addressing important question “why do Punjabis migrate abroad irregularly?”, the present study reveals that Punjabi, being far-sighted, endeavor irregular migration as it is, though, economically nonviable in short run, but offers lucrative economic gains as gets older. Despite its considerably higher cost viz-a-viz regular migration, it is the better employment option to irregular migrants with higher permanent income than local low paid jobs for which risking life has become the mindset of the rural Punjabis. Although, it carries considerably lower economic benefits as compared to regular migration, but provides the opportunity of migrating abroad to less educated, semi-skilled and language-test ineligible Punjabis who cannot migrate through regular channels. As its positive impacts on source and destination countries are evident, it might not be restricted, rather its effective management, through liberalising restrictive migration policies by destination nations, can protect the interests of all involved stakeholders.

Keywords: cost, migration, income, irregular, regular, remittances

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Authors: Filipa Cruz, Grecia P. Matos

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An Inexhaustible Will of Infinite is ongoing practice-based research focused on a psychophysiological conception of body and on the creative will that seeks to examine the possibility of art being simultaneously a pacifier and an intensifier in a physiological artistic production. This is a study where philosophy and art converge in a commentary on the affection of the concept of will to power in the art world through Nietzsche’s commentaries, through the analysis of case studies and a reflection arising from artistic practice. Through Nietzsche, it is sought to compare concepts that communicate with the artistic practice since creation is an intensification and engenders perspectives. It is also a practice highly embedded in the body, in the non-verbal, in the physiology of art and in the coexistence between the sensorial and the thought. It is questioned if the physiology of art could be thought of as a thinking-feeling with no primacy of the thought over the sensorial. Art as a manifestation of the will to power participates in a comprehension of the world. In this article, art is taken as a privileged way of communication – implicating corporeal-sensorial-conceptual – and of connection between humans. Problematized is the dream and the drunkenness as intensifications and expressions of life’s comprehension. Therefore, art is perceived as suggestion and invention, where the artistic intoxication breaks limits in the experience of life, and the artist, dominated by creative forces, claims, orders, obeys, proclaims love for life. The intention is also to consider how one can start from pain to create and how one can generate new and endless artistic forms through nightmares, daydreams, impulses, intoxication, enhancement, intensification in a plurality of subjects and matters. It is taken into consideration the fact that artistic creation is something that is intensified corporeally, expanded, continuously generated and acting on bodies. It is inextinguishable and a constant movement intertwining Apollonian and Dionysian instincts of destruction and creation of new forms. The concept of love also appears associated with conquering, that, in a process of intensification and drunkenness, impels the artist to generate and to transform matter. Just like a love relationship, love in Nietzsche requires time, patience, effort, courage, conquest, seduction, obedience, and command, potentiating the amplification of knowledge of the other / the world. Interlacing Nietzsche's philosophy, not with Modern Art, but with Contemporary Art, it is argued that intoxication, will to power (strongly connected with the creative will) and love still have a place in the artistic production as creative agents.

Keywords: artistic creation, body, intensification, psychophysiology, will to power

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Authors: Benlaifa Meriem, Berredjem Hajira, Bouasla Radia, Berredjem Malika, Djebar Med Reda

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Toxoplasmosis is a cosmopolitan infection due to Toxoplasma gondii (T.gondii). It is a significant cause of congenital disease and an important opportunistic pathogen which has become a worldwide increasing problem due to the AIDS epidemic. Current available drugs do not give satisfactory results and often have only a static and several adverse side effects as it is the case of pyrimethamine. So, the need to develop and evaluate new drugs is critical. The purpose of this study is to investigate the in vitro and in vivo effects of the new chiral N-acylsulfonamide bis-oxazolidin-2-ones on T.gondii. In this study, anti-T.gondii RH strain activities, of two new chiral N-acylsulfonamide bis-oxazolidin-2-ones were evaluated in vitro, using a MRC-5 fibroblast tissue cultures to determine the concentration that inhibit parasite multiplication by 50% (IC50) of each drug and in vivo, by PCR detection of the tachyzoites in mice ascites after new molecules treatment, using the 35-fold repetitive B1 gene of T.gondii. The in vitro results demonstrated that the treatment with the tested molecules decreased the amount of tachyzoites in cell culture in a dose-dependent manner. The inhibition was complete for concentrations over 4 mg/ml. The IC50 of Mol 1 and Mol 2 were 1.5 and 3 mg/ml, respectively, and were quite similar to the control one (2 mg/ml). The Mol 1 was highly active against T.gondii in cell cultures than Mol 2; these results were similar to those of sulfadiazine-treated group (p < 0.05). Toxoplasma-specific DNA was demonstrated in all ascites samples from infected mice of the different tested groups. Mol 1 showed better effect than Mol 2, but it did not completely inhibit the parasite proliferation. The intensity of amplification products increased when the treatment started late after infection. These findings suggest continuous parasite replication despite the treatment. In conclusion, our results showed a promising treatment effect of the tested molecules and suggest that in vitro, the Mol 1, and Mol 2 have a dose-dependent effect and a high cytotoxicity on the studied cells. The present study revealed that concentration and duration of tested molecules treatment are major factors that influence the course of Toxoplasma infection in infected mice.

Keywords: cytotoxicity, PCR, sulfonamide, Toxoplasma gondii

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Authors: Inayat Ur Rahman Arshad

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Stevia rebaudiana B. is a shrubby perennial herb of Asteraceae family that possesses the unique ability of accumulative non caloric sweet Steviol Glycosides (SGs). The purpose of the study is to optimize sugar concentration, pH level and inoculum size for inducing the callus with optimum growth and efficient antibacterial potential. Three different experiments were conducted in which Callus explant from three-months-old already established callus of Stevia reabudiana of four different sizes were inoculated on Murashige and Skoog (MS) basal medium supplemented with five different sucrose concentration and pH adjusted at four different levels. Maximum callus induction 100, 87.5 and 85.33% was resulted in the medium supplemented with 30g/l sucrose, pH maintained at 5.5 and inoculated with 1.25g inoculum respectively. Similarly, the highest fresh weight 65.00, 75.50 and 50.53g/l were noted in medium fortified with 40g/l sucrose, inoculated 1.25g inoculum and 6.0 pH level respectively. However, the callus developed in medium containing 50g/l sucrose found highly antibacterial potent with 27.3 and 26.5mm inhibition zone against P. vulgaris and B. subtilize respectively. Similarly, the callus grown on medium inoculated with 1.00g inoculum resulted in maximum antibacterial potential against S. aureus and P. vulgaris with 25 and 23.72mm inhibition zones respectively. However, in the case of pH levels the medium maintained at 6.5pH showed maximum antibacterial activity against P. vulgaris, B.subtilis and E.coli with 27.9, 25 and 23.72mm respectively. The ethyl acetate extract of Stevia callus and leaves did not show antibacterial potential against Xanthomonas campestris and Clavebactor michiganensis. In the entire experiment the standard antibacterial agent Streptomycin showed the highest inhibition zones from the rest of the callus extract, however the pure DMSO (Dimethyl Sulfoxide) caused no inhibitory zone against any bacteria. From these findings it is concluded that among various levels sucrose at the rate of 40g L-1, pH 6.0 and inoculums 0.75g was found best for most of the growth and quality attributes including fresh weight, dry weight and antibacterial activities and therefore can be recommended for callus proliferation and antibacterial potential of Stevia rebaudiana

Keywords: Steviol Glycosides, Skoog, Murashige, Clavebactor michiganensis

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Authors: Inayat Ur Rahman Arshad

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Background: Stevia rebaudiana B. is a shrubby perennial herb of Asteraceae family that possesses the unique ability of accumulative non-caloric sweet steviol glycosides (SGs). Purpose: The purpose of the study is to optimize sugar concentration, pH level, and inoculum size for inducing the callus with optimum growth and efficient antibacterial potential. Method: Three different experiments were conducted in which Callus explant from three-months-old already established callus of Stevia reabudiana of four different sizes was inoculated on Murashige and Skoog (MS) basal medium supplemented with five different sucrose concentration and pH adjusted at four different levels. Results: Maximum callus induction 100, 87.5, and 85.33% resulted in the medium supplemented with 30 g/l sucrose, pH maintained at 5.5, and inoculated with 1.25g inoculum, respectively. Similarly, the highest fresh weights 65.00, 75.50, and 50.53 g/l were noted in a medium fortified with 40 g/l sucrose, inoculated 1.25g inoculum, and 6.0 pH level, respectively. However, the callus developed in a medium containing 50 g/l sucrose was found to be highly antibacterial potent with 27.3 and 26.5 mm inhibition zone against P. vulgaris and B. subtilis, respectively. Similarly, the callus grown on a medium inoculated with 1.00 g inoculum resulted in maximum antibacterial potential against S. aureus and P. vulgaris with 25 and 23.72 mm inhibition zone, respectively. However, in the case of pH levels, the medium maintained at 6.5 pH showed maximum antibacterial activity against P. vulgaris, B.subtilis, and E.coli with 27.9, 25, and 23.72 mm, respectively. The ethyl acetate extract of Stevia callus and leaves did not show antibacterial potential against Xanthomonas campestris and Clavebactor michiganensis. In the entire experiment, the standard antibacterial agent Streptomycin showed the highest inhibition zones among the rest of the callus extract; however, the pure dimethyl sulfoxide (DMSO) caused no inhibitory zone against any bacteria. Conclusion: From these findings, it is concluded that among various levels, sucrose @ 40 g L⁻¹, pH 6.0, and inoculums at 0.75 g were found best for most of the growth and quality attributes, including fresh weight, dry weight, and antibacterial activities and therefore can be recommended for callus proliferation and antibacterial potential of Stevia rebaudiana.

Keywords: Stevia rebaudiana, Steviol Glycosides, callus, Xanthomonas campestris

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Authors: Hiroki Tsuneda, Takamasa Suzuki, Hideki Yamamoto, Kimito Kawamura, Eiji Tamura, Katharina Wochner, Roberto Plasenzotti

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Flow property of human blood is one of the important factors on the prevention of the circulatory condition such as a high blood pressure, a diabetes mellitus, and a cardiac infarction. However, the measurement of flow property of human blood, especially blood viscosity, is not so easy, because of their coagulation or aggregation behaviors after taking a sample from blood vessel. In the experiment, some kinds of anticoagulant were added into the human blood to avoid its solidification. Anticoagulant used in the blood test has been chosen for each purpose of blood test, for anticoagulant effect on blood is different mechanism for each. So that, there is a problem that the evaluation of measured blood property with different anticoagulant is so difficult. Therefore, it is so important to make clear the difference of anticoagulant effect on the blood property. In the previous work, a compact-size falling needle rheometer (FNR) has been developed in order to measure the flow property of human blood such as a flow curve, an apparent viscosity. It was found that FNR system can apply to a rheometer or a viscometry for various experimental conditions for not only human blood but also mammalians blood. In this study, the measurements of human blood viscosity with different anticoagulant (EDTA and Heparin) were carried out using newly developed FNR system. The effect of anticoagulant on blood viscosity was also tested by using the standard liquid for each. The accuracy on the viscometry was also tested by using the standard liquid for calibrating materials (JS-10, JS-20) and observed data have satisfactory agreement with reference data around 1.0% at 310K. The flow curve of six males and females with different anticoagulant were measured using FNR. In this experiment, EDTA and Heparin were chosen as anticoagulant for blood. Heparin can inhibit the coagulation of human blood by activating the body of anti-thrombin. To examine the effect of human blood viscosity on anticoagulant, flow curve was measured at high shear rate (＞350s-1), and apparent viscosity of each person were determined with different anticoagulant. The apparent viscosity of human blood with heparin was 2%-9% higher than that with EDTA. However, the difference of blood viscosity for two anticoagulants for same blood was different for each. Further discussion, we need the consideration of effect on other physical property, such as cellular component and plasma component.

Keywords: falling-needle rheometer, human blood, viscosity, anticoagulant

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Authors: Sungmin Park, Gyungmok Nam, Seungpyo Woo, Young Choi, Sangheon Park, Sang-Hee Yoon

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Puncturing human skin with microneedles is critically important for microneedle-mediate drug delivery. Despite of extensive efforts in the past decades, the scale-up fabrication of sharp-tipped and high-aspect-ratio microneedles, especially made of biodegradable polymers, is still a long way off. Here, we present a UV dose insensitive and cost-effective microfabrication method for the biodegradable polymer microneedles with sharp tips and long lengths which can pierce human skin with low insertion force. The biodegradable polymer microneedles are fabricated with the polymer solution casting where a poly(lactic-co-glycolic acid) (PLGA, 50:50) solution is coated onto a SU-8 mold prepared with a reverse, ramped, and rotational (R3) UV exposure. The R3 UV exposure is modified from the multidirectional UV exposure both to suppress UV reflection from the bottom surface without anti-reflection layers and to optimize solvent concentration in the SU-8 photoresist, therefore achieving robust (i.e., highly insensitive to UV dose) and cost-effective fabrication of biodegradable polymer microneedles. An optical model for describing the spatial distribution of UV irradiation dose of the R3 UV exposure is also developed to theoretically predict the microneedle geometry fabricated with the R3 UV exposure and also to demonstrate the insensitiveness of microneedle geometry to UV dose. In the experimental characterization, the microneedles fabricated with the R3 UV exposure are compared with those fabricated with a conventional method (i.e., multidirectional UV exposure). The R3 UV exposure-based microfabrication reduces the end-tip radius by a factor of 5.8 and the deviation from ideal aspect ratio by 74.8%, compared with conventional method-based microfabrication. The PLGA microneedles fabricated with the R3 UV exposure pierce full-thickness porcine skins successfully and are demonstrated to completely dissolve in PBS (phosphate-buffered saline). The findings of this study will lead to an explosive growth of the microneedle-mediated drug delivery market.

Keywords: R³ UV exposure, optical model, UV dose, reflection, solvent concentration, biodegradable polymer microneedle

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Authors: Barnali Saha

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Dalit writing is the interventionalist voice of the dispossessed subaltern in the cultural economy of the society. As such, Dalit writing, including Dalit poetry, considers the contradictions that permeate the socio-cultural structure historically allocated and religiously sanctioned in the Indian subcontinent. As an epicenter of all Dalit experiences of trauma and violence, the poetics the Dalit body is deeply rooted in the peripheral space socially assigned to it by anachronistic caste-based litigation. An appraisal of Dalit creative-critical work by writers like Sharan Kumar Limbale, Arjun Dangle, Namdeo Dhasal, Om Prakash Valmiki, Muktibodh and others underscore the conjunction of the physical, psychical and the psychological in their interpretation of Dalit consciousness. They put forward the idea that Dalit poetry is begotten by the trauma of societal oppression and therefore, Dalit language and its revitalization are two elements obdurately linked to Dalit poetics. The present research paper seeks to read the problematization of the Dalit agency through the conduit of the Dalit voice wherein the anatomical category of the mouth is closely related to the question of Dalit identity. Theoretically aligned to Heidegger’s notion of language as the house of being and Bachelard’s assertion of a house as an ideal metaphor of poetic imagination and Dylan Trigg’s view of the coeval existence of space and body, the paper examines a series of selected poems by Dalit poetic voices to examine how their distinct Dalit point of view underscores Dalit speech and directs our attention to the historical abstraction of it. The paper further examines how speech as a category in Dalit writing places the Dalit somatic entity as a site of contestation with the ‘Mouth’ as a loaded symbolic category inspiring rebellion and resistance. And as the quintessential purpose of Dalit literature is the unleashing of Dalit voice from the anti-verbal domain of social decrepitude, Dalit poetry needs to be critically read based on the experience of the mouth and the patois.

Keywords: Dalit, poetry, speech, mouth, subaltern, minority, exploitation, space

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Authors: Berkas Khaoula, Chaoui Kamel

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Polyethylene (PE) pipes are one of the best options for water and gas transmission networks. The main reason for such a choice is its high-quality performance in service conditions over long periods of time. PE pipes are installed in contact with different soils having various chemical compositions with confirmed aggressiveness. As a result, PE pipe surfaces undergo unwanted oxidation reactions. Usually, the polymer mixture is designed to include some additives, such as anti-oxidants, to inhibit or reduce the degradation effects. Some other additives are intended to increase resistance to the ESC phenomenon associated with polymers (ESC: Environmental Stress Cracking). This situation occurs in contact with aggressive external environments following different contaminations of soil, groundwater and transported fluids. In addition, bacterial activity and other physical or chemical media, such as temperature and humidity, can play an enhancing role. These conditions contribute to modifying the PE pipe structure and degrade its properties during exposure. In this work, the effect of distilled water, sodium hypochlorite (bleach), diluted sulfuric acid (H2SO4) and toluene-methanol (TM) mixture are studied when extruded PE samples are exposed to those environments for given periods. The chosen exposure periods are 7, 14 and 28 days at room temperature and in sealed glass containers. Post-exposure observations and ISO impact tests are presented as a function of time and chemical medium. Water effects are observed to be limited in explaining such use in real applications, whereas the changes in TM and acidic media are very significant. For the TM medium, the polymer toughness increased drastically (from 15.95 kJ/m² up to 32.01 kJ/m²), while sulfuric acid showed a steady augmentation over time. This situation may correspond to a hardening phenomenon of PE increasing its brittleness and its ability for structural degradation because of localized oxidation reactions and changes in crystallinity.

Keywords: polyethylene, toluene-methanol mixture, environmental stress cracking, degradation, impact resistance

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Authors: Afia Shahid

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The writing of Samuel Beckett is associated with meaning in the meaninglessness and the production of what he calls ‘literature of unword’. The casual escape from the world of words in the form of silences and pauses, in his play Waiting for Godot, urges to ask question of their existence and ultimately leads to investigate the theory behind their use in the play. This paper proposes that these absences (silence and pause) in Beckett’s play force to think ‘beyond’ language. This paper asks how silence and pause in Beckett’s text speak for the emergence of poststructuralist text. It aims to identify the significant features of the philosophy of deconstruction in the play of Beckett to demystify the hostile complicity between literature and philosophy. With the interpretive paradigm of poststructuralism this research focuses on the text as a research data. It attempts to delineate the relationship between poststructuralist theoretical concerns and text of Beckett. Keeping in view the theoretical concerns of Poststructuralist theorist Jacques Derrida, the main concern of the discussion is directed towards the notion of ‘beyond’ language into the absences that are aimed at silencing the existing discourse with the ‘radical irony’ of this anti-formal art that contains its own denial and thus represents the idea of ceaseless questioning and radical contradiction in art and any text. This article asks how text of Beckett vibrates with loud silence and has disrupted language to demonstrate the emptiness of words and thus exploring the limitless void of absences. Beckett’s text resonates with silence and pause that is neither negation nor affirmation rather a poststructuralist’s suspension of reality that is ever changing with the undecidablity of all meanings. Within the theoretical notion of Derrida’s Différance this study interprets silence and pause in Beckett’s art. The silence and pause behave like Derrida’s Différance and have questioned their own existence in the text to deconstruct any definiteness and finality of reality to extend an undecidable threshold of poststructuralists that aims to evade the ‘labyrinth of language’.

Keywords: Différance, language, pause, poststructuralism, silence, text

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Authors: William E. Bauta, Jennifer Rebeles, Reggie Jacob

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Porphyrins are noteworthy in biomedical science for their cancer tissue accumulation and photophysical properties. The preferential accumulation of some porphyrins in cancerous tissue has been known for many years. This, combined with their characteristic photophysical and photochemical properties, including their strong fluorescence and their ability to generate reactive oxygen species in vivo upon laser irradiation, has led to much research into the application of porphyrins as cancer diagnostic and therapeutic agents. Porphyrins have been used as dyes to detect cancer cells both in vivo and, less commonly, in vitro. In one example, human sputum samples from lung cancer patients and patients without the disease were dissociated and stained with the porphyrin TCPP (5,10,15,20-tetrakis-(4-carboxyphenyl)-porphine). Cells were analyzed by flow cytometry. Cancer samples were identified by their higher TCPP fluorescence intensity relative to the no-cancer controls. However, quantitative analysis of fluorescence in cell suspensions stained with multiple fluorophores requires particles stained with each of the individual fluorophores as controls. Fluorescent control particles must be compatible in size with flow cytometer fluidics and have favorable hydrodynamic properties in suspension. They must also display fluorescence comparable to the cells of interest and be stable upon storage amine-functionalized spherical polystyrene beads in the 5 to 20-micron diameter range that was reacted with TCPP and EDC in aqueous pH six buffer overnight to form amide bonds. Beads were isolated by centrifugation and tested by flow cytometry. The 10-micron amine-functionalized beads displayed the best combination of fluorescence intensity and hydrodynamic properties, such as lack of clumping and remaining in suspension during the experiment. These beads were further optimized by varying the stoichiometry of EDC and TCPP relative to the amine. The reaction was accompanied by the formation of a TCPP-related particulate, which was removed, after bead centrifugation, using a microfiltration process. The resultant TCPP-functionalized beads were compatible with flow cytometry conditions and displayed a fluorescence comparable to that of stained cells, which allowed their use as fluorescence standards. The beads were stable in refrigerated storage in the dark for more than eight months. This work demonstrates the first preparation of porphyrin-functionalized flow cytometry control beads.

Keywords: tetraaryl porphyrin, polystyrene beads, flow cytometry, peptide coupling

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Authors: Sarah Gounden, Mukesh Dheda, Boikhutso Tlou, Elizabeth Ojewole, Frasia Oosthuizen

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Background: Antiretroviral therapy (ART) has been effective in the reduction of mortality and resulted in an improvement in the prognosis of HIV-infected patients. However, treatment with antiretrovirals (ARVs) has led to the development of many adverse drug reactions (ADRs). It is, therefore, necessary to determine the safety profile of these medicines in a South African population in order to ensure safe and optimal medicine use. Objectives: The aim of this study was to quantify ADRs experienced with the different ARVs currently used in South Africa, to determine the safety profile of ARV medicine in South Africa based on reported ADRs, and to determine the ARVs with the lowest risk profile based on specific patient populations. Methodology: This was a quantitative study. Individual case safety reports for the period January 2010 – December 2013 were obtained from the National Pharmacovigilance Center; these reports contained information on ADRs, ARV medicine, and patient demographics. Data was analysed to find associations that may exist between ADRs experienced, ARV medicines used and patient demographics. Results: A total of 1916 patient reports were received of which 1534 met the inclusion criteria for the study. The ARV with the lowest risk of ADRs were found to be lamivudine (0.51%, n=12), followed by lopinavir/ritonavir combination (0.8%, n=19) and abacavir (0.64%, n=15). A higher incidence of ADRs was observed in females compared to males. The age group 31–50 years and the weight group 61–80 kg had the highest incidence of ADRs reported. Conclusion: This study found that the safest ARVs to be used in a South African population are lamivudine, abacavir, and the lopinavir/ritonavir combination. Gender differences play a significant role in the occurrence of ADRs and both anatomical and physiological differences account for this. An increased BMI (body mass index) in both men and women showed an increase in the incidence of ADRs associated with ARV therapy.

Keywords: adverse drug reaction, antiretrovirals, HIV/AIDS, pharmacovigilance, South Africa

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

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

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

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Authors: Cherif Y., Ghariani R., Derbal S., Farhati S., Ben Dahmen F., Abdallah M.

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Introduction: Tuberculosis (TBC) is a frequent infection and is still a major public health problem in Tunisia. The aim of this work is to focus on diagnostic and therapeutic characteristics of TBC in patients referred to our internal medicine department. Patients and Methods: The study was retrospective and descriptive of a cohort of consecutive cases treated from January 2016 to December 2019, collecting patients with latent or patent TBC. Twenty-eight medical records of adults diagnosed with TBC were reviewed. Results: Twenty-eight patients, including 18 women and 10 men, were diagnosed with TBC. Their mean age is 48 years (range: 22-78 years). Five patients have a medical history of diabetes mellitus, 1 patient was followed for systemic lupus erythematosus treated with corticosteroids and immunosuppressant drugs, and another was treated with corticosteroids for Mac Duffy syndrome. The TBC is latent in 12 cases and patent in 16 cases. The most common symptoms were fever and weight loss and were found in 10 cases, a cough in 2 cases, sputum in 3 cases, lymph nodes in 4 cases, erythema nodosum in 2 cases, and neurological signs in 3 cases. Lymphopenia is noticed in 3 cases and a biological inflammatory syndrome in 18 of the cases. The purified protein derivate reaction was positive in 17 cases, anergic in 3 cases, negative in 5 cases, and not done in 3 cases. The acid-fast bacilli stain culture was strongly positive in one patient. The histopathological study was conclusive in 11 patients and showed granulomatosis with caseous necrosis. TBC was pulmonary in 7 patients, lymph node in 7 cases, peritoneal in 7 cases, digestive in 1 case, neuromeningeal in 3 cases, and thyroïd in 1 case. Seven patients had multifocal TBC. All the patients received anti-tuberculosis treatment with a mean duration of 8 months with no failure or relapse with an average follow-up time of 10.58 months. Conclusion: Diagnosis and management of TBC remain essential to avoid serious complications. The survey is necessary to ensure timely detection and treatment of infected adults to decrease its incidence. The best treatment remains preventive through vaccination and improving social and economic conditions.

Keywords: tuberculosis, infection, autoimmune disease, granulomatosis

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Authors: Stoyanka Georgieva Vladeva, Elena Kirilova Kirilova, Nikola Kirilov Kirilov

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Summary: WHO (World Health Organization) recommends the elder people a certain amount of regular physical activity in order to prevent some of the health issues. Postmenopausal osteoporosis is one of the chronic diseases which requires the maintaining of regular physical activity. The regular activity combined with an adequate medical treatment greatly improves the quality of life of the patient. Objectives: Assessment of the effect of the regular physical activity recommended by WHO on the quality of life in patients with postmenopausal osteoporosis. Material and methods: For the period of one year 68 female patients treated with Denosumab have been monitored. The bone density has been measured with the DEXA method in accordance to the T-score. No patients having any oncologic diseases and secondary osteoporosis have been included in the study. The subjects have been divided into groups by their age. The first group – women aged under 65 years (27 subjects) and the second group – women aged over 65 years (41 subjects). All patients have been advised to maintain regular physical activity included in the recommendations of the WHO in accordance with the age and the disease. The quality of life has been assessed in the beginning and at the end of the one-year period using the SF 36V2 questionnaire. Results: Only 31% of the subjects have engaged into regular increased physical activities for the whole period. Among them are mostly patients of the second group (aged over 65 years, 71%). The women from the both groups who were engaging into regular activities for this one-year period all experience an improvement of the quality of life. These results show that older patients understand the necessity of the physical activity for their health. The comparison of the output data to the scales of physical activity, durability, body pain, vitality, social activity and emotional stability has found an improvement at the end of the period in all patients. The osteodensitometry showed general improvement of the T-score. Patients with additional visits to their rheumatologist have better results. Conclusion: Combination of regular physical activity in accordance to the recommendations of WHO and medical treatment including anti-osteoporotic drugs improves the quality of life of women with postmenopausal osteoporosis.

Keywords: elderly patients, osteoporosis, physical activity, quality of life

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Authors: Emielex M. Aguilar, Kristen Angela G. Cruz, Czarina Joie L. Rivera, Francis Dave C. Tan, Gavino Ivan N. Tanodra, Dianne Katrina G. Usana, Mary Grace T. Valentin, Nico Albert S. Vasquez, Edwin Monico C. Wee

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The risk of diabetes mellitus is increasing in the Philippines, with Metformin and Insulin as drugs commonly used for its management. The use of herbal medicines has grown increasingly, especially among the elderly population. Moringa oleifera or malunggay is one of the most common plants in the country, and several studies have shown the plant to exhibit a hypoglycemic property with its flavonoid content. This study aims to investigate the possible effects of concomitant use of Metformin and powdered M. oleifera leaves (PMOL) on blood glucose levels. Twenty male Sprague-Dawley rats were equally distributed into four groups. Fasting blood glucose levels of the rats were measured prior to experimentation. The following treatments were administered to the four groups, respectively: glucose only 2 g/kg; glucose 2 g/kg + Metformin 100 mg/kg; glucose 2 g/kg + PMOL 200 mg/kg; and glucose 2 g/kg + PMOL 200 mg/kg and Metformin 100 mg/kg. Blood glucose levels were determined on the 1st, 2nd, 3rd, and 4th hour post-treatment and compared between groups. Statistical analysis showed that the type of intervention did not show significance in the reduction of blood glucose levels when compared with the other groups (p=0.378), while the effect of time exhibited significance (p=0.000). The interaction between the type of intervention and time of blood glucose measurement was shown to be significant (p=0.024). Within each group, the control and PMOL-treated groups showed significant reduction in blood glucose levels over time with p-values of 0.000 and 0.000, respectively, while the Metformin-treated and the combination groups had p-values of 0.062 and 0.093, respectively, which are not significant. The descriptive data also showed that the mean total reduction of blood glucose levels of the Metformin and PMOL combination treatment group was lower than the PMOL-treated group alone, while the mean total reduction of blood glucose levels of the combination group was higher than the Metformin-treated group alone. Based on the results obtained, the combination of Metformin and PMOL did not significantly lower the blood glucose levels of the rats as compared to the other groups. However, the concomitant use of Metformin and PMOL may affect each other’s blood glucose lowering activity. Additionally, prolonged time of exposure and delay in the first blood glucose measurement after treatment could exhibit a significant effect in the blood glucose levels. Further studies are recommended regarding the effects of the concomitant use of the two agents on blood glucose levels.

Keywords: blood glucose levels, concomitant use, metformin, Moringa oleifera

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Authors: Yui Okuno, Mariko Era, Takayoshi Kawahara, Takahide Kanyama, Hiroshi Morita

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Introduction: Fungus and mite are known as allergens that cause an allergic disease for example asthma bronchiale and allergic rhinitis. Cladosporium cladosporioides is one of the most often detected fungi in the indoor environment and causes pollution and deterioration. Dermatophagoides farinae is major mite allergens indoors. Therefore, the creation of antifungal agents with high safety and the antifungal effect is required. Fatty acid salts are known that have antibacterial activities. This report describes the effects of fatty acid salts against Cladosporium cladosporioides NBRC 30314 and Dermatophagoides farinae. Methods: Potassium salts of 9 fatty acids (C4:0, C6:0, C8:0, C10:0, C12:0, C14:0, C18:1, C18:2, C18:3) were prepared by mixing the fatty acid with the appropriate amount of KOH solution to a concentration of 175 mM and pH 10.5. The antifungal method, the spore suspension (3.0×104 spores/mL) was mixed with a sample of fatty acid potassium (final concentration of 175 mM). Samples were counted at 0, 10, 60, 180 min by plating (100 µL) on PDA. Fungal colonies were counted after incubation for 3 days at 30 °C. The MIC (minimum inhibitory concentration) against the fungi was determined by the two-fold dilution method. Each fatty acid salts were inoculated separately with 400 µL of C. cladosporioides at 3.0 × 104 spores/mL. The mixtures were incubated at the respective temperature for each organism for 10 min. The tubes were then contacted with the fungi incubated at 30 °C for 7 days and examined for growth of spores on PDA. The acaricidal method, twenty D. farinae adult females were used and each adult was covered completely with 2 µL fatty acid potassium for 1 min. The adults were then dried with filter paper. The filter paper was folded and fixed by two clips and kept at 25 °C and 64 % RH. Mortalities were determained 48 h after treatment under the microscope. D. farina was considered to be dead if appendages did not move when prodded with a pin. Results and Conclusions: The results show that C8K, C10K, C12K, C14K was effective to decrease survival rate (4 log unit) of the fatty acids potassium incubated time for 10 min against C. cladosporioides. C18:3K was effective to decrease 4 log unit of the fatty acids potassium incubated time for 60 min. Especially, C12K was the highest antifungal activity and the MIC of C12K was 0.7 mM. On the other hand, the fatty acids potassium showed no acaricidal effects against D. farinae. The activity of D. farinae was not adversely affected after 48 hours. These results indicate that C12K has high antifungal activity against C. cladosporioides and suggest the fatty acid potassium will be used as an antifungal agent.

Keywords: fatty acid salts, antifungal effects, acaricidal effects, Cladosporium cladosporioides, Dermatophagoides farinae

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Authors: Avitus A. Agbor

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Numerous incidents, ranging from trivial to catastrophic, do come to mind when one reflects on hate. The victims of these belong to specific identifiable groups within communities. These experiences evoke discussions on Islamophobia, xenophobia, homophobia, anti-Semitism, racism, ethnic hatred, atheism, and other brutal forms of bigotry. Common to all these is an invisible but portent force that drives all of them: hatred. Such hatred is usually fueled by a profound degree of intolerance (to diversity) and the zeal to impose on others their beliefs and practices which they consider to be the conventional norm. More importantly, the perpetuation of these hateful acts is the unfortunate outcome of an overplay of invectives and hate speech which, to a greater extent, cannot be divorced from hate. From a legal perspective, acknowledging the existence of an undeniable link between hate speech and hate is quite easy. However, both within and without legal scholarship, the notion of “hate speech” remains a conundrum: a phrase that is quite easily explained through experiences than propounding a watertight definition that captures the entire essence and nature of what it is. The problem is further compounded by a few factors: first, within the international human rights framework, the notion of hate speech is not used. In limiting the right to freedom of expression, the ICCPR simply excludes specific kinds of speeches (but does not refer to them as hate speech). Regional human rights instruments are not so different, except for the subsequent developments that took place in the European Union in which the notion has been carefully delineated, and now a much clearer picture of what constitutes hate speech is provided. The legal architecture in domestic legal systems clearly shows differences in approaches and regulation: making it more difficult. In short, what may be hate speech in one legal system may very well be acceptable legal speech in another legal system. Lastly, the cornucopia of academic voices on the issue of hate speech exude the divergence thereon. Yet, in the absence of a well-formulated and universally acceptable definition, it is important to consider how hate speech can be defined. Taking an evidence-based approach, this research looks into the issue of defining hate speech in legal scholarship and how and why such a formulation is of critical importance in the prohibition and prosecution of hate speech.

Keywords: hate speech, international human rights law, international criminal law, freedom of expression

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Authors: O. Antypenko, I. Vasilieva, S. Kovalenko

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Investigations for new effective and less toxic antimicrobials agents are always up-to-date. The tetrazole derivatives are quite interesting objects as for synthesis as well as for pharmacological screening. Thus, some derivatives of tetrazole demonstrated antimicrobial activity, namely 5-phenyl-tetrazolo[1,5-c]quinazoline was effective one against Staphylococcus aureus and Esherichia faecalis (MIC = 250 mg/L). Besides, investigation of the 9-bromo(chloro)-5-morpholin(piperidine)-4-yl-tetrazolo[1,5-c]quinazoline’s antimicrobial activity against Esherichia coli and Enterococcus faecalis, Pseudomonas aeruginosa and Staphylococcus aureus revealed that sensitivity of Gram-positive bacteria to the compounds was higher than that of Gram-negative bacteria. So, our previously synthesized, 31 derivatives of 1-(2-(1H-tetrazol-5-yl)-R1-phenyl)-3-R2-phenyl(ethyl)ureas were decided to test for their in vitro antibacterial activity against Gram-positive bacteria (Staphylococcus aureus ATCC 25923, Enterobacter aerogenes, Enterococcus faecalis ATCC 29212), Gram-negative bacteria (Pseudomonas aeruginosa ATCC 9027, Escherichia coli ATCC 25922, Klebsiella pneumoniae 68) and antifungal properties against Candida albicans ATCC 885653. Agar-diffusion method was used for determination of the preliminary activity compared to well-known reference antimicrobials. All the compounds were dissolved in DMSO at a concentration of 100 μg/disk, using inhibition zone diameter (IZD, mm) as a measure for the antimicrobial activity. The most active turned to be 3 structures, that inhibited several bacterial strains: 1-ethyl-3-(5-fluoro-2-(1H-tetrazol-5-yl)phenyl)urea (1), 1-(4-bromo-2-(1H-tetrazol-5-yl)-phenyl)-3-(4-(trifluoromethyl)phenyl)urea (2) and 1-(4-chloro-2-(1H-tetrazol-5-yl)phenyl)-3-(3-(trifluoromethyl)phenyl)urea (3). IZM (mm) was 40 (Escherichia coli), 25 (Klebsiella pneumonia) for compound 1; 12 (Pseudomonas aeruginosa), 15 (Staphylococcus aureus), 10 (Enterococcus faecalis) for compound 2; 25 (Staphylococcus aureus), 15 (Enterococcus faecalis) for compound 3. The most sensitive to the activity of the substances were Gram-negative bacteria Pseudomonas aeruginosa. While none of compound effected on Candida albicans. Speaking about, reference drugs: Amikacin (30 µg/disk) showed 27 and Ceftazide (30 µg/disk) 25 against Pseudomonas aeruginosa. That is, unfortunately, higher than studied 1-(2-(1H-tetrazol-5-yl)-R1-phenyl)-3-R2-phenyl(ethyl)ureas. Obtained results will be used for further purposeful optimization of the leading compounds in the more effective antimicrobials because of the ever-mounting problem of microorganism’s resistance.

Keywords: antimicrobial, antifungal, compounds, 1-(2-(1H-tetrazol-5-yl)-R1-phenyl)-3-R2-phenyl(ethyl)ureas

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Authors: Mike Chia-Yu Huang

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China’s port facility construction projects in the Indian Ocean (IO) region, Gwadar Port and Djibouti Port projects in particular, have led to a heated debate among both Chinese and Western strategists over whether the country has literally been carrying out its “string of pearls” strategy, an alleged Chinese plan to challenge America’s military predominance in South Asia. Even though the Chinese government repeatedly denied the existence of such a strategy and highlighted the civilian/commercial nature of its port projects, it has significantly enhanced its strategic cooperation with littoral countries in the IO region since the “One Belt One Road” initiative was introduced by Chinese President Xi Jinping in 2013. Whether China does have a plan to expand its sphere of military influence westward concerns the balance of power in the IO region. If the answer is positive, the security environment there will be changed drastically. This paper argues that rather than simply copying the U.S. model of developing overseas military bases along the IO periphery, Beijing has been deliberating a more sophisticated plan for its physical presence there: creating a new set of “overseas strategic pivots.” These “pivots,” semi-military and semi-commercial in nature, are designed to help Beijing sustain its anti-piracy operations in the Gulf of Aden and serve as forward stations for the transportation of China’s imported energy and merchandise. They can support the Chinese Navy’s operations overseas but are not supposed to undertake face-to-face combat missions. This upgraded Chinese scheme can be identified as “string of pearls” strategy 2.0. Moreover, it is expected to help China deepen its roots in the IO region, implying that Beijing has to a large extent scratched its old diplomatic philosophy which highlighted the merits of non-interference and nonalignment. While a full-scale maritime confrontation between China and the U.S.-India security alliance is unlikely to be witnessed in the near future, an ambitious Chinese plan to step into the global maritime domain has been evidently shown.

Keywords: Chinese navy, Djibouti, Gwadar, Indian Ocean, string of pearls strategy

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Authors: Maciej Sobczak, Julita Pietrzak, Tomasz Płoszaj, Agnieszka Robaszkiewicz

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Brg1, a member of SWI/SNF complex, plays a role in chromatin remodeling, therefore, regulates expression of many genes. Brg1 is an ATPase of SWI/SNF complex, thus its activity requires ATP. Through its bromodomain recognizes acetylated histone residues and evicts them, thus promoting transcriptionally active state of chromatin. One of the enzymes that is responsible for acetylation of histone residues is Ep300. It was previously shown in the literature that cooperation of Brg1 and Ep300 occurs at the promoter regions that have binding sites for E2F-family transcription factors as well as CpG islands. According to literature, approximately 20% of human cancer possess mutation in Brg1 or any other crucial SWI/SNF subunit. That phenomenon makes Brg1-Ep300 a very promising target for anti-cancer therapy. Therefore in our study, we investigated if physical interaction between Brg1 and Ep300 exists and what impact those two proteins have on key for breast cancer cells processes such as DNA damage repair and cell proliferation. Bioinformatical analysis pointed out, that genes involved in cell proliferation and DNA damage repair are overexpressed in MCF7 and MDA-MB-231 cells. Moreover, promoter regions of these genes are highly acetylated, which suggests high transcriptional activity of those sites. Notably, many of those gene possess within their promoters an E2F, Brg1 motives, as well as CpG islands and acetylated histones. Our data show that Brg1 physically interacts with Ep300, and together they regulate expression of genes involved in DNA damage repair and cell proliferation. Upon inhibiting Brg1 or Ep300, expression of vital for cancer cell survival genes such as CDK2/4, BRCA1/2, PCNA, and XRCC1 is decreased in MDA-MB-231 and MCF7 cells. Moreover, inhibition or silencing of either Brg1 or Ep300 leads to cell cycle arrest in G1. After inhibition of BRG1 or Ep300 on tested gene promoters, the repressor complex including Rb, HDAC1, and EZH2 is formed, which inhibits gene expression. These results highlight potentially significant target for targeted anticancer therapy to be introduced as a supportive therapy.

Keywords: brg1, ep300, breast cancer, epigenetics

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Authors: S. Kozlovski, S.W. Feigelson, R. Alon

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The b2 integrin ligands ICAM-1 ICAM-2 and the endothelial VLA-4 integrin ligand VCAM-1 are constitutively expressed on different lung vessels and on high endothelial venules (HEVs), the main portal for lymphocyte entry from the blood into lung draining lymph nodes. ICAMs are also ubiquitously expressed by many antigen-presenting leukocytes and have been traditionally suggested as critical for the various antigen-specific immune synapses generated by these distinct leukocytes and specific naïve and effector T cells. Loss of both ICAM-1 and ICAM-2 on the lung vasculature reduces the ability to patrol monocytes and Tregs to patrol the lung vasculature at a steady state. Our new findings suggest, however, that in terms of innate leukocyte trafficking into the lung lamina propria, both constitutively expressed and virus-induced vascular VCAM-1 can functionally compensate for the loss of these ICAMs. In a mouse model for influenza infection, neutrophil and NK cell recruitment and clearance of influenza remained normal in mice deficient in both ICAMs. Strikingly, mice deficient in both ICAMs also mounted normal influenza-specific CD8 proliferation and differentiation. In addition, these mice normally combated secondary influenza infection, indicating that the presence of ICAMs on conventional dendritic cells (cDCs) that present viral antigens are not required for immune synapse formation between these APCs and naïve CD8 T cells as previously suggested. Furthermore, long-lasting humoral responses critical for protection from a secondary homosubtypic influenza infection were also normal in mice deficient in both ICAM-1 and ICAM-2. Collectively, our results suggest that the expression of ICAM-1 and ICAM-2 on lung endothelial and epithelial cells, as well as on DCs and B cells, is not critical for the generation of innate or adaptive anti-viral immunity in the lungs. Our findings also suggest that endothelial VCAM-1 can substitute for the functions of vascular ICAMs in leukocyte trafficking into various lung compartments.

Keywords: emigration, ICAM-1, lymph nodes, VCAM-1

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