Search results for: in vitro drug release
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3990

Search results for: in vitro drug release

1680 Quantification of Peptides (linusorbs) in Gluten-free Flaxseed Fortified Bakery Products

Authors: Youn Young Shim, Ji Hye Kim, Jae Youl Cho, Martin JT Reaney

Abstract:

Flaxseed (Linumusitatissimum L.) is gaining popularity in the food industry as a superfood due to its health-promoting properties. Linusorbs (LOs, a.k.a. Cyclolinopeptide) are bioactive compounds present in flaxseed exhibiting potential health effects. The study focused on the effects of processing and storage on the stability of flaxseed-derived LOs added to various bakery products. The flaxseed meal fortified gluten-free (GF) bakery bread was prepared, and the changes of LOs during the bread-making process (meal, fortified flour, dough, and bread) and storage (0, 1, 2, and 4 weeks) at different temperatures (−18 °C, 4 °C, and 22−23 °C) were analyzed by high-performance liquid chromatography-diode array detection. The total oxidative LOs and LO1OB2 were almost kept stable in flaxseed meals at storage temperatures of 22−23 °C, −18 °C, and 4 °C for up to four weeks. Processing steps during GF-bread production resulted in the oxidation of LOs. Interestingly, no LOs were detected in the dough sample; however, LOs appeared when the dough was stored at −18 °C for one week, suggesting that freezing destroyed the sticky structure of the dough and resulted in the release of LOs. The final product, flaxseed meal fortified bread, could be stored for up to four weeks at −18 °C and 4 °C, and for one week at 22−23 °C. All these results suggested that LOs may change during processing and storage and that flaxseed flour-fortified bread should be stored at low temperatures to preserve effective LOs components.

Keywords: linum usitatissimum L., flaxseed, linusorb, stability, gluten-free, peptides, cyclolinopeptide

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1679 Therapeutic Efficacy and Safety Profile of Tolvaptan Administered in Hyponatremia Patients

Authors: Sree Vennela P., V. Samyuktha Bhardwaj

Abstract:

Hyponatremia is an electrolyte disturbance in which the sodium ion concentration in the serum is lower than normal. Sodium is the dominant extracellular cation (positive ion) and cannot freely cross from the interstitial space through the cell membrane, into the cell. Its homeostasis (stability of concentration) inside the cell is vital to the normal function of any cell. Normal serum sodium levels are between 135 and 145 mEq/L. Hyponatremia is defined as a serum level of less than 135 mEq/L and is considered severe when the serum level is below 125 mEq/L. In the vast majority of cases, Hyponatremia occurs as a result of excess body water diluting the serum sodium (salt level in the blood). Hyponatremia is often a complication of other medical illnesses in which excess water accumulates in the body at a higher rate than can be excreted (for example in congestive heart failure, syndrome of inappropriate antidiuretic hormone, SIADH, or polydipsia). Sometimes it may be a result of over-hydration (drinking too much water).Lack of sodium (salt) is very rarely the cause of Hyponatremia, although it can promote Hyponatremia indirectly. In particular, sodium loss can lead to a state of volume depletion (loss of blood volume in the body), with volume depletion serving as a signal for the release of ADH (anti-diuretic hormone). As a result of ADH-stimulated water retention (too much water in the body), blood sodium becomes diluted and Hyponatremia results.

Keywords: Tolvaptan, hyponatremia, syndrome of insufficient anti diuretic hormone (SIADH), euvolemic hyponatremia

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1678 Cloning, Expression and N-Terminal Pegylation of Human Interferon Alpha-2b Analogs and Their Cytotoxic Evaluation against Cancer Cell Lines

Authors: Syeda Kiran Shahzadi, Nasir Mahmood, Muhammad Abdul Qadir

Abstract:

In the current research, three recombinant human interferon alpha-2b proteins (two modified and one normal form) were produced and Pegylated with an aim to produce more effective drugs against viral infections and cancers. The modified recombinant human interferon alpha-2b proteins were produced by site-directed modifications of interferon alpha 2b gene, targeting the amino acids at positions ‘R23’ and ‘H34’. The resulting chemically modified and unmodified forms of human interferon alpha 2b were conjugated with methoxy-polyethylene glycol propanealdehyde (400 KDa) and methoxy-polyethylene glycol succinimidyl succinate (400 KDa). Pegylation of normal and modified forms of Interferon alpha-2b prolong their release time and enhance their efficacy. The conjugation of PEG with modified and unmodified human interferon alpha 2b protein drugs was also characterized with 1H-NMR, HPLC, and SDS-PAGE. Antiproliferative assays of modified and unmodified forms of drugs were performed in cell based bioassays using MDBK cell lines. The results indicated that experimentally produced recombinant human interferon alpha-2b proteins were biologically active and resulted in significant inhibition of cell growth.

Keywords: protein refolding, antiproliferative activities, biomedical applications, human interferon alpha-2b, pegylation, mPEG-propionaldehyde, site directed mutagenesis, E. coli expression

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1677 Surface Flattening Assisted with 3D Mannequin Based on Minimum Energy

Authors: Shih-Wen Hsiao, Rong-Qi Chen, Chien-Yu Lin

Abstract:

The topic of surface flattening plays a vital role in the field of computer aided design and manufacture. Surface flattening enables the production of 2D patterns and it can be used in design and manufacturing for developing a 3D surface to a 2D platform, especially in fashion design. This study describes surface flattening based on minimum energy methods according to the property of different fabrics. Firstly, through the geometric feature of a 3D surface, the less transformed area can be flattened on a 2D platform by geodesic. Then, strain energy that has accumulated in mesh can be stably released by an approximate implicit method and revised error function. In some cases, cutting mesh to further release the energy is a common way to fix the situation and enhance the accuracy of the surface flattening, and this makes the obtained 2D pattern naturally generate significant cracks. When this methodology is applied to a 3D mannequin constructed with feature lines, it enhances the level of computer-aided fashion design. Besides, when different fabrics are applied to fashion design, it is necessary to revise the shape of a 2D pattern according to the properties of the fabric. With this model, the outline of 2D patterns can be revised by distributing the strain energy with different results according to different fabric properties. Finally, this research uses some common design cases to illustrate and verify the feasibility of this methodology.

Keywords: surface flattening, strain energy, minimum energy, approximate implicit method, fashion design

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1676 Usage of Cord Blood Stem Cells of Asphyxia Infants for Treatment

Authors: Ahmad Shah Farhat

Abstract:

Background: Prenatal asphyxia or birth asphyxia is the medical situation resulting from a newborn infant that lasts long enough during the birth process to cause physical harm, usually to the brain. Human umbilical cord blood (UCB) is a well-established source of hematopoietic stem/progenitor cells (HSPCs) for allogeneic stem cell transplantation. These can be used clinically to care for children with malignant diseases. Low O2 can cause in proliferation and differentiation of stem cells. Method: the cord blood of 11 infants with 3-5 Apgar scores or need to cardiac pulmonary Resuscitation as an asphyxia group and ten normal infants with more than 8 Apgar scores as the normal group was collected, and after isolating hematopoietic stem cells, the cells were cultured in enriched media for 14 days to compare the numbers of colonies by microscope. Results: There was a significant difference in the number of RBC precursor colonies (red colonies) in cultured media with 107 cord blood hematopoietic stem cells of infants who were exposed to hypoxemia in two wells of palate. There was not a significant difference in the number of white cell colonies in the two groups in the two wells of the plate. Conclusion: Hypoxia in the perinatal period can cause the increase of hematopoietic stem cells of cord blood, special red precursor stem cells in vitro, like an increase of red blood cells in the body when exposed to low oxygen conditions. Thus, it will be usable.

Keywords: asphyxia, neonre, stem cell, red cell

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1675 Chemical Mechanical Polishing Wastewater Treatment through Membrane Distillation

Authors: Imtisal-e-Noor, Andrew Martin, Olli Dahl

Abstract:

Chemical Mechanical Polishing (CMP) has developed as a chosen planarization technique in nano-electronics industries for fabrication of the integrated circuits (ICs). These CMP processes release a huge amount of wastewater that contains oxides of nano-particles (silica, alumina, and ceria) and oxalic acid. Since, this wastewater has high solid content (TS), chemical oxygen demand (COD), and turbidity (NTU); therefore, in order to fulfill the environmental regulations, it needs to be treated up to the local and international standards. The present study proposed a unique CMP wastewater treatment method called Membrane Distillation (MD). MD is a non-isothermal membrane separation process, which allows only volatiles, i.e., water vapors to permeate through the membrane and provides 100% contaminants rejection. The performance of the MD technology is analyzed in terms of total organic carbon (TOC), turbidity, TS, COD, and residual oxide concentration in permeate/distilled water while considering different operating conditions (temperature, flow rate, and time). The results present that high-quality permeate has been recovered after removing 99% of the oxide particles and oxalic acid. The distilled water depicts turbidity < 1 NTU, TOC < 3 mg/L, TS < 50 mg/L, and COD < 100 mg/L. These findings clearly show that the MD treated water can be reused further in industrial processes or allowable to discharge in any water body under the stringent environmental regulations.

Keywords: chemical mechanical polishing, environmental regulations, membrane distillation, wastewater treatment

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1674 Investigating Self-Confidence Influence on English as a Foreign Language Student English Language Proficiency Level

Authors: Ali A. Alshahrani

Abstract:

This study aims to identify Saudi English as a Foreign Language (EFL) students' perspectives towards using the English language in their studies. The study explores students' self-confident and its association with students' actual performance in English courses in their different academic programs. A multimodal methodology was used to fulfill the research purpose and answer the research questions. A 25-item survey questionnaire and final examination grades were used to collect data. Two hundred forty-one students agreed to participate in the study. They completed the questionnaire and agreed to release their final grades to be a part of the collected data. The data were coded and analyzed by SPSS software. The findings indicated a significant difference in students' performance in English courses between participants' academic programs on the one hand. Students' self-confidence in their English language skills, on the other hand, was not significantly different between participants' academic programs. Data analysis also revealed no correlational relationship between students' self-confidence level and their language skills and their performance. The study raises more questions about other vital factors such as course instructors' views of the materials, faculty members of the target department, family belief in the usefulness of the program, potential employers. These views and beliefs shape the student's preparation process and, therefore, should be explored further.

Keywords: English language intensive program, language proficiency, performance, self-confidence

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1673 Changes of pH and Pseudomonas Aeruginosa Growth in Liquid Media

Authors: Sayaka Ono, Ryutaro Imai, Tomoko Ehara, Tetsuya Matsumoto, Hajime Matsumura

Abstract:

Background: Wound pH affects a number of important factors in wound healing. We previously measured the pH value of the exudates collected from second-degree burns and found that the increase in pH was observed in the burn wounds in which colonized by Staphylococcus spp., and the increase in pH was evident prior to the clinical findings of local infection. To investigate the relationship between the changes of pH value and bacterial growth, we performed in vitro study using Pseudomonas aeruginosa and liquid medium as a locally infected wound equivalent model. Methods: Pseudomonas aeruginosa standard strain (ATCCR 10145TM) was cultured at 37 °C environment in Luria Broth Miller medium. The absorbance rate which means the amount of bacteria was measured by a microplate reader 2300EnSpireTM). The pH was measured using pH-indicator strips (MColorpHastTM). The statistical analysis was performed using the product-moment correlation coefficient of Pearson's. Results: The absorbance rate and pH value were increased along with culture period. There was a positive correlation between pH value and absorbance rate (n = 27, Pearson's r = 0.985). Moreover, there was a positive correlation between pH value and the culture period (n = 18, Pearson's r = 0.901). The bacteria was well growth in the media from pH 6.6 to pH 8.0 and the pH of culture media converged at 8 -9 along with the bacterial growth. Conclusion: From these results, we conclude that pH value of the wound is correlated with the number of viable bacteria and bacterial growth periods.

Keywords: colonization, potential of hydrogen, Pseudomonas aeruginosa, wound

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1672 Rapid Expansion Supercritical Solution (RESS) Carbon Dioxide as an Environmental Friendly Method for Ginger Rhizome Solid Oil Particles Formation

Authors: N. A. Zainuddin, I. Norhuda, I. S. Adeib, A. N. Mustapa, S. H. Sarijo

Abstract:

Recently, RESS (Rapid Expansion Supercritical Solution) method has been used by researchers to produce fine particles for pharmaceutical drug substances. Since RESS technology acknowledges a lot of benefits compare to conventional method of ginger extraction, it is suggested to use this method to explore particle formation of bioactive compound from powder ginger. The objective of this research is to produce direct solid oil particles formation from ginger rhizome which contains valuable compounds by using RESS-CO2 process. RESS experiments were carried using extraction pressure of 3000, 4000, 5000, 6000 and 7000psi and at different extraction temperature of 40, 45, 50, 55, 60, 65 and 70°C for 40 minutes extraction time and contant flowrate (24ml/min). From the studies conducted, it was found that at extraction pressure 5000psi and temperature 40°C, the smallest particle size obtained was 2.22μm on 99 % reduction from the original size of 370μm.

Keywords: particle size, RESS, solid oil particle, supercritical carbon dioxide,

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1671 The Cellular Internalization Mechanisms of Cationic Niosomes/DNA Complex in HeLa Cells

Authors: Orapan Paecharoenchai, Tanasait Ngawhirunpat, Theerasak Rojanarata, Auayporn Apirakaramwong, Praneet Opanasopit

Abstract:

Cationic niosomes formulated with Span20, cholesterol and novel synthesized spermine-cationic lipids (2-hydrocarbon tail and 4- hydrocarbon tail) in a molar ratio of 2.5:2.5:1 can mediate high gene transfection in vitro. However, the uptake mechanisms of these systems are not well clarified. In the present study, effect of endocytic inhibitors on the transfection efficiency of niosomes/DNA complexes was determined on a human cervical carcinoma cell line (HeLa cells) using the inhibitors of macropinocytosis (wortmannin), clathrin- and caveolae-mediated endocytosis (methyl-β-cyclodextrin), clathrin-mediated endocytosis (chlorpromazine), caveolae-mediated endocytosis (genistein and filipin), cytosolic transfer (ammonium chloride) and microtubules polymerization (nocodazole). The transfection of niosomes with 2-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride and filipin, respectively, whereas, the transfection of niosomes with 4-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride, methyl-β-cyclodextrin and filipin, respectively. It can be concluded that these niosomes/DNA complexes were internalized predominantly by endocytosis via clathrin and caveolae-independent pathway.

Keywords: cellular internalization, cationic niosomes, gene carriers, spermine-cationic lipids

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1670 Biochemical Changes in the Liver of Mice after Exposure to Different Doses of Diclofenac Sodium

Authors: Deepak Mohan, Sushma Sharma

Abstract:

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are a group of widely used drugs for the treatment of rheumatoid diseases and to relieve pain and inflammation due to their analgesic anti-pyretic and anti-inflammatory properties. The therapeutic and many of the toxic effects of NSAIDs result from reversible inhibition of enzymes in the cyclooxygenase (COX) group. In the present investigation the effect of the drug on the concentration of lipids, and on the activity of the enzymes i.e. acid and alkaline phosphatase, GOT, GPT and lipid peroxidase were studied. There was a significant enhancement in the activities of both acid and alkaline phosphatase after 21 days of treatment. Proportionate increase in the MDA contents was observed after different days of diclofenac treatment. Cellular damage in the liver resulted in decrease in the activity of both GOT (Glutamate oxaloacetate transaminase) and GPT (Glutamate pyruvate transaminase) in both low and high dose groups. Significant decrease in the liver contents was also observed in both dose groups.

Keywords: anti-inflammatory, cyclooxygenase, glutamate oxaloacetate transaminase, malondialdehyde

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1669 Genistein Suppresses Doxorubicin Associated Genotoxicity in Human Lymphocytes

Authors: Tanveer Beg, Yasir H. Siddique, Gulshan Ara, Asfar S. Azmi, Mohammad Afzal

Abstract:

Doxorubicin is a well-known DNA intercalating chemotherapy drug that is widely used for treatment of different cancers. Its clinical utility is limited due to the observed genotoxic side effects on healthy cells suggesting that newer combination and genoprotective regimens are urgently needed for the management of doxorubicin chemotherapy. Some dietary phytochemicals are well known for their protective mechanism of action and genistein from soy is recognized as an anti-oxidant with similar properties. Therefore, the present study investigates the effect of genistein against the genotoxic doses of doxorubicin by assessing chromosomal aberrations, sister chromatid exchanges, cell cycle kinetics, cell viability, apoptosis, and DNA damage markers in cultured human lymphocytes. Our results reveal that genistein treatment significantly suppresses genotoxic damage induced by doxorubicin. It is concluded that genistein has the potential to reduce the genotoxicity induced by anti-cancer drugs, thereby reducing the chances of developing secondary tumors during the therapy.

Keywords: apoptosis, DNA damage markers, doxorubicin, genistein, genotoxicity, human lymphocyte culture

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1668 Evaluation of Wound Healing Activity of Curcuma purpurascens BI. Rhizomes in Rats

Authors: Elham Rouhollahi, Soheil Zorofchian Moghadamtousi, Salma Baig, Mahmood Ameen Abdulla, Zahurin Mohamed

Abstract:

This study was designed to assess cutaneous wound healing potential of hexane extract of Curcuma purpurascens rhizomes (HECP). Twenty-four rats were divided into 4 groups: 1. Negative, 2. Low dose, 3. High dose and 4. Treatment, with 6 rats in each group. Full-thickness incisions with a diameter of 2 cm were made on the back of each rat. Rats were topically treated two times a day for 15 days. Group 1-4 were treated with sterile distilled water, 5% and 10% of extract and intrasite gel, respectively. Masson's trichrome and hematoxylin staining techniques are employed for histological analysis revealed strong wound healing potential closer to that of conventional drug intrasite gel. HECP significantly decreased wound area and an increase in hydroxyproline, cellular proliferation, the number of blood vessels and the level of collagen synthesis was observed. Thus, it could be concluded that HECP possesses strong wound healing potential.

Keywords: Curcuma purpurascens, wound healing, histopathology, hematoxylin staining

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1667 RACK1 Integrates Light and Brassinosteroid Signaling to Coordinate Cell Division During Root Soil Penetration

Authors: Liang Jiansheng, Zhu Wei

Abstract:

Light and brassinosteroids are essential external and internal cues for plant survival. Although the coordination of light with phytohormone signals is crucial for plant growth and development, the molecular connection between light and brassinosteroid signaling during root soil penetration remains elusive. Here, we reveal that light-stabilized RACK1 couples a brassinosteroid signaling cascade to drive cell division in root meristems. RACK1 family scaffold proteins positively regulate light-induced the promotion of root elongation during soil penetration. Under the light condition, RACK1A interacts with both phyB and SPA1, then reinforces the phyB-SPA1 association to accumulate its abundance in roots. In response to brassinosteroid signals, RACK1A competes with BKI1 to attenuate the BRI1-BKI1 interaction, thereby leading to activating BRI1 actions in root development. Furthermore, RACK1A binds to BES1 to repress its DNA binding activity toward the target gene CYCD3;1. This ultimately allows to release the inhibition of CYCD3;1 transcription, and promotes cell division during root growth. Our study illustrates a new mechanistic model of how plants engage scaffold proteins in transducing light information to facilitate brassinosteroid signaling for root growth in the soil.

Keywords: root growth, cell division, light signaling, brassinosteroid signaling, soil penetration, scaffold protein, RACK1

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1666 Screening the Best Integrated Pest Management Treatments against Helicoverpa armigera

Authors: Ajmal Khan Kassi, Humayun Javed, Tariq Mukhtar

Abstract:

The research was conducted to screen out resistance and susceptibility of okra varieties against Helicoverpa armigera under field conditions 2016. In this experiment, the different management practices viz. release Trichogramma chilonis, hoeing, and weeding, clipping, and lufenuron were tested individually and with all possible combinations for the controlling of American bollworm at 3 diverse localities viz. University research farm Koont, National Agriculture Research Centre (NARC) and farmer field Taxila by using resistant variety Arka Anamika. All the treatment combinations regarding damage of shoot and fruit showed significant results. The minimum fruit infestation, i.e., 3.20% and 3.58% was recorded with combined treatment (i.e., T. chilonis + hoeing + weeding + lufenuron) in two different localities. The minimum shoot infestation, i.e., 7.18%, 7.08%, and 6.85% was also observed with (T. chilonis + hoeing + weeding + lufenuron) combined treatment at all three different localities. The above-combined treatment (T. chilonis + hoeing + weeding + lufenuron) also resulted in maximum yield at NARC and Taxila, i.e., 57.67 and 62.66 q/ha respectively. On the basis of combined treatment (i.e., T. chilonis + hoeing + weeding + lufenuron) in three different localities, Arka Anamika variety proved to be comparatively resistant against H. armigera. So this variety is recommended for the cultivation in Pothwar region to get maximum yield and minimum losses against H. armigera.

Keywords: okra, screening, combine treatment, Helicoverpa armigera

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1665 Indigenous Patch Clamp Technique: Design of Highly Sensitive Amplifier Circuit for Measuring and Monitoring of Real Time Ultra Low Ionic Current through Cellular Gates

Authors: Moez ul Hassan, Bushra Noman, Sarmad Hameed, Shahab Mehmood, Asma Bashir

Abstract:

The importance of Noble prize winning “Patch Clamp Technique” is well documented. However, Patch Clamp Technique is very expensive and hence hinders research in developing countries. In this paper, detection, processing and recording of ultra low current from induced cells by using transimpedence amplifier is described. The sensitivity of the proposed amplifier is in the range of femto amperes (fA). Capacitive-feedback is used with active load to obtain a 20MΩ transimpedance gain. The challenging task in designing includes achieving adequate performance in gain, noise immunity and stability. The circuit designed by the authors was able to measure current in the rangeof 300fA to 100pA. Adequate performance shown by the amplifier with different input current and outcome result was found to be within the acceptable error range. Results were recorded using LabVIEW 8.5®for further research.

Keywords: drug discovery, ionic current, operational amplifier, patch clamp

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1664 Variation in the Traditional Knowledge of Curcuma longa L. in North-Eastern Algeria

Authors: A. Bouzabata, A. Boukhari

Abstract:

Curcuma longa L. (Zingiberaceae), commonly known as turmeric, has a long history of traditional uses for culinary purposes as a spice and a food colorant. The present study aimed to document the ethnobotanical knowledge about Curcuma longa and to assess the variation in the herbalists’ experience in Northeastern Algeria. Data were collected by semi-structured questionnaires and direct interviews with 30 herbalists. Ethnobotanical indices, including the fidelity level (FL%), the relative frequency citation (RFC) and use value (UV) were determined by quantitative methods. Diversity in the knowledge was analyzed using univariate, non-parametric and multivariate statistical methods. Three main categories of uses were recorded for C. longa: for food, for medicine and for cosmetic purposes. As a medicine, turmeric was used for the treatment of gastrointestinal, dermatological and hepatic diseases. Medicinal and food uses were correlated with both forms of use (rhizome and powder). The age group did not influence the use. Multivariate analyses showed a significant variation in traditional knowledge, associated with the use value, origin, quality and efficacy of the drug. These findings suggested that the geographical origin of C. longa affected the use in Algeria.

Keywords: curcuma, indices, knowledge, variation

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1663 Investigation of an Alkanethiol Modified Au Electrode as Sensor for the Antioxidant Activity of Plant Compounds

Authors: Dana A. Thal, Heike Kahlert, Fritz Scholz

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Thiol molecules are known to easily form self-assembled monolayers (SAM) on Au surfaces. Depending on the thiol’s structure, surface modifications via SAM can be used for electrode sensor development. In the presented work, 1-decanethiol coated polycrystalline Au electrodes were applied to indirectly assess the radical scavenging potential of plant compounds and extracts. Different plant compounds with reported antioxidant properties as well as an extract from the plant Gynostemma pentaphyllum were tested for their effectiveness to prevent SAM degradation on the sensor electrodes via photolytically generated radicals in aqueous media. The SAM degradation was monitored over time by differential pulse voltammetry (DPV) measurements. The results were compared to established antioxidant assays. The obtained data showed an exposure time and concentration dependent degradation process of the SAM at the electrode’s surfaces. The tested substances differed in their capacity to prevent SAM degradation. Calculated radical scavenging activities of the tested plant compounds were different for different assays. The presented method poses a simple system for radical scavenging evaluation and, considering the importance of the test system in antioxidant activity evaluation, might be taken as a bridging tool between in-vivo and in-vitro antioxidant assay in order to obtain more biologically relevant results in antioxidant research.

Keywords: alkanethiol SAM, plant antioxidant, polycrystalline Au, radical scavenger

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1662 Design and Identification of Mycobacterium tuberculosis Glutamate Racemase (MurI) Inhibitors

Authors: Prasanthi Malapati, R. Reshma, Vijay Soni, Perumal Yogeeswari, Dharmarajan Sriram

Abstract:

In the present study, we attempted to develop Mycobacterium tuberculosis (Mtb) inhibitors by exploring the pharmaceutically underexploited enzyme targets which are majorly involved in cell wall biosynthesis of mycobacteria. For this purpose, glutamate racemase (coded by MurI gene) was selected. This enzyme racemize L-glutamate to D-glutamate required for the construction of peptidoglycan in the bacterial cell wall synthesis process. Furthermore this enzyme is neither expressed nor its product, D-glutamate is normally found in mammals, and hence designing inhibitors against this enzyme will not affect the host system as well act as potential antitubercular drugs. A library of BITS in house compounds were screened against Mtb MurI enzyme. Based on docking score, interactions and synthetic feasibility one hit lead was identified. Further optimization of lead was attempted and its derivatives were synthesized. Forty eight derivatives of 2-phenylbenzo[d]oxazole and 2-phenylbenzo[d]thiazole were synthesized and evaluated for Mtb MurI inhibition study, in vitro activities against Mtb, cytotoxicity against RAW 264.7 cell line. Chemical derivatization of the lead resulted in compounds NR-1213 AND NR-1124 as the potent M. tuberculosis glutamate racemase inhibitors with IC50 of 4-5µM which are remarkable and were found to be non-cytotoxic. Molecular dynamics, dormant models and cardiotoxicity studies of the most active molecules are in process.

Keywords: cell wall biosynthesis, dormancy, glutamate racemase, tuberculosis

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1661 Assessment of Diagnostic Enzymes as Indices of Heavy Metal Pollution in Tilapia Fish

Authors: Justina I. R. Udotong, Essien U. Essien

Abstract:

Diagnostic enzymes like aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were determined as indices of heavy metal pollution in Tilapia guinensis. Three different sets of fishes treated with lead (Pb), iron (Fe) and copper (Cu) were used for the study while a fourth group with no heavy metal served as a control. Fishes in each of the groups were exposed to 2.65 mg/l of Pb, 0.85 mg/l of Fe and 0.35 mg/l of Cu in aerated aquaria for 96 hours. Tissue fractionation of the liver tissues was carried out and the three diagnostic enzymes (AST, ALT, and ALP) were estimated. Serum levels of the same diagnostic enzymes were also measured. The mean values of the serum enzyme activity for ALP in each experimental group were 19.5±1.62, 29.67±2.17 and 1.15±0.27 IU/L for Pb, Fe and Cu groups compared with 9.99±1.34 IU/L enzyme activity in the control. This result showed that Pb and Fe caused increased release of the enzyme into the blood circulation indicating increased tissue damage while Cu caused a reduction in the serum level as compared with the level in the control group. The mean values of enzyme activity obtained in the liver were 102.14±6.12, 140.17±2.06 and 168.23±3.52 IU/L for Pb, Fe and Cu groups, respectively compared to 91.20±9.42 IU/L enzyme activity for the control group. The serum and liver AST and ALT activities obtained in Pb, Fe, Cu and control groups are reported. It was generally noted that the presence of the heavy metal caused liver tissues damage and consequent increased level of the diagnostic enzymes in the serum.

Keywords: diagnostic enzymes, enzyme activity, heavy metals, tissues investigations

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1660 Technical and Environmental Improvement of LNG Carrier's Propulsion Machinery by Using Jatropha Biao Diesel Fuel

Authors: E. H. Hegazy, M. A. Mosaad, A. A. Tawfik, A. A. Hassan, M. Abbas

Abstract:

The rapid depletion of petroleum reserves and rising oil prices has led to the search for alternative fuels. A promising alternative fuel Jatropha Methyl Easter, JME, has drawn the attention of researchers in recent times as a high potential substrate for production of biodiesel fuel. In this paper, the combustion, performance and emission characteristics of a single cylinder diesel engine when fuelled with JME, diesel oil and natural gas are evaluated experimentally and theoretically. The experimental results showed that the thermal and volumetric efficiency of diesel engine is higher than Jatropha biodiesel engine. The specific fuel consumption, exhaust gas temperature, HC, CO2 and NO were comparatively higher in Jatropha biodiesel, while CO emission is appreciable decreased. CFD investigation was carried out in the present work to compare diesel fuel oil and JME. The CFD simulation offers a powerful and convenient way to help understanding physical and chemical processes involved internal combustion engines for diesel oil fuel and JME fuel. The CFD concluded that the deviation between diesel fuel pressure and JME not exceeds 3 bar and the trend for compression pressure almost the same, also the temperature deviation between diesel fuel and JME not exceeds 40 k and the trend for temperature almost the same. Finally the maximum heat release rate of JME is lower than that of diesel fuel. The experimental and CFD investigation indicated that the Jatropha biodiesel can be used instead of diesel fuel oil with safe engine operation.

Keywords: dual fuel diesel engine, natural gas, Jatropha Methyl Easter, volumetric efficiency, emissions, CFD

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1659 Advocating in the Criminal Justice System for Individuals Who Use Drugs: Advice from Advocates in the Greater Vancouver Area

Authors: Haley Hrymak

Abstract:

For decades drug addiction has been understood to be a health problem and not a social problem. While research has advanced to allow for a more comprehensive understanding of the factors affecting addiction, the justice system has lagged behind. Given all that is known about addiction as a health issue and the need for effective rehabilitation to prevent further involvement with crime, there is a need for a dramatic shift in order to ensure individual's human right to health is being upheld within the Canadian criminal justice system. This research employs the qualitative methodology to interview advocates who work with substance users within the Greater Vancouver area to explore best practices for representing individuals with substance abuse issues within the Canadian justice system. The research shows that treatment, not punishment, is what is needed in order for recidivism to be reduced for individuals with substance abuse issues. The creative options that advocates employ to work within the current system are intended to provide a guide for lawyers working within the current criminal justice system.

Keywords: addiction, criminal law, right to health, rehabilitation

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1658 Chemical Composition of Essential Oil and in vitro Antibacterial and Anticancer Activity of the Hydroalcolic Extract from Coronilla varia

Authors: A. A. Dehpour, B. Eslami, S. Rezaie, S. F. Hashemian, F. Shafie, M. Kiaie

Abstract:

The aims of study were investigation on chemical composition essential oil and the effect of extract of Coronilla varia on antimicrobial and cytotoxicity activity. The essential oils of Coronilla varia is obtained by hydrodistillation and analyzed by (GC/MS) for determining their chemical composition and identification of their components. Antibacterial activity of plant extract was determined by disc diffusion method. The effect of hydroalcolic extracts from Cornilla varia investigated on MCF7 cancer cell line by MTT assay. The major components were Caryophyllene Oxide (60.19%), Alphacadinol (4.13%) and Homoadantaneca Robexylic Acid (3.31%). The extracts from Coronilla varia had interesting activity against Proteus mirabilis in the concentration of 700 µg/disc and did not show any activity against Staphylococus aureus, Bacillus subtillis, Klebsiella pneumonia and Entrobacter cloacae. The positive control, Ampicillin, Chloramphenicol and Cenphalothin had shown zone of inhibition resistant all bacteria. Corohilla varia ethanol extract could inhibit the proliferation of MCF7 cell line in RPMI 1640 medium. IC50 5(mg/ml) was the optimum concentration of extract from Coronilla varia inhibition of cell line growth. The MCF7 cancer cell line and Proteus mirabilis were more sensitive to Coronilla varia ethanol extract.

Keywords: Coronilla varia, essential oil, antibacterial, anticancer, hela cell line

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1657 Secondary Metabolite Profiling and Antimicrobial Activity of Leaf Extract of Tecomella undulata (Sm.) Seem

Authors: Richa Bhardwaj

Abstract:

Tecomella undulata (Sm.) Seem is a monotypic genus belonging to family Bignoniaceae. The plant holds tremendous potential of medicinal value and has been traditionally used in various ailments like syphilis, leukoderma, blood disorders to name a few. The plant has gained prominence due to the presence of some prominent secondary metabolites. The present study focuses on the GC-MS analysis of leaf extracts of T. undulata which revealed the presence of certain bioactive compounds like stigmasterol, sitosterol, thiazoline, phytol, pthalic acid, methyl alpha ketopalmitate and so forth. A total of about 20 bioactive compounds were identified from the leaf extract spectra. Antimicrobial activity of the leaf extract was assayed against pathogenic bacteria and fungi. The alkaloids from leaf extracts showed antimicrobial activity against E.coli and B.subtilis. The flavonoids from leaves showed positive activity against Penicillium species and Candida albicans. The study thus infers that the presence of bioactive components may be the principle behind the antimicrobial property of different plant parts and therefore Tecomella forms a potential plant for herbal drug formulation.

Keywords: Tecomella undulata, bioactive compounds, GC-MS, antimicrobial activity

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1656 Central Palmar Necrosis Following Steroid Injections for the Treatment of Carpal Tunnel Syndrome: A Case Report

Authors: M. Ridwanul Hassan, Samuel George

Abstract:

Aims: Steroid injections are commonly used as a diagnostic tool or an alternative to surgical management of carpal tunnel syndrome (CTS) and are generally safe. Ischaemia is a rare complication with very few cases reported in the literature. Methods: We report a case of a 50-year-old female that presented with a necrotic wound to her left palm one month after a steroid injection into the carpal tunnel. She had a 2-year history of CTS in her left hand that was treated with six previous steroid injections in primary care during this period. The wound evolved from a blister to a necrotic ulcer which led to a painful, hollow defect in the centre of her palm. She did not report any history of trauma, nor did she have any co-morbidities. Clinical photographs were taken. Results: On examination, she had a 0.5 cmx1 cm defect in the palm of her left hand down to aponeurosis. There was purulent discharge in the wound with surrounding erythema but no spreading cellulitis. She had full function of her fingers but was very tender on movements and at rest. She was admitted for intravenous antibiotics and underwent a debridement, washout, and carpal tunnel release the next day. The defect was packed to heal by secondary intention and has now fully healed one month following her operation. Conclusions: This is an extremely rare complication of steroid injections to the carpal tunnel and may have been avoided by earlier referral for surgery rather than treatment using multiple steroid injections.

Keywords: hand surgery, complication, rare, carpal tunnel syndrome

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1655 The Influence of Ligands Molecular Structure on the Antibacterial Activity of Some Metal Complexes

Authors: Sanja O. Podunavac-Kuzmanović, Lidija R. Jevrić, Strahinja Z. Kovačević

Abstract:

In last decade, metal-organic complexes have captured intensive attention because of their wide range of biological activities such as antibacterial, antifungal, anticancerous, antimicrobial and antiHIV. Therefore, it is of great importance for the development of coordination chemistry to explore the assembly of functional organic ligands with metal ion and to investigate the relationship between the structure and property. In view of our studies, we reasoned that benzimidazoles complexed to metal ions could act as a potent antibacterial agents. Thus, we have bioassayed the inhibitory potency of benzimidazoles and their metal salts (Co or Ni) against Gram negative bacteria Escherichia coli. In order to validate our in vitro study, we performed in silico studies using molecular docking software’s. The investigated compounds and their metal complexes (Co, Ni) showed good antibacterial activity against Escherichia coli. In silico docking studies of the synthesized compounds suggested that complexed benzimidazoles have a greater binding affinity and enhanced antibacterial activity in comparison with noncomplexed ligands. In view of their enhanced inhibitory properties we propose that the studied complexes can be used as potential pharmaceuticals. This study is financially supported by COST action CM1306 and the project No. 114-451-347/2015-02, financially supported by the Provincial Secretariat for Science and Technological Development of Vojvodina.

Keywords: benzimidazoles, complexes, antibacterial, Escherichia coli, metal

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1654 X-Ray Crystallographic, Hirshfeld Surface Analysis and Docking Study of Phthalyl Sulfacetamide

Authors: Sanjay M. Tailor, Urmila H. Patel

Abstract:

Phthalyl Sulfacetamide belongs to well-known member of antimicrobial sulfonamide family. It is a potent antitumor drug. Structural characteristics of 4-amino-N-(2quinoxalinyl) benzene-sulfonamides (Phthalyl Sulfacetamide), C14H12N4O2S has been studied by method of X-ray crystallography. The compound crystallizes in monoclinic space group P21/n with unit cell parameters a= 7.9841 Ǻ, b= 12.8208 Ǻ, c= 16.6607 Ǻ, α= 90˚, β= 93.23˚, γ= 90˚and Z=4. The X-ray based three-dimensional structure analysis has been carried out by direct methods and refined to an R-value of 0.0419. The crystal structure is stabilized by intermolecular N-H…N, N-H…O and π-π interactions. The Hirshfeld surfaces and consequently the fingerprint analysis have been performed to study the nature of interactions and their quantitative contributions towards the crystal packing. An analysis of Hirshfeld surfaces and fingerprint plots facilitates a comparison of intermolecular interactions, which are the key elements in building different supramolecular architectures. Docking is used for virtual screening for the prediction of the strongest binders based on various scoring functions. Docking studies are carried out on Phthalyl Sulfacetamide for better activity, which is important for the development of a new class of inhibitors.

Keywords: phthalyl sulfacetamide, crystal structure, hirshfeld surface analysis, docking

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1653 Genome-Wide Functional Analysis of Phosphatase in Cryptococcus neoformans

Authors: Jae-Hyung Jin, Kyung-Tae Lee, Yee-Seul So, Eunji Jeong, Yeonseon Lee, Dongpil Lee, Dong-Gi Lee, Yong-Sun Bahn

Abstract:

Cryptococcus neoformans causes cryptococcal meningoencephalitis mainly in immunocompromised patients as well as immunocompetent people. But therapeutic options are limited to treat cryptococcosis. Some signaling pathways including cyclic AMP pathway, MAPK pathway, and calcineurin pathway play a central role in the regulation of the growth, differentiation, and virulence of C. neoformans. To understand signaling networks regulating the virulence of C. neoformans, we selected the 114 putative phosphatase genes, one of the major components of signaling networks, in the genome of C. neoformans. We identified putative phosphatases based on annotation in C. neoformans var. grubii genome database provided by the Broad Institute and National Center for Biotechnology Information (NCBI) and performed a BLAST search of phosphatases of Saccharomyces cerevisiae, Aspergillus nidulans, Candida albicans and Fusarium graminearum to Cryptococcus neoformans. We classified putative phosphatases into 14 groups based on InterPro phosphatase domain annotation. Here, we constructed 170 signature-tagged gene-deletion strains through homologous recombination methods for 91 putative phosphatases. We examined their phenotypic traits under 30 different in vitro conditions, including growth, differentiation, stress response, antifungal resistance and virulence-factor production.

Keywords: human fungal pathogen, phosphatase, deletion library, functional genomics

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1652 Improvement in Safety Profile of Semecarpus Anacardium Linn by Shodhana: An Ayurvedic Purification Method

Authors: Umang H. Gajjar, K. M. Khambholja, R. K. Patel

Abstract:

Semecarpus anacardium shows the presence of bioflavonoids, phenolic compounds, bhilawanols, minerals, vitamins and amino acids. Detoxified S. anacardium and its oils are considered to have anti-inflammatory properties and used in nervous debility, neuritis, rheumatism and leprous modules. S. anacardium if used without purification causes toxic skin inflammation problem because it contains toxic phenolic oil. During this Shodhana Process - An ayurvedic purification method, toxic phenolic oil was removed, have marked effect on the concentration of the phytoconstituent & antioxidant activity of S. anacardium. Total phenolic content decreased up to 70 % (from 28.9 %w/w to 8.94 %w/w), while there is a negligible effect on the concentration of total flavonoid (7.51 %w/w to 7.43 %w/w) and total carbohydrate (0.907 %w/w to 0.853 % w/w) content. IC50& EC50 value of extract of S. anacardium before and after purification are 171.7 & 314.3 while EC50values are 280.μg/ml & 304. μg/ml, shows that antioxidant activity of S. anacardium is decreased but the safety profile of the drug is increased as the toxic phenolic oil was removed during Shodhana - An ayurvedic purification method.

Keywords: Semecarpus anacardium, Shodhana process, safety profile, improvement

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1651 Mesenchymal Stem Cells (MSC)-Derived Exosomes Could Alleviate Neuronal Damage and Neuroinflammation in Alzheimer’s Disease (AD) as Potential Therapy-Carrier Dual Roles

Authors: Huan Peng, Chenye Zeng, Zhao Wang

Abstract:

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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