Search results for: MICE strategy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4298

Search results for: MICE strategy

4118 Expression of Micro RNAs in the Liver Tissue of Mice Generated through in vitro Embryo Culture and Embryo Transfer

Authors: Göksel Doğan, Murat Öztürk, Didar Tuğçe Karakulak, Mehmet Nurullah Orman, Nicolas Sylvius, Matthew Blades, Mustafa Sandıkçı, Cengiz Ünsal, Mehtap Kılıç Eren, Funda Kıral, Levent Karagenç

Abstract:

Assisted reproduction is associated with impaired glucose metabolism in adulthood. miRNAs are key regulators of glucose metabolism. Whether embryo culture and/or transfer alters the expression of miRNAs and to what extent this process affects glucose metabolism remain largely unknown. The purpose of the present study was to examine the expression of miRNAs in the liver in mice obtained by the transfer of blastocysts. The study was comprised of an experimental (EG) and a control group (CG). EG was generated by embryo transfer to pseudo-pregnant females. Mice born from naturally ovulating females were used as the CG. Differential expression of miRNAs, blood glucose, plasma insulin, liver glycogen, and activities of some of the rate-limiting enzymes involved in glucose metabolism were determined at ten weeks of age. Blood glucose, plasma insulin, and glycogen concentrations were similar between the groups in both sexes. Activities of enzymes were similar among females. EG males had significantly less glucokinase and phosphofructokinase activity compared to CG males. None of the miRNAs were differentially expressed in males. On the other hand, miR-143-3p expression was upregulated in EG females. Expression of none of the genes targeted by miR143-3p differed between the groups. These results demonstrate that miR143-3p, a novel regulator of type 2 diabetes, is upregulated in mice generated by assisted reproduction in a sexually-dimorphic manner with no apparent effect on glucose and insulin levels at ten weeks of age. It remains to be determined if this process is associated with impaired glucose homeostasis in the long term.

Keywords: assisted reproduction, blastocyst, embryo culture, glucose metabolism, miR143-3p, oxygen

Procedia PDF Downloads 185
4117 Hypoglycemic and Hypolipidemic Effects of Aqueous Flower Extract from Nyctanthes arbor-tristis L.

Authors: Brahmanage S. Rangika, Dinithi C. Peiris

Abstract:

Boiled Aqueous Flower Extract (AFE) of Nyctanthes arbor-tristis L. (Family: Oleaceae) is used in traditional Sri Lankan medicinal system to treat diabetes. However, this is not scientifically proven and the mechanisms by which the flowers reduce diabetes have not been investigated. The present study was carried out to examine the hypoglycemic potential and toxicity effects of aqueous flower extract of N. arbor-tristis. AFE was prepared and mice were treated orally either with 250, 500, and 750 mg/kg of AFE or distilled water (Control). Fasting and random blood glucose levels were determined. In addition, the toxicity of AFE was determined using chronic oral administration. In normoglycemic mice, mid dose (500mg/kg) of AFE significantly (p < 0.01) reduced fasting blood glucose levels by 49% at 4h post treatment. Further, 500mg/kg of AFE significantly (p < 0.01) lowered random blood glucose level of non-fasted normoglycemic mice. AFE significantly lowered total cholesterol and triglyceride levels while increasing the HDL levels in the serum. Further, AFE significantly inhibited the glucose absorption from the lumen of the intestine and it increases the diaphragm uptake of glucose. Alpha-amylase inhibitory activity was also evident. However, AFE did not induce any overt signs of toxicity or hepatotoxicity. There were no adverse effects on food and water intake and body weight of mice during the experimental period. It can be concluded that AFE of N. arbor-tristis posses safe oral anti diabetic potentials mediated via multiple mechanisms. Results of the present study scientifically proved the claims made about the uses of N. arbor-tristis in the treatment of diabetes mellitus in traditional Sri Lankan medicinal system. Further, flowers can also be used for as a remedy to improve blood lipid profile.

Keywords: aqueous extract, hypoglycemic hypolipidemic, Nyctanthes arbor-tristis flowers, hepatotoxicity

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4116 Neuroprotective Effect of Hypericum Perforatum against Neurotoxicity and Alzheimer's Disease (Experimental Study in Mice)

Authors: Khayra Zerrouki, Noureddine Djebli, Esra Eroglu, Afife Mat, Ozhan Gul

Abstract:

Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. Alzheimer’s disease (AD) is a complex, multifactorial, heterogeneous mental illness, which is characterized by an age-dependent loss of memory and an impairment of multiple cognitive functions, but this 10 last years it concerns the population most and most young. Hypericum perforatum has traditionally been used as an external anti-inflammatory and healing remedy for the treatment of swellings, wounds and burns, diseases of the alimentary tract and psychological disorders. It is currently of great interest due to new and important therapeutic applications. In this study, the chemical composition of methanolic extract of Hypericum perforatum (HPM) was analysed by using high performance liquid chromatography – diode array detector (HPLC-DAD). The in vitro antioxidant activity of HPM was evaluated by using several antioxidant tests. HSM exhibits inhibitory capacity against posphatidylcholine liposome peroxidation, induced with iron and ascorbic acid, scavenge DPPH and superoxide radicals and act as reductants. The cytotoxic activity of HSM was also determined by using MTT cell viability assay on HeLa and NRK-52E cell lines. The in vivo activity studies in Swiss mice were determined by using behavioral, memory tests and histological study. According to tests results HPM that may be relevant to the treatment of cognitive disorders. The results of chemical analysis showed a hight level of hyperforin and quercitin that had an important antioxidant activity proved in vitro with the DPPH, anti LPO and SOD; this antioxidant activity was confirmed in vivo after the non-toxic results by means of improvement in behavioral and memory than the reducing shrunken in pyramidal cells of mice brains.

Keywords: AlCl3, alzheimer, mice, neuroprotective, neurotoxicity, phytotherapy

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4115 The Mechanism of Parabacteroides goldsteinii on Immune Modulation and Anti-Obsogenicity

Authors: Yu-Ling Tsai, Chih-Jung Chang, Chia-Chen Lu, Eric Wu, Chuan-Sheng Lin, Tzu-Lung Lin, Hsin-Chih Lai

Abstract:

It is urgent that novel anti-obesity measures that are safe, effective and widely available are developed for counteracting the rapidly growing obesity epidemics. In the present study, we show that a probiotic bacterium Parabacteroides goldsteinii screened through culture under the high molecular weight polysaccharides prepared from two iconic medicinal fungi, the Ganoderma lucidum and the Hirsutella sinensis, reduced body weight by ca. 20% in high-fat diet (HFD)-fed mice. The bacterium also decreased intestinal permeability, metabolic endotoxemia, inflammation and insulin resistance. Notably, oral administration of live, but not high temperature-killed, P. goldsteinii to HFD fed mice considerably reduces weight gain and obesity-associated metabolic disorders. A three months feeding of the mice with P. goldsteinii did not show any aberrant side effects, indicating the safety of this bacterium. Transcriptome analysis indicated that P. goldsteinii enhances immunity in resting dendritic cells, but reduces inflammation in lipopolysaccharide (LPS)-induced dendritic cells. On top, Naïve T-cells were skewed towards regulatory T-cells after encountering with dendritic cells (DCs) pretreated with P. goldsteinii. These results indicated P. goldsteinii showed anti-inflammatory effects and can work as a potential probiotic ameliorating obesogenicity and related metabolic syndromes.

Keywords: Parabacteroides goldsteinii, gut microbiome, obesity, immune modulation

Procedia PDF Downloads 175
4114 Mediterranean Diet-Driven Changes in Gut Microbiota Decrease the Infiltration of Inflammatory Myeloid Cells into the Intestinal Tissue

Authors: Gema Gómez-Casado, Alba Rodríguez-Muñoz, Virginia Mela-Rivas, Pallavi Kompella, Francisco José Tinahones-Madueña, Isabel Moreno-Indias, Almudena Ortega-Gómez

Abstract:

Obesity is a high-priority health problem worldwide due to its high prevalence. The proportion of obese and overweight subjects in industrialized countries exceeds half of the population in most cases. Beyond the metabolic problem, obesity boosts inflammation levels in the organism. The gut microbiota, considered an organ by itself, controls a high variety of processes at a systemic level. In fact, the microbiota interacts closely with the immune system, being crucial in determining the maturation state of neutrophils, key effectors of the innate immune response. It is known that changes in the diet exert strong effects on the variety and activity of the gut microbiota. The effect that those changes have on the axis microbiota-immune response is an unexplored field. In this study, 10 patients with obesity (weight 114,3 ± 14,5Kg, BMI 40,47±3,66) followed a Mediterranean-hypocaloric diet for 3 months, reducing their initial weight by 12,71 ± 3%. A transplant of microbiota from these patients before and after the diet was performed into wild type “germ-free” mice (n=10/group), treated with antibiotics. Six weeks after the transplant, mice were euthanized, and the presence of cells from the innate immune system were analysed in different organs (bone marrow, blood, spleen, visceral adipose tissue, and intestine) by flow cytometry. No differences were observed in the number of myeloid cells in bone marrow, blood, spleen, or visceral adipose tissue of mice transplanted with patient’s microbiota before and after following the Mediterranean diet. However, the intestine of mice that received post-diet microbiota presented a marked decrease in the number of neutrophils (whose presence is associated with tissue inflammation), as well as macrophages. In line with these findings, intestine monocytes from mice with post-diet microbiota showed a less inflammatory profile (lower Ly6Gˡᵒʷ proportion of cells). These results point toward a decrease in the inflammatory state of the intestinal tissue, derived from changes in the gut microbiota, which occurred after a 3-month Mediterranean diet.

Keywords: obesity, nutrition, Mediterranean diet, gut microbiota, immune system

Procedia PDF Downloads 127
4113 Strategy in Practice: Strategy Development, Strategic Error and Project Delivery

Authors: Nipun Agarwal, David Paul, Fareed Un Din

Abstract:

Strategy development and implementation is the key to an organization’s success in today’s competitive marketplace. Many organizations develop excellent strategy but are unable to implement this strategy in order to succeed. The difference between strategic goals and its implementation is called strategic error. Strategic error occurs when an organization does not have structures in place to implement their strategy. Strategy implementation happens through projects and having a project management method that provides certainty and agility will help an organization become more competitive in implementing strategy. Numerous project management methods exist in theory and practice. However, projects mainly used the Waterfall method in the past that provides certainty in terms of budget, delivery date and resourcing. It is common practice now to utilise Agile based methods. However, Agile based methods do not provide specific deadlines and budgets. But provide agility in product design and project delivery, which is useful to companies. Both Waterfall and Agile methods in some forms are the opposites of each other. Executive management prefer agility in delivery projects as the competitive landscape changes frequently. However, they also appreciate certainty in the projects being able to quantify budgets, deadlines and resources that is harder for an Agile based method to provide. This paper attempts to develop a hybrid project management method that attempts to merge these Waterfall and Agile methods to provide the positives from both these approaches.

Keywords: strategy, project management, strategy implementation, agile

Procedia PDF Downloads 116
4112 Anticancer Activity of Milk Fat Rich in Conjugated Linoleic Acid Against Ehrlich Ascites Carcinoma Cells in Female Swiss Albino Mice

Authors: Diea Gamal Abo El-Hassan, Salwa Ahmed Aly, Abdelrahman Mahmoud Abdelgwad

Abstract:

The major conjugated linoleic acid (CLA) isomers have anticancer effect, especially breast cancer cells, inhibits cell growth and induces cell death. Also, CLA has several health benefits in vivo, including antiatherogenesis, antiobesity, and modulation of immune function. The present study aimed to assess the safety and anticancer effects of milk fat CLA against in vivo Ehrlich ascites carcinoma (EAC) in female Swiss albino mice. This was based on acute toxicity study, detection of the tumor growth, life span of EAC bearing hosts, and simultaneous alterations in the hematological, biochemical, and histopathological profiles. Materials and Methods: One hundred and fifty adult female mice were equally divided into five groups. Groups (1-2) were normal controls, and Groups (3-5) were tumor transplanted mice (TTM) inoculated intraperitoneally with EAC cells (2×106 /0.2 mL). Group (3) was (TTM positive control). Group (4) TTM fed orally on balanced diet supplemented with milk fat CLA (40 mg CLA/kg body weight). Group (5) TTM fed orally on balanced diet supplemented with the same level of CLA 28 days before tumor cells inoculation. Blood samples and specimens from liver and kidney were collected from each group. The effect of milk fat CLA on the growth of tumor, life span of TTM, and simultaneous alterations in the hematological, biochemical, and histopathological profiles were examined. Results: For CLA treated TTM, significant decrease in tumor weight, ascetic volume, viable Ehrlich cells accompanied with increase in life span were observed. Hematological and biochemical profiles reverted to more or less normal levels and histopathology showed minimal effects. Conclusion: The present study proved the safety and anticancer efficiency of milk fat CLA and provides a scientific basis for its medicinal use as anticancer attributable to the additive or synergistic effects of its isomers.

Keywords: anticancer activity, conjugated linoleic acid, Ehrlich ascites carcinoma, % increase in life span, mean survival time, tumor transplanted mice.

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4111 Relevance of Dosing Time for Everolimus Toxicity in Respect to the Circadian P-Glycoprotein Expression in Mdr1a::Luc Mice

Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

Abstract:

P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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4110 Green Synthesis of Silver Nanoparticles, Their Toxicity and Biomedical Applications

Authors: Kiran Shehzadi, Yasmeen Akhtar, Mujahid Ameen, Tabinda Ijaz, Shoukat Siddique

Abstract:

Nanoparticles, due to their different sizes and morphologies, are employed in various fields such as the medical field, cosmetics, pharmaceutical, textile industry as well as in paints, adhesives, and electronics. Metal nanoparticles exhibit excellent antimicrobial activity, dye degradation and can be used as anti-cancerous drug loading agents. In this study, sZilver nanoparticles (Ag-NPs) were synthesized employing doxycycline (antibiotic) as a reducing and capping agent (biological/green synthesis). Produced Ag-NPS were characterized using UV/VIS spectrophotometry, XRD, SEM, and FTIR. Surface plasmon resonance (SPR) of silver nanoparticles was observed at 411nm with 90nm size with homogenized spherical shape. These particles revealed good inhibition zones for Fungi such as Candida albicans and Candida tropicalis. In this study, toxic properties of Ag-NPs were monitored by allowing them to penetrate in the cell, causing an abrupt increase in oxidative stress, which resulted ultimately in cell death. Histopathological analysis of mice organs was performed by administering definite concentrations of silver nanoparticles orally to mice for 14 days. Toxic properties were determined, and it was revealed that the toxicity of silver nanoparticles mainly depends on the size. Silver nanoparticles of this work presented mild toxicity for different organs (liver, kidney, spleen, heart, and stomach) of mice.

Keywords: metal nanoparticles, green/biological methods, toxicity, Candida albicans, Candida tropicalis

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4109 Targetting T6SS of Klebsiella pneumoniae for Assessment of Immune Response in Mice for Therapeutic Lead Development

Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

Abstract:

Klebsiella pneumoniae bacteria is a global threat to human health due to an increase in multi-drug resistance among strains. The hypervirulent strains of Klebsiella pneumoniae is a major trouble due to their association with life-threatening infections in a healthy population. One of the major virulence factors of hyper virulent strains of Klebsiella pneumoniae is the T6SS (Type six secretary system) which is majorly involved in microbial antagonism and causes interaction with the host eukaryotic cells during infections. T6SS mediates some of the crucial factors for establishing infection by the bacteria, such as cell adherence, invasion, and subsequent in vivo colonisation. The antibacterial activity and the cell invasion property of the T6SS system is a major requirement for the establishment of K. pneumoniae infections within the gut. The T6SS can be an appropriate target for developing therapeutics. The T6SS consists of an inner tube comprising hexamers of Hcp (Haemolysin -regulated protein) protein, and at the top of this tube sits VgrG (Valine glycine repeat protein G); the tip of the machinery consists of PAAR domain containing proteins which act as a delivery system for bacterial effectors. For this study, immune response to recombinant VgrG protein was generated to establish this protein as a potential immunogen for the development of therapeutic leads. The immunogenicity of the selected protein was determined by predicting the B cell epitopes by the BCEP analysis tool. The gene sequence for multiple domains of VgrG protein (phage_base_V, T6SS_Vgr, DUF2345) was selected and cloned in pMAL vector in E. coli. The construct was subcloned and expressed as a fusion protein of 203 residue protein with mannose binding protein tag (MBP) to enhance solubility and purification of this protein. The purified recombinant VgrG fusion protein was used for mice immunisation. The antiserum showed reactivity with the recombinant VgrG in ELISA and western blot. The immunised mice were challenged with K. pneumoniae bacteria and showed bacterial clearance in immunised mice. The recombinant VgrG protein can further be used for studying downstream signalling of VgrG protein in mice during infection and for therapeutic MAb development to eradicate K. pneumoniae infections.

Keywords: immune response, Klebsiella pneumoniae, multi-drug resistance, recombinant protein expression, T6SS, VgrG

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4108 Ameliorating Effects of Silver Nanoparticles Synthesized Using Chlorophytum borivillianum against Gamma Radiation Induced Oxidative Stress in Testis of Swiss Albino Mice

Authors: Ruchi Vyas, Sanjay Singh, Rashmi Sisodia

Abstract:

Chlorophytum borivillianum root extract (CBE) was chosen as a reducing agent to fabricate silver nanoparticles with the aim of studying its radioprotective efficacy. The formation of synthesized nanoparticles was characterized by UV–visible analysis (UV–vis), Fourier transform infra-red (FT-IR), Transmission electron microscopy (TEM), Scanning electron microscope (SEM). TEM analysis showed particles size in the range of 20-30 nm. For this study, Swiss albino mice were selected from inbred colony and were divided into 4 groups: group I- control (irradiated-6 Gy), group II- normal (vehicle treated), group III- plant extract alone and group IV- CB-AgNPs (dose of 50 mg/kg body wt./day) administered orally for 7 consecutive days before irradiation to serve as experimental. CB-AgNPs pretreatment rendered significant increase in body weight and testes weight at various post irradiation intervals in comparison to irradiated group. Supplementation of CB-AgNPs reversed the adverse effects of gamma radiation on biochemical parameters as it notably ameliorated the elevation in lipid peroxidation and decline in glutathione concentration in testes. These observations indicate the radio-protective potential of CB-AgNPs in testicular constituents against gamma irradiation in mice.

Keywords: Chlorophytum borivillianum, gamma radiation, radioprotective, silver nanoparticles

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4107 Copywriting and the Creative Edge

Authors: Dandeswar Bisoyi, Preeti Yadav, Utpal Barua

Abstract:

This study address particular way that verbal information can affect the processing of positive and interesting qualities which help in making the brand attractive to the consumer. Also, it address the development of a communication strategy which is a very important part of the marketing plan we have to take into account many factors. Out of all the product strengths, the strategy has to outline one marked differential which will drive our brand. This is the fundamental base on which the entire creative strategy will be big idea-based.

Keywords: copy writing, advertisement, marketing, branding, recall

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4106 Effects of Supplementation with Annatto (Bixa Orellana)-Derived δ-Tocotrienol on the Nicotine-Induced Reduction in Body Weight and 8-Cell Preimplantation Embryonic Development in Mice

Authors: M. H. Rajikin, S. M. M. Syairah, A. R. Sharaniza

Abstract:

Effects of nicotine on pre-partum body weight and preimplantation embryonic development has been reported previously. Present study was conducted to determine the effects of annatto (Bixa orellana)-derived delta-tocotrienol (TCT) (with presence of 10% gamma-TCT isomer) on the nicotine-induced reduction in body weight and 8-cell embryonic growth in mice. Twenty four 6-8 weeks old (23-25g) female balb/c mice were randomly divided into four groups (G1-G4; n=6). Those groups were subjected to the following treatments for 7 consecutive days: G1 (control) were gavaged with 0.1 ml tocopherol stripped corn oil, G2 was subcutaneously (s.c.) injected with 3 mg/kg/day of nicotine, G3 received concurrent treatment of nicotine (3 mg/kg/day) and 60 mg/kg/day of δ-TCT mixture (contains 90% delta & 10% gamma isomers) and G4 was given 60 mg/kg/day of δ-TCT mixture alone. Body weights were recorded daily during the treatment. On Day 8, females were superovulated with 5 IU Pregnant Mare’s Serum Gonadotropin (PMSG) for 48 hours followed with 5 IU human Chorionic Gonadotropin (hCG) before mated with males at the ratio of 1:1. Females were sacrificed by cervical dislocation for embryo collection 48 hours post-coitum. Collected embryos were cultured in vitro. Results showed that throughout Day 1 to Day 7, the body weight of nicotine treated group (G2) was significantly lower (p<0.05) than that of G1, G3 and G4. Intervention with δ-TCT mixture (G3) managed to increase the body weight close to the control group. This is also observed in the group treated with δ-TCT mixture alone (G4). The development of 8-cell embryos following in vitro culture (IVC) was totally inhibited in G2. Intervention with δ-TCT mixture (G3) resulted in the production of 8-cell embryos, although it was not up to that of the control group. Treatment with δ-TCT mixture alone (G4) caused significant increase in the average number of produced 8-cell embryo compared to G1. Present data indicated that δ-TCT mixture was able to reverse the body weight loss in nicotine treated mice and the development of 8-cell embryos was also improved.

Keywords: δ-tocotrienol, body weight, nicotine, preimplantation embryonic development

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4105 Antiasthmatic Effect of Kankasava in OVA-Induced Asthma Mouse Model

Authors: Bharti Ahirwar

Abstract:

The main object of this study was to evaluate the effect of kankasava on OVA-induced asthma in mouse model. Present study has demonstrated that kankasava exhibited an antiasthmatic effect by attenuated AHR and reducing level of IgE, IL-5, and IL-13, in both serum and BALF in OVA induced asthmatic mice. Effect of kankasav on airway responsiveness was obtained by monitoring the enhanced pen value . Kankasava significantly reduced AHR can be explained, in part, by reduction in both IgE overexoression and cytokine levels. Kankasava significantly decreased IL-4, IL-5, and IL-13 in BALF indicate that it may suppress the excess activity of T-cells and Th2 cytokines, which are implicated in the pathogenesis of allergic asthma, and consequently restore the Th1/Th2 imbalance of the immune system. In summary, we hypothesize that kankasava effectively suppressed elevations in IgE and cytokines levels, AHR, and mucus overproduction in mice with OVA-induced asthma suggested kankasava could be effective in immunological and pharmacological modulation of allergic asthma.

Keywords: asthma, ayurveda, kankasava, cytokine

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4104 Create a Model of Production and Marketing Strategies in Alignment with Business Strategy Using QFD Approach

Authors: Hamed Saremi, Shahla Saremi

Abstract:

In today's competitive world, organizations are expected to surpass the competitors and benefit from the resources and benefits. Therefore, organizations need to improve the current performance is felt more than ever that this requires to identify organizational optimal strategies, and consider all strategies simultaneously. In this study, to enhance competitive advantage and according to customer requirements, alignment between business, production and marketing strategies, House of Quality (QFD) approach has been used and zero-one linear programming model has been studied. First, the alignment between production and marketing strategies with business strategy, independent weights of these strategies is calculated. Then with using QFD approach the aligned weights of optimal strategies in each production and marketing field will be obtained and finally the aligned marketing strategies selection with the purpose of allocating budget and specialist human resource to marketing functions will be done that lead to increasing competitive advantage and benefit.

Keywords: marketing strategy, business strategy, strategy alignment, house of quality deployment, production strategy

Procedia PDF Downloads 605
4103 Sponsorship Strategy, Its Visibility, and Return: A Case Study on Brazilian Olympic Games

Authors: Elizabeth F. Rodrigues, Julia da R. Mattos, Naira Q. Leitão, Roberta T. da Cunha

Abstract:

The business strategy of many companies has two factors in common: the search for the competitive edge and its long term maintenance. The thing that differentiates the companies’ performance in their abilities to set the right strategy, which depends on their capacity to analyze and apply all sort of management support tools. In this context, the sponsorship of events stands out as an important way to increase brand awareness, especially when it is a worldwide event, such as Rio 2016 Olympic and Paralympic Games. This paper will present the case of a car maker company, which chose to invest on sponsorship as a way to reach its goals and grow in the brazilian market.

Keywords: strategy, sponsorship, events, management

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4102 Fatty Acid Extracts of Sea Pen (Virgularia gustaviana) and Their Potential Applications as Antibacterial, Antifungal, and Anti-Inflammatory Agents

Authors: Sharareh Sharifi

Abstract:

In this study, the crude extracts of Virgularia gustavina were examined as antibacterial, antifungal and anti-inflammatory agent. To assess inflammation, Xylene was applied to the ear of mice. The mice of the experimental group were fed with doses of 10 mg/kg, 20 mg/kg, and 40 mg/kg of lipid extract of chloroform and hexane as a separate group and then statistical analysis was performed on the results. Chloroform and hexane extracts of sea pen have strong anti-inflammatory effects even at low doses which is probably due to 54% arachidonic acid. Antibacterial and antifungal effects of hexane and chloroform extracts were measured with MIC and MBC methods and it is shown that chloroform extract has best activity against Staphylococcus aureus on 125 µg/ml doze in MIC method.

Keywords: sea pen (virgularia gustaviana), lipid extract, anti-inflammatory and anti-bacterial activities, fatty acid

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4101 Shikonin Reduces Endometriosis by Inhibiting RANTES Secretion and Mononuclear Macrophage Chemotaxis

Authors: Dong-ping Yuan, Lin Gu, Jun Long, Jie Chen, Ni Jie, Ying-Li Shi

Abstract:

Endometriosis is a common disease in women of reproductive age, whose classic characteristic is mononuclear cell infiltration into lesions. Shikonin is an anti-inflammatory phytocompound from Lithospermum erythrorhizon, whose potential therapeutic effects for the endometriosis remain unclear. The working hypothesis was that shikonin can inhibit the development of endometriosis by the inhibition of chemotactic effect. Shikonin significantly inhibited the growth of human endometrial tissue implanted into mice (P<0.05). No observable adverse effects were found. The mouse regulated upon activation normal T-cell expressed and secreted (mRANTES) level in peritoneal fluid of animal endometriosis model was higher than that in normal SCID mice (P<0.05), and decreased dramatically after shikonin treatment in a dose-dependent manner (P<0.05). Peritoneal fluid from NOD/SCID mice treated with shikonin inhibited monocytes chemotaxis, which could be abolished by mRANTES antibody. In vitro, shikonin significantly inhibited RANTES expression of U937 cells cultured alone or co-cultured with human methothelail cells and endometrial stromal cells, and inhibited RANTES-induced chemotaxis of U937 cells (P<0.05). The present results suggest that shikonin can inhibit the development of endometriosis by mechanisms that at least include the inhibition of RANTES expression and decreased migration of mononuclear cells to lesions. Shikonin may be a useful and safe new approach for treating endometriosis.

Keywords: endometriosis, shikonin, RANTES chemotaxis

Procedia PDF Downloads 395
4100 Model of Production and Marketing Strategies in Alignment with Business Strategy using QFD Approach

Authors: Hamed Saremi, Suzan Taghavy, Shahla Saremi

Abstract:

In today's competitive world, organizations are expected to surpass the competitors and benefit from the resources and benefits. Therefore, organizations need to improve the current performance is felt more than ever that this requires to identify organizational optimal strategies, and consider all strategies simultaneously. In this study, to enhance competitive advantage and according to customer requirements, alignment between business, production and marketing strategies, House of Quality (QFD) approach has been used and zero-one linear programming model has been studied. First, the alignment between production and marketing strategies with business strategy, independent weights of these strategies is calculated. Then with using QFD approach the aligned weights of optimal strategies in each production and marketing field will be obtained and finally the aligned marketing strategies selection with the purpose of allocating budget and specialist human resource to marketing functions will be done that lead to increasing competitive advantage and benefit.

Keywords: strategy alignment, house of quality deployment, production strategy, marketing strategy, business strategy

Procedia PDF Downloads 435
4099 Effects of Jigsaw Strategy on Senior Secondary School Students’ Achievement in Ecology in Maitagari, Jigawa State, Nigeriaind Out the Effect of Jigsaw Strategy on Students’ Achievement in Ecology

Authors: Ozoji Bernadette, Sa’Ad-Abdullahi Abdulhafiz, Izundu Chike Leo

Abstract:

The study investigated the effect of Jigsaw strategy on senior secondary school students’ achievement in Maitagari, Jigawa State, Nigeria. The pre-test, post-test quasi experimental design was employed in the study. The sample for the study comprised 120 students from two public schools from the study area. An instrument namely, Ecological Achievement Test (EAT) was used to collect data from students. The data were analyzed using SPSS version 26.0. The EAT was validated by two experts, one, in Science Education unit and the other in Research, Measurement and Evaluation unit, both in the Faculty of Education, University of Jos, Nigeria. The reliability coefficient of the EAT was established as 0.85 using Kuder Richardson Formular 20. Mean and standard deviation were used to answer two research questions while Analysis of Covariance was used to test two hypotheses that guided the study. Results showed that students taught using jigsaw strategy achieved significantly better than their counterparts taught using the conventional method in ecology. Furthermore, it was revealed that gender had no significant influence on achievement of students exposed to jigsaw strategy. It was concluded that jigsaw strategy was effective in improving students’ achievement in ecology. The study recommended that teachers should incorporate jigsaw strategy into science classrooms for improved achievement outcome and gender equality.

Keywords: achievement, ecology, jigsaw strategy, lecture strategy

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4098 Direct Assessment of Cellular Immune Responses to Ovalbumin with a Secreted Luciferase Transgenic Reporter Mouse Strain IFNγ-Lucia

Authors: Martyna Chotomska, Aleksandra Studzinska, Marta Lisowska, Justyna Szubert, Aleksandra Tabis, Jacek Bania, Arkadiusz Miazek

Abstract:

Objectives: Assessing antigen-specific T cell responses is of utmost importance for the pre-clinical testing of prototype vaccines against intracellular pathogens and tumor antigens. Mainly two types of in vitro assays are used for this purpose 1) enzyme-linked immunospot (ELISpot) and 2) intracellular cytokine staining (ICS). Both are time-consuming, relatively expensive, and require manual dexterity. Here, we assess if a straightforward detection of luciferase activity in blood samples of transgenic reporter mice expressing a secreted Lucia luciferase under the transcriptional control of IFN-γ promoter parallels the sensitivity of IFNγ ELISpot assay. Methods: IFN-γ-LUCIA mouse strain carrying multiple copies of Lucia luciferase transgene under the transcriptional control of IFNγ minimal promoter were generated by pronuclear injection of linear DNA. The specificity of transgene expression and mobilization was assessed in vitro using transgenic splenocytes exposed to various mitogens. The IFN-γ-LUCIA mice were immunized with 50mg of ovalbumin (OVA) emulsified in incomplete Freund’s adjuvant three times every two weeks by subcutaneous injections. Blood samples were collected before and five days after each immunization. Luciferase activity was assessed in blood serum. Peripheral blood mononuclear cells were separated and assessed for frequencies of OVA-specific IFNγ-secreting T cells. Results: We show that in vitro cultured splenocytes of IFN-γ-LUCIA mice respond by 2 and 3 fold increase in secreted luciferase activity to T cell mitogens concanavalin A and phorbol myristate acetate, respectively but fail to respond to B cell-stimulating E.coli lipopolysaccharide. Immunization of IFN-γ-LUCIA mice with OVA leads to over 4 fold increase in luciferase activity in blood serum five days post-immunization with a barely detectable increase in OVA-specific, IFNγ-secreting T cells by ELISpot. Second and third immunizations, further increase the luciferase activity and coincidently also increase the frequencies of OVA-specific T cells by ELISpot. Conclusions: We conclude that minimally invasive monitoring of luciferase secretions in blood serum of IFN-γ-LUCIA mice constitutes a sensitive method for evaluating primary and memory Th1 responses to protein antigens. As such, this method may complement existing methods for rapid immunogenicity assessment of prototype vaccines.

Keywords: ELISpot, immunogenicity, interferon-gamma, reporter mice, vaccines

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4097 The Role of Female Population as a Consumer in Modern Marketing Strategy and Management

Authors: Jana Aleksić, Marijana Petković

Abstract:

Female population has an increasing role when it comes to purchase. Consequently, the female population has a greater role in modern marketing. Although it is thought that women buy more than men, marketing strategy was not directed specifically towards women. The thing that has changed regarding women’s role in modern marketing is the fact that the female population has a leading position when it comes to decision making in various fields and various sectors, which was not the case in the past. Marketing should be directed towards women but it should be done in the right way. Compared to men, women buy in a different way, and they look for more various advantages in the product itself, than men do. This paper aims to show the importance of the female role in the modern marketing and management and to redirect marketing in some way towards female population through new marketing strategies and management systems. Hypothesis is that women have an important role in marketing, and marketing strategy of modern society could and should be based on and directed towards female population and their tastes when it comes to purchasing. It is necessary and desirable to apply marketing strategy with a special strategy that has an emphasis on women and their purchase or in a word to apply WS- woman strategy. This research was carried out as a random sample research, where were obtained 212 valid surveys whose results serve as a basis for drawing conclusions about the research as well as to verify the formulated hypotheses. The research was carried out during 2011 and 2012. The study has shown a significant role of the female population in the marketing process.

Keywords: marketing, management, female, purchase, strategy

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4096 Origanum vulgare as a Possible Modulator of Testicular Endocrine Function in Mice

Authors: Eva Tvrdá, Barbora Babečková, Michal Ďuračka, Róbert Kirchner, Július Árvay

Abstract:

This study was designed to assess the in vitro effects of Origanum vulgare L. (oregano) extract on the testicular steroidogenesis. We focused on identifying major biomolecules present in the oregano extract, as well as to investigate its in vitro impact on the secretion of cholesterol, testosterone, dehydroepiandrosterone and androstenedione by murine testicular fragments. The extract was subjected to high performance liquid chromatography (HPLC) which identified cyranosid, daidzein, thymol, rosmarinic and trans-caffeic acid among the predominant biochemical components of oregano. For the in vitro experiments, testicular fragments from 20 sexually mature Institute of Cancer Research (ICR) mice were incubated in the absence (control group) or presence of the oregano extract at selected concentrations (10, 100 and 1000 μg/mL) for 24 h. Cholesterol levels were quantified using photometry and the hormones were assessed by ELISA (Enzyme-Linked Immunosorbent Assay). Our data revealed that the release of cholesterol and androstenedione (but not dehydroepiandrosterone and testosterone) by the testicular fragments was significantly impacted by the oregano extract in a dose-dependent fashion. Supplementation of the extract resulted in a significant decline of cholesterol (P < 0.05 in case of 100 μg/mL; P < 0.01 with respect 100 μg/mL extract), as well as androstenedione (P < 0.01 with respect to 100 and 1000 μg/mL extract). Our results suggest that the biomolecules present in Origanum vulgare L. could exhibit a dose-dependent impact on the secretion of male steroids, playing a role in the regulation of testicular steroidogenesis.

Keywords: mice, Origanum vulgare L., steroidogenesis, testes

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4095 Assessing Brain Targeting Efficiency of Ionisable Lipid Nanoparticles Encapsulating Cas9 mRNA/gGFP Following Different Routes of Administration in Mice

Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

Abstract:

Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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4094 Activity Anti-Motility Exstract Kedondong Leaf in Balb/C Strain Male Mice Invivo

Authors: Muhammad Abdul Latif, Edijanti Goenarwo , Intan Rahmania Eka

Abstract:

Diarrhea is one of the leading causes of morbidity and mortality in many countries, as well as responsible for the deaths of millions of people each year. Previous research showed that the leaves, bark, and root bark of kedondong contains saponins, tannins, and flavonoids. Tannins have anti-diarrheal effects that work as the freeze of protein / astrigen, and may inhibit the secretion of chloride over the tannate bonding between protein in the intestines. Chemical compounds of flavonoids also have an effect as anti-diarrheal block receptors Cl ˉ in intestinal thus reducing the secretion of Cl ˉ to the intestinal lume. This research aims to know the anti-diarrheal activity of extracts kedondong leaf in mice Balb/C strain males in vivo. This research also proves kedondong leaves as an anti-diarrhea through trial efficacy of kedondong leaves as antisekretori and antimotilitas. This research using post-test only controlled group design. Analysis of statistical data normality and homogenity were tested by Kolmogorov Smirnov. If the data obtained homogenous then using ANOVA test. This research using ethanolic extracts kedondong leaf 200, 400 and 800 mg/kg BW to prove there is anti-motility became five treatment groups. The result showed dose of ethanolic extracts kedondong leaf 800 mg/kg BW have significant value (p < 0.005). The conclusion from this extracts kedondong leaf research 800 mg/kg BW have pharmacological effects as antimotility on Balb/C strain male mice.

Keywords: anti-diarrhea, anti-motility, castrol oil, kedondong leaf

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4093 Hepatoprotective Action of Emblica officinalis Linn. against Radiation and Lead Induced Changes in Swiss Albino Mice

Authors: R. K. Purohit

Abstract:

Ionizing radiation induces cellular damage through direct ionization of DNA and other cellular targets and indirectly via reactive oxygen species which may include effects from epigenetic changes. So there is a need of hour is to search for an ideal radioprotector which could minimize the deleterious and damaging effects caused by ionizing radiation. Radioprotectors are agents which reduce the radiation effects on cell when applied prior to exposure of radiation. The aim of this study was to access the efficacy of Emblica officinalis in reducing radiation and lead induced changes in mice liver. For the present experiment, healthy male Swiss albino mice (6-8 weeks) were selected and maintained under standard conditions of temperature and light. Fruit extract of Emblica was fed orally at the dose of 0.01 ml/animal/day. The animal were divided into seven groups according to the treatment i.e. lead acetate solution as drinking water (group-II) or exposed to 3.5 or 7.0 Gy gamma radiation (group-III) or combined treatment of radiation and lead acetate (group-IV). The animals of experimental groups were administered Emblica extract seven days prior to radiation or lead acetate treatment (group V, VI and VII) respectively. The animals from all the groups were sacrificed by cervical dislocation at each post-treatment intervals of 1, 2, 4, 7, 14 and 28 days. After sacrificing the animals pieces of liver were taken out and some of them were kept at -20°C for different biochemical parameters. The histopathological changes included cytoplasmic degranulation, vacuolation, hyperaemia, pycnotic and crenated nuclei. The changes observed in the control groups were compared with the respective experimental groups. An increase in the value of total proteins, glycogen, acid phosphtase, alkaline phosphatase activity and RNA was observed up to day-14 in the non drug treated group and day 7 in the Emblica treated groups, thereafter value declined up to day-28 without reaching to normal. The value of cholesterol and DNA showed a decreasing trend up to day -14 in non drug treated groups and day-7 in drug treated groups, thereafter value elevated up to day-28. The biochemical parameters were observed in the form of increase or decrease in the values. The changes were found dose dependent. After combined treatment of radiation and lead acetate synergistic effect were observed. The liver of Emblica treated animals exhibited less severe damage as compared to non-drug treated animals at all the corresponding intervals. An early and fast recovery was also noticed in Emblica pretreated animals. Thus, it appears that Emblica is potent enough to check lead and radiation induced heptic lesion in Swiss albino mice.

Keywords: radiation, lead , emblica, mice, liver

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4092 Estimated Human Absorbed Dose of 111 In-BPAMD as a New Bone-Seeking Spect-Imaging Agent

Authors: H. Yousefnia, S. Zolghadri

Abstract:

An early diagnosis of bone metastases is very important for providing a profound decision on a subsequent therapy. A prerequisite for the clinical application of new diagnostic radiopharmaceutical is the measurement of organ radiation exposure dose from biodistribution data in animals. In this study, the dosimetric studies of a novel agent for SPECT-imaging of bone methastases, 111In-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (111In-BPAMD) complex, have been estimated in human organs based on mice data. The radiolabeled complex was prepared with high radiochemical purity at the optimal conditions. Biodistribution studies of the complex were investigated in male Syrian mice at selected times after injection (2, 4, 24 and 48 h). The human absorbed dose estimation of the complex was performed based on mice data by the radiation absorbed dose assessment resource (RADAR) method. 111In-BPAMD complex was prepared with high radiochemical purity >95% (ITLC) and specific activities of 2.85 TBq/mmol. Total body effective absorbed dose for 111In-BPAMD was 0.205 mSv/MBq. This value is comparable to the other 111In clinically used complexes. The results show that the dose to critical organs the complex is well within the acceptable considered range for diagnostic nuclear medicine procedures. Generally, 111In-BPAMD has interesting characteristics and can be considered as a viable agent for SPECT-imaging of the bone metastases in the near future.

Keywords: In-111, BPAMD, absorbed dose, RADAR

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4091 Effects of the Treatment by Polypill Combinations vs Identical Monopill Therapies in Patients with Cardiovascular Comorbid Diseases

Authors: Denys Sebov, Viktoriia Korotaieva, Kateryna Markina

Abstract:

The clinical advantage of the multipill combination drugs administration (polypill-strategy) over single-component drugs (monopill-strategy) has been established in patients with comorbid arterial hypertension, heart failure, chronic coronary syndrome, diabetes. It was found that polypill-strategy provides better treatment adherence in 33.4% of the patients. It was proven a significant decrease in systolic and diastolic blood pressure, as well as a decrease in dispersion index due to the stability of the blood pressure profile in patients with the polypill-strategy treatment.

Keywords: polypill, artetial hypertension, cardiovascular disease, compliance

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4090 The Antecedents of Customer-to-Customer Interaction to Brand and Communication Strategy: A Marketer’s Perspective

Authors: Kartina Sury Kariman

Abstract:

Brand-to-customer (B2C) engagement has been well established through the traditional platform such as direct sales, advertising, customer service center, customer hotline as well as brand usage experiences. Increasingly, interest to B2C has evolved to include customer-to-customer (C2C) interaction analysis aligned with the vast growth of web 2.0. Hence, discussion on C2C interaction and brand strategy have captured social media as it enables brands and C2C interaction to be connected in various ways, providing opportunities for marketers to shape their brand engagement strategy while reaching C2C as the targeted outcomes. The objective here is to provide a preliminary review of C2C interaction consisting the antecedents and consequences while highlighting areas of research interest within the context from marketers perspective and the business outcomes. This paper discusses how C2C interaction defines marketers’ brand and communication strategy and how social media trend shapes the strategy when promoting the awareness of life insurance industry and educating the target market.

Keywords: social media, brand engagement, customer interaction, customer engagement, brand strategy, life insurance

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4089 Involvement of Nrf2 in Kolaviron-Mediated Attenuation of Behavioural Incompetence and Neurodegeneration in a Murine Model of Parkinson's Disease

Authors: Yusuf E. Mustapha, Inioluwa A Akindoyeni, Oluwatoyin G. Ezekiel, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi

Abstract:

Background: Parkinson's disease (PD) is the most prevalent motor disorder. Available therapies are palliative with no effect on disease progression. Kolaviron (KV), a natural anti-inflammatory and antioxidant agent, has been reported to possess neuroprotective effects in Parkinsonian flies and rats. Objective: The present study investigates the neuroprotective effect of KV, focusing on the DJ1/Nrf2 signaling pathway. Methodology: All-trans retinoic acid (ATRA, 10 mg/kg, i.p.) was used to inhibit Nrf2. Murine model of PD was established with four doses of MPTP (20 mg/kg i.p.) at 2 hours interval. MPTP mice were pre-treated with either KV (200 mg/kg/day p.o), ATRA, or both conditions for seven days before PD induction. Motor behaviour was evaluated, and markers of oxidative stress/damage and its regulators were assessed with immunofluorescence and ELISA techniques. Results: MPTP-treated mice covered less distance with reduced numbers of anticlockwise rotations, heightened freezing, and prolonged immobility when compared to control. However, KV significantly attenuated these deficits. Pretreatment of MPTP mice with KV upregulated Nrf2 expression beyond MPTP level with a remarkable reduction in Keap1 expression and marked elevation of DJ-1 level, whereas co-administration with ATRA abrogated these effects. KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal oxidative stress, oxidative damage, and inhibition of acetylcholinesterase activity. However, ATRA treatment potentiated acetylcholinesterase inhibition and attenuated the protective effect of KV on the level of nitric oxide and activities of catalase and superoxide dismutase. Conclusion: Kolaviron protects Parkinsonian mice by stabilizing and activating the Nrf2 signaling pathway. Thus, kolaviron can be explored as a pharmacological lead in PD management.

Keywords: Garcinia kola, Kolaviron, Parkinson Disease, Nrf2, behavioral incompetence, neurodegeneration

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