Search results for: drug accessibility

Authors: Colleen Cleveland, W. Adam Baldowski

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In the dynamic realm of online education, the integration of games and entertainment has emerged as a powerful strategy to captivate learners, drive active participation, and cultivate meaningful learning experiences. This abstract presents an overview of the upcoming conference, "Game On," dedicated to exploring the transformative impact of gamification, interactive simulations, and multimedia content in the digital learning landscape. Introduction: The conference aims to blur the traditional boundaries between education and entertainment, inspiring learners of diverse ages and backgrounds to actively engage in their online learning journeys. By leveraging the captivating elements of games and entertainment, educators can enhance motivation, retention, and deep understanding among virtual classroom participants. Conference Highlights: Commencing with an exploration of theoretical foundations drawing from educational psychology, instructional design, and the latest pedagogical research, participants will gain valuable insights into the ways gamified elements elevate the quality of online education. Attendees can expect interactive sessions, workshops, and case studies showcasing best practices and innovative strategies, including game-based assessments and virtual reality simulations. Inclusivity and Diversity: The conference places a strong emphasis on inclusivity, accessibility, and diversity in the integration of games and entertainment for educational purposes. Discussions will revolve around accommodating diverse learning styles, overcoming potential challenges, and ensuring equitable access to engaging educational content for all learners. Educational Transformation: Educators, instructional designers, and e-learning professionals attending "Game On" will acquire practical techniques to elevate the quality of their online courses. The conference promises a stimulating and informative exploration of blending education with entertainment, unlocking the untapped potential of games and entertainment in online education. Conclusion: "Game On" invites participants to embark on a journey that transforms online education by harnessing the power of entertainment. This event promises to be a cornerstone in the evolution of virtual learning, offering valuable insights for those seeking to create a more engaging and effective online educational experience. Join us as we explore new horizons, pushing the boundaries of online education through the fusion of games and entertainment.

Keywords: online education, games, entertainment, psychology, therapy, pop culture

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Authors: Arjun Prakash, Vinutha H., Karthik N.

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BACKGROUND: Carpal tunnel syndrome (CTS) is a common entrapment neuropathy with an estimated prevalence of 0.6 - 5.8% in the general adult population. It is caused by compression of the Median Nerve (MN) at the wrist as it passes through a narrow osteofibrous canal. Presently, the diagnosis is established by the clinical symptoms and physical examination and Nerve conduction study (NCS) is used to assess its severity. However, it is considered to be painful, time consuming and expensive, with a false-negative rate between 16 - 34%. Ultrasonography (USG) is now increasingly used as a diagnostic tool in CTS due to its non-invasive nature, increased accessibility and relatively low cost. Elastography is a newer modality in USG which helps to assess stiffness of tissues. However, there is limited available literature about its applications in peripheral nerves. OBJECTIVES: Our objectives were to measure the Cross-Sectional Area (CSA) and elasticity of MN at the carpal tunnel using Grey scale Ultrasonography (USG), Strain Elastography (SE) and Shear Wave Elastography (SWE). We also made an attempt to independently evaluate the role of Gray scale USG, SE and SWE in grading the severity of CTS, keeping NCS as the gold standard. MATERIALS AND METHODS: After approval from the Institutional Ethics Review Board, we conducted a comparative cross sectional study for a period of 18 months. The participants were divided into two groups. Group A consisted of 54 patients with clinically diagnosed CTS who underwent NCS, and Group B consisted of 50 controls without any clinical symptoms of CTS. All Ultrasound examinations were performed on SAMSUNG RS 80 EVO Ultrasound machine with 2 - 9 Mega Hertz linear probe. In both groups, CSA of the MN was measured on Grey scale USG, and its elasticity was measured at the carpal tunnel (in terms of Strain ratio and Shear Modulus). The variables were compared between both groups by using ‘Independent t test’, and subgroup analyses were performed using one-way analysis of variance. Receiver operating characteristic curves were used to evaluate the diagnostic performance of each variable. RESULTS: The mean CSA of the MN was 13.60 + 3.201 mm2 and 9.17 + 1.665 mm2 in Group A and Group B, respectively (p < 0.001). The mean SWE was 30.65 + 12.996 kPa and 17.33 + 2.919 kPa in Group A and Group B, respectively (p < 0.001), and the mean Strain ratio was 7.545 + 2.017 and 5.802 + 1.153 in Group A and Group B respectively (p < 0.001). CONCLUSION: The combined use of Gray scale USG, SE and SWE is extremely useful in grading the severity of CTS and can be used as a painless and cost-effective alternative to NCS. Early diagnosis and grading of CTS and effective treatment is essential to avoid permanent nerve damage and functional disability.

Keywords: carpal tunnel, ultrasound, elastography, nerve conduction study

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Authors: Friman Hen, Banner Ifaa, Shalom-Tuchin Bosmat, Einav Yulia

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The action learning course is an academic course which involves academic learning and social activities. The courses deal with processes and social challenges, reveal different ideologies, and develop critical thinking and pragmatic ideas. Students receive course credits and a grade for being part of such courses. Participating students enroll in courses that involve action and activities to engage in the experiential learning process, thereby creating a dialogue and cross-fertilization between being taught in the classroom and experiencing the reality in the real world. A learning experience includes meeting with social organizations, institutions, and state authorities and carrying out practical work with diverse populations. Through experience, students strengthen their academic skills, formulate ethical attitudes toward reality, develop professional and civilian perspectives, and realize how they can influence their surrounding in the present and the hereafter. Under the guidance and supervision of Dr. Hen Friman, H.I.T. has built an innovative course that combines action and activities to increase the awareness and accessibility of the community in an experiential way. The end goal is to create Green Ambassadors—children with a high level of environmental awareness. This course is divided into two parts. The first part, focused on frontal teaching, delivers knowledge from extensive environmental fields to students. These areas include introduction to ecology, the process of electricity generation, air pollution, renewable energy, water economy, waste and recycling, and energy efficiency (first stage). In addition to the professional content in the environment field, students learn the method of effective and experiential teaching to younger learners (4 to 8 years old). With the attainment of knowledge, students are divided into operating groups. The second part of the course shows how the theory becomes practical and concrete. At this stage, students are asked to introduce to the first- and second-graders of ‘Revivim’ School in Holon a lesson of 90 minutes focused on presenting the issues and their importance during the course (second stage). This course is the beginning of a paradigm shift regarding energy usage in the modern society in Israel. The objective of the course is to expand worldwide and train the first and second-graders, and even pre-schoolers, in a wide scope to increase population awareness rate, both in Israel and all over the world, for a green future.

Keywords: air pollution, green ambassador, recycling, renewable energy

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Authors: Samir Kumar Pal

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Background: Targeted rapid degradation of bilirubin has the potential to thwart incipient bilirubin encephalopathy. Uncontrolled hyperbilirubinemia is a potential problem in developing countries, including India, because of the lack of reliable healthcare institutes for conventional phototherapy. In India, most of the rural subjects duel in the exchange limit during transport, leading to a risk of kernicterus when they arrive at the treatment centre. Thus, an alternative pharmaceutical agent is needed for the hours. Objective: Exploration of a distinct therapeutic strategy for the control of neonatal hyperbilirubinemia compared to conventional phototherapy in a clinical setting. Method: We synthesized, characterized and investigated a spinel-structured Manganese citrate nanocomplex (C-Mn₃O₄ NC, the nanodrug) along with conventional phototherapy in neonatal subjects. We have also observed BIND scores in order to assess neurological dysfunctions. Results: Our observational study clearly reveals that the rate of declination of bilirubin in neonatal subjects with nanodrug oral administration and phototherapy is faster compared to that in the case of phototherapy only. The associated neural dysfunctions were also found to be significantly lower in the case of combined therapy. Conclusion: This study demonstrates that combined therapy works better than conventional phototherapy only for the control of hyperbilirubinemia. We have observed that a significant portion of neonatal subjects requiring blood exchange has been prevented with the combined therapeutic strategy. Further compilation of a drug-safety-dossier is warranted to translate this novel therapeutic chemo preventive approach to clinical settings.

Keywords: nanodrug, nanoparticle, Neonatal hyperbilirubinemia, alternative to phototherapy, redox modulation, redox medicine

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Authors: M. Sangeetha, D. Chamundeeswari, C. Saravanababu, C. Rose, V. Gopal

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Rheumatoid arthritis (RA) is a chronic, progressive, systemic inflammatory disorder affecting the synovial joints and typically producing symmetrical arthritis that leads to joint destruction, which is responsible for the deformity and disability. Despite improvements in the treatment of RA over the past decade, there still is a need for new therapeutic agents that are efficacious, less expensive, and free of severe adverse reactions. The present study aimed to investigate role of inflammatory markers in arthritic rats treated with ethanolic bark extract of Albizia procera. The protective effect of ethanolic bark extract of Albizia procera against complete Freund’s adjuvant (CFA) induced arthritis in rats. Arthritis was induced by an intradermal injection of 0.1 ml FCA in the foot pad of left hind limb of rats. ETBE (100 and 200 mg/kg b.wt./p.o) and the reference drug diclofenac (25 mg/kg b.wt./p.o) were administered to arthritic rats. Paw volume was measured for all the animals before inducing arthritis and thereafter once in seven days by using plethysmometer for 42 days. Gene expression of inflammatory markers such as IL-1β and IL-10 were investigated in paw tissues. Up regulation of IL-1β and Down regulation IL-10 were observed in CFA injected rats when compared to normal rats. ETBE attenuated these alterations dose dependently when compared to the vehicle treated rats. These results provide insights into the mechanism of anti-arthritic activity, and unravel potential therapeutic use of Albizia procera in arthritis.

Keywords: CFA-Complete Freund’s adjuvant, ETBE – ethanolic bark extract, IL- interleukins, RA-rheumatoid arthritis

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Authors: Bhuvanesh Baniya

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Alzheimer disease is illnesses that are responsible for neuronal cell death and resulting in lifelong cognitive problems. Due to their unclear mechanism, there are no effective drugs available for the treatment. For a long time, herbal drugs have been used as a role model in the field of the drug discovery process. Holy basil in the Indian medicinal system (Ayurveda) is used for several neuronal disorders like insomnia and memory loss for decades. This study aims to identify active components of holy basil as potential inhibitors for the treatment of Alzheimer disease. To fulfill this objective, the Network pharmacology approach, gene ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics simulation (MDS) studies were performed. A total of 7 active components in holy basil, 12 predicted neurodegenerative targets of holy basil, and 8063 Alzheimer-related targets were identified from different databases. The network analysis showed that the top ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B were found as significant target related to Alzheimer disease. On the basis of gene ontology and topology analysis results, APP was found as a significant target related to Alzheimer’s disease pathways. Further, the molecular docking results to found that various compounds showed the best binding affinities. Further, MDS top results suggested could be used as potential inhibitors against APP protein and could be useful for the treatment of Alzheimer’s disease.

Keywords: holy basil, network pharmacology, neurodegeneration, active phytochemicals, molecular docking and simulation

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Authors: Suzanne L. Stewart, Sarah J. Ponton, Mikaela D. Gabriel, Roy Strebel, Xinyi Lu

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Indigenous Peoples have faced unique barriers to accessing and receiving culturally safe and appropriate mental health care while also facing daunting rates of mental health diagnoses and comorbidities. Indigenous researchers and clinicians have well established the connection of the current mental health issues in Indigenous communities as a direct result of colonization by way of intergenerational trauma throughout Canada’s colonial history. Such mental health barriers and challenges have become exacerbated during the COVID-19 pandemic. Throughout the pandemic, access to mental health, cultural, ceremonial, and community services were severely impacted and restricted; however, it is these same cultural activities and community resources that are key to supporting Indigenous mental health from a traditional and community-based perspective. This research employed a unique combination of a thorough, analytical scoping review of the existent mental health literature of Indigenous mental health in the COVID-19 pandemic, alongside narrative interviews employing an oral storytelling tradition methodology with key community informants that provide comprehensive cultural services to the Indigenous community of Toronto, as well as across Canada. These key informant interviews provided a wealth of insights into virtual transitions of Indigenous care and mental health support; intersections of historical underfunding and current financial navigation in technology infrastructure; accessibility and connection with Indigenous youth in remote locations; as well as maintaining community involvement and traditional practices in a current pandemic. Both the scoping review and narrative interviews were meticulously analyzed for overarching narrative themes to best explore the extent of the literature on Indigenous mental health and services during COVID-19; identify gaps in this literature; identify barriers and supports for the Indigenous community, and explore the intersection of community and cultural impacts to mental health. Themes of the scoping review included: Historical Context; Challenges in Culturally-Based Services; and Strengths in Culturally-Based Services. Meta themes across narrative interviews included: Virtual Transitions; Financial Support for Indigenous Services; Health Service Delivery & Wellbeing; and Culture & Community Connection. The results of this scoping review and narrative interviews provide wide application and contribution to the mental health literature, as well as recommendations for policy, service provision, autonomy in Indigenous health and wellbeing, and crucial insights into the present and enduring mental health needs of Indigenous Peoples throughout the COVID-19 pandemic.

Keywords: indigenous community services, indigenous mental health, indigenous scoping review, indigenous peoples and Covid-19

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Authors: Benchouala Amira, Bojic Clement, Poupin Pascal, Cossu Leguille-carole

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The objective of this study is to evaluate in vitro the cytotoxic and androgenic potential of several antifungal molecules (amphotericin B, econazole, ketoconazole and miconazole) on MDA-Kb2 cell lines. This biological model is an effective tool for the detection of endocrine disruptors because it responds well to the main agonist of the androgen receptor (testosterone) and also to an antagonist: flutamide. The cytotoxicity of each chemical compound tested was measured using an MTT assay (tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) which measures the activity of the reductase function of mitochondrial succinate dehydrogenase enzymes of cultured cells. This complementary cytotoxicity test is essential to ensure that the effects of reduction in luminescence intensity observed during androgenic tests are only attributable to the anti-androgenic action of the compounds tested and not to their possible cytotoxic properties. Tests of the androgenic activity of antifungals show that these compounds do not have the capacity to induce transcription of the luciferase gene. These compounds do not exert an androgenic effect on MDA-Kb2 cells in culture for the environmental concentrations tested. The addition of flutamide for the same tested concentrations of antifungal molecules reduces the luminescence induced by amphotericin B, econazole and miconazole, which is explained by a strong interaction of these molecules with flutamide which may have a greater toxic effect than when tested alone. The cytotoxicity test shows that econazole and ketoconazole can cause cell death at certain concentrations tested. This cell mortality is perhaps induced by a direct or indirect action on deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or proteins necessary for cell division.

Keywords: cytotoxicity, androgenic potential, antifungals, MDA-Kb2

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Authors: Ibrahim Iddrisu, Joseph Ayariga, Junhuan Xu, Ayomide Adebanjo, Boakai K. Robertson, Michelle Samuel-Foo, Olufemi Ajayi

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The rise of antimicrobial resistance is a global public health crisis that threatens the effective control and prevention of infections. Due to the emergence of pan drug-resistant bacteria, most antibiotics have lost their efficacy. Bacteriophages or their components are known to target bacterial cell walls, cell membranes, and lipopolysaccharides (LPS) and hydrolyze them. Bacteriophages, being the natural predators of pathogenic bacteria, are inevitably categorized as ‘human friends’, thus fulfilling the adage that ‘the enemy of my enemy is my friend’. Leveraging on their lethal capabilities against pathogenic bacteria, researchers are searching for more ways to overcome the current antibiotic resistance challenge. In this study, we expressed and purified epsilon 34 phage tail spike protein (E34 TSP) from the E34 TSP gene, then assessed the ability of this bacteriophage protein in the killing of two CBD-resistant strains of Salmonella spp. We also assessed the ability of the tail spike protein to cause bacteria membrane disruption and dehydrogenase depletion. We observed that the combined treatment of CBD-resistant strains of Salmonella with CBD and E34 TSP showed poor killing ability, whereas the mono treatment with E34 TSP showed considerably higher killing efficiency. This study demonstrates that the inhibition of the bacteria by E34 TSP was due in part to membrane disruption and dehydrogenase inactivation by the protein. The results of this work provide an interesting background to highlight the crucial role phage proteins such as E34 TSP could play in pathogenic bacterial control.

Keywords: cannabidiol, resistance, Salmonella, antimicrobials, phages

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Authors: Sushil Kumar Singh, Ashok Kumar, Ankit Ganeshpurkar, Ravi Singh, Devendra Kumar

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In spectrum of neurodegenerative diseases, Alzheimer’s disease (AD) is characterized by the presence of amyloid β plaques and neurofibrillary tangles in the brain. It results in cognitive and memory impairment due to loss of cholinergic neurons, which is considered to be one of the contributing factors. Donepezil, an acetylcholinesterase (AChE) inhibitor which also inhibits butyrylcholinesterase (BuChE) and improves the memory and brain’s cognitive functions, is the most successful and prescribed drug to treat the symptoms of AD. The present work is based on designing of the selective BuChE inhibitors using computational techniques. In this work, machine learning models were trained using classification algorithms followed by screening of diverse chemical library of compounds. The various molecular modelling and simulation techniques were used to obtain the virtual hits. The amide derivatives of 4-(phenylsulfonamido) benzoic acid were synthesized and characterized using 1H & 13C NMR, FTIR and mass spectrometry. The enzyme inhibition assays were performed on equine plasma BuChE and electric eel’s AChE by method developed by Ellman et al. Compounds 31, 34, 37, 42, 49, 52 and 54 were found to be active against equine BuChE. N-(2-chlorophenyl)-4-(phenylsulfonamido)benzamide and N-(2-bromophenyl)-4-(phenylsulfonamido)benzamide (compounds 34 and 37) displayed IC50 of 61.32 ± 7.21 and 42.64 ± 2.17 nM against equine plasma BuChE. Ortho-substituted derivatives were more active against BuChE. Further, the ortho-halogen and ortho-alkyl substituted derivatives were found to be most active among all with minimal AChE inhibition. The compounds were selective toward BuChE.

Keywords: Alzheimer disease, butyrylcholinesterase, machine learning, sulfonamides

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Authors: H. Aldewachi, M. Hines, M. McCulloch, N. Woodroofe, P. Gardiner

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DPP-IV is an enzyme whose expression is affected in a variety of diseases, therefore, has been identified as possible diagnostic or prognostic marker for various tumours, immunological, inflammatory, neuroendocrine, and viral diseases. Recently, DPP-IV enzyme has been identified as a novel target for type II diabetes treatment where the enzyme is involved. There is, therefore, a need to develop sensitive and specific methods that can be easily deployed for the screening of the enzyme either as a tool for drug screening or disease marker in biological samples. A variety of assays have been introduced for the determination of DPP-IV enzyme activity using chromogenic and fluorogenic substrates, nevertheless these assays either lack the required sensitivity especially in inhibited enzyme samples or displays low water solubility implying difficulty for use in vivo samples in addition to labour and time-consuming sample preparation. In this study, novel strategies based on exploiting the high extinction coefficient of gold nanoparticles (GNPs) are investigated in order to develop fast, specific and reliable enzymatic assay by investigating synthetic peptide sequences containing a DPP IV cleavage site and coupling them to GNPs. The DPP IV could be detected by colorimetric response of peptide capped GNPs (P-GNPS) that could be monitored by a UV-visible spectrophotometer or even naked eyes, and the detection limit could reach 0.01 unit/ml. The P-GNPs, when subjected to DPP IV, showed excellent selectivity compared to other proteins (thrombin and human serum albumin) , which led to prominent colour change. This provided a simple and effective colorimetric sensor for on-site and real-time detection of DPP IV.

Keywords: gold nanoparticles, synthetic peptides, colorimetric detection, DPP-IV enzyme

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Authors: B. Chandar, M. K. Ramasamy, P. Madasamy

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The discovery and development of newer antibiotics are limited with the increase in resistance of such multi-drug resistant bacteria creating the need for alternative new therapeutic agents. The recently discovered New Delhi Metallo-betalactamase-1 (NDM-1), which confers antibiotic resistance to most of the currently available β-lactams, except colistin and tigecycline, is a global concern. Several antibacterial drugs approved are natural products or their semisynthetic derivatives, but plant extracts remain to be explored to find molecules that are effective against NDM-1 bacteria. Therefore, it is necessary to explore the possibility of finding new and effective antibacterial compounds against NDM-1 bacteria. In the present study, we have screened a diverse set South Indian plant species, and report most plant species as a potential source for antimicrobial compounds against NDM-1 bacteria. Ethanol extracts from the leaves of taxonomically diverse South Indian medicinal plants were screened for antibacterial activity against NDM-1 E. coli using streak plate method. Among the plant screened against NDM-1 E. coli, the ethanol extracts from many plant extracts showed minimum bactericidal concentration between 5 and 15 mg /ml and MIC between 2.54 and 5.12 mg/ml. These extracts also showed a potent synergistic effect when combined with antibiotics colistin and tetracycline. Combretum albidum that was effective was taken for further analysis. At 5mg/L concentration, these extracts inhibited the NDM-1 enzyme in vitro, and residual activity for Combretum albidum was 33.09%. Treatment of NDM-1 E. coli with the extracts disrupted the cell wall integrity and caused 89.7% cell death. The plant extract of Combretum albidum that was effective was subjected to fractionation and the fraction was further subjected to HPLC, LC-MS for identification of antibacterial compound.

Keywords: antibacterial activity, combretum albidum, Escherichia coli, NDM-1

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Authors: Rajnarayan Damor, Gayatri Swarnakar

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Fasciola gigantica are present in the biliary ducts of liver and gall bladder of domestic buffaloes. They are very harmful and causes significant lose to live stock owners, on account of poor growth and lower productivity of domestic buffaloes. Synthetic veterinary drugs have been used to eliminate parasites from cattle but these drugs are unaffordable and inaccessible for poor cattle farmers. The in vitro anthelmintic effect of Citrullus colocynthis fruit extract against Fasciola gigantica parasites were observed by light and scanning electron microscopy. Fruit extracts of C. colocynthis exhibit highest mortality 100% at 50 mg/ml in 15th hour of exposure. The oral and ventral sucker appeared to be slightly more swollen than control and synthetic drug albendazole. The tegument showed submerged spines by the swollen tegument around them. The tegument of the middle region showed deep furrows, folding and submerged spines which either lied very flat against the surface or had become submerged in the tegument by the swollen tegument around them leaving deep furrows. Posterior region showed with deep folding in the tegument, completely disappearance of spines and swelling of the tegument led to completely submerged spines leaving spine socket. The present study revealed that fruit extracts of Citrullus colocynthis found to be potential sources for novel anthelmintic and justify their ethno-veterinary use.

Keywords: anthelmintic, buffalo, Citrullus colocynthis, Fasciola gigantica, mortality, tegument

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Authors: Fisseha Shiferie (Bpharm, Mpharm)

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Diarrhea is a common gastrointestinal disorder characterized by an increase in stool frequency and a change in stool consistency. Inspite of the availability of many drugs as antidiarrheal agents, the search for a drug with affordable cost and better efficacy is essential to overcome diarrheal problems. The root extract of Echinops kebericho, is used by traditional practitioners for the treatment of diarrhea. However, the scientific basis for this usage has not been yet established. The purpose of the present study was to evaluate the antidiarrheal and spasmolytic activities of the aqueous extract of the roots of E. kebericho in rodents and isolated guinea-pig ileum preparations. In the castor oil induced intestinal transit test, E. kebericho produced a significant (p < 0.01) dose dependent decrease in propulsion with peristaltic index values of 45.05±3.3, 42.71±2.25 and 33.17±3.3%, respectively at doses of 100, 200 and 400 mg/kg compared with 63.43±7.3% for control. In the castor oil-induced diarrhea test, the mean defecation was reduced from 1.81±0.18 to 0.99 ± 0.21 compared with 2.59 ±0.81 for control. The extract (at doses stated above) significantly decreased the volume of intestinal fluid secretion induced by castor oil (2.31±0.1 to 2.01±0.2) in relation to 3.28±0.3 for control. When tested on a guinea-pig ileum, root extract of Echinops kebericho exhibited a dose dependent spasmolytic effect, 23.07 % being its highest inhibitory effect. The results obtained in this study give some scientific support to the use of Echinops kebericho as an antidiarrheal agent due to its inhibitory effects on the different diarrheal parameters used in this study.

Keywords: antidiarrheal activity, E. kebericho, traditional medicine, diarrhea, enteropooling, and intestinal transit

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Authors: Alaa E. El-sisi, Sherin Zakaria

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Rebamipide is an antiulcer drug with unique properties such as anti-inflammatory action. It induces endogenous prostaglandin e2 (PGE2). PGE2 is considered as a potent physiological suppressor of liver fibrosis. Aim of study: This study investigated the effect of rebamipide on hepatic fibrosis. Material and Method: Hepatic fibrosis was induced by intraperitoneal injections (IP) injection of CCl4 (0.45 mL/kg) in corn oil 1:5 twice a week for 4 weeks. Rats were divided into four groups as follow: Group 1 treated with CCL4 only, group 2 and 3 treated with CCL4 and rebamipide 60 mg/kg/day (group2) or 100 mg/kg/day (group3), and the fourth group was considered as control group and treated with vehicles. ALT, AST, and Bilirubin were assayed in serum. Antioxidant markers such as malondialdhyde (MDA) and superoxide dismutase (SOD) and fibrotic markers such as hyaluronic acid (HA) and procollagen-III (procol-III) were evaluated in liver tissues. IL-10 as well as PGE2 were also assayed in liver tissues. Pathologic changes in the liver were detected by hematoxylin and eosin staining. Collagen precipitation in liver tissues was visualized using masson trichrom stain. Results: Rebamipide inhibit CCL4 induced increase in ALT and AST significantly (p < 0.05). Rebamipide exerted an antioxidant effect as it inhibits CCL4 induced increased MDA level and decreased SOD activity. Fibrotic markers assay revealed that repamipide (60 or 100 mg/kg/day) decreased the level of procol-III and HA compared to CCl4 (p < 0.05). Oral administration of Rebamipide was associated with a significant increase (p < 0.05) of PGE2 and IL-10. Rebamipide especially at the dose of (100 mg/kg/day) restores liver histology structure and abolish collagen precipitation in liver tissues. Conclusion: Rebamipide retards hepatic fibrosis induced by CCL4 may be through the induction of PGE2 level.

Keywords: fibrotic markers, hepatic fibrosis, PGE2, rebamipide

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Authors: Ana Teixeira, Joao Orvalho

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This paper describes experiments using Scratch games, to check the feasibility of employing cerebral palsy users gestures as an alternative of interaction with a computer carried out by students of Master Human Computer Interaction (HCI) of IPC Coimbra. The main focus of this work is to study the usability of a Web Camera as a motion tracking device to achieve a virtual human-computer interaction used by individuals with CP. An approach for Human-computer Interaction (HCI) is present, where individuals with cerebral palsy react and interact with a scratch game through the use of a webcam as an external interaction device. Motion tracking interaction is an emerging technology that is becoming more useful, effective and affordable. However, it raises new questions from the HCI viewpoint, for example, which environments are most suitable for interaction by users with disabilities. In our case, we put emphasis on the accessibility and usability aspects of such interaction devices to meet the special needs of people with disabilities, and specifically people with CP. Despite the fact that our work has just started, preliminary results show that, in general, computer vision interaction systems are very useful; in some cases, these systems are the only way by which some people can interact with a computer. The purpose of the experiments was to verify two hypothesis: 1) people with cerebral palsy can interact with a computer using their natural gestures, 2) scratch games can be a research tool in experiments with disabled young people. A game in Scratch with three levels is created to be played through the use of a webcam. This device permits the detection of certain key points of the user’s body, which allows to assume the head, arms and specially the hands as the most important aspects of recognition. Tests with 5 individuals of different age and gender were made throughout 3 days through periods of 30 minutes with each participant. For a more extensive and reliable statistical analysis, the number of both participants and repetitions in further investigations should be increased. However, already at this stage of research, it is possible to draw some conclusions. First, and the most important, is that simple scratch games on the computer can be a research tool that allows investigating the interaction with computer performed by young persons with CP using intentional gestures. Measurements performed with the assistance of games are attractive for young disabled users. The second important conclusion is that they are able to play scratch games using their gestures. Therefore, the proposed interaction method is promising for them as a human-computer interface. In the future, we plan to include the development of multimodal interfaces that combine various computer vision devices with other input devices improvements in the existing systems to accommodate more the special needs of individuals, in addition, to perform experiments on a larger number of participants.

Keywords: motion tracking, cerebral palsy, rehabilitation, HCI

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Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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Authors: Eman M. Morgan, Hayam M. Lotfy, Yasmin M. Fayez, Mohamed Abdelkawy, Engy Shokry

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Two simple, selective, economic, safe, accurate, precise and environmentally friendly methods were developed and validated for the quantitative determination of valaciclovir (VAL) in the presence of its related substances R1 (acyclovir), R2 (guanine) in bulk powder and in the commercial pharmaceutical product containing the drug. Method A is a colorimetric method where VAL selectively reacts with ferric hydroxamate and the developed color was measured at 490 nm over a concentration range of 0.4-2 mg/mL with percentage recovery 100.05 ± 0.58 and correlation coefficient 0.9999. Method B is a reversed phase ultra performance liquid chromatographic technique (UPLC) which is considered superior in technology to the high-performance liquid chromatography with respect to speed, resolution, solvent consumption, time, and cost of analysis. Efficient separation was achieved on Agilent Zorbax CN column using ammonium acetate (0.1%) and acetonitrile as a mobile phase in a linear gradient program. Elution time for the separation was less than 5 min and ultraviolet detection was carried out at 256 nm over a concentration range of 2-50 μg/mL with mean percentage recovery 100.11±0.55 and correlation coefficient 0.9999. The proposed methods were fully validated as per International Conference on Harmonization specifications and effectively applied for the analysis of valaciclovir in pure form and tablets dosage form. Statistical comparison of the results obtained by the proposed and official or reported methods revealed no significant difference in the performance of these methods regarding the accuracy and precision respectively.

Keywords: hydroxamic acid, related substances, UPLC, valaciclovir

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Authors: Huimin Zhao, Xiaoquan Liu, Haochen Liu

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The major challenge facing Alzheimer's Disease (AD) drug development is how to effectively improve cognitive function in clinical practice. Growing evidence indicates that stimulating hippocampal neurogenesis is a strategy for restoring cognition in animal models of AD. The mitogen-activated protein kinase (MAPK) pathway is a crucial factor in neurogenesis, which is negatively regulated by Dual-specificity phosphatase 16 (DUSP16). Transcriptome analysis of post-mortem brain tissue revealed up-regulation of DUSP16 expression in AD patients. Additionally, DUSP16 was involved in regulating the proliferation and neural differentiation of neural progenitor cells (NPCs). Nevertheless, whether the effect of DUSP16 on ameliorating cognitive disorders by influencing NPCs differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, we found that increased DUSP16 expression in both 3×Tg and SAMP8 models of AD led to NPC differentiation impairments. By silencing DUSP16, cognitive benefits, the induction of AHN and synaptic plasticity, were observed in AD mice. Furthermore, we found that DUSP16 is involved in the process of NPC differentiation by regulating c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, the increased DUSP16 may be regulated by the ETS transcription factor (ELK1), which binds to the promoter region of DUSP16. Loss of ELK1 resulted in decreased DUSP16 mRNA and protein levels. Our data uncover a potential regulatory role for DUSP16 in adult hippocampal neurogenesis and provide a possibility to find the target of AD intervention.

Keywords: alzheimer's disease, cognitive function, DUSP16, hippocampal neurogenesis

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Authors: Christiana Ene Ogwuche, Joseph Amupitan, George Ndukwe, Rachael Ayo

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Maesobotrya barteri (Baill), belonging to the family Euphorbiaceae, is a medicinal plant growing widely in tropical Africa. The Aerial plant parts of Maesobotrya barteri (Baill) were collected fresh from Orokam, Ogbadibo local Government of Benue State, Nigeria in July 2013. Taxonomical identification was done by Mallam Musa Abdullahi at the Herbarium unit of Biological Sciences Department, ABU, Zaria, Nigeria. Pulverized aerial parts of Maesobotrya barteri (960g) was exhaustively extracted successively using petroleum ether, chloroform, ethyl acetate and methanol and concentrated in the rotary evaporator at 40°C. The Petroleum ether extract had the second highest activity against test microbes from preliminary crude microbial screenings. The Petroleum ether extract was subjected to phytochemical studies, antimicrobial analysis and column chromatography (CC). The column chromatography yielded fraction PE, which was further purified using preparative thin layer chromatography to give PE1. The structure of the isolated compound was established using 1-D NMR and 2-D NMR spectroscopic analysis and by direct comparison with data reported in literature was confirmed to be a mixture, an isomer of Betulinic acid and Oleanolic acid, both with the molecular weight (C₃₀H₄₈O₃). The bioactivity of this compound was carried out using some clinical pathogens and the activity compared with standard drugs, and this was found to be comparable with the standard drug.

Keywords: Maesobotrya barteri, medicinal plant, bioactivity, petroleum spirit extract, butellinic acid, oleanilic acid

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Authors: Suzan Ghaddar, Aline Pinon, Manuel Gallardo-villagran, Mona Diab-assaf, Bruno Therrien, Bertrand Liagre

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Colorectal cancer (CRC) is the third most common cancer and exhibits a consistently rising incidence worldwide. Despite notable advancements in CRC treatment, frequent occurrences of side effects and the development of therapy resistance persistently challenge current approaches. Eventually, innovations in focal therapies remain imperative to enhance the patient’s overall quality of life. Photodynamic therapy (PDT) emerges as a promising treatment modality, clinically used for the treatment of various cancer types. It relies on the use of photosensitive molecules called photosensitizers (PS), which are photoactivated after accumulation in cancer cells, to induce the production of reactive oxygen species (ROS) that cause cancer cell death. Among commonly used metal-based drugs in cancer therapy, ruthenium (Ru) possesses favorable attributes that demonstrate its selectivity towards cancer cells and render it suitable for anti-cancer drug design. In vitro studies using distinct arene-Ru complexes, encapsulating porphin PS, are conducted on human HCT116 and HT-29 colorectal cancer cell lines. These studies encompass the evaluation of the antiproliferative effect, ROS production, apoptosis, cell cycle progression, molecular localization, and protein expression. Preliminary results indicated that these complexes exert significant photocytotoxicity on the studied colorectal cancer cell lines, representing them as promising and potential candidates for anti- cancer agents.

Keywords: colorectal cancer, photodynamic therapy, photosensitizers, arene-ruthenium complexes, apoptosis

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Authors: Mayank Mishra

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Market Economy can be broadly defined as economic system where supply and demand regulate the economy and in which decisions pertaining to production, consumption, allocation of resources, price and competition are made by collective actions of individuals or organisations with limited government intervention. On the other hand Market Society is one where instead of the economy being embedded in social relations, social relations are embedded in the economy. A market economy becomes a market society when all of land, labour and capital are commodified. This transition also has effect on people’s attitude and values. Such a transition commence impacting the non-material aspect of life such as public education, public health and the like. The inception of neoliberal policies in non-market norms altered the nature of social goods like public health that raised the following questions. What impact would the transition to a market society make on people in terms of accessibility to public health? Is healthcare a commodity that can be subjected to a competitive market place? What kind of private investments are being made in public health and how do private investments alter the nature of a public good like healthcare? This research problem will employ empirical-analytical approach that includes deductive reasoning which will be using the existing concept of market economy and market society as a foundation for the analytical framework and the hypotheses to be examined. The research also intends to inculcate the naturalistic elements of qualitative methodology which refers to studying of real world situations as they unfold. The research will analyse the existing literature available on the subject. Concomitantly the research intends to access the primary literature which includes reports from the World Bank, World Health Organisation (WHO) and the different departments of respective ministries of the countries for the analysis. This paper endeavours to highlight how the issue of commodification of public health would lead to perpetual increase in its inaccessibility leading to stratification of healthcare services where one can avail the better services depending on the extent of one’s ability to pay. Since the fundamental maxim of private investments is to churn out profits, these kinds of trends would pose a detrimental effect on the society at large perpetuating the lacuna between the have and the have-nots.The increasing private investments, both, domestic and foreign, in public health sector are leading to increasing inaccessibility of public health services. Despite the increase in various public health schemes the quality and impact of government public health services are on a continuous decline.

Keywords: commodity, India and Pakistan, market society, public health

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Authors: Cledinaldo A. Dias, Isabela C. Santos, Marcus V. S. Siqueira

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In the contemporary globalization, the competitiveness generated in the search of new markets aiming at the growth of productivity and, consequently, of profits, implies the redefinition of productive processes and new forms of work organization. As a result of this structuring, unemployment, labor force turnover and the increase in outsourcing and informal work occur. Considering the different relationships and working conditions of outsourced employees, this study aims to identify the most present stressors among outsourced service providers from a Federal Institution of Higher Education in Brazil. To reach this objective, a descriptive exploratory study with a quantitative approach was carried out. The qualitative approach was chosen to provide an in-depth analysis of the occupational conditions of outsourced workers since this method seeks to focus on the social as a world of investigated meanings and the language or speech of each subject as the object of this approach. The survey was conducted in the city of Montes Claros - Minas Gerais (Brazil) and involved eighty workers from companies hired by the institution, including armed security guards, porters, cleaners, drivers, gardeners, and administrative assistants. The choice of professionals obeyed non-probabilistic criteria for convenience or accessibility. Data collection was performed by means of a structured questionnaire composed of sixty questions, in a Likert-type frequency interval scale format, in order to identify potential organizational stressors. The results obtained evidence that the stress factors pointed out by the workers are, in most cases, a determining factor due to the low productive performance at work. Amongst the factors associated with stress, the ones that stood out most were those related to organizational communication failures, the incentive to competition, lack of expectations of professional growth, insecurity and job instability. Based on the results, the need for greater concern and organizational responsibility with the well-being and mental health of the outsourced worker and the recognition of their physical and psychological limitations, and care that goes beyond the functional capacity for the work. Specifically for the preservation of mental health, physical and quality of life, it is concluded that it is necessary for the professional to be inserted in the external world that favors it internally since this set is complemented so that the individual remains in balance and obtain satisfaction in your work.

Keywords: occupational health, outsourced, organizational studies, stressors

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Authors: Nurudeen Oluwasola Lasisi

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Newcastle disease is a highly contagious disease of birds caused by a para-myxo virus. In this paper, we presented Novel quarantine-adjusted incident and linear incident of Newcastle disease model equations. We considered the dynamics of transmission and control of Newcastle disease. The existence and uniqueness of the solutions were obtained. The existence of disease-free points was shown, and the model threshold parameter was examined using the next-generation operator method. The sensitivity analysis was carried out in order to identify the most sensitive parameters of the disease transmission. This revealed that as parameters β,ω, and ᴧ increase while keeping other parameters constant, the effective reproduction number R_ev increases. This implies that the parameters increase the endemicity of the infection of individuals. More so, when the parameters μ,ε,γ,δ_1, and α increase, while keeping other parameters constant, the effective reproduction number R_ev decreases. This implies the parameters decrease the endemicity of the infection as they have negative indices. Analytical results were numerically verified by the Differential Transformation Method (DTM) and quantitative views of the model equations were showcased. We established that as contact rate (β) increases, the effective reproduction number R_ev increases, as the effectiveness of drug usage increases, the R_ev decreases and as the quarantined individual decreases, the R_ev decreases. The results of the simulations showed that the infected individual increases when the susceptible person approaches zero, also the vaccination individual increases when the infected individual decreases and simultaneously increases the recovery individual.

Keywords: disease-free equilibrium, effective reproduction number, endemicity, Newcastle disease model, numerical, Sensitivity analysis

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Authors: Sadegh Lotfieblisofla, Arash Khodabakhshi

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Tissue plasminogen activator (tPA) as a serine protease plays an important role in the fibrinolytic system and the dissolution of fibrin clots in human body. The production of this drug in plants such as tobacco could reduce its production costs. In this study, expression of tPA gene and protein targeting to different plant cell compartments, using various signal peptides has been investigated. For high level of expression, Kozak sequence was used after CaMV35S in the beginning of the gene. In order to design the final construction, Extensin, KDEL (amino acid sequence including Lys-Asp-Glu-Leu) and SP (γ-zein signal peptide coding sequence) were used as leader signals to conduct this protein into apoplast, endoplasmic reticulum and cytosol spaces, respectively. Cloned human tPA gene under the CaMV (Cauliflower mosaic virus) 35S promoter and NOS (Nopaline Synthase) terminator into pBI121 plasmid was transferred into tobacco explants by Agrobacterium tumefaciens strain LBA₄₄₀₄. The presence and copy number of genes in transgenic tobacco was proved by Southern blotting. Enzymatic activity of the rt-PA protein in transgenic plants compared to non-transgenic plants was confirmed by Zymography assay. The presence and amount of rt-PA recombinant protein in plants was estimated by ELISA analysis on crude protein extract of transgenic tobacco using a specific antibody. The yield of recombinant tPA in transgenic tobacco for SP, KDEL, Extensin signals were counted 0.50, 0.68, 0.69 microgram per milligram of total soluble proteins.

Keywords: tPA, recombinant, transgenic, tobacco

Procedia PDF Downloads 133

Authors: Jie Gao

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The combination of chemotherapy with gene therapy is highly effective in cancer therapy. To achieve combined therapeutic effects in human gastric cancer over expressing EGFR, we developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab’ for co-delivery of doxorubicin (DOX) and ribonucleotide reductase M2 (RRM2) siRNA (DOX-RRM2-TLPD). The results showed that EGFR was over expressed in several gastric cancer cell lines and gastric cancer tissues. Gene Expression Omnibus (GEO) results showed that RRM2 expression was significantly higher in gastric cancer than in non-gastric cancer tissue, and RRM2 siRNA inhibited the proliferation of several gastric cancer cells, indicating that RRM2 is a candidate target for gastric cancer therapy. Confocal studies and flow cytometry showed that DOX-RRM2-TLPD delivered DOX and RRM2 siRNA to EGFR over expressing gastric cancer cells specifically and efficiently both in vitro and in vivo, resulting in enhanced therapeutic effects (cytotoxicity and apoptosis) compared with single-drug loaded or non-targeted controls, including DOX-NC-TLPD (targeted LPD co-delivering DOX and negative control siRNA), RRM2-TLPD (targeted LPD delivering RRM2 siRNA) and DOX-RRM2-NTLPD (non-targeted LPD co-delivering DOX and RRM2 siRNA). The in vivo antitumor assay showed that the average weight of the gastric cancer in mice treated with DOX-RRM2-TLPD was significantly lighter than that of mice treated with other controls. DOX-RRM2-TLPD represents an effective approach for combined therapy of gastric cancer over expressing EGFR.

Keywords: gene therapy, chemotherapy, immunoliposomes, gastric cancer

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Authors: S. K. Sharma, P. Kumar, Pratibha Singh

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Consumption of SNACK is growing its popularity every day in India and a broad range of these items are available in the market. The end user interest in ready-to-eat snack foods is constantly growing mainly due to their ease, ample accessibility, appearance, taste and texture. Food extrusion has been practiced for over fifty years. Its role was initially limited to mixing and forming cereal products. Although thermoplastic extrusion has been successful for starch products, extrusion of proteins has achieved only limited success. In this study, value-added extruded prawn product was prepared with prawn flavor powder and corn flour using a twin-screw extruder. Prawn flavor concentrates prepared from fresh prawn head (Solenocera indica). To prepare flavor concentrate prawn head washed with potable water and blended with 200ml 3% salt solution per 250gm head weight to make the slurry, which was further put in muslin cloth and boiled with salt and starch solution for 10 minutes, cooled to room temperature and filtered, starch added to the filtrate and made into powder in an electrically drier at 43-450c. The mixture was passed through the twin-screw extruder (co-rotating twin screw extruder - basic technology Pvt. Ltd., Kolkata) which was operated at a particular speed of rotation, die diameter, temperature, moisture, and fish powder concentration. Many trial runs were conducted to set up the process variables. The different extrudes produced after each trail were examined for the quality and characteristics. The effect of temperature, moisture, screw speed, protein, fat, ash and thiobarbituric acid (TBA) number and expansion ratio were studied. In all the four trials, moisture, temperature, speed and die diameter used was 20%, 100°C, 350 rpm and 4 mm, respectively. The ratio of prawn powder and cornstarch used in different trials ranged between 2:98 and 10:90. The storage characteristics of the final product were studied using three different types of packaging under nitrogen flushing, i.e. a- 12-pm polyester, 12-pm metalized polyester, 60-11m polyethylene (metalized polyester a), b- 12-11m metalized polyester, 37.5-11m polyethylene (metalized polyester b), c- 12-11m polyethylene, 9-11m aluminium foil, 37.5-11m polyethylene (aluminium foil). The organoleptic analysis was carried out on a 9-point hedonic scale. The study revealed that the fried product packed in aluminum foil under nitrogen flushing would remain acceptable for more than three months.

Keywords: extruded product, prawn flavor, twin-screw extruder, storage characteristics

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Authors: Obinna Emmanuel Nkomadu

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The sea attracts many criminal activities including drug trafficking. The illicit traffic in narcotic drugs and psychotropic substances by sea poses a serious threat to maritime security globally. The seizure of drugs, particularly, on the African continent is on the raise. In terms of Southern Africa, South Africa is a major transit point for Latin American drugs and South Africa is the largest market for illicit drugs entering the Southern African region. Nigeria and South Africa have taken a number of steps to address this scourge, but, despite those steps, drugs trafficking at sea continues. For that reason and to combat a number of other threats to maritime security around the continent, a substantial number of AU members in 2016 adopted the African Charter on Maritime Security and Safety and Development in Africa (“the Charter”). However, the Charter is yet to come into force due to the number of States required to accede or ratify the Charter. This paper set out the pre-existing international instruments on drugs, to ascertain the domestic laws of Nigeria and South Africa relating to drugs with the relevant provisions of the Lomé Charter in order to establish whether any legal steps are required to ensure that Nigeria and South Africa comply with its obligations under the Charter. Indeed, should Nigeria and South Africa decide to ratify it and should it come into force, both States must cooperate with other relevant States in establishing policies, as well as a regional and continental institutions, and ensure the implementation of such policies. The paper urged the States to urgently ratify the Charter as it is a step in the right direction in the prevention and repression of drugs trafficking on the African maritime domain.

Keywords: cooperation against drugs trafficking at sea, Lomé Charter, maritime security, Nigerian and South Africa legislation on drugs

Procedia PDF Downloads 76

Authors: Sangeeta Pilkhwal Sah, C. S. Mathela, Kanwaljit Chopra

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Valeriana wallichii DC, an ayurvedic traditional medicine, popularly named as Indian valerian exist as three chemotypes. GC-MS analysis of V. wallichii essential oil in present study showed maaliol as the major constituent followed by the presence of β-gurjunene, acoradiene, guaiol and α-santalene. The results thus confirmed it to be a maaliol chemotype. Further, the antidepressant-like effect of root essential oil (10, 20 and 40 mg/kg p.o.) was investigated in both acute and chronic treatment study using forced swim test in mice. Single administration of different doses produced an inverted U shaped curve and significantly inhibited the immobility period (39.7% and 58%) at doses 10 and 40 mg/kg respectively. Standard drug imipramine significantly decreased immobility period (59.8%). None of the doses altered locomotor activity except a significant decrease of 44.9% was observed with 40 mg/kg (p < 0.05). Similarly, daily administration of essential oil for 14 days produced a dose dependent effect with significantly reduced immobility period (70.9%) at 40 mg/kg dose only whereas imipramine produced 86% decrease (p < 0.05). The neurotransmitter levels in mouse brain were estimated on day 14 after the behavioral study. Significant increase in the level of norepinephrine (10%) and dopamine (23%) (p < 0.05) was found at 40 mg/kg dose, while no change was observed at 10 and 20 mg/kg doses. The antidepressant-like effect of essential oil (40 mg/kg) was prevented by pretreatment of mice with L-arginine (750 mg/kg i.p.) and sildenafil (5 mg/kg i.p). On the contrary, pretreatment of mice with L-NAME (10 mg/kg i.p.) or methylene blue (10 mg/kg i.p.) potentiated the antidepressant action of essential oil (20 mg/kg). The findings thus demonstrated that nitric oxide pathway is involved in mediating antidepressant like effect of essential oil from this chemotype.

Keywords: Valeriana wallichii DC chemotype, essential oil, forced swim test, nitric oxide modulators, neurotransmitters

Procedia PDF Downloads 287

Authors: Yasmin M. Attia, Hanan S. El-Abhar, Mahmoud M. Al Marzabani, Samia A. Shouman

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Background: Tamoxifen (TAM) is the most commonly used hormone therapy for the treatment of early and metastatic breast cancer. Although it significantly decreases the tumor recurrence rate and provides an overall benefit, as much as 20–30% of women still relapse during or after long-term therapy. 3-Bromopyruvate (3-BP) is a promising agent with impressive antitumor effects in several models of animal tumors and cell lines. Aim: This study was designed to investigate the combined effect of (TAM) and (3-BP) in breast cancer cells and to explore their molecular interaction via assessment of apoptotic, angiogenic, and metastatic markers. Methods: In vitro cytotoxicity study was carried out for both compounds to determine the combination regimen producing a synergistic effect and mechanistic pathways were studied using RT-PCR and western techniques. Moreover, the anti-oncolytic and anti-angiogenic potentials were assessed in mice bearing solid Ehrlich carcinoma (SEC). Results: The combined treatment significantly increased the expressions and protein levels of caspase 7, 9, and 3 and decreased of angiogenic markers VEGF, HIF-1α, and HK2 compared to cells treated with either drug individually. However, there were no significant changes in MMP-2 and MMP-9 protein levels. Interestingly, the in vivo results supported the in vitro findings; there was a decrease in the tumor volume and VEFG using immunohistochemistry in the combination-treated groups compared to either TAM or 3-BP treated one. Conclusion: 3-BP synergizes the cytotoxic effect of TAM by increasing apoptosis and decreasing angiogenesis which makes this combination a promising regimen to be applied clinically.

Keywords: tamoxifen, 3-bromopyruvate, breast cancer, cytotoxicity, angiogenesis

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