Search results for: bioactive agents

Authors: Sara Ataei, Molouk Hadjibabaie, Shirinsadat Badri, Amirhossein Moslehi, Iman Karimzadeh, Ardeshir Ghavamzadeh

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Purpose: To assess the pattern and probable risk factors for moderate and major drug–drug interactions in a referral hematology-oncology ward in Iran. Methods: All patients admitted to hematology–oncology ward of Dr. Shariati Hospital during a 6-month period and received at least two anti-cancer or non-anti-cancer medications simultaneously were included. All being scheduled anti-cancer and non-anti-cancer medications both prescribed and administered during ward stay were considered for drug–drug interaction screening by Lexi-Interact On- Desktop software. Results: One hundred and eighty-five drug–drug interactions with moderate or major severity were detected from 83 patients. Most of drug–drug interactions (69.73 %) were classified as pharmacokinetics. Fluconazole (25.95 %) was the most commonly offending medication in drug–drug interactions. Interaction of sulfamethoxazole-trimethoprim with fluconazole was the most common drug–drug interaction (27.27 %). Vincristine with imatinib was the only identified interaction between two anti-cancer agents. The number of administered medications during ward stay was considered as an independent risk factor for developing a drug–drug interaction. Conclusions: Potential moderate or major drug–drug interactions occur frequently in patients with hematological malignancies or related diseases. Performing larger standard studies are required to assess the real clinical and economical effects of drug–drug interactions on patients with hematological and non-hematological malignancies.

Keywords: drug–drug interactions, hematology–oncology ward, hematological malignancies

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Authors: Iddrisu Ibrahim, Joseph Atia Ayariga, Junhuan Xu, Daniel Abugri, Boakai Robertson, Olufemi S. Ajayi

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The emergence of multidrug resistance poses a huge risk to public health globally. Yet these recalcitrant pathogens continue to rise in incidence rate, with resistance rates significantly outpacing the speed of antibiotic development. This, therefore, presents an aura of related health issues such as untreatable nosocomial infections arising from organ transplants and surgeries, as well as community-acquired infections that are related to people with compromised immunity, e.g., diabetic and HIV patients, etc. There is a global effort to fight multidrug-resistant pathogens spearheaded by the World Health Organization, thus calling for research into novel antimicrobial agents to fight multiple drug resistance. Previously, our laboratory demonstrated that Cannabidiol (CBD) was an effective antimicrobial against Salmonella typhimurium (S. typhimurium). However, we observed resistance development over time. To understand the mechanisms S. typhimurium uses to develop resistance to Cannabidiol (CBD), we studied the abundance of bacteria lipopolysaccharide (LPS) and membrane sterols of both susceptible and resistant S. typhimurium. Using real-time quantitative polymerase chain reaction (RT-qPCR), we also analyzed the expression of selected genes known for aiding resistance development in S. typhimurium. We discovered that there was a significantly higher expression of blaTEM, fimA, fimZ, and integrons in the CBD-resistant bacteria, and these were also accompanied by a shift in abundance in cell surface molecules such as lipopolysaccharide (LPS) and sterols.

Keywords: antimicrobials, resistance, cannabidiol, gram-negative bacteria, integrons, blaTEM, Fim, LPS, ergosterols

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Authors: Nazmul Huda, Ashik Mosaddik, Abdul Awal, Shafiqur Rahman, Rukhsana Shaheen, Mustofa Nabi

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Polyherbal formulation Sharbat Deenar is a very popular unani medicine in Bangladesh. It is usually used for different kinds of liver disorders. In absence of reliable and inadequate hepatoprotective agents in conventional medicine, the herbal preparations are preferred for liver diseases. The present study was designed to evaluate the hepatoprotective activity of Sharbat Deenar on carbon tetrachloride (CCl₄) induced hepatotoxicity in male Long-Evans albino rats. Group I served as normal control and received neither formulation nor carbon tetrachloride. Group II received only CCl₄ 1mL/kg body weight of rat intraperitoneally for consecutive 14 days. Group III received CCl₄ 1mL/kg body weight of rat intraperitoneally and Silymarin, in dose 50mg/kg body weight of rat orally. Group IV received CCl₄ 1mL/kg body weight of rat intraperitoneally and Sharbat Deenar 1mL/kg body weight of rat for the same 14 consecutive days. At the end of the study, hepatoprotective activity was evaluated by the levels of total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Histopathological study of rat liver was also carried out. The results showed that polyherbal formulation Sharbat Deenar exhibited a significant hepatoprotective effect. Such an outcome seems to be the synergistic effect of all ingredients of tested herbal formulation. Although this study suggests that Sharbat Deenar may be used to cure or minimize various liver diseases, it needs further study to attain the clarity of mechanism and safety.

Keywords: polyherbal formulation, sharbat deenar, carbon tetrachloride, silymarin, hepatoprotective

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Authors: Manal M. Hamed, Mosad A. Ghareeb, Abdel-Aleem H. Abdel-Aleem, Amal M. Saad, Mohamed S. Abdel-Aziz, Asmaa H. Hadad

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Natural products derived from medicinal plants provide unlimited opportunities for a new medication leads because of the unmatched accessibility of chemical variation. Six compounds were isolated from the n-butanol extract of Callistemon citrinus (Family Myrtaceae), they were identified as; nepetolide (1), callislignan A (2), 6,8-dimethoxy-4,5-dimethyl-3-methyleneisochroman-1-one (3), 3-methyl-7-O-benzoyl-β-D-glucopyranoside (4), 5, 7, 3', 5'-tetrahydroxy-6, 8-di-C-methyl flavanone (5), and (2R,3R,4S,5S)-2,4-bis(4-hydroxyphenyl)-3,5-dihydroxy-tetrahydropyran (6). The isolated compounds were evaluated as antioxidant and antimicrobial agents. The antioxidant activities of the compounds were determined using DPPH-radical scavenging and total antioxidant capacity (TAC) assays. The results indicated that compound (5) was most active in its capacity to scavenge free radicals in the DPPH assay [SC50 value, 4.65 ± 0.74μg/mL] compared to the standard ascorbic acid and exhibited the highest activity in the TAC assay (610.45 ± 1.67mg AAE/g compound). The pure isolates were tested for their antimicrobial activity against four pathogenic microbial strains including Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and Candida albicans. Also, the GC/MS analysis of its leaves essential oil presented nine identified compounds representing 91% of the total oil constituents. The outcomes got from this study give a reasonable justification for the medicinal uses of Callistemon citrinus plant.

Keywords: Callistemon citrinus, flavanone, antioxidant activity, antimicrobial activity, essential oil, Myrtaceae

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Authors: Shayma Munqith Al-Baker, Fadhl Ahmed Saeed Al-Gasha’a, Samira Hamid Hanash, Ahmed Ali Al-Hazmi

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A total of 200 samples (180 fecal materials and 20 organ samples) were collected from (5 different poultry farms, 10 local poultry shops, 5 houses poultry, 5 Eggs stores shops and 5 hand slaughters centers) in Ibb city, Yemen, 2014. According to morphological, cultural, as well as biochemical characterization and serological tests, 59 29.5% isolates were identified as Salmonella spp. and all Salmonella isolates were categorized by serotype, which comprised of, 37 62.71% Salmonella Typhimurium serovar, 21 35.59%. Salmonella Enteritidis serovar and 11.69% Salmonella Heidelberg serovar. Antibiotic sensitivity test was done for bacterial isolates and the results showed there were clear differences in antibiotic resistant. Antimicrobial susceptibility of the isolates varies as follows: Ofloxacin 79.66%, Ciprofloxacin 67.80%, Colistin 59.32% and Gentamycin 52.54%. All of isolates were resistant to Erythromycin, Penicillin and Lincomycin. Antibacterial activity was done for both aqueous and ethanol extracts of Dodonaea viscosa plant by using well and disc diffusion assay. The results indicated that well diffusion assay had best results than disc diffusion assay, the highest inhibition zone was 22 mm for well diffusion and 15 mm for disc diffusion assay, the results observed that ethanol extract had best antibacterial effect than aqueous extract which the percentage of bacterial isolates affected with ethanol extract was 71.19% comparing with aqueous extract 28.81% by using disc diffusion assay, while the percentage of bacterial isolates affected with ethanol extract was 88.13% comparing with aqueous extract 52.54% by using will diffusion assay.

Keywords: Salmonella spp, Dodonaea viscosa, antimicrobial and salmonellosis

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Authors: Babu Shersad, Partha Banerjee

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Reduction in haemoglobin levels has been implicated to be a cause for reduced exercise tolerance and cardiovascular complications of chronic renal diseases. Trends of hemoglobin levels in patients on haemodialysis could be an indicator of efficacy of hemodialysis and an indicator of quality of life in haemodialysis patients. In the UAE, the rate of growth (of patients on dialysis) is 10 to 15 per cent per year. The primary mode of haemodialysis in the region is based on in-patient hospital-based hemodialysis units. The increase in risk of cardiovascular and cerebrovascular morbidity as well as mortality in pre-dialysis Chronic Renal Disease has been reported. However, data on the health burden on haemodialysis in standalone dialysis facilities is very scarce. This is mainly due to the paucity of ambulatory centres for haemodialysis in the region. AMSA is the first center to offer standalone dialysis in the UAE and a study over a one year period was performed. Patient data was analyzed using a questionnaire for 45 patients with an average of 2.5 dialysis sessions per week. All patients were on chronic haemodialysis as outpatients. The trends of haemoglobin levels as an independent variable were evaluated. These trends were interpreted in comparison with other parameters of renal function (creatinine, uric acid, blood pressure and ferritin). Trends indicate an increase in hemoglobin levels with increased supplementation of iron and erythropoietin over time. The adequacy of hemodialysis shows improvement concomitantly. This, in turn, correlates with better patient outcomes and has a direct impact on morbidity and mortality. This study is a pilot study and further studies are indicated so that objective parameters can be studied and validated for hemodialysis in the region.

Keywords: haemodialysis, haemoglobin in haemodialysis, haemodialysis parameters, erythropoietic agents in haemodialysis

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Authors: Sharifah I. N. A. Syed Azmi, Nazarina Mohd Nasir

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The Billing & Customer Relationship Management (BCRM) project is an important enabler towards realizing customer experience transformation. It involves technological shifts for future scalability, revision of multiple business processes and adoption of change by the users and impacted employees. This massive transition, if not managed properly, may result in the decline of business performance due to productivity drop. Organizational change management is an essential element in BCRM project implementation to ensure the system is well understood and embraced by all stakeholders. In order to move impacted employees from unaware state or denial mode to full-acceptance mindset and committing themselves in using the new system, their involvement in the whole change process starting from the initial stage is imperative. Through the BCRM Change Management Plan, a holistic approach was taken whereby the strategy and program for five key components namely executive sponsorship, continuous communication, process change readiness, organizational readiness and individual readiness were all carefully established. Roles of the project sponsor, change agents, change ambassadors and community of practice (CoP) were clearly defined in gaining high commitment and support across the entire organization. Continuous communication and engagement initiatives throughout project implementation have been carried out to reach all stakeholders. The business readiness was constantly monitored and assessed including effectiveness of end-user training, thorough review of process documentation and completion of roles realignment exercise.

Keywords: BCRM, change management, organizational change, transformation project

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Authors: Wafa Ghonaim

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Though quite fast on growth, Islamic financing at large, and its diverse instruments, is a controversial matter among scholars. This is evident from the ongoing debates on its Shariah compliance. Arguments, however, are inciting doubts and concerns among clients about its credibility, which is harming this lucrative sector. The work here investigates, particularly, some issues related to the Tawarruq instrument. The work examines the issues of linking Murabaha and Wakala contracts, the reselling of commodities to same traders, and the transfer of ownerships. The work affirms that a multi-agent smart electronic market design would facilitate Shariah compliance. The smart market exploits the rational decision-making capabilities of autonomous proxy agents that enable the clients, traders, brokers, and the bank buy and sell commodities, and manage transactions and cash flow. The smart electronic market design delivers desirable qualities that terminate the need for Wakala contracts and the reselling of commodities to the same traders. It also resolves the ownership transfer issues by allowing stakeholders to trade independently. The bank administers the smart electronic market and assures reliability of trades, transactions and cash flow. A multi-agent simulation is presented to validate the concept and processes. We anticipate that the multi-agent smart electronic market design would deliver Shariah compliance of personal financing to the aspiration of scholars, banks, traders and potential clients.

Keywords: Islamic finance, share'ah compliance, smart electronic markets design, multiagent systems

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Authors: Hunmin Jung, Michael Hawkins, Seongmin Lee

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The exocyclic amines of nucleobases can undergo deamination by various DNA damaging agents such as reactive oxygen species, nitric oxide, and water. The deamination of guanine and adenine generates the promutagenic xanthine and hypoxanthine, respectively. The exocyclic amines of bases in DNA are hydrogen bond donors, while the carbonyl moiety generated by the base deamination acts as hydrogen bond acceptors, which can alter base pairing properties of the purines. Xanthine is known to base pair with both cytosine and thymine, while hypoxanthine predominantly pairs with cytosine to promote A to G mutations. Despite the known promutagenicity of the major deaminated purines, structures of DNA polymerase bypassing these lesions have not been reported. To gain insights into the deaminated-induced mutagenesis, we solved crystal structures of human DNA polymerase η (polη) catalyzing across xanthine and hypoxanthine. In the catalytic site of polη, the deaminated guanine (i.e., xanthine) forms three Watson-Crick-like hydrogen bonds with an incoming dCTP, indicating the O2-enol tautomer of xanthine involves in the base pairing. The formation of the enol tautomer appears to be promoted by the minor groove contact by Gln38 of polη. When hypoxanthine is at the templating position, the deaminated adenine uses its O6-keto tautomer to form two Watson-Crick hydrogen bonds with an incoming dCTP, providing the structural basis for the high promutagenicity of hypoxanthine.

Keywords: DNA damage, DNA polymerase, deamination, mutagenesis, tautomerization, translesion synthesis

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Authors: Zoi Konsoula

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The increasing prevalence of Alzheimer’s disease (AD) and diabetes mellitus (DM) constitutes them major global health problems. Recently, the inhibition of key enzyme activity is considered a potential treatment of both diseases. Specifically, inhibition of acetylcholinesterase (AChE), the key enzyme involved in the breakdown of the neurotransmitter acetylcholine, is a promising approach for the treatment of AD, while inhibition of α-amylase retards the hydrolysis of carbohydrates and, thus, reduces hyperglycemia. Unfortunately, commercially available AChE and α-amylase inhibitors are reported to possess side effects. Consequently, there is a need to develop safe and effective treatments for both diseases. In the present study, pomegranate peel (PP) was extracted using various solvents of increasing polarity, while two extraction methods were employed, the conventional maceration and the ultrasound assisted extraction (UAE). The concentration of bioactive phytoconstituents, such as total phenolics (TPC) and total flavonoids (TFC) in the prepared extracts was evaluated by the Folin-Ciocalteu and the aluminum-flavonoid complex method, respectively. Furthermore, the anti-neurodegenerative and anti-hyperglycemic activity of all extracts was determined using AChE and α-amylase inhibitory activity assays, respectively. The inhibitory activity of the extracts against AChE and α-amylase was characterized by estimating their IC₅₀ value using a dose-response curve, while galanthamine and acarbose were used as positive controls, respectively. Finally, the kinetics of AChE and α-amylase in the presence of the most inhibitory potent extracts was determined by the Lineweaver-Burk plot. The methanolic extract prepared using the UAE contained the highest amount of phytoconstituents, followed by the respective ethanolic extract. All extracts inhibited acetylcholinesterase in a dose-dependent manner, while the increased anticholinesterase activity of the methanolic (IC₅₀ = 32 μg/mL) and ethanolic (IC₅₀ = 42 μg/mL) extract was positively correlated with their TPC content. Furthermore, the activity of the aforementioned extracts was comparable to galanthamine. Similar results were obtained in the case of α-amylase, however, all extracts showed lower inhibitory effect on the carbohydrate hydrolyzing enzyme than on AChE, since the IC₅₀ value ranged from 84 to 100 μg/mL. Also, the α-amylase inhibitory effect of the extracts was lower than acarbose. Finally, the methanolic and ethanolic extracts prepared by UAE inhibited both enzymes in a mixed (competitive/noncompetitive) manner since the Kₘ value of both enzymes increased in the presence of extracts, while the Vmax value decreased. The results of the present study indicate that PP may be a useful source of active compounds for the management of AD and DM. Moreover, taking into consideration that PP is an agro-industrial waste product, its valorization could not only result in economic efficiency but also reduce the environmental pollution.

Keywords: acetylcholinesterase, Alzheimer’s disease, α-amylase, diabetes mellitus, pomegranate

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Authors: Hiroyuki Aoki

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The optoacoustic effect is the energy conversion phenomenon from light to sound. In recent years, this optoacoustic effect has been utilized for an imaging agent to visualize a tumor site in a living body. The optoacoustic imaging agent absorbs the light and emits the sound signal. The sound wave can propagate in a living organism with a small energy loss; therefore, the optoacoustic imaging method enables the molecular imaging of the deep inside of the body. In order to improve the imaging quality of the optoacoustic method, the more signal intensity is desired; however, it has been difficult to enhance the signal intensity of the optoacoustic imaging agent because the fundamental mechanism of the signal generation is unclear. This study deals with the mechanism to generate the sound wave signal from the optoacoustic imaging agent following the light absorption by experimental and theoretical approaches. The optoacoustic signal efficiency for the nano-particles consisting of metal and polymer were compared, and it was found that the polymer particle was better. The heat generation and transfer process for optoacoustic agents of metal and polymer were theoretically examined. It was found that heat generated in the metal particle rapidly transferred to the water medium, whereas the heat in the polymer particle was confined in itself. The confined heat in the small particle induces the massive volume expansion, resulting in the large optoacoustic signal for the polymeric particle agent. Thus, we showed that heat confinement is a crucial factor in designing the highly efficient optoacoustic imaging agent.

Keywords: nano-particle, opto-acoustic effect, in vivo imaging, molecular imaging

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Authors: Anderson Chidi Amadioha, Promise Chidi Kenkwo, A. A. Markson

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Cassava (Manihot esculenta Crantz) is an important food and cash crop that provide cheap source of carbohydrate for food, feed and raw material for industries hence a commodity for feature economic development of developing countries. Despite the importance, its production potentials is undermined by disease agents that greatly reduce yield and render it unfit for human consumption and industrial use. Pathogenicity tests on fungal isolates from infected cassava revealed Aspergillus flavus, Rhizopus stolonifer, Aspergillus niger, and Trichodderma viride as rot-causing organisms. Water and ethanol extracts of Piper guineense, Ocimum graticimum, Cassia alata, and Tagetes erecta at 50% concentration significantly inhibited the radial growth of the pathogens in vitro and their development and spread in vivo. Low cassava rot incidence and severity was recorded when the extracts were applied before than after spray inoculating with spore suspension (1x105 spores/ml of distilled water) of the pathogenic organisms. The plant materials are readily available, and their extracts are biodegradable and cost effective. The fungitoxic potentials of extracts of these plant materials could be exploited as potent biopesticides in the management of postharvest fungal deterioration of cassava especially in developing countries where synthetic fungicides are not only scarce but also expensive for resource poor farmers who produce over 95% of the food consumed.

Keywords: cassava, biopesticides, in vitro, in vivo, pathogens, plant extracts

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Authors: Ş. Çiftcioğlu, E. Efe

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In recent years, cancer has been at the top of diseases that cause death in children. Adequate and balanced nutrition plays an important role in the treatment of cancer. Cancer and cancer treatment is affecting food intake, absorption and metabolism, causing nutritional disorders. Appropriate nutrition is very important for the cancerous child to feel well before, during and after the treatment. There are various difficulties in feeding children with cancer. These are the cancer-related factors. Other factors are environmental and behavioral. As health professionals who spend more time with children in the hospital, nurses should be able to support the children on nutrition and help them to have balanced nutrition. This study aimed to evaluate the importance of nursing approaches in the nutrition of children with cancer. This article is planned as a review article by searching the literature on this field. Anorexia may develop due to psychogenic causes or chemotherapeutic agents or accompanying infections and nutrient uptake may be reduced.  In addition, stomatitis, mucositis, taste and odor changes in the mouth, the feeling of nausea, vomiting and diarrhea can also reduce oral intake and result in significant losses in the energy deficit. In assessing the nutritional status of children with cancer, determining weight loss and good nutrition is essential anamnesis of a child.  Some anthropometric measurements and biochemical tests should be used to evaluate the nutrition of the child. The nutritional status of pediatric cancer patients has been studied for a long time and malnutrition, in particular under nutrition, in this population has long been recognized. Yet, its management remains variable with many malnourished children going unrecognized and consequently untreated. Nutritional support is important to pediatric cancer patients and should be integrated into the overall treatment of these children.

Keywords: cancer treatment, children, complication, nutrition, nursing approaches

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Authors: Monika Verma, Renuka Sharma, B. R. Gulati, Namita Singh

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In combination therapy, two chemotherapeutic agents work together in a collaborative action. It has appeared as one of the promising approaches to improve anti-cancer treatment efficacy. In the present investigation, piperine (P-NPS), paclitaxel (PTX NPS), and a combination of both, piperine-paclitaxel nanoparticle (Pip-PTX NPS), were made by the nanoprecipitation method and later characterized by PSA, DSC, SEM, TEM, and FTIR. All nanoparticles exhibited a monodispersed size distribution with a size of below 200 nm, zeta potential ranges from (-30-40mV) and a narrow polydispersity index (>0.3) of the drugs. The average encapsulation efficiency was found to be between 80 and 90%. In vitro release of drugs for nanoparticles was done spectrophotometrically. FTIR and DSC results confirmed the presence of the drug. The Pip-PTX NPS significantly inhibit cell proliferation as compared to the native drugs nanoparticles in the breast cancer cell line MCF-7. In addition, Pip-PTX NPS suppresses cells in colony formation and soft gel agar assay. Scratch migration and Transwell chamber invasion assays revealed that combined nanoparticles reduce the migration and invasion of breast cancer cells. Morphological studies showed that Pip-PTX NPS penetrates the cells and induces apoptosis, which was further confirmed by DNA fragmentation, SEM, and western blot analysis. Taken together, Pip-PTX NPS inhibits cell proliferation, anchorage dependent and anchorage independent cell growth, reduces migration and invasion, and induces apoptosis in cells. These findings support that combination therapy using Pip-PTX NPS represents a potential approach and could be helpful in the future for breast cancer therapy.

Keywords: piperine, paclitaxel, breast cancer, apoptosis

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Authors: Niharika Kaushal, Minni Singh

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Citrus fruits contain an abundance of phytochemicals that can promote health. A substantial amount of agrowaste is produced from the juice processing industries, primarily peels and seeds. This leftover agrowaste is a reservoir of nutraceuticals, particularly bioflavonoids which render it antioxidant and potentially anticancerous. It is, therefore, favorable to utilize this biomass and contribute towards sustainability in a manner that value-added products may be derived from them, nutraceuticals, in this study. However, the pre-systemic metabolism of flavonoids in the gastric phase limits the effectiveness of these bioflavonoids derived from mandarin biomass. In this study, ‘kinnow’ mandarin (Citrus nobilis X Citrus deliciosa) biomass was explored for its flavonoid profile. This work entails supercritical fluid extraction and identification of bioflavonoids from mandarin biomass. Furthermore, to overcome the limitations of these flavonoids in the gastrointestinal tract, a double-layered vehicular mechanism comprising the fabrication of nanoconjugates and edible hydrogels was adopted. Total flavonoids in the mandarin peel extract were estimated by the aluminum chloride complexation method and were found to be 47.3±1.06 mg/ml rutin equivalents as total flavonoids. Mass spectral analysis revealed the abundance of polymethoxyflavones (PMFs), nobiletin and tangeretin as the major flavonoids in the extract, followed by hesperetin and naringenin. Furthermore, the antioxidant potential was analyzed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, which showed an IC50 of 0.55μg/ml. Nanoconjugates were fabricated via the solvent evaporation method, which was further impregnated into hydrogels. Additionally, the release characteristics of nanoconjugate-laden hydrogels in a simulated gastrointestinal environment were studied. The PLGA-PMFs nanoconjugates exhibited a particle size between 200-250nm having a smooth and spherical shape as revealed by FE-SEM. The impregnated alginate hydrogels offered a dense network that ensured the holding of PLGA-PMF nanoconjugates, as confirmed by Cryo-SEM images. Rheological studies revealed the shear-thinning behavior of hydrogels and their high resistance to deformation. Gastrointestinal studies showed a negligible 4.0% release of flavonoids in the gastric phase, followed by a sustained release over the next hours in the intestinal environment. Therefore, based on the enormous potential of recovering nutraceuticals from agro-processing wastes, further augmented by nanotechnological interventions for enhancing the bioefficacy of these compounds, lays the foundation for exploring the path towards the development of value-added products, thereby contributing towards the sustainable use of agrowaste.

Keywords: agrowaste, gastrointestinal, hydrogel, nutraceuticals

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Authors: M. L. Moyo

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Concerns about climate change, food productivity, and the ever-increasing cost of commercial fertilizer products is forcing have spurred interest in the production of alternatives or substitutes for commercial fertilizer products. In this study, the potential of pyrolytic tire char (PT-char) to improve soil productivity was investigated. The use of carbonized biomass, which is commonly termed biochar or biofertilizer and exhibits similar properties to PT-char in agriculture is not new, with historical evidence pointing to the use of charcoal for soil improvement by indigenous Amazon people for several centuries. Due to minimal market value or use of PT-char, huge quantities are currently stockpiled in South Africa. This successively reduces revenue and decreases investments in waste tire recycling efforts as PT-char constitutes 40 % weight of the total waste tire pyrolysis products. The physicochemical analysis results reported in this study showed that PT-char contains a low concentration of essential plant elements (P and K) and, therefore, cannot be used for increasing nutrient availability in soils. A low presence of heavy metals (Ni, Pb, and Cd), which may be harmful to the environment at high application rates was also observed. In addition, the results revealed that PT-char contains very high levels of Zn, a widely known phytotoxicity causing agents in plants. However, the study also illustrated that PT-char is made up of a highly aromatic and condensed carbon structure. PT-char is therefore highly stable, less prone to microbial degradation, and has a low chemical reactivity in soils. Considering these characteristics, PT-char meets the requirements for use as a carbon sequestration agent, which may be useful in mitigating climate change.

Keywords: agriculture, carbon sequestration, physicochemical analysis, pyrolytic tire char, soil amendment.

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Authors: Bahadir Batar, Elif Serdal, Berna Erdal, Hasan Ogul

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Micro-ribonucleic acids (miRNAs) are small short non-coding ribonucleic acid molecules about 22 nucleotides long. miRNAs play a key role in response to chemotherapeutic agents. WW domain-containing oxidoreductase (WWOX) gene encodes a tumor suppressor protein. Loss or reduction of Wwox protein is observed in many breast cancer cases. WWOX protein deficiency is increased in triple-negative breast cancer (TNBC). TNBC is a heterogeneous, highly aggressive, and difficult to treat tumor type. WWOX loss contributes to resistance to cisplatin therapy in patients with TNBC. Here, the aim of the study was to investigate the potential role of miRNAs in cisplatin therapy resistance of WWOX-deficient TNBC cells. This was a cell culture study. miRNA expression profiling was analyzed by LightCycler 480 system. miRNA Set Enrichment Analysis tool was used to integrate experimental data with literature-based biological knowledge to infer a new hypothesis. Increased miR-182 and decreased miR-214 were significantly correlated with cisplatin resistance in WWOX-deficient TNBC cells. miR-182 and miR-214 may involve in cisplatin resistance of WWOX-deficient TNBC cells by deregulating the DNA repair, apoptosis, or protein kinase B signaling pathways. These data highlight the mechanism by which WWOX regulates cisplatin resistance of TNBC and the potential use of WWOX as a predictor biomarker for cisplatin resistance.

Keywords: cisplatin, microRNA, triple-negative breast cancer, WWOX

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Authors: Jin Boo Jeong

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In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A abolished cyclin D1 downregulation by DKC-E70. We also observed that DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was blocked in presence of the inhibitors of ERK1/2, p38 or GSK3β. In cyclin D1 transcriptional inhibition, DKC-E70 inhibited the expression of β-catenin and TCF4, and β–catenin/TCF-dependent luciferase activity. Our results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through cyclin D1 degradation by T286 phosphorylation dependent on ERK1/2, p38 or GSK3β, and cyclin D1 transcriptional inhibition through Wnt signaling. From these findings, DKC-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A3B03931713).

Keywords: anticancer, calyx of persimmon, cyclin D1, Diospyros kaki Thunb., human colorectal cancer

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Authors: Jean Berger, Nassirou Lo, Martin Noel

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Perfectly suited for natural or man-made emergency and disaster management situations such as flood, earthquakes, tornadoes, or tsunami, multi-target search path planning for a team of rescue agents is known to be computationally hard, and most techniques developed so far come short to successfully estimate optimality gap. A novel mixed-integer linear programming (MIP) formulation is proposed to optimally solve the multi-target multi-agent discrete search and rescue (SAR) path planning problem. Aimed at maximizing cumulative probability of successful target detection, it captures anticipated feedback information associated with possible observation outcomes resulting from projected path execution, while modeling agent discrete actions over all possible moving directions. Problem modeling further takes advantage of network representation to encompass decision variables, expedite compact constraint specification, and lead to substantial problem-solving speed-up. The proposed MIP approach uses CPLEX optimization machinery, efficiently computing near-optimal solutions for practical size problems, while giving a robust upper bound obtained from Lagrangean integrality constraint relaxation. Should eventually a target be positively detected during plan execution, a new problem instance would simply be reformulated from the current state, and then solved over the next decision cycle. A computational experiment shows the feasibility and the value of the proposed approach.

Keywords: search path planning, search and rescue, multi-agent, mixed-integer linear programming, optimization

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Authors: El Alia Boularas, H. Bekkar, H. Larachi, H. Rezk-kallah

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Introduction: Notwithstanding cosmetics are used in life every day, these products are not all innocuous and harmless, as they may contain ingredients responsible for allergic reactions and, possibly, for other health problems. Additionally, environmental pollution should be taken into account. Thus, it is time to investigate what is ‘hidden behind beauty’. Aims: 1.To investigate prevalence of 13 chemical ingredients in cosmetics being object of concern, which the Algerians use regularly. 2.To know the profile of questioned consumers and describe their opinion on cosmetics. Methods: The survey was carried out in year 2013 over a period of 3 months, among Algerian Internet users having an e-mail address or a Facebook account.The study investigated 13 chemical agents showing health and environmental problems, selected after analysis of the recent studies published on the subject, the lists of national and international regulatory references on chemical hazards, and querying the database Skin Deep presented by the Environmental Working Group. Results: 300 people distributed all over the Algerian territory participated in the survey, providing information about 731 cosmetics; 86% aged from 20 to 39 years, with a sex ratio=0,27. A percentage of 43% of the analyzed cosmetics contained at least one of the 13 toxic ingredients. The targeted ingredient that has been most frequently reported was ‘perfume’ followed by parabens and PEG.85% of the participants declared that cosmetics ‘can contain toxic substances’, 27% asserted that they verify regularly the list of ingredients when they buy cosmetics, 61% said that they try to avoid the toxic ingredients, among whom 24 % were more vigilant on the presence of parabens, 95% were in favour of the strengthening of the Algerian laws on cosmetics. Conclusion: The results of the survey provide the indication of a widespread presence of toxic chemical ingredients in personal care products that Algerians use daily.

Keywords: Algerians consumers, cosmetics, survey, toxic ingredients

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Authors: Sarra Boughaba

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The α-aminophosphonates have received considerable attention in organic and medicinal chemistry because of their structural resemblance with α-amino acids. They are used as antitumor agents, anti-inflammatory and antibiotics. As a result, a number of procedures have been developed for their synthesis. However, many of these methods suffer from some disadvantages such as long reaction times, environmental pollution caused by utilization of organic solvents, and expensive catalyst. On the other hand, thiazole components, particularly 2-aminothiazole is an important class of heterocyclic compounds. They appear in the structure of natural products and biologically actives compounds, thiamine (vitamin-B), and some antibiotics drugs (penicillin, micrococcin). In the past few years, heteropolyacids have received great attention as environmentally benign catalysts for organic synthetic processes, they possess unique physicochemical properties, such as super-acidity, high thermal and chemical stability, ability to accept and release electrons and high proton mobility, and the possibility of varying their acidity and oxidizing potential. In this study, an efficient and eco-friendly process has been developed for the synthesis of α-aminophosphonates containing aminothiazole moiety via Kabachnik-Field reaction catalyzed by H₆P₂W₁₈O₆₂.14H₂O as reusable catalyst, by condensation of aromatic aldehydes, 2-aminothiazole and triethylphosphite under free conditions. The X-ray crystallographic data of obtained compounds were provided. The main advantages of our protocol include the absence of solvent in the reaction, easy work-up, short reaction time, atom-economy and reusability of catalyst without significant loss of its activity.

Keywords: aminophosphonates, green synthesis, H₆P₂W₁₈O₆₂.14H₂O catalyst, x-ray study

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Authors: T. Scattolin, E. Cavarzerani, F. Visentin, F. Rizzolio

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Organopalladium compounds have recently attracted attention for their high stability even under physiological conditions and, above all, for their remarkable in vitro cytotoxicity towards cisplatin-resistant cell lines. Among the organopalladium derivatives, those bearing at least one N-heterocyclic carbene ligand (NHC) and the Pd(II)-η³-allyl fragment have exhibited IC₅₀ values in the micro and sub-micromolar range towards several cancer cell lines in vitro and in some cases selectivity towards cancerous vs. non-tumorigenic cells. Herein, a selection of allyl and indenyl palladates were synthesized using a solvent-free method consisting of grinding the corresponding palladium precursors with different saturated and unsaturated azolium salts. All compounds have been fully characterized by NMR, XRD and elemental analyses. The intramolecular H, Cl interaction has been elucidated and quantified using the Voronoi Deformation Density scheme. Most of the complexes showed excellent cytotoxicity towards ovarian cancer cell lines, with I₅₀ values comparable to or even lower than cisplatin. Interestingly, the potent anticancer activity was also confirmed in a high-serous ovarian cancer (HGSOC) patient-derived tumoroid, with a clear superiority of this class of compounds over classical platinum-based agents. Finally, preliminary enzyme inhibition studies of the synthesized palladate complexes against the model TrxR show that the compounds have high activity comparable to or even higher than auranofin and classical Au(I) NHC complexes. Based on such promising data, further in vitro and in vivo experiments and in-depth mechanistic studies are ongoing in our laboratories.

Keywords: anticancer activity, palladium complexes, organoids, indenyl and allyl ligands

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Authors: Zohreh Mohammadi, Jan Kaspar, Peter Lohmander, Robert Marusak, Harald Vacik, Ljusk Ola Eriksson

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Storms are important damaging agents in European forest ecosystems. In the latest decades, significant economic losses in European forestry occurred due to storms. This study investigates the problem of optimal harvest planning when forest stands risk to be felled by storms. One of the most applicable mathematical methods which are being used to optimize forest management is stochastic dynamic programming (SDP). This method belongs to the adaptive optimization class. Sequential decisions, such as harvest decisions, can be optimized based on sequential information about events that cannot be perfectly predicted, such as the future storms and the future states of wind protection from other forest stands. In this paper, stochastic dynamic programming is used to maximize the expected present value of the profits from an area consisting of several forest stands. The region of analysis is the Czech Republic. The harvest decisions, in a particular time period, should be simultaneously taken in all neighbor stands. The reason is that different stands protect each other from possible winds. The optimal harvest age of a particular stand is a function of wind speed and different wind protection effects. The optimal harvest age often decreases with wind speed, but it cannot be determined for one stand at a time. When we consider a particular stand, this stand also protects other stands. Furthermore, the particular stand is protected by neighbor stands. In some forest stands, it may even be rational to increase the harvest age under the influence of stronger winds, in order to protect more valuable stands in the neighborhood. It is important to integrate wind risk in forestry decision-making.

Keywords: Czech republic, forest stands, stochastic dynamic programming, wind risk

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Authors: Ozlem Temiz Arpaci, Meryem Tasci, Hakan Goker

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Benzimidazole, a structural isostere of indol and purine nuclei that can interact with biopolymers, can be identified as master key. So that benzimidazole compounds are important fragments in medicinal chemistry because of their wide range of biological activities including antimicrobial activity. We planned to synthesize some benzimidazole compounds for developing new antimicrobial drug candidates. In this study, we put some heterocyclic rings on second position and an amidine group on the fifth position of benzimidazole ring and synthesized them using a multiple step procedure. For the synthesis of the compounds, as the first step, 4-chloro-3-nitrobenzonitrile was reacted with cyclohexylamine in dimethyl formamide. Imidate esters (compound 2) were then prepared with absolute ethanol saturated with dry HCl gas. These imidate esters which were not too stable were converted to compound 3 by passing ammonia gas through ethanol. At the Pd / C catalyst, the nitro group is reduced to the amine group (compound 4). Finally, various aldehyde derivatives were reacted with sodium metabisulfite addition products to give compound 5-20. Melting points were determined on a Buchi B-540 melting point apparatus in open capillary tubes and are uncorrected. Elemental analyses were done a Leco CHNS 932 elemental analyzer. 1H-NMR and 13C-NMR spectra were recorded on a Varian Mercury 400 MHz spectrometer using DMSO-d6. Mass spectra were acquired on a Waters Micromass ZQ using the ESI(+) method. The structures of them were supported by spectral data. The 1H-NMR, 13C NMR and mass spectra and elemental analysis results agree with those of the proposed structures. Antimicrobial activity studies of the synthesized compounds are under the investigation.

Keywords: benzimidazoles, synthesis, structure elucidation, antimicrobial

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Authors: Suminar Pratapa, Agus Riyanto, Silmi Machmudah, Sri Yani Purwaningsih

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The objective of this study was to investigate the optical properties of polyvinyl alcohol (PVA) and its prospective applications by adding crystalline silica which is usually used as a reinforcing agent. To do this, we synthesized and evaluated PVA-based composites reinforced with silica crystals, namely cristobalite, derived from rice husk. The experimental procedure involved the production of SiO2 particles using rice husk precursors, which were subsequently subjected to calcination at a rate of 10 °C/min for a duration of 3 hours. This process primarily resulted in the formation of SiO2 crystals in the cristobalite phase, according to X-ray diffraction (XRD). Following this, the crystals were incorporated into polyvinyl alcohol (PVA) via a casting technique, resulting in the formation of composite sheets. The SiO2 contents in the composites were 0, 2.5, 5.0, and 10.%. XRD and Fourier-transform infrared spectroscopy (FTIR) techniques provided confirmation of the composites' successful synthesis, i.e., it did not yield any indications of chemical bonding between polyvinyl alcohol (PVA) and silicon dioxide (SiO2), indicating that the interaction was limited to interfacial reactions. The incorporation of SiO2 crystals resulted in a notable enhancement in UV-vis light absorption and a decrease in the optical band gap. Addition of 2.5, 5.0, and 10.% SiO2, for example, decreases the direct optical band gap of the composites form 5.37, 5.19, and 5.02 eV respectively, while the indirect band gaps of the samples were 4.44, 4.84, and 4.48 eV, correspondingly. These findings emphasize the efficacy of rice husk-derived SiO2 crystals as both reinforcement agents and modifiers of optical properties in the polymer composites, showcasing their significant potential to modify the composite's structural and optical characteristics.

Keywords: rice husk, cristaline SiO₂, PVA-based composites, structural characteristics, optical properties.

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Authors: Agnieszka Sobczak-Kupiec, Dagmara Malina, Klaudia Pluta, Wioletta Florkiewicz, Bozena Tyliszczak

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Introduction: Request for compound of phosphorus grows continuously, thus, it is searched for alternative sources of this element. One of these sources could be by-products from meat industry which contain prominent quantity of phosphorus compounds. Hydroxyapatite, which is natural component of animal and human bones, is leading material applied in bone surgery and also in stomatology. This is material, which is biocompatible, bioactive and osteoinductive. Methodology: Hydroxyapatite preparation: As a raw material was applied deproteinized and defatted bone pulp called bone sludge, which was formed as waste in deproteinization process of bones, in which a protein hydrolysate was the main product. Hydroxyapatite was received in calcining process in chamber kiln with electric heating in air atmosphere in two stages. In the first stage, material was calcining in temperature 600°C within 3 hours. In the next stage unified material was calcining in three different temperatures (750°C, 850°C and 950°C) keeping material in maximum temperature within 3.0 hours. Bone sludge: Bone sludge was formed as waste in deproteinization process of bones, in which a protein hydrolysate was the main product. Pork bones coming from the partition of meat were used as a raw material for the production of the protein hydrolysate. After disintegration, a mixture of bone pulp and water with a small amount of lactic acid was boiled at temperature 130-135°C and under pressure4 bar. After 3-3.5 hours boiled-out bones were separated on a sieve, and the solution of protein-fat hydrolysate got into a decanter, where bone sludge was separated from it. Results of the study: The phase composition was analyzed by roentgenographic method. Hydroxyapatite was the only crystalline phase observed in all the calcining products. XRD investigation was shown that crystallization degree of hydroxyapatite was increased with calcining temperature. Conclusion: The researches were shown that phosphorus content is around 12%, whereas, calcium content amounts to 28% on average. The conducted researches on bone-waste calcining at the temperatures of 750-950°C confirmed that thermal utilization of deproteinized bone-waste was possible. X-ray investigations were confirmed that hydroxyapatite is the main component of calcining products, and also XRD investigation was shown that crystallization degree of hydroxyapatite was increased with calcining temperature. Contents of calcium and phosphorus were distinctly increased with calcining temperature, whereas contents of phosphorus soluble in acids were decreased. It could be connected with higher crystallization degree of material received in higher temperatures and its stable structure. Acknowledgements: “The authors would like to thank the The National Centre for Research and Development (Grant no: LIDER//037/481/L-5/13/NCBR/2014) for providing financial support to this project”.

Keywords: bone by-products, bone sludge, calcination, hydroxyapatite

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Authors: Mayank, Navneet Kaur, Narinder Singh

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The V599 mutations in the BRAF protein are extremely oncogenic, responsible for countless of malignant conditions. Along with wild type, V599E, V599D, and V599R are the important mutated variants of the BRAF proteins. The BRAF inhibitory anticancer agents are continuously developing, and sorafenib is a BRAF inhibitor that is under clinical use. The crystal structure of sorafenib bounded to wild type, and V599 is known, showing a similar interaction pattern in both the case. The mutated 599th residue, in both the case, is also found not interacting directly with the co-crystallized sorafenib molecule. However, the IC50 value of sorafenib was found extremely different in both the case, i.e., 22 nmol/L for wild and 38 nmol/L for V599E protein. Molecular docking study and MMGBSA binding energy results also revealed a significant difference in the binding pattern of sorafenib in both the case. Therefore, to explore the role of distinctively situated 599th residue, we have further conducted comprehensive computational studies. The molecular dynamics simulation, residue interaction network (RIN) analysis, and residue correlation study results revealed the importance of the 599th residue on the therapeutic outcome and overall dynamic of the BRAF protein. Therefore, although the position of 599th residue is very much distinctive from the ligand-binding cavity of BRAF, still it has exceptional control over the overall functional outcome of the protein. The insight obtained here may seem extremely important and guide us while designing ideal BRAF inhibitory anticancer molecules.

Keywords: BRAF, oncogenic, sorafenib, computational studies

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Authors: Pakize Neslihan Taslı, Alev Cumbul, Gul Merve Yalcın, Fikrettin Sahin

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A key experimental trial in the regeneration of large oral and craniofacial defects is the neogenesis of osseous and ligamentous interfacial structures. Currently, oral regenerative medicine strategies are unpredictable for repair of tooth supporting tissues destroyed as a consequence of trauma, chronic infection or surgical resection. A different approach combining the gel-casting method with Hydroxy Apatite HA-based scaffold and different cell lineages as a hybrid system leads to successively mimic the early stage of tooth development, in vitro. HA is widely accepted as a bioactive material for guided bone and tooth regeneration. In this study, it was reported that, HA porous scaffold preparation, characterization and evaluation of structural and chemical properties. HA is the main factor that exists in tooth and it is in harmony with structural, biological, and mechanical characteristics. Here, this study shows mimicking immature tooth at the late bell stage design and construction of HA scaffolds for cell transplantation of human Adipose Stem Cells (hASCs), human Bone Marrow Stem Cells (hBMSCs) and Gingival Epitelial cells for the formation of human tooth dentin-pulp-enamel complexes in vitro. Scaffold characterization was demonstrated by SEM, FTIR and pore size and density measurements. The biological contraction of dental tissues against each other was demonstrated by mRNA gene expressions, histopatologic observations and protein release profile by ELISA tecnique. The tooth shaped constructs with a pore size ranging from 150 to 300 µm arranged by gathering right amounts of materials provide interconnected macro-porous structure. The newly formed tissue like structures that grow and integrate within the HA designed constructs forming tooth cementum like tissue, pulp and bone structures. These findings are important as they emphasize the potential biological effect of the hybrid scaffold system. In conclusion, this in vitro study clearly demonstrates that designed 3D scaffolds shaped as a immature tooth at the late bell stage were essential to form enamel-dentin-pulp interfaces with an appropriate cell and biodegradable material combination. The biomimetic architecture achieved here is providing a promising platform for dental tissue engineering.

Keywords: tooth regeneration, tissue engineering, adipose stem cells, hydroxyapatite tooth engineering, porous scaffold

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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

Procedia PDF Downloads 279

Authors: Zsanett Bahor, Cristina Nunes-Fonseca, Gillian L. Currie, Emily S. Sena, Lindsay D.G. Thomson, Malcolm R. Macleod

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Psychosis is ranked as the third most disabling medical condition in the world by the World Health Organization. Despite a substantial amount of research in recent years, available treatments are not universally effective and have a wide range of adverse side effects. Since many clinical drug candidates are identified through in vivo modelling, a deeper understanding of these models, and their strengths and limitations, might help us understand reasons for difficulties in psychosis drug development. To provide an unbiased summary of the preclinical psychosis literature we performed a systematic electronic search of PubMed for publications modelling a psychotic disorder in vivo, identifying 14,721 relevant studies. Double screening of 11,000 publications from this dataset so far established 2403 animal studies of psychosis, with the most common model being schizophrenia (95%). 61% of these models are induced using pharmacological agents. For all the models only 56% of publications test a therapeutic treatment. We propose a systematic review of these studies to assess the prevalence of reporting of measures to reduce risk of bias, and a meta-analysis to assess the internal and external validity of these animal models. Our findings are likely to be relevant to future preclinical studies of psychosis as this generation of strong empirical evidence has the potential to identify weaknesses, areas for improvement and make suggestions on refinement of experimental design. Such a detailed understanding of the data which inform what we think we know will help improve the current attrition rate between bench and bedside in psychosis research.

Keywords: animal models, psychosis, systematic review, schizophrenia

Procedia PDF Downloads 285