Search results for: cardiac toxicity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1398

Search results for: cardiac toxicity

198 Determination of the Informativeness of Instrumental Research Methods in Assessing Risk Factors for the Development of Renal Dysfunction in Elderly Patients with Chronic Ischemic Heart Disease

Authors: Aksana N. Popel, Volha A. Sujayeva, Olga V. Kоshlataja, Irеna S. Karpava

Abstract:

Introduction: It is a known fact that cardiovascular pathology and its complications cause a more severe course and worse prognosis in patients with comorbid kidney pathology. Chronic kidney disease (CKD) is associated with inflammation, endothelial dysfunction, and increased activity of the sympathoadrenal system. This circumstance increases the risk of cardiovascular diseases and the progression of kidney pathology. The above determines the need to identify cardiorenal changes at early stages to reduce the risks of cardiovascular complications and the progression of CKD. Objective: To identify risk factors (RF) for the development of CKD in elderly patients with chronic ischemic heart disease (CIHD). Methods: The study included 64 patients (40 women and 24 men) with a mean age of 74.4±4.5 years with coronary heart disease, without a history of structural kidney pathology and CKD. All patients underwent transthoracic echocardiography (TTE) and kidney ultrasound (KU) using GE Vivid 9 equipment (GE HealthCare, USA), and cardiac computed tomography (CCT) using Siemens Somatom Force equipment (Siemens Healthineers AG, Germany) in 3 months and in 1 year. Data obtained were analyzed using multiple regression analysis and nonparametric Mann-Whitney test. Statistical analysis was performed using the STATISTICA 12.0 program (StatSoft Inc.). Results: Initially, CKD was not diagnosed in all patients. In 3 months, CKD was diagnosed: stage C1 had 11 people (18%), stage C2 had 4 people (6%), stage C3A had 11 people (18%), stage C3B had 2 people (3%). After 1 year, CKD was diagnosed: stage C1 had 22 people (35%), stage C2 had 5 people (8%), stage C3A had 17 people (27%), stage C3B had 10 people (15%). In 3 months, statistically significant (p<0.05) risk factors were: 1) according to TTE: mitral peak E-wave velocity (U=678, p=0.039), mitral E-velocity DT (U=514, p=0.0168), mitral peak A-wave velocity (U=682, p=0.013). In 1 year, statistically significant (p<0.05) risk factors were: according to TTE: left ventricular (LV) end-systolic volume in B-mode (U=134, p=0.006), LV end-diastolic volume in B-mode (U=177, p=0.04), LV ejection fraction in B-mode (U=135, p=0.006), left atrial volume (U=178, p=0.021), LV hypertrophy (U=294, p=0.04), mitral valve (MV) fibrosis (U=328, p=0.01); according CCT: epicardial fat thickness (EFT) on the right ventricle (U=8, p=0.015); according to KU: interlobar renal artery resistance index (RI) (U=224, p=0.02), segmental renal artery RI (U=409, p=0.016). Conclusions: Both TTE and KU are very informative methods to determine the additional risk factors of CKD development and progression. The most informative risk factors were LV global systolic and diastolic functions, LV and LA volumes. LV hypertrophy, MV fibrosis, interlobar renal artery and segmental renal artery RIs, EFT.

Keywords: chronic kidney disease, ischemic heart disease, prognosis, risk factors

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197 Synthesis and Characterization of pH-Responsive Nanocarriers Based on POEOMA-b-PDPA Block Copolymers for RNA Delivery

Authors: Bruno Baptista, Andreia S. R. Oliveira, Patricia V. Mendonca, Jorge F. J. Coelho, Fani Sousa

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Drug delivery systems are designed to allow adequate protection and controlled delivery of drugs to specific locations. These systems aim to reduce side effects and control the biodistribution profile of drugs, thus improving therapeutic efficacy. This study involved the synthesis of polymeric nanoparticles, based on amphiphilic diblock copolymers, comprising a biocompatible, poly (oligo (ethylene oxide) methyl ether methacrylate (POEOMA) as hydrophilic segment and a pH-sensitive block, the poly (2-diisopropylamino)ethyl methacrylate) (PDPA). The objective of this work was the development of polymeric pH-responsive nanoparticles to encapsulate and carry small RNAs as a model to further develop non-coding RNAs delivery systems with therapeutic value. The responsiveness of PDPA to pH allows the electrostatic interaction of these copolymers with nucleic acids at acidic pH, as a result of the protonation of the tertiary amine groups of this polymer at pH values below its pKa (around 6.2). Initially, the molecular weight parameters and chemical structure of the block copolymers were determined by size exclusion chromatography (SEC) and nuclear magnetic resonance (1H-NMR) spectroscopy, respectively. Then, the complexation with small RNAs was verified, generating polyplexes with sizes ranging from 300 to 600 nm and with encapsulation efficiencies around 80%, depending on the molecular weight of the polymers, their composition, and concentration used. The effect of pH on the morphology of nanoparticles was evaluated by scanning electron microscopy (SEM) being verified that at higher pH values, particles tend to lose their spherical shape. Since this work aims to develop systems for the delivery of non-coding RNAs, studies on RNA protection (contact with RNase, FBS, and Trypsin) and cell viability were also carried out. It was found that they induce some protection against constituents of the cellular environment and have no cellular toxicity. In summary, this research work contributes to the development of pH-sensitive polymers, capable of protecting and encapsulating RNA, in a relatively simple and efficient manner, to further be applied on drug delivery to specific sites where pH may have a critical role, as it can occur in several cancer environments.

Keywords: drug delivery systems, pH-responsive polymers, POEOMA-b-PDPA, small RNAs

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196 Effect of a Synthetic Platinum-Based Complex on Autophagy Induction in Leydig TM3 Cells

Authors: Ezzati Givi M., Hoveizi E., Nezhad Marani N.

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Platinum-based anticancer therapeutics are the most widely used drugs in clinical chemotherapy but have major limitations and various side effects in clinical applications. Gonadotoxicity and sterility is one of the most common complications for cancer survivors, which seem to be drug-specific and dose-related. Therefore, many efforts have been dedicated to discovering a new structure of platinum-based anticancer agents with improved therapeutic index, fewer side effects. In this regard, new Pt(II)-phosphane complexes containing heterocyclic thionate ligands (PCTL) have been synthesized, which show more potent antitumor activities in comparison to cisplatin. Cisplatin, the best leading metal-based antitumor drug in the field, induces testicular toxicity on Leydig and Sertoli cells leading to serious side effects such as azoospermia and infertility. Therefore in the present study, we aimed to investigate the cytotoxicity effect of PCTL on mice TM4 Sertoli cells with particular emphasis on the role of autophagy in comparison to cisplatin. In this study, an MTT assay was performed to evaluate the IC50 of PCTL and to analyze the TM3 Leydig cell's viability. Cells morphology was evaluated via invert microscope and Changing in morphology for nuclei swelling or autophagic vacuoles formation were assessed by DAPI and MDC staining. Testosterone production in the culture medium was measured using an ELISA kit. Finally, the expression of Autophagy-related genes, Atg5, Beclin1 and p62, were analyzed by qPCR. Based on the obtained results by MTT, the IC50 value of PCTL was 50 μM in TM3 cells and cytotoxic effects was in a dose- and time-dependent manner. Cells morphological changes investigated by inverted microscopy, DAPI, and MDC staining which showed the cytotoxic concentrations of PCTL was significantly higher than cisplatin in the treated TM3 Leydig cells. The results of PCR showed a lack of expression of the p62, Atg5 and Beclin1 gene in TM3 cells treated with PCTL in comparison to cisplatin and control groups. It should be noted that the effects of 25 μM PCTL concentration on TM3 cells have been associated with increased testosterone production and secretion, which requires further study to explain the possible causes and involved molecular mechanisms. The results of the study showed that the PCTL had less-lethal effects on TM3 cells in comparison to cisplatin and probably did not induce autophagy in TM3 cells.

Keywords: platinum-based anticancer agents, cisplatin, Leydig TM3 cells, autophagy

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195 Standardizing and Achieving Protocol Objectives for ChestWall Radiotherapy Treatment Planning Process using an O-ring Linac in High-, Low- and Middle-income Countries

Authors: Milton Ixquiac, Erick Montenegro, Francisco Reynoso, Matthew Schmidt, Thomas Mazur, Tianyu Zhao, Hiram Gay, Geoffrey Hugo, Lauren Henke, Jeff Michael Michalski, Angel Velarde, Vicky de Falla, Franky Reyes, Osmar Hernandez, Edgar Aparicio Ruiz, Baozhou Sun

Abstract:

Purpose: Radiotherapy departments in low- and middle-income countries (LMICs) like Guatemala have recently introduced intensity-modulated radiotherapy (IMRT). IMRT has become the standard of care in high-income countries (HIC) due to reduced toxicity and improved outcomes in some cancers. The purpose of this work is to show the agreement between the dosimetric results shown in the Dose Volume Histograms (DVH) to the objectives proposed in the adopted protocol. This is the initial experience with an O-ring Linac. Methods and Materials: An O-Linac Linac was installed at our clinic in Guatemala in 2019 and has been used to treat approximately 90 patients daily with IMRT. This Linac is a completely Image Guided Device since to deliver each radiotherapy session must take a Mega Voltage Cone Beam Computerized Tomography (MVCBCT). In each MVCBCT, the Linac deliver 9 UM, and they are taken into account while performing the planning. To start the standardization, the TG263 was employed in the nomenclature and adopted a hypofractionated protocol to treat ChestWall, including supraclavicular nodes achieving 40.05Gy in 15 fractions. The planning was developed using 4 semiarcs from 179-305 degrees. The planner must create optimization volumes for targets and Organs at Risk (OARs); the difficulty for the planner was the dose base due to the MVCBCT. To evaluate the planning modality, we used 30 chestwall cases. Results: The plans created manually achieve the protocol objectives. The protocol objectives are the same as the RTOG1005, and the DHV curves look clinically acceptable. Conclusions: Despite the O-ring Linac doesn´t have the capacity to obtain kv images, the cone beam CT was created using MV energy, the dose delivered by the daily image setup process still without affect the dosimetric quality of the plans, and the dose distribution is acceptable achieving the protocol objectives.

Keywords: hypofrationation, VMAT, chestwall, radiotherapy planning

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194 Effect of Cutting Tools and Working Conditions on the Machinability of Ti-6Al-4V Using Vegetable Oil-Based Cutting Fluids

Authors: S. Gariani, I. Shyha

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Cutting titanium alloys are usually accompanied with low productivity, poor surface quality, short tool life and high machining costs. This is due to the excessive generation of heat at the cutting zone and difficulties in heat dissipation due to relatively low heat conductivity of this metal. The cooling applications in machining processes are crucial as many operations cannot be performed efficiently without cooling. Improving machinability, increasing productivity, enhancing surface integrity and part accuracy are the main advantages of cutting fluids. Conventional fluids such as mineral oil-based, synthetic and semi-synthetic are the most common cutting fluids in the machining industry. Although, these cutting fluids are beneficial in the industries, they pose a great threat to human health and ecosystem. Vegetable oils (VOs) are being investigated as a potential source of environmentally favourable lubricants, due to a combination of biodegradability, good lubricous properties, low toxicity, high flash points, low volatility, high viscosity indices and thermal stability. Fatty acids of vegetable oils are known to provide thick, strong, and durable lubricant films. These strong lubricating films give the vegetable oil base stock a greater capability to absorb pressure and high load carrying capacity. This paper details preliminary experimental results when turning Ti-6Al-4V. The impact of various VO-based cutting fluids, cutting tool materials, working conditions was investigated. The full factorial experimental design was employed involving 24 tests to evaluate the influence of process variables on average surface roughness (Ra), tool wear and chip formation. In general, Ra varied between 0.5 and 1.56 µm and Vasco1000 cutting fluid presented comparable performance with other fluids in terms of surface roughness while uncoated coarse grain WC carbide tool achieved lower flank wear at all cutting speeds. On the other hand, all tools tips were subjected to uniform flank wear during whole cutting trails. Additionally, formed chip thickness ranged between 0.1 and 0.14 mm with a noticeable decrease in chip size when higher cutting speed was used.

Keywords: cutting fluids, turning, Ti-6Al-4V, vegetable oils, working conditions

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193 Sustainable Production of Algae through Nutrient Recovery in the Biofuel Conversion Process

Authors: Bagnoud-Velásquez Mariluz, Damergi Eya, Grandjean Dominique, Frédéric Vogel, Ludwig Christian

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The sustainability of algae to biofuel processes is seriously affected by the energy intensive production of fertilizers. Large amounts of nitrogen and phosphorus are required for a large-scale production resulting in many cases in a negative impact of the limited mineral resources. In order to meet the algal bioenergy opportunity it appears crucial the promotion of processes applying a nutrient recovery and/or making use of renewable sources including waste. Hydrothermal (HT) conversion is a promising and suitable technology for microalgae to generate biofuels. Besides the fact that water is used as a “green” reactant and solvent and that no biomass drying is required, the technology offers a great potential for nutrient recycling. This study evaluated the possibility to treat the water HT effluent by the growth of microalgae while producing renewable algal biomass. As already demonstrated in previous works by the authors, the HT aqueous product besides having N, P and other important nutrients, presents a small fraction of organic compounds rarely studied. Therefore, extracted heteroaromatic compounds in the HT effluent were the target of the present research; they were profiled using GC-MS and LC-MS-MS. The results indicate the presence of cyclic amides, piperazinediones, amines and their derivatives. The most prominent nitrogenous organic compounds (NOC’s) in the extracts were carefully examined by their effect on microalgae, namely 2-pyrrolidinone and β-phenylethylamine (β-PEA). These two substances were prepared at three different concentrations (10, 50 and 150 ppm). This toxicity bioassay used three different microalgae strains: Phaeodactylum tricornutum, Chlorella sorokiniana and Scenedesmus vacuolatus. The confirmed IC50 was for all cases ca. 75ppm. Experimental conditions were set up for the growth of microalgae in the aqueous phase by adjusting the nitrogen concentration (the key nutrient for algae) to fit that one established for a known commercial medium. The values of specific NOC’s were lowered at concentrations of 8.5 mg/L 2-pyrrolidinone; 1mg/L δ-valerolactam and 0.5 mg/L β-PEA. The growth with the diluted HT solution was kept constant with no inhibition evidence. An additional ongoing test is addressing the possibility to apply an integrated water cleanup step making use of the existent hydrothermal catalytic facility.

Keywords: hydrothermal process, microalgae, nitrogenous organic compounds, nutrient recovery, renewable biomass

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192 Wastewater Treatment in the Abrasives Industry via Fenton and Photo-Fenton Oxidation Processes: A Case Study from Peru

Authors: Hernan Arturo Blas López, Gustavo Henndel Lopes, Antonio Carlos Silva Costa Teixeira, Carmen Elena Flores Barreda, Patricia Araujo Pantoja

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Phenols are toxic for life and the environment and may come from many sources. Uncured phenolic monomers present in phenolic resins used as binders in grinding wheels and emery paper can contaminate industrial wastewaters in abrasives manufacture plants. Furthermore, vestiges of resol and novolacs resins generated by wear and tear of abrasives are also possible sources of water contamination by phenolics in these facilities. Fortunately, advanced oxidation by dark Fenton and photo-Fenton techniques are capable of oxidizing phenols and their degradation products up to their mineralization into H₂O and CO₂. The maximal allowable concentrations for phenols in Peruvian waterbodies is very low, such that insufficiently treated effluents from the abrasives industry are a potential environmental noncompliance. The current case study highlights findings obtained during the lab-scale application of Fenton’s and photo-assisted Fenton’s chemistries to real industrial wastewater samples from an abrasives manufacture plant in Peru. The goal was to reduce the phenolic content and sample toxicity. For this purpose, two independent variables-reaction time and effect of ultraviolet radiation–were studied as for their impacts on the concentration of total phenols, total organic carbon (TOC), biological oxygen demand (BOD) and chemical oxygen demand (COD). In this study, diluted samples (1 L) of the industrial effluent were treated with Fenton’s reagent (H₂O₂ and Fe²⁺ from FeSO₄.H₂O) during 10 min in a photochemical batch reactor (Alphatec RFS-500, Brazil) at pH 2.92. In the case of photo-Fenton tests with ultraviolet lamps of 9 W, UV-A, UV-B and UV-C lamps were evaluated. All process conditions achieved 100% of phenols degraded within 5 minutes. TOC, BOD and COD decreased by 49%, 52% and 86% respectively (all processes together). However, Fenton treatment was not capable of reducing BOD, COD and TOC below a certain value even after 10 minutes, contrarily to photo-Fenton. It was also possible to conclude that the processes here studied degrade other compounds in addition to phenols, what is an advantage. In all cases, elevated effluent dilution factors and high amounts of oxidant agent impact negatively the overall economy of the processes here investigated.

Keywords: fenton oxidation, wastewater treatment, phenols, abrasives industry

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191 Factors Associated with Pesticides Used and Plasma Cholinesterase Level among Agricultural Workers in Rural Area, Thailand

Authors: Pirakorn Sukonthaman, Paphitchaya Temphattharachok, Warangkana Thammasanya, Kraichart Tantrakarnarpa, Tanongson Tientavorn

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Agriculture is the main occupation in Thailand. Excessive amount of pesticides are used to increase the products but are toxic to human body. In 2009, Bureau of Epidemiology received 1,691 cases reported with pesticides toxicity (2.66:100,000) which 10.61 % of them is caused by Organophosphate. The purposes are to find factors associated with pesticides used and plasma cholinesterase level and other emerging issues that previous studies did not explain among agricultural workers in Baan Na Yao, Chachoengsao, Thailand. This research was an exploratory mixed method study. Qualitative interviews and quantitative questionnaires were used together in order to gather information from the agricultural workers (mainly cassava and rice farming) directly exposed to pesticides within 2 months simultaneously. Qualitative participants were selected by purposive sampling and a total survey for quantitative ones. The quantitative data was statistically analyzed by using multiple logistic regression model. Qualitative data was transcribed verbatim and thematically analyzed. For qualitative study, 15 participants were interviewed and 300/323 participants (92.88%) were given questionnaires, of which were 175 male and 125 female and 113 among them were spraymen. The prevalence of abnormal plasma cholinesterase level was 92.28% (Safe 7.72% Risky 49.33% and Unsafe 42.95%). Participants with inappropriate behaviors during spraying had a significant association with plasma cholinesterase level (95%CI=1.399-14.858) but other factors such as age, gender, education, attitude and knowledge had no association. They also had encountered various symptoms from pesticides such as fatigue (61%), vertigo (59.67%) and headache (58.86%), etc. Although they had high knowledge and attitude they still had poor behaviors. Moreover, our qualitative component showed that though they had worn the personal protective equipment (PPE) regularly, their PPE was not standard. Not only substandard PPE, but also there were obstacles of wearing such as the hot climate and inconvenience. They misunderstood their symptoms from using pesticides as allergy. Therefore, they did not seek for proper medical check-ups and treatment. This research revealed almost all of the participants have abnormal levels of plasma cholinesterase related especially those with poor behaviors. They also wore PPE but inadequately and misunderstood the symptoms produced by organophosphate use as allergy. Therefore, they did not seek for medical treatment. Occupation health education, modification of PPE and periodic medical checking are ways to make agricultural workers concern and know if there is any progression in a long term.

Keywords: pesticides, plasma cholinesterase level, spraymen, agricultural workers

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190 Application of Zeolite Nanoparticles in Biomedical Optics

Authors: Vladimir Hovhannisyan, Chen Yuan Dong

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Recently nanoparticles (NPs) have been introduced in biomedicine as effective agents for cancer-targeted drug delivery and noninvasive tissue imaging. The most important requirements to these agents are their non-toxicity, biocompatibility and stability. In view of these criteria, the zeolite (ZL) nanoparticles (NPs) may be considered as perfect candidates for biomedical applications. ZLs are crystalline aluminosilicates consisting of oxygen-sharing SiO4 and AlO4 tetrahedral groups united by common vertices in three-dimensional framework and containing pores with diameters from 0.3 to 1.2 nm. Generally, the behavior and physical properties of ZLs are studied by SEM, X-ray spectroscopy, and AFM, whereas optical spectroscopic and microscopic approaches are not effective enough, because of strong scattering in common ZL bulk materials and powders. The light scattering can be reduced by using of ZL NPs. ZL NPs have large external surface area, high dispersibility in both aqueous and organic solutions, high photo- and thermal stability, and exceptional ability to adsorb various molecules and atoms in their nanopores. In this report, using multiphoton microscopy and nonlinear spectroscopy, we investigate nonlinear optical properties of clinoptilolite type of ZL micro- and nanoparticles with average diameters of 2200 nm and 240 nm, correspondingly. Multiphoton imaging is achieved using a laser scanning microscope system (LSM 510 META, Zeiss, Germany) coupled to a femtosecond titanium:sapphire laser (repetition rate- 80 MHz, pulse duration-120 fs, radiation wavelength- 720-820 nm) (Tsunami, Spectra-Physics, CA). Two Zeiss, Plan-Neofluar objectives (air immersion 20×∕NA 0.5 and water immersion 40×∕NA 1.2) are used for imaging. For the detection of the nonlinear response, we use two detection channels with 380-400 nm and 435-700 nm spectral bandwidths. We demonstrate that ZL micro- and nanoparticles can produce nonlinear optical response under the near-infrared femtosecond laser excitation. The interaction of hypericine, chlorin e6 and other dyes with ZL NPs and their photodynamic activity is investigated. Particularly, multiphoton imaging shows that individual ZL NPs particles adsorb Zn-tetraporphyrin molecules, but do not adsorb fluorescein molecules. In addition, nonlinear spectral properties of ZL NPs in native biotissues are studied. Nonlinear microscopy and spectroscopy may open new perspectives in the research and application of ZL NP in biomedicine, and the results may help to introduce novel approaches into the clinical environment.

Keywords: multiphoton microscopy, nanoparticles, nonlinear optics, zeolite

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189 Curcumin-Loaded Pickering Emulsion Stabilized by pH-Induced Self-Aggregated Chitosan Particles for Encapsulating Bioactive Compounds for Food, Flavor/Fragrance, Cosmetics, and Medicine

Authors: Rizwan Ahmed Bhutto, Noor ul ain Hira Bhutto, Mingwei Wang, Shahid Iqbal, Jiang Yi

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Curcumin, a natural polyphenolic compound, boasts numerous health benefits; however, its industrial applications are hindered by instabilities and poor solubility. Encapsulating curcumin in Pickering emulsion presents a promising strategy to enhance its bioavailability. Yet, the development of an efficient and straightforward method to fabricate a natural emulsifier for Pickering emulsion poses a significant challenge. Chitosan has garnered attention due to its non-toxicity and excellent emulsifying properties. This study aimed to prepare four distinct types of self-aggregated chitosan particles using a pH-responsive self-assembling approach. The properties of the aggregated particles were adjusted by pH, degree of deacetylation (DDA), and molecular weight (MW), thereby controlling surface charge, size (ranging from nano to micro and floc), and contact angle. Pickering emulsions were then formulated using these various aggregated particles. As MW and pH increased and DDA decreased, the networked structures of the aggregated particles formed, resulting in highly elastic gels that were more resistant to the breakdown of Pickering emulsion at ambient temperature. With elevated temperatures, the kinetic energy of the aggregated particles increased, disrupting hydrogen bonds and potentially transforming the systems from fluids to gels. The Pickering emulsion based on aggregated particles served as a carrier for curcumin encapsulation. It was observed that DDA and MW played crucial roles in regulating drug loading, encapsulation efficiency, and release profile. This research sheds light on selecting suitable chitosan for controlling the release of bioactive compounds in Pickering emulsions, considering factors such as adjustable rheological properties, microstructure, and macrostructure. Furthermore, this study introduces an environmentally friendly and cost-effective synthesis of pH-responsive aggregate particles without the need for high-pressure homogenizers. It underscores the potential of aggregate particles with various MWs and DDAs for encapsulating other bioactive compounds, offering valuable applications in industries including food, flavor/fragrance, cosmetics, and medicine.

Keywords: chitosan, molecular weight, rheological properties, curcumin encapsulation

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188 Pyrazolylpyrazolines: Design, Synthesis and Biological Evaluation as Dual Acting Antimalarial-Antileishmanial Agents

Authors: Adnan Bekhit, Eskedar Lodebo, Ariaya Hymete, Hanan Ragab, Alaa El-Din Bekhit

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Malaria and leishmaniasis have emerged as serious universal health problems throughout history of mankind. According to the WHO 2008 malarial report, half of the world population is at risk of malarial infection with an estimate of 1 million deaths occurring annually mainly in the African region. Furthermore, 12-15 million people are infected with Leishmaniasis worldwide. Despite the continuous introduction of a large number of agents for the treatment of malaria, there is still unmet medical needs due to the emergence of resistance. Resistance has occurred for almost all therapeutic agents approved for the treatment of malaria. Accordingly, it was the aim of this work to design and synthesis a group of antimalarial-antileshmanial agents that would show inhibitory activity against chloroquine-resistant strain of Plasmodium falciparum. The synthesized compounds were designed to contain a pyrazolylpyrazoline moiety having an aromatic group (p-tolyl or p-chlorophenyl) at N1-position of one pyrazoline ring due to the reports of promising activities of such compounds. A formyl or acyl substituent was introduced at the N1-position of the other pyrazoline ring, to investigate the effect of bulkiness of acyl substituents at this position. The synthesized compounds were evaluated for their in-vivo antimalarial activity against Plasmodium berghei infected mice at dose levels of 20 and 30 mg/Kg. the two most active compounds were evaluated for their antimalarial activity against chloroquin-resistant strain (RKL9) of Plasmodium falciparum. In addition, the synthesized compounds were tested for their in-vitro antileshmanial activity against Leishmania aethiopica promastigotes and amastigotes. For both antimalarial and antileishmanial activities, compounds having an N1-p-tolyl group at the first pyrazoline ring did not require bulkiness at the second pyrazoline ring nitrogen where the compound bearing an acetyl group proved to be the most active of the whole series. On the other hand, bulkiness at the N1-position of the second pyazoline ring was necessary in case of compounds carrying the p-chlorophenyl group, where the two derivatives having an N1-butanoyl and an N1-benzoyl moieties at the second pyrazoline showed the best activity. Furthermore, the toxicity of the active compounds were tested and were proved to be non-toxic at 125, 250 and 500 mg/Kg. In addition, docking of the most active compound (having a p-tolyl group at the first pyrazoline-N and an acetyl moiety on the other pyrazoline-N) was performed against dihydrofolate reductase enzyme.

Keywords: pyrazoline derivatives, in-vivo antimalarial activity, docking, dihydrofolate reductase

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187 Phytochemical Screening and Assessment of Hepatoprotective Activity of Geigeria alata Leaves Ethanolic Extract on Wistar Rats

Authors: Girgis Younan, Ikram Eltayeb

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Geigeria alata belongs to the family Asteraceae, is an effective plant traditionally used in Sudan as a therapy for hepatic disease and as an antiepileptic, antispasmodic and to treat cough and intestinal complaints.The liver is responsible for many critical functions within the body and any liver disease or injury will result in the loss of those functions leading to significant damage in the body. Liver diseases cause increase in liver enzymes (AST, ALP ALT) and total bilirubin and a decrease in total blood protein level. The objective of this study is to investigate the hepato-protective activity of Geigeria alata leaves ethanolic extract. The plant leaves were extracted using 96% ethanol using Soxhlet apparatus. The hepatoprotective effect was determined using 25 wistar rats, the rats was divided to 5 groups, each group contain 5 rats: [Normal control group] receiving purified water, liver damage was induced in wistar rats by administering a 1:1 (v/v) mixture of CCl4 (1.25 ml/kg) and olive oil once at day four of the experiment [negative control group]. Two doses of extract [400mg/kg and 200mg/kg] was applied daily for 7 days, and standard drug Silymarin (200 mg/kg) were administered daily for 7 days to CCl4-treated rats. The degree of hepato-protective activity was evaluated by determining the hepatic marker enzymes AST, ALP, ALT, total Bilirubin and total proteins (TP). Results have shown that, the extract of G.alata leaves reduced the level of liver enzymes ALT, AST, ALP, total bilirubin and increased the level of total proteins. Since the levels of liver enzymes; bilirubin and total protein are considered as markers of liver function, the extract has proven to reduce the detrimental effects of liver toxicity induced using CCl4. The hepato-protective effect of extract on liver was found to be dose dependent, where the 400mg/kg dose of the extract exhibited higher activity than 200mg/kg dose. In addition, the effect of the higher dose (400mg/kg) of the extract was found to be higher than Silymarin standard drug. The result concludes that, G.alata leaves extract was found to exhibit profound hepato-protective activity, which justifies the traditional use of the plant for the treatment of hepatic diseases.

Keywords: alata, extract, geigeria, hepatoprotective

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186 Toxin-Producing Algae of Nigerian Coast, Gulf of Guinea

Authors: Medina O. Kadiri, Jeffrey U. Ogbebor

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Toxin-producing algae are algal species that produce potent toxins, which accumulate in food chains and cause various gastrointestinal and neurological illnesses in humans and other animals. They result in shellfish toxicity, ecosystem alteration, cause fish kills and mortality of other animals and humans, in addition to compromised product quality as well as decreased consumer confidence. Animals, including man, are directly exposed to toxins by absorbing toxins from the water via swimming, drinking water with toxins, or ingestion of algal species via feeding on contaminated seafood. These toxins, algal toxins, undergo bioaccumulation, biotransformation, biotransferrence, and biomagnification through the natural food chains and food webs, thereby endangering animals and humans. The Nigerian coast is situated on the Atlantic Ocean, the Gulf of Guinea, one of Africa’s five large marine ecosystems (LME), and studies on toxic algae in this ecosystem are generally lacking. Algal samples were collected from eight coastal states and ten locations spanning the Bight of Bonny and the Bight of Benin. A total of 70 species of toxin-producing algae were found in the coastal waters of Nigeria. There was a great variety of toxin-producing algae in the coastal waters of Nigeria. They were Domoic acid-producing forms (DSP), Saxitoxin-producing, Gonyautoxin-producing, and Yessotoxin-producing (all PSP). Others were Okadaic acid-producing, Dinophysistoxin-producing, and Palytoxin-producing, which are representatives of DSP; CFP was represented by Ciguatoxin-producing forms and NSP by Brevitoxin-producing species. Emerging or new toxins are comprising of Gymnodimines, Spirolides, Palytoxins, and Prorocentrolidess-producing algae. The CyanoToxin Poisoning (CTP) was represented by Anatoxin-, Microcystin-, Cylindrospermopsis-Lyngbyatoxin-, Nordularin-Applyssiatoxin and Debromoapplatoxin-producing species. The highest group was the Saxitoxin-producing species, followed by Microcystin-producing species, then Anatoxin-producing species. Gonyautoxin (PSP), Palytoxin (DSP), Emerging toxins, and Cylindrospermopsin -producing species had a very substantial representation. Only Ciguatoxin-producing species, Lyngbyatoxin-Nordularin, Applyssiatoxin, and Debromoapplatoxin-producing species were represented by one taxon each. The presence of such overwhelming diversity of toxin-producing algae on the Nigerian coast is a source of concern for fisheries, aquaculture, human health, and ecosystem services. Therefore routine monitoring of toxic and harmful algae is greatly recommended.

Keywords: algal syndromes, Atlantic Ocean, harmful algae, Nigeria

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185 Anti-Phospholipid Antibody Syndrome Presenting with Seizure, Stroke and Atrial Mass: A Case Report

Authors: Rajish Shil, Amal Alduhoori, Vipin Thomachan, Jamal Teir, Radhakrishnan Renganathan

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Background: Antiphospholipid antibody syndrome (APS) has a broad spectrum of thrombotic and non-thrombotic clinical manifestations. We present a case of APS presenting with seizure, stroke, and atrial mass. Case Description: A 38-year-old male presented with headache of 10 days duration and tonic-clonic seizure. The neurological examination was normal. Magnetic resonance imaging of brain showed small acute right cerebellar infarct. Magnetic resonance angiography of brain and neck showed a focal narrowing in the origin of the internal carotid artery bilaterally. Electroencephalogram was normal. He was started on aspirin, atorvastatin, and carbamazepine. Transthoracic and trans-esophageal echocardiography showed a pedunculated and lobular atrial mass, measuring 1 X 1.5 cm, which was freely mobile across mitral valve opening across the left ventricular inflow. Autoimmune screening showed positive Antiphospholipid antibodies in high titer (Cardiolipin IgG > 120 units/ml, B2 glycoprotein IgG 90 units/mL). Anti-nuclear antibody was negative. Erythrocyte sedimentation rate and C-reactive protein levels were normal. Platelet count was low (111 x 109/L). The patient underwent successful surgical removal of the mass, which looked like a thrombotic clot, and Histopathological analysis confirmed it as a fibrinous clot, with no evidence of tumor cells. The patient was started on full anticoagulation treatment and was followed up regularly in the clinic, where our patient did not have any further complications from the disease. Discussion: Our patient was diagnosed to have APS based on the features of high positive anticardiolipin antibody IgG and B2 glycoprotein IgG levels, Stroke, thrombocytopenia, and abnormal echo findings. Thrombotic vegetation can mimic an atrial myxoma on echo. Conclusion: APS can present with neurological and cardiac manifestations, and therefore a high index of suspicion is necessary for a diagnosis of the disease as it can affect both short and long term treatment plans and prognosis. Therefore, in patients presenting with neurological symptoms like seizures, weakness and radiological diagnosis of stroke in a young patient, where atrial masses could be thought to be the cause of stroke, they should be screened for any concomitant findings of thrombocytopenia and/or activated partial thromboplastin time prolongation, which should raise the suspicion of vasculitis, specifically APS to be the primary cause of the clinical presentation.

Keywords: antiphospholipid syndrome, seizures, atrial mass, stroke

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184 Perovskite Nanocrystals and Quantum Dots: Advancements in Light-Harvesting Capabilities for Photovoltaic Technologies

Authors: Mehrnaz Mostafavi

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Perovskite nanocrystals and quantum dots have emerged as leaders in the field of photovoltaic technologies, demonstrating exceptional light-harvesting abilities and stability. This study investigates the substantial progress and potential of these nano-sized materials in transforming solar energy conversion. The research delves into the foundational characteristics and production methods of perovskite nanocrystals and quantum dots, elucidating their distinct optical and electronic properties that render them well-suited for photovoltaic applications. Specifically, it examines their outstanding light absorption capabilities, enabling more effective utilization of a wider solar spectrum compared to traditional silicon-based solar cells. Furthermore, this paper explores the improved durability achieved in perovskite nanocrystals and quantum dots, overcoming previous challenges related to degradation and inconsistent performance. Recent advancements in material engineering and techniques for surface passivation have significantly contributed to enhancing the long-term stability of these nanomaterials, making them more commercially feasible for solar cell usage. The study also delves into the advancements in device designs that incorporate perovskite nanocrystals and quantum dots. Innovative strategies, such as tandem solar cells and hybrid structures integrating these nanomaterials with conventional photovoltaic technologies, are discussed. These approaches highlight synergistic effects that boost efficiency and performance. Additionally, this paper addresses ongoing challenges and research endeavors aimed at further improving the efficiency, stability, and scalability of perovskite nanocrystals and quantum dots in photovoltaics. Efforts to mitigate concerns related to material degradation, toxicity, and large-scale production are actively pursued, paving the way for broader commercial application. In conclusion, this paper emphasizes the significant role played by perovskite nanocrystals and quantum dots in advancing photovoltaic technologies. Their exceptional light-harvesting capabilities, combined with increased stability, promise a bright future for next-generation solar cells, ushering in an era of highly efficient and cost-effective solar energy conversion systems.

Keywords: perovskite nanocrystals, quantum dots, photovoltaic technologies, light-harvesting, solar energy conversion, stability, device designs

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183 The Interventricular Septum as a Site for Implantation of Electrocardiac Devices - Clinical Implications of Topography and Variation in Position

Authors: Marcin Jakiel, Maria Kurek, Karolina Gutkowska, Sylwia Sanakiewicz, Dominika Stolarczyk, Jakub Batko, Rafał Jakiel, Mateusz K. Hołda

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Proper imaging of the interventricular septum during endocavital lead implantation is essential for successful procedure. The interventricular septum is located oblique to the 3 main body planes and forms angles of 44.56° ± 7.81°, 45.44° ± 7.81°, 62.49° (IQR 58.84° - 68.39°) with the sagittal, frontal and transverse planes, respectively. The optimal left anterior oblique (LAO) projection is to have the septum aligned along the radiation beam and will be obtained for an angle of 53.24° ± 9,08°, while the best visualization of the septal surface in the right anterior oblique (RAO) projection is obtained by using an angle of 45.44° ± 7.81°. In addition, the RAO angle (p=0.003) and the septal slope to the transverse plane (p=0.002) are larger in the male group, but the LAO angle (p=0.003) and the dihedral angle that the septum forms with the sagittal plane (p=0.003) are smaller, compared to the female group. Analyzing the optimal RAO angle in cross-sections lying at the level of the connections of the septum with the free wall of the right ventricle from the front and back, we obtain slightly smaller angle values, i.e. 41.11° ± 8.51° and 43.94° ± 7.22°, respectively. As the septum is directed leftward in the apical region, the optimal RAO angle for this area decreases (16.49° ± 7,07°) and does not show significant differences between the male and female groups (p=0.23). Within the right ventricular apex, there is a cavity formed by the apical segment of the interventricular septum and the free wall of the right ventricle with a depth of 12.35mm (IQR 11.07mm - 13.51mm). The length of the septum measured in longitudinal section, containing 4 heart cavities, is 73.03mm ± 8.06mm. With the left ventricular septal wall formed by the interventricular septum in the apical region at a length of 10.06mm (IQR 8.86 - 11.07mm) already lies outside the right ventricle. Both mentioned lengths are significantly larger in the male group (p<0.001). For proper imaging of the septum from the right ventricular side, an oblique position of the visualization devices is necessary. Correct determination of the RAO and LAO angle during the procedure allows to improve the procedure performed, and possible modification of the visual field when moving in the anterior, posterior and apical directions of the septum will avoid complications. Overlooking the change in the direction of the interventricular septum in the apical region and a significant decrease in the RAO angle can result in implantation of the lead into the free wall of the right ventricle with less effective pacing and even complications such as wall perforation and cardiac tamponade. The demonstrated gender differences can also be helpful in setting the right projections. A necessary addition to the analysis will be a description of the area of the ventricular septum, which we are currently working on using autopsy material.

Keywords: anatomical variability, angle, electrocardiological procedure, intervetricular septum

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182 Synthesis and Catalytic Activity of N-Heterocyclic Carbene Copper Catalysts Supported on Magnetic Nanoparticles

Authors: Iwona Misztalewska-Turkowicz, Agnieszka Z. Wilczewska, Karolina H. Markiewicz

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Carbenes - species which possess neutral carbon atom with two shared and two unshared valence electrons, are known for their high reactivity and instability. Nevertheless, it is also known, that some carbenes i.e. N-heterocyclic carbenes (NHCs), can form stable crystals. The usability of NHCs in organic synthesis was studied. Due to their exceptional properties (high nucleophilicity) NHCs are commonly used as organocatalysts and also as ligands in transition metal complexes. NHC ligands possess better electron-donating properties than phosphines. Moreover, they exhibit lower toxicity. Due to these features, phosphines are frequently replaced by NHC ligands. In this research is discussed the synthesis of five-membered NHCs which are mainly obtained by deprotonation of azolium salts, e.g., imidazolium or imidazolinium salts. Some of them are immobilized on a solid support what leads to formation of heterogeneous, recyclable catalysts. Magnetic nanoparticles (MNPs) are often used as a solid support for catalysts. MNPs can be easily separated from the reaction mixture using an external magnetic field. Due to their low size and high surface to volume ratio, they are a good choice for immobilization of catalysts. Herein is presented synthesis of N-heterocyclic carbene copper complexes directly on the surface of magnetic nanoparticles. Formation of four different catalysts is discussed. They vary in copper oxidation state (Cu(I) and Cu(II)) and structure of NHC ligand. Catalysts were tested in Huisgen reaction, a type of copper catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Huisgen reaction represents one of the few universal and highly efficient reactions in which 1,2,3-triazoles can be obtained. The catalytic activity of all synthesized catalysts was compared with activity of commercially available ones. Different reaction conditions (solvent, temperature, the addition of reductant) and reusability of the obtained catalysts were investigated and are discussed. The project was financially supported by National Science Centre, Poland, grant no. 2016/21/N/ST5/01316. Analyses were performed in Centre of Synthesis and Analyses BioNanoTechno of University of Bialystok. The equipment in the Centre of Synthesis and Analysis BioNanoTechno of University of Bialystok was funded by EU, as a part of the Operational Program Development of Eastern Poland 2007-2013, project: POPW.01.03.00-20-034/09-00 and POPW.01.03.00-20-004/11.

Keywords: N-heterocyclic carbenes, click reaction, magnetic nanoparticles, copper catalysts

Procedia PDF Downloads 154
181 Muscle and Cerebral Regional Oxygenation in Preterm Infants with Shock Using Near-Infrared Spectroscopy

Authors: Virany Diana, Martono Tri Utomo, Risa Etika

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Background: Shock is one severe condition that can be a major cause of morbidity and mortality in the Neonatal Intensive Care Unit. Preterm infants are very susceptible to shock caused by many complications such as asphyxia, patent ductus arteriosus, intra ventricle haemorrhage, necrotizing enterocolitis, persistent pulmonal hypertension of the newborn, and septicaemia. Limited hemodynamic monitoring for early detection of shock causes delayed intervention and comprises the outcomes. Clinical parameters still used in neonatal shock detection, such as Capillary Refill Time, heart rate, cold extremity, and urine production. Blood pressure is most frequently used to evaluate preterm's circulation, but hypotension indicates uncompensated shock. Near-infrared spectroscopy (NIRS) is known as a noninvasive tool for monitoring and detecting the state of inadequate tissue perfusion. Muscle oxygen saturation shows decreased cardiac output earlier than systemic parameters of tissue oxygenation when cerebral regional oxygen saturation is still stabilized by autoregulation. However, to our best knowledge, until now, no study has analyzed the decrease of muscle oxygen regional saturation (mRSO₂) and the ratio of muscle and cerebral oxygen regional saturation (mRSO₂/cRSO₂) by NIRS in preterm with shock. Purpose: The purpose of this study is to analyze the decrease of mRSO₂ and ratio of muscle to cerebral oxygen regional saturation (mRSO₂/cRSO₂) by NIRS in preterm with shock. Patients and Methods: This cross-sectional study was conducted on preterm infants with 28-34 weeks gestational age, admitted to the NICU of Dr. Soetomo Hospital from November to January 2022. Patients were classified into two groups: shock and non-shock. The diagnosis of shock is based on clinical criteria (tachycardia, prolonged CRT, cold extremity, decreased urine production, and MAP Blood Pressure less than GA in weeks). Measurement of mRSO₂ and cRSO₂ by NIRS was performed by the doctor in charge when the patient came to NICU. Results: We enrolled 40 preterm infants. The initial conventional hemodynamic parameter as the basic diagnosis of shock showed significant differences in all variables. Preterm with shock had higher mean HR (186.45±1.5), lower MAP (29.8±2.1), and lower SBP (45.1±4.28) than non-shock children, and most had a prolonged CRT. The patients’ outcome was not a significant difference between shock and non-shock patients. The mean mRSO₂ in the shock and non-shock groups were 33,65 ± 11,32 vs. 69,15 ± 3,96 (p=0.001), and the mean ratio mRSO₂/cRSO₂ 0,45 ± 0,12 vs. 0,84 ± 0,43 (p=0,001), were significantly different. The mean cRSO₂ in the shock and non-shock groups were 71,60 ± 4,90 vs. 81,85 ± 7,85 (p 0.082), not significantly different. Conclusion: The decrease of mRSO₂ and ratio of mRSO₂/cRSO₂ can differentiate between shock and non-shock in the preterm infant when cRSO₂ is still normal.

Keywords: preterm infant, regional muscle oxygen saturation, regional cerebral oxygen saturation, NIRS, shock

Procedia PDF Downloads 89
180 Anti-Neuroinflammatory and Anti-Apoptotic Efficacy of Equol, against Lipopolysaccharide Activated Microglia and Its Neurotoxicity

Authors: Lalita Subedi, Jae Kyoung Chae, Yong Un Park, Cho Kyo Hee, Lee Jae Hyuk, Kang Min Cheol, Sun Yeou Kim

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Neuroinflammation may mediate the relationship between low levels of estrogens and neurodegenerative disease. Estrogens are neuroprotective and anti-inflammatory in neurodegenerative disease models. Due to the long term side effects of estrogens, researches have been focused on finding an effective phytoestrogens for biological activities. Daidzein present in soybeans and its active metabolite equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) bears strong antioxidant and anticancer showed more potent anti-inflammatory and neuroprotective role in neuroinflammatory model confirmed its in vitro activity with molecular mechanism through NF-κB pathway. Three major CNS cells Microglia (BV-2), Astrocyte (C6), Neuron (N2a) were used to find the effect of equol in inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), MAPKs signaling proteins, apoptosis related proteins by western blot analysis. Nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Gries method and ELISA, respectively. Cytokines like tumor necrosis factor-α (TNF-α) and IL-6 were also measured in the conditioned medium of LPS activated cells with or without equol. Equol inhibited the NO production, PGE-2 production and expression of COX-2 and iNOS in LPS-stimulated microglial cells at a dose dependent without any cellular toxicity. At the same time Equol also showed promising effect in modulation of MAPK’s and nuclear factor kappa B (NF-κB) expression with significant inhibition of the production of proinflammatory cytokine like interleukin -6 (IL-6), and tumor necrosis factor -α (TNF-α). Additionally, it inhibited the LPS activated microglia-induced neuronal cell death by downregulating the apoptotic phenomenon in neuronal cells. Furthermore, equol increases the production of neurotrophins like NGF and increase the neurite outgrowth as well. In conclusion the natural daidzein metabolite equol are more active than daidzein, which showed a promising effectiveness as an anti-neuroinflammatory and neuroprotective agent via downregulating the LPS stimulated microglial activation and neuronal apoptosis. This work was supported by Brain Korea 21 Plus project and High Value-added Food Technology Development Program 114006-4, Ministry of Agriculture, Food and Rural Affairs.

Keywords: apoptosis, equol, neuroinflammation, phytoestrogen

Procedia PDF Downloads 359
179 Bioefficacy of Ocimum sanctum on Survival, Development and Reproduction of Dengue Vector Aedes aegypti L. (Diptera: Culicidae)

Authors: Mohd Shazad, K. K. Gupta

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Vector borne diseases are a serious global concern. Aedes aegypti, the primary vector for viruses that cause dengue fever, dengue haemorrhagic fever, chikungunya and yellow fever is widespread over large areas of the tropics and subtropics. In last decade, diseases transmitted by Aedes aegypti are of serious concern. In past decade, number of cases of dengue fever, dengue hemorrhagic fever, and chikungunya has increased multifold. Present research work focused on impact of ethanol extract of Ocimum sanctum on dengue vector Aedes aegypti. 0-24 hr. old fourth instar larvae of lab-bred population of Aedes aegypti were exposed to ethanol leaf extract of Ocimum with concentrations ranging from 50 ppm to 400 ppm. Survival and development and the treated larvae and reproductive behaviour of the adults emerged from the treated larvae was evaluated. Our results indicated larvicidal potential of the leaf ethanol extract. The influence of the extract was dose dependent. 77.2% mortality was observed in the larvae exposed to 400 ppm for 24 hr. Treatment at lower concentrations revealed delayed toxicity. The larvae survived after treatment showed severe developmental anomalies. Consequently, there was the significant increase in duration of fourth instar larva. The L4 treated with 400-ppm extract moulted after 4.6 days; this was in sharp contrast to control where the larval period of the fourth instar lasts three days. The treated fourth instar larvae in many cases transformed into larva-pupa intermediates with the combination of larva, pupa characters. The larva-pupa intermediates had reduced life span and failed to moult successfully. The adults emerged from the larvae treated with lower doses had reduced reproductive potential. The females exhibited longer preoviposition period, reduced oviposition rate, abnormal oviposition behaviour and decreased fertility. Our studies indicated the possibility of the presence of JH mimic or JH analogue in the leaf ethanol extract of Ocimum. The present research work explored the potentials of Ocimum sanctum, also known as the queen of herbs, in integrated vector management programme of Aedes aegypti, which is a serious threat to human health.

Keywords: Aedes aegypti, development, mortality, Ocimum sanctum reproduction

Procedia PDF Downloads 240
178 The Awareness of Cardiovascular Diseases among General Population in Western Regions of Saudi Arabia

Authors: Ali Saeed Alghamdi, Basel Mazen Alsolami, Basel Saeed Alghamdi, Muhanad Saleh Alzahrani Alamri, Salman Anwar Thabet, Abdulhalim J. Kinsara

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Objectives: This study measures the knowledge of the cardiovascular disease among the general population in western regions of Saudi Arabia, and it aimed to increase the level of awareness about cardiovascular diseases among the general population by providing an awareness lecture that included information about the risk factors, major symptoms, and prevention of cardiovascular diseases. The lecture has been attached at the end of the questionnaire. Setting: This study was conducted through an online questionnaire that included our aim and main objectives that targeted the general population in the Western regions of Saudi Arabia (Makkah and Madinah regions). Participants: This study participants were 460 collected through an online questionnaire. Methods: All Saudi citizens and residents who live in the western region of Saudi Arabia aged 18 years and above will be invited to participate voluntarily. A pre-structured questionnaire was designed to collect data on age, gender, marital status, education level, occupation, lifestyle habits, and history of heart diseases, with cardiac symptoms and risk factors sections. Results: The majority of respondents were females (74.8%) and Saudis. The knowledge about cardiovascular disease risk factors was weak. Only (18.5%) scores an excellent response regarding risk factors awareness. Lack of exercise, stress, and obesity were the most known risk factors. Regarding cardiovascular disease symptoms, chest pain scores the highest symptom (87.6%) among other symptoms like dyspnea, syncope, and excessive sweating. Participants revealed a poor awareness regarding cardiovascular disease symptoms also (0.9%). However, preventable factors for cardiovascular diseases were more knowledgeable than others categories in this study (60% fall into excellent knowledge). Smoking cessation, normal cholesterol level, and normal blood pressure score the highest preventable methods (92.2%), (88.6%), and (78.7%) respectively. 83.7% of the participant have attended the awareness lecture, and 99 of the attendees reported that the lecture increased their knowledge about cardiovascular disease. Conclusion: This study discussed the level of community awareness of cardiovascular disease in terms of symptoms, risk factors, and protective factors. We found a huge lack of the participant's level of knowledge about the disease and how to prevent it. Moreover, we measure the prevalence of the comorbidities among our participants (diabetes, hypertension, hypercholesterolemia/ hypertriglyceridemia) and their extent of adherence to their medication. In conclusion, this study not only demonstrates awareness of cardiovascular disease risk factors, symptoms, management, and the association between each domain but also provides educational material. Further educational material and campaigns are required to increase awareness and knowledge about cardiovascular diseases.

Keywords: awareness, cardiovascular diseases, education, prevention, risk factors

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177 Application of Free Living Nitrogen Fixing Bacteria to Increase Productivity of Potato in Field

Authors: Govinda Pathak

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In modern agriculture, the sustainable enhancement of crop productivity while minimizing environmental impacts remains a paramount challenge. Plant Growth Promoting Rhizobacteria (PGPR) have emerged as a promising solution to address this challenge. The rhizosphere, the dynamic interface between plant roots and soil, hosts intricate microbial interactions crucial for plant health and nutrient acquisition. PGPR, a subset of rhizospheric microorganisms, exhibit multifaceted beneficial effects on plants. Their abilities to stimulate growth, confer stress tolerance, enhance nutrient availability, and suppress pathogens make them invaluable contributors to sustainable agriculture. This work examines the pivotal role of free living nitrogen fixer in optimizing agricultural practices. We delve into the intricate mechanisms underlying PGPR-mediated plant-microbe interactions, encompassing quorum sensing, root exudate modulation, and signaling molecule exchange. Furthermore, we explore the diverse strategies employed by PGPR to enhance plant resilience against abiotic stresses such as drought, salinity, and metal toxicity. Additionally, we highlight the role of PGPR in augmenting nutrient acquisition and soil fertility through mechanisms such as nitrogen fixation, phosphorus solubilization, and mineral mobilization. Furthermore, we discuss the potential of PGPR in minimizing the reliance on chemical fertilizers and pesticides, thereby contributing to environmentally friendly agriculture. However, harnessing the full potential of PGPR requires a comprehensive understanding of their interactions with host plants and the surrounding microbial community. We also address challenges associated with PGPR application, including formulation, compatibility, and field efficacy. As the quest for sustainable agriculture intensifies, harnessing the remarkable attributes of PGPR offers a holistic approach to propel agricultural productivity while maintaining ecological balance. This work underscores the promising prospect of free living nitrogen fixer as a panacea for addressing critical agricultural challenges regarding chemical urea in an era of sustainable and resilient food production.

Keywords: PGPR, nitrogen fixer, quorum sensing, Rhizobacteria, pesticides

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176 Innovative Preparation Techniques: Boosting Oral Bioavailability of Phenylbutyric Acid Through Choline Salt-Based API-Ionic Liquids and Therapeutic Deep Eutectic Systems

Authors: Lin Po-Hsi, Sheu Ming-Thau

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Urea cycle disorders (UCD) are rare genetic metabolic disorders that compromise the body's urea cycle. Sodium phenylbutyrate (SPB) is a medication commonly administered in tablet or powder form to lower ammonia levels. Nonetheless, its high sodium content poses risks to sodium-sensitive UCD patients. This necessitates the creation of an alternative drug formulation to mitigate sodium load and optimize drug delivery for UCD patients. This study focused on crafting a novel oral drug formulation for UCD, leveraging choline bicarbonate and phenylbutyric acid. The active pharmaceutical ingredient-ionic liquids (API-ILs) and therapeutic deep eutectic systems (THEDES) were formed by combining these with choline chloride. These systems display characteristics like maintaining a liquid state at room temperature and exhibiting enhanced solubility. This in turn amplifies drug dissolution rate, permeability, and ultimately oral bioavailability. Incorporating choline-based phenylbutyric acid as a substitute for traditional SPB can effectively curtail the sodium load in UCD patients. Our in vitro dissolution experiments revealed that the ILs and DESs, synthesized using choline bicarbonate and choline chloride with phenylbutyric acid, surpassed commercial tablets in dissolution speed. Pharmacokinetic evaluations in SD rats indicated a notable uptick in the oral bioavailability of phenylbutyric acid, underscoring the efficacy of choline salt ILs in augmenting its bioavailability. Additional in vitro intestinal permeability tests on SD rats authenticated that the ILs, formulated with choline bicarbonate and phenylbutyric acid, demonstrate superior permeability compared to their sodium and acid counterparts. To conclude, choline salt ILs developed from choline bicarbonate and phenylbutyric acid present a promising avenue for UCD treatment, with the added benefit of reduced sodium load. They also hold merit in formulation engineering. The sustained-release capabilities of DESs position them favorably for drug delivery, while the low toxicity and cost-effectiveness of choline chloride signal potential in formulation engineering. Overall, this drug formulation heralds a prospective therapeutic avenue for UCD patients.

Keywords: phenylbutyric acid, sodium phenylbutyrate, choline salt, ionic liquids, deep eutectic systems, oral bioavailability

Procedia PDF Downloads 110
175 Efficacy and Safety of Updated Target Therapies for Treatment of Platinum-Resistant Recurrent Ovarian Cancer

Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan

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Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.

Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents

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174 Vagal Nerve Stimulator as a Treatment Approach in CHARGE Syndrome: A Case Report

Authors: Roya Vakili, Lekaa Elhajjmoussa, Barzin Omidi-Shal, Kim Blake

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Objective: The purpose of this case report is to highlight the successful treatment of a patient with Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness, (CHARGE syndrome) using a vagal nerve stimulator (VNS). Background: This is the first documented case report, to the authors' best knowledge, for a patient with CHARGE syndrome, epilepsy, autism, and postural orthostatic tachycardia syndrome (POTS) that was successfully treated with an implanted VNS therapeutic device. Methodology: The study is a case report. Results: This is the case of a 24-year-old female patient with CHARGE syndrome (non-random association of anomalies Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness) and several other comorbidities including refractory epilepsy, Patent Ductus Arteriosus (PDA) and POTS who had significant improvement of her symptoms after VNS implantation. She was a VNS candidate given her longstanding history of drug-resistant epilepsy and current disposition secondary to CHARGE syndrome. Prior to VNS implantation, she experienced three generalized seizures a year and daily POTS-related symptoms. She was having frequent lightheadedness and syncope spells due to a rapid heart rate and low blood pressure. The VNS device was set to detect a rapid heart rate and send appropriate stimulation anytime the heart rate exceeded 20% of the patient’s normal baseline. The VNS device demonstrated frequent elevated heart rates and concurrent VNS release every 8 minutes in addition to the programmed events. Following VNS installation, the patient became more active, alert, and communicative and was able to verbally communicate with words she was unable to say prior. Her GI symptoms also improved, as she was able to tolerate food better orally in addition to her G and J tube, likely another result of the vagal nerve stimulation. Additionally, the patient’s seizures and POTS-related cardiac events appeared to be well controlled. She had prolonged electroencephalogram (EEG) testing, showing no significant change in epileptiform activity. Improvements in the patient’s disposition are believed to be secondary to parasympathetic stimulation, adequate heart rate control, and GI stimulation, in addition to behavioral changes and other benefits via her implanted VNS. Conclusion: VNS showed promising results in improving the patient's quality of life and managing her diverse symptoms, including dysautonomia, POTs, gastrointestinal mobility, cognitive functioning as well seizure control.

Keywords: autism, POTs, CHARGE, VNS

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173 Sleep Quality as Perceived by Critically Ill Patients at El Manial University Hospitals

Authors: Mohamed Adel Ahmed, Warda Youssef Morsy , Hanaa Ali El Feky

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Background: Literature review cited that sleep is absolutely essential for surviving and reclamation of the quality of life. Critically ill patients often have poor sleep quality with prolonged sleep latency, sleep fragmentation, decreased sleep efficiency and frequent arousals. Nurses have a unique role for the early diagnosis of sleep disorders, decreasing stressors levels and providing the necessary environmental regulations to create a therapeutic ambiance. The aim of the study: to assess perceived sleep quality and identify factors affecting sleep quality among adult critically ill patients At El Manial University Hospital. Research Design: A descriptive exploratory design was utilized. Research questions: a) how do adult critically ill patients perceive sleep quality in the Critical Care Department of El Manial University Hospital? b) What are the factors affecting sleep quality among adult critically ill patients at El Manial University Hospital? Setting: selected critical and cardiac care units at El Manial University Hospital. Sample: A samples of convenience consisting of 100 adult male and female patients were included in the study. Tools of data collection: tool 1: Socio-demographic and Medical Data Sheet, tool 2: Modified St Mary's Hospital Sleep Questionnaire tool 3: Factors Affecting Sleep Quality Questionnaire among ICU Patients Results: The current study revealed that 76.0% of the studied sample had lack of sleep disturbance before hospitalization. However, 84 % had sleep disturbances during ICU stay, of these more than two-thirds (67 %) had moderate sleep disturbance. Presence of strange and bad odors, noise, having pain, fear of death and a loud voice produced by the ICU personnel had the most significant negative impact on patients’ sleep in percentage of 52.4, 50, 61.9, 45.2, 52.4, respectively. Conclusion: Sleep disturbances in the ICU are multifactorial, and ICU patients’ perceived degrees of sleep disturbance as a moderate. Recommendations: Based on findings of the present study, the following are recommended to be done by ICU nurses; create a healing ICU environment that should incorporate noise, light and temperature controls; decrease stimuli during night time hours to promote regulation of the circadian rhythm, allow usage of sleeping aids such as relaxing music, eye patches and earplugs into their daily nursing practice; cluster nursing activities and eliminate non-essential treatments during night time hours to allow uninterrupted sleep periods of at least 90 minutes to complete one sleep cycle , and minimize staff conversation, alarm noise and light during the quiet night time hours.

Keywords: sleep quality, critically ill, patients, perception

Procedia PDF Downloads 438
172 The Staphylococcus aureus Exotoxin Recognition Using Nanobiosensor Designed by an Antibody-Attached Nanosilica Method

Authors: Hamed Ahari, Behrouz Akbari Adreghani, Vadood Razavilar, Amirali Anvar, Sima Moradi, Hourieh Shalchi

Abstract:

Considering the ever increasing population and industrialization of the developmental trend of humankind's life, we are no longer able to detect the toxins produced in food products using the traditional techniques. This is due to the fact that the isolation time for food products is not cost-effective and even in most of the cases, the precision in the practical techniques like the bacterial cultivation and other techniques suffer from operator errors or the errors of the mixtures used. Hence with the advent of nanotechnology, the design of selective and smart sensors is one of the greatest industrial revelations of the quality control of food products that in few minutes time, and with a very high precision can identify the volume and toxicity of the bacteria. Methods and Materials: In this technique, based on the bacterial antibody connection to nanoparticle, a sensor was used. In this part of the research, as the basis for absorption for the recognition of bacterial toxin, medium sized silica nanoparticles of 10 nanometer in form of solid powder were utilized with Notrino brand. Then the suspension produced from agent-linked nanosilica which was connected to bacterial antibody was positioned near the samples of distilled water, which were contaminated with Staphylococcus aureus bacterial toxin with the density of 10-3, so that in case any toxin exists in the sample, a connection between toxin antigen and antibody would be formed. Finally, the light absorption related to the connection of antigen to the particle attached antibody was measured using spectrophotometry. The gene of 23S rRNA that is conserved in all Staphylococcus spp., also used as control. The accuracy of the test was monitored by using serial dilution (l0-6) of overnight cell culture of Staphylococcus spp., bacteria (OD600: 0.02 = 107 cell). It showed that the sensitivity of PCR is 10 bacteria per ml of cells within few hours. Result: The results indicate that the sensor detects up to 10-4 density. Additionally, the sensitivity of the sensors was examined after 60 days, the sensor by the 56 days had confirmatory results and started to decrease after those time periods. Conclusions: Comparing practical nano biosensory to conventional methods like that culture and biotechnology methods(such as polymerase chain reaction) is accuracy, sensitiveness and being unique. In the other way, they reduce the time from the hours to the 30 minutes.

Keywords: exotoxin, nanobiosensor, recognition, Staphylococcus aureus

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171 Internal Mercury Exposure Levels Correlated to DNA Methylation of Imprinting Gene H19 in Human Sperm of Reproductive-Aged Man

Authors: Zhaoxu Lu, Yufeng Ma, Linying Gao, Li Wang, Mei Qiang

Abstract:

Mercury (Hg) is a well-recognized environmental pollutant known by its toxicity of development and neurotoxicity, which may result in adverse health outcomes. However, the mechanisms underlying the teratogenic effects of Hg are not well understood. Imprinting genes are emerging regulators for fetal development subject to environmental pollutants impacts. In this study, we examined the association between paternal preconception Hg exposures and the alteration of DNA methylation of imprinting genes in human sperm DNA. A total of 618 men aged from 22 to 59 was recruited from the Reproductive Medicine Clinic of Maternal and Child Care Service Center and the Urologic Surgery Clinic of Shanxi Academy of Medical Sciences during April 2015 and March 2016. Demographic information was collected using questionnaires. Urinary Hg concentrations were measured using a fully-automatic double-channel hydride generation atomic fluorescence spectrometer. And methylation status in the DMRs of imprinting genes H19, Meg3 and Peg3 of sperm DNA were examined by bisulfite pyrosequencing in 243 participants. Spearman’s rank and multivariate regression analysis were used for correlation analysis between sperm DNA methylation status of imprinting genes and urinary Hg levels. The median concentration of Hg for participants overall was 9.09μg/l (IQR: 5.54 - 12.52μg/l; range = 0 - 71.35μg/l); no significant difference was found in median concentrations of Hg among various demographic groups (p > 0.05). The proportion of samples that a beyond intoxication criterion (10μg/l) for urinary Hg was 42.6%. Spearman’s rank correlation analysis indicates a negative correlation between urinary Hg concentrations and average DNA methylation levels in the DMRs of imprinted genes H19 (rs=﹣0.330, p = 0.000). However, there was no such a correlation found in genes of Peg3 and Meg3. Further, we analyzed of correlation between methylation level at each CpG site of H19 and Hg level, the results showed that three out of 7 CpG sites on H19 DMR, namely CpG2 (rs =﹣0.138, p = 0.031), CpG4 (rs =﹣0.369, p = 0.000) and CpG6 (rs=﹣0.228, p = 0.000), demonstrated a significant negative correlation between methylation levels and the levels of urinary Hg. After adjusting age, smoking, drinking, intake of aquatic products and education by multivariate regression analysis, the results have shown a similar correlation. In summary, mercury nonoccupational environmental exposure in reproductive-aged men associated with altered DNA methylation outcomes at DMR of imprinting gene H19 in sperm, implicating the susceptibility of the developing sperm for environmental insults.

Keywords: epigenetics, genomic imprinting gene, DNA methylation, mercury, transgenerational effects, sperm

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170 Phytochemical Screening, Proximate Analysis, Lethality Studies and Anti-Tumor Potential of Annona muricata L. (Soursop) Fruit Extract in Rattus novergicus

Authors: O. C. Abbah, O. Obidoa, J. Omale

Abstract:

Prostate tumor is fast becoming a leading cause of morbidity and mortality in human male adults, with 50 percent of men aged 50 years and above having histological evidence of the benign tumor. The study was set out to undertake phytochemical screening and proximate analysis of the pulp of A. muricata fruit - soursop; to determine the acute toxicity of the fruit pulp extract and its effect on male albino Wistar rats with concurrent induction of experimental benign prostate hyperplasia (BPH). Eighteen rats (average weight of 100g) were used for the lethality studies and were orally administered graded doses of aqueous extracts of the fruit pulp up to 5000 mg/kg body weight. Twenty five rats weighing 150-200g were divided into five groups of five rats each for the tumor studies. The groups included four controls – Hormone control, HC, which took Testosterone, T; and Estradiol, E2 – only, in olive oil as vehicle; Vehicle control, VC; Soursop control, SC, which received the extract only; VS, Vehicle and Soursop – and the Test group, TG (500mg/kg b.w.). All rats were dosed orally. Tumor was induced with exogenous Testosterone propionate: Estradiol valerate at 300µg: 80µg/kg b.w. (respectively) in olive oil, administered subcutaneously in the inguinal region of the rats on alternate days for 21 days. Administration of the fruit pulp at graded doses up to 5000mg/kg resulted in no lethality even after 72 hours. Results from tumor studies revealed that the administration of the fruit extracts significantly (p < 0.05) reduced the relative prostate weight of the TG compared with the HC, with values of 006±0.001 and 0.010±0.003 respectively. Treatment with vehicle, soursop and vehicle with soursop caused no significant (p>0.05) change in prostate size, with their respective relative prostate weights being 0.002±0.001, 0.004±0.002 and 0.002±0.001 compared with TG. Also, treatment with A. muricata fruit extract significantly decreased (p < 0.05) serum prostate specific antigen, PSA, in TG compared with HC, with values 0.055±0.017 and 0.194±0.068 ng/ml respectively. Furthermore, A. muricata administration displayed Testosterone boosting, Estradiol lowering and consequently testosterone-estradiol ratio increasing potential at the end of the 21 days. The preventive property of soursop against experimental BPH was corroborated by histological evidence in this study. The study concludes that A. muricata fruit holds a great potential for benign prostate tumor prevention and, possibly, management.

Keywords: annona muricata, benign prostate tumor, hormone, preventive potential, soursop

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169 A New Index for the Differential Diagnosis of Morbid Obese Children with and without Metabolic Syndrome

Authors: Mustafa M. Donma, Orkide Donma

Abstract:

Metabolic syndrome (MetS) is a severe health problem which is common among obese individuals. The components of MetS are rather stable in adults compared to the components discussed for children. Due to the ambiguity in this group of the population, how to diagnose MetS in morbid obese (MO) children still constitutes a matter of discussion. For this purpose, a formula, which facilitates the diagnosis of MetS in MO children, was investigated. The aim of this study was to develop a formula which was capable of discriminating MO children with and without MetS findings. Study population comprised MO children. Age and sex-dependent body mass index (BMI) percentiles of the children were above 99. Metabolic syndrome components were also determined. Elevated systolic and diastolic blood pressures (SBP and DBP), elevated fasting blood glucose (FBG), elevated triglycerides (TRG), and/or depressed high density lipoprotein cholesterol (HDL-C) in addition to central obesity were listed as MetS components for each child. Presence of at least two of these components confirmed that the case was MetS. Two groups were constituted. In the first group, there were forty-two MO children without MetS components. Second group was composed of forty-four MO children with at least two MetS components. Anthropometric measurements, including weight, height, waist, and hip circumferences, were performed following physical examination. Body mass index and homeostatic model assessment of insulin resistance values were calculated. Informed consent forms were obtained from the parents of the children. Institutional Non-Interventional Ethics Committee approved the study design. Blood pressure values were recorded. Routine biochemical analysis, including FBG, insulin (INS), TRG, HDL-C were performed. The performance and the clinical utility of the Diagnostic Obesity Notation Model Assessment Metabolic Syndrome Index (DONMA MetS index) [(INS/FBG)/(HDL-C/TRG)*100] was tested. Appropriate statistical tests were applied to the study data. p value smaller than 0.05 was defined as significant. Metabolic syndrome index values were 41.6±5.1 in MO group and 104.4±12.8 in MetS group. Corresponding values for HDL-C values were 54.5±13.2 mg/dl and 44.2±11.5 mg/dl. There were statistically significant differences between the groups (p<0.001). Upon evaluation of the correlations between MetS index and HDL-C values, a much stronger negative correlation was found in MetS group (r=-0.515; p=0.001) in comparison with the correlation detected in MO group (r=-0.371; p=0.016). From these findings, it was concluded that the statistical significance degree of the difference between MO and MetS groups was highly acceptable for this recently introduced MetS index as expected. This was due to the involvement of all of the biochemically defined MetS components into the index. This is particularly important because each of these four parameters used in the formula is cardiac risk factor. Aside from discriminating MO children with and without MetS findings, MetS index introduced in this study is important from the cardiovascular risk point of view in MetS group of children.

Keywords: children, fasting blood glucose, high density lipoprotein cholesterol, index, insulin, metabolic syndrome, morbid obesity, triglycerides.

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