Search results for: biological and chemical treatment
Commenced in January 2007
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Edition: International
Paper Count: 12888

Search results for: biological and chemical treatment

12018 Effects of Ultraviolet Treatment on Microbiological Load and Phenolic Content of Vegetable Juice

Authors: Kubra Dogan, Fatih Tornuk

Abstract:

Due to increasing consumer demand for the high-quality food products and awareness regarding the health benefits of different nutrients in food minimal processing becomes more popular in modern food preservation. To date, heat treatment is often used for inactivation of spoilage microorganisms in foods. However, it may cause significant changes in the quality and nutritional properties of food. In order to overcome the detrimental effects of heat treatment, several alternatives of non-thermal microbial inactivation processes have been investigated. Ultraviolet (UV) inactivation is a promising and feasible method for better quality and longer shelf life as an alternative to heat treatment, which aims to inhibit spoilage and pathogenic microorganisms and to inactivate the enzymes in vegetable juice production. UV-C is a sub-class of UV treatment which shows the highest microcidal effect between 250-270 nm. The wavelength of 254 nm is used for the surface disinfection of certain liquid food products such as vegetable juice. Effects of UV-C treatment on microbiological load and quality parameter of vegetable juice which is a mix of celery, carrot, lemon and orange was investigated. Our results showed that storing of UV-C applied vegetable juice for three months, reduced the count of TMAB by 3.5 log cfu/g and yeast-mold by 2 log cfu/g compared to control sample. Total phenolic content was found to be 514.3 ± 0.6 mg gallic acid equivalent/L, and there wasn’t a significant difference compared to control. The present work suggests that UV-C treatment is an alternative method for disinfection of vegetable juice since it enables adequate microbial inactivation, longer shelf life and has minimal effect on degradation of quality parameters of vegetable juice.

Keywords: heat treatment, phenolic content, shelf life, ultraviolet (UV-C), vegetable juice

Procedia PDF Downloads 198
12017 Biomedical Countermeasures to Category a Biological Agents

Authors: Laura Cochrane

Abstract:

The United States Centers for Disease Control and Prevention has established three categories of biological agents based on their ease of spread and the severity of the disease they cause. Category A biological agents are the highest priority because of their high degree of morbidity and mortality, ease of dissemination, the potential to cause social disruption and panic, special requirements for public health preparedness, and past use as a biological weapon. Despite the threat of Category A biological agents, opportunities for medical intervention exist. This work summarizes public information, consolidated and reviewed across the situational usefulness and disease awareness to offer discussion to three specific Category A agents: anthrax (Bacillus anthracis), botulism (Clostridium botulinum toxin), and smallpox (variola major), and provides an overview on the management of medical countermeasures available to treat these three (3) different types of pathogens. The medical countermeasures are discussed in the setting of pre-exposure prophylaxis, post-exposure prophylaxis, and therapeutic treatments to provide a framework for requirements in public health preparedness.

Keywords: anthrax, botulism, smallpox, medical countermeasures

Procedia PDF Downloads 60
12016 Genome-Wide Expression Profiling of Cicer arietinum Heavy Metal Toxicity

Authors: B. S. Yadav, A. Mani, S. Srivastava

Abstract:

Chickpea (Cicer arietinum L.) is an annual, self-pollinating, diploid (2n = 2x = 16) pulse crop that ranks second in world legume production after common bean (Phaseolus vulgaris). ICC 4958 flowers approximately 39 days after sowing under peninsular Indian conditions and the crop matures in less than 90 days in rained environments. The estimated collective yield losses due to abiotic stresses (6.4 million t) have been significantly higher than for biotic stresses (4.8 million t). Most legumes are known to be salt sensitive, and therefore, it is becoming increasingly important to produce cultivars tolerant to high-salinity in addition to other abiotic and biotic stresses for sustainable chickpea production. Our aim was to identify the genes that are involved in the defence mechanism against heavy metal toxicity in chickpea and establish the biological network of heavy metal toxicity in chickpea. ICC4958 variety of chick pea was taken and grown in normal condition and 150µM concentration of different heavy metal salt like CdCl₂, K₂Cr2O₇, NaAsO₂. At 15th day leave samples were collected and stored in RNA Later solution microarray was performed for checking out differential gene expression pattern. Our studies revealed that 111 common genes that involved in defense mechanism were up regulated and 41 genes were commonly down regulated during treatment of 150µM concentration of CdCl₂, K₂Cr₂O₇, and NaAsO₂. Biological network study shows that the genes which are differentially expressed are highly connected and having high betweenness and centrality.

Keywords: abiotic stress, biological network, chickpea, microarray

Procedia PDF Downloads 180
12015 Healthy Feeding and Drinking Troughs for Profitable Intensive Deep-Litter Poultry Farming

Authors: Godwin Ojochogu Adejo, Evelyn UnekwuOjo Adejo, Sunday UnenwOjo Adejo

Abstract:

The mainstream contemporary approach to controlling the impact of diseases among poultry birds rely largely on curative measures through the administration of drugs to infected birds. Most times as observed in the deep liter poultry farming system, entire flocks including uninfected birds receive the treatment they do not need. As such, unguarded use of chemical drugs and antibiotics has led to wastage and accumulation of chemical residues in poultry products with associated health hazards to humans. However, wanton and frequent drug usage in poultry is avoidable if feeding and drinking equipment are designed to curb infection transmission among birds. Using toxicological assays as guide and with efficiency and simplicity in view, two newly field-tested and recently patented equipments called 'healthy liquid drinking trough (HDT)' and 'healthy feeding trough (HFT)' that systematically eliminate contamination of the feeding and drinking channels, thereby, curbing wide-spread infection and transmission of diseases in the (intensive) deep litter poultry farming system were designed. Upon combined usage, they automatically and drastically reduced both the amount and frequency of antibiotics use in poultry by over > 50%. Additionally, they conferred optimization of feed and water utilization/elimination of wastage by > 80%, reduced labour by > 70%, reduced production cost by about 15%, and reduced chemical residues in poultry meat or eggs by > 85%. These new and cheap technologies which require no energy input are likely to elevate safety of poultry products for consumers' health, increase marketability locally and for export, and increase output and profit especially among poultry farmers and poor people who keep poultry or inevitably utilize poultry products in developing countries.

Keywords: healthy, trough, toxicological, assay-guided, poultry

Procedia PDF Downloads 138
12014 Magnetic Treatment of Irrigation Water and Its Effect on Water Salinity

Authors: Muhammad Waqar Ashraf

Abstract:

The influence of magnetic field on the structure of water and aqueous solutions are similar and can alter the physical and chemical properties of water-dispersed systems. With the application of magnetic field, hydration of salt ions and other impurities slides down and improve the possible technological characteristics of the water. Magnetic field can enhance the characteristic of water i.e. better salt solubility, kinetic changes in salt crystallization, accelerated coagulation, etc. Gulf countries are facing critical problem due to depletion of water resources and increasing food demands to cover the human needs; therefore water shortage is being increasingly accepted as a major limitation for increased agricultural production and food security. In arid and semi-arid regions sustainable agricultural development is influenced to a great extent by water quality that might be used economically and effectively in developing agriculture programs. In the present study, the possibility of using magnetized water to desalinate the soil is accounted for the enhanced dissolving capacity of the magnetized water. Magnetic field has been applied to treat brackish water. The study showed that the impact of magnetic field on saline water is sustained up to three hours (with and without shaking). These results suggest that even low magnetic field can decrease the electrical conductivity and total dissolved solids which are good for the removal of salinity from the irrigated land by using magnetized water.

Keywords: magnetic treatment, saline water, hardness of water, removal of salinity

Procedia PDF Downloads 474
12013 Development and Evaluation of an Internet-Based Transdiagnostic Therapy Intervention in the Arab World

Authors: Mariam Fishere

Abstract:

The proposed research study aims at developing an Internet-based transdiagnostic treatment and evaluating its efficacy. Based on the Common Elements Treatment Approach (CETA), a combined low-intensity and technology supported transdiagnostic treatment protocol will be culturally adapted for usage by nonprofessional therapists in Arabic-speaking countries. This Internet-based CETA intervention will target individuals suffering from one or more of the following disorders: depression, anxiety and posttraumatic stress disorder (PTSD), which are all major contributors to the global burden of mental illness. The growing body of research in the area of transdiagnostic treatment has proven to be effective in high-income countries (HICs), but there remain questions about its efficacy, cultural appropriateness, and validity for low- to middle-income countries (LMICs). The aim of this dissertation project is to investigate the efficacy of a newly developed Internet-delivery of an evidence-based transdiagnostic treatment – CETA – for a sample of Arabic-speaking individuals suffering from at least one of the following disorders; depression, anxiety, and PTSD.

Keywords: transdiagnostic, internet-based interventions, mental health, Arab world

Procedia PDF Downloads 212
12012 The Improved Therapeutic Effect of Trans-Cinnamaldehyde on Adipose-Derived Stem Cells without Chemical Induction

Authors: Karthyayani Rajamani, Yi-Chun Lin, Tung-Chou Wen, Jeanne Hsieh, Yi-Maun Subeq, Jen-Wei Liu, Po-Cheng Lin, Horng-Jyh Harn, Shinn-Zong Lin, Tzyy-Wen Chiou

Abstract:

Assuring cell quality is an essential parameter for the success of stem cell therapy, utilization of various components to improve this potential has been the primary goal of stem cell research. The aim of this study was not only to demonstrate the capacity of trans-cinnamaldehyde (TC) to reverse stress-induced senescence but also improve the therapeutic abilities of stem cells. Because of the availability and the promising application potential in regenerative medicine, adipose-derived stem cells (ADSCs) were chosen for the study. We found that H2O2 treatment resulted in the expression of senescence characteristics in the ADSCs, including decreased proliferation rate, increased senescence-associated- β-galactosidase (SA-β-gal) activity, decreased SIRT1 (silent mating type information regulation 2 homologs) expression and decreased telomerase activity. However, TC treatment was sufficient to rescue or reduce the effects of H2O2 induction, ultimately leading to an increased proliferation rate, a decrease in the percentage of SA-β-gal positive cells, upregulation of SIRT1 expression, and increased telomerase activity of the senescent ADSCs at the cellular level. Further recently it was observed that the ADSCs were treated with TC without induction of senescence, all the before said positives were observed. Moreover, a chemically induced liver fibrosis animal model was used to evaluate the functionality of these rescued cells in vivo. Liver dysfunction was established by injecting 200 mg/kg thioacetamide (TAA) intraperitoneally into Wistar rats every third day for 60 days. The experimental rats were separated into groups; normal group (rats without TAA induction), sham group (without ADSC transplantation), positive control group (transplanted with normal ADSCs); H2O2 group (transplanted with H2O2 -induced senescent ADSCs), H2O2+TC group (transplanted with ADSCs pretreated with H2O2 and then further treated with TC) and TC group (ADSC treated with TC without H2O2 treatment). In the transplantation group, 1 × 106 human ADSCs were introduced into each rat via direct liver injection. Based on the biochemical analysis and immunohistochemical staining results, it was determined that the therapeutic effects on liver fibrosis by the induced senescent ADSCs (H2O2 group) were not as significant as those exerted by the normal ADSCs (the positive control group). However, the H2O2+TC group showed significant reversal of liver damage when compared to the H2O2 group 1 week post-transplantation. Further ADSCs without H2O2 treatment but with just TC treatment performed much better than all the groups. These data confirmed that the TC treatment had the potential to improve the therapeutic effect of ADSCs. It is therefore suggested that TC has potential applications in maintaining stem cell quality and could possibly aid in the treatment of senescence-related disorders.

Keywords: senescence, SIRT1, adipose derived stem cells, liver fibrosis

Procedia PDF Downloads 244
12011 Outpatient Pelvic Nerve and Muscle Treatment Reduces Pain and Improves Functionality for Patients with Chronic Pelvic Pain and Erectile Dysfunction

Authors: Allyson Augusta Shrikhande, Alexa Rains, Tayyaba Ahmed, Marjorie Mamsaang, Rakhi Vyas, Janaki Natarajan, Erika Moody, Christian Reutter, Kimberlee Leishear, Yogita Tailor, Sandra Sandhu-Restaino, Lora Liu, Neha James, Rosemarie Filart

Abstract:

Characterized by consistent difficulty getting and keeping an erection firm enough for intercourse, Erectile Dysfunction may affect up to 15% of adult men. Although awareness and access to treatment have improved in recent years, many patients do not actively seek diagnosis or treatment due to the stigma surrounding this condition. Patients who do seek treatment are often dissatisfied by the efficacy of the medication. The condition inhibits patients’ quality of life by worsening mental health and relationships. The purpose of this study was to test the effectiveness of an outpatient neuromuscular treatment protocol in treating the symptoms of Chronic Pelvic Pain and Erectile Dysfunction, improving pain and function. 56 patients ages 20-79 presented to an outpatient clinic for treatment of pelvic pain and Erectile Dysfunction symptoms. These symptoms had persisted for an average of 4 years. All patients underwent external ultrasound-guided hydro-dissection technique targeted at pelvic peripheral nerves in combination with pelvic floor musculature trigger-point injections. To measure the effects of this treatment, a five question Erectile Dysfunction questionnaire was completed by each patient at their first visit to a clinic and three months after treatment began. Answers were summed for a total score of 5-25, with a higher score indicating optimal function. The average score before treatment was 14.125 (SD 5.411) (a=0.05; CI 12.708-15.542), which increased by 18% to an average of 16.625 (SD 6.423) (a=0.05; CI 14.943-18.307) after treatment (P=0.0004). Secondary outcome variables included a Visual Analogue Scale (VAS) to measure pelvic pain intensity and the Functional Pelvic Pain Scale (FPPS) to measure function across multiple areas. VAS scores reduced by 51% after three months. Before treatment, the mean VAS score was 5.87, and the posttreatment mean VAS score was 2.89. Pelvic pain functionality improved by 34% after three months. Pretreatment FPPS scores averaged at 7.48, decreasing to 4.91 after treatment. These results indicate that this unique treatment was very effective at relieving pain and increasing function for patients with Erectile Dysfunction.

Keywords: chronic pelvic pain, erectile dysfunction, nonsurgical, outpatient, trigger point injections

Procedia PDF Downloads 68
12010 Melt–Electrospun Polyprophylene Fabrics Functionalized with TiO2 Nanoparticles for Effective Photocatalytic Decolorization

Authors: Z. Karahaliloğlu, C. Hacker, M. Demirbilek, G. Seide, E. B. Denkbaş, T. Gries

Abstract:

Currently, textile industry has played an important role in world’s economy, especially in developing countries. Dyes and pigments used in textile industry are significant pollutants. Most of theirs are azo dyes that have chromophore (-N=N-) in their structure. There are many methods for removal of the dyes from wastewater such as chemical coagulation, flocculation, precipitation and ozonation. But these methods have numerous disadvantages and alternative methods are needed for wastewater decolorization. Titanium-mediated photodegradation has been used generally due to non-toxic, insoluble, inexpensive, and highly reactive properties of titanium dioxide semiconductor (TiO2). Melt electrospinning is an attractive manufacturing process for thin fiber production through electrospinning from PP (Polyprophylene). PP fibers have been widely used in the filtration due to theirs unique properties such as hydrophobicity, good mechanical strength, chemical resistance and low-cost production. In this study, we aimed to investigate the effect of titanium nanoparticle localization and amine modification on the dye degradation. The applicability of the prepared chemical activated composite and pristine fabrics for a novel treatment of dyeing wastewater were evaluated.In this study, a photocatalyzer material was prepared from nTi (titanium dioxide nanoparticles) and PP by a melt-electrospinning technique. The electrospinning parameters of pristine PP and PP/nTi nanocomposite fabrics were optimized. Before functionalization with nTi, the surface of fabrics was activated by a technique using glutaraldehyde (GA) and polyethyleneimine to promote the dye degredation. Pristine PP and PP/nTi nanocomposite melt-electrospun fabrics were characterized using scanning electron microscopy (SEM) and X-Ray Photon Spectroscopy (XPS). Methyl orange (MO) was used as a model compound for the decolorization experiments. Photocatalytic performance of nTi-loaded pristine and nanocomposite melt-electrospun filters was investigated by varying initial dye concentration 10, 20, 40 mg/L). nTi-PP composite fabrics were successfully processed into a uniform, fibrous network of beadless fibers with diameters of 800±0.4 nm. The process parameters were determined as a voltage of 30 kV, a working distance of 5 cm, a temperature of the thermocouple and hotcoil of 260–300 ºC and a flow rate of 0.07 mL/h. SEM results indicated that TiO2 nanoparticles were deposited uniformly on the nanofibers and XPS results confirmed the presence of titanium nanoparticles and generation of amine groups after modification. According to photocatalytic decolarization test results, nTi-loaded GA-treated pristine or nTi-PP nanocomposite fabric filtern have superior properties, especially over 90% decolorization efficiency at GA-treated pristine and nTi-PP composite PP fabrics. In this work, as a photocatalyzer for wastewater treatment, surface functionalized with nTi melt-electrospun fabrics from PP were prepared. Results showed melt-electrospun nTi-loaded GA-tretaed composite or pristine PP fabrics have a great potential for use as a photocatalytic filter to decolorization of wastewater and thus, requires further investigation.

Keywords: titanium oxide nanoparticles, polyprophylene, melt-electrospinning

Procedia PDF Downloads 253
12009 The Optimum Aeration Time of Wastewater Treatment by Surface Aerators in Suan Sunandha Rajabhat University

Authors: Anat Thanpinta

Abstract:

This research aimed to study on the efficiency of wastewater treatment by comparing the different aeration times of surface aerators in Suan Sunandha Rajabhat University. In doing so, the operation of surface aerators was divided into 2 groups which included the groups of 8 hours (8-0/opened-closed) and 4 hours (2-2/opened-closed) of aeration time per day. As a result of the study, it was found that the efficiency of wastewater treatment in the forms of DO, BOD, turbidity and NO2- by 8 hours (8-0/opened-closed) and 4 hours (2-2/opened-closed) of aeration time per day of surface aerators was not statistically different [Sig. = .644, .488, .716 and .054 > α (.05)] while the efficiency in the forms of NO3- and P was significantly different at the statistical level of .01 [Sig. = .001 and .000 < α (.01)].

Keywords: aeration time, surface aerator, wastewater treatment, efficiency

Procedia PDF Downloads 286
12008 Therapeutic Effect of Diisopropyldithiocarbamate Sodium Salt Against Diclofenac Induced Testicular Damage in Male Wistar Rats

Authors: Tella Toluwani, Adegbegi Ademuyiwa, Musei Chiedu, Adekunle Odola, Ayangbenro Ayansina, Adaramoye Oluwatosin

Abstract:

Dithiocarbamates are very useful biological agents with antioxidant properties. Diclofenac (DIC) is a non-steroidal analgesic, anti-inflammatory, and antipyretic agent. The use of diclofenac has been linked with reproductive toxicity/damage. The purpose of this study is (i) To investigate the therapeutic potential of diisopropyldithiocarbamate sodium salt (Na(i-Pr₂dtc)) and vitamin E (VIT E) against diclofenac induced toxicity in the testes of male Wistar rats. (ii) To investigate the effect of (Na(i-Pr₂dtc)) and vitamin E on ameliorating damage done to the testes through histological analysis of the testes. Thirty-six (36) male Wistar rats were used for the experiment, they were divided into six (6) groups, the animals in group 1 served as control, animals in groups 2, 3, 4, 5 and 6 received DIC only, DIC and (Na(i-Pr₂dtc)), DIC and VIT E, (Na(i-Pr₂dtc) only and VIT E only respectively. A single dose of 100 mg/kg body weight of DIC was administered to male Wistar rats, while 30 mg/kg body weight of (Na(i-Pr₂dtc)) was used to treat both normal and DIC treated animals, control animals were treated with the vehicle, after 24 hrs of treatment the animals were euthanized and the testes were removed for analysis. The treatment of rats with Na(i-Pr₂dtc) significantly restored catalase (CAT) activity depressed by diclofenac. (Na(i-Pr₂dtc)) also restored glutathione levels reduced by DIC treatment and this was also accompanied by reduced lipid peroxidation (LPO) level. VIT E significantly restored superoxide dismutase (SOD) activity when compared with DIC only treated animals. Photomicrographs of testes from (Na(i-Pr₂dtc)) treated rats showed seminiferous epithelium with no lesions. We conclude that (Na(i-Pr₂dtc)) has an antioxidant effect, which might be related to the dose and duration of administration.

Keywords: diisopropyldithiocarbamate sodium salt, diclofenac, vitamin E, testes

Procedia PDF Downloads 172
12007 Effect of Grayanotoxins on Skeletal Muscle Cell C2C12

Authors: Bayan Almofty, Yuto Yamaki, Tadamasa Terai, Sadahito Uto

Abstract:

Myopathy (muscles disease) treatment are expected in the field of regenerative medicine and applied research of cultured muscle to bio actuator is performed in Biomedical Engineering as applied research of cultured muscle. This study is about cultured myoblast C2C12 from mouse skeletal muscle and a mechanism of cultured muscle contraction by electric stimulation is investigated. Grayanotoxins (GTXs) belong to neurotoxins known to enhance the permeability of cell membrane for Na ions. Grayanotoxins are extracted from a famous Pieris japonica and Ericaceae as a phytotoxin. We investigated the functional role of GTXs on muscle cells (C2C12) contraction and membrane potential. A change in membrane potential is measured using a micro glass tube electrode contraction of myotubes is induced by applying an external electrical stimulation. The contraction and membrane potential change induced by injection of current using the micro glass electrode are also measured. From the result, contraction and membrane potential of muscle cells was affected by GTXs treatment, suggesting that the diverse chemical structures of GTXs are responsible for contraction and membrane potential of muscle cells.

Keywords: skeletal muscle, C2C12, myoblast, myotubes, contraction, Grayanotoxins, membrane potential, neurotoxins, phytotoxin

Procedia PDF Downloads 453
12006 Predictor Factors for Treatment Failure among Patients on Second Line Antiretroviral Therapy

Authors: Mohd. A. M. Rahim, Yahaya Hassan, Mathumalar L. Fahrni

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Second line antiretroviral therapy (ART) regimen is used when patients fail their first line regimen. There are many factors such as non-adherence, drug resistance as well as virological and immunological failure that lead to second line highly active antiretroviral therapy (HAART) regimen treatment failure. This study was aimed at determining predictor factors to treatment failure with second line HAART and analyzing median survival time. An observational, retrospective study was conducted in Sungai Buloh Hospital (HSB) to assess current status of HIV patients treated with second line HAART regimen. Convenience sampling was used and 104 patients were included based on the study’s inclusion and exclusion criteria. Data was collected for six months i.e. from July until December 2013. Data was then analysed using SPSS version 18. Kaplan-Meier and Cox regression analyses were used to measure median survival times and predictor factors for treatment failure. The study population consisted mainly of male subjects, aged 30-45 years, who were heterosexual, and had HIV infection for less than 6 years. The most common second line HAART regimen given was lopinavir/ritonavir (LPV/r)-based combination. Kaplan-Meier analysis showed that patients on LPV/r demonstrated longer median survival times than patients on indinavir/ritonavir (IDV/r) based combination (p<0.001). The commonest reason for a treatment to fail with second line HAART was non-adherence. Based on Cox regression analysis, other predictor factors for treatment failure with second line HAART regimen were age and mode of HIV transmission.

Keywords: adherence, antiretroviral therapy, second line, treatment failure

Procedia PDF Downloads 249
12005 Anti-Diarrheal Activity of Extracts Kedondong Leaf in Mice Balb/C Strain Males in Vivo

Authors: Johanrik, Arini Apriliani, Fikri Haikal, Dias Yuca, Muhammad Abdul Latif, Edijanti Goenarwo, Nurita Pratama Sari

Abstract:

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

Keywords: anti-diarrhea, anti-secretory, anti-motility, kedondong leaf

Procedia PDF Downloads 490
12004 Gossypol Extraction from Cotton Seed and Evaluation of Cotton Seed and Boll-cotton-pol Extract on Treatment of Cutaneous Leishmaniasis Resistant to Drugs

Authors: M. Mirmohammadi, S. Taghdisi, F. Anali

Abstract:

Gossypol is a yellow anti-nutritional compound found in the cotton plant. This substance exists in the cottonseed and other parts of the cotton plant, such as bark, leaves, and stems. Chemically, gossypol is a very active polyphenolic aldehyde compound, and due to this polyphenolic structure, it has antioxidant and therapeutic properties. On the other hand, this compound, especially in free form, has many toxic effects, that its excessive consumption can be very dangerous for humans and animals. In this study, gossypol was extracted as a derivative compound of gossypol acetic acid from cottonseed using the n-hexane solvent with an efficiency of 0.84 ± 0.04, which compared to the Gossypol extracted from cottonseed oil with the same method (cold press) showed a significant difference with its efficiency of 1.14 ± 0.06. Therefore, it can be suggested to use cottonseed oil to extract this valuable compound. In the other part of this research, cottonseed extracts and cotton bolls extracts were obtained by two methods of soaking and Soxhlet with hydroalcoholic solvent taken with a ratio of (25:75), then by using extracts and corn starch powder, four herbal medicine code was created and after receiving the code of ethics (IR.SSU.REC.1398.136) the therapeutic effect of each one on the Cutaneous leishmaniasis resistant to drugs (caused by the leishmaniasis parasite) was investigated in real patients and its results was compared with the common drug glucantime (local ampoule) (n = 36). Statistical studies showed that the use of herbal medicines prepared with cottonseed extract and cotton bolls extract has a significant positive effect on the treatment of the disease’s wounds (p-value > 0.05) compared to the control group (only ethanol). Also, by comparing the average diameter of the wounds after a two-month treatment period, no significant difference was found between the use of ointment containing extracts and local glucantime ampoules (p-value < 0.05). Bolls extract extracted with the Soxhlet method showed the best therapeutic effects, although there was no significant difference between them (p-value < 0.05). Therefore, there is acceptable reliability to recommend this medicine for the treatment of Cutaneous leishmaniasis resistant to drugs without the side effects of the chemical drug glucantime and the pain of injecting the ampoule.

Keywords: cottonseed oil, gossypol, cotton boll, cutaneous leishmaniasis

Procedia PDF Downloads 77
12003 Anticancer Effect of Resveratrol-Loaded Gelatin Nanoparticles in NCI-H460 Non-Small Cell Lung Carcinoma Cell Lines

Authors: N. Rajendra Prasad

Abstract:

Resveratrol (RSV), a grape phytochemical, has drawn greater attention because of its beneficial ef-fects against cancer. However, RSV has some draw-backs such as unstabilization, poor water solubility and short biological half time, which limit the utili-zation of RSV in medicine, food and pharmaceutical industries. In this study, we have encapsulated RSV in gelatin nanoparticles (GNPs) and studied its anti-cancer efficacy in NCI-H460 lung cancer cells. SEM and DLS studies have revealed that the prepared RSV-GNPs possess spherical shape with a mean diameter of 294 nm. The successful encapsulation of RSV in GNPs has been achieved by the cross-linker glutaraldehyde probably through Schiff base reaction and hydrogen bond interaction. Spectrophotometric analysis revealed that the max-imum of 93.6% of RSV has been entrapped in GNPs. In vitro drug release kinetics indicated that there was an initial burst release followed by a slow and sustained release of RSV from GNPs. The prepared RSV-GNPs exhibited very rapid and more efficient cellular uptake than free RSV. Further, RSV-GNPs treatment showed greater antiproliferative efficacy than free RSV treatment in NCI-H460 cells. It has been found that greater ROS generation, DNA damage and apoptotic incidence in RSV-GNPs treated cells than free RSV treatment. Erythrocyte aggregation assay showed that the prepared RSV-GNPs formulation elicit no toxic response. HPLC analysis revealed that RSV-GNPs was more bioavailable and had a longer half-life than free RSV. Hence, GNPs carrier system might be a promising mode for controlled delivery and for improved therapeutic index of poorly water soluble RSV.

Keywords: resveratrol, coacervation, anticancer gelatin nanoparticles, lung cancer, controlled release

Procedia PDF Downloads 433
12002 Role of Microplastics on Reducing Heavy Metal Pollution from Wastewater

Authors: Derin Ureten

Abstract:

Plastic pollution does not disappear, it gets smaller and smaller through photolysis which are caused mainly by sun’s radiation, thermal oxidation, thermal degradation, and biodegradation which is the action of organisms digesting larger plastics. All plastic pollutants have exceedingly harmful effects on the environment. Together with the COVID-19 pandemic, the number of plastic products such as masks and gloves flowing into the environment has increased more than ever. However, microplastics are not the only pollutants in water, one of the most tenacious and toxic pollutants are heavy metals. Heavy metal solutions are also capable of causing varieties of health problems in organisms such as cancer, organ damage, nervous system damage, and even death. The aim of this research is to prove that microplastics can be used in wastewater treatment systems by proving that they could adsorb heavy metals in solutions. Experiment for this research will include two heavy metal solutions; one including microplastics in a heavy metal contaminated water solution, and one that just includes heavy metal solution. After being sieved, absorbance of both mediums will be measured with the help of a spectrometer. Iron (III) chloride (FeCl3) will be used as the heavy metal solution since the solution becomes darker as the presence of this substance increases. The experiment will be supported by Pure Nile Red powder in order to observe if there are any visible differences under the microscope. Pure Nile Red powder is a chemical that binds to hydrophobic materials such as plastics and lipids. If proof of adsorbance could be observed by the rates of the solutions' final absorbance rates and visuals ensured by the Pure Nile Red powder, the experiment will be conducted with different temperature levels in order to analyze the most accurate temperature level to proceed with removal of heavy metals from water. New wastewater treatment systems could be generated with the help of microplastics, for water contaminated with heavy metals.

Keywords: microplastics, heavy metal, pollution, adsorbance, wastewater treatment

Procedia PDF Downloads 71
12001 Realization and Characterization of TiN Coating and Metal Working Application

Authors: Nadjette Belhamra, Abdelouahed Chala, Ibrahim Guasmi

Abstract:

Titanium nitride coatings have been extensively used in industry, such as in cutting tools. TiN coating were deposited by chemical vapour deposition (CVD) on carbide insert at a temperature between 850°C and 1100°C, which often exceeds the hardening treatment temperature of the metals. The objective of this work is to realize, to characterize of TiN coating and to apply it in the turning of steel 42CrMo4 under lubrification. Various experimental techniques were employed for the microstructural characterization of the coatings, e. g., X-ray diffraction (XRD), scanning electron microscope (SEM) model JOEL JSM-5900 LV, equipped with energy dispersive X-ray (EDX). The results show that TiN-coated demonstrate a good wear resistance.

Keywords: hard coating TiN, carbide inserts, machining, turning, wear

Procedia PDF Downloads 537
12000 The Application of Enzymes on Pharmaceutical Products and Process Development

Authors: Reginald Anyanwu

Abstract:

Enzymes are biological molecules that significantly regulate the rate of almost all of the chemical reactions that take place within cells, and have been widely used for products’ innovations. They are vital for life and serve a wide range of important functions in the body, such as aiding in digestion and metabolism. The present study was aimed at finding out the extent to which biological molecules have been utilized by pharmaceutical, food and beverage, and biofuel industries in commercial and scale up applications. Taking into account the escalating business opportunities in this vertical, biotech firms have also been penetrating enzymes industry especially that of food. The aim of the study therefore was to find out how biocatalysis can be successfully deployed; how enzyme application can improve industrial processes. To achieve the purpose of the study, the researcher focused on the analytical tools that are critical for the scale up implementation of enzyme immobilization to ascertain the extent of increased product yield at minimum logistical burden and maximum market profitability on the environment and user. The researcher collected data from four pharmaceutical companies located at Anambra state and Imo state of Nigeria. Questionnaire items were distributed to these companies. The researcher equally made a personal observation on the applicability of these biological molecules on innovative Products since there is now shifting trends toward the consumption of healthy and quality food. In conclusion, it was discovered that enzymes have been widely used for products’ innovations but there are however variations on their applications. It was also found out that pivotal contenders of enzymes market have lately been making heavy investments in the development of innovative product solutions. It was recommended that the applications of enzymes on innovative products should be widely practiced.

Keywords: enzymes, pharmaceuticals, process development, quality food consumption, scale-up applications

Procedia PDF Downloads 129
11999 Nose Macroneedling Tie Suture Hidden Technique

Authors: Mohamed Ghoz, Hala Alsabeh

Abstract:

Context: Macroscopic Nose Macroneedling (MNM) is a new non-surgical procedure for lifting and tightening the nose. It is a tissue-non-invasive technique that uses a needle to create micro-injuries in the skin. These injuries stimulate the production of collagen and elastin, which results in the tightening and lifting of the skin. Research Aim: The research aim of this study was to investigate the efficacy and safety of MNM for the treatment of nasal deformities. Methodology A total of 100 patients with nasal deformities were included in this study. The patients were randomly assigned to either the MNM group or the control group. The MNM group received a single treatment of MNM, while the control group received no treatment. The patients were evaluated at baseline, 6 months, and 12 months after treatment. Findings: The results of this study showed that MNM was effective in improving the appearance of the nose in patients with nasal deformities. At 6 months after treatment, the patients in the MNM group had significantly improved nasal tip projection, nasal bridge height, and nasal width compared to the patients in the control group. The improvements in nasal appearance were maintained at 12 months after treatment. Theoretical Importance: The findings of this study provide support for the use of MNM as a safe and effective treatment for nasal deformities. MNM is a non-surgical procedure that is associated with minimal downtime and no risk of scarring. This makes it an attractive option for patients who are looking for a minimally invasive treatment for their nasal deformities. Data Collection: Data was collected from the patients using a variety of methods, including clinical assessments, photographic assessments, and patient-reported outcome measures. Analysis Procedures: The data was analyzed using a variety of statistical methods, including descriptive statistics, inferential statistics, and meta-analysis. Question Addressed: The research question addressed in this study was whether MNM is an effective and safe treatment for nasal deformities. Conclusion: The findings of this study suggest that MNM is an effective and safe treatment for nasal deformities. MNM is a non-surgical procedure that is associated with minimal downtime and no risk of scarring. This makes it an attractive option for patients who are looking for a minimally invasive treatment for their nasal deformities.

Keywords: nose, surgery, tie, suture

Procedia PDF Downloads 58
11998 Comprehensive Investigation of Solving Analytical of Nonlinear Differential Equations at Chemical Reactions to Design of Reactors by New Method “AGM”

Authors: Mohammadreza Akbari, Pooya Soleimani Besheli, Reza khalili, Sara Akbari, Davood Domiri Ganji

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In this symposium, our aims are accuracy, capabilities and power at solving of the complicate non-linear differential at the reaction chemical in the catalyst reactor (heterogeneous reaction). Our purpose is to enhance the ability of solving the mentioned nonlinear differential equations at chemical engineering and similar issues with a simple and innovative approach which entitled ‘’Akbari-Ganji's Method’’ or ‘’AGM’’. In this paper we solve many examples of nonlinear differential equations of chemical reactions and its investigate. The chemical reactor with the energy changing (non-isotherm) in two reactors of mixed and plug are separately studied and the nonlinear differential equations obtained from the reaction behavior in these systems are solved by a new method. Practically, the reactions with the energy changing (heat or cold) have an important effect on designing and function of the reactors. This means that possibility of reaching the optimal conditions of operation for the maximum conversion depending on nonlinear nature of the reaction velocity toward temperature, results in the complexity of the operation in the reactor. In this case, the differential equation set which governs the reactors can be obtained simultaneous solution of mass equilibrium and energy and temperature changing at concentration.

Keywords: new method (AGM), nonlinear differential equation, tubular and mixed reactors, catalyst bed

Procedia PDF Downloads 364
11997 Sustainability Assessment of Municipal Wastewater Treatment

Authors: Yousra Zakaria Ahmed, Ahmed El Gendy, Salah El Haggar

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In this paper, our methodology to assess sustainability of wastewater treatment technologies in Egypt is presented. The preliminary list of factors to be considered, as well as their ranking listed. The factors include, but are not limited to pollutants removal efficiency and energy consumption under the environmental dimension, construction cost, operation and maintenance costs and required land area cost under the economic dimension and public acceptance, noise and generating job opportunities for local residents. This methodology is intended to be a user-friendly screening tool to support the decision making process when investigating different wastewater treatment technologies in Egypt. Based on the research work results presented in this paper, it can be generally concluded that the categorization of some of the social and environmental aspects of sustainability is subjective and highly dependent on the local conditions and researchers’ background.

Keywords: sustainability, wastewater treatment, sustainability assessment, Egypt

Procedia PDF Downloads 487
11996 Estimation of the Nutritive Value of Local Forage Cowpea Cultivars in Different Environments

Authors: Salem Alghamdi

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Genotypes collected from farmers at a different region of Saudi Arabia as well as from Egyptian cultivar and a new line from Yamen. Seeds of these genotypes were grown in Dirab Agriculture Research Station, (Middle Region) and Al-Ahsa Palms and Dates Research Center (East region), during summer of 2015. Field experiments were laid out in randomized complete block design on the first week of June with three replications. Each experiment plot contained 6 rows 3m in length. Inter- and intra-row spacing was 60 and 25cm, respectively. Seed yield and its components were estimated in addition to qualitative characters on cowpea plants grown only in Dirab using cowpea descriptor from IPGRI, 1982. Seeds for chemical composite and antioxidant contents were analyzed. Highly significant differences were detected between genotypes in both locations and the combined of two locations for seed yield and its components. Mean data clearly show exceeded determine genotypes in seed yield while indeterminate genotypes had higher biological yield that divided cowpea genotypes to two main groups 1- forage genotypes (KSU-CO98, KSU-CO99, KSU-CO100, and KSU-CO104) that were taller and produce higher branches, biological yield and these are suitable to feed on haulm 2- food genotypes (KSU-CO101, KSU-CO102, and KSU-CO103) that produce higher seed yield with lower haulm and also these genotypes characters by high seed index and light seed color. Highly significant differences were recorded for locations in all studied characters except the number of branches, seed index, and biological yield, however, the interaction of genotype x location was significant only for plant height, the number of pods and seed yield per plant.

Keywords: Cowpea, genotypes, antioxidant contents, yield

Procedia PDF Downloads 232
11995 Preliminary Proposal to Use Adaptive Computer Games in the Virtual Rehabilitation Therapy

Authors: Mamoun S. Ideis, Zein Salah

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Virtual Rehabilitation (VR) refers to using Virtual Reality’s hardware and simulations as means of exercising tools to rehabilitate patients in need. These patients will undergo their treatment exercises while playing different computer games, which helps achieve greater motivation for patients undergoing their therapeutic exercises. Virtual Rehabilitation systems adopt computer games as part of the treatment therapy. In this paper, we present a preliminary proposal to using adaptive computer games in Virtual Rehabilitation therapy. We also present some tips in designing those adaptive computer games by using different machine learning algorithms in order to create a personalized experience for each patient, which in turn, increases the potential benefits of the treatment that each patient receives. Furthermore, we propose a method of comparing the results of treatment using the adaptive computer games with the results of using static and classical computer games.

Keywords: virtual rehabilitation, physiotherapy, adaptive computer games, post-stroke, game design

Procedia PDF Downloads 277
11994 Natural Preservatives: An Alternative for Chemical Preservative Used in Foods

Authors: Zerrin Erginkaya, Gözde Konuray

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Microbial degradation of foods is defined as a decrease of food safety due to microorganism activity. Organic acids, sulfur dioxide, sulfide, nitrate, nitrite, dimethyl dicarbonate and several preservative gases have been used as chemical preservatives in foods as well as natural preservatives which are indigenous in foods. It is determined that usage of herbal preservatives such as blueberry, dried grape, prune, garlic, mustard, spices inhibited several microorganisms. Moreover, it is determined that animal origin preservatives such as whey, honey, lysosomes of duck egg and chicken egg, chitosan have antimicrobial effect. Other than indigenous antimicrobials in foods, antimicrobial agents produced by microorganisms could be used as natural preservatives. The antimicrobial feature of preservatives depends on the antimicrobial spectrum, chemical and physical features of material, concentration, mode of action, components of food, process conditions, and pH and storage temperature. In this review, studies about antimicrobial components which are indigenous in food (such as herbal and animal origin antimicrobial agents), antimicrobial materials synthesized by microorganisms, and their usage as an antimicrobial agent to preserve foods are discussed.

Keywords: animal origin preservatives, antimicrobial, chemical preservatives, herbal preservatives

Procedia PDF Downloads 354
11993 Essential Oil Analysis of the Aerial Parts of Sideritis incana and Calamitha hispidula

Authors: Smain Amiraa, Hocine Laouerb, Fatima Benchikh-Amiraa, Guido Flaminic

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The aerial parts of Sideritis incana and Calamintha hispidula at the flowering stage were submitted to hydrodistillation in a Clevenger–type apparatus for 3 hours and the chemical composition of the essential oil was analyzed by GC coupled to GC-MS. The essential oil contained a total of 99 constituents for S. incana and 31 for C. hispidula representing 95.7% and 99.6 of the total oils, rerspectively. The mains components of S. incana oil were linalool (25.2), cedrol (13.7%), geraniol (7%) and α-terpineol (5.4%). The chemical constituents of the oil from C. hispidula were predominated by pulegone (43.2%), isomenthone (36%), piperitone (3.2%), limonene (2.6%) and 4-terpineol (2.5%). The results revealed that the oil of the plants is characterized by the presence of many important components which could be applied in food, pharmaceutical and perfume industry.

Keywords: essential oils, Calamintha hispidula, Sideritis incana, chemical and molecular engineering

Procedia PDF Downloads 229
11992 Plackett-Burman Design to Evaluate the Influence of Operating Parameters on Anaerobic Orthophosphate Release from Enhanced Biological Phosphorus Removal Sludge

Authors: Reza Salehi, Peter L. Dold, Yves Comeau

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The aim of the present study was to investigate the effect of a total of 6 operating parameters including pH (X1), temperature (X2), stirring speed (X3), chemical oxygen demand (COD) (X4), volatile suspended solids (VSS) (X5) and time (X6) on anaerobic orthophosphate release from enhanced biological phosphorus removal (EBPR) sludge. An 8-run Plackett Burman design was applied and the statistical analysis of the experimental data was performed using Minitab16.2.4 software package. The Analysis of variance (ANOVA) results revealed that temperature, COD, VSS and time had a significant effect with p-values of less than 0.05 whereas pH and stirring speed were identified as non-significant parameters, but influenced orthophosphate release from the EBPR sludge. The mathematic expression obtained by the first-order multiple linear regression model between orthophosphate release from the EBPR sludge (Y) and the operating parameters (X1-X6) was Y=18.59+1.16X1-3.11X2-0.81X3+3.79X4+9.89X5+4.01X6. The model p-value and coefficient of determination (R2) value were 0.026 and of 99.87%, respectively, which indicates the model is significant and the predicted values of orthophosphate release from the EBPR sludge have been excellently correlated with the observed values.

Keywords: anaerobic, operating parameters, orthophosphate release, Plackett-Burman design

Procedia PDF Downloads 263
11991 IoT Continuous Monitoring Biochemical Oxygen Demand Wastewater Effluent Quality: Machine Learning Algorithms

Authors: Sergio Celaschi, Henrique Canavarro de Alencar, Claaudecir Biazoli

Abstract:

Effluent quality is of the highest priority for compliance with the permit limits of environmental protection agencies and ensures the protection of their local water system. Of the pollutants monitored, the biochemical oxygen demand (BOD) posed one of the greatest challenges. This work presents a solution for wastewater treatment plants - WWTP’s ability to react to different situations and meet treatment goals. Delayed BOD5 results from the lab take 7 to 8 analysis days, hindered the WWTP’s ability to react to different situations and meet treatment goals. Reducing BOD turnaround time from days to hours is our quest. Such a solution is based on a system of two BOD bioreactors associated with Digital Twin (DT) and Machine Learning (ML) methodologies via an Internet of Things (IoT) platform to monitor and control a WWTP to support decision making. DT is a virtual and dynamic replica of a production process. DT requires the ability to collect and store real-time sensor data related to the operating environment. Furthermore, it integrates and organizes the data on a digital platform and applies analytical models allowing a deeper understanding of the real process to catch sooner anomalies. In our system of continuous time monitoring of the BOD suppressed by the effluent treatment process, the DT algorithm for analyzing the data uses ML on a chemical kinetic parameterized model. The continuous BOD monitoring system, capable of providing results in a fraction of the time required by BOD5 analysis, is composed of two thermally isolated batch bioreactors. Each bioreactor contains input/output access to wastewater sample (influent and effluent), hydraulic conduction tubes, pumps, and valves for batch sample and dilution water, air supply for dissolved oxygen (DO) saturation, cooler/heater for sample thermal stability, optical ODO sensor based on fluorescence quenching, pH, ORP, temperature, and atmospheric pressure sensors, local PLC/CPU for TCP/IP data transmission interface. The dynamic BOD system monitoring range covers 2 mg/L < BOD < 2,000 mg/L. In addition to the BOD monitoring system, there are many other operational WWTP sensors. The CPU data is transmitted/received to/from the digital platform, which in turn performs analyses at periodic intervals, aiming to feed the learning process. BOD bulletins and their credibility intervals are made available in 12-hour intervals to web users. The chemical kinetics ML algorithm is composed of a coupled system of four first-order ordinary differential equations for the molar masses of DO, organic material present in the sample, biomass, and products (CO₂ and H₂O) of the reaction. This system is solved numerically linked to its initial conditions: DO (saturated) and initial products of the kinetic oxidation process; CO₂ = H₂0 = 0. The initial values for organic matter and biomass are estimated by the method of minimization of the mean square deviations. A real case of continuous monitoring of BOD wastewater effluent quality is being conducted by deploying an IoT application on a large wastewater purification system located in S. Paulo, Brazil.

Keywords: effluent treatment, biochemical oxygen demand, continuous monitoring, IoT, machine learning

Procedia PDF Downloads 61
11990 Endoscopic Depiction and Treatment Evaluation of Spirocerca lupi in Dogs

Authors: ELdessouky Sheta, Sayed Elzomor, Haithem Farghali, Kawkab A. Ahmed, Naglaa A. Abd Elkader

Abstract:

The present investigation has been dealt with Spirocerca (S.) lupi infested mongrel dogs. This parasitic disease is highly infective to human beings and carnivores. The diagnosis march has been comprised the lateral contrast thoracic radiographs, fecal examination, blood profile, endoscopic examination and histopathological sections of deep seated pinch biopsies. These infested dogs have been put under an adopted treatment with Ivermectin injection combined with oral prednisolone. The obtained results reveal an absence of the pessimistic recognitions particularly after 3 weeks from the onset of treatment. Endoscopically the presented esophageal nodules are marked out in the distal third of infested dogs' esophagus as masses assigned into the esophageal lumen and fundus of stomach. The endoscopic outlook of Spirocerca lupi lesions has been considered an integral procedure of the diagnostic march and for evaluation of treatment follow up. The diagnostic procedures and the recommended treatment are the vet's guidance to care for Spirocerca lupi in dogs, hoping in future to prevent this disease from being spread among human beings and other carnivores.

Keywords: endoscopy, esophagus, stomach spirocercosis, dogs

Procedia PDF Downloads 372
11989 Identification, Synthesis, and Biological Evaluation of the Major Human Metabolite of NLRP3 Inflammasome Inhibitor MCC950

Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

Abstract:

MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

Procedia PDF Downloads 235