Search results for: basal cell skin cancer

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 361

Authors: Subrat Kumar Bhattamisra, Vivian Lee Yean Yan, Chin Koh Lee, Chew Hui Kuean, Yun Khoon Liew, Mayuren Candasamy

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Geraniol, an acyclic monoterpenoid is the main active constituent in the essential oils of rose and palmorosa. Antioxidant, antibacterial, anticancer and antiulcer activity of geraniol was reported by many researchers. The present investigation was designed to study in vivo antiulcer and anti-Helicobacter pylori activity of geraniol. Antiulcer and anti-H. pylori activity of geraniol was evaluated on acetic acid plus H. pylori induced ulcer in rats. Acetic acid (0.03 mL) was injected to the sub-serosal layer of the stomach through laparotomy under anaesthesia. Orogastric inoculation of H. pylori (ATCC 43504) was done twice daily for 7 days. Geraniol (15 and 30 mg/kg), vehicle and standard drugs (Amoxicillin, 50 mg/kg; clarithromycin, 25 mg/kg & omeprazole, 20 mg/kg) was administered twice daily for 14 days. Antiulcer activity of geraniol was examined by the determination of gastric ulcer index, measuring the volume of gastric juice, pH and total acidity, myeloperoxidase activity and histopathological examination. Histopathological investigation for the presence of inflammation, white blood cell infiltration, edema, the mucosal damage was studied. The presence of H. pylori was detected by placing a biopsy sample from antral part of the stomach into rapid urease test. Ulcer index in H. pylori inoculated control group was 4.13 ± 0.85 and was significantly (P < 0.05) lowered in geraniol (30 mg/kg) and reference drug treated group. Geraniol increase the pH of the gastric juice (2.18 ± 0.13 in control vs. 4.14 ± 0.57 in geraniol 30mg/kg) and lower total acidity significantly (P < 0.01) in geraniol (15 & 30 mg/kg). Myeloperoxidase (MPO) activity was measured in stomach homogenate of all the groups. H. pylori control group has significant (P < 0.05) increase in MPO activity compared to normal control group. Geraniol (30 mg/kg) was showed significant (P < 0.05) and most effective among all the groups. Histopathological examination of rat stomach was scored and the total score for H. pylori control group was 8. After geraniol (30 mg/kg) and reference drug treatment, the histopathological score was significantly decreased and it was observed to be 3.5 and 2.0 respectively. Percentage inhibition of H. pylori infection in geraniol (30 mg/kg) and reference drug were found to be 40% and 50% respectively whereas, 100% infection in H. pylori control group was observed. Geraniol exhibited significant antiulcer and anti- H. pylori activity in the rats. Thus, geraniol has the potential for the further development as an effective medication in treating H. pylori associated ulcer.

Keywords: geraniol, helicobacter pylori atcc 43504, myeloperoxidase, ulcer

Procedia PDF Downloads 343

Authors: Elizabeth Adebomi Akinlotan, Olukemi Odukoya

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INTRODUCTION: Physical Activity is defined as activity that involves bodily movement which is done as a part of daily activity in the form of working, playing, active transportation such as walking and also as a form of recreational activity. Physical inactivity has been identified as the fourth leading risk factor for global mortality and morbidity causing an estimated 3.2 million deaths globally and 5.5% of total deaths and it remains a pressing public health issue. There is a shift in the major causes of death from communicable to non-communicable diseases in many developed countries and this is fast becoming the case in developing countries. Physical activity is an important determinant of health and has been associated with lower mortality rates as it reduces the risk of developing chronic diseases such as diabetes mellitus, hypertension, stroke, cancer and osteoporosis. It improves musculoskeletal health, controls weight and reduces symptoms of depression. AIM: The aim is to study the knowledge, attitude and practices of physical activity among adults in Alimosho local government area. METHODOLOGY: This was a descriptive cross sectional survey designed to study the knowledge, attitude and practice of physical activity among adults in Alimosho Local Government Area. The study population were 250 adults aged 18-65 who were residents of the area of more than 6 months duration and had no chronic disease condition or physical disability. A multistage sampling method was used to select the respondents and data was collected using interviewer administered questionnaires. The data was analyzed with the use of EPI-info 2007 statistical software. Chi Square was thereafter used to test the association between selected variables. The level of statistical significance was set at 5% (p<0.05). RESULTS: In general, majority (61.6%) of the respondents had a good knowledge of what physical activity entails, 34.0% had fair knowledge and 4.4% had poor knowledge. There was a favorable attitude towards physical activity among the respondents with 82.4% having an overall positive attitude. Below a third of the respondents (26.4%) reported having a high physical activity (METS > 3001) while 40.0% had moderate (601-3000 METS) levels of activity and 33.6% were inactive (<600METS). There is statistical significance between the gender of the respondent and the levels of physical activity (p=0.0007); 75.2% males reached the minimum recommendations while 24.8% were inactive and 55.0% females reached the minimum recommendations while 45.0% were inactive. Results also showed that of 95 respondents who were satisfied with their levels of physical activity, 33.7% were insufficiently active while 66.3% were either minimally active or highly active and of 110 who were unsatisfied with their levels of physical activity, 72.0% were above the minimum recommendations while 38.0% were insufficiently active. CONCLUSION: In contrast to the high level of knowledge and favorable attitude towards physical activity, there was a lower level of practice of high or moderate physical activities. It is recommended that more awareness should be created on the recommended levels of physical activity especially for the vigorous intensity and moderate intensity physical activity.

Keywords: METS, physical activity, physical inactivity, public health

Procedia PDF Downloads 233

Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

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This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

Procedia PDF Downloads 288

Authors: Simona Dostalova, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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Protein apoferritin seems to be a very promising structure for use as a nanocarrier. It is prepared from intracellular ferritin protein naturally found in most organisms. The role of ferritin proteins is to store and transport ferrous ions. Apoferritin is a hollow protein cage without ferrous ions that can be prepared from ferritin by reduction with thioglycolic acid or dithionite. The structure of apoferritin is composed of 24 protein subunits, creating a sphere with 12 nm in diameter. The inner cavity has a diameter of 8 nm. The drug encapsulation process is based on the response of apoferritin structure to the pH changes of surrounding solution. In low pH, apoferritin is disassembled into individual subunits and its structure is “opened”. It can then be mixed with any desired cytotoxic drug and after adjustment of pH back to neutral the subunits are reconnected again and the drug is encapsulated within the apoferritin particles. Excess drug molecules can be removed by dialysis. The receptors for apoferritin, SCARA5 and TfR1 can be found in the membrane of both healthy and cancer cells. To enhance the specific targeting of apoferritin nanocarrier, it is possible to modify its surface with targeting moieties, such as antibodies. To ensure sterically correct complex, we used a a peptide linker based on a protein G with N-terminus affinity towards Fc region of antibodies. To connect the peptide to the surface of apoferritin, the C-terminus of peptide was made of cysteine with affinity to gold. The surface of apoferritin with encapsulated doxorubicin (ApoDox) was coated either with gold nanoparticles (ApoDox-Nano) or gold (III) chloride hydrate reduced with sodium borohydride (ApoDox-HAu). The applied amount of gold in form of gold (III) chloride hydrate was 10 times higher than in the case of gold nanoparticles. However, after removal of the excess unbound ions by electrophoretic separation, the concentration of gold on the surface of apoferritin was only 6 times higher for ApoDox-HAu in comparison with ApoDox-Nano. Moreover, the reduction with sodium borohydride caused a loss of doxorubicin fluorescent properties (excitation maximum at 480 nm with emission maximum at 600 nm) and thus its biological activity. Fluorescent properties of ApoDox-Nano were similar to the unmodified ApoDox, therefore it was more suited for the intended use. To evaluate the specificity of apoferritin modified with antibodies, we used ELISA-like method with the surface of microtitration plate wells coated by the antigen (goat anti-human IgG antibodies). To these wells, we applied ApoDox without targeting antibodies and ApoDox-Nano modified with targeting antibodies (human IgG antibodies). The amount of unmodified ApoDox on antigen after incubation and subsequent rinsing with water was 5 times lower than in the case of ApoDox-Nano modified with targeting antibodies. The modification of non-gold ApoDox with antibodies caused no change in its targeting properties. It can therefore be concluded that the demonstrated procedure allows us to create nanocarrier with enhanced targeting properties, suitable for nanomedicine.

Keywords: apoferritin, doxorubicin, nanocarrier, targeting antibodies

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Authors: Ren-Jy Ben, Jo-Chi Jao, Chiu-Ya Liao, Ya-Ru Tsai, Lain-Chyr Hwang, Po-Chou Chen

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Cancer is still one of the serious diseases threatening the lives of human beings. How to have an early diagnosis and effective treatment for tumors is a very important issue. The animal carcinoma model can provide a simulation tool for the study of pathogenesis, biological characteristics and therapeutic effects. Recently, drug delivery systems have been rapidly developed to effectively improve the therapeutic effects. Liposome plays an increasingly important role in clinical diagnosis and therapy for delivering a pharmaceutic or contrast agent to the targeted sites. Liposome can be absorbed and excreted by the human body, and is well known that no harm to the human body. This study aimed to compare the therapeutic effects between encapsulated (doxorubicin liposomal, LipoDox) and un-encapsulated (doxorubicin, Dox) anti-tumor drugs using Magnetic Resonance Imaging (MRI). Twenty-four New Zealand rabbits implanted with VX2 carcinoma at left thigh were classified into three groups: control group (untreated), Dox-treated group and LipoDox-treated group, 8 rabbits for each group. MRI scans were performed three days after tumor implantation. A 1.5T GE Signa HDxt whole body MRI scanner with a high resolution knee coil was used in this study. After a 3-plane localizer scan was performed, Three-Dimensional (3D) Fast Spin Echo (FSE) T2-Weighted Images (T2WI) was used for tumor volumetric quantification. And Two-Dimensional (2D) spoiled gradient recalled echo (SPGR) dynamic Contrast-enhanced (DCE) MRI was used for tumor perfusion evaluation. DCE-MRI was designed to acquire four baseline images, followed by contrast agent Gd-DOTA injection through the ear vein of rabbits. Afterwards, a series of 32 images were acquired to observe the signals change over time in the tumor and muscle. The MRI scanning was scheduled on a weekly basis for a period of four weeks to observe the tumor progression longitudinally. The Dox and LipoDox treatments were prescribed 3 times in the first week immediately after VX2 tumor implantation. ImageJ was used to quantitate tumor volume and time course signal enhancement on DCE images. The changes of tumor size showed that the growth of VX2 tumors was effectively inhibited for both LipoDox-treated and Dox-treated groups. Furthermore, the tumor volume of LipoDox-treated group was significantly lower than that of Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is significantly lower than that of the other two groups, which implies that targeted therapeutic drug remained in the tumor tissue. This study provides a radiation-free and non-invasive MRI method for therapeutic monitoring of targeted liposome on an animal tumor model.

Keywords: doxorubicin, dynamic contrast-enhanced MRI, lipodox, magnetic resonance imaging, VX2 tumor model

Procedia PDF Downloads 457

Authors: Uraporn Vongvatcharanon, Kochakorn Sukjan, Wandee Udomuksorn, Ekkasit Kumarnsit, Surapong Vongvatcharanon

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Sarcopenia is a loss of muscle mass, and strength frequently found in menopause. Estrogen replacement has been shown to improve such a loss of muscle functions. However, there is an increased risk of cancer that has to be considered because of the estrogen replacement therapy. Thus, phytoestrogen supplementation has been suggested as an alternative therapy. Pueraria mirifica (PM) is a plant in the family Leguminosae, that is known to be phytoestrogen-rich and has been traditionally used for the treatment of menopausal symptoms. It contains isoflavones and other compounds such as miroestrol and its derivatives. Parvalbumin (PV) is a calcium binding protein and functions as a relaxing factor in fast twitch muscle fibers. A decrease of the PV level results in a reduction of the speed of the twitch relaxation. Therefore, this study aimed to investigate the effect of an ethanolic extract from Pueraria mirifica on the estrogen levels, skeletal muscle functions and PV levels in the extensor digitorum longus (EDL) and gastrocnemius of ovariectomized rats. Twelve-week old female Wistar rats (200-250 g) were divided into 6 groups: SHAM (un-ovariectomized rats, that received double distilled water), PM-0 (ovariectomized rats, OVX, receiving double distilled water), E (OVX, receiving an estradiol benzoate dose of 0.04 mg/kg), PM-50 (OVX receiving PM 50 mg/kg), PM-500 (OVX receiving PM 500 mg/kg), PM-1000 (OVX receiving PM 1000 mg/kg) all for 90 days. The PM-0 group had estrogen levels, uterus weights, muscle mass, myofiber cross-section areas, peak tension, fatigue resistance, speed of relaxation and parvalbumin levels of both EDL and gastrocnemius that were significantly reduced compared to those of the SHAM group (p<0.05). Also the α and β estrogen receptor immunoreactivities and the parvalbumin immunoreactivities of both EDL and gastrocnemius were decreased in the PM-0 group. In contrast the E, PM-50, PM-500 and PM-1000 group had estrogen levels, uterus weights, muscle mass, myofiber cross-section areas, peak tension, fatigue resistance, speed of relaxation of both EDL and gastrocnemius that were significantly increased compared with PM-0 group (p<0.05). In addition, the α and β estrogen receptor immunoreactivities and parvalbumin immunoreactivity of both the EDL and gastrocnemius were increased in the E, PM-50, PM-500 and PM-1000 group. In addition the extract of Pueraria mirifica replacement group at 50 and 500 mg/kg had significantly increased parvalbumin levels in the EDL muscle but in the gastrocnemius, only the dose of 500 mg/kg increased the parvalbumin levels (p<0.05). These results have demonstrated that the use of the Pueraria mirifica extract as a replacement therapy for estrogen produced estrogenic activity that was similar to that produced by the estradiol benzoate replacement. It seems that the phytoestrogens could bind with the estrogen receptors and stimulate the transcriptional activity to synthesise muscle protein that caused an increase in muscle mass and parvalbumin levels. Thus, muscle synthesis may restore parvalbumin levels resulting in an enhanced relaxation efficiency that would lead to a shortened latent period before the next contraction.

Keywords: Puereria mirifica, Parvalbumin, estrogen, ovariectomized rats

Procedia PDF Downloads 382

Authors: Zeynep Yilmazer Hitit, Patrick C. Hallenbeck

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Fuel reserve requirements due to depletion of fossil fuels have increased interest in biohydrogen since the 1990’s. In fermentative hydrogen production, pure, mixed, and co-cultures can be used to produce hydrogen. Several previous studies have evaluated hydrogen production by pure cultures of Clostridium butyricum or Enterobacter aerogenes. Evaluating hydrogen production by co-culture of these microorganisms is an interestıng approach since E. aerogenes is a facultative microorganism with resistance to oxygen in contrast to the strict anaerobe C. butyricum, and therefore has the ability to maintain anaerobic conditions. It was found that using co-cultures of facultative E. aerogenes (as a reducing agent and H2 producer) and the obligate anaerobe C. butyricum for producing hydrogen increases the yield of hydrogen by about 50% compared to C. butyricum by itself. Also, using different types of microorganisms for hydrogen production eliminates the need to use expensive reducing agents. C. butyricum strain pre-cultured anaerobically at 37 0C for 15h by inoculating 100 mL of GP medium (pH 6.8) consisting of 1% glucose, 2% polypeptone, 0.2% KH2PO4, 0.05% yeast extract, 0.05% MgSO4. 7H2O and E. aerogenes strain was pre-cultured aerobically at 30 0C, 150 rpm for 9 h by inoculating 100 mL of TGY medium (pH 6.8), consisting of 0.1% glucose, 0.5% tryptone, 0.1% K2HPO4, 0.5% yeast extract. All duplicate batch experiments were conducted in 100 mL bottles with different inoculum ratios of Clostridium butyricum and Enterobater aerogenes (C:E) using 5x diluted rich media (GP) consisting of 2 g/L glucose, 4g/L polypeptone, 0.4 g/L KH2PO4, 0.1 g/L yeast extract, 0.1 MgSO4.7H2O. The range of inoculum ratio of C. butyricum to E. aerogenes were 2:1,4:1,8:1, 1:2,1:4, 1:8, 1:0, 0:1. Using glucose as a carbon source aided in the observation of microbial behavior as well as making the effect of inoculum ratio more evident. Nearly all the glucose in the medium was used to produce hydrogen, except at a 1:0 ratio of inoculum (i.e. containing only C. butyricum). Low glucose consumption leads to a higher hydrogen yield due to cumulative hydrogen production and consumption of glucose, but not as much as C:E, 8:1. The lowest hydrogen yield was achieved in 1:8 inoculum ratio of C:E, 71.9 mL, 1.007±0.01 mol H2/mol glucose and the highest cumulative hydrogen, hydrogen yield and dry cell weight were achieved in 8:1 inoculum ratio of C:E, 117.4 mL, 2.035±0.082 mol H2/mol glucose, 0.4 g/L respectively. In this study effect of inoculum ratio on dark fermentative biohydrogen production using C. butyricum and E. aerogenes was investigated. The maximum hydrogen yield of 2.035mol H2/mol glucose was obtained using 2g/L glucose, an initial pH of 6 and an inoculum ratio of C. butyricum to E. aerogenes of 8:1. Results showed that inoculum ratio is an important parameter on hydrogen production due to competition between the two microorganisms in using substrate for growth and production of by-products. The results presented here could be of great significance for further waste management studies using co-culture hydrogen production.

Keywords: biohydrogen, Clostridium butyricum, dark fermentation, Enterobacter aerogenes, inoculum ratio in biohydrogen production

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Authors: Calister Wingang Makebe, Wilson Ambindei Agwanande, Emmanuel Jong Nso, P. Nisha

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Traditional liquid-state fermentation processes of Annona muricata L. juice can result in fluctuating product quality and quantity due to difficulties in control and scale up. This work describes a laboratory-scale batch fermentation process to produce a probiotic Annona muricata L. enzymatically extracted juice, which was modeled using the Doehlert design with independent extraction factors being incubation time, temperature, and enzyme concentration. It aimed at a better understanding of the traditional process as an initial step for future optimization. Annona muricata L. juice was fermented with L. acidophilus (NCDC 291) (LA), L. casei (NCDC 17) (LC), and a blend of LA and LC (LCA) for 72 h at 37 °C. Experimental data were fitted into mathematical models (Monod, Logistic and Luedeking and Piret models) using MATLAB software, to describe biomass growth, sugar utilization, and organic acid production. The optimal fermentation time was obtained based on cell viability, which was 24 h for LC and 36 h for LA and LCA. The model was particularly effective in estimating biomass growth, reducing sugar consumption, and lactic acid production. The values of the determination coefficient, R2, were 0.9946, 0.9913 and 0.9946, while the residual sum of square error, SSE, was 0.2876, 0.1738 and 0.1589 for LC, LA and LCA, respectively. The growth kinetic parameters included the maximum specific growth rate, µm, which was 0.2876 h-1, 0.1738 h-1 and 0.1589 h-1 as well as the substrate saturation, Ks, with 9.0680 g/L, 9.9337 g/L and 9.0709 g/L respectively for LC, LA and LCA. For the stoichiometric parameters, the yield of biomass based on utilized substrate (YXS) was 50.7932, 3.3940 and 61.0202, and the yield of product based on utilized substrate (YPS) was 2.4524, 0.2307 and 0.7415 for LC, LA, and LCA, respectively. In addition, the maintenance energy parameter (ms) was 0.0128, 0.0001 and 0.0004 with respect to LC, LA and LCA. With the kinetic model proposed by Luedeking and Piret for lactic acid production rate, the growth associated, and non-growth associated coefficients were determined as 1.0028 and 0.0109, respectively. The model was demonstrated for batch growth of LA, LC, and LCA in Annona muricata L. juice. The present investigation validates the potential of Annona muricata L. based medium for heightened economical production of a probiotic medium.

Keywords: L. acidophilus, L. casei, fermentation, modelling, kinetics

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Authors: Vimal Kumar Dewangan, T. S. Sampath Kumar, Mukesh Doble, Viju Daniel Varghese

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The apatite-based, i.e., calcium-deficient hydroxyapatite (CDHAp) bone cement is well-known potential bone graft/substitute in orthopaedics due to its similar chemical composition with natural bone minerals. Therefore, an easy approach was attempted to fabricate the apatite-based (CDHAp) bone cement with improved injectability, bioresorbability, and macroporosity. In this study, the desired bone cement was developed by mixing the solid phase (consisting of wet chemically synthesized nanocrystalline hydroxyapatite and commercially available (synthetic) tricalcium phosphate) and the liquid phase (consisting of cement binding accelerator with few biopolymers in a dilute acidic solution) along with a liquid porogen as polysorbate or a solid porogen as mannitol (for comparison) in an optimized liquid-to-powder ratio. The fabricated cement sets within clinically preferred setting time (≤20 minutes) are better injectable (>70%) and also stable at ~7.3-7.4 (physiological pH). The CDHAp phased bone cement was resulted by immersing the fabricated after-set cement in phosphate buffer solution and other similar artificial body fluids and incubated at physiological conditions for seven days, confirmed through the X-ray diffraction and Fourier transform-infrared spectroscopy analyses. The so-formed synthetic apatite-based bone cement holds the acceptable compressive strength (within the range of trabecular bone) with average interconnected pores size falls in a macropores range (~50-200μm) inside the cement, verified by scanning electron microscopy (SEM), mercury intrusion porosimetry and micro-CT analysis techniques. Also, it is biodegradable (degrades ~19-22% within 10-12 weeks) when incubated in artificial body fluids under physiological conditions. The biocompatibility study of the bone cement, when incubated with MG63 cells, shows a significant increase in the cell viability after 3rd day of incubation compared with the control, and the cells were well-attached and spread completely on the surface of the bone cement, confirmed through SEM and fluorescence microscopy analyses. With this all, we can conclude that the developed synthetic macroporous apatite-based bone cement may have the potential to become promising material used as a trabecular bone substitute.

Keywords: calcium deficient hydroxyapatite, synthetic apatite-based bone cement, injectability, macroporosity, trabecular bone substitute

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Authors: Rohit Vashistha, Amit Kumar Gupta, G. P. Ravishankar, Mahesh P. Padwale

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Accurate thrust measurement is required for aircraft during takeoff and after ski-jump. In a developmental aircraft, takeoff from ship is extremely critical and thrust produced by the engine should be known to the pilot before takeoff so that if thrust produced is not sufficient then take-off can be aborted and accident can be avoided. After ski-jump, thrust produced by engine is required because the horizontal speed of aircraft is less than the normal takeoff speed. Engine should be able to produce enough thrust to provide nominal horizontal takeoff speed to the airframe within prescribed time limit. The contemporary low bypass gas turbine engines generally have three mounts where the two side mounts transfer the engine thrust to the airframe. The third mount only takes the weight component. It does not take any thrust component. In the present method of thrust estimation, the strain gauging of the two side mounts is carried out. The strain produced at various power settings is used to estimate the thrust produced by the engine. The quarter Wheatstone bridge is used to acquire the strain data. The engine mount assembly is subjected to Universal Test Machine for determination of equivalent elasticity of assembly. This elasticity value is used in the analytical approach for estimation of engine thrust. The estimated thrust is compared with the test bed load cell thrust data. The experimental strain data is also compared with strain data obtained from FEM analysis. Experimental setup: The strain gauge is mounted on the tapered portion of the engine mount sleeve. Two strain gauges are mounted on diametrically opposite locations. Both of the strain gauges on the sleeve were in the horizontal plane. In this way, these strain gauges were not taking any strain due to the weight of the engine (except negligible strain due to material's poison's ratio) or the hoop's stress. Only the third mount strain gauge will show strain when engine is not running i.e. strain due to weight of engine. When engine starts running, all the load will be taken by the side mounts. The strain gauge on the forward side of the sleeve was showing a compressive strain and the strain gauge on the rear side of the sleeve shows a tensile strain. Results and conclusion: the analytical calculation shows that the hoop stresses dominate the bending stress. The estimated thrust by strain gauge shows good accuracy at higher power setting as compared to lower power setting. The accuracy of estimated thrust at max power setting is 99.7% whereas at lower power setting is 78%.

Keywords: engine mounts, finite elements analysis, strain gauge, stress

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Authors: Sushil Pradhan

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Biotechnology contributes to sustainable development in several ways such as biofertilizer production, biopesticide production and management of environmental pollution, tissue culture and biodiversity conservation in vitro, in vivo and in situ, Insectivorous medicinal plant Drosera burmannii Vahl belongs to the Family-Droseraceae under Order-Caryophyllales, Dicotyledoneae, Angiospermeae which has 31 (thirty one) living genera and 194 species besides 7 (seven) extinct (fossil) genera. Locally it is known as “Patkanduri” in Odia. Its Hindi name is “Mukhajali” and its English name is “Sundew”. The earliest species of Drosera was first reported in 1753 by Carolous Linnaeus called Drosera indica L (Indian Sundew). The latest species of Drosera reported by Fleisch A, Robinson, AS, McPherson S, Heinrich V, Gironella E and Madulida D.A. (2011) is Drosera ultramafica from Malaysia. More than 50 % species of Drosera have been reported from Australia and next to Australia is South Africa. India harbours only 3 species such as D. indica L, Drosera burmannii Vahl and D. peltata L. From our Odisha only D. burmannii Vahl is being reported for the first time from the district of Subarnapur near Sonepur (Arjunpur Reserve Forest Area). Drosera plant is autotrophic but to supplement its Nitrogen (N2) requirement it adopts heterotrophic mode of nutrition (insectivorous/carnivorous) as well. The colour of plant in mostly red and about 20-30cm in height with beautiful pink or white pentamerous flowers. Plants grow luxuriantly during November to February in shady and moist places near small water bodies of running water stream. Medicinally it is a popular herb in the locality for the treatment of cold and cough in children in rainy season by the local Doctors (Kabiraj and Baidya). In the present field investigation an attempt has been made to understand the unique reproductive phase and life cycle of the plant thereby planning for its conservation and propagation through various techniques of tissue culture and biotechnology. More importantly besides morphological and anatomical studies, cytological investigation is being carried out to find out the number of chromosomes in the cell and its genomics as there is no such report as yet for Drosera burmannii Vahl. The ecological significance and biodiversity conservation of Drosera with special reference to energy, environmental and chemical engineering has been discussed in the research paper presentation.

Keywords: insectivorous, medicinal, drosera, biotechnology, chromosome, genome

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Authors: W. Q. Wang, Y. Yin, D. B. Zou, T. P. Yu, J. M. Ouyang, F. Q. Shao

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High-energy-density state, i.e., matter and radiation at energy densities in excess of 10^11 J/m^3, is related to material, nuclear physics, astrophysics, and geophysics. Laser-driven particle beams are better suited to heat the matter as a trigger due to their unique properties of ultrashort duration and low emittance. Compared to X-ray and electron sources, it is easier to generate uniformly heated large-volume material for the proton and ion beams because of highly localized energy deposition. With the construction of state-of-art high power laser facilities, creating of extremely conditions of high-temperature and high-density in laboratories becomes possible. It has been demonstrated that on a picosecond time scale the solid density material can be isochorically heated to over 20 eV by the ultrafast proton beam generated from spherically shaped targets. For the above-mentioned technique, the proton energy density plays a crucial role in the formation of warm dense matter states. Recently, several methods have devoted to realize the focusing of the accelerated protons, involving externally exerted static-fields or specially designed targets interacting with a single or multi-pile laser pulses. In previous works, two co-propagating or opposite direction laser pulses are employed to strike a submicron plasma-shell. However, ultra-high pulse intensities, accurately temporal synchronization and undesirable transverse instabilities for a long time are still intractable for currently experimental implementations. A mechanism of the focusing of laser-driven proton beams from two-ion-species arched targets is investigated by multi-dimensional particle-in-cell simulations. When an intense linearly-polarized laser pulse impinges on the thin arched target, all electrons are completely evacuated, leading to a Coulomb-explosive electric-field mostly originated from the heavier carbon ions. The lighter protons in the moving reference frame by the ionic sound speed will be accelerated and effectively focused because of this radially isotropic field. At a 2.42×10^21 W/cm^2 laser intensity, a ballistic proton bunch with its energy-density as high as 2.15×10^17 J/m^3 is produced, and the highest proton energy and the focusing position agree well with that from the theory.

Keywords: Coulomb explosion, focusing, high-energy-density, ion acceleration

Procedia PDF Downloads 344

Authors: Piotr J. Skusiewicz, Johnathan Saul, Ijhar Rusli, Svetlana Aleksandrova, Stephen. F. Benjamin, Miroslaw Gall, Steve Pierson, Carol A. Roberts

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The application of turbocharging in automotive engines leads to swirling flow entering the catalyst. The behaviour of this type of flow within the catalyst has yet to be adequately documented. This work discusses the effect of swirling flow on the flow distribution in automotive exhaust catalysts. Compressed air supplied to a moving-block swirl generator allowed for swirling flow with variable intensities to be generated. Swirl intensities were measured at the swirl generator outlet using single-sensor hot-wire probes. The swirling flow was fed into diffusers with total angles of 10°, 30° and 180°. Downstream of the diffusers, a wash-coated diesel oxidation catalyst (DOC) of length 143.8 mm, diameter 76.2 mm and nominal cell density of 400 cpsi was fitted. Velocity profiles were measured at the outlet sleeve about 30 mm downstream of the monolith outlet using single-sensor hot-wire probes. Wall static pressure was recorded using a multi-tube manometer connected to pressure taps positioned along the diffuser walls. The results show that as swirl is increased, more of the flow is directed towards the diffuser walls. The velocity decreases around the centre-line and maximum velocities are observed close to the outer radius of the monolith for all flow rates. At the maximum swirl intensity, reversed flow was recorded near the centre of the monolith. Wall static pressure measurements in the 180° diffuser indicated no pressure recovery as the flow enters the diffuser. This is indicative of flow separation at the inlet to the diffuser. To gain insight into the flow structure, CFD simulations have been performed for the 180° diffuser for a flow rate of 63 g/s. The geometry of the model consists of the complete assembly from the upstream swirl generator to the outlet sleeve. Modelling of the flow in the monolith was achieved using the porous medium approach, where the monolith with parallel flow channels is modelled as a porous medium that resists the flow. A reasonably good agreement was achieved between the experimental and CFD results downstream of the monolith. The CFD simulations allowed visualisation of the separation zones and central toroidal recirculation zones that occur within the expansion region at certain swirl intensities which are highlighted.

Keywords: catalyst, computational fluid dynamics, diffuser, hot-wire anemometry, swirling flow

Procedia PDF Downloads 304

Authors: Kamran Jawed, Anu Jose Mattam, Zia Fatma, Saima Wajid, Malik Z. Abdin, Syed Shams Yazdani

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Worldwide demand of natural and sustainable fuels and chemicals have encouraged researchers to develop microbial platform for synthesis of short chain fatty acids as they are useful precursors to replace petroleum-based fuels and chemicals. In this study, we evaluated the role of fatty acid synthesis and β-oxidation cycle of Escherichia coli to produce butyric acid, a 4-carbon short chain fatty acid, with the help of three thioesterases, i.e., TesAT from Anaerococcus tetradius, TesBF from Bryantella formatexigens and TesBT from Bacteroides thetaiotaomicron. We found that E. coli strain transformed with gene for TesBT and grown in presence of 8 g/L glucose produced maximum butyric acid titer at 1.46 g/L, followed by that of TesBF at 0.85 g/L and TesAT at 0.12 g/L, indicating that these thioesterases were efficiently converting short chain fatty acyl-ACP intermediate of fatty acid synthesis pathway into the corresponding acid. The titer of butyric acid varied significantly depending upon the plasmid copy number and strain genotype. Deletion of genes for fatty acyl-CoA synthetase and acyl-CoA dehydrogenase, which are involved in initiating the fatty acid degradation cycle, and overexpression of FadR, which is a dual transcriptional regulator and exerts negative control over fatty acid degradation pathway, reduced up to 30% of butyric acid titer. This observation suggested that β-oxidation pathway is working synergistically with fatty acid synthesis pathway in production of butyric acid. Moreover, accelerating the fatty acid elongation cycle by overexpressing acetyl-CoA carboxyltransferase (Acc) and 3-hydroxy-acyl-ACP dehydratase (FabZ) or by deleting FabR, the transcription suppressor of elongation, did not improve the butyric acid titer, rather favored the long chain fatty acid production. Finally, a balance between cell growth and butyric acid production was achieved with the use of phosphorous limited growth medium and 14.3 g/L butyric acid, and 17.5 g/L total free fatty acids (FFAs) titer was achieved during fed-batch cultivation. We have engineered an E. coli strain which utilizes the intermediate of both fatty acid synthesis and degradation pathway, i.e. butyryl-ACP and -CoA, to produce butyric acid from glucose. The strategy used in this study resulted in highest reported titers of butyric acid and FFAs in engineered E. coli.

Keywords: butenoic acid, butyric acid, Escherichia coli, fed-batch fermentation, short chain fatty acids, thioesterase

Procedia PDF Downloads 371

Authors: Sibghat Mansoor Rana, Muhammad Islam, Hamid Saeed, Hummera Rafique, Muhammad Majid, Muhammad Tahir Aqeel, Fariha Imtiaz, Zaman Ashraf

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The 1,3,4-oxadiazole derivatives Ox-6a-f have been synthesized by incorporating flur- biprofen moiety with the aim to explore the potential of target molecules to decrease the oxidative stress. The title compounds Ox-6a-f were prepared by simple reactions in which a flurbiprofen –COOH group was esterified with methanol in an acid-catalyzed medium, which was then reacted with hydrazine to afford the corresponding hydrazide. The acid hydrazide was then cyclized into 1,3,4-oxadiazole-2-thiol by reacting with CS2 in the presence of KOH. The title compounds Ox-6a-f were synthesized by the reaction of an –SH group with various alkyl/aryl chlorides, which involves an S-alkylation reaction. The structures of the synthesized Ox-6a-f derivatives were ascer- tained by spectroscopic data. The in silico molecular docking was performed against target proteins cyclooxygenase-2 COX-2 (PDBID 5KIR) and cyclooxygenase-1 COX-1 (PDBID 6Y3C) to determine the binding affinity of the synthesized compounds with these structures. It has been inferred that most of the synthesized compounds bind well with an active binding site of 5KIR compared to 6Y3C, and especially compound Ox-6f showed excellent binding affinity (7.70 kcal/mol) among all synthesized compounds Ox-6a-f. The molecular dynamic (MD) simulation has also been performed to check the stability of docking complexes of ligands with COX-2 by determining their root mean square deviation and root mean square fluctuation. Little fluctuation was observed in case of Ox-6f, which forms the most stable complex with COX-2. The comprehensive antioxidant potential of the synthesized compounds has been evaluated by determining their free radical scavenging activity, including DPPH, OH, nitric oxide (NO), and iron chelation assay. The derivative Ox-6f showed promising results with 80.23% radical scavenging potential at a dose of 100 μg/mL while ascorbic acid exhibited 87.72% inhibition at the same dose. The anti-inflammatory activity of the final products has also been performed, and inflammatory markers were assayed, such as a thiobarbituric acid-reducing substance, nitric oxide, interleukin-6 (IL-6), and COX-2. The derivatives Ox-6d and Ox-6f displayed higher anti-inflammatory activity, exhibiting 70.56% and 74.16% activity, respectively. The results were compared with standard ibuprofen, which showed 84.31% activity at the same dose, 200 μg/mL. The anti-inflammatory potential has been performed by following the carrageen-induced hind paw edema model, and results showed that derivative Ox-6f exhibited 79.83% reduction in edema volume compared to standard ibuprofen, which reduced 84.31% edema volume. As dry lab and wet lab results confirm each other, it has been deduced that derivative Ox-6f may serve as the lead structure to design potent compounds to address oxidative stress.

Keywords: synthetic chemistry, pharmaceutical chemistry, oxadiazole derivatives, anti-inflammatory, anti-cancer compounds

Procedia PDF Downloads 15

Authors: A. Y. Tsidulko, T. M. Pankova, E. V. Grigorieva

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High-grade gliomas are the most frequent and most aggressive brain tumors which are characterized by active invasion of tumor cells into the surrounding brain tissue, where the extracellular matrix (ECM) plays a crucial role. Disruption of ECM can be involved in anticancer drugs effectiveness, side-effects and also in tumor relapses. The anti-inflammatory agent dexamethasone is a common drug used during high-grade glioma treatment for alleviating cerebral edema. Although dexamethasone is widely used in the clinic, its effects on normal brain tissue ECM remain poorly investigated. It is known that proteoglycans (PGs) are a major component of the extracellular matrix in the central nervous system. In our work, we studied the effects of dexamethasone on the ECM proteoglycans (syndecan-1, glypican-1, perlecan, versican, brevican, NG2, decorin, biglican, lumican) using RT-PCR in the experimental animal model. It was shown that proteoglycans in rat brain have age-specific expression patterns. In early post-natal rat brain (8 days old rat pups) overall PGs expression was quite high and mainly expressed PGs were biglycan, decorin, and syndecan-1. The overall transcriptional activity of PGs in adult rat brain is 1.5-fold decreased compared to post-natal brain. The expression pattern was changed as well with biglycan, decorin, syndecan-1, glypican-1 and brevican becoming almost equally expressed. PGs expression patterns create a specific tissue microenvironment that differs in developing and adult brain. Dexamethasone regimen close to the one used in the clinic during high-grade glioma treatment significantly affects proteoglycans expression. It was shown that overall PGs transcription activity is 1.5-2-folds increased after dexamethasone treatment. The most up-regulated PGs were biglycan, decorin, and lumican. The PGs expression pattern in adult brain changed after treatment becoming quite close to the expression pattern in developing brain. It is known that microenvironment in developing tissues promotes cells proliferation while in adult tissues proliferation is usually suppressed. The changes occurring in the adult brain after dexamethasone treatment may lead to re-activation of cell proliferation due to signals from changed microenvironment. Taken together obtained data show that dexamethasone treatment significantly affects the normal brain ECM, creating the appropriate microenvironment for tumor cells proliferation and thus can reduce the effectiveness of anticancer treatment and promote tumor relapses. This work has been supported by a Russian Science Foundation (RSF Grant 16-15-10243)

Keywords: dexamthasone, extracellular matrix, glioma, proteoglycan

Procedia PDF Downloads 199

Authors: Bo Keun Lee, Doo Yeon Kwon, Ji Hoon Park, Gun Hee Lee, Ji Hye Baek, Heung Jae Chun, Young Joo Koh, Moon Suk Kim

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Thermo-responsive materials are viscoelastic materials that undergo a sol-to-gel phase transition at a specific temperature and many materials have been developed. MPEG-b-PCL (MPC) as a thermo-responsive material contained hydrophilic and hydrophobic segments and it formed an ordered crystalline structure of hydrophobic PCL segments in aqueous solutions. The ordered crystalline structure packed tightly or aggregated and finally induced an aggregated gel through intra- and inter-molecular interactions as a function of temperature. Thus, we introduced anionic and cationic groups into the end positions of the PCL chain to alter the hydrophobicity of the PCL segment. Introducing anionic and cationic groups into the PCL end position altered their solubility by changing the crystallinity and hydrophobicity of the PCL block domains. These results indicated that the properties of the end group in the hydrophobic PCL blockand the balance between hydrophobicity and hydrophilicity affect thermo-responsivebehavior of the copolymers in aqueous solutions. Thus, we concluded that determinant of the temperature-dependent thermo-responsive behavior of MPC depend on the ionic end group in the PCL block. So, we introduced zwitterionic end groups to investigate the thermo-responsive behavior of MPC. Methoxypoly(ethylene oxide) and ε-caprolactone (CL) were randomly copolymerized that introduced varying hydrophobic PCL lengths and an MPC featuring a zwitterionic sulfobetaine (MPC-ZW) at the chain end of the PCL segment. The MPC and MPC-ZW copolymers were obtained formed sol-state at room temperature when prepared as 20-wt% aqueous solutions. The solubility of MPC decreased when the PCL block was increased from molecular weight. The solubilization time of MPC-2.4k was around 20 min and MPC-2.8k, MPC-3.0k increased to 30 min and 1 h, respectively. MPC-3.6k was not solubilized. In case of MPC-ZW 3.6k, However, the zwitterion-modified MPC copolymers were solubilized in 3–5 min. This result indicates that the zwitterionic end group of the MPC-ZW diblock copolymer increased the aqueous solubility of the diblock copolymer even when the length of the hydrophobic PCL segment was increased. MPC and MPC-ZW diblock copolymers that featuring zwitterionic end groups were synthesized successfully. The sol-to-gel phase-transition was formed that specific temperature depend on the length of the PCL hydrophobic segments introduced and on the zwitterion groups attached to the MPC chain end. This result indicated that the zwitterionic end groups reduced the hydrophobicity in the PCL block and changed the solubilization. The MPC-ZW diblock copolymer can be utilized as a potential injectable drug and cell carrier.

Keywords: thermo-responsive material, zwitterionic, hydrophobic, crystallization, phase transition

Procedia PDF Downloads 507

Authors: Aniruddha Mitra, Abbas Rashidi, Shane Lewis, Jefferson Doehling, Alexis Pawlak, Jacob Schwartz, Imaobong Ekpo, Atin Adhikari

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Working or living close to demolition sites can increase risks of dust-related health problems. Demolition of concrete buildings may produce crystalline silica dust, which can be associated with a broad range of respiratory diseases including silicosis and lung cancers. Previous studies demonstrated significant associations between demolition dust exposure and increase in the incidence of mesothelioma or asbestos cancer. Dust is a generic term used for minute solid particles of typically <500 µm in diameter. Dust particles in demolition sites vary in a wide range of sizes. Larger particles tend to settle down from the air. On the other hand, the smaller and lighter solid particles remain dispersed in the air for a long period and pose sustained exposure risks. Submicron ultrafine particles and nanoparticles are respirable deeper into our alveoli beyond our body’s natural respiratory cleaning mechanisms such as cilia and mucous membranes and are likely to be retained in the lower airways. To our knowledge, how various demolition tasks release nanoparticles are largely unknown and previous studies mostly focused on course dust, PM2.5, and PM10. General belief is that the dust generated during demolition tasks are mostly large particles formed through crushing, grinding, or sawing of various concrete and wooden structures. Therefore, little consideration has been given to the generated submicron ultrafine and nanoparticles and their exposure levels. These data are, however, critically important because recent laboratory studies have demonstrated cytotoxicity of nanoparticles on lung epithelial cells. The above-described knowledge gaps were addressed in this study by a novel newly developed nanoparticle monitor, which was used for nanoparticle monitoring at two adjacent indoor and outdoor building demolition sites in southern Georgia. Nanoparticle levels were measured (n = 10) by TSI NanoScan SMPS Model 3910 at four different distances (5, 10, 15, and 30 m) from the work location as well as in control sites. Temperature and relative humidity levels were recorded. Indoor demolition works included acetylene torch, masonry drilling, ceiling panel removal, and other miscellaneous tasks. Whereas, outdoor demolition works included acetylene torch and skid-steer loader use to remove a HVAC system. Concentration ranges of nanoparticles of 13 particle sizes at the indoor demolition site were: 11.5 nm: 63 – 1054/cm³; 15.4 nm: 170 – 1690/cm³; 20.5 nm: 321 – 730/cm³; 27.4 nm: 740 – 3255/cm³; 36.5 nm: 1,220 – 17,828/cm³; 48.7 nm: 1,993 – 40,465/cm³; 64.9 nm: 2,848 – 58,910/cm³; 86.6 nm: 3,722 – 62,040/cm³; 115.5 nm: 3,732 – 46,786/cm³; 154 nm: 3,022 – 21,506/cm³; 205.4 nm: 12 – 15,482/cm³; 273.8 nm: Keywords: demolition dust, industrial hygiene, aerosol, occupational exposure

Procedia PDF Downloads 423

Authors: Ravisinh Solanki, Ravi Patel, Chhaganbhai Patel

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Purpose: The purpose of this study is to develop a methodology for the risk assessment and evaluation of nitrosamine impurities in Glipizide antidiabetic formulations. Nitroso compounds, including nitrosamines, have emerged as significant concerns in drug products, as highlighted by the ICH M7 guidelines. This study aims to identify known and potential sources of nitrosamine impurities that may contaminate Glipizide formulations and assess their presence. By determining observed or predicted levels of these impurities and comparing them with regulatory guidance, this research will contribute to ensuring the safety and quality of combination antidiabetic drug products on the market. Factors contributing to the presence of genotoxic nitrosamine contaminants in glipizide medications, such as secondary and tertiary amines, and nitroso group-complex forming molecules, will be investigated. Additionally, conditions necessary for nitrosamine formation, including the presence of nitrosating agents, and acidic environments, will be examined to enhance understanding and mitigation strategies. Method: The methodology for the study involves the implementation of the N-Nitroso Acid Precursor (NAP) test, as recommended by the WHO in 1978 and detailed in the 1980 International Agency for Research on Cancer monograph. Individual glass vials containing equivalent to 10mM quantities of Glipizide is prepared. These compounds are dissolved in an acidic environment and supplemented with 40 mM NaNO2. The resulting solutions are maintained at a temperature of 37°C for a duration of 4 hours. For the analysis of the samples, an HPLC method is employed for fit-for-purpose separation. LC resolution is achieved using a step gradient on an Agilent Eclipse Plus C18 column (4.6 X 100 mm, 3.5µ). Mobile phases A and B consist of 0.1% v/v formic acid in water and acetonitrile, respectively, following a gradient mode program. The flow rate is set at 0.6 mL/min, and the column compartment temperature is maintained at 35°C. Detection is performed using a PDA detector within the wavelength range of 190-400 nm. To determine the exact mass of formed nitrosamine drug substance related impurities (NDSRIs), the HPLC method is transferred to LC-TQ-MS/MS with the same mobile phase composition and gradient program. The injection volume is set at 5 µL, and MS analysis is conducted in Electrospray Ionization (ESI) mode within the mass range of 100−1000 Daltons. Results: The samples of NAP test were prepared according to the protocol. The samples were analyzed using HPLC and LC-TQ-MS/MS identify possible NDSRIs generated in different formulations of glipizide. It was found that the NAP test generated a various NDSRIs. The new finding, which has not been reported yet, discovered contamination of Glipizide. These NDSRIs are categorised based on the predicted carcinogenic potency and recommended its acceptable intact in medicines. The analytical method was found specific and reproducible.

Keywords: NDSRI, nitrosamine impurities, antidiabetic, glipizide, LC-MS/MS

Procedia PDF Downloads 33

Authors: Premalatha B. S., Shenoy A. M.

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Background: Rehabilitation of swallowing is as vital as speech in surgically treated head and neck cancer patients to maintain nutritional support, enhance wound healing and improve quality of life. Aspiration following supraglottic laryngectomy is very common, and rehabilitation of the same is crucial which requires involvement of speech therapist in close contact with head and neck surgeon. Objectives: To examine the functions of swallowing outcomes after intensive therapy in supraglottic laryngectomy. Materials: Thirty-nine supra glottic laryngectomees were participated in the study. Of them, 36 subjects were males and 3 were females, in the age range of 32-68 years. Eighteen subjects had undergone standard supra glottis laryngectomy (Group1) for supraglottic lesions where as 21 of them for extended supraglottic laryngectomy (Group 2) for base tongue and lateral pharyngeal wall lesion. Prior to surgery visit by speech pathologist was mandatory to assess the sutability for surgery and rehabilitation. Dysphagia rehabilitation started after decannulation of tracheostoma by focusing on orientation about anatomy, physiological variation before and after surgery, which was tailor made for each individual based on their type and extent of surgery. Supraglottic diet - Soft solid with supraglottic swallow method was advocated to prevent aspiration. The success of intervention was documented as number of sessions taken to swallow different food consistency and also percentage of subjects who achieved satisfactory swallow in terms of number of weeks in both the groups. Results: Statistical data was computed in two ways in both the groups 1) to calculate percentage (%) of subjects who swallowed satisfactorily in the time frame of less than 3 weeks to more than 6 weeks, 2) number of sessions taken to swallow without aspiration as far as food consistency was concerned. The study indicated that in group 1 subjects of standard supraglottic laryngectomy, 61% (n=11) of them were successfully rehabilitated but their swallowing normalcy was delayed by an average 29th post operative day (3-6 weeks). Thirty three percentages (33%) (n=6) of the subjects could swallow satisfactorily without aspiration even before 3 weeks and only 5 % (n=1) of the needed more than 6 weeks to achieve normal swallowing ability. Group 2 subjects of extended SGL only 47 %( n=10) of them could achieved satisfactory swallow by 3-6 weeks and 24% (n=5) of them of them achieved normal swallowing ability before 3 weeks. Around 4% (n=1) needed more than 6 weeks and as high as 24 % (n=5) of them continued to be supplemented with naso gastric feeding even after 8-10 months post operative as they exhibited severe aspiration. As far as type of food consistencies were concerned group 1 subject could able to swallow all types without aspiration much earlier than group 2 subjects. Group 1 needed only 8 swallowing therapy sessions for thickened soft solid and 15 sessions for liquids whereas group 2 required 14 sessions for soft solid and 17 sessions for liquids to achieve swallowing normalcy without aspiration. Conclusion: The study highlights the importance of dysphagia intervention in supraglottic laryngectomees by speech pathologist.

Keywords: dysphagia management, supraglotic diet, supraglottic laryngectomy, supraglottic swallow

Procedia PDF Downloads 231

Authors: Ladda Thiamwong, Renata Komalasari

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Falls are the leading cause of disability and hospitalization in low-income older adults. Fear of falling is present in 20% to 85 % of older adults and has been identified as an independent risk factor of fall risk, activity restriction, and loss of independence. About 12% of American older adults have subjective cognitive decline. Cognitive impairment is also an established factor of fall risk. However, it is unclear whether measures of fear of falling and subjective cognitive decline have the greatest association with fall risk in low-income older adults. The aim of this study was to evaluate the association between fear of falling, subjective cognitive decline-functional performance (SCD-FP), and fall risk using simple screening tools. In this cross-section study, we collected data from community-dwelling older adults 60 years or older in low-income settings in Central Florida, and 86 participants were included in the data analysis. Fear of falling was assessed by the Short Fall Efficacy Scale- International (Short FES-I) with seven items. Subjective cognitive decline-functional performance (SCD-FP) was assessed by a self-reported experience of worsening or more frequent confusion or memory loss in the past 12 months and its functional implications. Fall risk was evaluated by the Centers for Disease Control and Prevention (CDC)'s Stay Independent checklist with 12 items. The majority of participants were female, and more than half of the participants were African American. More than half of the participants had a higher school degree or higher, and less than 20% had no financial problems. Less than 30% of the participants perceived their general health as very good- excellent. More than half of the participants lived alone, and less than 15% lived with a partner or spouse. About 60% of the participants had hypertension, 40% had diabetes, 16% had cancer, and 50% had arthritis. About 30% of the participants had difficulty walking up ten steps without resting, more than 40% felt unsteady when walking, and 30% had been advised to use a cane or walker to get around safely. Regression analysis showed that fall risk was associated with fear of falling ( = .524, p <.001) and subjective cognitive decline-functional performance ( = .465, p =.027). The structure coefficient showed that fear of falling (rs2 = .922) was a stronger predictor of fall risk than subjective cognitive decline-functional performance (rs2= .200). Fear of falling and subjective cognitive decline-functional performance are growing public health issues, and addressing those issues is a public priority. Proactive screening for fear of falling and subjective cognitive decline-functional performance is critical in fall prevention. A combination of all three self-reported tools (Short FES-I, SCD-FP, and CDC's Stay Independent checklist) takes less than 5 minutes to complete. Primary care providers or public health professionals should consider including these tools to screen fear of falling and subjective cognitive decline-functional performance as part of fall risk assessment, especially in low-income settings. Thus, encouraging older adults and healthcare professionals to discuss fear of falling, subjective cognitive decline, and fall risk during routine medical office visits.

Keywords: falls, fall risk, fear of falling, cognition, subjective cognitive decline, low-income, older adults, community, screening, nursing, primary care

Procedia PDF Downloads 74

Authors: Jineetkumar Gawad, Chandrakant Bonde

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Tuberculosis (TB) is a major worldwide concern whose control has been exacerbated by HIV, the rise of multidrug-resistance (MDR-TB) and extensively drug resistance (XDR-TB) strains of Mycobacterium tuberculosis. The interest for newer and faster acting antitubercular drugs are more remarkable than any time. To search potent compounds is need and challenge for researchers. Here, we tried to design lead for inhibition of Decaprenyl phosphoryl-β-D-ribose 2′-epimerase (DprE1) enzyme. Arabinose is an essential constituent of mycobacterial cell wall. DprE1 is a flavoenzyme that converts decaprenylphosphoryl-D-ribose into decaprenylphosphoryl-2-keto-ribose, which is intermediate in biosynthetic pathway of arabinose. Latter, DprE2 converts keto-ribose into decaprenylphosphoryl-D-arabinose. We had a selection of 23 compounds from azaindole series for computational study, and they were drawn using marvisketch. Ligands were prepared using Maestro molecular modeling interface, Schrodinger, v10.5. Common pharmacophore hypotheses were developed by applying dataset thresholds to yield active and inactive set of compounds. There were 326 hypotheses were developed. On the basis of survival score, ADRRR (Survival Score: 5.453) was selected. Selected pharmacophore hypotheses were subjected to virtual screening results into 1000 hits. Hits were prepared and docked with protein 4KW5 (oxydoreductase inhibitor) was downloaded in .pdb format from RCSB Protein Data Bank. Protein was prepared using protein preparation wizard. Protein was preprocessed, the workspace was analyzed using force field OPLS 2005. Glide grid was generated by picking single atom in molecule. Prepared ligands were docked with prepared protein 4KW5 using Glide docking. After docking, on the basis of glide score top-five compounds were selected, (5223, 5812, 0661, 0662, and 2945) and the glide docking score (-8.928, -8.534, -8.412, -8.411, -8.351) respectively. There were interactions of ligand and protein, specifically HIS 132, LYS 418, TRY 230, ASN 385. Pi-pi stacking was observed in few compounds with basic Imidazo [4,5-b] pyridine ring. We had basic azaindole ring in parent compounds, but after glide docking, we received compounds with Imidazo [4,5-b] pyridine as a basic ring. That might be the new lead in the process of drug discovery.

Keywords: DprE1 inhibitors, in silico drug designing, imidazo [4, 5-b] pyridine, lead, tuberculosis

Procedia PDF Downloads 154

Authors: Calister Wingang Makebe, Wilson Agwanande Ambindei, Zangue Steve Carly Desobgo, Abraham Billu, Emmanuel Jong Nso, P. Nisha

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Traditional liquid-state fermentation processes of Annona muricata L. juice can result in fluctuating product quality and quantity due to difficulties in control and scale up. This work describes a laboratory-scale batch fermentation process to produce a probiotic Annona muricata L. enzymatically extracted juice, which was modeled using the Doehlert design with independent extraction factors being incubation time, temperature, and enzyme concentration. It aimed at a better understanding of the traditional process as an initial step for future optimization. Annona muricata L. juice was fermented with L. acidophilus (NCDC 291) (LA), L. casei (NCDC 17) (LC), and a blend of LA and LC (LCA) for 72 h at 37 °C. Experimental data were fitted into mathematical models (Monod, Logistic and Luedeking and Piret models) using MATLAB software, to describe biomass growth, sugar utilization, and organic acid production. The optimal fermentation time was obtained based on cell viability, which was 24 h for LC and 36 h for LA and LCA. The model was particularly effective in estimating biomass growth, reducing sugar consumption, and lactic acid production. The values of the determination coefficient, R2, were 0.9946, 0.9913 and 0.9946, while the residual sum of square error, SSE, was 0.2876, 0.1738 and 0.1589 for LC, LA and LCA, respectively. The growth kinetic parameters included the maximum specific growth rate, µm, which was 0.2876 h-1, 0.1738 h-1 and 0.1589 h-1, as well as the substrate saturation, Ks, with 9.0680 g/L, 9.9337 g/L and 9.0709 g/L respectively for LC, LA and LCA. For the stoichiometric parameters, the yield of biomass based on utilized substrate (YXS) was 50.7932, 3.3940 and 61.0202, and the yield of product based on utilized substrate (YPS) was 2.4524, 0.2307 and 0.7415 for LC, LA, and LCA, respectively. In addition, the maintenance energy parameter (ms) was 0.0128, 0.0001 and 0.0004 with respect to LC, LA and LCA. With the kinetic model proposed by Luedeking and Piret for lactic acid production rate, the growth associated and non-growth associated coefficients were determined as 1.0028 and 0.0109, respectively. The model was demonstrated for batch growth of LA, LC, and LCA in Annona muricata L. juice. The present investigation validates the potential of Annona muricata L. based medium for heightened economical production of a probiotic medium.

Keywords: L. acidophilus, L. casei, fermentation, modelling, kinetics

Procedia PDF Downloads 68

Authors: Savitha Janakiraman, Shivakumar M. C

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Anidulafungin, an advanced class of antifungal agent used for the treatment of chronic fungal infections, is derived from Echinocandin B nucleus, an intermediate metabolite of Echinocandin B produced by Aspergillus nidulans. The enzyme acylase derived from the fermentation broth of Actinoplanes utahensis (NRRL 12052) plays a key role in the bioconversion of echinocandin B to echinocandin B nucleus. The membrane-bound nature of acylase and low levels of expression contributes to the rate-limiting process of enzymatic deacylation, hence low yields of ECB nucleus and anidulafungin. In the present study, this is addressed through novel genetic engineering approaches of overexpression and heterologous expression studies, immobilization of whole cells of Actinoplanes utahensis (NRRL 12052) and Co-cultivation studies. Overexpression of the acylase gene in Actinoplanes utahensis (NRRL 12052) was done by increasing the gene copy number to increase the echinocandin B nucleus production. Echinocandin B acylase gene, under the control of a PermE* promoter, was cloned in pSET152 vector and introduced into Actinoplanes utahensis (NRRL12052) by a ɸC31-directed site-specific recombination method. The resultant recombinant strain (C2-18) showed a 3-fold increase in acylase expression, which was confirmed by HPLC analysis. Pichia pastoris is one of the most effective and versatile host systems for the production of heterologous proteins. The ECB acylase gene was cloned into pPIC9K vector with AOX1 promoter and was transformed into Pichia pastoris (GS115). The acylase expression was confirmed by protein expression and bioconversion studies. The heterologous expression of acylase in Pichia pastoris, is a milestone in the development of antifungals. Actively growing cells of Actinoplanes utahensis (NRRL 12052) were immobilized and tested for bioconversion ability which showed >90% conversion in each cycle. The stability of immobilized cell beads retained the deacylation ability up to 60 days and reusability was confirmed up to 4 cycles. The significant findings from the study have revealed that immobilization of whole cells of Actinoplanes utahensis (NRRL 12052) could be an alternative option for bioconversion of echinocandin B to echinocandin B nucleus, which has not been reported to date. The concept of co-cultivation of Aspergillus nidulans and Actinoplanes utahensis strains for the production of the echinocandin B nucleus was also carried out in order to produce echinocandin B nucleus. The process completely reduced the ECB purification step and, therefore, could be recommended as an ingenious method to improve the yield of the ECB nucleus.

Keywords: acylase, anidulafungin, antifungals, Aspergillus nidulans

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Authors: Ogunlesi Olufunso, John Ogunsola, Omolade Oladele, Benjamin Emikpe

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Context: Coccidiosis is a parasitic disease that affects poultry production, leading to economic losses. Garlic is known for medicinal properties and has been used as a natural remedy for various diseases. This study aims to investigate the prophylactic effect of garlic inclusion in the feed of commercial broilers with coccidiosis. Research Aim: The aim of this study is to determine the possible effect of garlic meal inclusion in poultry feed on the body weight gain of commercial broilers and to investigate it's therapeutic effect on broilers with coccidiosis. Methodology: The study conducted a case-control study for eight weeks with One hundred Arbor acre commercial broilers separated into five (5) groups from day-old, where 6,000 Eimeria oocysts were orally inoculated into each broiler in the different groups. Feed intake, body weight gain, feed conversion ratio, oocyt shedding rate, histopathology and erythrocyte indices were assessed. Findings: The inclusion of garlic meal in the broilers' diet resulted in an improved feed conversion ratio, decreased oocyst counts, reduced diarrhoeic fecal spots, decreased susceptibility to coccidial infection, and increased packed cell volume (PCV). Theoretical Importance: This study contributes to the understanding of the prophylactic effect of garlic supplementation, including its antiparasitic properties on commercial broilers with coccidiosis. It highlights the potential use of non-conventional feed additives or ayurvedic herb and spices in the treatment of poultry diseases. Data Collection and Analysis Procedures: The study collected data on feed intake, body weight gain, oocyst shedding rate, histopathological observations, and erythrocyte indices. Data were analyzed using Analysis of Variance and Duncan's Multiple range Test. Questions Addressed: The study addressed the possible effect of garlic meal inclusion in poultry feed on the body weight gain of broilers and its therapeutic effect on broilers with coccidiosis. Conclusion: The study concludes that garlic inclusion in the feed of broilers has a prophylactic effect, including antiparasitic properties, resulting in improved feed conversion ratio, reduced oocyst counts and increased PCV.

Keywords: broilers, eimeria spp, garlic, Ibadan

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Authors: Orit Shamir Balderman, Shamir Michal

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Israel often deals with crisis situations, but most have been characterized as security crises (e.g., war). This is the first time that the Israel has dealt with a health and social emergency as part of a global crisis. The crisis began in January 2020 with the emergence of the novel coronavirus (Covid-19), which was defined as a pandemic (World Health Organization, 2020) and arrived in Israel in early March 2020. This study examined how single mothers by choice (SMBC) experience state anxiety (SA), social support, work–family conflict (WFC), and happiness. This group has not been studied in the context of crises in general or a global crisis. Using a snowball sample, 386 SMBCanswered an online questionnaire. The findings show a negative relationship between income and level of state anxiety. State anxiety was also negatively associated with social support, level of happiness, and WFC. Finally, a stepwise regression analysis indicated that happiness explained 34% of the variance in SA. We also found that most of the women did not turn to formal support agencies such as social workers, other Government Ministries, or municipal welfare. A positive and strong correlations was also found between SA and WFC. The findings of the study reinforce the understanding that although these women made a conscious and informed decision regarding the choice of their family cell, their situation is more complex in the absence of a spouse support. Therefore, this study, as other future studies in the field of SMBC, may contribute to the improvement of their social status and the understanding that they are a unique group. Although SMBC are a growing sector of society in the past few years, there are still special needs and special attention that is needed from the formal and informal supports systems. A comparative study of these two groups and in different countries would shed light on SA among mothers in general, regardless of their relationship status and location.Researchers should expand this study by comparing mothers in relationships and exploring how SMBC coped in other countries. In summary, the findings of the study contribute knowledge on three levels: (a) knowledge about SMBC in general and during crisis situations; (b) examination of social support using tools assessing receipt of assistance and support, some of which were developed for the present study; and (c) insights regarding counseling, accompaniment, and guidance of welfare mechanisms.

Keywords: single mothers by choice, state anxiety, social support, happiness, work–family conflict

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Authors: Mantas Sriubas, Kristina Bockute, Darius Virbukas, Giedrius Laukaitis

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In this work, the doped TiO2 (dopants – Ca, Mg) was investigated. The comparison between the physical vapour deposition methods as electron beam vapour deposition and magnetron sputtering was performed and the structural and electrical properties of the formed thin films were investigated. Thin films were deposited on different type of substrates: SiO2, Alloy 600 (Fe-Ni-Cr) and Al2O3 substrates. The structural properties were investigated using Ambios XP-200 profilometer, scanning electron microscope (SEM) Hitachi S-3400N, X-ray energy-dispersive spectroscope (EDS) Quad 5040 (Bruker AXS Microanalysis GmbH), X-ray diffractometer (XRD) D8 Discover (Bruker AXS GmbH) with glancing angles focusing geometry in a 20 – 70° range using the Cu Kα1 λ = 0.1540562 nm radiation). The impedance spectroscopy measurements were performed using Probostat® (NorECs AS) measurement cell in the frequency range from 10-1-106 Hz under reducing and oxidizing conditions in temperature range of 200 °C to 1200 °C. The investigation of the e-beam deposited Ca and Mg doped-TiO2 thin films shows that the thin films are dense without any visible pores and cavities and the thin films grow in zone T according Barna-Adamik SZM. Substrate temperature was kept 600 °C during the deposition and Ts/Tm ≈ 0.32 (substrate temperature (Ts) and coating material melting temperature (Tm)). The surface diffusion is high however, the grain boundary migration is strongly limited at this temperature. This means that structure is inhomogeneous and the columnar structure is mostly visible in the upper part of the films. According to XRD, the increasing of the Ca dopants’ concentration increases the crystallinity of the formed thin films and the crystallites size increase linearly and Ca dopants act as prohibitors. Thin films are comprised of anatase TiO2 phase with an exception of 2 % Ca doped TiO2, where a small peak of Ca arise. In the case of Mg doped-TiO2 the intensities of the XRD peaks decreases with increasing Mg molar concentration. It means that there are less diffraction planes of the particular orientation in thin films with higher impurities concentration. Thus, the crystallinity decreases with increasing Mg concentration and Mg dopants act as inhibitors. The impedance measurements show that the dopants changed the conductivity of the formed thin films. The conductivity varies from 10-3 S/cm to 10-4 S/cm at 800 °C under wet reducing conditions. The microstructure of the magnetron sputtered thin TiO2 films is different comparing to the thin films deposited using e-beam deposition therefore influencing other structural and electrical properties.

Keywords: electrical properties, electron beam deposition, magnetron sputtering, microstructure, titanium dioxide

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Authors: Giulia Bonaldo, Alberto Vaccheri, Ottavio D'Annibali, Domenico Motola

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The Human Papilloma Virus (HPV) was shown to be the cause of different types of carcinomas, first of all of the cervical intraepithelial neoplasia. Since the early 80s to today, thanks first to the preventive screening campaigns (pap-test) and following to the introduction of HPV vaccines on the market; the number of new cases of cervical cancer has decreased significantly. The HPV vaccines currently approved are three: Cervarix® (HPV2 - virus type: 16 and 18), Gardasil® (HPV4 - 6, 11, 16, 18) and Gardasil 9® (HPV9 - 6, 11, 16, 18, 31, 33, 45, 52, 58), which all protect against the two high-risk HPVs (6, 11) that are mainly involved in cervical cancers. Despite the remarkable effectiveness of these vaccines has been demonstrated, in the recent years, there have been many complaints about their risk-benefit profile due to Adverse Events Following Immunization (AEFI). The purpose of this study is to provide a support about the ongoing discussion on the safety profile of HPV vaccines based on real life data deriving from spontaneous reports of suspected AEFIs collected in the Vaccine Adverse Events Reporting System (VAERS). VAERS is a freely-available national vaccine safety surveillance database of AEFI, co-administered by the Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA). We collected all the reports between January 2007 to December 2017 related to the HPV vaccines with a brand name (HPV2, HPV4, HPV9) or without (HPVX). A disproportionality analysis using Reporting Odds Ratio (ROR) with 95% confidence interval and p value ≤ 0.05 was performed. Over the 10-year period, 54889 reports of AEFI related to HPV vaccines reported in VAERS, corresponding to 224863 vaccine-event pairs, were retrieved. The highest number of reports was related to Gardasil (n = 42244), followed by Gardasil 9 (7212) and Cervarix (3904). The brand name of the HPV vaccine was not reported in 1529 cases. The two events more frequently reported and statistically significant for each vaccine were: dizziness (n = 5053) ROR = 1.28 (CI95% 1.24 – 1.31) and syncope (4808) ROR = 1.21 (1.17 – 1.25) for Gardasil. For Gardasil 9, injection site pain (305) ROR = 1.40 (1.25 – 1.57) and injection site erythema (297) ROR = 1.88 (1.67 – 2.10) and for Cervarix, headache (672) ROR = 1.14 (1.06 – 1.23) and loss of consciousness (528) ROR = 1.71 (1.57 – 1.87). In total, we collected 406 reports of death and 2461 cases of permanent disability in the ten-year period. The events consisting of incorrect vaccine storage or incorrect administration were not considered. The AEFI analysis showed that the most frequently reported events are non-serious and listed in the corresponding SmPCs. In addition to these, potential safety signals arose regarding less frequent and severe AEFIs that would deserve further investigation. This already happened with the referral of the European Medicines Agency (EMA) for the adverse events POTS (Postural Orthostatic Tachycardia Syndrome) and CRPS (Complex Regional Pain Syndrome) associated with anti-papillomavirus vaccines.

Keywords: adverse drug reactions, pharmacovigilance, safety, vaccines

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Authors: Frans J. Smit, Wisdom A. Munzeiwa, Hermanus C. M. Vosloo, Lyn-Marie Birkholtz, Richard K. Haynes

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Malaria and antimicrobial infections remain significant global health concerns, necessitating the continuous search for novel therapeutic approaches. This abstract presents an overview of the potential use of triazenes as effective agents against malaria and various antimicrobial pathogens. Triazenes are a class of compounds characterized by a linear arrangement of three nitrogen atoms, rendering them structurally distinct from their cyclic counterparts. This study investigates the efficacy of triazenes against malaria and explores their antimicrobial activity. Preliminary results revealed significant antimalarial activity of the triazenes, as evidenced by in vitro screening against P. falciparum, the causative agent of malaria. Furthermore, the compounds exhibited broad-spectrum antimicrobial activity, indicating their potential as effective antimicrobial agents. These compounds have shown inhibitory effects on various essential enzymes and processes involved in parasite survival, replication, and transmission. The mechanism of action of triazenes against malaria involves interactions with critical molecular targets, such as enzymes involved in the parasite's metabolic pathways and proteins responsible for host cell invasion. The antimicrobial activity of the triazenes against bacteria and fungi was investigated through disc diffusion screening. The antimicrobial efficacy of triazenes has been observed against both Gram-positive and Gram-negative bacteria, as well as multidrug-resistant strains, making them potential candidates for combating drug-resistant infections. Furthermore, triazenes possess favourable physicochemical properties, such as good stability, solubility, and low toxicity, which are essential for drug development. The structural versatility of triazenes allows for the modification of their chemical composition to enhance their potency, selectivity, and pharmacokinetic properties. These modifications can be tailored to target specific pathogens, increasing the potential for personalized treatment strategies. In conclusion, this study highlights the potential of triazenes as promising candidates for the development of novel antimalarial and antimicrobial therapeutics. Further investigations are necessary to determine the structure-activity relationships and optimize the pharmacological properties of these compounds. The results warrant additional research, including MIC studies, to further explore the antimicrobial activity of the triazenes. Ultimately, these findings contribute to the development of more effective strategies for combating malaria and microbial infections.

Keywords: malaria, anti-microbials, triazene, resistance

Procedia PDF Downloads 103