Search results for: illicit drugs
854 Biosynthesis of Tumor Inhibitory Podophyllotoxin, Quercetin and Kaempferol from Callogenesis of Dysosma Pleiantha (Hance) Woodson
Authors: Palaniyandi Karuppaiya, Hsin Sheng Tsay, Fang Chen
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Medicinal herbs do represent a huge and noteworthy reservoir for novel anticancer drugs discovery. Dysosma pleiantha (Hance) Woodson (Berberidaceae), one of the oldest traditional Chinese medicinal herb, highly prized by the mountain tribes of Taiwan and China for its medicinal properties contained pharmaceutically important antitumor compounds podophyllotoxin, quercetin and kaempferol. Among lignans, podophyllotoxin is an active antitumor compound and has now been modified to produce clinically useful drugs etoposide and teniposide. In recent years, natural populations of D. peliantha have declined considerably due to anthropogenic activities such as habitat destruction and commercial exploitation for medicinal applications. As to its overall conservation status, D. pleiantha has been ranked as threatened on the China Species Red List. In the present study, an efficient in vitro callus culture system of D. pleiantha was established on Gamborg’s medium with various combinations and concentrations of different auxins and cytokinins under dark condition. Best callus induction was recorded in 2 mg/L 2, 4 - Dichlorophenoxyacetic acid (2,4-D) along with 0.2 mg/L kinetin and the maximum callus proliferation was achieved at 1 mg/L 2,4-D. Among the explants tested, maximum callus induction (86 %) was achieved from tender leaves. Hence, in subsequent experiments, leaf callus was further investigated for suitable callus biomass and production level of anticancer compounds under the influence of different additives. A maximum fresh callus biomass (8.765 g) was recorded in callus proliferation medium contained 500 mg/L casein hydrolysate. High performance liquid chromatography results revealed that the addition of different concentrations of peptone (1, 2 and 4 g/L) in callus proliferation medium enhanced podophyllotoxin (16 fold), quercetin (12 fold) and kaempferol (5 fold) accumulation than control. Thus, the established in vitro callus culture under the influence of different additives may offer an alternative source of enhanced production of podophyllotoxin, kaempferol and quecertin without harming natural plant population.Keywords: dysosma pleiantha, kaempferol, podophyllotoxin, quercetin
Procedia PDF Downloads 273853 Immunoliposome-Mediated Drug Delivery to Plasmodium-Infected and Non-Infected Red Blood Cells as a Dual Therapeutic/Prophylactic Antimalarial Strategy
Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets
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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery
Procedia PDF Downloads 369852 Synthesis, Characterization and Biological Properties of Half-Sandwich Complexes of Ruthenium(II), Rhodium(II) and Iridium(III)
Authors: A. Gilewska, J. Masternak, K. Kazimierczuk, L. Turlej, J. Wietrzyk, B. Barszcz
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Platinum-based drugs are now widely used as chemotherapeutic agents. However the platinum complexes show the toxic side-effects: i) the development of platinum resistance; ii) the occurrence of severe side effects, such as nephro-, neuro- and ototoxicity; iii) the high toxicity towards human fibroblast. Therefore the development of new anticancer drugs containing different transition-metal ions, for example, ruthenium, rhodium, iridium is a valid strategy in cancer treatment. In this paper, we reported the synthesis, spectroscopic, structural and biological properties of complexes of ruthenium, rhodium, and iridium containing N,N-chelating ligand (2,2’-bisimidazole). These complexes were characterized by elemental analysis, UV-Vis and IR spectroscopy, X-ray diffraction analysis. These complexes exhibit a typical pseudotetrahedral three-legged piano-stool geometry, in which the aromatic arene ring forms the seat of the piano-stool, while the bidentate 2,2’-bisimidazole (ligand) and the one chlorido ligand form the three legs of the stool. The spectroscopy data (IR, UV-Vis) and elemental analysis correlate very well with molecular structures. Moreover, the cytotoxic activity of the complexes was carried out on human cancer cell lines: LoVo (colorectal adenoma), MV-4-11 (myelomonocytic leukaemia), MCF-7 (breast adenocarcinoma) and normal healthy mouse fibroblast BALB/3T3 cell lines. To predict a binding mode, a potential interaction of metal complexes with calf thymus DNA (CT-DNA) and protein (BSA) has been explored using UV absorption and circular dichroism (CD). It is interesting to note that the investigated complexes show no cytotoxic effect towards the normal BALB/3T3 cell line, compared to cisplatin, which IC₅₀ values was determined as 2.20 µM. Importantly, Ru(II) displayed the highest activity against HL-60 (IC₅₀ 4.35 µM). The biological studies (UV-Vis and circular dichroism) suggest that arene-complexes could interact with calf thymus DNA probably via an outside binding mode and interact with protein (BSA).Keywords: ruthenium(II) complex, rhodium(III) complex, iridium(III) complex, biological activity
Procedia PDF Downloads 122851 Comparative Efficacy of Angiotensin Converting Enzymes Inhibitors and Angiotensin Receptor Blockers in Patients with Heart Failure in Tanzania: A Prospective Cohort Study
Authors: Mark P. Mayala, Henry Mayala, Khuzeima Khanbhai
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Background: Heart failure has been a rising concern in Tanzania. New drugs have been introduced, including the group of drugs called Angiotensin receptor Neprilysin Inhibitor (ARNI), but due to their high cost, angiotensin-converting enzymes inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs) have been mostly used in Tanzania. However, according to our knowledge, the efficacy comparison of the two groups is yet to be studied in Tanzania. The aim of this study was to compare the efficacy of ACEIs and ARBs among patients with heart failure. Methodology: This was a hospital-based prospective cohort study done at Jakaya Kikwete Cardiac Institution (JKCI), Tanzania, from June to December 2020. Consecutive enrollment was done until fulfilling the inclusion criteria. Clinical details were measured at baseline. We assessed the relationship between ARBs and ACEIs users with N-terminal pro-brain natriuretic peptide (NT pro-BNP) levels at admission and at 1-month follow-up using a chi-square test. A Kaplan-Meier curve was used to estimate the survival time of the two groups. Results: 155 HF patients were enrolled, with a mean age of 48 years, whereby 52.3% were male, and their mean left ventricular ejection fraction (LVEF) was 37.3%. 52 (33.5%) heart failure patients were on ACEIs, 57 (36.8%) on ARBs, and 46 (29.7%) were neither using ACEIs nor ARBs. At least half of the patients did not receive a guideline-directed medical therapy (GDMT), with only 82 (52.9%) receiving a GDMT. A drop in NT pro-BNP levels was observed during admission and at 1-month follow-up on both groups, from 6389.2 pg/ml to 4000.1 pg/ml for ARB users and 5877.7 pg/ml to 1328.2 pg/ml for the ACEIs users. There was no statistical difference between the two groups when estimated by the Kaplan-Meier curve, though more deaths were observed in those who were neither on ACEIs nor ARBs, with a calculated P value of 0.01. Conclusion: This study demonstrates that ACEIs have more efficacy and overall better clinical outcome than ARBs, but this should be taken under the patient-based case, considering the side effects of ACEIs and patients’ adherence.Keywords: angiotensin converting enzymes inhibitors, angiotensin receptor blockers, guideline direct medical therapy, N-terminal pro-brain natriuretic peptide
Procedia PDF Downloads 82850 Solid Dosages Form Tablet: A Summary on the Article by Shashank Tiwari
Authors: Shashank Tiwari
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The most common method of drug delivery is the oral solid dosage form, of which tablets and capsules are predominant. The tablet is more widely accepted and used compared to capsules for a number of reasons, such as cost/price, tamper resistance, ease of handling and packaging, ease of identification, and manufacturing efficiency. Over the past several years, the issue of tamper resistance has resulted in the conversion of most over-the-counter (OTC) drugs from capsules to predominantly all tablets.Keywords: capsule, drug delivery, dosages, solid, tablet
Procedia PDF Downloads 430849 Gadolinium-Based Polymer Nanostructures as Magnetic Resonance Imaging Contrast Agents
Authors: Franca De Sarno, Alfonso Maria Ponsiglione, Enza Torino
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Recent advances in diagnostic imaging technology have significantly contributed to a better understanding of specific changes associated with diseases progression. Among different imaging modalities, Magnetic Resonance Imaging (MRI) represents a noninvasive medical diagnostic technique, which shows low sensitivity and long acquisition time and it can discriminate between healthy and diseased tissues by providing 3D data. In order to improve the enhancement of MRI signals, some imaging exams require intravenous administration of contrast agents (CAs). Recently, emerging research reports a progressive deposition of these drugs, in particular, gadolinium-based contrast agents (GBCAs), in the body many years after multiple MRI scans. These discoveries confirm the need to have a biocompatible system able to boost a clinical relevant Gd-chelate. To this aim, several approaches based on engineered nanostructures have been proposed to overcome the common limitations of conventional CAs, such as the insufficient signal-to-noise ratios due to relaxivity and poor safety profile. In particular, nanocarriers, labeling or loading with CAs, capable of carrying high payloads of CAs have been developed. Currently, there’s no a comprehensive understanding of the thermodynamic contributions enable of boosting the efficacy of conventional CAs by using biopolymers matrix. Thus, considering the importance of MRI in diagnosing diseases, here it is reported a successful example of the next generation of these drugs where the commercial gadolinium chelate is incorporate into a biopolymer nanostructure, formed by cross-linked hyaluronic acid (HA), with improved relaxation properties. In addition, they are highlighted the basic principles ruling biopolymer-CA interactions in the perspective of their influence on the relaxometric properties of the CA by adopting a multidisciplinary experimental approach. On the basis of these discoveries, it is clear that the main point consists in increasing the rigidification of readily-available Gd-CAs within the biopolymer matrix by controlling the water dynamics, the physicochemical interactions, and the polymer conformations. In the end, the acquired knowledge about polymer-CA systems has been applied to develop of Gd-based HA nanoparticles with enhanced relaxometric properties.Keywords: biopolymers, MRI, nanoparticles, contrast agent
Procedia PDF Downloads 148848 Microbiological Examination and Antimicrobial Susceptibility of Microorganisms Isolated from Salt Mining Site in Ebonyi State
Authors: Anyimc, C. J. Aneke, J. O. Orji, O. Nworie, U. C. C. Egbule
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The microbial examination and antimicrobial susceptibility profile of microorganism isolated from the salt mining site in Ebonyi state were evaluated in the present study using a standard microbiological technique. A total of 300 samples were randomly collected in three sample groups (A, B, and C) of 100 each. Isolation, Identification and characterization of organization present on the soil samples were determined by culturing, gram-staining and biochemical technique. The result showed the following organisms were isolated with their frequency as follow: Bacillus species (37.3%) and Staphylococcus species(23.5%) had the highest frequency in the whole Sample group A and B while Klebsiella specie (15.7%), Pseudomonas species(13.7%), and Erwinia species (9.8%) had the least. Rhizopus species (42.0%) and Aspergillus species (26.0%) were the highest fungi isolated, followed by Penicillum species (20.0%) while Mucor species (4.0%), and Fusarium species (8.0%) recorded the least. Sample group C showed high microbial population of all the microbial isolates when compared to sample group A and B. Disc diffusion method was used to determine the susceptibility of isolated bacteria to various antibiotics (oxfloxacin, pefloxacin, ciprorex, augumentin, gentamycin, ciproflox, septrin, ampicillin), while agar well diffusion method was used to determine the susceptibility of isolated fungi to some antifungal drugs (metronidazole, ketoconazole, itraconazole fluconazole). The antibacterial activity of the antibiotics used showed that ciproflux has the best inhibitory effect on all the test bacteria. Ketoconazole showed the highest inhibitory effect on the fungal isolates, followed by itraconazole, while metronidazole and fluconazole showed the least inhibitory effect on the entire test fungal isolates. Hence, the multiple drug resistance of most isolates to appropriate drugs of choice are of great public health concern and cells for periodic monitoring of antibiograms to detect possible changing patterns. Microbes isolated in the salt mining site can also be used as a source of gene(s) that can increase salt tolerance in different crop species through genetic engineering.Keywords: microorganisms, antibacterial, antifungal, resistance, salt mining site, Ebonyi State
Procedia PDF Downloads 311847 Drug Design Modelling and Molecular Virtual Simulation of an Optimized BSA-Based Nanoparticle Formulation Loaded with Di-Berberine Sulfate Acid Salt
Authors: Eman M. Sarhan, Doaa A. Ghareeb, Gabriella Ortore, Amr A. Amara, Mohamed M. El-Sayed
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Drug salting and nanoparticle-based drug delivery formulations are considered to be an effective means for rendering the hydrophobic drugs’ nano-scale dispersion in aqueous media, and thus circumventing the pitfalls of their poor solubility as well as enhancing their membrane permeability. The current study aims to increase the bioavailability of quaternary ammonium berberine through acid salting and biodegradable bovine serum albumin (BSA)-based nanoparticulate drug formulation. Berberine hydroxide (BBR-OH) that was chemically synthesized by alkalization of the commercially available berberine hydrochloride (BBR-HCl) was then acidified to get Di-berberine sulfate (BBR)₂SO₄. The purified crystals were spectrally characterized. The desolvation technique was optimized for the preparation of size-controlled BSA-BBR-HCl, BSA-BBR-OH, and BSA-(BBR)₂SO₄ nanoparticles. Particle size, zeta potential, drug release, encapsulation efficiency, Fourier transform infrared spectroscopy (FTIR), tandem MS-MS spectroscopy, energy-dispersive X-ray spectroscopy (EDX), scanning and transmitting electron microscopic examination (SEM, TEM), in vitro bioactivity, and in silico drug-polymer interaction were determined. BSA (PDB ID; 4OR0) protonation state at different pH values was predicted using Amber12 molecular dynamic simulation. Then blind docking was performed using Lamarkian genetic algorithm (LGA) through AutoDock4.2 software. Results proved the purity and the size-controlled synthesis of berberine-BSA-nanoparticles. The possible binding poses, hydrophobic and hydrophilic interactions of berberine on BSA at different pH values were predicted. Antioxidant, anti-hemolytic, and cell differentiated ability of tested drugs and their nano-formulations were evaluated. Thus, drug salting and the potentially effective albumin berberine nanoparticle formulations can be successfully developed using a well-optimized desolvation technique and exhibiting better in vitro cellular bioavailability.Keywords: berberine, BSA, BBR-OH, BBR-HCl, BSA-BBR-HCl, BSA-BBR-OH, (BBR)₂SO₄, BSA-(BBR)₂SO₄, FTIR, AutoDock4.2 Software, Lamarkian genetic algorithm, SEM, TEM, EDX
Procedia PDF Downloads 165846 In Silico Screening, Identification and Validation of Cryptosporidium hominis Hypothetical Protein and Virtual Screening of Inhibitors as Therapeutics
Authors: Arpit Kumar Shrivastava, Subrat Kumar, Rajani Kanta Mohapatra, Priyadarshi Soumyaranjan Sahu
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Computational approaches to predict structure, function and other biological characteristics of proteins are becoming more common in comparison to the traditional methods in drug discovery. Cryptosporidiosis is a major zoonotic diarrheal disease particularly in children, which is caused primarily by Cryptosporidium hominis and Cryptosporidium parvum. Currently, there are no vaccines for cryptosporidiosis and recommended drugs are not effective. With the availability of complete genome sequence of C. hominis, new targets have been recognized for the development of effective and better drugs and/or vaccines. We identified a unique hypothetical epitopic protein in C. hominis genome through BLASTP analysis. A 3D model of the hypothetical protein was generated using I-Tasser server through threading methodology. The quality of the model was validated through Ramachandran plot by PROCHECK server. The functional annotation of the hypothetical protein through DALI server revealed structural similarity with human Transportin 3. Phylogenetic analysis for this hypothetical protein also showed C. hominis hypothetical protein (CUV04613) was the closely related to human transportin 3 protein. The 3D protein model is further subjected to virtual screening study with inhibitors from the Zinc Database by using Dock Blaster software. Docking study reported N-(3-chlorobenzyl) ethane-1,2-diamine as the best inhibitor in terms of docking score. Docking analysis elucidated that Leu 525, Ile 526, Glu 528, Glu 529 are critical residues for ligand–receptor interactions. The molecular dynamic simulation was done to access the reliability of the binding pose of inhibitor and protein complex using GROMACS software at 10ns time point. Trajectories were analyzed at each 2.5 ns time interval, among which, H-bond with LEU-525 and GLY- 530 are significantly present in MD trajectories. Furthermore, antigenic determinants of the protein were determined with the help of DNA Star software. Our study findings showed a great potential in order to provide insights in the development of new drug(s) or vaccine(s) for control as well as prevention of cryptosporidiosis among humans and animals.Keywords: cryptosporidium hominis, hypothetical protein, molecular docking, molecular dynamics simulation
Procedia PDF Downloads 358845 Evaluation of the Effects of Antiepileptic Therapy on Cognitive and Psychical Functioning and Quality of Life in School-Age Children With New-Onset Epilepsy
Authors: Željka Rogač, Dejan Stevanović, Sara Bečanović, Ljubica Božić, Aleksandar Dimitrijević, Dragana Bogićević, Dimitrije Nikolić
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Children with epilepsy face changes in cognitive functioning, the appearance of symptoms of psychopathology and a decline in their quality of life. Factors related to epileptic seizures and the side effects of AEDs are considered to be potential causes of these changes.These changes can be prevented by prompt action, replacement of AEDs, psychological and psychiatric treatment, and social support. However, a review of literature has not yielded a conclusion as to when it is best to react, i.e., when changes in the functioning of children with newly-diagnosed epilepsy appears. The primary goal of this study was to investigate the impact of the most commonly used AEDs on cognitive status, behavior, anxiety and depression, as well as quality of life of children with newly-diagnosed epilepsy, during the first six months of treatment. This is a non-interventional, prospective study involving six-month monitoring of cognitive status, internalizing and externalizing symptoms, as well as quality of life of children with newly-diagnosed epilepsy, and the impact of antiepileptic drugs on these domains. Children with new-onset epilepsy and their parents, immediately after the introduction of antiepileptic drugs as well as six months later, filled out appropriate questionnaires (RCADS, NCBRF, CHEQOL-25, KIDSCREEN-10, AEP). At the same time, a psychologist performed the psychological testing of the child (REVISK). At the very beginning of REVISK treatment, a reduced VIQ was established, while after six months there was a significant decrease in IQ, VIQ and especially PIQ, under the influence of primary cognitive potentials and the development of depressive symptoms. All scores of the RCADS and NCBFR questionnaires were significantly elevated after six months while internalizing and externalizing symptoms affected each other. The development of depressive symptoms was significantly influenced by AED. The scores of the CHEQOL25 and KIDSCREEN10 questionnaires were significantly reduced, influenced by the adverse effects of AED and quality of life at the start of treatment. Side effects of AEDs, were significantly associated with depressive symptoms and reduced quality of life and did not significantly affect cognitive decline, anxiety, ADHD, and behavioral disorders during the first six months.Keywords: epilepsy, children, AEDs, cognition, behavior, ADHD, anxiety, depression, QOL
Procedia PDF Downloads 87844 New Approach for Melanoma Skin Cancer Controled Releasing Drugs for Neutron Capture Therapy: A Review
Authors: Lucas Bernardes Naves, Luis Almeida
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The paper includes a review concerning the use of some composites including poly(lactide-co-glycolide) (PGLA), zeolite and Gadopentetic acid (Gd-DTPA) loaded chitosan nanoparticles (Gd-nanoCPs) in order to establish a new alternative for the treatment of Melanoma Skin Cancer. The main goal of this paper it to make a review of what scientist have done in the last few years, as well as to propose a less invasive therapy for skin cancer, by using Hydrocolloid, based on PLGA coated with Gd-nanoCPs for Neutron Capture Therapy.Keywords: cancer therapy, dressing polymers, melanoma, wound healing
Procedia PDF Downloads 487843 Success of Trabeculectomy: May Not Always Depend on Mitomycin C
Authors: Sushma Tejwani, Shoruba Dinakaran, Rupa Rokhade, K. Bhujang Shetty
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Introduction and aim: One of the major causes for failure of trabeculectomy is fibrosis and scarring of subconjunctival tissue around the bleb, and hence intra operative usage of anti-fibrotic agents like Mitomycin C (MMC) has become very popular. However, the long term effects of MMC like thin, avascular bleb, hypotony, bleb leaks and late onset endophthalmitis cannot be ignored, and may preclude its usage in routine trabeculectomy. In this particular study we aim to study the outcomes of trabeculectomy with and without MMC in uncomplicated glaucoma patients. Methods: Retrospective study of series of patients that underwent trabeculectomy with or without cataract surgery in glaucoma department of a tertiary eye care centre by a single surgeon for primary open angle glaucoma (POAG), angle closure glaucoma (PACG), Pseudoexfoliation glaucoma (PXF glaucoma). Patients with secondary glaucoma, juvenile and congenital glaucoma were excluded; also patients undergoing second trabeculectomy were excluded. The outcomes were studied in terms of IOP control at 1 month, 6 months, and 1 year and were analyzed separately for surgical outcomes with and without MMC. Success was considered if IOP was < 16 mmHg on applanation tonometry. Further, the necessity of medication, 5 fluorouracil (5FU) postoperative injections, needling post operatively was noted. Results: Eighty nine patient’s medical records were reviewed, of which 58 patients had undergone trabeculectomy without MMC and 31 with MMC. Mean age was 62.4 (95%CI 61- 64), 34 were females and 55 males. MMC group (n=31): Preoperative mean IOP was 21.1mmHg (95% CI: 17.6 -24.6), and 22 patients had IOP > 16. Three out of 33 patients were on single medication and rests were on multiple drugs. At 1 month (n=27) mean IOP was 12.4 mmHg (CI: 10.7-14), and 31/33 had success. At 6 months (n=18) mean IOP was 13mmHg (CI: 10.3-14.6) and 16/18 had good outcome, however at 1 year only 11 patients were available for follow up and 91% (10/11) had success. Overall, 3 patients required medication and one patient required postoperative injection of 5 FU. No MMC group (n=58): Preoperative mean IOP was 21.9 mmHg (CI: 19.8-24.2), and 42 had IOP > 16 mmHg. 12 out of 58 patients were on single medication and rests were on multiple drugs. At 1 month (n=52) mean IOP was14.6mmHg (CI: 13.2-15.9), and 45/ 58 had IOP < 16mmHg. At 6 months (n=31) mean IOP was 13.5 mmHg (CI: 11.9-15.2) and 26/31 had success, however at 1 year only 23 patients came for follow up and of these 87% (20/23) patients had success. Overall, 1 patient required needling, 5 required 5 FU injections and 5 patients required medication. The success rates at each follow up visit were not significantly different in both the groups. Conclusion: Intra-operative MMC usage may not be required in all patients undergoing trabeculectomy, and the ones without MMC also have fairly good outcomes in primary glaucoma.Keywords: glaucoma filtration surgery, mitomycin C, outcomes of trabeculectomy, wound modulation
Procedia PDF Downloads 271842 Effect of Locally Produced Sweetened Pediatric Antibiotics on Streptococcus mutans Isolated from the Oral Cavity of Pediatric Patients in Syria - in Vitro Study
Authors: Omar Nasani, Chaza Kouchaji, Muznah Alkhani, Maisaa Abd-alkareem
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Objective: To evaluate the influence of sweetening agents used in pediatric medications on the growth of Streptococcus mutans colonies and its effect on the cariogenic activity in the oral cavity. No previous studies are registered yet in Syrian children. Methods: Specimens were isolated from the oral cavity of pediatric patients, then in-vitro study is applied on locally manufactured liquid pediatric antibiotic drugs, containing natural or synthetic sweeteners. The selected antibiotics are Ampicillin (sucrose), Amoxicillin (sucrose), Amoxicillin + Flucloxacillin (sorbitol), Amoxicillin+Clavulanic acid (Sorbitol or sucrose). These antibiotics have a known inhibitory effect on gram positive aerobic/anaerobic bacteria especially Streptococcus mutans strains in children’s oral biofilm. Five colonies are studied with each antibiotic. Saturated antibiotics were spread on a 6mm diameter filter disc. Incubated culture media were compared with each other and with the control antibiotic discs. Results were evaluated by measuring the diameter of the inhibition zones. The control group of antibiotic discs was resourced from Abtek Biologicals Ltd. Results: The diameter of inhibition zones around discs of antibiotics sweetened with sorbitol was larger than those sweetened with sucrose. The effect was most important when comparing Amoxicillin + Clavulanic Acid (sucrose 25mm; versus sorbitol 27mm). The highest inhibitory effect was observed with the usage of Amoxicillin + Flucloxacillin sweetened with sorbitol (38mm). Whereas the lowest inhibitory effect was observed with Amoxicillin and Ampicillin sweetened with sucrose (22mm and 21mm). Conclusion: The results of this study indicate that although all selected antibiotic produced an inhibitory effect on S. mutans, sucrose weakened the inhibitory action of the antibiotic to varying degrees, meanwhile antibiotic formulations containing sorbitol simulated the effects of the control antibiotic. This study calls attention to effects of sweeteners included in pediatric drugs on the oral hygiene and tooth decay.Keywords: pediatric, dentistry, antibiotics, streptococcus mutans, biofilm, sucrose, sugar free
Procedia PDF Downloads 65841 Substance Use and Association of Adverse Childhood Experience and Mental Health in Young Adults
Authors: Sreelekha Prakash, Yulong Gu
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Background: About 61% of adults surveyed across 25 states reported they had experienced at least one type of Adverse Childhood Experience (ACE) before 18 years of age. Relationships between ACEs and a variety of substance-related behaviors and behavioral health have been reported in previous studies. ACEs can have lasting, negative effects on health, well-being, as well as life opportunities such as education and job potential. Objectives: For the current research, the aim was to assess the factors affecting substance use behavior in young adults. The further onset of drug use and its association was analyzed with ACEs and mental health. Method: The young adults from a county in the north-eastern United States were invited to participate in an online questionnaire survey with prior consent through an IRB approved study. The Survey included questions related to social determinants of health, 10 item ACE questionnaire, and substance use related to Alcohol, Marijuana, Opioids, Stimulants, and other drugs. PHQ-9 questionnaire was used to assess cognitive health. Results: Data was analyzed for the 244 completed surveys {68% (165) were females, and 78% (190) were Whites}. The average age of the participants was 26.7 years, and approximately 80% were lifelong residents of the county or year-round residents. Of the respondents, 50% (122) were high school graduates with some college education, and 56% (136) had a full-time jobs. Past 30-day usage for alcohol was 76% (72), and marijuana was 28.4% (27). The data showed that the higher the ACE scores, the younger they start using any substance (p < 0.0001). The data for PHQ-9 and ACE scores showed that the higher the ACE score, the higher the PHQ-9 score, with a significant p-value (p 0.0001). The current data also showed a significant association with other drugs; marijuana use showed significance for 30 days of use (p 0.0001), stimulant use (0.0008), prescription drug misuse (0.01), and opioids (0.01). Conclusion: These findings further support the association between ACEs and initiation of drug use and its correlation with mental health symptoms. Promoting a safe and supportive environment for children and youth in their earlier ages can prevent the youth and young adults from the effects of drug use and create healthy living habits for young adults.Keywords: subtance use, young adults, adverse childhood experience, PHQ-9
Procedia PDF Downloads 79840 Development and Validation of First Derivative Method and Artificial Neural Network for Simultaneous Spectrophotometric Determination of Two Closely Related Antioxidant Nutraceuticals in Their Binary Mixture”
Authors: Mohamed Korany, Azza Gazy, Essam Khamis, Marwa Adel, Miranda Fawzy
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Background: Two new, simple and specific methods; First, a Zero-crossing first-derivative technique and second, a chemometric-assisted spectrophotometric artificial neural network (ANN) were developed and validated in accordance with ICH guidelines. Both methods were used for the simultaneous estimation of the two closely related antioxidant nutraceuticals ; Coenzyme Q10 (Q) ; also known as Ubidecarenone or Ubiquinone-10, and Vitamin E (E); alpha-tocopherol acetate, in their pharmaceutical binary mixture. Results: For first method: By applying the first derivative, both Q and E were alternatively determined; each at the zero-crossing of the other. The D1 amplitudes of Q and E, at 285 nm and 235 nm respectively, were recorded and correlated to their concentrations. The calibration curve is linear over the concentration range of 10-60 and 5.6-70 μg mL-1 for Q and E, respectively. For second method: ANN (as a multivariate calibration method) was developed and applied for the simultaneous determination of both analytes. A training set (or a concentration set) of 90 different synthetic mixtures containing Q and E, in wide concentration ranges between 0-100 µg/mL and 0-556 µg/mL respectively, were prepared in ethanol. The absorption spectra of the training sets were recorded in the spectral region of 230–300 nm. A Gradient Descend Back Propagation ANN chemometric calibration was computed by relating the concentration sets (x-block) to their corresponding absorption data (y-block). Another set of 45 synthetic mixtures of the two drugs, in defined range, was used to validate the proposed network. Neither chemical separation, preparation stage nor mathematical graphical treatment were required. Conclusions: The proposed methods were successfully applied for the assay of Q and E in laboratory prepared mixtures and combined pharmaceutical tablet with excellent recoveries. The ANN method was superior over the derivative technique as the former determined both drugs in the non-linear experimental conditions. It also offers rapidity, high accuracy, effort and money saving. Moreover, no need for an analyst for its application. Although the ANN technique needed a large training set, it is the method of choice in the routine analysis of Q and E tablet. No interference was observed from common pharmaceutical additives. The results of the two methods were compared togetherKeywords: coenzyme Q10, vitamin E, chemometry, quantitative analysis, first derivative spectrophotometry, artificial neural network
Procedia PDF Downloads 439839 An Effective Preventive Program of HIV/AIDS among Hill Tribe Youth, Thailand
Authors: Tawatchai Apidechkul
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This operational research was conducted and divided into two phases: the first phase aimed to determine the risk behaviors used a cross-sectional study design, following by the community participatory research design to develop the HIV/AIDS preventive model among the Akha youths. The instruments were composed of completed questionnaires and assessment forms that were tested for validity and reliability before use. Study setting was Jor Pa Ka and Saen Suk Akha villages, Mae Chan District, Chiang Rai, Thailand. Study sample were the Akha youths lived in the villages. Means and chi-square test were used for the statistical testing. Results: Akha youths in the population mobilization villages live in agricultural families with low income and circumstance of narcotic drugs. The average age was 16 (50.00%), 51.52% Christian, 48.80% completed secondary school, 43.94% had annual family income of 30,000-40,000 baht. Among males, 54.54% drank, 39.39% smoked, 7.57% used amphetamine, first sexual intercourse reported at 14 years old, 50.00% had 2-5 partners, 62.50% had unprotected sex (no-condom). Reasons of unprotected sex included not being able to find condom, unawareness of need to use condoms, and dislike. 28.79% never been received STI related information, 6.06% had STI. Among females, 15.15% drank, 28.79% had sexual intercourse and had first sexual intercourse less than 15 year old. 40.00% unprotected sex (no-condom), 10.61% never been received STI related information, and 4.54% had STI. The HIV/AIDS preventive model contained two components. Peer groups among the youths were built around interests in sports. Improving knowledge would empower their capability and lead to choices that would result in HIV/AIDS prevention. The empowering model consisted of 4 courses: a. human reproductive system and its hygiene, b. risk-avoid skills, family planning, and counseling techniques, c. HIV/AIDS and other STIs, d. drugs and related laws and regulations. The results of the activities found that youths had a greater of knowledge and attitude levels for HIV/AIDS prevention with statistical significance (χ2-τεστ= 12.87, p-value= 0.032 and χ2-τεστ= 9.31, p-value<0.001 respectively). A continuous and initiative youths capability development program is the appropriate process to reduce the spread of HIV/AIDS in youths, particularly in the population who have the specific of language and culture.Keywords: AIV/AIDS, preventive program, effective, hill tribe
Procedia PDF Downloads 361838 Repeatable Surface Enhanced Raman Spectroscopy Substrates from SERSitive for Wide Range of Chemical and Biological Substances
Authors: Monika Ksiezopolska-Gocalska, Pawel Albrycht, Robert Holyst
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Surface Enhanced Raman Spectroscopy (SERS) is a technique used to analyze very low concentrations of substances in solutions, even in aqueous solutions - which is its advantage over IR. This technique can be used in the pharmacy (to check the purity of products); forensics (whether at a crime scene there were any illegal substances); or medicine (serving as a medical test) and lots more. Due to the high potential of this technique, its increasing popularity in analytical laboratories, and simultaneously - the absence of appropriate platforms enhancing the SERS signal (crucial to observe the Raman effect at low analyte concentration in solutions (1 ppm)), we decided to invent our own SERS platforms. As an enhancing layer, we have chosen gold and silver nanoparticles, because these two have the best SERS properties, and each has an affinity for the other kind of particles, which increases the range of research capabilities. The next step was to commercialize them, which resulted in the creation of the company ‘SERSitive.eu’ focusing on production of highly sensitive (Ef = 10⁵ – 10⁶), homogeneous and reproducible (70 - 80%) substrates. SERStive SERS substrates are made using the electrodeposition of silver or silver-gold nanoparticles technique. Thanks to a very detailed analysis of data based on studies optimizing such parameters as deposition time, temperature of the reaction solution, applied potential, used reducer, or reagent concentrations using a standardized compound - p-mercaptobenzoic acid (PMBA) at a concentration of 10⁻⁶ M, we have developed a high-performance process for depositing precious metal nanoparticles on the surface of ITO glass. In order to check a quality of the SERSitive platforms, we examined the wide range of the chemical compounds and the biological substances. Apart from analytes that have great affinity to the metal surfaces (e.g. PMBA) we obtained very good results for those fitting less the SERS measurements. Successfully we received intensive, and what’s more important - very repetitive spectra for; amino acids (phenyloalanine, 10⁻³ M), drugs (amphetamine, 10⁻⁴ M), designer drugs (cathinone derivatives, 10⁻³ M), medicines and ending with bacteria (Listeria, Salmonella, Escherichia coli) and fungi.Keywords: nanoparticles, Raman spectroscopy, SERS, SERS applications, SERS substrates, SERSitive
Procedia PDF Downloads 146837 The in Vitro and in Vivo Antifungal Activity of Terminalia Mantaly on Aspergillus Species Using Drosophila melanogaster (UAS-Diptericin) As a Model
Authors: Ponchang Apollos Wuyep, Alice Njolke Mafe, Longchi Satkat Zacheaus, Dogun Ojochogu, Dabot Ayuba Yakubu
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Fungi causes huge losses when infections occur both in plants and animals. Synthetic Antifungal drugs are mostly very expensive and highly cytotoxic when taken. This study was aimed at determining the in vitro and in vivo antifungal activities of the leaves and stem extracts of Terminalia mantaly (Umbrella tree)H. Perrier on Aspergillus species in a bid to identify potential sources of cheap starting materials for the synthesis of new drugs to address the growing antimicrobial resistance. T. mantaly leave and stem powdered plant was extracted by fractionation using the method of solvent partition co-efficient in their graded form in the order n-hexane, Ethyl acetate, methanol and distilled water and phytochemical screening of each fraction revealed the presence of alkaloids, saponins, Tannins, flavonoids, carbohydrates, steroids, anthraquinones, cardiac glycosides and terpenoids in varying degrees. The Agar well diffusion technique was used to screen for antifungal activity of the fractions on clinical isolates of Aspergillus species (Aspergillus flavus and Aspergillus fumigatus). Minimum inhibitory concentration (MIC50) of the most active extracts was determined by the broth dilution method. The fractions test indicated a high antifungal activity with zones of inhibition ranging from 6 to 26 mm and 8 to 30mm (leave fractions) and 10mm to 34mm and 14mm to36mm (stem fractions) on A. flavus and A. fumigatus respectively. All the fractions indicated antifungal activity in a dose response relationship at concentrations of 62.5mg/ml, 125mg/ml, 250mg/ml and 500mg/ml. Better antifungal efficacy was shown by the Ethyl acetate, Hexane and Methanol fractions in the in vitro as the most potent fraction with MIC ranging from 62.5 to 125mg/ml. There was no statistically significant difference (P>0.05) in the potency of the Eight fractions from leave and stem (Hexane, Ethyl acetate, methanol and distilled water, antifungal (fluconazole), which served as positive control and 10% DMSO(Dimethyl Sulfoxide)which served as negative control. In the in vivo investigations, the ingestion technique was used for the infectious studies Female Drosophilla melanogaster(UAS-Diptericin)normal flies(positive control),infected and not treated flies (negative control) and infected flies with A. fumigatus and placed on normal diet, diet containing fractions(MSM and HSM each at concentrations of 10mg/ml 20mg/ml, 30mg/ml, 40mg/ml, 50mg/ml, 60mg/ml, 70mg/ml, 80mg/ml, 90mg/ml and 100mg/ml), diet containing control drugs(fluconazole as positive control)and infected flies on normal diet(negative control), the flies were observed for fifteen(15) days. Then the total mortality of flies was recorded each day. The results of the study reveals that the flies were susceptible to infection with A. fumigatus and responded to treatment with more effectiveness at 50mg/ml, 60mg/ml and 70mg/ml for both the Methanol and Hexane stem fractions. Therefore, the Methanol and Hexane stem fractions of T. mantaly contain therapeutically useful compounds, justifying the traditional use of this plant for the treatment of fungal infections.Keywords: Terminalia mantaly, Aspergillus fumigatus, cytotoxic, Drosophila melanogaster, antifungal
Procedia PDF Downloads 76836 Effect of Surfactant Concentration on Dissolution of Hydrodynamically Trapped Sparingly Soluble Oil Micro Droplets
Authors: Adil Mustafa, Ahmet Erten, Alper Kiraz, Melikhan Tanyeri
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Work presented here is based on a novel experimental technique used to hydrodynamically trap oil microdroplets inside a microfluidic chip at the junction of microchannels known as stagnation point. Hydrodynamic trapping has been recently used to trap and manipulate a number of particles starting from microbeads to DNA and single cells. Benzyl Benzoate (BB) is used as droplet material. The microdroplets are trapped individually at stagnation point and their dissolution was observed. Experiments are performed for two concentrations (10mM or 10µM) of AOT surfactant (Docusate Sodium Salt) and two flow rates for each case. Moreover, experimental data is compared with Zhang-Yang-Mao (ZYM) model which studies dissolution of liquid microdroplets in the presence of a host fluid experiencing extensional creeping flow. Industrial processes like polymer blending systems in which heat or mass transport occurs experience extensional flow and an insight into these phenomena is of significant importance to many industrial processes. The experimental technique exploited here gives an insight into the dissolution of liquid microdroplets under extensional flow regime. The comparison of our experimental results with ZYM model reveals that dissolution of microdroplets at lower surfactant concentration (10µM) fits the ZYM model at saturation concentration (Cs) value reported in literature (Cs = 15×10⁻³Kg\m³) while for higher surfactant concentration (10mM) which is also above the critical micelle concentration (CMC) of surfactant (5mM) the data fits ZYM model at (Cs = 45×10⁻³Kg\m³) which is 3X times the value reported in literature. The difference in Cs value from the literature shows enhancement in dissolution rate of sparingly soluble BB microdroplets at surfactant concentrations higher than CMC. Enhancement in the dissolution of sparingly soluble materials is of great importance in pharmaceutical industry. Enhancement in the dissolution of sparingly soluble drugs is a key research area for drug design industry. The experimental method is also advantageous because it is robust and has no mechanical contact with droplets under study are freely suspended in the fluid as compared existing methods used for testing dissolution of drugs. The experiments also give an insight into CMC measurement for surfactants.Keywords: extensional flow, hydrodynamic trapping, Zhang-Yang-Mao, CMC
Procedia PDF Downloads 338835 Nanoparticles-Protein Hybrid-Based Magnetic Liposome
Authors: Amlan Kumar Das, Avinash Marwal, Vikram Pareek
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Liposome plays an important role in medical and pharmaceutical science as e.g. nano scale drug carriers. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment. Magnet-driven liposome used for the targeted delivery of drugs to organs and tissues1. These liposome preparations contain encapsulated drug components and finely dispersed magnetic particles. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment that are generated in vitro. These are useful in terms of biocompatibility, biodegradability, and low toxicity, and can control biodistribution by changing the size, lipid composition, and physical characteristics2. Furthermore, liposomes can entrap both hydrophobic and hydrophilic drugs and are able to continuously release the entrapped substrate, thus being useful drug carriers. Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magneticor paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI)3. The biological synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology4. Green-synthesized magnetite nanoparticles-protein hybrid has been produced by treating Iron (III)/Iron(II) chloride with the leaf extract of Dhatura Inoxia. The phytochemicals present in the leaf extracts act as a reducing as well stabilizing agents preventing agglomeration, which include flavonoids, phenolic compounds, cardiac glycosides, proteins and sugars. The magnetite nanoparticles-protein hybrid has been trapped inside the aqueous core of the liposome prepared by reversed phase evaporation (REV) method using oleic and linoleic acid which has been shown to be driven under magnetic field confirming the formation magnetic liposome (ML). Chemical characterization of stealth magnetic liposome has been performed by breaking the liposome and release of magnetic nanoparticles. The presence iron has been confirmed by colour complex formation with KSCN and UV-Vis study using spectrophotometer Cary 60, Agilent. This magnet driven liposome using nanoparticles-protein hybrid can be a smart vesicles for the targeted drug delivery.Keywords: nanoparticles-protein hybrid, magnetic liposome, medical, pharmaceutical science
Procedia PDF Downloads 245834 Antioxidative, Anticholinesterase and Anti-Neuroinflammatory Properties of Malaysian Brown and Green Seaweeds
Authors: Siti Aisya Gany, Swee Ching Tan, Sook Yee Gan
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Diminished antioxidant defense or increased production of reactive oxygen species in the biological system can result in oxidative stress which may lead to various neurodegenerative diseases including Alzheimer’s disease (AD). Microglial activation also contributes to the progression of AD by producing several pro-inflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2). Oxidative stress and inflammation have been reported to be possible pathophysiological mechanisms underlying AD. In addition, the cholinergic hypothesis postulates that memory impairment in patient with AD is also associated with the deficit of cholinergic function in the brain. Although a number of drugs have been approved for the treatment of AD, most of these synthetic drugs have diverse side effects and yield relatively modest benefits. Marine algae have great potential in pharmaceutical and biomedical applications as they are valuable sources of bioactive properties such as anti-coagulation, anti-microbial, anti-oxidative, anti-cancer and anti-inflammatory. Hence, this study aimed to provide an overview of the properties of Malaysian seaweeds (Padina australis, Sargassum polycystum and Caulerpa racemosa) in inhibiting oxidative stress, neuroinflammation and cholinesterase enzymes. All tested samples significantly exhibit potent DPPH and moderate Superoxide anion radical scavenging ability (P<0.05). Hexane and methanol extracts of S. polycystum exhibited the most potent radical scavenging ability with IC50 values of 0.1572 ± 0.004 mg/ml and 0.8493 ± 0.02 for DPPH and ABTS assays, respectively. Hexane extract of C. racemosa gave the strongest superoxide radical inhibitory effect (IC50 of 0.3862± 0.01 mg/ml). Most seaweed extracts significantly inhibited the production of cytokine (IL-6, IL-1 β, TNFα) and NO in a concentration-dependent manner without causing significant cytotoxicity to the lipopolysaccharide (LPS)-stimulated microglia cells (P<0.05). All extracts suppressed cytokine and NO level by more than 80% at the concentration of 0.4mg/ml. In addition, C. racemosa and S. polycystum also showed anti-acetylcholinesterase activities with the IC50 values ranging from 0.086-0.115 mg/ml. Moreover, C. racemosa and P. australis were also found to be active against butyrylcholinesterase with IC50 values ranging from 0.118-0.287 mg/ml.Keywords: anti-cholinesterase, anti-oxidative, neuroinflammation, seaweeds
Procedia PDF Downloads 660833 Glucose Uptake Rate of Insulin-Resistant Human Liver Carcinoma Cells (IR/HepG2) by Flavonoids from Enicostema littorale via IR/IRS1/AKT Pathway
Authors: Priyanka Mokashi, Aparna Khanna, Nancy Pandita
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Diabetes mellitus is a chronic metabolic disorder which will be the 7th leading cause of death by 2030. The current line of treatment for the diabetes mellitus is oral antidiabetic drugs (biguanides, sulfonylureas, meglitinides, thiazolidinediones and alpha-glycosidase inhibitors) and insulin therapy depending upon the type 1 or type 2 diabetes mellitus. But, these treatments have their disadvantages, ranging from the developing of resistance to the drugs and adverse effects caused by them. Alternative to these synthetic agents, natural products provides a new insight for the development of more efficient and safe drugs due to their therapeutic values. Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. It is widely distributed in Asia, Africa, and South America. There are few reports on Swrtiamarin, major component of this plant for its antidiabetic activity. However, the antidiabetic activity of flavonoids from E. littorale and their mechanism of action have not yet been elucidated. Flavonoids have a positive relationship with disease prevention and can act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, adipocytes, hepatocytes and skeletal myofibers. They may exert beneficial effects in diabetes by (i) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (ii) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (iii) increasing glucose uptake in hepatocytes, skeletal muscle and white adipose tissue (iv) reducing insulin resistance, inflammation and oxidative stress. Therefore, we have isolated four flavonoid rich fractions, Fraction A (FA), Fraction B (FB), Fraction C (FC), Fraction D (FD) from crude alcoholic hot (AH) extract from E. littorale, identified by LC/MS. Total eight flavonoids were identified on the basis of fragmentation pattern. Flavonoid FA showed the presence of swertisin, isovitexin, and saponarin; FB showed genkwanin, quercetin, isovitexin, FC showed apigenin, swertisin, quercetin, 5-O-glucosylswertisin and 5-O-glucosylisoswertisin whereas FD showed the presence of swertisin. Further, these fractions were assessed for their antidiabetic activity on stimulating glucose uptake in insulin-resistant HepG2 cell line model (IR/HepG2). The results showed that FD containing C-glycoside Swertisin has significantly increased the glucose uptake rate of IR/HepG2 cells at the concentration of 10 µg/ml as compared to positive control Metformin (0.5mM) which was determined by glucose oxidase- peroxidase method. It has been reported that enhancement of glucose uptake of cells occurs due the translocation of Glut4 vesicles to cell membrane through IR/IRS1/AKT pathway. Therefore, we have studied expressions of three genes IRS1, AKT and Glut4 by real-time PCR to evaluate whether they follow the same pathway or not. It was seen that the glucose uptake rate has increased in FD treated IR/HepG2 cells due to the activation of insulin receptor substrate-1 (IRS1) followed by protein kinase B (AKT) through phosphoinositide 3-kinase (PI3K) leading to translocation of Glut 4 vesicles to cell membrane, thereby enhancing glucose uptake and insulin sensitivity of insulin resistant HepG2 cells. Hence, the up-regulation indicated the mechanism of action through which FD (Swertisin) acts as antidiabetic candidate in the treatment of type 2 diabetes mellitus.Keywords: E. littorale, glucose transporter, glucose uptake rate, insulin resistance
Procedia PDF Downloads 302832 Synthesis and Characterization of pH-Responsive Nanocarriers Based on POEOMA-b-PDPA Block Copolymers for RNA Delivery
Authors: Bruno Baptista, Andreia S. R. Oliveira, Patricia V. Mendonca, Jorge F. J. Coelho, Fani Sousa
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Drug delivery systems are designed to allow adequate protection and controlled delivery of drugs to specific locations. These systems aim to reduce side effects and control the biodistribution profile of drugs, thus improving therapeutic efficacy. This study involved the synthesis of polymeric nanoparticles, based on amphiphilic diblock copolymers, comprising a biocompatible, poly (oligo (ethylene oxide) methyl ether methacrylate (POEOMA) as hydrophilic segment and a pH-sensitive block, the poly (2-diisopropylamino)ethyl methacrylate) (PDPA). The objective of this work was the development of polymeric pH-responsive nanoparticles to encapsulate and carry small RNAs as a model to further develop non-coding RNAs delivery systems with therapeutic value. The responsiveness of PDPA to pH allows the electrostatic interaction of these copolymers with nucleic acids at acidic pH, as a result of the protonation of the tertiary amine groups of this polymer at pH values below its pKa (around 6.2). Initially, the molecular weight parameters and chemical structure of the block copolymers were determined by size exclusion chromatography (SEC) and nuclear magnetic resonance (1H-NMR) spectroscopy, respectively. Then, the complexation with small RNAs was verified, generating polyplexes with sizes ranging from 300 to 600 nm and with encapsulation efficiencies around 80%, depending on the molecular weight of the polymers, their composition, and concentration used. The effect of pH on the morphology of nanoparticles was evaluated by scanning electron microscopy (SEM) being verified that at higher pH values, particles tend to lose their spherical shape. Since this work aims to develop systems for the delivery of non-coding RNAs, studies on RNA protection (contact with RNase, FBS, and Trypsin) and cell viability were also carried out. It was found that they induce some protection against constituents of the cellular environment and have no cellular toxicity. In summary, this research work contributes to the development of pH-sensitive polymers, capable of protecting and encapsulating RNA, in a relatively simple and efficient manner, to further be applied on drug delivery to specific sites where pH may have a critical role, as it can occur in several cancer environments.Keywords: drug delivery systems, pH-responsive polymers, POEOMA-b-PDPA, small RNAs
Procedia PDF Downloads 254831 Effects of Using a Recurrent Adverse Drug Reaction Prevention Program on Safe Use of Medicine among Patients Receiving Services at the Accident and Emergency Department of Songkhla Hospital Thailand
Authors: Thippharat Wongsilarat, Parichat tuntilanon, Chonlakan Prataksitorn
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Recurrent adverse drug reactions are harmful to patients with mild to fatal illnesses, and affect not only patients but also their relatives, and organizations. To compare safe use of medicine among patients before and after using the recurrent adverse drug reaction prevention program . Quasi-experimental research with the target population of 598 patients with drug allergy history. Data were collected through an observation form tested for its validity by three experts (IOC = 0.87), and analyzed with a descriptive statistic (percentage). The research was conducted jointly with a multidisciplinary team to analyze and determine the weak points and strong points in the recurrent adverse drug reaction prevention system during the past three years, and 546, 329, and 498 incidences, respectively, were found. Of these, 379, 279, and 302 incidences, or 69.4; 84.80; and 60.64 percent of the patients with drug allergy history, respectively, were found to have caused by incomplete warning system. In addition, differences in practice in caring for patients with drug allergy history were found that did not cover all the steps of the patient care process, especially a lack of repeated checking, and a lack of communication between the multidisciplinary team members. Therefore, the recurrent adverse drug reaction prevention program was developed with complete warning points in the information technology system, the repeated checking step, and communication among related multidisciplinary team members starting from the hospital identity card room, patient history recording officers, nurses, physicians who prescribe the drugs, and pharmacists. Including in the system were surveillance, nursing, recording, and linking the data to referring units. There were also training concerning adverse drug reactions by pharmacists, monthly meetings to explain the process to practice personnel, creating safety culture, random checking of practice, motivational encouragement, supervising, controlling, following up, and evaluating the practice. The rate of prescribing drugs to which patients were allergic per 1,000 prescriptions was 0.08, and the incidence rate of recurrent drug reaction per 1,000 prescriptions was 0. Surveillance of recurrent adverse drug reactions covering all service providing points can ensure safe use of medicine for patients.Keywords: recurrent drug, adverse reaction, safety, use of medicine
Procedia PDF Downloads 449830 In vivo Antidiabetic and in vitro Antioxidant Activity of Myrica salicifolia Hochst. ex A. Rich. (Myricaceae) Root Extract in Streptozotocin-Induced Diabetic Mice
Authors: Yohannes Kelifa, Gomathi Periasamy, Aman Karim
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Introduction: Diabetes mellitus has become a major public health and economical problem across the globe. Modern antidiabetic drugs have a number of limitations, and scientific investigation of traditional herbal remedies used for diabetes may provide novel leads for the development of new antidiabetic drugs that can be used as alternative or complementary to available antidiabetic allopathic medications. Though Myrica salicifolia Hochst. ex A. Rich. is used for the management of diabetes in Ethiopian traditional medicine, there was no previous scientific evidence about its antidiabetic effect to the authors’ knowledge. This study was undertaken to evaluate the antidiabetic activity the root extracts of Myrica salicifolia in streptozotocin (STZ)-induced diabetic mice. Methods: Experimental diabetes was induced by intraperitoneal administration of STZ (150 mg/kg) in male mice. Diabetic mice were treated with oral doses of M. salicifolia root extracts at 200, 400 and 600 mg/kg, and its fractions (chloroform, ethyl acetate, n-butanol and aqueous) at a dose of 400 mg/kg daily for 15 days. Fasting blood glucose level (BGL) was measured at 0, 5th,10th, and 15th day. The free radical scavenging activity of the crude extract was determined using in vitro by DPPH assay. The statistical significance was assessed by one-way ANOVA, followed by Tukey’s multiple comparison tests. Results were considered significant when p < 0.05. Results: Daily administration of the M. salicifolia 80% methanol root extracts (at three different doses (200, 400 and 600 mg/kg) significantly (p < 0.05, p < 0.01 and p < 0.001) reduced fasting BGL compared with diabetic control. The aqueous and butanol fractions at a dose of 400 mg/kg resulted in maximum reduction of fasting BGL by 42.39%, and 52.13%, respectively at the 15th day in STZ-induced diabetic mice. Free radical scavenging activity of the 80% methanol extract of M. salicifolia was comparable to ascorbic acid. The IC50 values of the crude extract and ascorbic acid (a reference compound) were found to be 4.54 μg/ml and 4.39 μg/ml, respectively. Conclusion: These findings demonstrated that the methanolic extracts of M. salicifolia root and its fractions (n-butanol and aqueous) exhibit a significant antihyperglycemic activity in STZ-induced diabetic mice. Furthermore, the result of the present study indicates that M. salicifolia root extract is a potential source of natural antioxidants.Keywords: antidiabetic, diabetes mellitus, DPPH, mice, Myrica salicifolia, streptozotocin
Procedia PDF Downloads 189829 Theoretical Study of Carbonic Anhydrase-Ii Inhibitors for Treatment of Glaucoma
Authors: F. Boukli Hacene, W. Soufi, S. Ghalem
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Glaucoma disease is a progressive degenerative optic neuropathy, with irreversible visual field deficits and high eye pressure being one of the risk factors. Sulfonamides are carbonic anhydrase-II inhibitors that aim to decrease the secretion of aqueous humor by direct inhibition of this enzyme at the level of the ciliary processes. These drugs present undesirable effects that are difficult to accept by the patient. In our study, we are interested in the inhibition of carbonic anhydrase-II by different natural ligands (curcumin analogues) using molecular modeling methods using molecular operating environment (MOE) software to predict their interaction with this enzyme.Keywords: carbonic anhydrase-II, curcumin analogues, drug research, molecular modeling
Procedia PDF Downloads 82828 Pharmacokinetics of First-Line Tuberculosis Drugs in South African Patients from Kwazulu-Natal: Effects of Pharmacogenetic Variation on Rifampicin and Isoniazid Concentrations
Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi
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Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis
Procedia PDF Downloads 178827 Virtual Screening and in Silico Toxicity Property Prediction of Compounds against Mycobacterium tuberculosis Lipoate Protein Ligase B (LipB)
Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy
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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT
Procedia PDF Downloads 416826 Effects of Cuminum cyminum L. Essential Oil Supplementation on Components of Metabolic Syndrome: A Clinical Trial
Authors: Ashti Morovati, Hushyar Azari, Bahram Pourghassem Gargari
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Objectives and goals: The prevalence of metabolic syndrome (MetS), as a major health burden for societies, is increasing. This clinical trial was conducted to evaluate the effects of CuEO supplementation on anthropometric indices, systolic and diastolic blood pressure, blood glucose level, insulin resistance and serum lipid level in patients suffering from MetS. Methods: This was a randomized, triple‐blind, placebo‐controlled clinical trial in which 56 patients with MetS aged 18–60 years who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Inclusion criteria for the study were comprised of diagnosis of MetS according to the new International Federation of Diabetes. The exclusion criteria were defined as: taking herbal supplements, use of drugs having evident interaction with cumin such as anti‐depressant drugs, vitamin D, omega 3, selenium, zinc, smoking, pregnancy, or breastfeeding, suffering from cancer, having any history of gastrointestinal and hepatic, cardiovascular, thyroid and kidney disorders, and menopause. 75 mg CuEO or placebo soft gels were administered three times daily to the participants for eight weeks. The soft gel consumption was checked by asking the participants to bring the medication containers in the follow‐up visits at the 4th and the 8th weeks of the study. Data pertaining to blood pressure, height, weight, waist circumference, hip circumference and BMI, as well as food consumption were collected at the beginning and end of the study. Fasting blood samples ( glucose, triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol) were obtained and biochemical measurements were assessed at the beginning and end of the study. Results: At eight weeks, a total of 44 patients completed this study. Except for diastolic blood pressure (DBP), the other assessed variables were not significantly different between the two groups. In intra group analysis, placebo and CuEO groups both had insignificant decrements in DBP (mean difference [MD] with 95% CI: −3.31 [−7.11, 0.47] and −1.77 [−5.95, 2.40] mmHg, respectively). However, DBP was significantly lower in CuEO compared with the placebo group at the end of study (81.41 ± 5.88 vs. 84.09 ± 5.54 mmHg, MD with 95% CI: −3.98 [−7.60, −0.35] mmHg, p < .05). Conclusions: The results of this study indicated that CuEO does not have any effect on MetS components, except for DBP in patients with MetS.Keywords: blood pressure, fasting blood glucose, lipid profile, waist circumference
Procedia PDF Downloads 145825 Transdermal Delivery of Sodium Diclofenac from Palm Kernel Oil Esteres Nanoemulsions
Authors: Malahat Rezaee, Mahiran Basri, Abu Bakar Salleh, Raja Noor Zaliha Raja Abdul Rahman
Abstract:
Sodium diclofenac is one of the most commonly used drugs of nonsteroidal anti-inflammatory drugs (NSAIDs). It is especially effective in the controlling the severe conditions of inflammation and pain, musculoskeletal disorders, arthritis, and dysmenorrhea. Formulation as nanoemulsions is one of the nanoscience approaches that has been progressively considered in pharmaceutical science for transdermal delivery of the drug. Nanoemulsions are a type of emulsion with particle sizes ranging from 20 nm to 200 nm. An emulsion is formed by the dispersion of one liquid, usually the oil phase in another immiscible liquid, water phase that is stabilized using the surfactant. Palm kernel oil esters (PKOEs), in comparison to other oils, contain higher amounts of shorter chain esters, which suitable to be applied in micro and nanoemulsion systems as a carrier for actives, with excellent wetting behavior without the oily feeling. This research aimed to study the effect of terpene type and concentration on sodium diclofenac permeation from palm kernel oil esters nanoemulsions and physicochemical properties of the nanoemulsions systems. The effect of various terpenes of geraniol, menthone, menthol, cineol and nerolidol at different concentrations of 0.5, 1.0, 2.0, and 4.0% on permeation of sodium diclofenac were evaluated using Franz diffusion cells and rat skin as permeation membrane. The results of this part demonstrated that all terpenes showed promoting effect on sodium diclofenac penetration. However, menthol and menthone at all concentrations showed significant effects (<0.05) on drug permeation. The most outstanding terpene was menthol with the most significant effect for skin permeability of sodium diclofenac. The effect of terpenes on physicochemical properties of nanoemulsion systems was investigated on the parameters of particle size, zeta potential, pH, viscosity and electrical conductivity. The result showed that all terpenes had the significant effect on particle size and non-significant effects on the zeta potential of the nanoemulsion systems. The effect of terpenes was significant on pH, excluding the menthone at concentrations of 0.5 and 1.0%, and cineol and nerolidol at the concentration of 2.0%. Terpenes also had significant effect on viscosity of nanoemulsions exception of menthone and cineol at the concentration of 0.5%. The result of conductivity measurements showed that all terpenes at all concentration except cineol at the concentration of 0.5% represented significant effect on electrical conductivity.Keywords: nanoemulsions, palm kernel oil esters, sodium diclofenac, terpenes, skin permeation
Procedia PDF Downloads 414