Search results for: antiepileptic drugs

Authors: Ashit Syngle, Nidhi Garg, Pawan Krishan

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Background: Endothelial Progenitor Cells (EPCs) are depleted and contribute to increased cardiovascular (CV) risk in rheumatoid arthritis (RA). Statins exert a protective effect in CAD partly by promoting EPC mobilization. This vasculoprotective effect of statin has not yet been investigated in RA. We aimed to investigate the effect of rosuvastatin on EPCs in RA. Methods: 50 RA patients were randomized to receive 6 months of treatment with rosuvastatin (10 mg/day, n=25) and placebo (n=25) as an adjunct to existing stable antirheumatic drugs. EPCs (CD34+/CD133+) were quantified by Flow Cytometry. Inflammatory measures included DAS28, CRP and ESR were measured at baseline and after treatment. Lipids and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1) were estimated at baseline and after treatment. Results: At baseline, inflammatory measures and pro-inflammatory cytokines were elevated and EPCs depleted among both groups. At baseline, EPCs inversely correlated with DAS28 and TNF-α in both groups. EPCs increased significantly (p < 0.01) after treatment with rosuvastatin but did not show significant change with placebo. Rosuvastatin exerted positive effect on lipid spectrum: lowering total cholesterol, LDL, non HDL and elevation of HDL as compared with placebo. At 6 months, DAS28, ESR, CRP, TNF-α and IL-6 improved significantly in rosuvastatin group. Significant negative correlation was observed between EPCs and DAS28, CRP, TNF-α, and IL-6 after treatment with rosuvastatin. Conclusion: First study to show that rosuvastatin improves inflammation and EPC biology in RA possibly through its anti-inflammatory and lipid lowering effect. This beneficial effect of rosuvastatin may provide a novel strategy to prevent cardiovascular events in RA.

Keywords: RA, Endothelial Progenitor Cells, rosuvastatin, cytokines

Procedia PDF Downloads 258

Authors: Murtada Ahmed Oshi, Jin-Wook Yoo

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Layer-by-layer (LBL) coating has gained popularity for drug delivery of therapeutic drugs. Herein we described a novel approach for enhancing the therapeutic efficiency of the locally administered dexamethasone (Dex) for inflammatory bowel disease (IBD). We utilized a LBL-coating technique on Dex microcrystals (DexMCs) with multiple layers of polyelectrolytes composed of poly (allylamine hydrochloride) (PAH), poly (sodium 4-styrene sulfonate) (PSS) and Eudragit® S100 (ES). The successful deposition of the layers onto DexMCs surfaces were confirmed through zeta potential measurement and confocal laser scanning microscopy. The surface morphology was investigated through scanning electron microscopy. The drug encapsulation efficiency was 95% with a mean particle size of 2 µm and negative surface charge (-40 mV). Moreover, in vitro drug release study showed a minimum release of the drug ( 15%) at an acidic condition during initial first 5 h, followed by sustained-release at an alkaline condition. For in vivo study, LBL-DxMCs were administered orally to ICR mice suffering from dextran sulfate sodium-induced colitis. LBL-DxMCs substantially enhanced anti-IBD activities as compared to DxMCs. Macroscopic, histological and biochemical (tumor necrosis factor-α, interleukin-6 and myeloperoxidase) examinations revealed marked improvements of colitis signs in the mice treated with LBL-DxMCs compared with those treated with DxMCs. Overall, LBL-DxMCs could be a suitable candidate for the treatment of IBD.

Keywords: dexamethasone, inflammatory bowel disease, LBL-coating, polyelectrolytes

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Authors: Afsal Mohammed Kadavilpparampu, Haider A. J. Al Lawati, Fakhr Eldin O. Suliman, Salma M. Z. Al Kindy

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In this work, we evaluated the appropriateness of various oxidants that can be used potentially with Ru(bipy)32+ CL system while performing CL detection in a microfluidic device using eight common active pharmaceutical ingredients- ciprofloxacin, hydrochlorothiazide, norfloxacin, buspirone, fexofenadine, cetirizine, codeine, and dextromethorphan. This is because, microfludics have very small channel volume and the residence time is also very short. Hence, a highly efficient oxidant is required for on-chip CL detection to obtain analytically acceptable CL emission. Three common oxidants were evaluated, lead dioxide, cerium ammonium sulphate and ammonium peroxydisulphate. Results obtained showed that ammonium peroxydisulphate is the most appropriate oxidant which can be used in microfluidic setup and all the tested analyte give strong CL emission while using this oxidant. We also found that Ru(bipy)33+ generated off-line by oxidizing [Ru(bipy)3]Cl2.6H2O in acetonitrile under acidic condition with lead dioxide was stable for more than 72 hrs. A highly sensitive microbore HPLC- CL method using ammonium peroxydisulphate as an oxidant in a microfluidic on-chip CL detection has been developed for the analyses of fixed-dose combinations of pseudoephedrine (PSE), fexofenadine (FEX) and cetirizine (CIT) in biological fluids and pharmaceutical formulations with minimum sample pre-treatment.

Keywords: oxidants, microbore High Performance Liquid Chromatography, chemiluminescence, microfluidics

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Authors: Yousef M. Abouzeed A. Elfahem, F. Zgheel, M. A. Saad, Mohamed O. Ahmed

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The bioactive properties of phytochemicals indicate their potential as natural drug products to prevent and treat human disease; in particular, compounds with antioxidant and antimicrobial activities may represent a novel class of safe and effective drugs. Following desiccation, grapes (Vitis vinifera) become more resistant to microbial-based degradation, suggesting that raisins may be a source of antimicrobial compounds. To investigate this hypothesis, total phenolic extracts were obtained from common raisins, local market-sourced. The acetone extract was tested for antibacterial activity against four prevalent bacterial pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella spp. and Escherichia coli). Antibiotic sensitivity and the Minimum Inhibitory Concentration (MIC) were determined for each bacterium. High performance liquid chromatography was used to identify compounds in the total phenolic extract. The raisin phenolic extract inhibited growth of all the tested bacteria; the greatest inhibitive effect (normalized to cefotaxime sodium control antibiotic) occurred against P. aeruginosa, followed by S. aureus > Salmonella spp.= E. coli. The phenolic extracts contained the bioactive compounds catechin, quercetin, and rutin. Thus, phytochemicals in raisin extract have antibacterial properties; this plant-based extract, or its bioactive constituents, may represent a promising natural preservative or antimicrobial agent for the food industry or anti-infective drug.

Keywords: Vitis vinifera raisin, extraction, phenolic compounds, antibacterial activity

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Authors: Prabha Rohatgi

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To obtain an efficient control over a huge amount of inventory of drugs in pharmacy department of any hospital, generally, the medicines are categorized on the basis of their cost ‘ABC’ (Always Better Control), first and then categorize on the basis of their criticality ‘VED’ (Vital, Essential, desirable) for prioritization. About one-third of the annual expenditure of a hospital is spent on medicines. To minimize the inventory investment, the hospital management may like to keep the medicines inventory low, as medicines are perishable items. The main aim of each and every hospital is to provide better services to the patients under certain limited resources. To achieve the satisfactory level of health care services to outdoor patients, a hospital has to keep eye on the wastage of medicines because expiry date of medicines causes a great loss of money though it was limited and allocated for a particular period of time. The objectives of this study are to identify the categories of medicines requiring incentive managerial control. In this paper, to minimize the total inventory cost and the cost associated with the wastage of money due to expiry of medicines, an inventory control model is used as an estimation tool and then nonlinear programming technique is used under limited budget and fixed number of orders to be placed in a limited time period. Numerical computations have been given and shown that by using scientific methods in hospital services, we can give more effective way of inventory management under limited resources and can provide better health care services. The secondary data has been collected from a hospital to give empirical evidence.

Keywords: ABC-VED inventory classification, multi item inventory problem, nonlinear programming technique, optimization of EOQ

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Authors: Pedro Ferraz-Gameiro

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Introduction: The Pellegrini-Stieda lesion is the result of post-traumatic calcification and/or ossification on the medial collateral ligament (MCL) of the knee. When this calcification is accompanied by gonalgia and limitation of knee flexion, it is called Pellegrini-Stieda syndrome. The pathogenesis is probably the calcification of a post-traumatic hematoma at least three weeks after the initial trauma or secondary to repetitive microtrauma. On anteroposterior radiographs, a Pellegrini-Stieda lesion is a linear vertical ossification or calcification of the proximal portion of the MCL and usually near the medial femoral condyle. Patients with Pellegrini-Stieda syndrome present knee pain associated with loss of range of motion. The treatment is usually conservative with analgesic and anti-inflammatory drugs, either systemic or intra-articular. Physical medicine and rehabilitation techniques associated with shock wave therapy can be a way of reduction of pain/inflammation. Patients who maintain instability with significant limitation of knee mobility may require surgical excision. Methods: Research was done using PubMed central using the terms Pellegrini-Stieda syndrome. Discussion/conclusion: Medical treatment is the rule, with initial rest, anti-inflammatory, and physiotherapy. If left untreated, this ossification can potentially form a significant bone mass, which can compromise the range of motion of the knee. Physical medicine and rehabilitation techniques associated with shock wave therapy are a way of reduction of pain/inflammation.

Keywords: knee, Pellegrini-Stieda syndrome, rehabilitation, shock waves therapy

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Authors: S. V. Patil, P. S. Dounde, S. S. Patil

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Emulgels have emerged as one of the most interesting topical delivery system as it has dual release control system that is gel and emulsion. The major objective behind this formulation is delivery of hydrophobic drugs to systemic circulation via skin. In fact presence of a gelling agent in water phase converts a classical emulsion in to emulgel. The emulgel for dermatological use has several favorable properties such as being thixotropic, greaseless, easily spreadable, easily removable, emollient, non-staining, water-soluble, longer shelf life, bio-friendly, transparent and pleasing appearance. Various penetration enhancers can potentiate the effect. So this can be used as better topical drug delivery systems over present conventional systems available in market. Piroxicam is a non-steroidal anti-inflammatory drug that has major problems when administered orally; it is an insoluble drug and has irritant effect on gastro intestinal tract lead to ulceration and bleeding. The aim of this study was to overcoming these problems through preparation of topical emulgel of this drug. Emulgel of Piroxicam was prepared using Carbopol 940 along with mentha oil and clove oil as permeation enhancer. The prepared emulgel were evaluated for their physical appearance, pH determination, viscosity, spreadability, in vitro drug release, ex vivo permeation studies. All the prepared formulations showed acceptable physical properties, homogeneity, consistency, spreadability, viscosity and pH value. The emulgel was found to be stable with respect to physical appearance, pH, rheological properties and drug content at all temperature and conditions for three month.

Keywords: emulgel, piroxicam, menthe oil, clove oil

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Authors: Sonia Lachowska, Agnieszka Antonczyk, Joanna Tunikowska, Pawel Kucharski, Bartlomiej Liszka

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Isoflurane is one of the most commonly used anaesthetic gases in veterinary medicine. Due to its numerous side effects, intravenous anaesthesia is more often used. The combination of tiletamine with zolazepam has proved to be a safe and pharmacologically beneficial combination. Analgesic effect, fast induction time, effective myorelaxation, and smooth recovery are the main advantages of this combination of drugs. In the following study, the authors verified the necessity of isoflurane to maintain anaesthesia in dogs after the use of tiletamine-zolazepam for induction. 12 dogs were selected to the group with the inclusion criteria: ASA (American Society of Anaesthesiology) I or II. Each dog received premedication intramuscularly with medetomidine-butorfanol (10 μg/kg, 0,1 mg/kg respectively). 15 minutes from premedication, preoxygenation lasting 5 minutes was started. Anaesthesia was induced with tiletamine-zolazepam at the dose of 5 mg/kg. Then the dogs were intubated and anaesthesia was maintained with isoflurane. Initially, MAC (Minimum Alveolar Concentration) was set to 0.7 vol.%. After 15 minutes equilibration, MAC was determined using Dixon’s up-and-down method. Painful stimulation including compressions of paw pad, phalange, groin area, and clamping Backhaus on skin. Hemodynamic and ventilation parameters were measured and noted in 2 minutes intervals. In this method, the positive or negative response to the noxious stimulus is estimated and then used to determine the concentration of isoflurane for next patient. The response is only assessed once in each patient. The results show that isoflurane is not necessary to maintain anaesthesia after tiletamine-zolazepam induction. This is clinically important because the side effects resulting from using isoflurane are eliminated.

Keywords: anaesthesia, dog, Isoflurane, The Dixon's up-and-down method, Tiletamine, Zolazepam

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Authors: Jaspal Rana, Alkem Laboratories, Baddi, Himachal Pradesh, India Chitkara University, Punjab, India

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Oxidative stress has been identified as an underlying cause of ischemia-reperfusion (IR) related cognitive dysfunction and brain damage. Therefore, antioxidant based therapies to treat IR injury are being investigated. Allium cepa L. (onion) is used as culinary medicine and is documented to have marked antioxidant effects. Hence, the present study was designed to evaluate the effect of A. cepa outer scale extract (ACE) against IR induced cognition and biochemical deficit in mice. ACE was prepared by maceration with 70% methanol and fractionated into ethylacetate and aqueous fractions. Bilateral common carotid artery occlusion for 10 min followed by 24 h reperfusion was used to induce cerebral IR injury. Following IR injury, ACE (100 and 200 mg/kg) was administered orally to animals for 7 days once daily. Behavioral outcomes (memory and sensorimotor functions) were evaluated using Morris water maze and neurological severity score. Cerebral infarct size, brain thiobarbituric acid reactive species, reduced glutathione, and superoxide dismutase activity was also determined. Treatment with ACE significantly ameliorated IR mediated deterioration of memory and sensorimotor functions and rise in brain oxidative stress in animals. The results of the present investigation revealed that ACE improved functional outcomes after cerebral IR injury, which may be attributed to its antioxidant properties.

Keywords: stroke, neuroprotection, ischemia reperfusion, herbal drugs

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Authors: D. J. Kalita

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Cancer is one of the prime causes of early death worldwide. Mutation of the gene involve in DNA repair and damage, like BRCA2 (Breast cancer gene two) genes, can be detected efficiently by PCR-RFLP to early breast cancer diagnosis and adopt the suitable method of treatment. Host Defense Peptide can be used as blueprint for the design and synthesis of novel anticancer drugs to avoid the side effect of conventional chemotherapy and chemo resistance. The change at nucleotide position 392 of a -› c in the cancer sample of dog mammary tumour at BRCA2 (exon 7) gene lead the creation of a new restriction site for SsiI restriction enzyme. This SNP may be a marker for detection of canine mammary tumour. Support vector machine (SVM) algorithm was used to design and predict the anticancer peptide from the mature functional peptide. MTT assay of MCF-7 cell line after 48 hours of post treatment showed an increase in the number of rounded cells when compared with untreated control cells. The ability of the synthesized peptide to induce apoptosis in MCF-7 cells was further investigated by staining the cells with the fluorescent dye Hoechst stain solution, which allows the evaluation of the nuclear morphology. Numerous cells with dense, pyknotic nuclei (the brighter fluorescence) were observed in treated but not in control MCF-7 cells when viewed using an inverted phase-contrast microscope. Thus, PCR-RFLP is one of the attractive approach for early diagnosis, and synthetic cationic peptide can be used for the treatment of canine mammary tumour.

Keywords: cancer, cationic peptide, host defense peptides, Breast cancer genes

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Authors: Abdollah Sobhani, Hossein Vaseghi-Dodaran

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Proteomics is defined as the study of the component of a cell, tissue and biological fluid. This technique has the potential to identify protein biomarkers of a disease states. In this study which was performed on bovine ovarian follicular cysts (BOFC), eight proteins are over expressed in BOFC that these proteins could be useful biomarkers for BOFC. The difference between serum proteome pattern cows affected by postpartum endometritis with healthy cows revealed that concentrations orosomucoid was decreased in endometritis. The comparison proteome of brucella abortus between laboratory adapted strains and clinical isolates could be useful to better understand this disease and vaccine development. Proteomics experiments identified new proteins and pathways that may be important in future hypothesis-driven studies of glucocorticoid-induced immunosuppression. Understanding the molecular mechanisms of effective parameters on male fertility is essential for obtaining high reproductive efficiency by decreasing cost and time. The investigations on proteome of high fertility spermatozoa indicated that expression of some proteins such as casein kinase 2 (CKII) prime poly peptide and tyrosine kinase in high fertility spermatozoa was higher compared to low fertility spermatozoa. Also, some evidence has indicated that variation in protein types and amounts in seminal fluid regulates fertility indexes in dairy bull. In conclusion, proteomics is a useful technique for discovering drugs, vaccine development, and diagnosis disease by biomarkers and improvement of reproduction efficiency.

Keywords: proteomics, reproduction, biomarker, immunity

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Authors: Jabulani Gilford Kheswa

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This paper reports on the effects of unemployment on the sexual behaviour of male youth. Drawing from Jahoda’s deprivation theory, unemployed male youth is prone to psychological distress and as a result, they resort to drugs and alcohol abuse as a way to cope with discrimination. Studies showed that such youth is more inclined to be sexually aggressive and very often engage in criminal activities and risky sexual behaviour such as multiple sexual partners and unprotected sex to cover their feelings of emotional insecurities and negative self-concept. The purpose of the study was to investigate the impact of unemployment on the sexual behaviour of Xhosa- speaking male youth, aged 19-35, from Quzini Location, Eastern Cape, South Africa. A qualitative, explorative, descriptive and contextual design was followed using phenomenological method. The purposively sampled comprised fifteen unemployed males who gave their informed consent to be interviewed. For trustworthiness of the study, the researcher met the Lincoln and Guba’s principles, namely; credibility, dependability confirmability and transferability. The following themes were identified, namely; patriarchy, gender- based violence, drug abuse, stigma and discrimination, criminal activities, depression and low- self-esteem. Based on the findings, the recommendations are that the government and private sectors should create jobs aimed at reducing unemployment for unemployed youth and psycho-educational programmes that will equip them in the areas of sexual values and attitudes, communication and decision-making skills.

Keywords: discrimination, male-youth, sex, unemployment

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Authors: Hend K. Moosa, Eman A. Rashwan, Ezzat M. Hassan, Amany A. Ghazy, Amel G. Sheredy

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The stability of microRNA (miR) in the circulation can show a great progress toward the discovery of non-invasive diagnostic and prognostic biomarkers in many diseases. In the present study, circulatory miR-122 and miR-130a were analysed in chronic hepatitis C Egyptian patients in predicting the clinical outcome of interferon treatment. In addition, their expression levels were correlated to viral RNA levels, necro-inflammatory markers (AST, ALT) and to each other. This study was conducted on 51 subjects where 36 were chronic HCV patients in which they were divided into naive and interferon treated HCV patients (responders and non-responders) and 15 matched healthy controls. Serum quantification of miR-122 and miR-130a were performed by quantitative Real-time Polymerase Chain Reaction (qRT-PCR). The results showed a significant upregulation of miR-122 in non-responder patients (P=0.049). By receiver operating characteristic analysis curve, miR-122 revealed 65% sensitivity and 92.3% specificity in predicting non-responsiveness of patients to IFN treatment, while miR-130a showed a sensitivity of 100% and specificity of 53.85%. Remarkably, there was a significant positive correlation between miR-122 and miR-130a in naive HCV patients (r=0.714, p=0.003). However, there was no significant correlation between serum miR-122, miR-130a expression levels and necro-inflammatory markers (AST, ALT). To conclude, miR-122 and miR-130a have a significant association with viral RNA levels and accordingly, they may have a synergistic power in promoting viral replication. Interestingly, miR-122 and miR-130a have a predictive power in predicting clinical outcome of IFN treatment which can be further studied in currently used drugs in order to reduce the socio-economic burden of potentially non-responders.

Keywords: hepatitis C, microRNA, miR-122, miR-130a

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Authors: Oluwatofunmi Musa-Ajakaiye, Paul Olorunfemi M.D MPH, John Obafaiye

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Introduction: The U.S Food and Drug Administration (FDA) reports the public notices for recalled FDA-regulated products over periods of time. It study reviewed the primary reasons for recalls of products of various types over a period of 7 years. Methods: The study analyzed data provided in the FDA’s archived recalls for the years 2010-2017. It identified the various reasons for product recalls in the categories of foods, beverages, drugs, medical devices, animal and veterinary products, and dietary supplements. Using SPSS version 29, descriptive statistics and chi-square analysis of the data were performed. Results (numbers, percentages, p-values, chi-square): Over the period of analysis, a total of 931 recalls were reported. The most frequent reason for recalls was undeclared products (36.7%). The analysis showed that the most recalled product type in the data set was foods and beverages, representing 591 of all recalled products (63.5%).In addition, it was observed that foods and beverages represent 77.2% of products recalled due to the presence of microorganisms. Also, a sub-group analysis of recall reasons of food and beverages found that the most prevalent reason for such recalls was undeclared products (50.1%) followed by Listeria (17.3%) then Salmonella (13.2%). Conclusion: This analysis shows that foods and beverages have the greatest percentages of total recalls due to the presence of undeclared products listeria contamination and Salmonella contamination. The prevalence of Salmonella and Listeria contamination suggests that there is a high risk of microbial contamination in FDA-approved products and further studies on the effects of such contamination must be conducted to ensure consumer safety.

Keywords: food, beverages, listeria, salmonella, FDA, contamination, microbial

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Authors: Tien S. H. Pham, Peter J. Mahon, Aimin Yu

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The detection of drug molecules by voltammetry has attracted great interest over the past years. However, many drug molecules exhibit poor electrochemical signals at common electrodes which result in low sensitivity in detection. An efficient way to overcome this problem is to modify electrodes with functional materials. Since discovered in 2004, graphene (or reduced graphene oxide) has emerged as one of the most studied two-dimensional carbon materials in condensed matter physics, electrochemistry, and so on due to its exceptional physicochemical properties. Additionally, the continuous development of technology has opened the new window for the successful fabrications of many novel graphene-based nanomaterials to serve in electrochemical analysis. This research aims to synthesize and characterize gold nanoparticle coated beta-cyclodextrin functionalized reduced graphene oxide (Au NP–β-CD–RGO) nanocomposites with highly conductive and strongly electro-catalytic properties as well as excellent supramolecular recognition abilities for the modification of electrodes. The electrochemical responses of ciprofloxacin at the as-prepared nanocomposite modified electrode was effectively amplified was much higher in comparison with that at the bare electrode. The linear concentration range was from 0.01 to 120 µM, with a detection limit of 2.7 nM using differential pulse voltammetry. Thus, Au NP–β-CD–RGO nanocomposite has great potential as an ideal material to construct sensitive sensors for the electrochemical determination of ciprofloxacin or similar antibacterial drugs in the future based on its excellent stability, selectivity, and reproducibility.

Keywords: Au nanoparticles, β-CD, ciprofloxacin, electrochemical determination, graphene based nanomaterials

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Authors: Riddhi Shukla, Rajeshri Patel, Prakruti Buch, Tejas Sharma, Mihir Raval, Navin Sheth

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Many classical drugs are claimed to have blood sugar lowering properties that make them valuable for people with or at high risk of type 2 diabetes. Vijaysar (Pterocarpus marsupium) and Gaumutra (Indian cow urine) both have been shown antidiabetic property since primordial time and both shows synergistic effect in combination for hypoglycaemic activity. The study was undertaken to investigate the hypoglycaemic and anti-diabetic effects of the combination of Vijaysar and Gaumutra which is a classical preparation mentioned in Ayurveda named as Pramehari ark. Rats with Type 2 diabetes which is induced by streptozotocin (STZ, 35mg/kg) given a high-fat diet for one month and compared with normal rats. Diabetic rats showed raised level of body weight, triglyceride (TG), total cholesterol, HDL, LDL, and D-glucose concentration and other serum, cardiac and hypertrophic parameters in comparison of normal rats. After treatment of different doses of drug the level of parameters like TG, total cholesterol, HDL, LDL, and D-glucose concentration found to be decreased in standard as well as in treatment groups. In addition treatment groups also found to be decreased in the level of serum markers, cardiac markers, and hypertrophic parameters. The findings demonstrated that Pramehari ark prevented the pathological progression of type 2 diabetes in rats.

Keywords: cow urine, hypoglycemic effect, synergic effect, type 2 diabetes, vijaysar

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Authors: Mehrnoosh Azimi Sanavi, Hamed Ghazvini, Mehryar Zargari, Hossein Ghalehnoei, Zahra Hosseini-khah

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Objectives: Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C) is one of the most important genes associated with schizophrenia. Methods: 45 male Wistar rats were divided into 5 groups: saline, control, ketamine, clozapine, and risperidone. Animals in ketamine, risperidone, and clozapine groups received ketamine (30 mg/ kg-i.p.) for 10 days. After the last injection of ketamine, we started injecting clozapine (7.5 mg/kg-i.p.) risperidone (1 mg/kg-i.p.) for up to 28 days. Twenty-four hours after the last injection, open field, social interaction, and elevated plus-maze tests, and gene expression in the hippocampus were performed. Results: The results of the social interaction test revealed a significant decrease in cumulative time with ketamine compared with the saline group and an increase with clozapine and risperidone compared with the ketamine group. Moreover, results from the elevated plus-maze test demonstrated a critical decrease in open-arm time and an increase in close-arm time with ketamine compared with saline, as well as an increase in open-arm time with risperidone compared with ketamine. Further results revealed a significant increase in rearing and grooming with ketamine compared to saline, as well as a decrease with risperidone and clozapine compared to ketamine. There were no significant differences in CACNA1C gene expression between groups in the rat hippocampus. In brief, the results of this study indicated that clozapine and risperidone could partially improve cognitive impairments in the rat. However, our findings demonstrated that this treatment is not related to CACNA1C gene expression.

Keywords: schizophrenia, ketamine, clozapine, risperidone

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Authors: M. Klimova, O. Semyachkina-Glushkovskaya, J. Kurts, E. Zinchenko, N. Navolokin, A. Shirokov, A. Dubrovsky, A. Abdurashitov, A. Terskov, A. Mamedova, I. Agranovich, T. Antonova, I. Blokhina

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The direction for research of Alzheimer's disease is to find an effective non-invasive and non-pharmacological way of treatment. Here we tested our hypothesis that the opening of the blood-brain barrier (BBB) induces activation of lymphatic drainage and clearing functions that can be used as a method for non-invasive stimulation of clearance of beta-amyloid and therapy of Alzheimer’s disease (AD). To test our hypothesis, in this study on healthy male mice we analyzed the interaction between BBB opening by repeated loud music (100-10000 Hz, 100 dB, duration 2 h: 60 sec – sound; 60 sec - pause) and functional changes in the meningeal lymphatic vessels (MLVs). We demonstrate clearance of dextran 70 kDa (i.v. injection), fluorescent beta-amyloid (intrahippocampal injection) and gold nanorods (intracortical injection) via MLV that significantly increased after the opening of BBB. Our studies also demonstrate that the BBB opening was associated with the improvement of neurocognitive status in mice with AD. Thus, we uncover therapeutic effects of BBB opening by loud music, such as non-invasive stimulation of lymphatic clearance of beta-amyloid in mice with AD, accompanied by improvement of their neurocognitive status. Our data are consistent with other results suggesting the therapeutic effect of BBB opening by focused ultrasound without drugs for patients with AD. This research was supported by a grant from RSF 18-75-10033

Keywords: Alzheimer's disease, beta-amyloid, blood-brain barrier, meningeal lymphatic vessels, repeated loud music

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Authors: Maryam Nazari, Majid Karandish, Alihossein Saberi

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Obesity as a global health challenge motivates pharmaceutical industries to produce anti-obesity drugs. However, effectiveness of these agents is remained unclear. Because of popularity of dietary supplements, the aim of this study was tp investigate the effects of Conjugated Linoleic Acid (CLA) and L-carnitine (LC) on serum glucose, triglyceride, cholesterol and weight changes in diet induced obese rats. 48 male Wistar rats were randomly divided into two groups: Normal fat diet (n=8), and High fat diet (HFD) (n=32). After eight weeks, the second group which was maintained on HFD until the end of study, was subdivided into four categories: a) 500 mg Corn Oil (as control group), b) 500 mg CLA, c) 200 mg LC, d) 500 mg CLA+ 200 mg LC.All doses are planned per kg body weights, which were administered by oral gavage for four weeks. Body weights were measured and recorded weekly by means of a digital scale. At the end of the study, blood samples were collected for biochemical markers measurement. SPSS Version 16 was used for statistical analysis. At the end of 8^th week, a significant difference in weight was observed between HFD and NFD group. After 12 weeks, LC significantly reduced weight gain by 4.2%. Trend of weight gain in CLA and CLA+LC groups was insignificantly decelerated. CLA+LC reduced triglyceride level significantly, but just CLA had significant influence on total cholesterol and insignificant decreasing effect on FBS. Our results showed that an obesogenic diet in a relative short time led to obesity and dyslipidemia which can be modified by LC and CLA to some extent.

Keywords: conjugated linoleic acid, high fat diet, L-Carnitine, obesity

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Authors: Carol Yue-En Ong, Angelina Hui-Min Tan, Quan Liu, Paul Chi-Lui Ho

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A public general hospital in Singapore has recently implemented an automated unit-dose machine in their inpatient dispensary, Swisslog, with the objective of reducing human error and improving patient safety. However, a concern in stability arises as tablets are removed from their original packaging (bottled loose tablets/capsules) and are repackaged into individual, clear plastic wrappers as unit doses in the system. Drugs that are light-sensitive and hygroscopic would be more susceptible to degradation as the wrapper does not offer full protection. Hence, this study was carried out to study the stability of haloperidol tablets and phenytoin capsules that are light-sensitive and hygroscopic respectively. Validated HPLC-UV assays were first established for quantification of these two compounds. The medications involved were put in the Swisslog and sampled every week for one month. The collected data was analysed and showed no degradation over time. This study also explored an alternative approach for drug stability determination-Raman spectroscopy. The advantage of Raman spectroscopy is its high time efficiency and non-destructive nature. The results suggest that drug degradation can indeed be detected using Raman microscopy, but further research is needed to establish this approach for quantification or qualification of compounds. NanoRam®, a portable Raman spectrocope was also used alongside Raman microscopy but was unsuccessful in detecting degradation in this study.

Keywords: drug stability, haloperidol, HPLC, phenytoin, raman spectroscopy, Swisslog

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Authors: Andreas Aceranti, Sergio Romanò, Simonetta Vernocchi, Silvia Arnaboldi, Emilio Mazza

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As a result of the Sars-Cov2 pandemic, the incidence of thymism disorders has significantly increased and, often, patients are reluctant to want to take drugs aimed at stabilizing mood. In order to provide an alternative approach to drug therapies, we have prepared a study in order to evaluate the possibility of improving the quality of life of these subjects through osteopathic treatment. Patients were divided into visceral and fascial manual treatment with the aim of increasing serotonin levels and stimulating the vagus nerve through validated techniques. The results were evaluated through the administration of targeted questionnaires in order to assess quality of life, mood, sleep and intestinal functioning. At a first endpoint we found, in patients undergoing fascial treatment, an increase in quality of life and sleep: in fact, they report a decrease in the number of nocturnal awakenings; a reduction in falling asleep times and greater rest upon waking. In contrast, patients undergoing visceral treatment, as well as those included in the control group, did not show significant improvements. Patients in the fascial group have, in fact, reported an improvement in thymism and subjective quality of life with a generalized improvement in function. Although the study is still ongoing, based on the results of the first endpoint we can hypothesize that fascial stimulation of the vagus nerve with manual and osteopathic techniques may be a valid alternative to pharmacological treatments in mood and sleep disorders.

Keywords: ostheopathy, insomnia, noctural awakening, thymism

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Authors: Maninderjeet K. Grewal, Sakshi Bhatnor, Renu Chadha

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The composition of pharmaceutical entities and the molecular interactions can be altered to optimize drug properties such as solubility and bioavailability by the crystal engineering technique. The present work has emphasized on the preparation, characterization, and biopharmaceutical evaluation of co-crystal of BCS Class II anti-osteoarthritis drug, Oxaprozin (OXA) with aspartic acid (ASPA) as co-former. The co-crystals were prepared through the mechanochemical solvent drop grinding method. Characterization of the prepared co-crystal (OXA-ASPA) was done by using analytical tools such as differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD). DSC thermogram of OXA-ASPA cocrystal showed a single sharp melting endotherm at 235 ºC, which was between the melting peaks of the drug and the counter molecules suggesting the formation of a new phase which is a co-crystal that was further confirmed by using other analytical techniques. FT-IR analysis of OXA-ASPA cocrystal showed a shift in a hydroxyl, carbonyl, and amine peaks as compared to pure drugs indicating all these functional groups are participating in cocrystal formation. The appearance of new peaks in the PXRD pattern of cocrystals in comparison to individual components showed that a new crystalline entity has been formed. The Crystal structure of cocrystal was determined using material studio software (Biovia) from PXRD. The equilibrium solubility study of OXA-ASPA showed improvement in solubility as compared to pure drug. Therefore, it was envisioned to prepare the co-crystal of oxaprozin with a suitable conformer to modulate its physiochemical properties and consequently, the biopharmaceutical parameters.

Keywords: cocrystals, coformer, oxaprozin, solubility

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Authors: Vinod Nair, C. Sadasivan

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Beta-lactam antibiotics are the most frequently prescribed medications in modern medicine. The antibiotic resistance by the production of enzyme beta-lactamase is an important mechanism seen in microorganisms. Resistance to beta-lactams mediated by beta-lactamases can be overcome successfully with the use of beta-lactamase inhibitors. New generations of the antibiotics contain mostly synthetic compounds, and many side effects have been reported for them. Combinations of beta-lactam and beta-lactamase inhibitors have become one of the most successful antimicrobial strategies in the current scenario of bacterial infections. Plant-based drugs are very cheap and having lesser adverse effect than synthetic compounds. The synergistic effect of eugenol acetate with beta-lactams restores the activity of beta-lactams, allowing their continued clinical use. It is reported here the enhanced inhibitory effect of phytochemical, eugenol acetate, isolated from the plant Syzygium aromaticum with beta-lactams on beta-lactamase. The compound was found to have synergistic effect with the antibiotic amoxicillin against antibiotic-resistant strain of S.aureus. The enzyme was purified from the organism and incubated with the compound. The assay showed that the compound could inhibit the enzymatic activity of beta-lactamase. Modeling and molecular docking studies indicated that the compound can fit into the active site of beta-lactamase and can mask the important residue for hydrolysis of beta-lactams. The synergistic effects of eugenol acetate with beta-lactam antibiotics may justify, the use of these plant compounds for the preparation of β-lactamase inhibitors against β-lactam resistant S.aureus.

Keywords: betalactamase, eugenol acetate, synergistic effect, molecular modeling

Procedia PDF Downloads 249

Authors: S. Rajeswari

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Medicinal Plant extracts and their bioactive compounds have been used for antimicrobial activities and have significant remedial properties. In the recent years, a wide range of investigations have been carried out throughout the world to confirm antimicrobial properties of different medicinally important plants. A number of plants showed efficient antimicrobial activities, which were comparable to that of synthetic standard drugs or antimicrobial agents. The large family Euphorbiaceae contains nearly about 300 genera and 7,500 speciesand one among is Ricinus communis or castor plant which has high traditional and medicinal value for disease free healthy life. Traditionally the plant is used as laxative, purgative, fertilizer and fungicide etc. whereas the plant possess beneficial effects such as anti-oxidant, antihistamine, antinociceptive, antiasthmatic, antiulcer, immunomodulatory anti diabetic, hepatoprotective, anti inflammatory, antimicrobial, and many other medicinal properties. This activity of the plant possess due to the important phytochemical constituents like flavonoids, saponins, glycosides, alkaloids and steroids. The presents study includes the phytochemical properties of Ricinus communis and to prediction of the anti-microbial activity of Ricinus communis using DNA gyrase of Staphylococcus aureus as molecular target. Docking results of varies chemicals compounds of Ricinus communis against DNA gyrase of Staphylococcus aureus by maestro 9.8 of Schrodinger show that the phytochemicals are effective against the target protein DNA gyrase. our studies suggest that the phytochemical from Ricinus communis such has INDICAN (G.Score 4.98) and SUPLOPIN-2(G.Score 5.74) can be used as lead molecule against Staphylococcus infections.

Keywords: euphorbiaceae, antimicrobial activity, Ricinus communis, Staphylococcus aureus

Procedia PDF Downloads 479

Authors: Asamaporn Puetpaiboon, Sunisa Chatmongkolchart, Nalinee Kovitwanawong, Osaree Akaraborworn

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Traumatic patients with massive bleeding require intensive resuscitation. The actual cost of anesthesia per case has never been clarified, so our study aimed to quantify the direct cost, and cost-to-charge ratio of anesthetic care in traumatic patients with intraoperative massive bleeding. This study was a prospective, observational, cost analysis study, conducted in Prince of Songkla University hospital, Thailand, with traumatic patients, of any mechanisms being recruited. Massive bleeding was defined as estimated blood loss of at least one blood volume in 24 hours, or a half of blood volume in 3 hours. The cost components were identified by the micro-costing method, and valued by the bottom-up approach. The direct cost was divided into 4 categories: the labor cost, the capital cost, the material cost and the cost of drugs. From September 2017 to August 2018, 10 patients with multiple injuries were included. Seven patients had motorcycle accidents, two patients fell from a height and another one was in a minibus accident. Two patients died on the operating table, and another two died within 48 hours. The median Sequential Organ Failure Assessment (SOFA) score was 8. The median intraoperative blood loss was 3,500 ml. The median direct cost, per case, was 250 United States Dollars (2017 exchange rate), and the cost-to-charge ratio was 0.53. In summary, the direct cost was nearly half of the hospital charge, for these traumatic patients with massive bleeding. However, our study did not analyze the indirect cost.

Keywords: cost, cost-to-charge ratio, micro-costing, trauma

Procedia PDF Downloads 148

Authors: Alex Soares Castro, Matheus Manoel Teles de Menezes, Larissa Silva de Azevedo, Ana Carolina Caleffi Patelli, Osmair Vital de Oliveira, Aline Thais Bruni, Marcelo Firmino de Oliveira

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Considering the problem of the seizure of illicit drugs, as well as the development of electrochemical sensors using chemically modified electrodes, this work shows the study of the electrochemical activity of cocaine in carbon paste electrode chemically modified with Cu (II) trans 3-MeO salcn complex. In this context, cyclic voltammetry was performed on 0.1 mol.L⁻¹ KCl supporting electrolyte at a scan speed of 100 mV s⁻¹, using an electrochemical cell composed of three electrodes: Ag /AgCl electrode (filled KCl 3 mol.L⁻¹) from Metrohm® (reference electrode); a platinum spiral electrode, as an auxiliary electrode, and a carbon paste electrode chemically modified with Cu (II) trans 3-MeO complex (as working electrode). Two forms of cocaine were analyzed: cocaine hydrochloride (pH 3) and cocaine free base form (pH 8). The PM7 computational method predicted that the hydrochloride form is more stable than the free base form of cocaine, so with cyclic voltammetry, we found electrochemical signal only for cocaine in the form of hydrochloride, with an anodic peak at 1.10 V, with a linearity range between 2 and 20 μmol L⁻¹ had LD and LQ of 2.39 and 7.26x10-5 mol L⁻¹, respectively. The study also proved that cocaine is adsorbed on the surface of the working electrode, where through an irreversible process, where only anode peaks are observed, we have the oxidation of cocaine, which occurs in the hydrophilic region due to the loss of two electrons. The mechanism of this reaction was confirmed by the ab-inito quantum method.

Keywords: ab-initio computational method, analytical method, cocaine, Schiff base complex, voltammetry

Procedia PDF Downloads 194

Authors: Linda Chularojmontri, Seewaboon Sireeratawong, Suvara Wattanapitayakul

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Terminalia arjuna Roxb. (family Combretaceae) is commonly known as ‘Sa maw thet’ in Thai. The fruit is used in traditional medicine as natural mild laxatives, carminative and expectorant. Aim of the study: This research aims to study the anti-inflammatory, analgesic and antipyretic activities of Terminalia arjuna extract by using animal models in comparison to the reference drugs. Materials and Methods: The anti-inflammatory study was conducted by two experimental animal models namely ethyl phenylpropionate (EPP)-induced ear edema and carrageenan-induced paw edema. The study of analgesic activity used two methods of pain induction including acetic acid and heat-induced pain. In addition, the antipyretic activity study was performed by induced hyperthermia with yeast. Results: The results showed that the oral administration of Terminalia arjuna extract possessed acute anti-inflammatory effect in carrageenan-induced paw edema. Terminalia arjuna extract showed the analgesic activity in acetic acid-induced writhing response and heat-induced pain. This indicates its peripheral effect by inhibiting the biosynthesis and/or release of some pain mediators and some mechanism through Central nervous system. Moreover, Terminalia arjuna extract at the dose of 1000 and 1500 mg/kg body weight showed the antipyretic activity, which might be because of the inhibition of prostaglandins. Conclusion: The findings of this study indicated that the Terminalia arjuna extract possesses the anti-inflammatory, analgesic and antipyretic activities in animals.

Keywords: analgesic activity, anti-inflammatory activity, antipyretic activity, Terminalia arjuna extract

Procedia PDF Downloads 263

Authors: Ashit Syngle, Nidhi Garg, Pawan Krishan

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Objective: Bone marrow derived stem cells, endothelial progenitor cells (EPCs), protect against atherosclerotic vascular damage. However, EPCs are depleted in AS and contribute to the enhanced cardiovascular risk. Statins have a protective effect in CAD and diabetes by enhancing the proliferation, migration and survival of EPCs. Therapeutic potential of augmenting EPCs to treat the heightened cardiovascular risk of AS has not yet been exploited. We aimed to investigate the effect of rosuvastatin on EPCs population and inflammation in AS. Methods: 30 AS patients were randomized to receive 6 months of treatment with rosuvastatin (10 mg/day, n=15) and placebo (n=15) as an adjunct to existing stable anti-rheumatic drugs. EPCs (CD34+/CD133+) were quantified by Flow Cytometry. Inflammatory measures (BASDAI, BASFI, CRP and ESR), pro-inflammatory cytokines (TNF-α, IL-6 and IL-1) and lipids were measured at baseline and after treatment. Results: At baseline, inflammatory measures and pro-inflammatory cytokines were elevated and EPCs depleted among both groups. EPCs increased significantly (p < 0.01) after treatment with rosuvastatin. At 6 months, BASDAI, BASFI, ESR, CRP, TNF-α, and IL-6 improved significantly in rosuvastatin group. Significant negative correlation was observed between EPCs and BASDAI, CRP and IL-6 after rosuvastatin treatment. Conclusion: First study to show that rosuvastatin augments EPCs population in AS. This defines a novel mechanism of rosuvastatin treatment in AS: the augmentation of EPCs with improvement in proinflammatory cytokines and inflammatory disease activity. The augmentation of EPCs by rosuvastatin may provide a novel strategy to prevent cardiovascular events in AS.

Keywords: ankylosing spondylitis, Endothelial Progenitor Cells, inflammation, pro-inflammatory cytokines, rosuvastatin

Procedia PDF Downloads 353

Authors: Natida Thongsima, Patompong Satapornpong

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Introduction: Lamotrigine is widely used in the treatment of epilepsy and bipolar disorder. However, lamotrigine leads to adverse drug reactions (ADRs) consist of severe cutaneous adverse reactions (SCARs) include Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug rash with eosinophilia and systemic symptoms (DRESS). Moreover, lamotrigine-induced SCARs are usually manifested between 2 and 8 weeks after treatment initiation. According to a previous study, the association between HLA-B*15:02 and lamotrigine-induced cutaneous adverse drug reactions in the Thai population (odds ratio 4.89; 95% CI 1.28–18.66; p-value = 0.014) was found. Therefore, the distribution of pharmacogenetics markers a major role in predicting the culprit drugs for SCARs in many populations. Objective: In this study, we want to investigate the prevalence of HLA-B allele, which correlates with lamotrigine-induced SCARs in the healthy Thai population. Materials and Methods: We enrolled 350 healthy Thai individuals and were approved by the ethics committee of Rangsit University. HLA-B alleles were genotyped by the Lifecodes HLA SSO typing kits (Immucor, West Avenue, Stamford, USA). Results: The results presented HLA-B allele frequency in healthy Thai population were 14.71% (HLA-B*46:01), 8.57% (HLA-B*15:02), 6.71% (HLA-B*40:01), 5.86% (HLA-B*13:01), 5.71% (HLA-B*58:01), 5.14% (HLA-B*38:02), 4.86% (HLA-B*18:01), 4.86% (HLA-B*51:01), 3.86% (HLA-B*44:03) and 2.71% (HLA-B*07:05). Especially, HLA-B*15:02 allele was the high frequency in the Thais (8.57%), Han Chinese (7.30%), Vietnamese (13.50%), Malaysian (6.06%) and Indonesian (11.60%). Nevertheless, this allele was much lower in other populations, namely, Africans, Caucasians, and Japanese. Conclusions: Although the sample size of the healthy Thai population in this research was limited, there were found the frequency of the HLA-B*15:02 allele could predispose them toward to lamotrigine-induced SCARs in Thailand.

Keywords: lamotrigine, cutaneous adverse drug reactions, HLA-B, Thai population

Procedia PDF Downloads 191

Authors: Milena Trevisan Pelegrino, Bruna De Araujo Lima, Mônica H. M. Do Nascimento, Christiane B. Lombello, Marcelo Brocchi, Amedea B. Seabra

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Nitric oxide (NO) is a small molecule involved in a wide range of physiological and pathophysiological processes, including vasodilatation, control of inflammatory pain, wound healing, and antibacterial activities. As NO is a free radical, the design of drugs that generates therapeutic amounts of NO in controlled spatial and time manners is still a challenge. In this study, the NO donor S-nitrosoglutathione (GSNO) was incorporated into the thermoresponsive Pluronic F-127 (PL) - chitosan (CS) hydrogel, in an easy and economically feasible methodology. CS is a polysaccharide with known antimicrobial and biocompatibility properties. Scanning electron microscopy, rheology and differential scanning calorimetry techniques were used for hydrogel characterization. The results demonstrated that the hydrogel has a smooth surface, thermoresponsive behavior, and good mechanical stability. The kinetics of NO release and GSNO diffusion from GSNO-containing PL/CS hydrogel demonstrated a sustained NO/GSNO release, in concentrations suitable for biomedical applications, at physiological and skin temperatures. The GSNO-PL/CS hydrogel demonstrated a concentration-dependent toxicity to Vero cells, and antimicrobial activity to Pseudomonas aeruginosa (minimum inhibitory concentration and minimum bactericidal concentration values of 0.5 µg·mL-1 of hydrogel, which correspondents to 1 mmol·L-1 of GSNO). Interesting, the concentration range in which the NO-releasing hydrogel demonstrated antibacterial effect was not found toxic to Vero mammalian cell. Thus, GSNO-PL/CS hydrogel is suitable biomaterial for topical NO delivery applications.

Keywords: antimicrobial, chitosan, biocompatibility, S-nitrosothiols

Procedia PDF Downloads 185