World Academy of Science, Engineering and Technology

Authors: Osman Turkoglu, Alvin Estilo, Ritu Gupta, Liliam Pineda-Salgado, Rajesh Pandey

Abstract:

Background: Hepatotoxicity can be linked to a variety of clinical symptoms and histopathological signs, posing a great challenge in the surveillance of suspected drug-induced liver injury (DILI) cases in the safety database. Additionally, the majority of such cases are rare, idiosyncratic, highly unpredictable, and tend to demonstrate unique individual susceptibility; these qualities, in turn, lend to a pharmacovigilance monitoring process that is often tedious and time-consuming. Objective: Develop a multifactorial algorithm to assist pharmacovigilance physicians in identifying high-risk hepatotoxicity cases associated with DILI from the sponsor’s safety database (Argus). Methods: Multifactorial selection criteria were established using Structured Query Language (SQL) and the TIBCO Spotfire® visualization tool, via a combination of word fragments, wildcard strings, and mathematical constructs, based on Hy’s law criteria and pattern of injury (R-value). These criteria excluded non-eligible cases from monthly line listings mined from the Argus safety database. The capabilities and limitations of these criteria were verified by comparing a manual review of all monthly cases with system-generated monthly listings over six months. Results: On an average, over a period of six months, the algorithm accurately identified 92% of DILI cases meeting established criteria. The automated process easily compared liver enzyme elevations with baseline values, reducing the screening time to under 15 minutes as opposed to multiple hours exhausted using a cognitively laborious, manual process. Limitations of the algorithm include its inability to identify cases associated with non-standard laboratory tests, naming conventions, and/or incomplete/incorrectly entered laboratory values. Conclusions: The newly developed multifactorial algorithm proved to be extremely useful in detecting potential DILI cases, while heightening the vigilance of the drug safety department. Additionally, the application of this algorithm may be useful in identifying a potential signal for DILI in drugs not yet known to cause liver injury (e.g., drugs in the initial phases of development). This algorithm also carries the potential for universal application, due to its product-agnostic data and keyword mining features. Plans for the tool include improving it into a fully automated application, thereby completely eliminating a manual screening process.

Keywords: automation, drug-induced liver injury, pharmacovigilance, post-marketing

Procedia PDF Downloads 125

Authors: Dalia O. Saleha, Gehad A. Abdel Jaleela, Sally W. Al-Awdana

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Diabetes mellitus (DM) is known to exacerbate cerebral ischemic injury. The present study aimed to investigate the anti-oxidant and anti-inflammatory effects of oral supplementation of melatonin (MLN) on cerebral injury caused by middle cerebral artery occlusion and reperfusion (MCAO/Re) in streptozotocin (STZ)-induced hyperglycemic rats. Hyperglycemia was induced by a single injection of STZ (55mg/kg; i.p.), six weeks later the cerebral injury was induced by MCAO/Re. Twenty-four hours after the MCAO/Re the MLN (10 mg/kg) was injected for 14 consecutive days. Results of the present study revealed that MCAO/Re in STZ-induced hyperglycemia in rats causes an increase in the oxidative stress biomarkers; it increased brain lipid peroxidation (measured as malondialdehyde; MDA) and brain level of nitric oxide (NO). Moreover, MCAO/Reproduces a prominent increase in the brain inflammatory markers viz. interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis nuclear factor-alpha (TNF-α). Oral treatment of MCAO/Re in STZ-induced hyperglycemic rats with MLN (10 mg/kg) for two weeks restored the brain levels of MDA, GSH, NO, IL-6, IL-1β and the TNF-α. MLN succeeded to suppress the exacerbation of damage in the brain of hyperglycemic rats. These results suggest that daily intake of MLN attenuates the exacerbation of cerebral ischemic injury in a diabetic state, which may be attributed to anti-oxidant and anti-inflammatory effects in the brain.

Keywords: melatonin, brain injury, cerebral ischemia/reperfusion, hyperglycemia, rats

Procedia PDF Downloads 130

Authors: L. Ebralidze, A. Tsertsvadze, D. Berashvili, A. Bakuridze

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Current cancer therapy strategies are based on surgery, radiotherapy and chemotherapy. The problems associated with chemotherapy are one of the biggest challenges for clinical medicine. These include: low specificity, broad spectrum of side effects, toxicity and development of cellular resistance. Therefore, anti-cance drugs need to be develop urgently. Particularly, in order to increase efficiency of anti-cancer drugs and reduce their side effects, scientists work on formulation of nano-drugs. The objective of this study was to develop composition and technology of vincristine nanoparticles using high-molecular carbohydrates of plant origin. Plant polysacharides, particularly, soy bean seed polysaccharides, flaxseed polysaccharides, citrus pectin, gum arabic, sodium alginate were used as objects. Based on biopharmaceutical research, vincristine containing nanoparticle formulations were prepared. High-energy emulsification and solvent evaporation methods were used for preparation of nanosystems. Polysorbat 80, polysorbat 60, sodium dodecyl sulfate, glycerol, polyvinyl alcohol were used in formulation as emulsifying agent and stabilizer of the system. The ratio of API and polysacharides, also the type of the stabilizing and emulsifying agents are very effective on the particle size of the final product. The influence of preparation technology, type and concentration of stabilizing agents on the properties of nanoparticles were evaluated. For the next stage of research, nanosystems were characterized. Physiochemical characterization of nanoparticles: their size, shape, distribution was performed using Atomic force microscope and Scanning electron microscope. The present study explored the possibility of production of NPs using plant polysaccharides. Optimal ratio of active pharmaceutical ingredient and plant polysacharids, the best stabilizer and emulsifying agent was determined. The average range of nanoparticles size and shape was visualized by SEM.

Keywords: nanoparticles, target delivery, natural high molecule carbohydrates, surfactants

Procedia PDF Downloads 243

Authors: Chand Pasha

Abstract:

A Simple, accurate and precise spectrophotometric method for the quantitative analysis of determination of 5-aminosalicylic acid is described. This method is based on the reaction of 5-aminosalicylic acid with nitrite in acid medium to form diazonium ion, which is coupled with acetylacetone in basic medium to form azo dyes, which shows absorption maxima at 470 nm. The method obeys Beer’s law in the concentration range of 0.5-11.2 gml-1 of 5-aminosalicylic acid with acetylacetone. The molar absorptivity and Sandell’s sensitivity of 5-aminosalicylic acid -acetylacetone azo dye is 2.672 ×104 lmol-1cm-1, 5.731 × 10-3 gcm-2 respectively. The dye formed is stable for 10 hrs. The optimum reaction conditions and other analytical parameters are evaluated. Interference due to foreign organic compounds have been investigated. The method has been successfully applied to the determination of 5-aminosalicylic acid in pharmaceutical samples.

Keywords: spectrophotometry, diazotization, mesalazine, nitrite, acetylacetone

Procedia PDF Downloads 156

Authors: Yadav Shyamjeet Maniram

Abstract:

Despite reports of more than seventy million population of India affected by rare diseases, it rarely figured on the agenda of the Indian scientist and policymakers. Hitherto ignored, a fresh initiative is being attempted to establish the first national registry for rare diseases. Though there are registries for rare diseases, established by the clinicians and patient advocacy groups, they are isolated, scattered and lacks information sharing mechanism. It is the first time that there is an effort from the government of India to make an initiative on the rare disease registries, which would be more formal and systemic in nature. Since there is lack of epidemiological evidence for the rare disease in India, it is interesting to note how rare disease policy is being attempted in the vacuum of evidence required for the policy process. The objective of this study is to analyse rare disease registry creation and implementation from the parameters of evolutionary policy perspective in the absence of evidence for the policy process. This study will be exploratory and qualitative in nature, primarily based on the interviews of stakeholders involved in the rare disease registry creation and implementation. Some secondary data will include various documents related to rare disease registry. The expected outcome of this study would be on the role of stakeholders in the generation of evidence for the rare disease registry creation and implementation. This study will also try to capture negotiations and deliberations on the ethical issues in terms of data collection, preservation, and protection.

Keywords: evolutionary policy perspective, evidence for policy, rare disease policy, rare disease in India

Procedia PDF Downloads 180

Authors: I. V. Palamarchuk, N. V. Zaichko

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Background and Aims: Galectin-3 is a marker of subclinical cardiac injury and is elevated in individuals with type 2 diabetes mellitus; while hydrogen sulfide (H₂S), metabolite of sulfur-containing amino acids, is considered having antifibrogenic effects. This study was designed to investigate whether metformin and its combination with NaHS can influence plasma galectin-3 and cystathionine-γ-lyase/hydrogen sulfide (CSE/H₂S) system in diabetic rat’s heart. Methods: 32 healthy male rats (180-250 g) were divided into 4 groups. To induct diabetes, rats (group 2-4) were injected with streptozotocin (STZ, 40 mg/kg/i.p., 0.1 M citrate buffer (pH 4.5). Rats from 3d (STZ+Metf) and 4th (STZ+Metf+NaHS) groups were given metformin (500 mg/kg/day) orally, and rats from 4th (STZ+Metf+NaHS) group were injected sodium hydrosulfide (NaHS, 3 mg/kg/i.p.) once per day starting from 3 to 28 day after streptozotocin injection. Rats of first group (control) were administered the equivalent volumes of 0.9% NaCl. Plasma galectin-3 was measured by ELISA. Rats’ hearts were sampled for determination of H2S by reaction with N,N-Dimethyl-p-phenylenediamine. Determination of CSE gene expression was performed in real time using PCR in the presence of SYBR Green I, using DT-Light detecting amplifier ('DNA-technology', Russia). Results: Induction of streptozotocin diabetes (STZ-diabetes, group 2) was followed by low myocardial H2S concentration and CSE expression (by 35%, p < 0.05 and 60.5%, p < 0.001 respectively, than that in controls), while plasma galectin-3 in this group was significantly higher than in controls (by 3.8 times, p < 0.05). Administration of metformin (group 3) resulted in significantly higher H₂S concentration (by 28.5%, p < 0.05), whereas CSE expression was only by 6% more than that in STZ-diabetes, as well as plasma galectin-3 was only by 14.8% lower in comparison with untreated diabetic rats. The inhibition of H₂S generation and CSE activity by diabetes was greatly attenuated in STZ+Metf+NaHS group. The combination of metformin with NaHS significantly stimulated H₂S production (by 48%, p < 0.05 and 15%, p < 0.05 more than STZ-diabetes and STZ+Metf respectively) and CSE gene expression (by 64.8%, p < 0.05 compared to STZ-diabetes and by 55.4%,p < 0.05 compared to STZ+Metf). Besides, plasma galectin-3 in rats receiving metformin and NaHS was significantly lower by 42%, p < 0.05 and 32.5%, p < 0.05 compared to STZ-diabetes and STZ+Metf groups respectively. Conclusions: To summarize, dysfunction of CSE/H2S system and galectin-3 stimulation was found in streptozotocin-induced diabetic rats. Metformin and its combination with exogenous H2S effectively prevented the development of metabolic changes induced by diabetes. These findings suggest that CSE/H₂S system can be integrated into pathogenesis of diabetic complications through modulation of pro-inflammatory and pro-fibrogenic mediator galectin-3.

Keywords: cystathionine-γ-lyase, diabetic heart, galectin-3, hydrogen sulfide, metformin, sodium hydrosulfide

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Authors: Indra Gonzalez Ojeda, Tatiana Quinones, Manuel Rosario, Igor Lednev, Juan Lopez Garriga

Abstract:

Amyloid fibrils are stable aggregates of misfolded protein associated with many neurodegenerative disorders. It has been shown that hydrogen sulfide (H2S), inhibits the fibrillation of lysozyme through the formation of trisulfide (S-S-S) bonds. However, the overall mechanism remains elusive. Here, the concentration dependence of H2S effect was investigated using Atomic force microscopy (AFM), non-resonance Raman spectroscopy, Deep-UV Raman spectroscopy and circular dichroism (CD). It was found that small spherical aggregates with trisulfide bonds and a unique secondary structure were formed instead of amyloid fibrils when adding concentrations of 25 mM and 50 mM of H2S. This could indicate that H2S might serve as a protecting agent for the protein. However, further characterization of these aggregates and their trisulfide bonds is needed to fully unravel the function H2S has on protein fibrillation.

Keywords: amyloid fibrils, hydrogen sulfide, protein folding, raman spectroscopy

Procedia PDF Downloads 190

Authors: Madhavi S. Apte, Milind Bhitre

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In pharmaceutical research and new drug development, medicinal plants have important roles. Similarly, Indian dhak tree belonging to family Fabaceae has been widely used in the traditional Indian medical system of ‘Ayurveda’ for the treatment of a variety of ailments. Hence the cell viability study was undertaken to evaluate and compare the activity of extracts of various parts like flower, bark, leaf, seed by conducting MTT assay method along with other pharmacognostical studies. The methanolic extracts of bark, flowers, leaves, and seeds were used for the study. The cell viability MTT assay was performed using the standard operating procedures. The extracts were dissolved in DMSO and serially diluted with complete medium to get the concentrations range of test concentration. DMSO concentration was kept < 0.1% in all the samples. HUVEC cells maintained in appropriate conditions were seeded in 96 well plates and treated with different concentrations of the test samples and incubated at 37°C, 5% CO₂ for 96 hours. MTT reagent was added to the wells and incubated for 4 hours; the dark blue formazan product formed by the cells was dissolved in DMSO under a safety cabinet and read at 550nm. Percentage inhibitions were calculated and plotted with the concentrations used to calculate the IC50 values. The bark, flower, leaves and seed extracts have shown the cytotoxicity activity and can be further studied for antiangiogenesis activity.

Keywords: pharmacognosy, Cell viability, MTT assay, anti-angiogenesis

Procedia PDF Downloads 264

Authors: Parimalakrishnan Sundararjan, Madheswaran Murugan, Dhanya Dharman, Yatindra Kumar, Sudhir Singh Gangwar, Guru Prasad Mohanta

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Antibiotic resistance AR is a global issue, India started to redress the issues of antibiotic resistance late and it plans to have: active surveillance of microbial resistance and promote appropriate use of antibiotics. The present study attempted to achieve appropriate use of antibiotics through pharmacists’ intervention at practice point. In a quasi-experimental prospective cohort study, the cases with bacteremia from four hospitals were identified during 2015 and 2016 for intervention. The pharmacists centered intervention: active screening of each prescription and comparing with the selection of antibiotics with susceptibility of the bacteria. Wherever irrationality noticed, it was brought to the notice of the treating physician for making changes. There were two groups: intervention group and control group without intervention. The active screening and intervention in 915 patients has reduced therapeutic regimen time in patients with bacteremia. The intervention group showed the decreased duration of hospital stay 3.4 days from 5.1 days. Further, multivariate modeling of patients who were in control group showed that patients in the intervention group had a significant decrease in both duration of hospital stay and infection-related mortality. Unlike developed countries, pharmacists are not active partners in patient care in India. This unique attempt of pharmacist’ invention was planned in consultation with hospital authorities which proved beneficial in terms of reducing the duration of treatment, hospital stay, and infection-related mortality. This establishes the need for a collaborative decision making among the health workforce in patient care at least for promoting rational use of antibiotics, an attempt to combat resistance.

Keywords: antibiotics resistance, intervention, bacteremia, multivariate modeling

Procedia PDF Downloads 158

Authors: Neelam Rashid, Muhammad Zafar, Mushtaq Ahmad, Khafsa Malik, Syed Nasar Shah

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The present study was conducted to study the role of medicinal plants used to cure different ailments in Azad Kashmir. Various ethno medicinal surveys were carried out during 2016 to enlist the uses of plants against various ailments by rural communities of the area. Information was obtained from 60 local people including 45 males (10 traditional health practitioners) and 15 females by semi structured interviews and group discussions. 65 plant species belonging to 45 families were reported. The dominant plant habit was herbaceous (56%) while decoction was the most common method of utilization (40%). The most cited turmoil was the gastrointestinal disorders. The data obtained were analyzed using ethno medicinal indices such as FL, UV, ICF, FC, and RFC. Results revealed that various species had numerous uses in curing of diseases. So conservation of biodiversity of these medicinal plants and traditional knowledge can play important role in improving the local health conditions of rural people and modern drug discovery and development.

Keywords: medicinal plants, ailments, drug, health, traditional

Procedia PDF Downloads 218

Authors: Yasin I. Tayem, Jamil Ahmed, Mahmood Bahzad, Abdullah Alnama, Fahad Al Asfoor, Mahmood A. Jalil, Mohammed Radhi, Ahmed Alenezi, Khalid A. J. Al-Khaja

Abstract:

Drug-drug interactions (DDIs) represent a significant cause of patient’s morbidity and mortality. The rate of DDIs is rapidly increasing worldwide with the increasing proportion of ageing population and frequent requirement of polypharmacy-prescription of multiple drugs to treat comorbidities. Prescribing physicians are responsible for checking their prescriptions for the presence and severity of DDIs. However, since a large number of new drugs are approved and marketed every year, new interactions between medications are increasingly reported. Consequently, it is no longer practical for physicians to rely only upon their previous knowledge of medicine to avoid potential DDIs. The aim of this study was to explore the perceptions of physicians working at primary healthcare centers in Bahrain towards DDIs and how they manage them during their practice. Methodology: In this cross-sectional study, physicians working at all governmental primary healthcare centers in Bahrain were invited to voluntarily, privately and anonymously respond to a self-administered questionnaire. The questionnaire aims to assess their self-reported knowledge of DDIs and how they check for them in their practice. The participants were requested to provide socio demographic data and information related to their attitudes towards DDIs including strategies they employ for detecting and managing them, and their awareness of drugs which commonly cause DDIs. At the end of the questionnaire, an open-ended item was added to allow participants to further add any comment. Findings and Conclusions: The study is going on currently, and the results and conclusions will be presented at the conference.

Keywords: awareness, drug interactions, health centres, physicians

Procedia PDF Downloads 217

Authors: Amarjyoti Das Mahapatra, Umesh Kumar, Bhaskar Datta

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A pseudo peptide can mimic the biological or structural properties of natural peptides. They have become an increasing attention in medicinal chemistry because of their interesting advantages like more bioavailability and less biodegradation than compare to the physiologically active native peptides which increase their therapeutic applications. Many biologically active compounds contain urea as functional groups, and they have improved pharmacokinetic properties because of their bioavailability and metabolic stability. Recently we have reported a single-step synthesis of sulfonyl urea and sulfonyltriuret from sulfonyl chloride and sodium cyanate. But the yield of sulfonyltriuret was less around 40-60% because of the formation of other products like sulfonamide and sulfonylureas. In the present work, we mainly focused on the selective synthesis of sulfonyltriuret using tetrabutylammonium cyanate and sulfonyl chloride. More precisely, we are interested in the controlled synthesis of oligomeric urea mainly sulfonyltriuret as a new class of pseudo peptide and their application as protease modulators. The distinctive architecture of these molecules in the form of their pseudo-peptide backbone offers promise as a potential pharmacophore. The synthesized molecules have been screened on trypsin enzyme, and we observed that these molecules are the efficient modulator of trypsin enzyme.

Keywords: pseudo peptide, pharmacophore, sulfonyltriuret, trypsin

Procedia PDF Downloads 143

Authors: Dwarakanadha Reddy Peram, D. Swarnalatha, C. Gopinath

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The main aim of this research work was to design and development characterization of Pioglitazone transdermal drug delivery system by using various polymers such as Olibanum with different concentration by solvent evaporation technique. The prepared formulations were evaluated for different physicochemical characteristics like thickness, folding endurance, drug content, percentage moisture absorption, percentage moisture loss, percentage elongation break test and weight uniformity. The diffusion studies were performed by using modified Franz diffusion cells. The result of dissolution studies shows that formulation, F3 (Olibanum with 50 mg) showed maximum release of 99.95 % in 12hrs, whereas F1 (Olibanum and EC backing membrane) showed minimum release of 93.65% in 12 hr. Based on the drug release and physicochemical values obtained the formulation F3 is considered as an optimized formulation which shows higher percentage of drug release of 99.95 % in 12 hr. The developed transdermal patches increase the therapeutic efficacy and reduced toxic effect of pioglitazone.

Keywords: pioglitazone, olibanum, transdermal drug delivery system, drug release percantage

Procedia PDF Downloads 184

Authors: Natalia C. E. S. Nascimento, Mercia L. Oliveira, Fernando R. A. Lima, Leonardo T. C. do Nascimento, Marina B. Silveira, Brigida G. A. Schirmer, Andrea V. Ferreira, Carlos Malamut, Juliana B. da Silva

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Tissue hypoxia is a common characteristic of solid tumors leading to decreased sensitivity to radiotherapy and chemotherapy. In the clinical context, tumor hypoxia assessment employing the positron emission tomography (PET) tracer ¹⁸F-fluoromisonidazole ([¹⁸F]FMISO) is helpful for physicians for planning and therapy adjusting. The aim of this work was to implement the synthesis of 18F-FMISO in a TRACERlab® MXFDG module and also to establish the quality control procedure. [¹⁸F]FMISO was synthesized at Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN/Brazil) using an automated synthesizer (TRACERlab® MXFDG, GE) adapted for the production of [¹⁸F]FMISO. The FMISO chemical standard was purchased from ABX. 18O- enriched water was acquired from Center of Molecular Research. Reagent kits containing eluent solution, acetonitrile, ethanol, 2.0 M HCl solution, buffer solution, water for injections and [¹⁸F]FMISO precursor (dissolved in 2 ml acetonitrile) were purchased from ABX. The [¹⁸F]FMISO samples were purified by Solid Phase Extraction method. The quality requirements of [¹⁸F]FMISO are established in the European Pharmacopeia. According to that reference, quality control of [¹⁸F]FMISO should include appearance, pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins, and sterility. The duration of the synthesis process was 53 min, with radiochemical yield of (37.00 ± 0.01) % and the specific activity was more than 70 GBq/µmol. The syntheses were reproducible and showed satisfactory results. In relation to the quality control analysis, the samples were clear and colorless at pH 6.0. The spectrum emission, measured by using a High-Purity Germanium Detector (HPGe), presented a single peak at 511 keV and the half-life, determined by the decay method in an activimeter, was (111.0 ± 0.5) min, indicating no presence of radioactive contaminants, besides the desirable radionuclide (¹⁸F). The samples showed concentration of tetrabutylammonium (TBA) < 50μg/mL, assessed by visual comparison to TBA standard applied in the same thin layer chromatographic plate. Radiochemical purity was determined by high performance liquid chromatography (HPLC) and the results were 100%. Regarding the residual solvents tested, ethanol and acetonitrile presented concentration lower than 10% and 0.04%, respectively. Healthy female mice were injected via lateral tail vein with [¹⁸F]FMISO, microPET imaging studies (15 min) were performed after 2 h post injection (p.i), and the biodistribution was analyzed in five-time points (30, 60, 90, 120 and 180 min) after injection. Subsequently, organs/tissues were assayed for radioactivity with a gamma counter. All parameters of quality control test were in agreement to quality criteria confirming that [¹⁸F]FMISO was suitable for use in non-clinical and clinical trials, following the legal requirements for the production of new radiopharmaceuticals in Brazil.

Keywords: automatic radiosynthesis, hypoxic tumors, pharmacopeia, positron emitters, quality requirements

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Authors: Renata L. C. Leão, João E. Nascimento, Natalia C. E. S. Nascimento, Elaine S. Vasconcelos, Mércia L. Oliveira

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The quality control procedures of a radiopharmaceutical include the assessment of its chemical purity. The method suggested by international pharmacopeias consists of a thin layer chromatographic run. In this paper, the method proposed by the United States Pharmacopeia (USP) is compared to a direct method to determine the final concentration of aminopolyether in Fludeoxyglucose (¹⁸F-FDG) preparations. The approach (no chromatographic run) was achieved by placing the thin-layer chromatography (TLC) plate directly on an iodine vapor chamber. Both methods were validated and they showed adequate results to determine the concentration of aminopolyether in ¹⁸F-FDG preparations. However, the direct method is more sensitive, faster and simpler when compared to the reference method (with chromatographic run), and it may be chosen for use in routine quality control of ¹⁸F-FDG.

Keywords: chemical purity, Kryptofix 222, thin layer chromatography, validation

Procedia PDF Downloads 178

Authors: M. G. Gopisankar, A. Surendiran, M. Hemachandren

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The dose requirement of warfarin to achieve target INR range varies in patients with prosthetic heart valve. This variation in is affected by both genetic and non-genetic factors. Earlier studies have identified role of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirement. Warfarin being a substrate for drug transporter, P-glycoprotein coded by ABCB1 gene, may also be influenced by its genetic polymorphisms. This study was aimed to study the effect of single nucleotide polymorphism (SNP), ABCB1 2677G > T on warfarin maintenance dose requirement in patients with steady-state International Normalized Ratio (INR). The median dose requirement was significantly different between the genotype groups GG vs. GT (35 ± 20; 42.5 ± 18, p < 0.05), GG vs. TT (35 ± 20; 41.25 ± 25, p<0.05). There was no significant difference between GT vs. TT. In conclusion, patients with variant allele require a higher weekly maintenance dose of warfarin compared to patients without variant allele.

Keywords: warfarin pharamcogenetics, pharmacogenomics of warfarin, ABCB1 and warfarin, pglycoprotein and warfarin

Procedia PDF Downloads 232

Authors: Son Nguyen, Thanh Van, Ly Le

Abstract:

Ca2+ - dependent calmodulin kinase IIa (CaMKIIa) has recently been found to associate with protein tau missorting and polymerization in Alzheimer’s Disease (AD). However, there has yet inhibitors targeting CaMKIIa to investigate the correlation between CaMKIIa activity and protein tau polymer formation. Combining virtual screening and our statistics in binding contribution scoring function (BCSF), we rationally identified potential compounds that bind to specific CaMKIIa active site and specificity-affinity distribution of the ligand within the active site. Using molecular dynamics simulation, we identified structural stability of CaMKIIa and potent inhibitors, and site-directed bonding, separating non-specific and specific molecular interaction features. Despite of variation in confirmation of simulation time, interactions of the potent inhibitors were found to be strongly associated with the unique chemical features extracted from molecular binding poses. In addition, competitive inhibitors within CaMKIIa showed an important molecular recognition pattern toward specific ligand features. Our approach combining virtual screening with BCSF may provide an universally applicable method for precise identification in the discovery of compounds.

Keywords: Alzheimer’s disease, Ca 2+ -dependent calmodulin kinase IIa, protein tau, molecular docking

Procedia PDF Downloads 251

Authors: Dong Tran, Thanh Dac Van, Ly Le

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Hemagglutinin (HA) and Neuraminidase (NA) play an important role in host immune evasion across influenza virus evolution process. The correlation between HA and NA evolution in respect to epitopic evolution and drug interaction has yet to be investigated. In this study, combining of sequence to structure evolution and statistical analysis on epitopic/binding site specificity, we identified potential therapeutic features of HA and NA that show specific antibody binding site of HA and specific binding distribution within NA active site of current inhibitors. Our approach introduces the use of sequence variation and molecular interaction to provide an effective strategy in establishing experimental based distributed representations of protein-protein/ligand complexes. The most important advantage of our method is that it does not require complete dataset of complexes but rather directly inferring feature interaction from sequence variation and molecular interaction. Using correlated sequence analysis, we additionally identified co-evolved mutations associated with maintaining HA/NA structural and functional variability toward immunity and therapeutic treatment. Our investigation on the HA binding specificity revealed unique conserved stalk domain interacts with unique loop domain of universal antibodies (CR9114, CT149, CR8043, CR8020, F16v3, CR6261, F10). On the other hand, NA inhibitors (Oseltamivir, Zaninamivir, Laninamivir) showed specific conserved residue contribution and similar to that of NA substrate (sialic acid) which can be exploited for drug design. Our study provides an important insight into rational design and identification of novel therapeutics targeting universally recognized feature of influenza HA/NA.

Keywords: influenza virus, hemagglutinin (HA), neuraminidase (NA), sequence evolution

Procedia PDF Downloads 135

Authors: Mindaugas Liaudanskas, Darius Kviklys, Kristina Zymonė, Raimondas Raudonis, Jonas Viškelis, Norbertas Uselis, Pranas Viškelis, Valdimaras Janulis

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Apples are among the most commonly consumed fruits in the world. Based on data from the year 2014, approximately 84.63 million tons of apples are grown per annum. Apples are widely used in food industry to produce various products and drinks (juice, wine, and cider); they are also used unprocessed. Apples in human diet are an important source of different groups of biological active compounds that can positively contribute to the prevention of various diseases. They are a source of various biologically active substances – especially vitamins, organic acids, micro- and macro-elements, pectins, and phenolic, triterpenic, and other compounds. Triterpenic compounds, which are characterized by versatile biological activity, are the biologically active compounds found in apples that are among the most promising and most significant for human health. A specific analytical procedure including sample preparation and High Performance Liquid Chromatography (HPLC) analysis was developed, optimized, and validated for the detection of triterpenic compounds in the samples of different apples, their peels, and flesh from widespread apple cultivars 'Aldas', 'Auksis', 'Connel Red', 'Ligol', 'Lodel', and 'Rajka' grown in Lithuanian climatic conditions. The conditions for triterpenic compound extraction were optimized: the solvent of the extraction was 100% (v/v) acetone, and the extraction was performed in an ultrasound bath for 10 min. Isocratic elution (the eluents ratio being 88% (solvent A) and 12% (solvent B)) for a rapid separation of triterpenic compounds was performed. The validation of the methodology was performed on the basis of the ICH recommendations. The following characteristics of validation were evaluated: the selectivity of the method (specificity), precision, the detection and quantitation limits of the analytes, and linearity. The obtained parameters values confirm suitability of methodology to perform analysis of triterpenic compounds. Using the optimised and validated HPLC technique, four triterpenic compounds were separated and identified, and their specificity was confirmed. These compounds were corosolic acid, betulinic acid, oleanolic acid, and ursolic acid. Ursolic acid was the dominant compound in all the tested apple samples. The detected amount of betulinic acid was the lowest of all the identified triterpenic compounds. The greatest amounts of triterpenic compounds were detected in whole apple and apple peel samples of the 'Lodel' cultivar, and thus apples and apple extracts of this cultivar are potentially valuable for use in medical practice, for the prevention of various diseases, for adjunct therapy, for the isolation of individual compounds with a specific biological effect, and for the development and production of dietary supplements and functional food enriched in biologically active compounds. Acknowledgements. This work was supported by a grant from the Research Council of Lithuania, project No. MIP-17-8.

Keywords: apples, HPLC, triterpenic compounds, validation

Procedia PDF Downloads 152

Authors: Alireza Shams, Ali Zamanian, Atefehe Shamosi, Farnaz Ghorbani

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Introduction: Although the application of a new strategy remains a remarkable challenge for treatment of disabilities due to neuronal defects, progress in Nanomedicine and tissue engineering, suggesting the new medical methods. One of the promising strategies for reconstruction and regeneration of nervous tissue is replacing of lost or damaged cells by specific scaffolds after Compressive, ischemic and traumatic injuries of central nervous system. Furthermore, ultrastructure, composition, and arrangement of tissue scaffolds are effective on cell grafts. We followed implantation and differentiation of mesenchyme stem cells to neural cells on Gelatin Polylactic-co-glycolic acid (PLGA) scaffolds coated with iron nanoparticles. The aim of this study was to evaluate the capability of stem cells to differentiate into motor neuron-like cells under topographical cues and morphogenic factors. Methods and Materials: Bone marrow mesenchymal stem cells (BMMSCs) was obtained by primary cell culturing of adult rat bone marrow got from femur bone by flushing method. BMMSCs were incubated with DMEM/F12 (Gibco), 15% FBS and 100 U/ml pen/strep as media. Then, BMMSCs seeded on Gel/PLGA scaffolds and tissue culture (TCP) polystyrene embedded and incorporated by Fe Nano particles (FeNPs) (Fe3o4 oxide (M w= 270.30 gr/mol.). For neuronal differentiation, 2×10 5 BMMSCs were seeded on Gel/PLGA/FeNPs scaffolds was cultured for 7 days and 0.5 µ mol. Retinoic acid, 100 µ mol. Ascorbic acid,10 ng/ml. Basic fibroblast growth factor (Sigma, USA), 250 μM Iso butyl methyl xanthine, 100 μM 2-mercaptoethanol, and 0.2 % B27 (Invitrogen, USA) added to media. Proliferation of BMMSCs was assessed by using MTT assay for cell survival. The morphology of BMMSCs and scaffolds was investigated by scanning electron microscopy analysis. Expression of neuron-specific markers was studied by immunohistochemistry method. Data were analyzed by analysis of variance, and statistical significance was determined by Turkey’s test. Results: Our results revealed that differentiation and survival of BMMSCs into motor neuron-like cells on Gel/PLGA/FeNPs as a biocompatible and biodegradable scaffolds were better than those cultured in Gel/PLGA in absence of FeNPs and TCP scaffolds. FeNPs had raised physical power but decreased capacity absorption of scaffolds. Well defined oriented pores in scaffolds due to FeNPs may activate differentiation and synchronized cells as a mechanoreceptor. Induction effects of magnetic FeNPs by One way flow of channels in scaffolds help to lead the cells and can facilitate direction of their growth processes. Discussion: Progression of biological properties of BMMSCs and the effects of FeNPs spreading under magnetic field was evaluated in this investigation. In vitro study showed that the Gel/PLGA/FeNPs scaffold provided a suitable structure for motor neuron-like cells differentiation. This could be a promising candidate for enhancing repair and regeneration in neural defects. Dynamic and static magnetic field for inducing and construction of cells can provide better results for further experimental studies.

Keywords: differentiation, mesenchymal stem cells, nano particles, neuronal defects, Scaffolds

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Authors: M. E. Abalaka, O. A. Falusi, M. Galadima, D. Damisa

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The antimicrobial activity of aqueous, ethanolic and methanolic extracts of Chromolaena odorata (Siam weed) was evaluated against four wound isolates: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae at the concentrations of 200mg/ml, 100mg/ml, 50mg/ml and 25mg/ml respectively. S. aureus and E. coli showed high susceptibility to the various extracts than the other test isolates. The aqueous extract showed activity against Staphylococcus aureus with a mean diameter of zone of inhibition of 16 ± 3.00 at concentration of 200mg/ml and as low as 8 ± 0.00 at concentration of 25mg/ml; E. coli showed susceptibility with a mean diameter of zone of inhibition of 18 ± 2.00 and 10 ± 0.00 at a concentration of 200mg/ml and 25mg/ml respectively. Pseudomonas aeruginosa and Klebsiella pneumoniae were resistant to the aqueous extract. Methanol extract showed activity against Staphylococcus aureus with a mean diameter of zone of inhibition at 28 ± 4.00 and 12 ± 2.30 at a concentration of 200mg/ml and 25mg/ml respectively; while E. coli was susceptible with mean diameter of zone of inhibition of 18 ± 2.00 and as low as 12 ± 0.00 at a concentration of 200mg/ml and 50mg/ml respectively, Pseudomonas aeruginosa showed considerable susceptibility with mean diameter of zone of inhibition of 13 ± 1.00 and 12 ± 0.00 at a concentration of 200mg/ml and 100mg/ml respectively. The ethanol extract showed activity against S. aureus with a mean diameter zone of inhibition of 15 ± 2.00 and 9 ± 0.00 at a concentration of 200mg/ml and 25mg/ml respectively: E. coli showed susceptibility with a mean diameter zone of inhibition of 20 ± 4.00 and 13 ± 2.00 at a concentration of 200mg/ml and 25mg/ml respectively. Pseudomonas aeruginosa showed considerable susceptibility with a mean diameter zone of inhibition of 13 ± 1.00 and 9 ± 0.00 at a concentration of 200mg/ml and 100mg/ml respectively. The results above indicate the efficacy and potency of the crude extracts of Chromolaena odorata leaf on the tested wound isolates.

Keywords: antibacterial, Chromolaena odorata, leaf extracts, test isolates

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Authors: Moleseng Claude Moshobane

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Alien species cause considerable negative impacts on biodiversity, economy and public health. Impacts of alien species on public health have received a degree of attention worldwide, largely in developed countries, but scarce in developing countries. Here, we provide a review of human exposures and poisonings cases from native and alien plant species reported to poison information centers. A retrospective review of the Tygerberg Poison Information Centre (TPIC) and Poisons Information Centre (PIC) at Red Cross War Memorial Children's Hospital (RCWMCH) was conducted over approximately 2-year period (1 June 2015 through to 06 March 2017). Combined, TPIC and PIC handled 626 cases during the 2-year period. Toxicity cases were more abundant in Gauteng (47.1%), followed by Western Cape (29.4%). The primary mechanism of injury was ingestion (96.7%), and all cases were predominantly accidental. Most reported cases involved infants (20.6%), with few fully-grown adults related cases (5.8%). Adults presented minor to moderate toxicity, while infants none to minor toxicity. We conclude that reported toxicity cases on human health are biased towards few alien species and that several cases relate to unknown species of mushrooms. Public awareness is essential to reducing the poisoning incidences.

Keywords: alien species, poisoning, invasive species, public health

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Authors: Vipin Saini, Manish Kumar, Shailendra Bhatt, A. Pandurangan

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The aim of the present study was to fabricate a thermo sensitive gel containing Chlorpheniramine maleate (CPM) loaded nanoparticles following intranasal administration for effective treatment of allergic rhinitis. Chitosan based nanoparticles were prepared by precipitation method followed by the addition of developed NPs within the Poloxamer 407 and carbopol 934P based mucoadhesive thermo-reversible gel. Developed formulations were evaluated for Particle size, PDI, % entrapment efficiency and % cumulative drug permeation. NP3 formulation was found to be optimized on the basis of minimum particle size (143.9 nm), maximum entrapment efficiency (80.10±0.414 %) and highest drug permeation (90.92±0.531 %). The optimized formulation NP3 was then formulated into thermo reversible in situ gel. This intensifies the contact between nasal mucosa and the drug, increases and facilitates the drug absorption which results in increased bioavailability. G4 formulation was selected as the optimize on the basis of gelation ability and mucoadhesive strength. Histology was carried out to examine the damage caused by the optimized G4 formulation. Results revealed no visual signs of tissue damage thus indicated safe nasal delivery of nanoparticulate in situ gel formulation G4. Thus, intranasal CPM NP-loaded in situ gel was found to be a promising formulation for the treatment of allergic rhinitis.

Keywords: chitosan, nanoparticles, in situ gel, chlorpheniramine maleate, poloxamer 407

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Authors: Amberkar Mohanbabu Vittalrao, Avin, Meena Kumari Kamalkishore, Padmanabha Udupa, Vinaykumar Bavimane, Honnegouda

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Objective: To evaluate the hepato-protective activity of Tinospora cordiofolia (Tc) against paracetamol induced hepatic damage in rats. Methods: The plant stem (test drug) was procured locally, shade dried, powdered and extracted with water. Silymarin was used as standard hepatoprotective drugs and 2% gum acacia as a control (vehicle) against paracetamol (PCT) induced hepatotoxicity. Results and Discussion: The hepato-protective activity of aqueous stem extract was assessed by paracetamol induced hepatotoxicity preventive model in rats. Alteration in the levels of biochemical markers of hepatic damage like AST, ALT, ALP and lipid peroxides were tested in both paracetamol treated and untreated groups. Paracetamol (3g/kg) had enhanced the AST, ALT, ALP and the lipid peroxides in the serum. Treatment of silymarin and aqueous stem extract of Tc (200 and 400mg/kg) extract showed significant hepatoprotective activity by altering biochemical marker levels to the near normal. Preliminary phytochemical tests were done. Aqueous Tc extract showed presence of phenolic compound and flavonoids. Our findings suggested that Tc extract possessed hepatoprotective activity in a dose dependent manner. Conclusions: Tc was found to possess significant hepatoprotective property when treated with PCT. This was evident by decreasing the liver enzymes significantly when treated with PCT as compared to PCT only treated group (P < 0.05). Hence Tinospora cardiofolia could be a good, promising, preventive agent against PCT induced hepatotoxicity.

Keywords: Tinospora cardiofolia, hepatoprotection, paracetamol, silymarin

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Authors: Hulya Tuba Kiyan, Nilgun Ozturk

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Gentiana, a member of Gentianaceae, is represented by approximately 400 species in the world and 12 species in Turkey. Flavonoids, iridoids, triterpenoids and also xanthones are the major compounds of this genus, have been previously reported to have antiinflammatory, antimicrobial, antioxidant, hepatoprotective, hypotensive, hypoglycaemic, DNA repair and immunomodulatory properties. The methanolic extract of the aerial parts of Gentiana brachyphylla Vill. from Turkey was evaluated for its biological activities and its total phenolic content in the present study. According to the antioxidant activity results, G. brachyphylla methanolic extract showed very strong anti-DNA damage antioxidant activity with an inhibition of 81.82%. It showed weak ferric-reducing power with a EC50 value of 0.65 when compared to BHT (EC50 = 0.2). Also, at 0.5 mg/ml concentration, the methanolic extract inhibited ABTS radical cation activity with an inhibition of 20.13% when compared to Trolox (79.01%). Chelating ability of G. brachyphylla was 44.71% whereas EDTA showed 78.87% chelating activity at 0.2 mg/ml. Also G. brachyphylla showed weak 27.21% AChE, 20.23% BChE, strong 67.86% MAO-A and moderate 50.06% MAO-B, weak 19.14% COX-1, 29.11% COX-2 inhibitory activities at 0.25 mg/ml. The total phenolic content of G. brachyphylla was 156.23 ± 2.73 mg gallic acid equivalent/100 g extract.

Keywords: antioxidant activity, cholinesterase inhibitory activity, Gentiana brachyphylla Vill., total phenolic content

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Authors: Nilgün Öztürk, Hakan Sabahtin Ali, Hülya Tuba Kıyan

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The genus Chenopodium belongs to Amaranthaceae, is represented by approximately 250 species in the world and 15 species and three subspecies in Turkey. Chenopodium species are traditionally used to treat chest and abdominal pain, shortness of breath, cough and neurological disorders. Chenopodium quinoa Willd. (Quinoa) is native to Andes region of South America (especially Peru and Bolivia) and cultivated in many countries include also Turkey in the world nowadays. The seeds of quinoa are rich in protein, and the phytochemical composition consists of antioxidant substances such as polyphenolic compounds, flavonoids, vitamins, and minerals; anticancer and neuroprotective compounds such as tocotrienols; anti-inflammatory compounds such as carotenoids and anthocyanins and also saponins and starch. Food products of quinoa such as quinoa cereal bar, pasta and cornflakes are used in the diet made during many disorders like obesity, cardiovascular disorder, hypertension and Celiac disease. Also quinoa seems to have antimicrobial, anti-inflammatory and cholesterol-lowering properties because of its bioactive compounds. In this present study, the aqueous ethanolic extracts of the seeds of three different coloured genotypes of quinoa were investigated for their antioxidant activities using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, ferrous ion-chelating effect, ferric-reducing antioxidant power, ABTS radical cation decolorization assays and total phenolic contents using Folin-Ciocalteu assay. Among the three genotypes of quinoa; the aqueous ethanolic extract of the red genotype had the highest total phenolic content (83.54 ± 2.12 mg gallic acid/100 g extract) whereas the extract of the white genotype had the lowest total phenolic content (70.66 ± 0.25 mg gallic acid/100 g). According to the antioxidant activity results; the extracts showed moderate reducing power effect whereas weak ABTS radical cation decolorization and ferrous ion-chelating effect and also too weak DPPH radical scavenging activity when compared to the positive standards.

Keywords: amaranthaceae, antioxidant activity, Chenopodium quinoa willd., total phenolic content

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Authors: Dolly Gadhiya, Jayvadan Patel, Mihir Raval

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Lercanidipine hydrochloride is a calcium channel blockers used for treating angina pectoris and hypertension. Lercanidipine is a BCS Class II drug having poor aqueous solubility. Absolute bioavailability of Lercanidipine is very low and the main reason ascribed for this is poor aqueous solubility of the drug. Design and formulatation of nanocrystals by media milling method was main focus of this study. In this present study preliminary optimization was carried out with one factor at a time (OFAT) approach. For this different parameters like size of milling beads, amount of zirconium beads, types of stabilizer, concentrations of stabilizer, concentrations of drug, stirring speeds and milling time were optimized on the basis of particle size, polydispersity index and zeta potential. From the OFAT model different levels for above parameters selected for Plackett - Burman Design (PBD). Plackett-Burman design having 13 runs involving 6 independent variables was carried out at higher and lower level. Based on statistical analysis of PBD it was found that concentration of stabilizer, concentration of drug and stirring speed have significant impact on particle size, PDI, zeta potential value and saturation solubility. These experimental designs for preparation of nanocrystals were applied successfully which shows increase in aqueous solubility and dissolution rate of Lercanidipine hydrochloride.

Keywords: Lercanidipine hydrochloride, nanocrystals, OFAT, Plackett Burman

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Authors: Arti Bagada, Kantilal Vadalia, Mihir Raval

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Cilnidipine is practically insoluble in water which results in its insufficient oral bioavailability. The purpose of the present investigation was to formulate cilnidipine nanoparticles by nanoprecipitation method to increase the aqueous solubility and dissolution rate and hence bioavailability by utilizing various experimental statistical design modules. Experimental design were used to investigate specific effects of independent variables during preparation cilnidipine nanoparticles and corresponding responses in optimizing the formulation. Plackett Burman design for independent variables was successfully employed for optimization of nanoparticles of cilnidipine. The influence of independent variables studied were drug concentration, solvent to antisolvent ratio, polymer concentration, stabilizer concentration and stirring speed. The dependent variables namely average particle size, polydispersity index, zeta potential value and saturation solubility of the formulated nanoparticles of cilnidipine. The experiments were carried out according to 13 runs involving 5 independent variables (higher and lower levels) employing Plackett-Burman design. The cilnidipine nanoparticles were characterized by average particle size, polydispersity index value, zeta potential value and saturation solubility and it results were 149 nm, 0.314, 43.24 and 0.0379 mg/ml, respectively. The experimental results were good correlated with predicted data analysed by Plackett-Burman statistical method.

Keywords: dissolution enhancement, nanoparticles, Plackett-Burman design, nanoprecipitation

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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

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Authors: Kingston Rajiah, Mari Kannan Maharajan, Si Jen Yeen, Sara Lew

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder with evolving layers of complexity. Both motor and non-motor symptoms of PD may affect patients’ quality of life (QoL). Life expectancy for an individual with Parkinson’s disease depends on the level of care the individual has access to, can have a direct impact on length of life. Therefore, improvement of the QoL is a significant part of therapeutic plans. Patients with PD, especially those who are in advanced stages, are in great need of assistance, mostly from their family members or caregivers in terms of medical, emotional, and social support. The role of a caregiver becomes increasingly important with the progression of PD, the severity of motor impairment and increasing age of the patient. The nature and symptoms associated with PD can place significant stresses on the caregivers’ burden. As the prevalence of PD is estimated to more than double by 2030, it is important to recognize and alleviate the burden experienced by caregivers. This study focused on the impact of the clinical features on the QoL of PD patients, and of their caregivers. This study included PD patients along with their caregivers and was undertaken at the Malaysian Parkinson's Disease Association from June 2016 to November 2016. Clinical features of PD patients were assessed using the Movement Disorder Society revised Unified Parkinson Disease Rating Scale (MDS-UPDRS); the Hoehn and Yahr Staging of Parkinson's Disease were used to assess the severity and Parkinson's disease activities of daily living scale were used to assess the disability of Parkinson’s disease patients. QoL of PD patients was measured using the Parkinson's Disease Questionnaire-39 (PDQ-39). The revised version of the Zarit Burden Interview assessed caregiver burden. At least one of the clinical features affected PD patients’ QoL, and at least one of the QoL domains affected the caregivers’ burden. Clinical features ‘Saliva and Drooling’, and ‘Dyskinesia’ explained 29% of variance in QoL of PD patients. The QoL domains ‘stigma’, along with ‘emotional wellbeing’ explained 48.6% of variance in caregivers’ burden. Clinical features such as saliva, drooling and dyskinesia affected the QoL of PD patients. The PD patients’ QoL domains such as ‘stigma’ and ‘emotional well-being’ influenced their caregivers’ burden.

Keywords: carers, quality of life, clinical features, Malaysia

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