Excellence in Research and Innovation for Humanity

International Science Index

Commenced in January 1999 Frequency: Monthly Edition: International Abstract Count: 39602

Pharmacological and Pharmaceutical Sciences

Effect of Honey on Rate of Healing of Socket after Tooth Extraction in Rabbits
Background: Honey is the worlds’ oldest known wound dressing. Its wound healing properties are not fully established till today. Concerns about antibiotic resistance, and a renewed interest in natural remedies have prompted the resurgence in the antimicrobial and wound healing properties of Honey. Evidence from animal studies and some trials has suggested that honey may accelerate wound healing in burns, infected wounds and open wounds. None of these reports have documented the effect of honey on the healing of socket after tooth extraction. Therefore, the present experimental study was planned to evaluate the efficacy of honey on the healing of socket after tooth extraction in rabbits. Materials and Methods: An experimental study was conducted in six New Zealand White rabbits. Extraction of first premolar tooth on both sides of the lower jaw was done under anesthesia produced by Ketamine and Xylazine followed by application of honey on one socket (test group) and normal saline (control group) in the opposite socket. The intervention was continued for two more days. On the 7th day, the biopsy was taken from the extraction site, and histopathological examination was done. Student’s t-test was used for comparison between the groups and differences were considered to be statistically significant at p-value less than 0.05. Results: There was a significant difference between control group and test group in terms of fibroblast proliferation (p = 0.0019) and bony trabeculae formation (p=0.0003). Inflammatory cells were also observed in both groups, and it was not significant (p=1.0). Overlying epithelium was hyperplastic in both the groups. Conclusion: The study showed that local application of honey promoted the rapid healing process particularly by increasing fibroblast proliferation and bony trabeculae.
Ph-Triggered Cationic Solid Lipid Nanoparticles Mitigated Colitis in Mice
In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.
Establishment of an Information Platform Increases Spontaneous Reporting of Adverse Drug Reactions
Introduction: The pharmacist is responsible for encouraging adverse drug reaction (ADR) reporting. In a local center in Northern Taiwan, promotion and rewarding of ADR reporting have continued for over six years but failed to bring significant changes. This study aims to find a solution to increase ADR reporting. Research question or hypothesis: We hypothesized that under-reporting is due to the inconvenience of the reporting system. Reports were made conventionally through printed sheets. We proposed that reports made per month will increase if they were computerized. Study design: An ADR reporting platform was established in April 2015, before which was defined as the first stage of this study (January-March, 2015) and after which the second stage. The third stage commenced in November, 2015, after adding a reporting module to physicians prescription system. ADRs could be reported simultaneously when documenting drug allergies. Methods: ADR report rates during the three stages of the study were compared. Effects of the information platform on reporting were also analyzed. Results: During the first stage, the number of ADR reports averaged 6 per month. In the second stage, the number of reports per month averaged 1.86. Introducing the information platform had little effect on the monthly number of ADR reports. The average number of reports each month during the third stage of the study was 11±3.06, with 70.43% made electronically. Reports per month increased significantly after installing the reporting module in November, 2015 (P< 0.001, t-test). In the first two stages, 29.03% of ADR reports were made by physicians, as compared to 70.42% of cases in the third stage of the study. Increased physician reporting possibly account for these differences. Conclusion: Adding a reporting module to the prescription system significantly increased ADR reporting. Improved accessibility is likely the cause. The addition of similar modules to computer systems of other healthcare professions may be considered to encourage spontaneous ADR reporting.
Synthesis and Biological Evaluation of Some Benzoxazole Derivatives as Inhibitors of Acetylcholinesterase / Butyrylcholinesterase and Tyrosinase
Alzheimer’s disease (AD), a neurodegenerative disorder characterized by a progressive deterioration of memory and cognition, occurs more frequently in elderly people. Current treatment approaches in this disease with the major therapeutic strategy are based on the AChE and BChE inhibition. On the other hand, tyrosinase inhibition has become a target for the treatment of Parkinson’s disease (PD) since this enzyme may play a role in neuromelanin formation in the human brain and could be critical in the formation of dopamine neurotoxicity associated with neurodegeneration linked to PD. Also benzoxazoles are structural isosteres of natural nucleotides that can interact with biopolymers so that benzoxazoles showed a lot of different biological activities. In this study, a series of 2,5-disubstituted-benzoxazole derivatives were synthesized and were evaluated as possible inhibitors of acetylcholinesterase (AChE) / butyrylcholinesterase (BChE) and tyrosinase. The results demonstrated that the compounds exhibited a weak spectrum of AChE / BChE inhibitory activity ranging between 3.92% - 54.32% except compound 8 which showed no activity against AChE and compound 4 which showed no activity against BChE at the specified molar concentrations. Also, the compounds indicated lower than tyrosinase inhibitory activity of ranging between 8.14% - 22.90% to that of reference (kojic acid).
Optimation of Ethanol Extract of Gotu Kola and Majapahit Composition as Natural Antioxidant Source
The development of natural antioxidants in the Centella asiatica and Majapahit is a great potential. This research has been optimizing the composition of ethanol extract of Centella asiatica and leaves Majapahit as an antioxidants source using measure the free radical scavenging activity of DPPH. The results of the research showed that both the ethanol extract of Centella asiatica and leaves Majapahit has a total content of phenol. It is shown with the ability to reduce reagent Folin Ciocalteu become blue colour. The composition optimization of extract Centella asiatica leaves Majapahit = 30:70 has free radical scavenging activity of DPPH most well compared ethanol extract of Centella asiatica and leaves Majapahit. IC50 values for the composition of ethanol extract of Centella asiatica : leaves Majapahit = 30:70 is 0,103 mg/mL.
Formulation of Sun Screen Cream and Sun Protecting Factor Activity from Standardized–Partition Compound of Mahkota Dewa Leaf, (Phaleria macrocarpa (Scheff.) Boerl.)
Mahkota Dewa contains phalerin which has activity as sun screen. In this study, 13 formulations of cream oil in water (o/w) were prepared and tested for their physical characteristics. The physical characteristics were then used for determining the optimum formula. This study aimed to explore the physical stability of optimized formulation of cream, its sun protecting factor (SPF) values using in vitro and in vivo tests. The optimum formula of o/w cream were prepared based on Simplex Lattice Design (LSD) method using software Design Expert®. The formulation of o/w cream were varied based on the proportion of cetyl alcohol, mineral oil and tween 80. The difference of physical characteristic of optimum and predicted formula was tested using t-test with significant level of 95%. The optimum formula of o/w cream was the formula which consists of cetyl alcohol 9.71%, mineral oil, 29%, and tween 80 3.29. Based on t-test, there was no significant difference of physical characteristics of optimum and predicted formulation. Viscosity, spread power, adhesive power, and separation volume ratio of o/w at week 0-4 were relatively stable. The o/w creams were relatively stable at extreme temperature. The o/w creams from mahkota dewa, phalerin, and benzophenone have SPF values of 21.32, 33.12, and 42.49, respectively. The formulas did not irritate the skin based on in vivo test.
Hepatoprotective Assessment of L-Ascorbate 1-(2-Hydroxyethyl)-4,6-Dimethyl-1, 2-Dihydropyrimidine-2-On Exposure to Carbon Tetrachloride
Among hepatic pyrimidine used as a means of stimulating protein synthesis and recovery of liver cells in her damaged toxic and infectious etiology. When an experimental toxic hepatitis hepatoprotective activity detected some pyrimidine derivatives. There are literature data on oksimetiluratcila hepatoprotective effect. For analogs of pyrimidine nucleobases - drugs Methyluracilum pentoxy and hepatoprotective effect of weakly expressed. According to the American scientists broad spectrum of biological activity, including hepatoprotective properties, have a 2,4-dioxo-5-arilidenimino uracils. Influenced Xymedon medicinal preparation (1- (beta-hydroxyethyl) -4,6-dimethyl-1,2-dihydro-2-oksopirimidin) developed as a means of stimulating the regeneration of tissue revealed increased activity of microsomal oxidases human liver. In studies on the model of toxic liver damage in rats have shown hepatoprotective effect xymedon and stimulating its impact on the recovery of the liver tissue. Hepatoprotective properties of the new compound in the series of pyrimidine derivatives L-ascorbate 1-(2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropirimidine-2-one synthesized on the basis Xymedon preparation were firstly investigated on rats under the carbon tetrachloride action. It was shown the differences of biochemical parameters from the reference value and severity of structural-morphological liver violations decreased in comparison with control group under the influence of the compound injected before exposure carbon tetrachloride. Hepatoprotective properties of the investigated compound were more pronounced in comparison with Xymedon.
Study of Actoprotective Properties of Xymedon and Its Analogs
The effects of the drug xymedon and its six new analogues containing xymedon fragments and biogenic acids, on the physical performance of rats in the test "Swimming to the full". It has been shown that single and multiple doses (21 days) of the studied compounds does not cause a statistically significant effect in this test. In 11-day conditions intraperitoneal administration of pyrimidine derivatives among the studied most pronounced effect aktoprotektornyh has L-ascorbate compound is 1- (2-hydroxyethyl) -4,6-dimethyl-1,2-dihydropyrimidine-2-one, the introduction of which 20 mg/kg caused a statistically significant increase in the duration of swimming of rats on the 14th day of the experiment at 440% compared to the control group. The compound is a conjugate comprising moieties xymedon and ascorbic acid. The introduction of the compound for 11 days under conditions of physical activity does not affect the leucopoiesis but stimulates erythropoiesis, resulting in the increase in the number of erythrocytes and hemoglobin level. The introduction of the substance in a mixed character debilitating stress prevents the reduction of glucose levels, increased levels of urea and lactic acid, which indicates an improvement loads of animals and tolerability of anti-catabolic effect of the compound. The absence of hepato and cardiotoxic effects of the substance.
Design of Experiment for Optimization of Lercanidipine Nanocrystals
Lercanidipine hydrochloride is a calcium channel blockers used for treating angina pectoris and hypertension. Lercanidipine is poorly water soluble drug having BCS Class II. 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 the 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 the 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 18 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 an increase in aqueous solubility and dissolution rate of Lercanidipine hydrochloride.
Comparative Therapeutic Effect of Acalypha Indica Linn. Extract and Gemfibrozil on High Fructose and Cholesterol Diet Induced Pancreas Steatosis in Sprague-Dawley Mice
Sedentary lifestyle and imbalance consumption pattern has made metabolic syndrome as the global time bomb phenomenon in the world. The increasing tendency of people in consuming high amount of fructose and cholesterol food has worsened this issue in the society. Pancreas steatosis become one of the most comorbid when early diagnosis and prompt treatment has not been applied on hyperglycemic and hyperlipidemic condition in metabolic syndrome patient. Gemfibrozil become the drug of choice to prevent this issue, yet the efficacy of this regiment was still questionable. Acalypha indica Linn. is the herb that has protective effect on hyperlipidemic and hyperglycemic condition. This study was aimed to compare therapeutic effect of gemfibrozil (G) and Acalypha indica Linn. (AI) on high fructose and cholesterol diet-induced pancreas steatosis in Sprague-Dawley mice. The post induction mice were divided into four groups: control, gemfibrozil, AI extract, and G+AI combination regiment. Each group received four weeks intervention. The result of statistical analysis using the One-Way ANOVA test and Tukey Post Hoc test showed significant decrease in pancreatic steatosis between the control group and administered Acalypha indica group (p = 0.004, 95% CI: 0.170-0.959) and the group administered with a combination of Gemfibrozil-Acalypha indica (p = 0.023, 95% CI: 0.537-0.813). The protective effect of Acalypha indica Linn. shows that this plant has the potential as therapeutic option in overcoming the condition of pancreas steatosis in metabolic syndrome.
Patient Support Program in Pharmacovigilance: Foster Patient Confidence and Compliance
The Pharmaceutical companies are getting more inclined towards Patient support programmes (PSPs), which assists patients and /or Healthcare professionals (HCPs) in more desirable disease management and cost-effective treatment. The utmost objective of these programmes is patient care. The PSPs may include financial assistance to patients, medicine compliance programmes, access to HCPs via phone or online chat centers etc. The PSP has a crucial role in terms of customer acquisition and retention strategies. During the conduct of these programmes, Marketing Authorisation Holder (MAH) may receive information related to concerned medicinal products, which is usually reported by patients or involved HCPs. This information may include suspected adverse reaction(s) while/after administration of medicinal products. Hence, the MAH should design PSP to comply with regulatory reporting requirements and avoid non-compliance during PV inspection. The emergence of wireless health devices is lowering the burden on patients to manually incorporate safety data, and building a significant option for patients to observe major swings in reference to drug safety. Therefore, to enhance the adoption of these programmes, MAH not only needs to aware patients about advantages of the program, but also recognizes the importance of time of patients and commitments made in a constructive manner. It is indispensable that strengthening the public health is considered as the topmost priority in such programmes and the MAH is compliant to Pharmacovigilance (PV) requirements along with regulatory obligations.
Psychometric Properties of the Eq-5d-3l and Eq-5d-5l Instruments for Health Related Quality of Life Measurement in Indonesian Population
Cost utility analysis is the most recommended pharmacoeconomic method since it allows widely comparison of cost-effectiveness results from different interventions. The method uses outcome of quality-adjusted life year (QALY) or disability-adjusted life year (DALY). Measurement of QALY requires the data of utility dan life years gained. Utility is measured with the instrument for quality of life measurement such as EQ-5D. Recently, the EQ-5D is available in two versions which are EQ-5D-3L and EQ-5D-5L. This study aimed to compare the EQ-5D-3L and EQ-5D-5L to examine the most suitable version for Indonesian population. This study was an observational study employing cross sectional approach. Data of quality of life measured with EQ-5D-3L and EQ-5D-5L were collected from several groups of population which were respondent with chronic diseases, respondent with acute diseases, and respondent from general population (without illness) in Yogyakarta Municipality, Indonesia. Convenience samples of hypertension patients (83), diabetes mellitus patients (80), and osteoarthritis patients (47), acute respiratory tract infection (81), cephalgia (43), dyspepsia (42), and respondent from general population (293) were recruited in this study. Responses on the 3L and 5L versions of EQ-5D were compared by examining the psychometric properties including agreement, internal consistency, ceiling effect, and convergent validity. Based on psychometric properties tests of EQ-5D-3L dan EQ-5D-5L, EQ-5D-5L tended to have better psychometric properties compared to EQ-5D-3L. Future studies for health related quality of life (HRQOL) measurements for pharmacoeconomic studies in Indonesia should apply EQ-5D-5L.
Cedrela Toona Roxb.: An Exploratory Study Describing Its Antidiabetic Property
Diabetes mellitus is considered to be a serious endocrine syndrome. Synthetic hypoglycemic agents can produce serious side effects including hematological effects, coma, and disturbances of the liver and kidney. In addition, they are not suitable for use during pregnancy. In recent years, there have been relatively few reports of short-term side effects or toxicity due to sulphonylureas. Published figures and frequency of side effects in large series of patient range from about 1 to 5%, with symptoms severe enough to lead to the withdrawal of the drug in less than 1 to 2%. Adverse effects, in general, have been of the following type: allergic skin reactions, gastrointestinal disturbances, blood dyscrasias, hepatic dysfunction, and hypoglycemia. The associated disadvantages with insulin and oral hypoglycemic agents have led to stimulation in the research for locating natural resources showing antidiabetic activity and to explore the possibilities of using traditional medicines with proper chemical and pharmacological profiles. Literature survey reveals that the inhabitants of Abbottabad district of Pakistan use the dried leaf powder along with table salt and water orally for treating diabetes, skin allergy, wounds and as a blood purifier, where they pronounced the plant locally as ‘Nem.' The detailed phytochemical investigation of the Cedrela toona Roxb. leaves for antidiabetic activity has not been documented. Hence, there is a need for phytochemical investigation of the leaves for antidiabetic activity. The collection of fresh leaves and authentification followed by successive extraction, phytochemical screening, and testing of antidiabetic activity. The blood glucose level was reduced maximum in ethanol extract at 5th and 7th h after treatment. Blood glucose was depressed by 8.2% and 10.06% in alloxan – induced diabetic rats after treatment which was comparable to the standard drug, Glibenclamide. This may be due to the activation of the existing pancreatic cells in diabetic rats by the ethanolic extract.
Short-Term versus Long-Term Effect of Waterpipe Smoking Exposure on Cardiovascular Biomarkers in Mice
Introduction: Tobacco use is one of the main risk factors to cardiovascular diseases (CVD) and atherosclerosis in particular. WPS contains several toxic materials such as: nicotine, carcinogens, tar, carbon monoxide and heavy metals. Thus, WPS is considered to be as one of the toxic environmental factors that should be investigated intensively. Therefore, the aim of this study is to investigate the effect of WPS on several cardiovascular biological markers that may cause atherosclerosis in mice. The study also conducted to study the temporal effects of WPS on the atherosclerotic biomarkers upon short (2 weeks) and long-term (8 weeks) exposures. Methods: mice were exposed to WPS and heart homogenates were analyzed to elucidate the effects of WPS on matrix metalloproteinase (MMPs), endothelin-1 (ET-1) and, myeloperoxidase (MPO). Following protein estimation, enzyme-linked immunosorbent assays were done to measure the levels of MMPs (isoforms 1, 3, and 9), MPO, and ET-1 protein expressions. Results: our data showed that acute exposure to WPS significantly enhances the levels of MMP-3, MMP- 9, and MPO expressions (p < 0.05) compared to their corresponding control. However, the body was capable to normalize the level of expressions for such parameters following continuous exposure for 8 weeks (p > 0.05). Additionally, we showed that the level of ET-1 expression was significantly higher upon chronic exposure to WPS compared to both control and acute exposure groups (p < 0.05). Conclusion: Waterpipe exposure has a significant negative effect on atherosclerosis and the enhancement of the atherosclerotic biomarkers expression (MMP-3 and 9, MPO, and ET-1) might represent an early scavenger of compensatory efforts to maintain cardiac function after WP exposure.
Cycas beddomei Dyer: An Endemic and Endangered Indian Medicinal Plant
Herbal medicines are gaining importance due to holistic nature and lesser side effects. Cycas beddomei Dyer is one of the highly exploited medicinal plants in India. Due to over-exploitation of male and female cones, young leaves and starch-bearing pithy stems for edible, medicinal and socio-cultural practices by the locals, tribals and traders, the plant population has drastically declined in its natural habitats. Cycas beddomei is an endemic to India. The current IUCN status of this plant species in the wild is endangered. Perhaps, it is the only species of Cycas enlisted in Appendix I of CITES (Convention on International Trade in Endangered Species of wild fauna and flora). Endorsing the CITES decisions, the Government of India has placed C. beddomei in the “Negative List of Exports” during 1998. Though this plant has been banned legally, but illegally, it is highly exploited by different means. Therefore, conservation of this species is an urgent need of the hour. The present paper highlights unique morphological and anatomical characters of C. beddomei, along with its present status, major threats and conservation measures. Cycas beddomei can easily be identified by some of the distinguishing morphological and anatomical characters, viz., 2–4 mm wide leaflets with revolute margins; the apices of microsporophylls from the middle to apex of the pollen cones turn downwards on maturity; mucilage canal cells are seen in the midrib region of the leaflets; stomatal frequency is about 18 numbers at 250x; pollen grains are monocolpate and their diameter ranging from 22.5 to 30 µm.
Aqueous Extract of Picrorrhiza kurroa Royle ex Benth: A Potent Inhibitor of Human Topoisomerases
Topoisomerase I and II α plays a crucial role in the DNA-maintenance in all living cells, and for this reason, inhibitors of this enzyme have been much studied. In this paper, we have described the inhibitory effect of the aqueous extract of Picrorrhiza kurroa on human topoisomerases by measuring the relaxation of superhelical plasmid pBR322 DNA. The aqueous extract inhibited topoisomerase I and II α in a concentration-dependent manner (Inhibitory concentration (IC) ≈ 25 and 50 µg, respectively). By stabilization studies of topoisomerase I-DNA complex and preincubation studies of topoisomerase I and II α with the extract; we conclude that the possible mechanism of inhibition is both; 1) stabilization of covalent complex of topo I-DNA complex and 2) direct inhibition of the enzyme topoisomerases. These findings might explain the antineoplastic activity of Picrorrhiza kurroa and encourage new studies to elucidate the usefulness of the extract as a potent antineoplastic agent.
Electrospinning of Nanofibrous Meshes and Surface-Modification for Biomedical Application
Biomedical applications of electrospun nanofibrous meshes have been received tremendous attentions because of their unique structures and versatilities as biomaterials. Incorporation of growth factors in fibrous meshes can be performed by surface-modification and encapsulation. Those growth factors stimulate differentiation and proliferation of specific types of cells and thus lead tissue regenerations of specific cell types. Topographical cues of electrospun nanofibrous meshes also increase differentiation of specific cell types according to alignments of fibrous structures. Wound healing treatments of diabetic ulcers were performed using nanofibrous meshes encapsulating multiple growth factors. Aligned nanofibrous meshes and those with random configuration were compared for differentiating mesenchymal stem cells into neuronal cells. Thus, nanofibrous meshes can be applied to drug delivery carriers and matrix for promoting cellular proliferation.
Investigation of Ameliorative Effect of a Polyphenolic Compound of Green Tea Extract against Rotenone Induced Neurotoxicity: A Mechanistic Approach
Natural antioxidants have major role in maintenance of health. Green tea extract principally contains epigallocatechin-3-gallate (EGCG), as its abundant antioxidant constituent. Green tea is consumed daily worldwide as antioxidant to combat CNS diseases and has traditional importance also. EGCG has neuroprotective potential in various animal models of Parkinson disease, Alzheimer’s disease etc. but its exact mechanism has not been ruled out. The present study has been designed to investigate the anti-inflammatory, antioxidant and mitochondrial modulating mechanism of neuroprotective effect of epigallocatechin-3-gallate against rodent model of rotenone induced Parkinson’s disease (PD). The behavioural alterations were assessed by using open field test apparatus, Chatilon’s grip strength test apparatus and elevated plus maze for determining the locomotor activity, grip strength and cognition respectively. Biochemically, various parameters to assess oxidative stress, neuroinflammation and neurochemical estimations were performed on rat brain homogenates. A histological examination of rat brain striatum was done to check the neurodegeneration. Epigallocatechin-3-gallate (EGCG) at 10 & 20 mg/kg, were investigated for their neuroprotective potential along with levodopa as a standard agent. Minocycline, a microglial activation inhibitor, was administered alone and in combination with EGCG. EGCG and minocycline produced ameliorative effect against rotenone induced PD like symptoms by significantly reduced behavioral, biochemical and histological alterations. Results of our study reveal the neuroprotective effect of EGCG and minocycline against rotenone induced PD. Results of our study indicate that EGCG exerted neuroprotective effect against rotenone induced PD via its antioxidant, anti-inflammatory and mitochondrial modulating mechanisms and substantiate its previously reported and traditional claims for its use in CNS diseases.
Evaluation of Medication Errors in Outpatient Pharmacies: Electronic Prescription System vs. Paper System
Background: Medication errors are among the most common medical errors. Their occurrences result in patient’s mortality, morbidity, and additional healthcare costs. Continuous monitoring and detection is required. Objectives: The aim of this study was to compare medication errors in outpatient’s prescriptions in two different hospitals (paper system vs. electronic system). Methods: This was a cross sectional observational study conducted in two major hospitals; King Abdullah University Hospital (KAUH) and Princess Bassma Teaching Hospital (PBTH) over three months period. Data collection was conducted by two trained pharmacists at each site. During the study period, medication prescriptions and dispensing procedures were screened for medication errors in both participating centers by two trained pharmacist. Results: In the electronic prescription hospital, 2500 prescriptions were screened in which 631 medication errors were detected. Prescription errors were 231 (36.6%), and dispensing errors were 400 (63.4%) of all errors. On the other side, analysis of 2500 prescriptions in paper-based hospital revealed 3714 medication errors, of which 288 (7.8%) were prescription errors, and 3426 (92.2%) were dispensing errors. A significant number of 2496 (67.2%) were inadequately and/or inappropriately labeled. Conclusion: This study provides insight for healthcare policy makers, professionals, and administrators to invest in advanced technology systems, education, and epidemiological surveillance programs to minimize medication errors.
Cross-Sectional Analysis of the Health Product E-Commerce Market in Singapore
Introduction: The size of Singapore’s online health product (HP) market (e-commerce) is largely unknown. However, it is recognized that a large majority comes from overseas and thus, unregulated. As buying HP from unauthorized sources significantly compromises public health safety, understanding e-commerce users’ demographics and their perceptions on online HP purchasing becomes a pivotal first step to form a basis for recommendations in Singapore’s pharmacovigilance efforts. Objective: To assess the prevalence of online HP purchasing behaviour among Singaporean e-commerce users. Methodology: This is a cross-sectional study targeting Singaporean e-commerce users recruited from various local websites and online forums. Participants were not randomized into study arms but instead stratified by random sampling method based on participants’ age. A self-administered anonymous questionnaire was used to explore participants' demographics, online HP purchasing behaviour, knowledge and attitude. The association of different variables with online HP purchasing behaviour was analysed using logistic regression statistics. Main outcome measures: Prevalence of HP e-commerce users in Singapore (%) and variables that contribute to the prevalence (adjusted prevalent ratio). Results: The study recruited 372 complete and valid responses. The prevalence of online HP consumers among e-commerce users in Singapore is estimated to be 55.9% (1.7 million consumers). Online purchasing of complementary HP (46.9%) was the most prevalent, followed by medical devices (21.6%) and Western medicine (20.5%). Multivariate analysis showed that age is an independent variable that correlates with the likelihood of buying HP online. The prevalence of HP e-commerce users is highest in the 35-44 age group (64.1%) and lowest among the 16-24 age group (36.4%). The most bought HP through the internet are vitamins and minerals (21.5%), non-herbal (15.9%), herbal (13.9%), weight loss (8.7%) and sports (8.4%) supplements. While the top 3 products are distributed equally between the genders, there is a skew towards female respondents (12.4% in females vs. 4.9% in males) for weight loss supplements and towards males (13.2% in males vs. 3.7% in females) for sports supplements. Even though online consumers are in the younger age brackets, our study found that up to 72.0% of HP bought online are bought for others (buyer’s family and/or friends). Multivariate analysis showed a statistically significant association between purchasing HP through online means and the perceptions that 'internet is safe' (adjusted Prevalence Ratio=1.15, CI 1.03-1.28), 'buying HP online is time saving' (PR=1.17, CI 1.01-1.36), and 'recognition of HP brand' (PR=1.21 CI 1.06-1.40). Conclusions: This study has provided prevalence data for online HP market in Singapore, and has allowed the country’s regulatory body to formulate a targeted pharmacovigilance approach to this growing problem.
Preventive Effect of Stem Back Extracts of Coula edulis Baill. against High-Fat / High Sucrose Diet-Induced Insulin Resistance and Oxidative Stress in Rats
Background: Insulin resistance (IR) and oxidative stress are associated with obesity, diabetes mellitus, and other cardio metabolic disorders. The aim of this study was to investigate the effect of Coula edulis extracts (CEE) on insulin resistance and oxidative stress markers in high-fat/high sucrose diet-induced insulin resistance in rats. Materials and Methods: Thirty male rats were divided into 6 groups of 5 rats each fed, received daily oral administration of CE extracts for 8 weeks as follows: Group 1 or negative control group, fed with standard diet (SD); Group 2 fed with high-fat/high sucrose diet (HFHS) only; Group3 fed with HFHS + CEAq 200; Group 4 fed with HFHS + CEAq 400; Group 5 fed with HFHS + CEEt 200; Group 6 fed with HFHS + CEEt 400. At the end of the experiment (8 weeks), animals were sacrificed plasma lipid profile, glucose, insulin, oxidative marker and digestive enzyme activities were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was determined. Results: Feedings with HFHS significantly (p < 0.01) induced plasma hyperglycaemia, hyperinsulinaemia, increased triglyceride, total cholesterol, and low-density lipoprotein levels, decreased high-density lipoprotein levels, alterations of α amylase, and glucose-6-phosphatase activities, and oxidative stress. Daily oral administration with CEE for eight weeks after insulin resistance induction had a hypolipidaemic action, antioxidative activities and modulated metabolic markers. Ethanolic extract at the higher dose had the best effect on body weight gain and insulin resistance, whereas aqueous extract showed the better activity on hyperlipidemia. Conclusion: These results suggest that CEAq and CEEt at 400mg/kg are promising complementary supplements that can be used to protect better from metabolic disorders associated with HFHS.
Evaluation of Chemoprotective Effect of NBRIQU16 against N-Methyl-N-Nitro-N-Nitrosoguanidine and NaCl-Induced Gastric Carcinomas in Wistar Rats
To investigate the chemoprotective potential of NBRIQU16 chemotype isolated from Argyreia speciosa (Family: Convolvulaceae) on N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and NaCl-induced gastric carcinomas in Wistar rats. Forty-six male 6-week-old Wistar rats were divided into two groups. Thirty rats in group A were fed with a diet supplemented with 8 % NaCl for 20 weeks and simultaneously given N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in drinking water at a concentration of 100 ug/ml for the first 17 weeks. After administration of the carcinogen, 200 and 400 mg/kg of NBRIQU16 were administered orally once a day throughout the study. From week 18, these rats were given normal water. From week 21, these rats were fed with a normal diet for 15 weeks. Group B containing 16 rats was fed standard diet for thirty-five days. It served as control. Ten rats from group A were sacrificed after 20 weeks. Scarification of remaining animals was conducted after 35 weeks. Entire stomach and some part of the duodenum were incised parallel to the greater curvature, and the samples were collected. After opening the stomach location and size of tumors were recorded. The number of tumors with their locations and sizes were recorded. Expression of survivin was examined by recording the Immunohistochemistry of the specimens. The treatment with NBRIQU16 significantly reduced the nodule incidence and nodule multiplicity in the rats after MNNG administration. Surviving expression in glandular stomachs of normal rats, of rats in middle induction period, in adenocarcinomas and NBRIQU16 treated tissues adjacent to tumor were 0, 42.0 %, 79.3%, and 36.4 %, respectively. Expression of survivin was significantly different as compared to the normal rats. Histological observations of stomach tissues too correlated with the biochemical observations.These finding powerfully supports that NBRIQU16 chemopreventive effect by suppressing the tumor burden and restoring the activities of gastric cancer marker enzymes on MNNG and NaCl-induced gastric carcinomas in Wistar rats.
An In-silico Pharmacophore-Based Anti-Viral Drug Development for Hepatitis C Virus
Millions of people worldwide suffer from Hepatitis C, one of the fatal diseases. Interferon (IFN) and ribavirin are the available treatments for patients with Hepatitis C, but these treatments have their own side-effects. Our research focused on the development of an orally taken small molecule drug targeting the proteins in Hepatitis C Virus (HCV), which has lesser side effects. Our current study aims to the Pharmacophore based drug development of a specific small molecule anti-viral drug for Hepatitis C Virus (HCV). Drug designing using lab experimentation is not only costly but also it takes a lot of time to conduct such experimentation. Instead in this in silico study, we have used computer-aided techniques to propose a Pharmacophore-based anti-viral drug specific for the protein domains of the polyprotein present in the Hepatitis C Virus. This study has used homology modeling and ab initio modeling for protein 3D structure generation followed by pocket identification in the proteins. Drug-able ligands for the pockets were designed using de novo drug design method. For ligand design, pocket geometry is taken into account. Out of several generated ligands, a new Pharmacophore is proposed, specific for each of the protein domains of HCV.
Preparation, Solid State Characterization of Etraverine Co-Crystals with Improved Solubility for the Treatment of Human Immunodeficiency Virus
Introduction: Preparation of binary cocrystals of Etraverine (ETR) by using Tartaric Acid (TAR) as a conformer was the main focus of this study. Etravirine is a Class IV drug, as per the BCS classification system. Methods: Cocrystals were prepared by slow evaporation technique. A mixture of total 500mg of ETR: TAR was weighed in molar ratios of 1:1 (371.72mg of ETR and 128.27mg of TAR). Saturated solution of Etravirine was prepared in Acetone: Methanol (50:50) mixture in which tartaric acid is dissolved by sonication and then this solution was stirred using a magnetic stirrer until the solvent got evaporated. Shimadzu FTIR – 8300 system was used to acquire the FTIR spectra of the cocrystals prepared. Shimadzu thermal analyzer was used to achieve DSC measurements. X-ray diffractometer was used to obtain the X-ray powder diffraction pattern. Shake flask method was used to determine the equilibrium dynamic solubility of pure, physical mixture and cocrystals of ETR. USP buffer (pH 6.8) containing 1% of Tween 80 was used as the medium. The pure, physical mixture and the optimized cocrystal of ETR were accurately weighed sufficient to maintain the sink condition and were filled in hard gelatine capsules (size 4). Electrolab-Tablet Dissolution tester using basket apparatus at a rotational speed of 50 rpm and USP phosphate buffer (900 mL, pH = 6.8, 37 ˚C) + 1% Tween80 as a media, was used to carry out dissolution. Shimadzu LC-10 series chromatographic system was used to perform the analysis with PDA detector. An Hypersil BDS C18 (150mm ×4.6 mm ×5 µm) column was used for separation with mobile phase comprising of a mixture of ace¬tonitrile and phosphate buffer 20mM, pH 3.2 in the ratio 60:40 v/v. The flow rate was 1.0mL/min and column temperature was set to 30°C. The detection was carried out at 304 nm for ETR. Results and discussions: The cocrystals were subjected to various solid state characterization and the results confirmed the formation of cocrystals. The C=O stretching vibration (1741cm-1) in tartaric acid was disappeared in the cocrystal and the peak broadening of primary amine indicates hydrogen bond formation. The difference in the melting point of cocrystals when compared to pure Etravirine (265 °C) indicates interaction between the drug and the coformer which proves that first ordered transformation i.e. melting endotherm has disappeared. The difference in 2θ values of pure drug and cocrystals indicates the interaction between the drug and the coformer. Dynamic solubility and dissolution studies were also conducted by shake flask method and USP apparatus one respectively and 3.6 fold increase in the dynamic solubility were observed and in-vitro dissolution study shows four fold increase in the solubility for the ETR: TAR (1:1) cocrystals. The ETR: TAR (1:1) cocrystals shows improved solubility and dissolution as compared to the pure drug which was clearly showed by solid state characterization and dissolution studies.
Bioanalytical Method Development and Validation of Aminophylline in Rat Plasma Using Reverse Phase High Performance Liquid Chromatography: An Application to Preclinical Pharmacokinetics
Introduction: Aminophylline is a methylxanthine derivative belonging to the class bronchodilator. From the literature survey, reported methods reveals the solid phase extraction and liquid liquid extraction which is highly variable, time consuming, costly and laborious analysis. Present work aims to develop a simple, highly sensitive, precise and accurate high-performance liquid chromatography method for the quantification of Aminophylline in rat plasma samples which can be utilized for preclinical studies. Method: Reverse Phase high-performance liquid chromatography method. Results: Selectivity: Aminophylline and the internal standard were well separated from the co-eluted components and there was no interference from the endogenous material at the retention time of analyte and the internal standard. The LLOQ measurable with acceptable accuracy and precision for the analyte was 0.5 µg/mL. Linearity: The developed and validated method is linear over the range of 0.5-40.0 µg/mL. The coefficient of determination was found to be greater than 0.9967, indicating the linearity of this method. Accuracy and precision: The accuracy and precision values for intra and inter day studies at low, medium and high quality control samples concentrations of aminophylline in the plasma were within the acceptable limits Extraction recovery: The method produced consistent extraction recovery at all 3 QC levels. The mean extraction recovery of aminophylline was 93.57 ± 1.28% while that of internal standard was 90.70 ± 1.30%. Stability: The results show that aminophylline is stable in rat plasma under the studied stability conditions and that it is also stable for about 30 days when stored at -80˚C. Pharmacokinetic studies: The method was successfully applied to the quantitative estimation of aminophylline rat plasma following its oral administration to rats. Discussion: Preclinical studies require a rapid and sensitive method for estimating the drug concentration in the rat plasma. The method described in our article includes a simple protein precipitation extraction technique with ultraviolet detection for quantification. The present method is simple and robust for fast high-throughput sample analysis with less analysis cost for analyzing aminophylline in biological samples. In this proposed method, no interfering peaks were observed at the elution times of aminophylline and the internal standard. The method also had sufficient selectivity, specificity, precision and accuracy over the concentration range of 0.5 - 40.0 µg/mL. An isocratic separation technique was used underlining the simplicity of the presented method.
In-Vivo Study of Annacardium occidentale L. Emulgel Extract Using Non-Invasive Probes
The focus of the study was to design, develop and characterize in vivo, a stable Emulgel formulation containing Anacardium occidentale L.(cashew extract) as an active ingredient. The formulation was prepared and kept at 8ºC, 25 ºC, 40ºC and 40ºC±RH for a period of 28 days. During this time period, stability, pH values, conductivity, organoleptic features (color, liquefaction, phase separation) were conducted at the intervals of day 1st, 2nd, 3rd , 7th, 14th and 28th days. In In vivo studies, the test formulation (5% Anacardium occidentale L, extract) and a base formulation (without cashew extract) were prepared and both were applied on cheek areas of healthy human female volunteers, after the skin sensitivity test of each volunteer, for a study period of 8 weeks after getting consent from them. Various parameters of skin like Melanin level, Erythema level, and skin elasticity were measured at regular time intervals. Results of the study were analyzed by statistical techniques i.e. Two Way ANOVA and paired sample t-test. The result showed significant results as the p ≤ 0.05. Findings of paired sample t-test explained that test formulation have profound effects on skin parameters when compared with control formulation.
How Addictive Are They: Effects of E-Cigarette Vapor on Intracranial Self-Stimulation Compared to Nicotine Alone
Electronic cigarettes (e-cigarettes) use vapor to deliver nicotine, have recently become popular, especially amongst adolescents. Because of this, the FDA has decided to regulate e-cigarettes, and therefore would like to determine the abuse liability of the products compared to traditional nicotine products. This will allow them to determine the impact of regulating them on public health and shape the decisions they make when creating new laws. This study assessed the abuse liability of Aroma E-juice Dark Honey Tobacco compared to nicotine using an animal model. This e-liquid contains minor alkaloids that may increase abuse liability compared to nicotine alone. The abuse liability of nicotine alone and e-juice liquid were compared in rats using intracranial self-stimulation (ICSS) thresholds. E-liquid had less aversive effects at high nicotine doses in the ICSS model, suggesting that the minor alkaloids in the e-liquid allow users to use higher doses without experiencing the negative effects felt when using high doses of nicotine alone. This finding could mean that e-cigarettes have a higher abuse liability than nicotine alone, but more research is needed before this can be concluded. These findings are useful in observing the abuse liability of e-cigarettes and will help inform the FDA while regulating these products.
Ultra-Fast pH-Gradient Ion Exchange Chromatography for the Separation of Monoclonal Antibody Charge Variants
Purpose: Demonstration of fast high resolution charge variant analysis for monoclonal antibody (mAb) therapeutics within 5 minutes. Methods: Three commercially available mAbs were used for all experiments. The charge variants of therapeutic mAbs (Bevacizumab, Cetuximab, Infliximab, and Trastuzumab) are analyzed on a strong cation exchange column with a linear pH gradient separation method. The linear gradient from pH 5.6 to pH 10.2 is generated over time by running a linear pump gradient from 100% Thermo Scientific™ CX-1 pH Gradient Buffer A (pH 5.6) to 100% CX-1 pH Gradient Buffer B (pH 10.2), using the Thermo Scientific™ Vanquish™ UHPLC system. Results: The pH gradient method is generally applicable to monoclonal antibody charge variant analysis. In conjunction with state-of-the-art column and UHPLC technology, ultra fast high-resolution separations are consistently achieved in under 5 minutes for all mAbs analyzed. Conclusion: The linear pH gradient method is a platform method for mAb charge variant analysis. The linear pH gradient method can be easily optimized to improve separations and shorten cycle times. Ultra-fast charge variant separation is facilitated with UHPLC that complements, and in some instances outperforms CE approaches in terms of both resolution and throughput.
In silico Designing and Insight into Antimalarial Potential of Chalcone-Quinolinylpyrazole Hybrids by Preclinical Study in Mice
The quinoline scaffold is one of the most widely studied in the discovery of derivatives with various heterocyclic moieties due to its potential antimalarial activities. In the present study, a chalcone series of quinoline derivatives clubbed with pyrazole were synthesized to evaluate their antimalarial property by in vitro schizont maturation inhibition assay against both chloroquine sensitive, 3D7 and chloroquine resistant, RKL9 strain of Plasmodium falciparum. Further, top five compounds were studied for in vivo preclinical study for antimalarial potential against P. berghei in Swiss albino mice. To understand the mechanism of synthesized analogues, they were screened computationally by molecular docking techniques. Compounds were docked into the active site of a protein receptor, Plasmodium falciparum Cysteine Protease Falcipain-2. The compounds were successfully synthesized, and structural confirmation was performed by FTIR, 1H-NMR, mass spectrometry and elemental analysis. In vitro study suggested that the compounds 5b, 5g, 5l, 5s and 5u possessed best antimalarial activity and further tested for in vivo screening. Compound 5u (CH₃ on both rings) with EC₅₀ 0.313 & 0.801 µg/ml against CQ-S & CQ-R strains of P. falciparum respectively and 78.01% suppression of parasitemia. The molecular docking studies of the compounds helped in understanding the mechanism of action against falcipain-2. The present study reveals the binding signatures of the synthesized ligands within the active site of the protein, and it explains the results from in vitro study in their EC₅₀ values and percentage parasitemia.
High Power Thermal Energy Storage for Industrial Applications Using Phase Change Material Slurry
The successful integration of thermal energy storage in industrial processes is expected to play an important role in the energy turnaround. Latent heat storage technologies can offer more compact thermal storage at a constant temperature level, in comparison to conventional, sensible thermal storage technologies. The focus of this study is the development of latent heat storage solutions based on the Phase Change Slurry (PCS) concept. Such systems promise higher energy densities both as refrigerants and as storage media while presenting better heat transfer characteristics than conventional latent heat storage technologies. This technology is expected to deliver high thermal power and high-temperature stability which makes it ideal for storage of process heat. An evaluation of important batch processes in industrial applications set the focus on materials with a melting point in the range of 55 - 90 °C. Aluminium ammonium sulfate dodecahydrate (NH₄Al(SO₄)₂·12H₂O) was chosen as the first interesting PCM for the next steps of this study. The ability of this material to produce slurries at the relevant temperatures was demonstrated in a continuous mode in a laboratory test-rig. Critical operational and design parameters were identified.