Search results for: multi drug resistant

Authors: Irene Alevizos, Jessica Lewis, Marina Harper, John Boyce

Abstract:

Acinetobacter baumannii causes a range of severe nosocomial-acquired infections, and many strains are multi-drug resistant. A. baumannii possesses survival mechanisms allowing it to thrive in competitive polymicrobial environments, including a Type VI Secretion System (T6SS) that injects effector proteins into other bacteria to give a competitive advantage. The effects of T6SS firing are broad and depend entirely on the effector that is delivered. Effects can include toxicity against prokaryotic or eukaryotic cells and the acquisition of essential nutrients. The T6SS of some species can deliver ‘specialised effectors’ that are fused directly to T6SS components, such as PAAR proteins. PAAR proteins are predicted to form the piercing tip of the T6SS and are essential for T6SS function. Although no specialised effectors have been identified in A. baumannii, many strains encode multiple PAAR proteins. Analysis of PAAR proteins across the species identified 12 families of PAAR proteins with distinct C-terminal extensions. A. baumannii AB307-0294 encodes two PAAR proteins, one of which has a C-terminal extension. Mutation of one or both of the PAAR-encoding genes in this strain showed that expression of either PAAR protein was sufficient for T6SS function. We employed a heterologous expression approach and determined that PAAR proteins from different A. baumannii strains, as well as the closely related A. baylyi species, could complement the A. baumannii ∆paar mutant and restore T6SS function. Furthermore, we showed that PAAR fusions could be used to deliver artificially cloned protein fragments by generating Histidine- and Streptavidin- tagged PAAR specialised effectors, which restored T6SS activity. This provides evidence that the fusion of protein fragments onto PAAR proteins in A. baumannii is compatible with a functional T6SS. Successful delivery by this mechanism extends the scope of what the T6SS can deliver, including user designed proteins.

Keywords: A. baumannii, effectors, PAAR, T6SS

Procedia PDF Downloads 61

Authors: Vadim Makarov, Stewart T.Cole

Abstract:

PBTZ169 is novel drug candidate with high efficacy in animals models, and its combination treatment of PBTZ169 with BDQ and pyrazinamide was shown to be more efficacious than the standard treatment for tuberculosis in a mouse model. The target of PBTZ169 is famous DprE1, an essential enzyme in cell wall biosynthesis. The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site and explains the irreversible inactivation of the enzyme. Furthermore, this drug candidate demonstrated during preclinical research ‘drug like’ properties what made it an attractive drug candidate to treat tuberculosis in humans. During first clinical trials several cohorts of the healthy volunteers were treated by the single doses of PBTZ169 as well as two weeks repeated treatment was chosen for two maximal doses. As expected PBTZ169 was well tolerated, and no significant toxicity effects were observed during the trials. The study of the metabolism shown that human metabolism of PBTZ169 is very different from microbial or animals compound transformation. So main pathway of microbial, mice and less rats metabolism connected with reduction processes, but human metabolism mainly connected with oxidation processes. Due to this difference we observed several metabolites of PBTZ169 in humans with antitubercular activity, and now we can conclude that animal antituberculosis activity of PBTZ169 is a result not only activity of the drug itself, but it is a result of the sum activity of the drug and its metabolites. Direct antimicrobial plasma activity was studied, and such activity was observed for 24 hours after human treatment for some doses. This data gets high chance for good efficacy of PBTZ169 in human for treatment TB infection. Second phase of clinical trials was started summer of 2017 and continues to the present day. Available data will be presented.

Keywords: clinical trials, DprE1, PBTZ169, metabolism

Procedia PDF Downloads 137

Authors: A. Hilsana, Vinay U. Rao, M. Sudhakar

Abstract:

Even though a number of non-steroidal anti-inflammatory drugs (NSAIDS) are available with different chemistries, they share a common solubility characteristic that is they are relatively more soluble in alkaline environment and practically insoluble in acidic environment. This work deals with developing a wax matrix drug delivery platform for controlled delivery of three model NSAIDS, Diclofenac sodium (DNa), Mefenamic acid (MA) and Naproxen (NPX) using the melt granulation technique. The aim of developing the platform was to have a general understanding on how an erodible matrix system modulates drug delivery rate and extent and how it can be optimized to give a delivery system which shall release the drug as per a common target product profile (TPP). Commonly used waxes like Cetostearyl alcohol and stearic acid were used singly an in combination to achieve a TPP of not 15 to 35% in 1 hour and not less than 80% Q in 24 hours. Full factorial design of experiments was followed for optimization of the formulation.

Keywords: NSAIDs, controlled delivery, target product profile, melt granulation

Procedia PDF Downloads 307

Authors: Friday G. Okibe, Edit B. Agbaji, Victor O. Ajibola, Christain C. Onoyima

Abstract:

Controlled drug delivery systems reduce dose-dependent toxicity associated with potent drugs, including anticancer drugs. In this research, hydroxyapatite (HA) and hydroxyapatite-sodium alginate nanocomposites (HASA) were successfully prepared and characterized using Fourier Transform Infrared spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). The FTIR result showed absorption peaks characteristics of pure hydroxyapatite (HA), and also confirmed the chemical interaction between hydroxyapatite and sodium alginate in the formation of the composite. Image analysis from SEM revealed nano-sized hydroxyapatite and hydroxyapatite-sodium alginate nanocomposites with irregular morphologies. Particle size increased with the formation of the nanocomposites relative to pure hydroxyapatite, with no significant change in particles morphologies. Drug loading and in-vitro drug release study were carried out using synthetic body fluid as the release medium, at pH 7.4 and 37 °C and under perfect sink conditions. The result shows that drug loading is highest for pure hydroxyapatite and decreased with increasing quantity of sodium alginate. However, the release study revealed that HASA-5%wt and HASA-20%wt presented better release profile than pure hydroxyapatite, while HASA-33%wt and HASA-50%wt have poor release profiles. This shows that Methotrexate-loaded hydroxyapatite-sodium alginate if prepared under optimal conditions is a potential carrier for effective delivery of Methotrexate.

Keywords: drug-delivery, hydroxyapatite, methotrexate, nanocomposites, sodium alginate

Procedia PDF Downloads 247

Authors: Fasil Wagnew, Kerri Viney, Kefyalew Addis Alene, Matthew Kelly, Darren Gray

Abstract:

Background: Undernutrition is a risk factor for tuberculosis (TB), including poor treatment outcomes. However, evidence regarding the effect of undernutrition on TB treatment outcomes is not well understood. We aimed to evaluate the effect of undernutrition on sputum culture conversion and treatment outcomes among people with multi-drug resistance (MDR)-TB. Methods: We searched for publications in the Medline, Embase, Scopus, and Web of Science databases without restrictions on geography or year of publication. We conducted a random-effect meta-analysis to estimate the effects of undernutrition on sputum culture conversion and treatment outcomes. Two reviewers independently assessed the study eligibility, extracted the necessary information, and assessed the risk of bias. Depending on the nature of the data, odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CIs) were used to summarize the effect estimates. Potential publication bias was checked using funnel plots and Egger’s tests. Results: Of 2358 records screened, 59 studies comprising a total of 31,254 people with MDR-TB were included. Undernutrition was significantly associated with a lower sputum culture conversion rate (HR 0·7, 95% CI 0·6–0·9, I2=67·1%) and a higher rate of mortality (OR 2·9, 95%CI 2·1–3·8, I2=23·7%) and unfavourable treatment outcomes (OR 1·8, 95%CI 1·5–2·0, I2=72·7%). There was no statistically significant publication bias in the included studies. Three studies were low, forty-two studies were moderate, and fourteen studies were high quality. Interpretations: Undernutrition was significantly associated with unfavourable treatment outcomes, including mortality and lower sputum culture conversion among people with MDR-TB. These findings have implications for supporting targeted nutritional interventions alongside standardised second-line TB drugs.

Keywords: undernutrition, MDR-TB, sputum culture conversion, treatment outcomes, meta-analysis

Procedia PDF Downloads 120

Authors: Gajera Lalit, Shah Pranav, Shah Shailesh

Abstract:

Venlafaxine hydrochloride has a short elimination half-life of 5 ± 2 hr, and absorption window in the upper part of gastrointestinal tract. The conventional tablets need to be administered two to three times a day and possess an oral bioavailability of 45%. The purpose of this study was to formulate gastroretentive effervescent floating tablets of Venlafaxine HCl. Different grades of HPMC namely K15M, K4M, K100M and E15LV were employed as swelling polymers whereas sodium bicarbonate was employed as gas generating agent. The direct compression method was employed for the formulation of tablets. The tablets were evaluated in terms of hardness, friability, weight variation, drug content, water uptake, in-vitro floating behavior and in-vitro drug release study. All the formulations exhibited very short floating lag time of < 1 min and total floating time of 12 hr. Formulation L3 containing 25 mg and 75 mg of HPMC E15 LV and HPMC K15M respectively exhibited complete drug release within 12 hrs.

Keywords: venlafaxine HCl, hydroxyl propyl methylcellulose, floating gastro retentive tablets, in-vitro drug release, non-fickian diffusion

Procedia PDF Downloads 512

Authors: Yasmin Begum Mohammed

Abstract:

Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

Procedia PDF Downloads 273

Authors: Phenphak Horadee, Rodchares Hanrinth, Saithip Suttiruksa

Abstract:

Inappropriate use of antibiotics has happened in several hospitals, Thailand. Drug use evaluation (DUE) is one strategy to overcome this difficulty. However, most community hospitals still encounter incomplete evaluation resulting overuse of antibiotics with high cost. Consequently, drug-resistant bacteria have been rising due to inappropriate antibiotic use. The aim of this study was to involve stakeholders in conceptualizing, developing, and prioritizing a feasible intervention strategy to promote and support appropriate antibiotic prescribing in a community hospital, Thailand. Study antibiotics included four antibiotics such as Meropenem, Piperacillin/tazobactam, Amoxicillin/clavulanic acid, and Vancomycin. The study was conducted for the 1-year period between March 1, 2018, and March 31, 2019, in a community hospital in the northeastern part of Thailand. Concept mapping was used in a purposive sample, including doctors (one was an administrator), pharmacists, and nurses who involving drug use evaluation of antibiotics. In-depth interviews for each participant and survey research were conducted to seek the problems for inappropriate use of antibiotics based on drug use evaluation system. Seventy-seven percent of DUE reported appropriate antibiotic prescribing, which still did not reach the goal of 80 percent appropriateness. Meropenem led other antibiotics for inappropriate prescribing. The causes of the unsuccessful DUE program were classified into three themes such as personnel, lack of public relation and communication, and unsupported policy and impractical regulations. During the first meeting, stakeholders (n = 21) expressed the generation of interventions. During the second meeting, participants who were almost the same group of people in the first meeting (n = 21) were requested to independently rate the feasibility and importance of each idea and to categorize them into relevant clusters to facilitate multidimensional scaling and hierarchical cluster analysis. The outputs of analysis included the idealist, cluster list, point map, point rating map, cluster map, and cluster rating map. All of these were distributed to participants (n = 21) during the third meeting to reach consensus on an intervention model. The final proposed intervention strategy included 29 feasible and crucial interventions in seven clusters: development of information technology system, establishing policy and taking it into the action plan, proactive public relations of the policy, action plan and workflow, in cooperation of multidisciplinary teams in drug use evaluation, work review and evaluation with performance reporting, promoting and developing professional and clinical skill for staff with training programs, and developing practical drug use evaluation guideline for antibiotics. These interventions are relevant and fit to several intervention strategies for antibiotic stewardship program in many international organizations such as participation of the multidisciplinary team, developing information technology to support antibiotic smart use, and communication. These interventions were prioritized for implementation over a 1-year period. Once the possibility of each activity or plan is set up, the proposed program could be applied and integrated into hospital policy after evaluating plans. Effectiveness of each intervention could be promoted to other community hospitals to promote and support antibiotic smart use.

Keywords: antibiotic, concept mapping, drug use evaluation, multidisciplinary teams

Procedia PDF Downloads 97

Authors: Farzad Khajavi, Farzaneh Jalilfar, Faranak Jafari, Leila Shokrani

Abstract:

Formulation of Ranolazine in the form of extended-release tablet in 500 mg dosage form was performed using Eudragit L100-55 as a retarding agent. Drug-release profiles were investigated in comparison with the reference Ranexa extended-release 500 mg tablet. F₂ and f₁ were calculated as 64.16 and 8.53, respectively. According to Peppas equation, the release of drug is controlled by diffusion (n=0.5). The tablets were put into accelerated stability conditions (40 °C, 75% humidity) for 3 and 6 months. The dissolution release profiles and other physical and chemical characteristics of the tablets confirmed the robustness and stability of formulation in this condition.

Keywords: drug release, extended-release tablet, ranolazine, stability

Procedia PDF Downloads 127

Authors: Alireza Jalalvand, Maryam Saleh, Somayeh Behjat Khatouni, Zahra Bahri Najafi, Foroozan Fatahinia, Narges Ismailzadeh, Behrokh Farahmand

Abstract:

Object: In the last two decades, the recent outbreak of Coronavirus (SARS-CoV-2) imposed a global pandemic in the world. Despite the increasing prevalence of the disease, there are no effective drugs to treat it. A suitable and rapid way to afford an effective drug and treat the global pandemic is a computational drug study. This study used molecular docking methods to examine the potential inhibition of over 50 antiviral drugs against three fundamental proteins of SARS-CoV-2. METHODS: Through a literature review, three important proteins (a key protease, RNA-dependent RNA polymerase (RdRp), and spike) were selected as drug targets. Three-dimensional (3D) structures of protease, spike, and RdRP proteins were obtained from the Protein Data Bank. Protein had minimal energy. Over 50 antiviral drugs were considered candidates for protein inhibition and their 3D structures were obtained from drug banks. The Autodock 4.2 software was used to define the molecular docking settings and run the algorithm. RESULTS: Five drugs, including indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, exhibited the highest inhibitory potency against all three proteins based on the binding energies and drug binding positions deduced from docking and hydrogen-bonding analysis. Conclusions: According to the results, among the drugs mentioned, saquinavir and lopinavir showed the highest inhibitory potency against all three proteins compared to other drugs. It may enter laboratory phase studies as a dual-drug treatment to inhibit SARS-CoV-2.

Keywords: covid-19, drug repositioning, molecular docking, lopinavir, saquinavir

Procedia PDF Downloads 61

Authors: Lynn Louis, Bor Shin Chee, Marion McAfee, Michael Nugent

Abstract:

This article aims to develop a sustained release formulation of microspheres containing the mTOR inhibitor Everolimus (EVR) using Polyvinyl alcohol (PVA) to enhance the bioavailability of the drug and to overcome poor solubility characteristics of Everolimus. This paper builds on recent work in the manufacture of microspheres using the sessile droplet technique by freezing the polymer-drug solution by suspending the droplets into pre-cooled ethanol vials immersed in liquid nitrogen. The spheres were subjected to 6 freezing cycles and 3 freezing cycles with thawing to obtain proper geometry, prevent aggregation, and achieve physical cross-linking. The prepared microspheres were characterised for surface morphology by SEM, where a 3-D porous structure was observed. The in vitro release studies showed a 62.17% release over 12.5 days, indicating a sustained release due to good encapsulation. This result is comparatively much more than the 49.06% release achieved within 4 hours from the solvent cast Everolimus film as a control with no freeze-thaw cycles performed. The solvent cast films were made in this work for comparison. A prolonged release of Everolimus using a polymer-based drug delivery system is essential to reach optimal therapeutic concentrations in treating SEGA tumours without systemic exposure. These results suggest that the combination of PVA and Everolimus via a rheological synergism enhanced the bioavailability of the hydrophobic drug Everolimus. Physical-chemical characterisation using DSC and FTIR analysis showed compatibility of the drug with the polymer, and the stability of the drug was maintained owing to the high molecular weight of the PVA. The obtained results indicate that the developed PVA/EVR microsphere is highly suitable as a potential drug delivery system with improved bioavailability in treating Subependymal Giant cell astrocytoma (SEGA).

Keywords: drug delivery system, everolimus, freeze-thaw cycles, polyvinyl alcohol

Procedia PDF Downloads 91

Authors: Nihad Karim Chowdhury, Mohammad Sanaullah Chowdhury, Muhammed Jamshed Alam Patwary, Rubel Biswas

Abstract:

In content-based 3D shape retrieval system, achieving high search performance has become an important research problem. A challenging aspect of this problem is to find an effective shape descriptor which can discriminate similar shapes adequately. To address this problem, we propose a new shape descriptor for 3D shape models by combining multi-resolution with multi-block center-symmetric local binary pattern operator. Given an arbitrary 3D shape, we first apply pose normalization, and generate a set of multi-viewed 2D rendered images. Second, we apply Gaussian multi-resolution filter to generate several levels of images from each of 2D rendered image. Then, overlapped sub-images are computed for each image level of a multi-resolution image. Our unique multi-block CS-LBP comes next. It allows the center to be composed of m-by-n rectangular pixels, instead of a single pixel. This process is repeated for all the 2D rendered images, derived from both ‘depth-buffer’ and ‘silhouette’ rendering. Finally, we concatenate all the features vectors into one dimensional histogram as our proposed 3D shape descriptor. Through several experiments, we demonstrate that our proposed 3D shape descriptor outperform the previous methods by using a benchmark dataset.

Keywords: 3D shape retrieval, 3D shape descriptor, CS-LBP, overlapped sub-images

Procedia PDF Downloads 420

Authors: H. R. Kelidari, M. Saeedi, J. Akbari, K. Morteza-Semnani, H. Valizadeh

Abstract:

Spironolactoe (SP) a synthetic steroid diuretic is a poorly water-soluble drug with a low and variable oral bioavailability. Regarding to the good solubility of SP in lipid materials, SP loaded Solid lipid nanoparticles (SP-SLNs) and nanostructured lipid carrier (SP-SLNs) were thus prepared in this work for accelerating dissolution of this drug. The SP loaded NLC with stearic acid (SA) as solid lipid and different Oleic Acid (OA) as liquid lipid content and SLN without OA were prepared by probe ultrasonication method. With increasing the percentage of OA from 0 to 30 wt% in SLN/NLC, the average size and zeta potential of nanoparticles felled down and entrapment efficiency (EE %) rose dramatically. The obtained micrograph particles showed pronounced spherical shape. Differential Scanning Calorimeter (DSC) measurements indicated that the presence of OA reduced the melting temperature and melting enthalpy of solid lipid in NLC structure. The results reflected good long-term stability of the nanoparticles and the measurements show that the particle size remains lower in NLC compare to SLN formulations, 6 months after production. Dissolution of SP-SLN and SP-NLC was about 5.1 and 7.2 times faster than raw drugs in 120 min respectively. These results indicated that the SP loaded NLC containing 70:30 solid lipid to liquid lipid ratio is a suitable carrier of SP with improved drug EE and steady drug release properties.

Keywords: drug release, lipid nanoparticles, spironolactone, stability

Procedia PDF Downloads 305

Authors: Fatma Susilawati Mohamad, Azizah Abdul Manaf, Fadhillah Ahmad, Zarina Mohamad, Wan Suryani Wan Awang

Abstract:

A simple and robust multi-class linear classifier is proposed and implemented. For a pair of classes of the linear boundary, a collection of segments of hyper planes created as perpendicular bisectors of line segments linking centroids of the classes or part of classes. Nearest Neighbor and Linear Discriminant Analysis are compared in the experiments to see the performances of each classifier in discriminating ripeness of oil palm. This paper proposes a multi-class linear classifier using Linear Discriminant Analysis (LDA) for image identification. Result proves that LDA is well capable in separating multi-class features for ripeness identification.

Keywords: multi-class, linear classifier, nearest neighbor, linear discriminant analysis

Procedia PDF Downloads 507

Authors: Assem I. El-Ansary

Abstract:

This paper illustrates the event-oriented Behavioral Pattern Analysis (BPA) modeling approach in developing an Multi-Agent Railway Control System (MARCS). The Event defined in BPA is a real-life conceptual entity that is unrelated to any implementation. The major contributions of this research are the Behavioral Pattern Analysis (BPA) modeling methodology, and the development of an interactive software tool (DECISION), which is based on a combination of the Analytic Hierarchy Process (AHP) and the ELECTRE Multi-Criteria Decision Making (MCDM) methods.

Keywords: analysis, multi-agent, railway control, modeling methodology, software modeling, event-oriented, behavioral pattern, use cases

Procedia PDF Downloads 516

Authors: Sean Hall

Abstract:

Nanosystems for drug delivery are not new; as medicines evolve, so too does the desire to deliver a more targeted, patient-compliant medicine. Though, historically the widespread use of nanosystems for drug delivery has been fouled by non-replicability, scalability, toxicity issues, and economics. Examples include steps of manufacture and thus cost to manufacture, toxicity for nanoparticle scaffolding, autoimmune response, and considerable technical expertise for small non-commercial yields. This, unfortunately, demonstrates the not-so-obvious chasm between science and drug formulation for regulatory approval. Regardless there is a general and global desire to improve the delivery of medicines, reduce potential side effect profiles, promote increased patient compliance, and increase and/or speed public access to medicine availability. In this paper, the author will discuss NanoCelle®, a nano-delivery platform that specifically addresses degradation and solubility issues that expands from fundamental micellar preparations. NanoCelle® has been deployed in several Australian listed medicines and is in use of several drug candidates across small molecules, with research endeavors now extending into large molecules. The author will discuss several research initiatives as they relate to NanoCelle® to demonstrate similarities seen in various drug substances; these examples will include both in vitro and in vivo work.

Keywords: NanoCelle®, micellar, degradation, solubility, toxicity

Procedia PDF Downloads 157

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

Abstract:

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

Keywords: emulgel, piroxicam, menthe oil, clove oil

Procedia PDF Downloads 434

Authors: Guoliang Lu, Changhou Lu, Xueyong Li

Abstract:

In action recognition, previous studies have demonstrated the effectiveness of using multiple features to improve the recognition performance. We focus on two practical issues: i) most studies use a direct way of concatenating/accumulating multi features to evaluate the similarity between two actions. This way could be too strong since each kind of feature can include different dimensions, quantities, etc; ii) in many studies, the employed classification methods lack of a flexible and effective mechanism to add new feature(s) into classification. In this paper, we explore an unified scheme based on recently-proposed multi-dimensional dynamic time warping (MD-DTW). Experiments demonstrated the scheme's effectiveness of combining multi-feature and the flexibility of adding new feature(s) to increase the recognition performance. In addition, the explored scheme also provides us an open architecture for using new advanced classification methods in the future to enhance action recognition.

Keywords: action recognition, multi features, dynamic time warping, feature combination

Procedia PDF Downloads 416

Authors: Zeynep Yazgan, Gökhan Aygün, Reyhan Çalışkan

Abstract:

Objective: Invasive fungal infections are a serious threat in terms of morbidity and mortality, especially in immunocompromised patients. The most frequently isolated agents are Aspergillus genus fungi, and sensitivity to azoles, which are the first choice in treatment, decreases. In our study, we aimed to investigate the use of the agar plate screening method as a fast, easy, and practical method in determining azole resistance in Aspergillus spp. species. Methods: Our study was conducted with 125 Aspergillus spp. isolates produced from various clinical samples. Aspergillus spp. isolates were identified by conventional methods and azole resistance was determined by gradient test and agar plate screening method. Broth microdilution method was applied to resistant isolates, and CypA-L98H and CypA-M220 mutations in the cyp51A gene were investigated. Results: In our study, 55 A. fumigatus complex (44%), 42 A. flavus (33.6%), 6 A. terreus (5%), 4 A. niger (3%) and 18 Aspergillus spp. (14%) were identified. With the gradient test method, resistance to VOR and POS was detected in 1 (1.8%) of A.fumigatus isolates, and resistance to ITR was detected in 3 (5.45%). With the agar plate method, 1 of the A.fumigatus isolates (1.8%) had VOR, ITR, POS, 1 of the A.terreus isolates (16.7%) had VOR, 1 of the A.niger isolates (25%) had ITR. Resistance to VOR and POS was detected in 2 Aspergillus spp. isolates (11%), and resistance to ITR was detected in 1 (5.6%). Sensitivity and specificity were determined as 100% for VOR and POS in A. fumigatus species, 33.3% and 100% for ITR, respectively, 100% for ITR in A. flavus species, and 100% for ITR and POS in A. terreus species. By broth microdilution method in 7 isolates in which resistance was detected by gradient test and/or agar plate screening method; 1 A.fumigatus resistant to ITR, VOR, POS, 2 A.fumigatus resistant to ITR, 2 Aspergillus spp. ITR, VOR, POS MICs were determined as 2µg/ml and 8µg/ml, 8µg/ml and >32µg/ml, 0.5µg/ml and 4µg/ml, respectively. CypA-L98H mutations were detected in 5 of these isolates, CypA-M220 mutations were detected in 6, and no mutation was detected in 1. CypA-L98H and CypA-M220 mutations were detected in 1 isolate for which resistance was not detected. Conclusion: The need for rapid antifungal susceptibility screening tests is increasing in the treatment of aspergillosis. Although the sensitivity of the agar plate method was determined to be 33.3% for A.fumigatus ITR in our study, its sensitivity and specificity were determined to be 100% for ITR, VOR, and POS in other species. The low sensitivity value detected for A.fumigatus showed that agar plate drug concentrations should be updated in accordance with the latest regulations of EUCAST guidelines. The CypA-L98H and CypA-M220 mutations detected in our study suggested that the distribution of azole resistance-related mutations in different regions in our country should be investigated. In conclusion, it is thought that the agar plate method, which can be easily applied to detect azole resistance, is a fast and practical method in routine use and can contribute to both the determination of effective treatment strategies and the generation of epidemiological data.

Keywords: Aspergillus, agar plate, azole resistance, cyp51A, cypA-L98H, cypA-M220

Procedia PDF Downloads 41

Authors: Yuhua Wang, Mu Li, Jinggen Liu

Abstract:

Aim: To investigate the different effects of heroin and milk in activating the corticostriatal system that plays a critical role in reward reinforcement learning. Methods: Male SD rats were trained daily for 15 d to self-administer heroin or milk tablets in a classic runway drug self-administration model. Immunohistochemical assay was used to quantify Arc protein expression in the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc), the dorsomedial striatum (DMS) and the ventrolateral striatum (VLS) in response to chronic self-administration of heroin or milk tablets. NMDA receptor antagonist MK801 (0.1 mg/kg) or dopamine D1 receptor antagonist SCH23390 (0.03 mg/kg) were intravenously injected at the same time as heroin was infused intravenously. Results: Runway training with heroin resulted in robust enhancement of Arc expression in the mPFC, the NAc and the DMS on d 1, 7, and 15, and in the VLS on d 1 and d 7. However, runway training with milk led to increased Arc expression in the mPFC, the NAc and the DMS only on d 7 and/or d 15 but not on d 1. Moreover, runway training with milk failed to induce increased Arc protein in the VLS. Both heroin-seeking behavior and Arc protein expression were blocked by MK801 or SCH23390 administration. Conclusion: The VLS is likely to be critically involved in drug-seeking behavior. The NMDA and D1 receptor-dependent Arc expression is important in drug-seeking behavior.

Keywords: arc, mesocorticolimbic system, drug rewarding behavior, NMDA receptor

Procedia PDF Downloads 361

Authors: Debalke Dale, Bezabh Geneta, Yohannes Amene, Yordanos Bergene, Mohammed Yimam

Abstract:

Background: A drug therapy problem (DTP) is an event or circumstance that involves drug therapies that actually or potentially interfere with the desired outcome and requires professional judgment to resolve. Heart failure is an emerging worldwide threat whose prevalence and health loss burden constantly increase, especially in the young and in low-to-middle-income countries. There is a lack of population-based incidence and prevalence of heart failure (HF) studies in sub-Saharan African countries, including Ethiopia. Objective: The aim of this study was designed to assess drug therapy problems and associated factors among patients with HF in the medical ward of Arba Minch General Hospital(AGH), Ethiopia, from June 5 to August 20, 2022. Methods: A retrospective cross-sectional study was conducted among 180 patients with HF who were admitted to the medical ward of AGH. Data were collected from patients' cards by using questionnaires. The data were categorized and analyzed by using SPSS version 25.0 software, and data were presented in tables and words based on the nature of the data. Result: Out of the total, 85 (57.6%) were females, and 113 (75.3%) patients were aged over fifty years. Of the 150 study participants, 86 (57.3%) patients had at least one DTP identified, and a total of 116 DTPs were identified, which is 0.77 DTPs per patient. The most common types of DTP were unnecessary drug therapy (32%), followed by the need for additional drug therapy (36%), and dose too low (15%). Patients who used polypharmacy were 5.86 (AOR) times more likely to develop DTPs than those who did not (95% CI = 1.625–16.536, P = 0.005), and patients with more co-morbid conditions developed 3.68 (AOR) times more DTPs than those who had fewer co-morbidities (95% CI = 1.28–10.5, P = 0.015). Conclusion: The results of this study indicated that drug therapy problems were common among medical ward patients with heart failure. These problems are adversely affecting the treatment outcomes of patients, so it requires the special attention of healthcare professionals to optimize them.

Keywords: heart failure, drug therapy problems, Arba Minch general hospital, Ethiopia

Procedia PDF Downloads 74

Authors: Humraaz Kaja, Kofi Mensah, Frasia Oosthuizen

Abstract:

Background and Aim: Vilazodone was approved in 2011 as an antidepressant to treat the major depressive disorder. As a relatively new drug, it is not clear if all adverse effects have been identified. The aim of this study was to review the adverse effects reported to the WHO Programme for International Drug Monitoring (PIDM) in order to add to the knowledge about the safety profile and adverse effects caused by vilazodone. Method: Data on adverse effects reported for vilazodone was obtained from the database VigiAccess managed by PIDM. Data was extracted from VigiAccess using Excel® and analyzed using descriptive statistics. The data collected was compared to the patient information leaflet (PIL) of Viibryd® and the FDA documents to determine adverse drug reactions reported post-marketing. Results: A total of 9708 adverse events had been recorded on VigiAccess, of which 6054 were not recorded on the PIL and the FDA approval document. Most of the reports were received from the Americas and were for adult women aged 45-64 years (24%, n=1059). The highest number of adverse events reported were for psychiatric events (19%; n=1889), followed by gastro-intestinal effects (18%; n=1839). Specific psychiatric disorders recorded included anxiety (316), depression (208), hallucination (168) and agitation (142). The systematic review confirmed several psychiatric adverse effects associated with the use of vilazodone. The findings of this study suggested that these common psychiatric adverse effects associated with the use of vilazodone were not known during the time of FDA approval of the drug and is not currently recorded in the patient information leaflet (PIL). Conclusions: In summary, this study found several adverse drug reactions not recorded in documents emanating from clinical trials pre-marketing. This highlights the importance of continued post-marketing surveillance of a drug, as well as the need for further studies on the psychiatric adverse events associated with vilazodone in order to improve the safety profile.

Keywords: adverse drug reactions, pharmacovigilance, post-marketing surveillance, vilazodone

Procedia PDF Downloads 89

Authors: Mia I. Allen, Bernard N. Johnson, Gagan Deep, Yixin Su, Sangeeta Singth, Ashish Kumar, , Michael A. Nader

Abstract:

With no FDA-approved treatments for cocaine use disorders (CUD), research has focused on the behavioral and neuropharmacological effects of cocaine in animal models, with the goal of identifying novel interventions. While the majority of people with CUD also use tobacco/nicotine, the majority of preclinical cocaine research does not include the co-use of nicotine. The present study examined nicotine and cocaine co-use under several conditions of intravenous drug self-administration in monkeys. In Experiment 1, male rhesus monkeys (N=3) self-administered cocaine (0.001-0.1 mg/kg/injection) alone and cocaine+nicotine (0.01-0.03 mg/kg/injection) under a progressive-ratio schedule of reinforcement. When nicotine was added to cocaine, there was a significant leftward shift and significant increase in peak break point. In Experiment 2, socially housed female and male cynomolgus monkeys (N=14) self-administered cocaine under a concurrent drug-vs-food choice schedule. Combining nicotine significantly decreased cocaine choice ED50 values (i.e., shifted the cocaine dose-response curve to the left) in females but not in males. There was no evidence of social rank differences. In delay discounting studies, the co-use of nicotine and cocaine required significantly larger delays to the preferred drug reinforcer to reallocate choice compared with cocaine alone. Overall, these results suggest drug interactions of nicotine and cocaine co-use is not simply a function of potency but rather a fundamentally distinctive condition that should be utilized to better understand the neuropharmacology of CUD and the evaluation of potential treatments.

Keywords: polydrug use, animal models, nonhuman primates, behavioral pharmacology, drug self-administration

Procedia PDF Downloads 57

Authors: Chuan Yin

Abstract:

Cancer stem cells (CSCs) represent a subpopulation of cancer cells that possess the characteristics associated with normal stem cells. CD133 is a phenotype of melanoma CSCs responsible for melanoma metastasis and drug resistance. Although adriamycin (ADR) is commonly used drug in melanoma therapy, but it is ineffective in the treatment of melanoma CSCs. In this study, we constructed CD133 antibody conjugated ADR immunoliposomes (ADR-Lip-CD133) to target CD133+ melanoma CSCs. The results showed that the immunoliposomes possessed a small particle size (~150 nm), high drug encapsulation efficiency (~90%). After 72 hr treatment on the WM266-4 melanoma tumorspheres, the IC50 values of the drug formulated in ADR-Lip-CD133, ADR-Lip (ADR liposomes) and ADR are found to be 24.42, 57.13 and 59.98 ng/ml respectively, suggesting that ADR-Lip-CD133 was more effective than ADR-Lip and ADR. Significantly, ADR-Lip-CD133 could almost completely abolish the tumorigenic ability of WM266-4 tumorspheres in vivo, and showed the best therapeutic effect in WM266-4 melanoma xenograft mice. It is noteworthy that ADR-Lip-CD133 could selectively kill CD133+ melanoma CSCs of WM266-4 cells both in vitro and in vivo. ADR-Lip-CD133 represent a potential approach in targeting and killing CD133+ melanoma CSCs.

Keywords: cancer stem cells, melanoma, immunoliposomes, CD133

Procedia PDF Downloads 357

Authors: Myung-Gon Yoon, Jung-Ho Moon, Tae Kwon Ha

Abstract:

This paper deals with a stabilization problem for multi-agent systems, when all agents in a multi-agent system receive the same broadcasting control signal and the controller can measure not each agent output but the sum of all agent outputs. It is analytically shown that when the sum of all agent outputs is bounded with a certain broadcasting controller for a given reference, each agent output is separately bounded:stabilization of the sum of agent outputs always results in the stability of every agent output. A numerical example is presented to illustrate our theoretic findings in this paper.

Keywords: broadcasting control, multi-agent system, transfer function, stabilization

Procedia PDF Downloads 358

Authors: Hak-Ryul Kim, Hyung-Geun Lee, Qi Long, Ching Hou

Abstract:

Structural modification of natural lipids via chemical reaction or microbial bioconversion can change their properties or even create novel functionalities. Enzymatic oxidation of lipids leading to formation of oxylipin is one of those modifications. Hydroxy fatty acids, one of those oxylipins have gained important attentions because of their structural and functional properties compared with other non-hydroxy fatty acids. Recently 7,10-dihydroxy-8(E)-octadecenoic acid (DOD) was produced with high yield from lipid-containing oleic acid by microbial conversion, and the further study confirmed that DOD contained strong antimicrobial activities against a broad range of microorganisms. In this study, we tried to modify DOD molecules by the enzymatic or physical reaction to create new functionality or to enhance the antimicrobial activity of DOD. After modification of DOD molecules by different ways, we confirmed that the antimicrobial activity of DOD was highly enhanced and presented strong antimicrobial activities against multidrug-resistant Staphylococcus aureus, suggesting that DOD and its derivatives can be used as efficient antimicrobial agents for medical and industrial applications.

Keywords: biocatalysis, antimicrobial agent, multidrug-resistant bacteria, vegetable oil

Procedia PDF Downloads 176

Authors: Raj Kumar, Prem Felix Siril

Abstract:

The poor aqueous solubility of many pharmaceutical drugs and potential drug candidates is a big challenge in drug development. Nanoformulation of such candidates is one of the major solutions for the delivery of such drugs. We initially developed the evaporation assisted solvent-antisolvent interaction (EASAI) method. EASAI method is use full to prepared nanoparticles of poor water soluble drugs with spherical morphology and particles size below 100 nm. However, to further improve the effect formulation to reduce number of dose and side effect it is important to control the delivery of drugs. However, many drug delivery systems are available. Among the many nano-drug carrier systems, solid lipid nanoparticles (SLNs) have many advantages over the others such as high biocompatibility, stability, non-toxicity and ability to achieve controlled release of drugs and drug targeting. SLNs can be administered through all existing routes due to high biocompatibility of lipids. SLNs are usually composed of lipid, surfactant and drug were encapsulated in lipid matrix. A number of non-steroidal anti-inflammatory drugs (NSAIDs) have poor bioavailability resulting from their poor aqueous solubility. In the present work, SLNs loaded with NSAIDs such as Nabumetone (NBT), Ketoprofen (KP) and Ibuprofen (IBP) were successfully prepared using different lipids and surfactants. We studied and optimized experimental parameters using a number of lipids, surfactants and NSAIDs. The effect of different experimental parameters such as lipid to surfactant ratio, volume of water, temperature, drug concentration and sonication time on the particles size of SLNs during the preparation using hot-melt sonication was studied. It was found that particles size was directly proportional to drug concentration and inversely proportional to surfactant concentration, volume of water added and temperature of water. SLNs prepared at optimized condition were characterized thoroughly by using different techniques such as dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR). We successfully prepared the SLN of below 220 nm using different lipids and surfactants combination. The drugs KP, NBT and IBP showed 74%, 69% and 53% percentage of entrapment efficiency with drug loading of 2%, 7% and 6% respectively in SLNs of Campul GMS 50K and Gelucire 50/13. In-vitro drug release profile of drug loaded SLNs is shown that nearly 100% of drug was release in 6 h.

Keywords: nanoparticles, delivery, solid lipid nanoparticles, hot-melt sonication, poor water soluble drugs, solubility, bioavailability

Procedia PDF Downloads 290

Authors: Danilo F. Rodrigues, Hérida Regina N. Salgado

Abstract:

Introduction: The emergence of resistant microorganisms to a large number of clinically approved antimicrobials has been increasing, which restrict the options for the treatment of bacterial infections. As a strategy, drugs with high antimicrobial activities are in evidence. Stands out a class of antimicrobial, the cephalosporins, having as fourth generation cefepime (CEF) a semi-synthetic product which has activity against various Gram-positive bacteria (e.g. oxacillin resistant Staphylococcus aureus) and Gram-negative (e.g. Pseudomonas aeruginosa) aerobic. There are few studies in the literature regarding the development of microbiological methodologies for the analysis of this antimicrobial, so researches in this area are highly relevant to optimize the analysis of this drug in the industry and ensure the quality of the marketed product. The development of microbiological methods for the analysis of antimicrobials has gained strength in recent years and has been highlighted in relation to physicochemical methods, especially because they make possible to determine the bioactivity of the drug against a microorganism. In this context, the aim of this work was the development and validation of a microbiological method for quantitative analysis of CEF in powder lyophilized for injectable solution by turbidimetric assay. Method: For performing the method, Staphylococcus aureus ATCC 6538 IAL 2082 was used as the test microorganism and the culture medium chosen was the Casoy broth. The test was performed using temperature control (35.0 °C ± 2.0 °C) and incubated for 4 hours in shaker. The readings of the results were made at a wavelength of 530 nm through a spectrophotometer. The turbidimetric microbiological method was validated by determining the following parameters: linearity, precision (repeatability and intermediate precision), accuracy and robustness, according to ICH guidelines. Results and discussion: Among the parameters evaluated for method validation, the linearity showed results suitable for both statistical analyses as the correlation coefficients (r) that went 0.9990 for CEF reference standard and 0.9997 for CEF sample. The precision presented the following values 1.86% (intraday), 0.84% (interday) and 0.71% (between analyst). The accuracy of the method has been proven through the recovery test where the mean value obtained was 99.92%. The robustness was verified by the parameters changing volume of culture medium, brand of culture medium, incubation time in shaker and wavelength. The potency of CEF present in the samples of lyophilized powder for injectable solution was 102.46%. Conclusion: The turbidimetric microbiological method proposed for quantification of CEF in lyophilized powder for solution for injectable showed being fast, linear, precise, accurate and robust, being in accordance with all the requirements, which can be used in routine analysis of quality control in the pharmaceutical industry as an option for microbiological analysis.

Keywords: cefepime hydrochloride, quality control, turbidimetric assay, validation

Procedia PDF Downloads 337

Authors: Dau Lal Bohra, Sradha Vyas

Abstract:

Bird species are already showing climate-related changes in the dates they migrate and breed, and in the timing of other key life-history events. Treats of feeding managements raptors have performed important ecological, traditional and aesthetic functions throughout the Indian subcontinent. The declines in India result from elevated adult and juvenile mortality, and low breeding success. The widespread and rapid pattern of declines, i.e. in all areas irrespective of habitat or protection status suggest that persecution through shooting or poisoning, whilst important at a local scale, are unlikely to have caused the declines. A mass killing of several species of vultures in the Indian subcontinent over the last two decades is largely blamed on the presence of a drug. Veterinary diclofenac caused an unprecedented decline in South Asia’s Gyps vulture populations, with some species declining by more than 97% between 1992 and 2007. Veterinary diclofenac causes renal failure in vultures, and killed tens of millions of such birds in the Indian sub-continent. The drug was finally banned there for veterinary purposes in 2006. This drug is now ‘a global problem’ threatening many vulnerable birds of prey. Recently, stappe eagles are also susceptible to veterinary diclofenac, effectively increasing the potential threat level, and the risks for European biodiversity. Steppe eagles are closely related with golden eagles (Aquila chrysaetus), imperial eagles (Aquila heliaca) and Spanish imperial eagles (Aquila adalberti), and all these species scavenge opportunistically on carcasses throughout their range. The Spanish imperial eagle, considered Vulnerable at global level, is now particularly at risk, due to the availability of diclofenac in Spain. These findings strengthen the case for banning veterinary diclofenac across. From year 2011 to 2014 more than 300 hundred birds dead in jorbeer, Bikaner. Now, with unequivocal evidence that this veterinary drug can cause a much wider impact on Europe´s biodiversity, it is time for action – please ban diclofenac human brand also in multi-dose vial from market.

Keywords: mortility, prey of birds, diclofenac, Rajasthan

Procedia PDF Downloads 348

Authors: Assem El-Ansary

Abstract:

This paper illustrates the event-oriented Behavioral Pattern Analysis (BPA) modeling approach in developing an Multi-Agent TeleRobotic Security Control System (MTSCS). The event defined in BPA is a real-life conceptual entity that is unrelated to any implementation. The major contributions of this research are the Behavioral Pattern Analysis (BPA) modeling methodology, and the development of an interactive software tool (DECISION), which is based on a combination of the Analytic Hierarchy Process (AHP) and the ELECTRE Multi-Criteria Decision Making (MCDM) methods.

Keywords: analysis, multi-agent, TeleRobotics control, security, modeling methodology, software modeling, event-oriented, behavioral pattern, use cases

Procedia PDF Downloads 412