Search results for: drug therapy problem

Authors: Agung A. Ginanjar, Lilitasari, Indra Prasetya, Rizal R. Hanif, Yusrina Rismandini, Atina Hussaana, Nurita P. Sari

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Hyperlipidemia is an increase of lipids and cholesterol in the blood that causes the formation of atherosklerosis. The recent pharmacological therapy nowadays is statin. Many Indonesian people use of medicinal plants. There are several medical plants that people always use to cure hyperlipidemia such as bulbs onion sabrang, areca nuts, and seed of fenugreek. Most people often use a combination therapy of conventional medicine and herbs to achieve the desired therapeutic effect of combination therapy. The use of combination therapy might cause the interaction of pharmacodynamic from those medicines so that it influences the pharmacological effect of one of medicine. The aim of this study is to know the interaction of simvastatin and a cholesterol-lowering herb seen in rats pharmacodynamic simvastatin phase. This research used post-test only controlled group design. Analysis of statistical data normality and homogenity were tested by Kolmogorov Smirnov. The ANOVA test is used when the data is obtained homogeneous but if it is found that the data are not homogeneous then kruskal-wallis test is used. Normal (63.196 mg/dl), negative (70.604 mg/dl), positive (62.512 mg/dl), areca nuts (56.564 mg/dl), fenugreek seed (47.538 ,g/dl), onion sabrang (62.312 mg/dl). The results prove that the combination of herbs and simvastatin did not have a significant difference (P>0,05). The conclusion of this study is that the combination of simvastatin and a cholesterol-lowering herb can cause some pharmacodynamic interactions such as a synergistic effect, antagonist, and a powerful additive, so that combination therapy is not more effective than single simvastatin therapy. The use of the combination therapy is not given in the same time. It would be better if there are some period of time when the combination therapy is applied.

Keywords: onion bulb sabrang, areca nuts, seed of fenugreek, interaction medicine, hyperlipidemia

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Authors: Norma Binti Alias, Che Rahim Che The, Norfarizan Mohd Said, Sakinah Abdul Hanan, Akhtar Ali

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This paper discusses on the transportation of magnetic drug targeting through blood within vessels, tissues and cells. There are three integrated mathematical models to be discussed and analyze the concentration of drug and blood flow through magnetic nanoparticles. The cell therapy brought advancement in the field of nanotechnology to fight against the tumors. The systematic therapeutic effect of Single Cells can reduce the growth of cancer tissue. The process of this nanoscale phenomena system is able to measure and to model, by identifying some parameters and applying fundamental principles of mathematical modeling and simulation. The mathematical modeling of single cell growth depends on three types of cell densities such as proliferative, quiescent and necrotic cells. The aim of this paper is to enhance the simulation of three types of models. The first model represents the transport of drugs by coupled partial differential equations (PDEs) with 3D parabolic type in a cylindrical coordinate system. This model is integrated by Non-Newtonian flow equations, leading to blood liquid flow as the medium for transportation system and the magnetic force on the magnetic nanoparticles. The interaction between the magnetic force on drug with magnetic properties produces induced currents and the applied magnetic field yields forces with tend to move slowly the movement of blood and bring the drug to the cancer cells. The devices of nanoscale allow the drug to discharge the blood vessels and even spread out through the tissue and access to the cancer cells. The second model is the transport of drug nanoparticles from the vascular system to a single cell. The treatment of the vascular system encounters some parameter identification such as magnetic nanoparticle targeted delivery, blood flow, momentum transport, density and viscosity for drug and blood medium, intensity of magnetic fields and the radius of the capillary. Based on two discretization techniques, finite difference method (FDM) and finite element method (FEM), the set of integrated models are transformed into a series of grid points to get a large system of equations. The third model is a single cell density model involving the three sets of first order PDEs equations for proliferating, quiescent and necrotic cells change over time and space in Cartesian coordinate which regulates under different rates of nutrients consumptions. The model presents the proliferative and quiescent cell growth depends on some parameter changes and the necrotic cells emerged as the tumor core. Some numerical schemes for solving the system of equations are compared and analyzed. Simulation and computation of the discretized model are supported by Matlab and C programming languages on a single processing unit. Some numerical results and analysis of the algorithms are presented in terms of informative presentation of tables, multiple graph and multidimensional visualization. As a conclusion, the integrated of three types mathematical modeling and the comparison of numerical performance indicates that the superior tool and analysis for solving the complete set of magnetic drug delivery system which give significant effects on the growth of the targeted cancer cell.

Keywords: mathematical modeling, visualization, PDE models, magnetic nanoparticle drug delivery model, drug release model, single cell effects, avascular tumor growth, numerical analysis

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Authors: Sunil K. Jena, Sanjaya K. Samal, Mahesh Chand, Abhay T. Sangamwar

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Tamoxifen (TMX) and its analogues are approved as a first line therapy for the treatment of estrogen receptor-positive tumors. However, clinical development of TMX has been hampered by its low bioavailability and severe hepatotoxicity. Herein, we attempt to design a new drug delivery vehicle that could enhance the pharmacokinetic performance of TMX. Initially, high-molecular weight carboxymethyl chitosan was hydrolyzed to low-molecular weight carboxymethyl chitosan (LMW CMC) with hydrogen peroxide under the catalysis of phosphotungstic acid. Amphiphilic block copolymers of LMW CMC were synthesized via amidation reaction between the carboxyl group of α-tocopherol succinate (TS) and an amine group of LMW CMC. These amphiphilic block copolymers were self-assembled to nanosize core-shell-structural micelles in the aqueous medium. The critical micelle concentration (CMC) decreased with the increasing substitution of TS on LMW CMC, which ranged from 1.58 × 10-6 to 7.94 × 10-8 g/mL. Maximum TMX loading up to 8.08 ± 0.98% was achieved with Cmc-TS4.5 (TMX/Cmc-TS4.5 with 1:8 weight ratio). Both blank and TMX-loaded polymeric micelles (TMX-PM) of Cmc-TS4.5 exhibits spherical shape with the particle size below 200 nm. TMX-PM has been found to be stable in the gastrointestinal conditions and released only 44.5% of the total drug content by the first 72 h in simulated gastric fluid (SGF), pH 1.2. However, the presence of pepsin does not significantly increased the TMX release in SGF, pH 1.2, released only about 46.2% by the first 72 h suggesting its inability to cleave the peptide bond. In contrast, the release of TMX from TMX-PM4.5 in SIF, pH 6.8 (without pancreatin) was slow and sustained, released only about 10.43% of the total drug content within the first 30 min and nearly about 12.41% by the first 72 h. The presence of pancreatin in SIF, pH 6.8 led to an improvement in drug release. About 28.09% of incorporated TMX was released in the presence of pancreatin in 72 h. A cytotoxicity study demonstrated that TMX-PM exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. Pharmacokinetic studies on Sprague-Dawley rats revealed a remarkable increase in oral bioavailability (1.87-fold) with significant (p < 0.0001) enhancement in AUC0-72 h, t1/2 and MRT of TMX-PM4.5 than that of TMX-suspension. Thus, the results suggested that CMC-TS micelles are a promising carrier for TMX delivery.

Keywords: carboxymethyl chitosan, d-α-tocopherol succinate, pharmacokinetic, polymeric micelles, tamoxifen

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Authors: Kaveh Qaderi Bagajan, Osman Khanahmadi, Ziba Mamaghani Chaharborj, Majid Chenaparchi

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The purpose of this study is to investigate the efficacy of the solution-focused brief therapy on improving the psychological wellbeing of family supervisor woman. This study has been carried out by semi-experimental method and in the form of pre-test, post-test performance on two groups (experimental and control), so that one sample group of 30 individuals was randomly achieved and were randomly divided in two groups of experimental (n=15) and control (n=15). To collect data, Ryff scale psychological wellbeing was used. After conducting pre-test (RSPWB) for two experimental and control groups, Solution-focused brief therapy interference was conducted on the experimental group during five two-hour sessions. Finally, Ryff scale psychological wellbeing was reused for the two groups as post-test and achieved outcomes that were analyzed using covariance. The results indicated that the significant increase of average marks of the experimental group in psychological wellbeing had better function than that of the control group. Finally, solution-focused brief therapy for improving psychological well-being of family supervisor women has a suitable capability and could be used in this way.

Keywords: solution-focused brief therapy, short-term therapy, family supervisor women, psychological well-being

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Authors: Venkata Srikanth Meka, Nur Arthirah Binti Ahmad Tarmizi Tan, Muhammad Syahmi Bin Md Nazir, Adinarayana Gorajana, Senthil Rajan Dharmalingam

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Biphasic drug delivery systems are designed to release drug at two different rates, either fast/prolonged or prolonged/fast. A fast/prolonged release system provides a burst drug release at initial stage followed by a slow release over a prolonged period of time and in case of prolonged/fast release system, the release pattern is vice versa. Terminalia catappa gum (TCG) is a natural polymer and was successfully proven as a novel pharmaceutical excipient. The main objective of the present research is to investigate the applicability of natural polymer, Terminalia catappa gum in the design of oral biphasic drug delivery system in the form of mini tablets by using a model drug, buspirone HCl. This investigation aims to produce a biphasic release drug delivery system of buspirone by combining immediate release and prolonged release mini tablets into a capsule. For immediate release mini tablets, a dose of 4.5 mg buspirone was prepared by varying the concentration of superdisintegrant; crospovidone. On the other hand, prolonged release mini tablets were produced by using different concentrations of the natural polymer; TCG with a buspirone dose of 3mg. All mini tablets were characterized for weight variation, hardness, friability, disintegration, content uniformity and dissolution studies. The optimized formulations of immediate and prolonged release mini tablets were finally combined in a capsule and was evaluated for release studies. FTIR and DSC studies were conducted to study the drug-polymer interaction. All formulations of immediate release and prolonged release mini tablets were passed all the in-process quality control tests according to US Pharmacopoeia. The disintegration time of immediate release mini tablets of different formulations was varied from 2-6 min, and maximum drug release was achieved in lesser than 60 min. Whereas prolonged release mini tablets made with TCG have shown good drug retarding properties. Formulations were controlled for about 4-10 hrs with varying concentration of TCG. As the concentration of TCG increased, the drug release retarding property also increased. The optimised mini tablets were packed in capsules and were evaluated for the release mechanism. The capsule dosage form has clearly exhibited the biphasic release of buspirone, indicating that TCG is a suitable natural polymer for this study. FTIR and DSC studies proved that there was no interaction between the drug and polymer. Based on the above positive results, it can be concluded that TCG is a suitable polymer for the biphasic drug delivery systems.

Keywords: Terminalia catappa gum, biphasic release, mini tablets, tablet in capsule, natural polymers

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Authors: Sharjeel Abid, Tanveer Hussain, Ahsan Nazir, Abdul Zahir, Nabyl Khenoussi

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Localized application of drug has various advantages and fewer side effects as compared with other methods. Burn patients suffer from swear pain and the major aspects that are considered for burn victims include pain and infection management. Nano-fibers (NFs) loaded with drug, applied on local wound area, can solve these problems. Therefore, this study dealt with the fabrication of drug loaded NFs for better pain management. Two layers of NFs were fabricated with different drugs. Contact layer was loaded with Gabapentin (a nerve painkiller) and the second layer with acetaminophen. The fabricated dressing was characterized using scanning electron microscope, Fourier Transform Infrared Spectroscopy, X-Ray Diffraction and UV-Vis Spectroscopy. The double layered based NFs dressing was designed to have both initial burst release followed by slow release to cope with pain for two days. The fabricated nanofibers showed diameter < 300 nm. The liquid absorption capacity of the NFs was also checked to deal with the exudate. The fabricated double layered dressing with dual drug loading and release showed promising results that could be used for dealing pain in burn victims. It was observed that by the addition of drug, the size of nanofibers was reduced, on the other hand, the crystallinity %age was increased, and liquid absorption decreased. The combination of fast nerve pain killer release followed by slow release of non-steroidal anti-inflammatory drug could be a good tool to reduce pain in a more secure manner with fewer side effects.

Keywords: pain management, burn wounds, nano-fibers, controlled drug release

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Authors: Anshu Gupta, Charu Gupta

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Background: Punjab, a border state in India has achieved notoriety world over for its drug abuse problem. People right from school kids to elderly are hooked to drugs. This pattern of substance abuse is prevalent in both cities and villages alike. Excess of younger population in India has further aggravated the situation. It is feared that the benefits of India’s economic growth may well be negated by the rising substance abuse especially in this part of the country. It is quite evident that the pattern of substance abuse tends to change over time which is an impediment in the formulation of effective strategies to tackle this issue. Aim: Purpose of the study was to ascertain the change in the pattern of drug abuse for two consecutive years in the out patient department (OPD) population. Method: The study population comprised of all the patients reporting for deaddiction to the psychiatry outpatient department over a period of twelve months for two consecutive years. All the patients were evaluated by the International Classification of Diseases; 10 criteria for substance abuse/dependence. Results: A considerably high prevalence of substance abuse was present in the Indian population. In general, there was an increase in prevalence from first to the second year, especially among the female population. Increase in prevalence of substance abuse appeared to be more prominent among the younger age group of both the sexes. A significant increase in intravenous drug abuse was observed. Peer pressure and parental imitation were the major factors fueling substance abuse. Precipitation or fear of withdrawal symptoms was the major factor preventing abstinence. Substance abuse had a significant effect on the health and interpersonal relations of these patients. Summary/Conclusion: Drug abuse and addiction are on the rise throughout India. Changing cultural values, increasing economic stress and dwindling supportive bonds appear to be leading to initiation of substance abuse. Need of the hour is to formulate a comprehensive strategy to bring about an overall reduction in the use of drugs.

Keywords: deaddiction, peer pressure, parental imitation, substance abuse/dependance

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Authors: S. S. Patil, R. M. Mhetre, S. V. Patil

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Lisinopril is an angiotensin converting enzyme inhibitor used in the treatment of hypertension and heart failure in prophylactic treatment after myocardial infarction and in diabetic nephropathy. However, it is very poorly absorbed from gastro-intestinal tract. Intranasal administration is an ideal alternative to the parenteral route for systemic drug delivery. Formulating multiparticulate system with mucoadhesive polymers provide a significant increase in the nasal residence time. The aim of the present approach was to overcome the drawbacks of the conventional dosage forms of lisinopril by formulating intranasal microspheres with Carbopol 974P NF and HPMC K4 M along with film forming polymer ethyl cellulose.The microspheres were prepared by emulsion solvent evaporation method. The prepared microspheres were characterized for encapsulation efficiency, drug loading, particle size, and surface morphology, degree of swelling, ex vivo mucoadhesion, drug release, ex vivo diffusion studies. All formulations has shown entrapment efficiency between 80 to more than 95%, mucoadhesion was more than 80 % and drug release up to 90 %. Ex vivo studies revealed tht the improved bioavailability of drug compared to oral drug administration. Both in vitro and in vivo studies conclude that combination of Carbopol and HPMC based microspheres shown better results than single carbopol based microspheres for the delivery of lisinopril.

Keywords: microspheres, lisinopril, nasal delivery, solvent evaporation method

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Authors: Rashi Rajput, Manisha Singh

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Escitalopram oxalate (ETP), an FDA approved antidepressant drug from the category of SSRI (selective serotonin reuptake inhibitor) and is used in treatment of general anxiety disorder (GAD), major depressive disorder (MDD).When taken orally, it is metabolized to S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT) in the liver with the help of enzymes CYP2C19, CYP3A4 and CYP2D6. Hence, causing side effects such as dizziness, fast or irregular heartbeat, headache, nausea etc. Therefore, targeted and sustained drug delivery will be a helpful tool for increasing its efficacy and reducing side effects. The present study is designed for formulating mucoadhesive nanoparticle formulation for the same Escitalopram loaded polymeric nanoparticles were prepared by ionic gelation method and characterization of the optimised formulation was done by zeta average particle size (93.63nm), zeta potential (-1.89mV), TEM (range of 60nm to 115nm) analysis also confirms nanometric size range of the drug loaded nanoparticles along with polydispersibility index of 0.117. In this research, we have studied the in vitro drug release profile for ETP nanoparticles, through a semi permeable dialysis membrane. The three important characteristics affecting the drug release behaviour were – particle size, ionic strength and morphology of the optimised nanoparticles. The data showed that on increasing the particle size of the drug loaded nanoparticles, the initial burst was reduced which was comparatively higher in drug. Whereas, the formulation with 1mg/ml chitosan in 1.5mg/ml tripolyphosphate solution showed steady release over the entire period of drug release. Then this data was further validated through mathematical modelling to establish the mechanism of drug release kinetics, which showed a typical linear diffusion profile in optimised ETP loaded nanoparticles.

Keywords: ionic gelation, mucoadhesive nanoparticle, semi-permeable dialysis membrane, zeta potential

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Authors: Beata Jackowska-Zduniak

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We formulate and analyze a mathematical model describing dynamics of cancer growth under the influence of radiation therapy. The effect of this type of therapy is considered as an additional equation of discussed model. Numerical simulations show that delay, which is added to ordinary differential equations and represent time needed for transformation from one type of cells to the other one, affects the behavior of the system. The validation and verification of proposed model is based on medical data. Analytical results are illustrated by numerical examples of the model dynamics. The model is able to reconstruct dynamics of treatment of cancer and may be used to determine the most effective treatment regimen based on the study of the behavior of individual treatment protocols.

Keywords: mathematical modeling, numerical simulation, ordinary differential equations, radiation therapy

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Authors: Jichan Jang

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Mycobacterium abscessus is a rapidly growing life-threatening mycobacterium with multiple drug-resistance mechanisms. In this study, we screened the library to identify active molecules targeting Mycobacterium abscessus using resazurin live/dead assays. In this screening assay, the Z-factor was 0.7, as an indication of the statistical confidence of the assay. A cut-off of 80% growth inhibition in the screening resulted in the identification of four different compounds at a single concentration (20 μM). Dose-response curves identified three different hit candidates, which generated good inhibitory curves. All hit candidates were expected to have different molecular targets. Thus, we found that compound X, identified, may be a promising candidate in the M. abscessus drug discovery pipeline.

Keywords: Mycobacterium abscessus, antibiotics, drug discovery, emerging Pathogen

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Authors: Abdelhadi Adam Salih Denei

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Silver nanoparticles (AgNPs) have been used in cancer therapy, and the area of nanomedicine has made unheard-of strides in recent years. A thorough summary of the development and assessment of AgNPs for their possible use in the fight against cancer is the goal of this review. Targeted delivery methods have been designed to optimise therapeutic efficacy by using AgNPs' distinct physicochemical features, such as their size, shape, and surface chemistry. Firstly, the study provides an overview of the several synthesis routes—both chemical and green—that are used to create AgNPs. Natural extracts and biomolecules are used in green synthesis techniques, which are becoming more and more popular since they are biocompatible and environmentally benign. It is next described how synthesis factors affect the physicochemical properties of AgNPs, emphasising how crucial it is to modify these parameters for particular therapeutic uses. An extensive analysis is conducted on the anticancer potential of AgNPs, emphasising their capacity to trigger apoptosis, impede angiogenesis, and alter cellular signalling pathways. The analysis also investigates the potential benefits of combining AgNPs with currently used cancer treatment techniques, including radiation and chemotherapy. AgNPs' safety profile for use in clinical settings is clarified by a comprehensive evaluation of their cytotoxicity and biocompatibility.

Keywords: silver nanoparticles, cancer, nanocarrier system, targeted delivery

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Authors: Azza H. El-Medany, Hanan H. Hagar, Omnia A. Nayel, Jamila H. El-Medany

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In search for drugs that can target cancer cell micro-environment in as much as being able to halt malignant cellular transformation, the natural dietary phytochemical curcumin was currently assessed in DMH-induced colorectal cancer rat model. The study enrolled 50 animals divided into a control group (n=10) and DMH-induced colorectal cancer control group (n=20) (20mg/kg-body weight for 28 weeks) versus curcumin-treated group (n=20) (160 mg/kg suspension daily oral for further 8 weeks). Treatment by curcumin succeeded to significantly decrease the percent of ACF and tended to normalize back the histological changes retrieved in adenomatous and stromal cells induced by DMH. The drug also significantly elevated GSH and significantly reduced most of the accompanying biochemical elevations (namely MDA, TNF-α, TGF-β and COX2) observed in colonic carcinomatous tissue, induced by DMH, thus succeeding to revert that of MDA, COX2 and TGF-β back to near normal as justified by being non-significantly altered as compared to normal controls. The only exception was PAF that was insignificantly altered by the drug. When taken together, it could be concluded that curcumin possess the potentiality to halt some of the orchestrated cross-talk between cancerous transformation and its micro-environmental niche that contributes to cancer initiation, progression and metastasis in this experimental cancer colon model. Envisioning these merits to a drug with already known safety preferentiality, awaits final results of current ongoing clinical trials, before curcumin can be added to the new therapeutic armamentarium of anticancer therapy.

Keywords: curcumin, dimethyl hydralazine, aberrant crypt foci, malondialdehyde, reduced glutathione, cyclooxygenase-2, tumour necrosis factor-alpha, transforming growth factor-beta, platelet activating factor

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Authors: Nik Siti Hanifah Nik Ahmad

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This research discuss about teaching cupping therapy or hijama by using an online 3D Virtual Learning Environment. The experimental platform was using of flash and Second Life as 2D and 3D comparison. 81 samples have been used in three experiments with 21 in the first and 30 in each second and third. The design of the presentation was tested in five categories such as effectiveness, ease of use, efficacy, aesthetic and users’ satisfaction. The results from three experiments had shown promising outcome for usage of the technique to be implement in teaching Cupping Therapy as well as other alternative or conventional medicine knowledge especially for training.

Keywords: medical and health, cupping therapy or hijama, second life, online 3D VLE, virtual worlds

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Authors: Hui-Yi Wang, Shu-Mei Chen, Mei-Fang Liu

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Background and purpose: Providing clinical experience in medical education is an important discipline method where students can gradually apply their academic knowledge to clinical situations. The purpose of this study was to establish self-assessment questionnaires for students to assess their learning outcomes for two fields of physical therapy, orthopedic physical therapy, and pediatric physical therapy, in a clinical fieldwork course. Methods: The questionnaires were developed based on the core competence dimensions of the course. The content validity of the questionnaires was evaluated and established by expert meetings. Among the third-year undergraduate students who took the clinical fieldwork course, there were 49 students participated in this study. Teachers arranged for the students to study two professional fields, and each professional field conducted a three-week clinical lesson. The students filled out the self-assessment questionnaires before and after each three-week lesson. Results: The self-assessment questionnaires were established by expert meetings that there were six core competency dimensions in each of the two fields, with 20 and 21 item-questions, respectively. After each three-week clinical fieldwork, the self-rating scores in each core competency dimension were higher when compared to those before the course, indicating having better clinical abilities after the lessons. The best self-rating scores were the dimension of attitude and humanistic literacy, and the two lower scores were the dimensions of professional knowledge and skills and problem-solving critical thinking. Conclusions: This study developed questionnaires for clinical fieldwork courses to reflect students' learning outcomes, including the performance of professional knowledge, practice skills, and professional attitudes. The use of self-assessment of learning performance can help students build up their reflective competencies. Teachers can guide students to pay attention to the performance of abilities in each core dimension to enhance the effectiveness of learning through self-reflection and improvement.

Keywords: physical therapy, clinical fieldwork course, learning outcomes assessment, medical education, self-reflection ability

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Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

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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.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

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Authors: Esra Turker, Umit Hakan Yildiz, Ahu Arslan Yildiz

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The key of regenerative medicine is mimicking natural three dimensional (3D) microenvironment of tissues by utilizing appropriate biomaterials. In this study, a synthetic biodegradable polymer; poly (L-lactide-co-ε-caprolactone) (PLLCL) and a natural polymer; collagen was used to mimic the biochemical structure of the natural extracellular matrix (ECM), and by means of electrospinning technique the real physical structure of ECM has mimicked. PLLCL/Collagen biocomposite scaffolds enables cell attachment, proliferation and nutrient transport through fabrication of micro to nanometer scale nanofibers. Biocomposite materials are commonly preferred due to limitations of physical and biocompatible properties of natural and synthetic materials. Combination of both materials improves the strength, degradation and biocompatibility of scaffold. Literature studies have shown that collagen is mostly solved with heavy chemicals, which is not suitable for cell culturing. To overcome this problem, a new approach has been developed in this study where polyvinylpyrrolidone (PVP) is used as co-electrospinning agent. PVP is preferred due to its water solubility, so PLLCL/collagen biocomposite scaffold can be easily and rapidly produced. Hydrolytic and enzymatic biodegradation as well as mechanical strength of scaffolds were examined in vitro. Cell adhesion, proliferation and cell morphology characterization studies have been performed as well. Further, on-chip drug screening analysis has been performed over 3D tumor models. Overall, the developed biocomposite scaffold was used for 3D tumor model formation and obtained results confirmed that developed model could be used for drug screening studies to predict clinical efficacy of a drug.

Keywords: biomaterials, 3D cell culture, drug screening, electrospinning, lab-on-a-chip, tissue engineering

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Authors: Umairah Natasya Binti Mohd Omeershffudin, Suresh Kumar

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Klebsiella pneumoniae, a Gram-negative enteric bacterium that causes nosocomial and urinary tract infections. Particular concern is the global emergence of multidrug-resistant (MDR) strains of Klebsiella pneumoniae. Characterization of antibiotic resistance determinants at the genomic level plays a critical role in understanding, and potentially controlling, the spread of multidrug-resistant (MDR) pathogens. In this study, drug-resistant Klebsiella pneumoniae strain 825795-1 was investigated with extensive computational approaches aimed at identifying novel drug targets among hypothetical proteins. We have analyzed 1099 hypothetical proteins available in genome. We have used in-silico genome subtraction methodology to design potential and pathogen-specific drug targets against Klebsiella pneumoniae. We employed bioinformatics tools to subtract the strain-specific paralogous and host-specific homologous sequences from the bacterial proteome. The sorted 645 proteins were further refined to identify the essential genes in the pathogenic bacterium using the database of essential genes (DEG). We found 135 unique essential proteins in the target proteome that could be utilized as novel targets to design newer drugs. Further, we identified 49 cytoplasmic protein as potential drug targets through sub-cellular localization prediction. Further, we investigated these proteins in the DrugBank databases, and 11 of the unique essential proteins showed druggability according to the FDA approved drug bank databases with diverse broad-spectrum property. The results of this study will facilitate discovery of new drugs against Klebsiella pneumoniae.

Keywords: pneumonia, drug target, hypothetical protein, subtractive genomics

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Authors: Umme Hani, Mohammed Rahmatulla, Mohammed Ghazwani, Ali Alqahtani, Yahya Alhamhoom

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Background and introduction: Neratinib is a potent anticancer drug used for the treatment of breast cancer. It is poorly soluble at higher pH, which tends to minimize the therapeutic effects in the lower gastrointestinal tract (GIT) leading to poor bioavailability. An attempt has been made to prepare and develop a gastro-retentive system of Neratinib to improve the drug bioavailability in the GIT by enhancing the gastric retention time. Materials and methods: In the present study a three-factor at two-level (23) factorial design based optimization was used to inspect the effects of three independent variables (factors) such as sodium alginate (A), sodium bicarbonate (B) and sodium citrate (C) on the dependent variables like in vitro gelation, in vitro floating, water uptake and percentage drug release. Results: All the formulations showed pH in the range 6.7 ±0.25 to 7.4 ±0.24, percentage drug content was observed to be 96.3±0.27 to 99.5 ±0.28%, in vitro gelation observed as gelation immediate remains for an extended period. Percentage of water uptake was in the range between 9.01±0.15 to 31.01±0.25%, floating lag time was estimated form 7±0.39 to 57±0.36 sec. F4 and F5 showed floating even after 12hrs. All formulations showed a release of around 90% drug release within 12hr. It was observed that the selected independent variables affect the dependent variables. Conclusion: The developed system may be a promising and alternative approach to augment gastric retention of drugs and enhances the therapeutic efficacy of the drug.

Keywords: neratinib, 2³ factorial design, sodium alginate, floating, in situ gelling system

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Authors: M. Kumpugdee-Vollrath, J.-P. Krause, S. Bürk

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Most of the drugs used for pharmaceutical purposes are poorly water-soluble drugs. About 40% of all newly discovered drugs are lipophilic and the numbers of lipophilic drugs seem to increase more and more. Drug delivery systems such as nanoparticles, micelles or liposomes are applied to improve their solubility and thus their bioavailability. Besides various techniques of solubilization, oil-in-water emulsions are often used to incorporate lipophilic drugs into the oil phase. To stabilize emulsions surface active substances (surfactants) are generally used. An alternative method to avoid the application of surfactants was of great interest. One possibility is to develop O/W-emulsion without any addition of surface active agents or the so called “surfactant-free emulsion or SFE”. The aim of this study was to develop and characterize SFE as a drug carrier by varying the production conditions. Lidocaine base was used as a model drug. The injection method was developed. Effects of ultrasound as well as of temperature on the properties of the emulsion were studied. Particle sizes and release were determined. The long-term stability up to 30 days was performed. The results showed that the surfactant-free O/W emulsions with pharmaceutical oil as drug carrier can be produced.

Keywords: emulsion, lidocaine, Miglyol, size, surfactant, light scattering, release, injection, ultrasound, stability

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Authors: Naima Nur, Safa Islam, Saeema Islam, Faridul Alam

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Background: Drug-resistant pulmonary tuberculosis (DR-PTB), particularly multidrug-resistant tuberculosis (MDR-TB) and pre-extensive drug-resistant (pre-XDR), is a major challenge in effectively controlling TB, especially in developing. This study aimed to identify the strains of M. tuberculosis complex (MTC) and drug resistance patterns among the pulmonary tuberculosis patients. Methods: The study used a cross-sectional design, and 815 patients were recruited randomly in three study periods. In the first-period, 210 treated PTB patients, who were completed their treatment, received their diagnoses using light microscopy, fluorescence microscopy and cultured on Lowenstein-Jensen (L-J) slant, and then strains were identified as MTC by biochemical tests, and then sensitivity test in National Institute of Diseases of the Chest and Hospital. In the second-period, 220 re-treated PTB patients, who were completed their treatment, received their diagnoses using culture on L-J slant, line probe assay (LPA), and GeneXpert in the same hospital. In the last-period, during treatment, 385 MDR-PTB patients received their diagnoses using culture on L-J slant and LPA in the same hospital. Results: Among sixty-two (29.5%) PTB patients, 13% were sensitive to all first-line anti-TB drugs, 26% were MDR-TB patients, and 14.2% were pre-XDR-TB among 14 MDR-TB patients. After three years, 31% were MDR-TB among 220 re-treated PTB patients. After five years, 16.4% was pre-XDR-TB among 385 MDR-TB patients. Compared to females, male patients were significantly higher at all times. Conclusion: The current study demonstrated that in three study periods, the proportions of DR-TB, MDR-TB, and pre-XDR patients were an alarming issue and increasing daily.

Keywords: multi-drug resistant, drug-resistant, pre-extensive drug resistant, pulmonary tuberculosis

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Authors: Won Man Park, Dae Kyung Choi, Kyungsoo Kim, Yoon Hyuk Kim

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Traction therapy has been used in the treatment of spinal pain for decades. However, a case study reported the occurrence of large disc protrusion during motorized traction therapy. In this study, we hypothesized that additional local decompression with a global axial traction could be helpful for risk reduction of intervertebral disc damage. A validated three dimensional finite element model of the lumbar spine was used. Two-step traction therapy using the axial global traction (the first step) with 1/3 body weight and the additional local decompression (the second step) with 7 mm translation of L4 spinal bone was determined for the traction therapy. During two-step traction therapy, the sacrum was constrained in all translational directions. Reduced lordosis angle by the global axial traction recovered with the additional local decompression. Stress on fibers of the annulus fibrosus by the axial global traction decreased with the local decompression by 17%~96% in the posterior region of intervertebral disc. Stresses on ligaments except anterior longitudinal ligaments in all motion segments decreased till 4.9 mm~5.6 mm translation of L4 spinal bone. The results of this study showed that the additional local decompression is very useful for reducing risk of damage in the intervertebral disc and ligaments caused by the global axial traction force. Moreover, the local decompression could be used to enhance reduction of intradiscal pressure.

Keywords: lumbar spine, traction-therapy, biomechanics, finite element analysis

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Authors: Courtney Evans, Yuto Morimitsu, Tsubasa Hisadome, Futo Inomoto, Masahiro Yoshida, Takayuki Takei

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Hydrogels are useful biomaterials due to their highly biocompatible nature and their ability to absorb large quantities of liquid and mimic soft tissue. They are often used as therapeutic drug delivery systems. However, it is sometimes difficult to sustain controlled release when using hydrophobic medicines, as hydrogels are frequently hydrophilic. As such, this research shows the success of chitosan hydrogels modified through hydrophobic interaction. This was done through the imide bonding of the alkyl groups in fatty aldehydes and the amino groups in chitosan, followed by reductive animation. The resulting cryogels could be optimized for strength as well as sorption and desorption (of a hydrophobic dye used to mimic hydrophobic medicine) by varying the alkyl chain length and the substitution degree of the fatty aldehyde. Optimized cryogels showed potential as biomedical materials, particularly as drug delivery systems.

Keywords: biomedical materials, chitosan, drug carriers, hydrophobic modification

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Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz

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Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.

Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging

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Authors: Chui Ling Teng, R. Matsa

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We report a case with combined overdose of Lercanidipine (non-dihydropyridine calcium channel blocker), Quetiapine (Atypical antipsychotic), Ramipril and Duloxetine. A 66-year old male presented to the Emergency Department 12-hours after the ingestion of 1.2g Lercanidipine, 3g Quetiapine, 280mg of Ramipril and 420mg of Duloxetine. He describes lethargic, drowsiness and was unable to pass any urine since overdosed. He was found to be bradycardic, hypotensive and anuric. He had refractory hypotension and anuric despite fluid resuscitation, glucagon therapy and intravenous naloxone. His care was escalated to Intensive care, requiring noradrenaline, adrenaline, vasopressin, and hyperinsulinaemic euglycaemia therapy. He achieved haemodynamic stability and kidney function improved gradually with the support received. The total length of therapy lasted for 30 horus in which individual therapy was weaned down based on the requirement. He was then transferred to medical ward for further psychiatric assessment. This is a the first repored case of mixed overdose with lercanidipine, Quetiapine, Rampmipril and Duloxetine.

Keywords: calcium channel blocker, hyperinsulinaemic Euglycaemia therapy, lercanidipine, overdose

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Authors: Justina I. Reamen

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The study examined the influence of rational emotive therapy on the treatment of substance abuse among Senior Secondary School Students in Makurdi metropolis Benue State Nigeria. This research adopted youth self report scale which was distributed to 1,690 SSS Students drawn from Government day Secondary School Makurdi and Government Model College Makurdi. Afterwards, 200 who were identified to indulge in substance abuse were selected for the study, 100 each from the two schools. 100 were taken as the control group and 100 as the experimental group, (50 of each group from each school). The Rational Emotive Behavior Therapy (REBT) intervention program was presented to the experimental group for seven (7) weeks. The students were taught how to apply REBT’s cognitive, Emotive and Behavioral techniques on their problems. After which post test was conducted to find out the impact of REBT on the treatment of adolescent students with substance abuse problem. GLM repeated measures of ANOVA were used to analyze the data from the study. The study reveals that REBT has positive impact on the treatment of adolescent students that abuse substances in the study area. Between pretest to post-test scores, a significant difference was observed (F=26.939; P=000) in substance abuse where a decrease of 1.12 (pre-10.91, post-9.79) scores was noticed irrespective of the groups. However, when the decrease in substance abuse were analyzed group wise, (experimental control) again significant F value (F=38.782; P=000) was obtained. From the mean scores it is evident that experimental group decreased it means by 2.56 (Pre-10.04 - Post-8.83) scores compared to control group, which changed its scores by only 0.32 scores (pre 11.04 - Post 11.36). Recommendations were made based on the findings of the research.

Keywords: abuse, influence, substance, therapy, treatment

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Authors: Phill-Seung Jung, Dae-Yeon Kim

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Objectives: In young, especially nulliparous women, it is not easy to decide on excisional therapy for cervical intraepithelial neoplasia (CIN). We aimed to evaluate how effective topical imiquimod is in the treatment of high-grade CIN so that excisional therapy can be avoided in young women. Methods: Patients with CIN were allocated to this pilot study. They did not want excisional therapy and agreed with topical imiquimod therapy, which required once-a-week hospital visit for 8 weeks for the application of imiquimod to the cervix by a gynecologic oncologist. If the lesion got worse during treatment, it was decided to convert imiquimod therapy to excisional therapy. Results: A total of 36 patients with a median age of 29 years (range, 22–41 years) agreed to receive topical imiquimod therapy. Of these, 32 patients (88.9%) were positive for high-risk human papillomavirus (HR HPV). Twenty-five patients (69.4%) had low-grade squamous intraepithelial lesion (LSIL), and 11 (30.6%) had high-grade squamous intraepithelial lesion (HSIL) on their initial LBC. Twenty-eight patients underwent punch biopsy, which showed CIN 1 in 7 (19.4%), CIN 2 in 11 (30.6%), and CIN 3 in 10 (27.8%) patients. Twenty patients finished the 8-week imiquimod therapy. Among them, 14 patients had CIN 2 or 3, and 6 patients had CIN 1. HR HPV was positive in 12 patients. On the last examination, 14 patients (70.0%) had negative intraepithelial lesions, 3 (15.0%) had atypical squamous cells of undetermined significance, and 1 (5.0%) had LSIL. Two patients had persistent HSIL: 1 patient underwent loop electrosurgical excision procedure, resulting in CIN 3 with positive resection margin, and the other patient underwent punch biopsy, resulting in intermediate cells and restarted imiquimod therapy. Only 7 patients were negative for HR HPV. Conclusions: This study showed that topical imiquimod therapy was effective for the treatment of high-grade CIN, with a histologic regression rate of 85.7% (14/20) and HPV eradication rate of 25.0% (8/32). Based on our findings, topical imiquimod therapy might have a successful therapeutic effect in young women with CIN 2-3 so that they can avoid excisional therapy. In addition, it could be a more reassuring treatment option for CIN 1 than just follow-up after few months. To confirm its efficacy, a phase II study with larger cohort would be needed.

Keywords: Imiquimod, Cervical Intraepthelial Neoplasia, Cervical Dysplasia, Human Papillomavirus

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Authors: Kheireddine El-Boubbou

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Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC₅₀ values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.

Keywords: magnetic nanoparticles, drug delivery, acute myeloid leukemia, iron oxide, cancer nanotherapy

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Authors: Alireza Monzavi Chaleshtari, Mahnaz Aliakbari Dehkordi, Seyedeh Somayeh Amiri, Mozhgan Shakhseniaei, Amin Asadi Hieh

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The purpose of this research was to determine the effectiveness of sexual cognitive behavioral therapy on strategic thinking and communication patterns of couples in colostomy patients. In this study, experimental research was conducted with a pre-test and post-test design with a control group and a follow-up period. The statistical population studied were married female colostomy patients referring to the Iranian Ostomy Association. 30 qualified people were selected by voluntary sampling and randomly divided into two experimental and control groups (15 people in each group). Both groups responded to Goleman's strategic thinking (2007) and the communication patterns of Christensen and Sulawai questionnaires (1984). The results of covariance analysis showed that sexual cognitive behavioral therapy has an effect on improving strategic thinking. Based on the results of this test, sexual cognitive behavioral therapy is effective in improving the strategic thinking of colostomy patients until the follow-up stage. Also, sexual cognitive behavioral therapy has an effect on improving the communication patterns of couples in colostomy patients. Based on the results of this test, sexual cognitive behavioral therapy is effective in improving communication patterns of couples in patients with colostomy until the follow-up stage. Based on the results of this research, sexual cognitive behavioral therapy can be used to improve strategic thinking and communication patterns of couples of colostomy patients.

Keywords: sexual cognitive behavioral therapy, strategic thinking, communication patterns of couples, colostomy

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Authors: Adrian Craig, Jonathan Easaw, Rose Jordan, Ben Hall

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The prescription of intravenous fluids is a fundamental component of inpatient management, but it is one which usually lacks thought. Fluids are a drug, which like any other can cause harm when prescribed inappropriately or wrongly. However, it is well recognised that it is poorly done, especially in the acute portals. The National Institute for Health and Care Excellence (NICE) recommends 1mmol/kg of potassium, sodium, and chloride per day. With various options of fluids, clinicians tend to face difficulty in choosing the most appropriate maintenance fluid, and there is a reluctance to prescribe potassium as part of an intravenous maintenance fluid regime. The aim was to prospectively audit the prescription of the first bag of intravenous maintenance fluids, the use of urea and electrolytes results to guide the choice of fluid and the use of fluid prescription charts, in a busy emergency department of a major trauma centre in Stoke-on-Trent, United Kingdom. This was undertaken over a week in early November 2016. Of those prescribed maintenance fluid only 8.9% were prescribed a fluid which was most appropriate for their daily electrolyte requirements. This audit has helped to highlight further the issues that are faced in busy Emergency Departments within hospitals that are stretched and lack capacity for prompt transfer to a ward. It has supported the findings of NICE, that emergency admission portals such as Emergency Departments poorly prescribed intravenous fluid therapy. The findings have enabled simple steps to be taken to educate clinicians about their fluid of choice. This has included: posters to remind clinicians to consider the urea and electrolyte values before prescription, suggesting the inclusion of a suggested intravenous fluid of choice in the prescription chart of the trust and the inclusion of a session within the introduction programme revising intravenous fluid therapy and daily electrolyte requirements. Moving forward, once the interventions have been implemented then, the data will be reaudited in six months to note any improvement in maintenance fluid choice. Alongside this, an audit of the rate of intravenous maintenance fluid therapy would be proposed to further increase patient safety by avoiding unintentional fluid overload which may cause unnecessary harm to patients within the hospital. In conclusion, prescription of maintenance fluid therapy was poor within the Emergency Department, and there is a great deal of opportunity for improvement. Therefore, the measures listed above will be implemented and the data reaudited.

Keywords: chloride, electrolyte, emergency department, emergency medicine, fluid, fluid therapy, intravenous, maintenance, major trauma, potassium, sodium, trauma

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