Search results for: drug delivery to the brain

Authors: Jiji Jose, R. Narayanacharyulu, Molly Mathew, Jisha Prems

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Introduction: Lercanidipine hydrochloride (LD), an effective calcium channel blocker, widely used for the treatment of chronic stable angina and hypertension seems to be potential transdermal therapeutic system candidate, mainly due to its low oral bio availability, short half life and high first-pass metabolism. Objective: To develop transdermal therapeutic systems for LD and to evaluate its in vivo performance in rabbits. Methodology: Transdermal patches of LD were formulated using the polymer blend of eudragit RL100 (ERL) and polyvinyl pyrolidone (PVP) by casting method Propylene glycol (PG) and tween 80 were used as plasticizer and permeation enhancer respectively. The pharmaco kinetic parameters of LD after the administration of transdermal patches was compared with that of oral administration. The study was carried out in a two way crossover design in male New Zealand albino rabbits. Results: The formulation with ERL: PVP ratio 1:4 with 15% w/w PG as plasticizer and 4% w/w tween 80 as permeation enhancer showed the best drug release results. The pharmacokinetic parameters such as Cmax, tmax, mean residence time (MRT) and area under the curve (AUC 0-∞) were significantly different following transdermal administration compared to oral administration. The terminal half life of transdermally administered LD was found to similar that of oral administration. A sustained drug release over a period of 24 hrs was observed after transdermal administration. Conclusion: The fabricated transdermal delivery system have the potential to provide controlled and extended drug release, better bio availability and thus, this may improve the patient compliance.

Keywords: transdermal therapeutic system, lercanidipine hydrochloride, eudragit, skinpermeation

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Authors: Endri Rama, Genci Capi, Shigenori Kawahara

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The mobile robot ability to navigate autonomously in its environment is very important. Even though the advances in technology, robot self-localization and goal directed navigation in complex environments are still challenging tasks. In this article, we propose a novel method for robot navigation based on rat’s brain signals (Local Field Potentials). It has been well known that rats accurately and rapidly navigate in a complex space by localizing themselves in reference to the surrounding environmental cues. As the first step to incorporate the rat’s navigation strategy into the robot control, we analyzed the rats’ strategies while it navigates in a multiple Y-maze, and recorded Local Field Potentials (LFPs) simultaneously from three brain regions. Next, we processed the LFPs, and the extracted features were used as an input in the artificial neural network to predict the rat’s next location, especially in the decision-making moment, in Y-junctions. We developed an algorithm by which the robot learned to imitate the rat’s decision-making by mapping the rat’s brain signals into its own actions. Finally, the robot learned to integrate the internal states as well as external sensors in order to localize and navigate in the complex environment.

Keywords: brain-machine interface, decision-making, mobile robot, neural network

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Authors: Ozlem Karabulutlu, Kiymet Yesilcicek Calik, Nazli Akar

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Objectives: To examine fear of childbirth according to parity, gestational age, prenatal education, and obstetric history. Methods: The study was performed as a questionnaire design in a State Hospital in Kars, Turkey with 403 unselected pregnant who were recruited from the delivery unit. The data were collected via 3 questionnaires; the first with sociodemographic and obstetric features, the second with Wijma Delivery Expectance/Experience Questionnaire (W-DEQ) scale, and the third with the scale of Beck Anxiety Inventory (BAI). Results: The W-DEQ and BAI scores were higher in nulliparous than multiparous woman (W-DEQ 67.08±28.33, 59.87±26.91, P=0.039<0.05, BAI 18.97±9.5, 16.65±11.83, P=0.0009<0.05 respectively). Moreover, W-DEQ and BAI scores of pregnant whose gestational week was ≤37 / ≥41 and who didn’t receive training and had vaginal delivery was higher than those whose gestational week was 38-40 weeks and who received prenatal training and had cesarean delivery (W-DEQ 67.54±29.20, 56.44±22.59, 69.72±25.53 p<0.05, BAI 21.41±9.07; 15.77±11.20, 18.36±10.57 p<0.05 respectively). Both in nulliparous and multiparous, as W-DEQ score increases BAI score increases too (r=0.256; p=0.000<0.05). Conclusions: Severe fear of childbirth and anxiety was more common in nulliparous women, preterm and post-term pregnancy and who did not receive prenatal training and had vaginal delivery.

Keywords: Beck Anxiety Inventory (BAI), fear of birth, parity, pregnant women, Wijma Delivery Expectance/Experience Questionnaire (W-DEQ)

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Authors: Mandisi Matyana

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Although the South African local government is doing all the best in ensuring improved service delivery for the citizens, service delivery disparity still remains the real challenge for other municipalities. The unequal distribution of services within municipal wards is causing unequal happiness among the citizens; hence others do enjoy different provided municipal services, while others do not. It is acknowledged that less access to municipal services infringes one’s rights, such as the right to human dignity and the right to life. Some of the municipal services are basic services and they are the mainstay of human survival, such as water, housing, etc. It is quite evident that the service delivery disparity could be caused by the various factors within the local municipality affairs, including both administrative and political factors. Therefore, this study is undertaken to check and evaluate the main foundations of service delivery disparity in ensuring equal development of the state, particularly for local communities. The study used the qualitative method to collect the data from the citizens of Winnie Madikizela Mandela Local Municipality. An extensive literature was also conducted in understanding the causes of service delivery disparity. Study findings prove that the service delivery disparity could be caused by factors such as political interference in administration, corruption and fraud, elevated unemployment levels, inadequate institutional capacity, etc. Therefore, the study recommends strong community participation and constant external supervision in the local government so as to encourage openness in local government to ensure fair administration towards services to be provided.

Keywords: administration, development, municipal services, service delivery disparity, Winnie Madikizela Mandela local municipality

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Authors: Lilian A. Okeke, I. Okeke, N. Waziri, S. Balogun, P. Nguku, O. Fawole

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Background: Access to ante-natal care services promotes safe motherhood and delivery with improved maternal and neonatal outcome. We conducted this study to identify factors influencing the utilization of antenatal care (ANC) and health delivery services. Methods: We conducted a cross sectional study. Households were numbered and a one in three sample was selected using a systematic sampling method. One hundred and ninety eight women who were either pregnant or had previous deliveries were interviewed using pretested structured questionnaires to obtain information on their socio-demographic characteristics, and reasons for non-utilization of ANC and health delivery services. We performed univariate and bivariate analysis using Epi info version 3.5.3. Results: The age of respondents ranged from (17-55 years) with a median age of 29 years. One hundred and ninety two (97%) utilized antenatal care services. Ninety three (47.9%) attended ANC at second trimester. More than half (58.6%) had ≥ 4 visits to ANC. One hundred and thirty one (66.2%) had their last delivery at home by a traditional birth attendant. Factors associated with ANC and health facility delivery services utilization were: age group 45-55 (OR 0.01; 95% CI: 0.00-0.16) and > 55 years (OR 0.03; 95% CI: 0.00-0.60), wife’s educational status (OR 3.17; 95% CI: 1.66-8.30), husband’s permission (OR 11.8; 95% CI 2.19-63.62), and distance ≥ 5km (OR 0.33; 95% CI: 0.16-0.60). Conclusion: ANC services were well utilized. Most women did not book early and had their last delivery at home. Predictors of ANC use and health facility delivery were age, wife’s educational status, husband's permission and long distance from health facility. A one-day health sensitization of the benefits of ANC utilization and the dangers of delivering at home was implemented.

Keywords: ante natal care, health facility, delivery services, rural area, Plateau state

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Authors: Fernando G. Torres, Omar P. Troncoso

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Starch is a highly biocompatible, non-toxic, and biodegradable polymer. It is widely used in biomedical applications, including drug delivery systems and tissue engineering scaffolds. Curcumin, a phenolic compound found in the dried root of Curcuma longa, has been used as a nutritional supplement due to its antimicrobial, anti-inflammatory, and antioxidant effects. However, the major problem with ingesting curcumin by itself is its poor bioavailability due to its poor absorption and rapid metabolism. In this study, we report a novel methodology to prepare starch nanoparticles loaded with curcumin. The nanoparticles were synthesized via nanoprecipitation of starch granules extracted from native Andean potatoes (Solanum tuberosum ssp. and Andigena var Huamantanga varieties). The nanoparticles were crosslinked and stabilized by using sodium tripolyphosphate and Tween®80, respectively. The characterization of the nanoparticles loaded with curcumin was assessed by Fourier Transform Infrared Spectroscopy, Dynamic Light Scattering, Zeta potential, and Differential scanning calorimetry. UV-vis spectrophotometry was used to evaluate the loading efficiency and capacity of the samples. The results showed that native starch nanoparticles could be used to prepare promising nanocarriers for the controlled release of curcumin.

Keywords: starch nanoparticle, nanoprecipitation, curcumin, biomedical applications

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Authors: Azwin Lubis, Rika Hapsari, Zahrah Hikmah, Anang Endaryanto, Ariyanto Harsono

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Erythema Multiforme Exudativum Major (EMEM) is one of the drug allergy diseases. Drug allergies caused by isoniazid rarely causes EMEM. Cutaneous reactions caused by isoniazid were obtained in 0.98% of patients, but the precise occurrence of Steven Johnson’s Syndrome (SJS) and Toxic Epidermolisis Necrolisis (TEN) due to isoniazid is not known for certain. We present this case to show hypersensitivity of isoniazid in a child. Based on the history of drug intake, physical diagnostic tests, drug elimination and provocation; we established the diagnosis of isoniazid hypersensitivity. The child showed improvement on skin manifestation after stopped isoniazid therapy.

Keywords: erythema multiforme exudativum major, hypersensitivity, elimination test, provocation test

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Authors: E. Kilicay, Z. Karahaliloglu, B. Hazer, E. B. Denkbas

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In this study, we have prepared concanavaline A (ConA) functionalized curcumin (CUR) loaded PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles as a novel and efficient drug delivery system. CUR is a promising anticancer agent for various cancer types. The aim of this study was to evaluate therapeutic potential of curcumin loaded PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin loaded NPs (ConA-CUR NPs) for ovarian cancer treatment. ConA was covalently connected to the carboxylic group of nanoparticles by EDC/NHS activation method. In the ligand attachment experiment, the binding capacity of ConA on the surface of NPs was found about 90%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were smooth and spherical in shape. The size and zeta potential of prepared NPs were about 228±5 nm and −21.3 mV respectively. ConA-CUR NPs were characterized by FT-IR spectroscopy which confirmed the existence of CUR and ConA in the nanoparticles. The entrapment and loading efficiencies of different polymer/drug weight ratios, 1/0.125 PHBHHx/CUR= 1.25CUR-NPs; 1/0.25 PHBHHx/CUR= 2.5CUR-NPs; 1/0.5 PHBHHx/CUR= 5CUR-NPs, ConA-1.25CUR NPs, ConA-2.5CUR NPs and ConA-5CUR NPs were found to be ≈ 68%-16.8%; 55%-17.7 %; 45%-33.6%; 70%-15.7%; 60%-17%; 51%-30.2% respectively. In vitro drug release showed that the sustained release of curcumin was observed from CUR-NPs and ConA-CUR NPs over a period of 19 days. After binding of ConA, the release rate was slightly increased due to the migration of curcumin to the surface of the nanoparticles and the matrix integrities was decreased because of the conjugation reaction. This functionalized nanoparticles demonstrated high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. Anticancer activity of ConA-CUR NPs was proved by MTT assay and reconfirmed by apoptosis and necrosis assay. The anticancer activity of ConA-CUR NPs was measured in ovarian cancer cells (SKOV-3) and the results revealed that the ConA-CUR NPs had better tumor cells decline activity than free curcumin. The nacked nanoparticles have no cytotoxicity against human ovarian carcinoma cells. Thus the developed functionalized nanoformulation could be a promising candidate in cancer therapy.

Keywords: curcumin, curcumin-PHBHHx nanoparticles, concanavalin A, concanavalin A-curcumin PHBHHx nanoparticles, PHBHHx nanoparticles, ovarian cancer cell

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Authors: Shweta Singh, Dipali Bansal, Rashima Mahajan

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Psychoacoustics has become a potential area of research due to the growing interest of both laypersons and medical and mental health professionals. Non-invasive brain computer interface like Electroencephalography (EEG) is widely being used in this field. An attempt has been made in this paper to examine the response of EEG signals to acoustic stimuli further analysing the brain electrical activity. The real time EEG is acquired for 6 participants using a cost effective and portable EMOTIV EEG neuron headset. EEG data analysis is further done using EMOTIV test bench, EDF browser and EEGLAB (MATLAB Tool) application software platforms. Spectral analysis of acquired neural signals (AF3 channel) using these software platforms are clearly indicative of increased brain activity in various bands. The inferences drawn from such an analysis have significant correlation with subject’s subjective reporting of the experiences. The results suggest that the methodology adopted can further be used to assist patients with sleeping and depressive disorders.

Keywords: OM chant, spectral analysis, EDF browser, EEGLAB, EMOTIV, real time acquisition

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Authors: Saeedeh Ahmadi Basir, Mohammad Mahdavi Mazdeh, Mohammad Namakshenas

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Manufacturers often dispatch jobs in batches to reduce delivery costs. However, sending several jobs in batches can have a negative effect on other scheduling-related objective functions such as minimizing the number of tardy jobs which is often used to rate managers’ performance in many manufacturing environments. This paper aims to minimize the number of weighted tardy jobs and the sum of delivery costs of a two-stage assembly flow-shop problem in a batch delivery system. We present a mixed-integer linear programming (MILP) model to solve the problem. As this is an MILP model, the commercial solver (the CPLEX solver) is not guaranteed to find the optimal solution for large-size problems at a reasonable amount of time. We present several numerical examples to confirm the accuracy of the model.

Keywords: scheduling, two-stage assembly flow-shop, tardy jobs, batched delivery system

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Authors: Shilpa Bhilegaonkar, Ram Gaud

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Candesartan cilexetil is a poorly soluble antihypertensive agent with solubility limited bioavailability (15%). To initiate process of solubilisation, it is very much necessary to displace the air at the surface and wet the drug surface with a solvent, with which drug is compatible. Present research adopts the same principle to improve solubility and dissolution of candesartan cilexetil. Solvents used here are surfactant and modified surfactant in different drug: solvent (1:1-1:9) ratio’s for preparation of adsorbates. Adsorbates were then converted into free flowing powders as liquisolid compacts and compressed to form tablets. Liquisolid compacts were evaluated for improvement in saturation solubility and dissolution of candesartan cilexetil. All systems were evaluated for improvement in saturation solubility and dissolution in different medias such as water, 0.1 N HCl, Phosphate buffer pH 6.8 and media given by office of generic drugs along with other physicochemical testing. All systems exhibited a promising advantage in terms of solubility and dissolution without affecting the drug structure as confirmed by IR and XRD. No considerable advantage was seen of increasing solvent ratio with drug.

Keywords: candesartan cilexetil, improved dissolution, solubility, liquisolid

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Authors: Rui Chen, Jinfeng Zhang, Chun-Sing Lee

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In the past couple of decades, nanoscale metal-organic frameworks (NMOFs) have been highlighted as promising delivery platforms for biomedical applications, which combine many potent features such as high loading capacity, progressive biodegradability and low cytotoxicity. While NMOF has been extensively used as carriers for drugs of different modalities, so far there is no report on exploiting the advantages of NMOF for combination therapy. Herein, we prepared core-shell nanoparticles, where each nanoparticle contains a single graphitic-phase carbon nitride (g-C3N4) nanosheet encapsulated by a zeolitic-imidazolate frameworks-8 (ZIF-8) shell. The g-C3N4 nanosheets are effective visible-light photosensitizer for photodynamic therapy (PDT). When hosting DOX (doxorubicin), the as-synthesized core-shell nanoparticles could realize combinational photo-chemo therapy and provide dual-color fluorescence imaging. Therefore, we expect NMOFs-based core-shell nanoparticles could provide a new way to achieve much-enhanced cancer therapy.

Keywords: carbon nitride, combination therapy, drug delivery, nanoscale metal-organic frameworks

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Authors: Priyadarsini Samal, Rajesh Singla

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Many mobile games come with the benefits of entertainment by introducing stress to the human brain. In recognizing this mental stress, the brain-computer interface (BCI) plays an important role. It has various neuroimaging approaches which help in analyzing the brain signals. Electroencephalogram (EEG) is the most commonly used method among them as it is non-invasive, portable, and economical. Here, this paper investigates the pattern in brain signals when introduced with mental stress. Two healthy volunteers played a game whose aim was to search hidden words from the grid, and the levels were chosen randomly. The EEG signals during gameplay were recorded to investigate the impacts of stress with the changing levels from easy to medium to hard. A total of 16 features of EEG were analyzed for this experiment which includes power band features with relative powers, event-related desynchronization, along statistical features. Support vector machine was used as the classifier, which resulted in an accuracy of 93.9% for three-level stress analysis; for two levels, the accuracy of 92% and 98% are achieved. In addition to that, another game that was similar in nature was played by the volunteers. A suitable regression model was designed for prediction where the feature sets of the first and second game were used for testing and training purposes, respectively, and an accuracy of 73% was found.

Keywords: brain computer interface, electroencephalogram, regression model, stress, word search

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Authors: Ghaleb A. Husseini, Salma E. Ahmed, Hesham G. Moussa, Ana M. Martins, Mohammad Al-Sayah, Nasser Qaddoumi

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This abstract aims to investigate the use of targeted liposomes as anticancer drug carriers in vitro in combination with ultrasound applied as drug trigger; in order to reduce the side effects caused by traditional chemotherapy. Pegylated liposomes were used to encapsulate calcein and then release this model drug when 20-kHz, 40-kHz, 1-MHz and 3-MHz ultrasound were applied at different acoustic power densities. Fluorescence techniques were then used to measure the percent drug release of calcein from these targeted liposomes. Results showed that as the power density increases, at the four frequencies studied, the release of calcein also increased. Based on these results, we believe that ultrasound can be used to increase the rate and amount of chemotherapeutics release from liposomes.

Keywords: liposomes, calcein release, high frequency ultrasound, low frequency ultrasound, fluorescence techniques

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Authors: Nipun Agarwal, David Paul, Fareed Un Din

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Every organization develops a strategy that needs to be implemented and is undertaken through project delivery. In essence, project requirements should exactly replicate an organization’s strategy. In reality this does not happen, and behavioral factors deviate the project delivery from the strategic objectives. This occurs as project stakeholders can have competing objectives. Resultantly, requirements that are implemented through projects are less aligned to the strategy. This paper develops a game theoretic model to simulate why such deviations occur. That explains the difference between strategy development and implementation.

Keywords: strategy, simulation, project management, game theory

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Authors: Abhay Asthana, Shally Toshkhani, Gyati Shilakari

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The objective of the present research work is to develop a topical biodegradable dermal patch based formulation to aid accelerated wound healing. It is always better for patient compliance to be able to reduce the frequency of dressings with improved drug delivery and overall therapeutic efficacy. In present study optimized formulation using biodegradable components was obtained evaluating polymers and excipients (HPMC K4M, Ethylcellulose, Povidone, Polyethylene glycol and Gelatin) to impart significant folding endurance, elasticity, and strength. Molten gelatin was used to get a mixture using ethylene glycol. Chitosan dissolved in acidic medium was mixed with stirring to Gelatin mixture. With continued stirring to the mixture Curcumin was added with the aid of DCM and Methanol in an optimized ratio of 60:40 to get homogenous dispersion. Polymers were dispersed with stirring in the final formulation. The mixture was sonicated casted to get the film form. All steps were carried out under strict aseptic conditions. The final formulation was a thin uniformly smooth textured film with dark brown-yellow color. The film was found to have folding endurance was around 20 to 21 times without a crack in an optimized formulation at RT (23°C). The drug content was in range 96 to 102% and it passed the content uniform test. The final moisture content of the optimized formulation film was NMT 9.0%. The films passed stability study conducted at refrigerated conditions (4±0.2°C) and at room temperature (23 ± 2°C) for 30 days. Further, the drug content and texture remained undisturbed with stability study conducted at RT 23±2°C for 45 and 90 days. Percentage cumulative drug release was found to be 80% in 12h and matched the biodegradation rate as tested in vivo with correlation factor R2>0.9. In in vivo study administration of one dose in equivalent quantity per 2 days was applied topically. The data demonstrated a significant improvement with percentage wound contraction in contrast to control and plain drug respectively in given period. The film based formulation developed shows promising results in terms of stability and in vivo performance.

Keywords: wound healing, biodegradable, polymers, patch

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Authors: Asher John Mohan, Krishna K. L.

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Objectives: (1) To assess the extent of memory impairment induced by Phenytoin (PHT) at normal and reduced dose on temporal lobe epileptic mice. (2) To evaluate the protective effect of Levetiracetam (LEV) on aggravation of memory impairment in temporal lobe epileptic mice by PHT. Materials and Methods: Albino mice of either sex (n=36) were used for the study for a period of 64 days. Convulsions were induced by intraperitoneal administration of pilocarpine 280 mg/kg on every 6th day. Radial arm maze (RAM) was employed to evaluate the memory impairment activity on every 7th day. The anticonvulsant and memory impairment activity were assessed in PHT normal and reduced doses both alone and in combination with LEV. RAM error scores and convulsive scores were the parameters considered for this study. Brain acetylcholine esterase and glutamate were determined along with histopathological studies of frontal cortex. Results: Administration of PHT for 64 days on mice has shown aggravation of memory impairment activity on temporal lobe epileptic mice. Although the reduction in PHT dose was found to decrease the degree of memory impairment the same decreased the anticonvulsant potency. The combination with LEV not only brought about the correction of impaired memory but also replaced the loss of potency due to the reduction of the dose of the antiepileptic drug employed. These findings were confirmed with enzyme and neurotransmitter levels in addition to histopathological studies. Conclusion: This study thus builds a foundation in combining a nootropic anticonvulsant with an antiepileptic drug to curb the adverse effect of memory impairment associated with temporal lobe epilepsy. However further extensive research is a must for the practical incorporation of this approach into disease therapy.

Keywords: anti-epileptic drug, Phenytoin, memory impairment, Pilocarpine

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Authors: Somdutt Mujwar, Kamal Raj Pardasani

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Cholera pandemics are caused by facultative pathogenic Vibrio cholera bacteria persisting in the countries having warmer climatic conditions as well as the presence of large water bodies with huge amount of organic matter, it is responsible for the millions of deaths annually. Presently the available therapy for cholera is Oral Rehydration Therapy (ORT) with an antibiotic drug. Excessive utilization of life saving antibiotics drugs leads to the development of resistance by the infectious micro-organism against the antibiotic drugs resulting in loss of effectiveness of these drugs. Also, many side effects are also associated with the use of these antibiotic drugs. This riboswitch is explored as an alternative drug target for Vibrio cholera bacteria to overcome the problem of drug resistance as well as side effects associated with the antibiotics drugs. The bacterial riboswitch is virtually screened with 24407 legends to get possible drug candidates. The 10 ligands showing best binding with the riboswitch are selected to design a pharmacophore, which can be utilized to design lead molecules by using the phenomenon of bioisosterism.

Keywords: cholera, drug design, ligand, riboswitch, pharmacophore

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Authors: A. Alao Olumuyiwa

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Health hazards reported to be associated with exposure to electromagnetic radiations which include brain tumors, genotoxic effects, neurological effects, immune system deregulation, allergic responses and some cardiovascular effects are discussed under a closed tabular model in this study. This review however showed that there is strong and robust evidence that chronic exposures to electromagnetic frequency across the spectrum, through strength, consistency, biological plausibility and many dose-response relationships, may result in brain cancer and other carcinogenic disease symptoms. There is therefore no safe threshold because of the genotoxic nature of the mechanism that may however be involved. The discussed study explains that the cell phone has induced effects upon the blood –brain barrier permeability and the cerebellum exposure to continuous long hours RF radiation may result in significant increase in albumin extravasations. A physical Biomodeling approach is however employed to review this health effects using Specific Absorption Rate (SAR) of different GSM machines to critically examine the symptoms such as a decreased loco motor activity, increased grooming and reduced memory functions in a variety of animal spices in classified grouped and sub grouped models.

Keywords: brain cancer, electromagnetic radiations, physical biomodeling, specific absorption rate (SAR)

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Authors: Mumuni Sumaila, Viness Pillay, Yahya E. Choonara, Pradeep Kumar, Pierre P. Kondiah

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Tuberculosis (TB) remains a serious challenge to public health globally, despite every effort put together to curb the disease. Current TB therapeutics available have proven to be inefficient due to a multitude of drawbacks that range from serious adverse effects/drug toxicity to inconsistent bioavailability, which ultimately contributes to the emergence of drug-resistant TB. An effective ‘cargo’ system designed to cleverly deliver therapeutic doses of anti-TB drugs to infection sites and in a sustained-release manner may provide a better therapeutic choice towards winning the war against TB. In the current study, we investigated mannose-functionalized lipopolysaccharide hybrid nanoparticles for safety and efficacy towards macrophage-targeted simultaneous delivery of the two first-line anti-TB drugs, rifampicin (RF) and isoniazid (IS). RF-IS-loaded lipopolysaccharide hybrid nanoparticles were fabricated using the solvent injection technique (SIT), incorporating soy lecithin (SL) and low molecular weight chitosan (CS) as the lipid and polysaccharide components, respectively. Surface-functionalized nanoparticles were obtained through the reaction of the aldehyde group of mannose with free amine functionality present at the surface of the nanoparticles. The functionalized nanocarriers were spherical with average particle size and surface charge of 107.83 nm and +21.77 mV, respectively, and entrapment efficiencies (EE) were 53.52% and 69.80% for RF and IS, respectively. FTIR spectrum revealed high-intensity bands between 1663 cm⁻¹ and 1408 cm⁻¹ wavenumbers (absent in non-functionalized nanoparticles), which could be attributed to the C=N stretching vibration produced by the formation of Schiff’s base (–N=CH–) during the mannosylation reaction. In vitro release studies showed a sustained-release profile for RF and IS, with less than half of the total payload released over a 48-hour period. The nanocarriers were biocompatible and safe, with more than 80% cell viability achieved when incubated with RAW 264.7 cells at concentrations 30 to 500 μg/mL over a 24-hour period. Cellular uptake studies (after a 24-hour incubation period with the murine macrophage cells, RAW 264.7) revealed a 13- and a 9-fold increase in intracellular accumulation of RF and IS, respectively, when compared with the unformulated RF+IS solution. A 6- and a 3-fold increase in intracellular accumulation of RF and IS, respectively, were observed when compared with the non-functionalized nanoparticles. Furthermore, fluorescent microscopy images showed nanoparticle internalization and accumulation within the RAW 264.7 cells, which was more significant in the mannose-functionalized system compared to the non-functionalized nanoparticles. The overall results suggested that the fabricated mannose-functionalized lipopolysaccharide nanoparticles are a safe and promising platform for macrophage-targeted delivery of anti-TB therapeutics. However, in vivo pharmacokinetic/pharmacodynamics studies are required to further substantiate the therapeutic efficacy of the nanosystem.

Keywords: anti-tuberculosis therapeutics, hybrid nanosystem, lipopolysaccharide nanoparticles, macrophage-targeted delivery

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Authors: Kensho Takahashi, Ko Watanabe, Takashi Kaburagi, Hiroshi Tanaka, Kajiro Watanabe, Yosuke Kurihara

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Near-infrared spectroscopy (NIRS) has been widely used as a non-invasive method to measure brain activity, but it is corrupted by baseline drift noise. Here we present a method to measure regional cerebral blood flow as a derivative of NIRS output. We investigate whether, when listening to languages, blood flow can reasonably localize and represent regional brain activity or not. The prefrontal blood flow distribution pattern when advanced second-language listeners listened to a second language (L2) was most similar to that when listening to their first language (L1) among the patterns of mean and standard deviation. In experiments with 25 healthy subjects, the maximum blood flow was localized to the left BA46 of advanced listeners. The blood flow presented is robust to baseline drift and stably localizes regional brain activity.

Keywords: NIRS, oxy-hemoglobin, baseline drift, blood flow, working memory, BA46, first language, second language

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Authors: Vano Tsertsvadze, Marina Chavchanidze, Lali Khurtsia

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Problem of drug use is often seen as a combination of psychological and social problems, but this problem can be considered as economically rational decision in the process of buying pleasure (looking after children, reading, harvesting fruits in the fall, sex, eating, etc.). Before the adoption of the decisions people face to a trade-off - when someone chooses a delicious meal, she takes a completely rational decision, that the pleasure of eating has a lot more value than the pleasure which she will experience after two months diet on the summer beach showing off her beautiful body. This argument is also true for alcohol, drugs and cigarettes. Smoking has a negative effect on health, but smokers are not afraid of the threat of a lung cancer after 40 years, more valuable moment is a pleasure from smoking. Our hypothesis - unsatisfied pleasure and frustration, probably determines the risk of dependence on drug abuse. The purpose of research: 1- to determine the relative measure unit of pleasure, which will be used to measure and assess the intensity of various human pleasures. 2- to compare the intensity of the pleasure from different kinds of activity, with pleasures received from drug use. 3- Based on the analysis of data, to identify factors affecting the rational decision making. Research method: Respondents will be asked to recall the greatest pleasure of their life, which will be used as a measure of the other pleasures. The study will use focus groups and structured interviews.

Keywords: drug, drug-user, measurement, satisfaction

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Authors: Nagasamy Venkatesh Dhandapani, Amged Awad El-Gied

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Cefixime, a BCS class II drug, is insoluble in water but freely soluble in acetone and in alcohol. The aqueous solubility of cefixime in water is poor and exhibits exceptionally slow and intrinsic dissolution rate. In the present study, cefixime and β-Cyclodextrin (β-CD) solid dispersions were prepared with a view to study the effect and influence of β-CD on the solubility and dissolution rate of this poorly aqueous soluble drug. Phase solubility profile revealed that the solubility of cefixime was increased in the presence of β-CD and was classified as A_L-type. Effect of variable, such as drug:carrier ratio, was studied. Physical characterization of the solid dispersion was characterized by Fourier transform infrared spectroscopy (FT-IR) and Differential scanning calorimetry (DSC). These studies revealed that a distinct loss of drug crystallinity in the solid molecular dispersions is ostensibly accounting for enhancement of dissolution rate in distilled water. The drug release from the prepared solid dispersion exhibited a first order kinetics. Solid dispersions of cefixime showed a 6.77 times fold increase in dissolution rate over the pure drug.

Keywords: β-cyclodextrin, cefixime, dissolution, Kneading method, solid dispersions, release kinetics

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Authors: Minh Thi Hai Vo

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This article draws on in-depth interviews with state employees at public hospitals and universities in its institutional analysis of the autonomy practices of public service delivery units in Vietnam. Unlike many empirical and theoretical studies that view formal and informal institutions as complements or substitutes, this article finds no evidence of complementary or substitutive relationships. Instead, the article finds that formal institutions accommodate informal ones and that informal institutions tend to compete and interfere, with the existing and ineffective formal institutions. The result of such conflicting relationship is that the actual autonomy of public service delivery units is, in most cases, perceived to be greater than the formal autonomy they are given. In the condition of poor regulation, the informal autonomy may result in unethical practices including rent-seeking and corruption. The implication of the study finding is policy-makers need to redesign and reorganize the autonomisation of public service delivery units to make informal institutions support and reinforce formal ones in a complementary manner.

Keywords: autonomy, formal institutions, informal institutions, public service delivery units, Vietnam

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Authors: Surajj Sarode, G. Vidya Sagar, G. P. Vadnere

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The purpose of the present study was to prolong the gastric residence time of Stavudine by developing gastric floating drug delivery system (GFDDS). Moreover, to study influence of different polymers on its release rate using gas-forming agents, like sodium bicarbonate, citric acid. Floating tablets were prepared by wet granulation method using PVP K-30 as a binder and the other polymers include Pullulan Gum, HPMC K100M, six different formulations with the varying concentrations of polymers were prepared and the tablets were evaluated in terms of their pre-compression parameters like bulk density, tapped density, Haunsner ratio, angle of repose, compressibility index, post compression physical characteristics, in vitro release, buoyancy, floating lag time (FLT), total floating time (TFT) and swelling index. All the formulations showed good floating lag time i.e. less than 3 mins. The batch containing combination of Pullulan Gum and HPMC 100M (i.e. F-6) showed total floating lag time more than 12 h., the highest swelling index among all the prepared batches. The drug release was found to follow zero order kinetics.

Keywords: Suavudine, floating, total floating time (TFT), gastric residence

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Authors: Hyuk-Hoon Kim, Young Gi Min

Abstract:

Background: In carbon monoxide (CO) intoxication, the pathophysiology of delayed neurological sequelae (DNS) is very complex and remains poorly understood. And predicting whether patients who exhibit resolved acute symptoms have escaped or will experience DNS represents a very important clinical issue. Brain magnetic resonance (MR) imaging has been conducted to assess the severity of brain damage as an objective method to predict prognosis. And co-ingestion of a second poison in patients with intentional CO poisoning occurs in almost one-half of patients. Among patients with co-ingestions, 66% ingested ethanol. We assessed the effects of ethanol on neurologic sequelae prevalence in acute CO intoxication by means of abnormal lesion in brain MR. Method: This study was conducted retrospectively by collecting data for patients who visited an emergency medical center during a period of 5 years. The enrollment criteria were diagnosis of acute CO poisoning and the measurement of the serum ethanol level and history of taking a brain MR during admission period. Official readout data by radiologist are used to decide whether abnormal lesion is existed or not. The enrolled patients were divided into two groups: patients with abnormal lesion and without abnormal lesion in Brain MR. A standardized extraction using medical record was performed; Mann Whitney U test and logistic regression analysis were performed. Result: A total of 112 patients were enrolled, and 68 patients presented abnormal brain lesion on MR. The abnormal brain lesion group had lower serum ethanol level (mean, 20.14 vs 46.71 mg/dL) (p-value<0.001). In addition, univariate logistic regression analysis showed the serum ethanol level (OR, 0.99; 95% CI, 0.98 -1.00) was independently associated with the development of abnormal lesion in brain MR. Conclusion: Ethanol could have neuroprotective effect in acute CO intoxication by sedative effect in stressful situation and mitigative effect in neuro-inflammatory reaction.

Keywords: carbon monoxide, delayed neuropsychological sequelae, ethanol, intoxication, magnetic resonance

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Authors: Rania F. Ahmed, Sally A. El Awdan, Gehad A. Abdel Jaleel, Dalia O. Saleh, Omar A. H. Ahmed-Farid

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The metabolic syndrome is an important public health concern often related to obesity, improper diet, and sedentary lifestyles and can predispose individuals to the development of many dangerous health conditions, disability and early death. This research aimed to investigate the efficacy of resveratrol (RSV) to reverse the neuro-complications associated with metabolic syndrome experimentally-induced in rats using an eight weeks high fat, high fructose diet (HFHF) model. The corresponding drug treatments were administered orally during the last 10 days of the diet. Behavioural tests namely the open field test (OFT) and the forced swimming test (FST) were conducted. Brain levels of monoamines viz. serotonin, norepinephrine and dopamine as well as their metabolites were assessed. 8-hydroxyguanosine (8-OHDG) as an indicative of DNA-fragmentation, nitric oxide (NOx) and tumor necrosis factor-α (TNF- α) were estimated. Finally, brain antioxidant parameters namely malondialdehyde (MDA), reduced and oxidized glutathione (GSH, GSSG) were evaluated. HFHF-induced metabolic syndrome resulted in decreased activity in the OFT and increased immobility duration in the FST. Furthermore, HFHF-induced metabolic syndrome lead to a significant increase in brain monoamines turn over as well as elevation in 8-OHDG, NOx, TNF- α, MDA and GSSG; and reduction in GSH. Ten days daily treatment with RSV (20 and 40 mg/kg p.o) dose dependently increased activity in the OFT and decreased immobility duration in the FST. Moreover, RSV normalized brain monoamines contents, reduced 8-OHDG, NOx, TNF- α, MDA and GSSG; and elevated GSH. In conclusion, we can say that RSV showed neuro-protective properties against HFHF-induced metabolic syndrome represented by monoamines preservation, prevention of neurodegeneration, anti-inflammatory and antioxidant potentials and could be recommended as a beneficial daily dietary supplement to treat the neuronal side effects associated with HFHF-induced metabolic syndrome.

Keywords: antioxidants, DNA-fragmentation, forced swimming test, HFHF-induced metabolic syndrome, monoamines, nitric oxide (NOx), open field, resveratrol, tumor necrosis factor-α (TNF- α), 8-hydroxyguanosine (8-OHDG)

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Authors: Desalegn Feyissa Desu

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Drug therapy problem is a significant challenge to provide high quality health care service for the patients. It is associated with morbidity, mortality, increased hospital stay, and reduced quality of life. Moreover, pediatric patients are quite susceptible to drug therapy problems. Thus this study aimed to assess drug therapy problem and its contributing factors among pediatric patients diagnosed with infectious disease admitted to pediatric ward of Jimma university medical center, from April 1 to June 30, 2018. Prospective observational study was conducted among pediatric patients with infectious disease admitted from April 01 to June 30, 2018. Drug therapy problems were identified by using Cipolle’s and strand’s drug related problem classification method. Patient’s written informed consent was obtained after explaining the purpose of the study. Patient’s specific data were collected using structured questionnaire. Data were entered into Epi data version 4.0.2 and then exported to statistical software package version 21.0 for analysis. To identify predictors of drug therapy problems occurrence, multiple stepwise backward logistic regression analysis was done. The 95% CI was used to show the accuracy of data analysis and statistical significance was considered at p-value < 0.05. A total of 304 pediatric patients were included in the study. Of these, 226(74.3%) patients had at least one drug therapy problem during their hospital stay. A total of 356 drug therapy problems were identified among two hundred twenty six patients. Non-compliance (28.65%) and dose too low (27.53%) were the most common type of drug related problems while disease comorbidity [AOR=3.39, 95% CI= (1.89-6.08)], Polypharmacy [AOR=3.16, 95% CI= (1.61-6.20)] and more than six days stay in hospital [AOR=3.37, 95% CI= (1.71-6.64) were independent predictors of drug therapy problem occurrence. Drug therapy problems were common in pediatric patients with infectious disease in the study area. Presence of comorbidity, polypharmacy and prolonged hospital stay were the predictors of drug therapy problem in study area. Therefore, to overcome the significant gaps in pediatric pharmaceutical care, clinical pharmacists, Pediatricians, and other health care professionals have to work in collaboration.

Keywords: drug therapy problem, pediatric, infectious disease, Ethiopia

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Authors: Savaş Karpuz, Sami Küçükşen

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The aim of this study is to investigate the effectiveness of neurological rehabilitation in patients with traumatic brain injury. Participants were 45 consecutive adults with traumatic brain injury who were received the neurologic rehabilitation. Sociodemographic characteristics of the patients, the cause of the injury, the duration of the coma and posttraumatic amnesia, the length of stay in the other inpatient clinics before rehabilitation, the time between injury and admission to the rehabilitation clinic, and the length of stay in the rehabilitation clinic were recorded. The differences in functional status between admission and discharge were determined with Disability Rating Scale (DRS), Functional Independence Measure (FIM), and Functional Ambulation Scale (FAS) and levels of cognitive functioning determined with Ranchos Los Amigos Scale (RLAS). According to admission time, there was a significant improvement identified in functional status of patients who had been given the intensive in-hospital cognitive rehabilitation program. At discharge time, the statistically significant differences were obtained in DRS, FIM, FAS and RLAS scores according to admission time. Better improvement in functional status was detected in patients with lower scores in DRS, and higher scores FIM and RLAS scores at the entry time. The neurologic rehabilitation significantly affects the recovery of functional status after traumatic brain injury.

Keywords: traumatic brain injury, rehabilitation, functional status, neurological

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Authors: Elaheh Jooybar, Mohammad J. Abdekhodaie, Marcel Karperien, Pieter J. Dijkstra

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In this study, hyaluronic acid (HA) microgels were developed for the goal of protein delivery. First, a hyaluronic acid-tyramine conjugate (HA-TA) was synthesized with a degree of substitution of 13 TA moieties per 100 disaccharide units. Then, HA-TA microdroplets were produced using a water in oil emulsion method and crosslinked in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H₂O₂). Loading capacity and the release kinetics of lysozyme and BSA, as model proteins, were investigated. It was shown that lysozyme, a cationic protein, can be incorporated efficiently in the HA microgels, while the loading efficiency for BSA, as a negatively charged protein, is low. The release profile of lysozyme showed a sustained release over a period of one month. The results demonstrated that the HA-TA microgels are a good carrier for spatial delivery of cationic proteins for biomedical applications.

Keywords: microgel, inverse emulsion, protein delivery, hyaluronic acid, crosslinking

Procedia PDF Downloads 169