Search results for: targeted drug delivery

Authors: Alamgir Naushad, Ghulam Abbas, Shehzad Ali Shah, Ziaul Haq Abbas

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Unlike conventional networks, it is particularly challenging to manage resources efficiently in Wireless Sensor Networks (WSNs) due to their inherent characteristics, such as dynamic network topology and limited bandwidth and battery power. To ensure energy efficiency, this paper presents a routing protocol for WSNs, namely, Enhanced Hybrid Multipath Routing (EHMR), which employs hierarchical clustering and proposes a next hop selection mechanism between nodes according to a maximum residual energy metric together with a minimum hop count. Load-balancing of data traffic over multiple paths is achieved for a better packet delivery ratio and low latency rate. Reliability is ensured in terms of higher data rate and lower end-to-end delay. EHMR also enhances the fast-failure recovery mechanism to recover a failed path. Simulation results demonstrate that EHMR achieves a higher packet delivery ratio, reduced energy consumption per-packet delivery, lower end-to-end latency, and reduced effect of data rate on packet delivery ratio when compared with eminent WSN routing protocols.

Keywords: energy efficiency, load-balancing, hierarchical clustering, multipath routing, wireless sensor networks

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Authors: M. H. Pazandeh, M. Doudi, S. Barahimi, L. Rahimzadeh Torabi

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The use of antibiotics is essential in reducing the occurrence of adverse effects and inhibiting the emergence of antibiotic resistance in microbial populations. The necessity for a novel methodology concerning local administration of antibiotics has arisen, with particular focus on dealing with localized infections prompted by bacterial colonization of medical devices or implant materials. Bioactive glasses (BG) are extensively employed in the field of regenerative medicine, encompassing a diverse range of materials utilized for drug delivery systems. In the present investigation, various drug carriers for imipenem and tetracycline, namely single systems BG/SnO2, BG/NiO with varying proportions of metal oxide, and nanocomposite BG/SnO2/NiO, were synthesized through the sol-gel technique. The antibacterial efficacy of the synthesized samples was assessed through the utilization of the disk diffusion method with the aim of neutralizing Staphylococcus aureus as the bacterial model. The current study involved the examination of the bioactivity of two samples, namely BG10SnO2/10NiO and BG20SnO2, which were chosen based on their heightened bacterial inactivation properties. This evaluation entailed the employment of two techniques: the measurement of the pH of simulated body fluid (SBF) solution and the analysis of the sample tablets through X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. The sample tablets were submerged in SBF for varying durations of 7, 14, and 28 days. The bioactivity of the composite bioactive glass sample was assessed through characterization of alterations in its surface morphology, structure, and chemical composition. This evaluation was performed using scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction spectroscopy. Subsequently, the sample was immersed in simulated liquids to simulate its behavior in biological environments. The specific body fat percentage (SBF) was assessed over a 28-day period. The confirmation of the formation of a hydroxyapatite surface layer serves as a distinct indicator of bioactivity. The infusion of antibiotics into the composite bioactive glass specimen was done separately, and then the release kinetics of tetracycline and imipenem were tested in simulated body fluid (SBF). Antimicrobial effectiveness against various bacterial strains have been proven in numerous instances using both melt and sol-gel techniques to create multiple bioactive glass compositions. An elevated concentration of calcium ions within a solution has been observed to cause an increase in the pH level. In aqueous suspensions, bioactive glass particles manifest a significant antimicrobial impact. The composite bioactive glass specimen exhibits a gradual and uninterrupted release, which is highly desirable for a drug delivery system over a span of 72 hours. The reduction in absorption, which signals the loss of a portion of the antibiotic during the loading process from the initial phosphate-buffered saline solution, indicates the successful bonding of the two antibiotics to the surfaces of the bioactive glass samples. The sample denoted as BG/10SnO2/10NiO exhibits a higher loading of particles compared to the sample designated as BG/20SnO2 in the context of bioactive glass. The enriched sample demonstrates a heightened bactericidal impact on the bacteria under investigation while concurrently preserving its antibacterial characteristics. Tailored bioactive glass that incorporates hydroxyapatite, with a regulated and efficient release of drugs targeting bacterial infections, holds promise as a potential framework for bone implant scaffolds following rigorous clinical evaluation, thereby establishing potential future biomedical uses. During the modification process, the introduction of metal oxides into bioactive glass resulted in improved antibacterial characteristics, particularly in the composite bioactive glass sample that displayed the highest level of efficiency.

Keywords: antibacterial, bioactive glasses, implant infections, multi drug resistant

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Authors: Lichung Jen, Yi Chun Liu, Kuan-Wei Lee

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Fruitful data has been accumulated in database nowadays and is commonly used as support for decision-making. In the healthcare industry, hospital, for instance, ordering pharmacy inventory is one of the key decision. With large drug inventory, the current cost increases and its expiration dates might lead to future issue, such as drug disposal and recycle. In contrast, underestimating demand of the pharmacy inventory, particularly standing drugs, affects the medical treatment and possibly hospital reputation. Prescription behaviour of hospital physicians is one of the critical factor influencing this decision, particularly irregular prescription behaviour. If a drug’s usage amount in the month is irregular and less than the regular usage, it may cause the trend of subsequent stockpiling. On the contrary, if a drug has been prescribed often than expected, it may result in insufficient inventory. We proposed a hierarchical Bayesian mixture model with two components to identify physicians’ regular/irregular prescription patterns with probabilities. Heterogeneity of hospital is considered in our proposed hierarchical Bayes model. The result suggested that modeling the prescription patterns of physician is beneficial for estimating the order quantity of medication and pharmacy inventory management of the hospital. Managerial implication and future research are discussed.

Keywords: hierarchical Bayesian model, poission mixture model, medicines prescription behavior, irregular behavior

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Authors: Amanda C. Q. M. Vieira, Cybelly M. Melo, Camila B. M. Figueirêdo, Giovanna C. R. M. Schver, Salvana P. M. Costa, Magaly A. M. de Lyra, Ping I. Lee, José L. Soares-Sobrinho, Pedro J. Rolim-Neto, Mônica F. R. Soares

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Epiisopiloturine (EPI) is a drug candidate that is extracted from Pilocarpus microphyllus and isolated from the waste of Pilocarpine. EPI has demonstrated promising schistosomicidal, leishmanicide, anti-inflammatory and antinociceptive activities, according to in vitro studies that have been carried out since 2009. However, this molecule shows poor aqueous solubility, which represents a problem for the release of the drug candidate and its absorption by the organism. The purpose of the present study is to investigate the extent of enhancement of kinetic solubility of a solid solution (SS) of EPI in hipromellose phthalate HP-55 (HPMCP), an enteric polymer carrier. SS was obtained by the solvent evaporation methodology, using acetone/methanol (60:40) as solvent system. Both EPI and polymer (drug loading 10%) were dissolved in this solvent until a clear solution was obtained, and then dried in oven at 60ºC during 12 hours, followed by drying in a vacuum oven for 4 h. The results show a considerable modification in the crystalline structure of the drug candidate. For instance, X-ray diffraction (XRD) shows a crystalline behavior for the EPI, which becomes amorphous for the SS. Polarized light microscopy, a more sensitive technique than XRD, also shows completely absence of crystals in SS sample. Differential Scanning Calorimetric (DSC) curves show no signal of EPI melting point in SS curve, indicating, once more, no presence of crystal in this system. Interaction between the drug candidate and the polymer were found in Infrared microscopy, which shows a carbonyl 43.3 cm-1 band shift, indicating a moderate-strong interaction between them, probably one of the reasons to the SS formation. Under sink conditions (pH 6.8), EPI SS had its dissolution performance increased in 2.8 times when compared with the isolated drug candidate. EPI SS sample provided a release of more than 95% of the drug candidate in 15 min, whereas only 45% of EPI (alone) could be dissolved in 15 min and 70% in 90 min. Thus, HPMCP demonstrates to have a good potential to enhance the kinetic solubility profile of EPI. Future studies to evaluate the stability of SS are required to conclude the benefits of this system.

Keywords: epiisopiloturine, hipromellose phthalate HP-55, pharmaceuticaltechnology, solubility

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Authors: Hind Bouami

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Handling life-critical systems complexity requires to be equipped with appropriate technology and the right human agents’ functions such as knowledge, experience, and competence in problem’s prevention and solving. Human agents are involved in the management and control of human-machine system’s performance. Documenting human agent’s situation awareness is crucial to support human-machine designers’ decision-making. Knowledge about risks, critical parameters and factors that can impact and threaten automation system’s performance should be collected using preventive and retrospective approaches. This paper aims to document operators’ situation awareness through the analysis of automated organizations’ feedback. The analysis of automated hospital pharmacies feedbacks helps to identify and control critical parameters influencing human machine interaction in order to enhance system’s performance and security. Our human machine system evaluation approach has been deployed in Macon hospital center’s pharmacy which is equipped with automated drug dispensing systems since 2015. Automation’s specifications are related to technical aspects, human-machine interaction, and human aspects. The evaluation of drug delivery automation performance in Macon hospital center has shown that the performance of the automated activity depends on the performance of the automated solution chosen, and also on the control of systemic factors. In fact, 80.95% of automation specification related to the chosen Sinteco’s automated solution is met. The performance of the chosen automated solution is involved in 28.38% of automation specifications performance in Macon hospital center. The remaining systemic parameters involved in automation specifications performance need to be controlled.

Keywords: life-critical systems, situation awareness, human-machine interaction, decision-making

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Authors: Yang Cui, Yong Qiang Chen

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An appropriate project delivery system (PDS) is crucial to the success of a construction project. Case-based reasoning (CBR) is a useful support for PDS selection. However, the traditional CBR approach represents cases as attribute-value vectors without taking relations among attributes into consideration, and could not calculate the similarity when the structures of cases are not strictly same. Therefore, this paper solves this problem by adopting the relational case-based reasoning (RCBR) approach for PDS selection, considering both the structural similarity and feature similarity. To develop the feature terms of the construction projects, the criteria and factors governing PDS selection process are first identified. Then, feature terms for the construction projects are developed. Finally, the mechanism of similarity calculation and a case study indicate how RCBR works for PDS selection. The adoption of RCBR in PDS selection expands the scope of application of traditional CBR method and improves the accuracy of the PDS selection system.

Keywords: relational cased-based reasoning, case-based reasoning, project delivery system, PDS selection

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Authors: Shweta Sinha, Mukesh Doble, Manju S. L.

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Pyrazole scaffold is an important group of compound in heterocyclic chemistry and is found to possess numerous uses in chemistry. Pyrazole derivatives are also known to possess important biological activities including antitumor, antimicrobial, antiviral, antifungal, anticancer and anti-inflammatory. Inflammation is associated with pain, allergy and asthma. Leukotrienes are mediators of various inflammatory and allergic disorders. 5-Lipoxygenase (5-LOX) is an important enzyme involved in the biosynthesis of leukotrienes and metabolism of arachidonic acid (AA) and thus targeted for anti-inflammation. In vitro inhibitory activity of pyrazol-3-yl thiazole 4-carboxylic acid derivatives is tested against enzyme 5-LOX. Most of these compounds exhibit good inhibitory activity against this enzyme. Binding mode study of these compounds is determined by computational tool. Further experiments are being done to understand the mechanism of action of these compounds in inhibiting this enzyme. To conclude, these compounds appear to be a promising target in drug design against 5-LOX.

Keywords: inflammation, inhibition, 5-lipoxygenase, pyrazole

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Authors: Ziyad S. Haidar

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Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

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Authors: Tadesse Melaku Abegaz

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Background: there was paucity of data on the self-reported adverse drug reactions (ADRs), level of adherence and clinical outcomes with antidepressants among major depressive disorder (MDD) patients in Ethiopia. Hence, the present study sought to determine the level of adherence for and clinical outcome with antidepressants and the magnitude of ADRs. Methods: A prospective cross-sectional study was employed on MDD patients from September 2016 to January 2017 at Gondar university hospital psychiatry clinic. All patients who were available during the study period were included under the study population. The Naranjo adverse drug reaction probability scale was employed to assess the adverse drug reaction. The rate of medication adherence was determined using morisky medication adherence measurement scale eight. Clinical Outcome of patients was measured by using patient health questionnaire. Multivariable logistic carried out to determine factors for adherence and patient outcome. Results: two hundred seventy patients were participated in the study. More than half of the respondents were males 122(56.2%). The mean age of the participants was 30.94 ± 8.853. More than one-half of the subjects had low adherence to their medications 124(57.1%). About 186(85.7%) of patients encountered ADR. The most common ADR was weight gain 29(13.2). Around 198(92.2%) ADRs were probable and 19(8.8%) were possible. Patients with long standing MDD had high risk of non-adherence COR: 2.458[4.413-4.227], AOR: 2.424[1.185-4.961]. More than one-half 125(57.6) of respondents showed improved outcome. Optimal level of medication adherence was found to be associated with reduced risk of progression of the diseases COR: 0.37[0.110-5.379] and AOR: 0.432[0.201-0.909]. Conclusion: Patient reported adverse drug reactions were more prevalent in major depressive disorder patients. Adherence to medications was very poor in the setup. However, the clinical outcome was relatively higher. Long standing depression was associated with non-adherence. In addition, clinical outcome of patients were affected by non-adherence. Therefore, adherence enhancing interventions should be provided to improve medication adherence and patient outcome.

Keywords: adverse drug reactions, clinical outcomes, Ethiopia, prospective study, medication adherence

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Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, C. V. Rao

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Elvitegravir is the mainstay of anti-HIV combination therapy in most endemic countries presently. However, it cannot be used alone owing to its long onset time of action. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one (Quercetin: QU) is a polyphenolic compound obtained from Argeria speciosa Linn (Family: Convolvulaceae), an anti-HIV candidate. In the present study, a sensitive, simple and rapid high-performance liquid chromatography coupled with positive ion electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the simultaneous determination elvitegravir and Quercetin, in rat plasma. The method was linear over a range of 0.2–500 ng/ml. All validation parameters met the acceptance criteria according to regulatory guidelines. LC–MS/MS method for determination of Elvitegravir and Quercetin was developed and validated. Results show the potential of drug–drug interaction upon co-administration this marketed drugs and plant derived secondary metabolite.

Keywords: anti-HIV resistance, extraction, HPLC-ESI-MS-MS, validation

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Authors: D. Ravinder

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Nickel ferrites and Ni doped Lithium nano ferrites [Li0.5Fe0.5]1-xNixFe2O4 with x= 0.8 and 1.0 synthesized by citrate-gel auto combustion method. The broad peaks in the X-ray diffraction pattern (XRD) indicate a crystalline behavior of the prepared samples. Low temperature magnetization studies i,e Field Cooled (FC) and Zero Field Cooled (ZFC) magnetic studies of the investigated samples are measured by using vibrating sample magnetometer (VSM). The magnetization of the prepared samples as a function of an applied magnetic field 10 T was measured at two different temperatures 5 K and 310 K. Field Cooled (FC) and Zero Field Cooled (ZFC) magnetization measurements under an applied field of 100 Oe and 1000 Oe in the temperature range of 5–375 K were carried out.

Keywords: ferro-spinels, field cooled (FC), Zero Field Cooled (ZFC) and blocking temperature, superpara magnetism, drug delivery applications

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Authors: Idris Lawal

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Electronic payment system is simply a payment or monetary transaction made over the internet or a network of computers. This study was carried out in order to assess how electronic payment system has impacted on banks service delivery, to examine the efficiency of electronic payment system in Nigeria and to determine the level of customer's satisfaction as a direct result of the deployment of electronic payment systems. It is an empirical study conducted using structured questionnaire distributed to officials and customers of Access Bank plc. Chi-square(x2) was adopted for the purpose of data analysis. The result of the study showed that the development of electronic payment system offer great benefit to bank customers including improved services, reduced turn-around time, ease of banking transaction, significant cost saving etc. The study recommends that customer protection laws should be properly put in place to safeguard the interest of end users of e-payment instruments.

Keywords: bank, electronic payment systems, service delivery, customer's satisfaction

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Authors: Qurat-ul-Ain, Humaira Mehmood

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Background: HIV infection (a global pandemic) in pregnant women has turn out to be an emerging aspect of public health because of its role in the spread of HIV infection, predominantly among children. Aim: The aim was to analyze the trends of diagnosis with respect to gestational age and an overview of the mode of delivery over ten years. Methods: A retrospective data collection from clinical records of diagnosed HIV infected pregnant females attended at HIV antenatal clinic (special clinic), at Pakistan Institute of Medical Sciences, Islamabad, for various complaints during the period of 10 years from February 2007 to December 2016 was done. Results: A total of 113 pregnancies were reported with HIV infection in 10 years. Cases diagnosed at the 1st trimester (1-12 weeks) of pregnancy were (50.4%, 57/113), at the 2nd trimester (13-26 weeks) were (24.8%, 28/113), at the 3rd trimester (27-40+ weeks) were (24.7%, 28/113). Most deliveries were by caesarean section (53.1%, 60/113), elective caesarean sections were (58.3%, 35/60) and emergency caesarean sections were (41.6%,25/60). Vaginal deliveries were (26.5%, 30/113). Reported miscarriages were (17.7%, 20/113). Conclusion: At 1st trimester, 50% of the females were diagnosed with HIV infection, and 50% remained undiagnosed at their 1st trimester. Routine antenatal HIV testing throughout the country is vastly needed for timely diagnoses and prompt treatment(antiretroviral therapy), to suppress the virus, to reduce the risk of spread of HIV infection, to plan elective caesarean section delivery and to prevent mother-to-child transmission.

Keywords: gestational age, HIV infection, mode of delivery, pregnancy

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Authors: Yinghui Shang, Ziqing Zhou, Rong Han, Hang Wang, Xiaodi Liu, Yong Yang

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The design of advanced amorphous solids, such as metallic glasses, with targeted properties through artificial intelligence signifies a paradigmatic shift in physical metallurgy and materials technology. Here, we developed a machine-learning architecture that facilitates the generation of metallic glasses with targeted multifunctional properties. Our architecture integrates the state-of-the-art unsupervised generative adversarial network model with supervised models, allowing the incorporation of general prior knowledge derived from thousands of data points across a vast range of alloy compositions, into the creation of data points for a specific type of composition, which overcame the common issue of data scarcity typically encountered in the design of a given type of metallic glasses. Using our generative model, we have successfully designed copper-based metallic glasses, which display exceptionally high hardness or a remarkably low modulus. Notably, our architecture can not only explore uncharted regions in the targeted compositional space but also permits self-improvement after experimentally validated data points are added to the initial dataset for subsequent cycles of data generation, hence paving the way for the customized design of amorphous solids without human intervention.

Keywords: metallic glass, artificial intelligence, mechanical property, automated generation

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Authors: Levente Kovács, Fruzsina Luca Kézér, Ottó Szenci

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Prediction of the onset of calving and recognizing difficulties at calving has great importance in decreasing neonatal losses and reducing the risk of health problems in the early postpartum period. In this study, changes of rumination time, reticuloruminal pH and temperature were investigated in eutocic (EUT, n = 10) and dystocic (DYS, n = 8) dairy cows around parturition. Rumination time was continuously recorded using an acoustic biotelemetry system, whereas reticuloruminal pH and temperature were recorded using an indwelling and wireless data transmitting system. The recording period lasted from 3 d before calving until 7 days in milk. For the comparison of rumination time and reticuloruminal characteristics between groups, time to return to baseline (the time interval required to return to baseline from the delivery of the calf) and area under the curve (AUC, both for prepartum and postpartum periods) were calculated for each parameter. Rumination time decreased from baseline 28 h before calving both for EUT and DYS cows (P = 0.023 and P = 0.017, respectively). After 20 h before calving, it decreased onwards to reach 32.4 ± 2.3 and 13.2 ± 2.0 min/4 h between 8 and 4 h before delivery in EUT and DYS cows, respectively, and then it decreased below 10 and 5 min during the last 4 h before calving (P = 0.003 and P = 0.008, respectively). Until 12 h after delivery rumination time reached 42.6 ± 2.7 and 51.0 ± 3.1 min/4 h in DYS and EUT dams, respectively, however, AUC and time to return to baseline suggested lower rumination activity in DYS cows than in EUT dams for the 168-h postpartum observational period (P = 0.012 and P = 0.002, respectively). Reticuloruminal pH decreased from baseline 56 h before calving both for EUT and DYS cows (P = 0.012 and P = 0.016, respectively), but did not differ between groups before delivery. In DYS cows, reticuloruminal temperature decreased from baseline 32 h before calving by 0.23 ± 0.02 °C (P = 0.012), whereas in EUT cows such a decrease was found only 20 h before delivery (0.48 ± 0.05 °C, P < 0.01). AUC of reticuloruminal temperature calculated for the prepartum period was greater in EUT cows than in DYS cows (P = 0.042). During the first 4 h after calving, it decreased from 39.7 ± 0.1 to 39.00 ± 0.1 °C and from 39.8 ± 0.1 to 38.8 ± 0.1 °C in EUT and DYS cows, respectively (P < 0.01 for both groups) and reached baseline levels after 35.4 ± 3.4 and 37.8 ± 4.2 h after calving in EUT and DYS cows, respectively. Based on our results, continuous monitoring of changes in rumination time and reticuloruminal temperature seems to be promising in the early detection of cows with a higher risk of dystocia. Depressed postpartum rumination time of DYS cows highlights the importance of the monitoring of cows experiencing difficulties at calving.

Keywords: reticuloruminal pH, reticuloruminal temperature, rumination time, dairy cows, dystocia

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Authors: Azeez Yusuf, Alan Casey

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Silver nanoparticles (AgNP) are one of the most widely investigated metallic nanoparticles due to their promising antibacterial activities. In recent years, AgNP research has shifted beyond antimicrobial use to potential applications in the medical arena. This shift coupled with the extensive commercial applications of AgNP will further increase human exposure, and the subsequent risk of adverse effects that may result from repeated exposures and inefficient delivery meaning research into improved AgNP delivery is of paramount importance. In this study, AgNP were encapsulated in a natural bio-surfactant, dipalmitoylphosphatyidyl choline (DPPC), in an attempt to enhance the intracellular delivery and simultaneously mediate the associated cytotoxicity of the AgNP. It was noted that as a result of the encapsulation, liposomal-AgNP (Lipo-AgNP) at 0.625 μg/ml induced significant cell death in THP1 cell lines a notably lower dose than that of the uncoated AgNP induced cytotoxicity. The induced cytotoxicity was shown to result in an increased level of DNA fragmentation resulting in a cell cycle interruption at the S phase of the cell cycle. It was shown that the predominate form of cell death upon exposure to both uncoated and Lipo-AgNP was apoptosis, however, a ROS-independent activation of the executioner caspases 3/7 occurred when exposed to the Lipo-AgNP. These findings showed that encapsulation of AgNP enhances AgNP cytotoxicity and mediates an ROS-independent induction of apoptosis.

Keywords: silver nanoparticles, AgNP, cytotoxicity, encapsulation, liposome

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Authors: Huafeng Wei

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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: Ahmad Nazrun Shuid, Isa Naina Mohamed, Nurul Izzah Ibrahim, Norazlina Mohamed

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Studies have shown that oral tocotrienol, a potent vitamin E, promoted fracture healing of osteoporotic bone. In this study, tocotrienol was combined with a polymer carrier (PLGA), and injected to the fracture site. The slow and constant release of tocotrienol particles would promote fracture healing of post-menopausal osteoporosis rat model. Fracture healing was assessed using micro-CT. Twenty-four Sprague-Dawley rats were ovariectomised or sham-operated and the left tibiae were fractured and fixed with plate and screws. The fractures were created at the upper third of the left tibiae. The rats were divided into 3 groups: sham-operated (SO), ovariectomised-control (OVxC) and PLGA-incorporated tocotrienol treatment (OVx + TT) groups. After 4 weeks, the OVx + TT group showed significantly better callus fracture healing than the OVxC group. In conclusion, tocotrienol-incorporated PLGA was able to promote fracture healing of osteoporotic bone.

Keywords: osteoporosis, micro-CT, tocotrienol, PLGA, fracture

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Authors: Zhi Hao Chow, Cian Mulligan, Jack Walsh, Antonio Garzon Vico, Dimitar Krastev

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Drug development is resource-intensive, time-consuming, and increasingly expensive with each developmental stage. The success rates of drug development are also relatively low, and the resources committed are wasted with each failed candidate. As such, a reliable method of predicting the success of drug development is in demand. The hypothesis was that some examples of failed drug candidates are pushed through developmental pipelines based on false confidence and may possess common linguistic features identifiable through sentiment analysis. Here, the concept of using text analysis to discover such features in research publications and investor reports as predictors of success was explored. R studios were used to perform text mining and lexicon-based sentiment analysis to identify affective phrases and determine their frequency in each document, then using SPSS to determine the relationship between our defined variables and the accuracy of predicting outcomes. A total of 161 publications were collected and categorised into 4 groups: (i) Cancer treatment, (ii) Neurodegenerative disease treatment, (iii) Vaccines, and (iv) Others (containing all other drugs that do not fit into the 3 categories). Text analysis was then performed on each document using 2 separate datasets (BING and AFINN) in R within the category of drugs to determine the frequency of positive or negative phrases in each document. A relative positivity and negativity value were then calculated by dividing the frequency of phrases with the word count of each document. Regression analysis was then performed with SPSS statistical software on each dataset (values from using BING or AFINN dataset during text analysis) using a random selection of 61 documents to construct a model. The remaining documents were then used to determine the predictive power of the models. Model constructed from BING predicts the outcome of drug performance in clinical trials with an overall percentage of 65.3%. AFINN model had a lower accuracy at predicting outcomes compared to the BING model at 62.5% but was not effective at predicting the failure of drugs in clinical trials. Overall, the study did not show significant efficacy of the model at predicting outcomes of drugs in development. Many improvements may need to be made to later iterations of the model to sufficiently increase the accuracy.

Keywords: data analysis, drug development, sentiment analysis, text-mining

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Authors: Paresh Patel, Priya Patel, Vaidehi Sorathiya, Navin Sheth

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The aim of present work was to fabricate Salmeterol Xinafoate (SX) metered dose inhaler (MDI) for asthma and to evaluate the SX loaded solid lipid nanoparticles (SLNs) for pulmonary delivery. Solid lipid nanoparticles can be used to deliver particles to the lungs via MDI. A modified solvent emulsification diffusion technique was used to prepare Salmeterol Xinafoate loaded solid lipid nanoparticles by using compritol 888 ATO as lipid, tween 80 as surfactant, D-mannitol as cryoprotecting agent and L-leucine was used to improve aerosolization behaviour. Box-Behnken design was applied with 17 runs. 3-D surface response plots and contour plots were drawn and optimized formulation was selected based on minimum particle size and maximum % EE. % yield, in vitro diffusion study, scanning electron microscopy, X-ray diffraction, DSC, FTIR also characterized. Particle size, zeta potential analyzed by Zetatrac particle size analyzer and aerodynamic properties was carried out by cascade impactor. Pre convulsion time was examined for control group, treatment group and compare with marketed group. MDI was evaluated for leakage test, flammability test, spray test and content per puff. By experimental design, particle size and % EE found to be in range between 119-337 nm and 62.04-76.77% by solvent emulsification diffusion technique. Morphologically, particles have spherical shape and uniform distribution. DSC & FTIR study showed that no interaction between drug and excipients. Zeta potential shows good stability of SLNs. % respirable fraction found to be 52.78% indicating reach to the deep part of lung such as alveoli. Animal study showed that fabricated MDI protect the lungs against histamine induced bronchospasm in guinea pigs. MDI showed sphericity of particle in spray pattern, 96.34% content per puff and non-flammable. SLNs prepared by Solvent emulsification diffusion technique provide desirable size for deposition into the alveoli. This delivery platform opens up a wide range of treatment application of pulmonary disease like asthma via solid lipid nanoparticles.

Keywords: salmeterol xinafoate, solid lipid nanoparticles, box-behnken design, solvent emulsification diffusion technique, pulmonary delivery

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Authors: Marinna Madrid, Nabiha Saklayen, Marinus Huber, Nicolas Vogel, Christos Boutopoulos, Michel Meunier, Eric Mazur

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Delivering material into cells is important for a diverse range of biological applications, including gene therapy, cellular engineering and imaging. We present a plasmonic substrate for delivering membrane-impermeable material into cells at high throughput and high efficiency while maintaining cell viability. The substrate fabrication is based on an affordable and fast colloidal self-assembly process. When illuminated with a femtosecond laser, the light interacts with the electrons at the surface of the metal substrate, creating localized surface plasmons that form bubbles via energy dissipation in the surrounding medium. These bubbles come into close contact with the cell membrane to form transient pores and enable entry of membrane-impermeable material via diffusion. We use fluorescence microscopy and flow cytometry to verify delivery of membrane-impermeable material into HeLa CCL-2 cells. We show delivery efficiency and cell viability data for a range of membrane-impermeable cargo, including dyes and biologically relevant material such as siRNA. We estimate the effective pore size by determining delivery efficiency for hard fluorescent spheres with diameters ranging from 20 nm to 2 um. To provide insight to the cell poration mechanism, we relate the poration data to pump-probe measurements of micro- and nano-bubble formation on the plasmonic substrate. Finally, we investigate substrate stability and reusability by using scanning electron microscopy (SEM) to inspect for damage on the substrate after laser treatment. SEM images show no visible damage. Our findings indicate that self-assembled plasmonic substrates are an affordable tool for high-throughput, high-efficiency delivery of material into mammalian cells.

Keywords: femtosecond laser, intracellular delivery, plasmonic, self-assembly

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Authors: Taus Muganda

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This research explores the intricate relationship between e-procurement adoption and effective service delivery in the Uganda Coffee Industry, focusing on the processes involved, key actors, and the impact of digital transformation. The study is guided by three prominent theories, Actor-Network Theory, Resource-Based View Theory, and Institutional Theory to comprehensively explore the dynamics of e-procurement in the context of the coffee sector. The primary aim of this project is to examine the e-procurement adoption process and its role in enhancing service delivery within the Uganda Coffee Industry. The research questions guiding this inquiry are: firstly, whether e-procurement adoption and implementation contribute to achieving quality service delivery; and secondly, how e-procurement adoption can be effectively realized within the Uganda Coffee Industry. To address these questions, the study has laid out specific objectives. Firstly, it seeks to investigate the impact of e-procurement on effective service delivery, analysing how the integration of digital processes influences the overall quality of services provided in the coffee industry. Secondly, it aims to critically analyse the measures required to achieve effective delivery outcomes through the adoption and implementation of e-procurement, assessing the strategies that can maximize the benefits of digital transformation. Furthermore, the research endeavours to identify and examine the key actor’s instrumental in achieving effective service delivery within the Uganda Coffee Industry. By utilizing Actor-Network Theory, the study will elucidate the network of relationships and collaborations among actors involved in the e-procurement process. The research contributes to addressing a critical gap in the sector. Despite coffee being the leading export crop in Uganda, constituting 16% of total exports, there is a recognized need for digital transformation, specifically in the realm of e-procurement, to enhance the productivity of producers and contribute to the economic growth of the country. The study aims to provide insights into transforming the Uganda Coffee Industry by focusing on improving the e-procurement services delivered to actors in the coffee sector. The three forms of e-procurement investigated in this research—E-Sourcing, E-Payment, and E-Invoicing—serve as focal points in understanding the multifaceted dimensions of digital integration within the Uganda Coffee Industry. This research endeavours to offer practical recommendations for policymakers, industry stakeholders, and the UCDA to strategically leverage e-procurement for the benefit of the entire coffee value chain.

Keywords: e-procurement, effective service delivery, actors, actor-network theory, resource-based view theory, institutional theory, e-invocing, e-payment, e-sourcing

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Authors: Alaa Eddien Abdallah, Bajes Yousef Alskarnah

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Ant colony based routing algorithms are known to grantee the packet delivery, but they suffer from the huge overhead of control messages which are needed to discover the route. In this paper we utilize the network nodes positions to group the nodes in connected clusters. We use clusters-heads only on forwarding the route discovery control messages. Our simulations proved that the new algorithm has decreased the overhead dramatically without affecting the delivery rate.

Keywords: ad-hoc network, MANET, ant colony routing, position based routing

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Authors: Minh-Phuong Ngoc Bui, Abdennour Abbas

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Microbial spoilage of food/drug has been a constant nuisance and an unavoidable problem throughout history that affects food/drug quality and safety in a variety of ways. A simple and rapid test of fungi and bacteria in food/drugs and environmental clinical samples is essential for proper management of contamination. A number of different techniques have been developed for detection and enumeration of foodborne microorganism including plate counting, enzyme-linked immunosorbent assay (ELISA), polymer chain reaction (PCR), nucleic acid sensor, electrical and microscopy methods. However, the significant drawbacks of these techniques are highly demand of operation skills and the time and cost involved. In this report, we introduce a rapid method for detection of bacteria and fungi in food/drug products using a specific interaction between a reducing agent (tris(2-carboxylethyl)phosphine (TCEP)) and the microbial surface proteins. The chemical reaction was transferred to a transduction system using gold nanoplates-enhanced chemiluminescence. We have optimized our nanoplates synthetic conditions, characterized the chemiluminescence parameters and optimized conditions for the microbial assay. The new detection method was applied for rapid detection of bacteria (E.coli sp. and Lactobacillus sp.) and fungi (Mucor sp.), with limit of detection as low as single digit cells per mL within 10 min using a portable luminometer. We expect our simple and rapid detection method to be a powerful alternative to the conventional plate counting and immunoassay methods for rapid screening of microorganisms in food/drug products.

Keywords: microorganism testing, gold nanoplates, chemiluminescence, reducing agents, luminol

Procedia PDF Downloads 277

Authors: Hamida Hamed Said Al Harthi

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Background: Illegal drug use is a rising problem that affects Omani youth. This research aimed to study a group of young Omani men who were imprisoned more than once for illegal drug use, focusing on exploring their lifestyle experiences inside and outside the prison and whether these contributed to their early relapse and re-imprisonment. This is the first study of its kind from Oman conducted in a prison setting. Methods: 19 Omani males aged 18–35 years imprisoned in Oman Central Prison were recruited using purposive sampling. Focused ethnography was conducted over 8 months to explore the drug-related experiences outside the prison and during imprisonment. Face-to-face semi-structured interviews with the participants yielded detailed transcripts and field notes. These were thematically analyzed, and the results were compared with the existing literature. Results: The participants’ voices yielded new insights into the lives of young Omani men imprisoned for illegal drug use, including their sufferings and challenges in prison. These included: entry shock, timing and boredom, drug trafficking in prison, as well as physical and psychological health issues. Overall, imprisonment was reported to have negatively impacted the participants’ health, personality, self-concept, emotions, attitudes, behavior and life expectations. The participants reported how their efforts to reintegrate into the Omani community after release from prison were rebuffed due to stigmatization and rejection from society and family. They also experienced frequent unemployment, police surveillance, accommodation problems and a lack of rehabilitation facilities. The immensity of the accumulated psychophysiological trauma contributed to their early relapse and re-imprisonment. Conclusion: This thesis concludes that imprisonment is largely ineffective in controlling drug use in Oman. Urgent action is required across multiple sectors to improve the lives and prospects of users of illegal drugs within and outside the prison to minimize factors contributing to early relapse. Key Words: illegal drugs, drug users, Oman, addiction, Omani culture, prisoners, relapse, re-imprisonment, qualitative research, ethnography.

Keywords: illigal drugs, Prison, Omani culture lifestyle, post prison life

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Authors: Odigie Veronica

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The paper focused on the application of Information and Communication Technology (ICT) in effective service delivery in view of the ongoing COVID-19 experience. It adopted the exploratory research method with three research objectives captured. Consequently, the objectives were to ascertain the meaning of online education, understand the concept of COVID-19 and to determine the relevance of online education in effective service delivery in institutions of learning. It is evident from the findings that through ICT, online mode of learning can be adopted in schools which helps greatly in promoting continual education. Online mode of education is practiced online; it brings both the teacher and learners from different places together, without any physical boundary/contact (at least 75%); and has helped greatly in human development in countries where it has been practiced. It is also a welcome development owing to its many benefits such as exposure to digital learning, having access to works of great teachers and educationists such as Socrates, Plato, Dewey, R.S. Peters, J. J. Rosseau, Nnamdi Azikwe, Carol Gilligan, J. I. Omoregbe, Jane Roland Martin, Jean Piaget, among others; and the facilitation of uninterrupted learning for class promotion and graduation of students. Developing the learners all round is part of human development which helps in developing a nation. These and many more are some benefits online education offers which make ICT very relevant in our contemporary society

Keywords: online education, COVID-19 pandemic, effective service delivery, human development

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Authors: Yuvraj Singh Dangi, Kamta Prasad Namdeo, Surendra Bodhake

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The purpose of this research was to develop and evaluate mucoadhesive films for buccal administration of itraconazole using film-forming and mucoashesive polymers. Buccal films of chitosan bearing Itraconazole were prepared by solvent casting technique. The films have been evaluated in terms of film weight, thickness, density, surface pH, FTIR, X-ray diffraction analysis, bioadhesion, swelling properties, and in vitro drug release studies. It was found that film formulations of 2 cm2 size having weight in the range of 204 ± 0.76 to 223 ± 2.09 mg and film thickness were in the range of 0.44 ± 0.11 to 0.57 ± 0.19 mm. Density of the films was found to be 0.102 to 0.126 g/ml. Drug content was found to be uniform in the range of 8.23 ± 0.07 to 8.73 ± 0.09 mg/cm2 for formulation A1 to A4. Maximum bioadhesion force was recorded for HPMC buccal films (A2) i.e. 0.57 ± 0.47 as compared to other films. In vitro residence time was in range of 1.7 ± 0.12 to 7.65 ± 0.15 h. The drug release studies show that formulations follow non-fickian diffusion. These mucoadhesive formulations could offer many advantages in comparison to traditional treatments.

Keywords: biovariability, buccal patches, itraconazole, Mucoadhesion

Procedia PDF Downloads 490

Authors: Esther Kelechi Soyele

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Job satisfaction is the expression of an organisation's fulfillment of work output. In order to achieve effective job satisfaction, the motivation of employees is very essential in stimulating their obligation towards their work. The study examined the motivational strategies, job satisfaction as a correlation of library service delivery in some selected tertiary institutions in southwest Nigeria. The study adopted a descriptive survey research design. A simple random sampling method was employed to select 200 library staff consisting of both library professionals and para-professionals. Two hundred (200) questionnaires were given out, but only one hundred and twenty-nine 129 (96% response rate) were used for the study. Both simple percentage and one and two way ANOVA was used for data analysis. Findings revealed that 60.4% of the respondents were males while 39.6% were female; most of the respondents’ relatively belong to the age group of 31-40 and 41-50, 93.3% were within the age range of 21-50 years, and 43.2 % were M.Sc degree holders. The result revealed a (p < 0.05) significant relationship between work motivational strategies and library service delivery. The results also revealed that motivational development program strategies and job satisfaction have (p < 0.05) a positive significant relationship with library service delivery. It was concluded that work motivation strategies are essential for job satisfaction which is very important in any organization in the attainment of its goals and objectives and helps in maintaining a high standard. The study recommended that more incentive plans that will enhance job satisfaction should be put in place to encourage employees to be more active in carrying out their job effectively.

Keywords: job satisfaction, library, library services, motivational strategies

Procedia PDF Downloads 186

Authors: Alok Shiomurti Tripathi, Ajay Kumar Timiri, Papiya Mitra Mazumder, Anil Chandewar

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The present study evaluates the possible drug interaction between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ) induced in diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction by molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg/kg, ip) and confirms it by assessing the blood and urine biochemical parameters on 28th day of its induction. Selected DN animals were used for the drug interaction between GLIM (0.5mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) after 29th and 70th day of protocol. Drug interaction were assessed by evaluating the plasma drug concentration using HPLC-UV and also determine the change in the biochemical parameter in blood and urine. Mechanism of the interaction was postulated by molecular modeling study using Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in the blood and urine biochemical parameter in STZ treated groups. The concentration of SIL increased significantly (p<0.001) in rat plasma when co administered with GLIM after 70th day of protocol. Molecular modelling study revealed few important interactions with rat serum albumin and CYP2C9.GLIM has strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL. Whereas, for CYP2C9, GLIM has strong hydrogen bond with polar contacts and hydrophobic interactions than SIL. Present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals and mechanism has been supported by molecular modeling studies.

Keywords: diabetic nephropathy, glimepiride, sildenafil citrate, pharmacokinetics, homology modeling, schrodinger

Procedia PDF Downloads 356

Authors: Rahmi Yetri Kasri, Paulus Wirutomo

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Citizen engagement approach has become increasingly important in the rural water sector. However, the question remains as to what exactly is meant by citizen engagement and how this approach can lead to sustainable service delivery. To understand citizen engagement, this paper argues that we need to understand basic elements of social life that consist of social structure, process, and culture within the realm of community’s living environment. Extracting from empirical data from Pamsimas villages in rural West Java, Indonesia, this paper will identify basic elements of social life and environment that influence and form the engagement of citizen and government in delivering and sustaining rural water supply services in Indonesia. Pamsimas or the Water Supply and Sanitation for Low Income Communities project is the biggest rural water program in Indonesia, implemented since 1993 in more than 27,000 villages. The sustainability of this sector is explored through a rural water supply service delivery life-cycle, starts with capital investment, operational and maintenance, asset expansion or renewal, strategic planning for future services and matching cost with financing. Using mixed-method data collection in case study research, this paper argues that increased citizen engagement contributes to a more sustainable rural water service delivery.

Keywords: citizen engagement, rural water supply, sustainability, Indonesia

Procedia PDF Downloads 248