International Science Index

International Journal of Pharmacological and Pharmaceutical Sciences

657
57801
Antihyperglycemic Potential of Chrysin and Diosmin alone or in Combination against Streptozotocin-Induced Hyperglycemia in Rats: Anti-Inflammatory and Antioxidant Mechanisms
Abstract:
Background: Diabetes is a metabolic disease that affects a wide range of people worldwide and results in serious complications. Streptozotocin (STZ) causes selective cytotoxicity in the pancreatic β-cell, and it has been extensively used to induce diabetes mellitus in rats. The present study investigated the effects of diosmin and chrysin alone or in combination with each other on glucose level and on liver in STZ diabetic rats. Methods: In this study, rats were divided into six experimental groups (normal, untreated STZ-diabetic (60 mg/kg B.W., IP), treated STZ-diabetic with glycazide (10 mg/kg B.W, oral), treated STZ-diabetic with diosmin (100 mg/kg B. W., oral), treated STZ-diabetic with chrysin (80 mg/kg B.W., oral), treated STZ-diabetic with diosmin (50 mg/kg B.W, oral) + chrysin (40 mg/kg B.W., oral). After 2 weeks blood samples were withdrawn and glucose was measured. Animals were anaesthetized with an intraperitoneal injection of sodium pentobarbital (60 mg/kg), and sacrificed for dissecting liver. Results: Throughout the experimental period, all treatments significantly (P
656
57801
Antihyperglycemic Potential of Chrysin and Diosmin alone or in Combination against Streptozotocin-Induced Hyperglycemia in Rats: Anti-Inflammatory and Antioxidant Mechanisms
Abstract:
Background: Diabetes is a metabolic disease that affects a wide range of people worldwide and results in serious complications. Streptozotocin (STZ) causes selective cytotoxicity in the pancreatic β-cell, and it has been extensively used to induce diabetes mellitus in rats. The present study investigated the effects of diosmin and chrysin alone or in combination with each other on glucose level and on liver in STZ diabetic rats. Methods: In this study, rats were divided into six experimental groups (normal, untreated STZ-diabetic (60 mg/kg B.W., IP), treated STZ-diabetic with glycazide (10 mg/kg B.W, oral), treated STZ-diabetic with diosmin (100 mg/kg B. W., oral), treated STZ-diabetic with chrysin (80 mg/kg B.W., oral), treated STZ-diabetic with diosmin (50 mg/kg B.W, oral) + chrysin (40 mg/kg B.W., oral). After 2 weeks blood samples were withdrawn and glucose was measured. Animals were anaesthetized with an intraperitoneal injection of sodium pentobarbital (60 mg/kg), and sacrificed for dissecting liver. Results: Throughout the experimental period, all treatments significantly (P
655
57851
Differentiation of Drug Stereoisomers by Their Stereostructure-Selective Membrane Interactions as One of Pharmacological Mechanisms
Abstract:
Since drugs exhibit significant structure-dependent differences in activity and toxicity, their differentiation based on the mechanism of action should have implications for comparative drug efficacy and safety. We aimed to differentiate drug stereoisomers by their stereostructure-selective membrane interactions underlying pharmacological and toxicological effects. Biomimetic lipid bilayer membranes were prepared with phospholipids and sterols (either cholesterol or epicholesterol) to mimic the lipid compositions of neuronal and cardiomyocyte membranes and to provide these membranes with the chirality. The membrane preparations were treated with different classes of stereoisomers at clinically- and pharmacologically-relevant concentrations (25-200 μM), followed by measuring fluorescence polarization to determine the membrane interactivity of drugs to change the physicochemical property of membranes. All the tested drugs acted on lipid bilayers to increase or decrease the membrane fluidity. Drug stereoisomers could not be differentiated when interacting with the membranes consisting of phospholipids alone. However, they stereostructure-selectively interacted with neuro-mimetic and cardio-mimetic membranes containing 40 mol% cholesterol ((3β)-cholest-5-en-3-ol) to show the relative potencies being local anesthetic R(+)-bupivacaine > rac-bupivacaine > S(‒)-bupivacaine, α2-adrenergic agonistic D-medetomidine > rac-medetomidine > L-medetomidine, β-adrenergic antagonistic R(+)-propranolol > rac-propranolol > S(–)-propranolol, NMDA receptor antagonistic S(+)-ketamine > rac-ketamine, analgesic monoterpenoid (+)-menthol > (‒)-menthol, non-steroidal anti-inflammatory S(+)-ibuprofen > rac-ibuprofen > R(‒)-ibuprofen, and bioactive flavonoid (+)-epicatechin > (‒)-epicatechin. All of the order of membrane interactivity were correlated to those of beneficial and adverse effects of the tested stereoisomers. In contrast, the membranes prepared with epicholesterol ((3α)-chotest-5-en-3-ol), an epimeric form of cholesterol, reversed the rank order of membrane interactivity to be S(‒)-enantiomeric > racemic > R(+)-enantiomeric bupivacaine, L-enantiomeric > racemic > D-enantiomeric medetomidine, S(–)-enantiomeric > racemic > R(+)-enantiomeric propranolol, racemic > S(+)-enantiomeric ketamine, (‒)-enantiomeric > (+)-enantiomeric menthol, R(‒)-enantiomeric > racemic > S(+)-enantiomeric ibuprofen, and (‒)-enantiomeric > (+)-enantiomeric epicatechin. The opposite configuration allows drug molecules to interact with chiral sterol membranes enantiomer-selectively. From the comparative results, it is speculated that a 3β-hydroxyl group in cholesterol is responsible for the enantioselective interactions of drugs. In conclusion, the differentiation of drug stereoisomers by their stereostructure-selective membrane interactions would be useful for designing and predicting drugs with higher activity and/or lower toxicity.
654
55073
Proniosomes as a Carrier for Ocular Drug Delivery
Abstract:
Background: Bacterial infections of the eye are the clinical conditions responsible for ocular morbidity and blindness. Conjunctivitis is an inflammation of the conjunctiva, due to Staphylococcus aureus. Lomefloxacin HCl (LXN) is a third generation flouroquinolone antibiotic with a broad spectrum against wide range of bacteria and very effective against Staph infections especially in conjunctiva (conjunctivitis). The present study aims to develop and evaluate novel ocular proniosomal gels of Lomefloxacin Hcl (LXN); in order to improve its ocular bioavailability for the management of bacterial conjunctivitis. Materials and methods: Proniosomes were prepared by coacervation phase separation method using different types of nonionic surfactants (Span 60,40,20,Tween 20,40,60,80,Brij 35,98,72) solely and as mixtures with Span® 60. The formed gels were characterized for entrapment efficiency, vesicle size and in vitro drug release. The optimum proniosomal gel; P-LXN 7 were characterized for pH measurement, transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) as well as Stability study and microbiological evaluation .The results revealed that only Span 60 was able to form stable LXN proniosomal gel when used individually while the other nonionic surfactants formed gels only in combination with Span 60 at different ratios. The optimum proniosomal gel; P-LXN 7 (Span60:Tween60, 9:1) appeared as spherical shaped vesicles having high entrapment efficiency (>80 %), appropriate vesicle size (187 nm) as well as controlled drug release over 12h. DSC confirmed the amorphous nature and the uniformity of LXN inclusion within the vesicles. Physical stability study did not show any significant changes in appearance or entrapment efficiency or vesicle size after storage for 3 months at 4°C. Ocular irritancy test revealed that P-LXN 7 was safe, well tolerable and suitable for ocular delivery. In vivo antibacterial activity of P-LXN 7 evaluated using the susceptibility test and topical therapy of induced ocular conjunctivitis confirmed the enhanced antibacterial therapeutic efficacy of the LXN-proniosomal gel compared to the commercially available LXN eye drops; Orchacin®. Conclusions: Our results suggest that proniosomal gels could provide a promising carrier of LXN for efficient ocular treatment of bacterial conjunctivitis.
653
60611
The Development of The New Drug Delivery Systems Based on Magnetic Zeolites
Abstract:
Magnetic nanocomposites based on zeolite and magnetite nanoparticles were prepared and used as delivery systems for loading and release of drug molecules. Synthesis of magnetic nanocomposite was carried out in the presence of magnetite as the core. Thiamin hydrochloride was used as model drugs. Samples were prepared with different content of magnetite in the zeolite structure and magnetic characteristics and sorption capacity were studied. The magnetic nanocomposites were studied on drug loading and release from these porous systems. The materials were extensively characterized using various physicochemical techniques such as powder X-ray diffraction, nitrogen adsorption isotherms, infrared spectroscopy, thermogravimetric analysis and Scanning Electron Microscopy. The magnetic nanocomposite due to the porous structure of zeolite matrix has good sorption characteristics and can be used as drug delivery systems for controlled release molecules.
652
60428
Misplacing Punishment for Drug Users in Indonesia
Abstract:
Indonesia essentially have regulated medical and social rehabilitation for drug users in its Narcotics Law. Rehabilitation is viewed as an alternative punishment for drug users which still considered as a crime. This idea aims to reduce problem at prison such as overcrowding, overdosing, and HIV/AIDS infection. The rehabilitation program also have an objection to treat drug addiction. Law enforcement especially judge, however, rarely punish drug users with the rehabilitation program. Based on 427 court decision randomly selected, there are 95% of drug addicts who were detained by either police or prosecutor. Moreover, the judge put 90% of them into prison. This practice is not only disregard the Narcotics Law, but also Supreme Court Regulation which guides judge to punish drug addict with medical and social rehabilitation. Consequently, there are more than 45% of detainee and inmate are drug related crime. In addition, the problem also because of lack of control and poor quality on health facility. It caused drug addict were placed to prison rahtern than into medical or social rehabilitation institution. We suggest that structural interventions is should be done in order to fix regulation to decriminalize drug user, build more health facility, and improve medical/social rehabilitation institution mechanism.
651
60524
Evaluation of Free Radical Scavenging and Antiulcer Potential of Methanolic Extract of Benincasa Hispida Seeds
Abstract:
In the present study free radical scavenging and antiulcer potential of Benincasa hispida seeds was evaluated. The powdered seeds were extracted with methanol. The extract was evaluated for its free radical scavenging activity by DPPH method followed by antiulcer activity using pyloric ligation, water immersion stress and NSAID (indomethacin) induced gastric ulcer model (NIU) in rats. The parameters assessed were gastric volume, free acidity, total acidity, ulcer index and percentage ulcer protection. Ranitidine was used as the reference antiulcer drug. The methanolic extract showed concentration dependent DPPH radical scavenging activity. The methanolic extract of Benincasa hispida seeds (MEBH) inhibited gastric ulceration by decreasing the gastric volume, free and total acidity. The high dose (300mg/kg) showed significant reduction in the above parameters which was comparable to the standard drug ranitidine (p< 0.05). The MEBH caused 52.7%, 67.4% and 61.2% inhibition of ulcers in pyloric ligation, water immersion stress and NSAID induced ulcer models respectively at 300mg/kg. Thus it can be concluded that the seeds of Benincasa hispida possess potent antiulcer activity. The antiulcer action may be exerted through free radical scavenging mechanism
650
60109
Evaluation of the Cytotoxicity and Cellular Uptake of a Cyclodextrin-Based Drug Delivery System for Cancer Therapy
Abstract:
Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.
649
60433
Plga Nanoparticles Entrapping dual anti-TB drugs of Amikacin and Moxifloxacin as a Potential Host-Directed Therapy for Multidrug Resistant Tuberculosis
Abstract:
Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles were also readily internalised into macrophages, leading to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into PLGA nanoparticles. The novelty of this work appears in: (1) the efficient encapsulation of two hydrophilic second-line anti-TB drugs,and (2) intramacrophage delivery of this synergistic combination potentially for rapid treatment of multi-drug resistant TB (MDR-TB). Two water-oil-water (w/o/w) emulsion strategies were employed in this study: (1) alginate coated PLGA nanoparticles, and (2) alginate entrapped PLGA nanoparticles. The average particle size and polydispersity index (PDI) of the alginate coated PLGA nanoparticles were found to be unfavourably high with values of 640 ± 32 nm and 0.63 ± 0.09, respectively. In contrast, the alginate entrapped PLGA nanoparticles were within the desirable particle size range of 282 - 315 nm and the PDI was 0.08 - 0.16, and therefore were chosen for subsequent studies. Alginate entrapped PLGA nanoparticles yielded a drug loading of over 10 µg/mg powder for amikacin, and more than 5 µg/mg for moxifloxacin and entrapment efficiencies range of approximately 25-31% for moxifloxacin and 51-59% for amikacin. To study macrophage uptake efficiency, the nanoparticles of alginate entrapped nanoparticle formulation were loaded with acridine orange as a marker, seeded to THP-1 derived macrophages and viewed under confocal microscopy. The particles were readily internalised into the macrophages and highly concentrated in the nucleus region. Furthermore, the anti-mycobacterial activity of the drug-loaded particles was evaluated using M. tuberculosis-infected macrophages, which revealed a significant reduction (4 log reduction) of viable bacterial count compared to the untreated group. In conclusion, the amikacin-moxifloxacin alginate entrapped PLGA nanoparticles are promising for further in vivo studies.
648
56054
Accelerating Square Root Computations over Large Galois Fields GF(2ᵐ)
Abstract:
In this paper, an efficient method for high speed calculation of square root is proposed over Galois Fields GF(2ᵐ). The method is based on using the results of certain pre-computations, and transforming the square root calculations into solving a system of linear logical equations. It is proved that the computational complexity of the proposed method for computing the square root in GF(2m) is O(m), and it is significantly less than the complexity of known methods with O(m2). The proposed method was implemented using different types of multipliers over several polynomial degrees. Software and hardware implementations were done in NTL-C++ and VHDL, respectively. The hardware experimental results show that up to 55% less LUTs and 13% higher speed are obtained comparing with the known works. Moreover, the software experimental results show up to 750% faster than other known methods.
647
56054
Accelerating Square Root Computations over Large Galois Fields GF(2ᵐ)
Abstract:
In this paper, an efficient method for high speed calculation of square root is proposed over Galois Fields GF(2ᵐ). The method is based on using the results of certain pre-computations, and transforming the square root calculations into solving a system of linear logical equations. It is proved that the computational complexity of the proposed method for computing the square root in GF(2m) is O(m), and it is significantly less than the complexity of known methods with O(m2). The proposed method was implemented using different types of multipliers over several polynomial degrees. Software and hardware implementations were done in NTL-C++ and VHDL, respectively. The hardware experimental results show that up to 55% less LUTs and 13% higher speed are obtained comparing with the known works. Moreover, the software experimental results show up to 750% faster than other known methods.
646
56285
A Parallel Cellular Automaton Model of Tumor Growth for Multicore and GPU Programming
Abstract:
Tumor growth from a transformed cancer-cell up to a clinically apparent mass spans through a range of spatial and temporal magnitudes. Through computer simulations, Cellular Automata (CA) can accurately describe the complexity of the development of tumors. Tumor development prognosis can now be made -without making patients undergo through annoying medical examinations or painful invasive procedures- if we develop appropriate CA-based software tools. In silico testing mainly refers to Computational Biology research studies of application to clinical actions in Medicine. To establish sound computer-based models of cellular behavior, certainly reduces costs and saves precious time with respect to carrying out experiments in vitro at labs or in vivo with living cells and organisms. These aim to produce scientifically relevant results compared to traditional in vitro testing, which is slow, expensive, and does not generally have acceptable reproducibility under the same conditions. For speeding up computer simulations of cellular models, specific literature shows recent proposals based on the CA approach that include advanced techniques, such the clever use of supporting efficient data structures when modeling with deterministic stochastic cellular automata. Multiparadigm and multiscale simulation of tumor dynamics is just beginning to be developed by the concerned research community. The use of stochastic cellular automata (SCA), whose parallel programming implementations are open to yield a high computational performance, are of much interest to be explored up to their computational limits. There have been some approaches based on optimizations to advance in multiparadigm models of tumor growth, which mainly pursuit to improve performance of these models through efficient memory accesses guarantee, or considering the dynamic evolution of the memory space (grids, trees,…) that holds crucial data in simulations. In our opinion, the different optimizations mentioned above are not decisive enough to achieve the high performance computing power that cell-behavior simulation programs actually need. The possibility of using multicore and GPU parallelism as a promising multiplatform and framework to develop new programming techniques to speed-up the computation time of simulations is just starting to be explored in the few last years. This paper presents a model that incorporates parallel processing, identifying the synchronization necessary for speeding up tumor growth simulations implemented in Java and C++ programming environments. The speed up improvement that specific parallel syntactic constructs, such as executors (thread pools) in Java, are studied. The new tumor growth parallel model is proved using implementations with Java and C++ languages on two different platforms: chipset Intel core i-X and a HPC cluster of processors at our university. The parallelization of Polesczuk and Enderling model (normally used by researchers in mathematical oncology) proposed here is analyzed with respect to performance gain. We intend to apply the model and overall parallelization technique presented here to solid tumors of specific affiliation such as prostate, breast, or colon. Our final objective is to set up a multiparadigm model capable of modelling angiogenesis, or the growth inhibition induced by chemotaxis, as well as the effect of therapies based on the presence of cytotoxic/cytostatic drugs.
645
56285
A Parallel Cellular Automaton Model of Tumor Growth for Multicore and GPU Programming
Abstract:
Tumor growth from a transformed cancer-cell up to a clinically apparent mass spans through a range of spatial and temporal magnitudes. Through computer simulations, Cellular Automata (CA) can accurately describe the complexity of the development of tumors. Tumor development prognosis can now be made -without making patients undergo through annoying medical examinations or painful invasive procedures- if we develop appropriate CA-based software tools. In silico testing mainly refers to Computational Biology research studies of application to clinical actions in Medicine. To establish sound computer-based models of cellular behavior, certainly reduces costs and saves precious time with respect to carrying out experiments in vitro at labs or in vivo with living cells and organisms. These aim to produce scientifically relevant results compared to traditional in vitro testing, which is slow, expensive, and does not generally have acceptable reproducibility under the same conditions. For speeding up computer simulations of cellular models, specific literature shows recent proposals based on the CA approach that include advanced techniques, such the clever use of supporting efficient data structures when modeling with deterministic stochastic cellular automata. Multiparadigm and multiscale simulation of tumor dynamics is just beginning to be developed by the concerned research community. The use of stochastic cellular automata (SCA), whose parallel programming implementations are open to yield a high computational performance, are of much interest to be explored up to their computational limits. There have been some approaches based on optimizations to advance in multiparadigm models of tumor growth, which mainly pursuit to improve performance of these models through efficient memory accesses guarantee, or considering the dynamic evolution of the memory space (grids, trees,…) that holds crucial data in simulations. In our opinion, the different optimizations mentioned above are not decisive enough to achieve the high performance computing power that cell-behavior simulation programs actually need. The possibility of using multicore and GPU parallelism as a promising multiplatform and framework to develop new programming techniques to speed-up the computation time of simulations is just starting to be explored in the few last years. This paper presents a model that incorporates parallel processing, identifying the synchronization necessary for speeding up tumor growth simulations implemented in Java and C++ programming environments. The speed up improvement that specific parallel syntactic constructs, such as executors (thread pools) in Java, are studied. The new tumor growth parallel model is proved using implementations with Java and C++ languages on two different platforms: chipset Intel core i-X and a HPC cluster of processors at our university. The parallelization of Polesczuk and Enderling model (normally used by researchers in mathematical oncology) proposed here is analyzed with respect to performance gain. We intend to apply the model and overall parallelization technique presented here to solid tumors of specific affiliation such as prostate, breast, or colon. Our final objective is to set up a multiparadigm model capable of modelling angiogenesis, or the growth inhibition induced by chemotaxis, as well as the effect of therapies based on the presence of cytotoxic/cytostatic drugs.
644
57402
Pushing the Boundary of Parallel Tractability for Ontology Materialization via Boolean Circuits
Abstract:
Materialization is an important reasoning service for applications built on the Web Ontology Language (OWL). To make materialization efficient in practice, current research focuses on deciding tractability of an ontology language and designing parallel reasoning algorithms. However, some well-known large-scale ontologies, such as YAGO, have been shown to have good performance for parallel reasoning, but they are expressed in ontology languages that are not parallelly tractable, i.e., the reasoning is inherently sequential in the worst case. This motivates us to study the problem of parallel tractability of ontology materialization from a theoretical perspective. That is we aim to identify the ontologies for which materialization is parallelly tractable, i.e., in the NC complexity. Since the NC complexity is defined based on Boolean circuit that is widely used to investigate parallel computing problems, we first transform the problem of materialization to evaluation of Boolean circuits, and then study the problem of parallel tractability based on circuits. In this work, we focus on datalog rewritable ontology languages. We use Boolean circuits to identify two classes of datalog rewritable ontologies (called parallelly tractable classes) such that materialization over them is parallelly tractable. We further investigate the parallel tractability of materialization of a datalog rewritable OWL fragment DHL (Description Horn Logic). Based on the above results, we analyze real-world datasets and show that many ontologies expressed in DHL belong to the parallelly tractable classes.
643
57402
Pushing the Boundary of Parallel Tractability for Ontology Materialization via Boolean Circuits
Abstract:
Materialization is an important reasoning service for applications built on the Web Ontology Language (OWL). To make materialization efficient in practice, current research focuses on deciding tractability of an ontology language and designing parallel reasoning algorithms. However, some well-known large-scale ontologies, such as YAGO, have been shown to have good performance for parallel reasoning, but they are expressed in ontology languages that are not parallelly tractable, i.e., the reasoning is inherently sequential in the worst case. This motivates us to study the problem of parallel tractability of ontology materialization from a theoretical perspective. That is we aim to identify the ontologies for which materialization is parallelly tractable, i.e., in the NC complexity. Since the NC complexity is defined based on Boolean circuit that is widely used to investigate parallel computing problems, we first transform the problem of materialization to evaluation of Boolean circuits, and then study the problem of parallel tractability based on circuits. In this work, we focus on datalog rewritable ontology languages. We use Boolean circuits to identify two classes of datalog rewritable ontologies (called parallelly tractable classes) such that materialization over them is parallelly tractable. We further investigate the parallel tractability of materialization of a datalog rewritable OWL fragment DHL (Description Horn Logic). Based on the above results, we analyze real-world datasets and show that many ontologies expressed in DHL belong to the parallelly tractable classes.
642
59115
Parallel Vector Processing Using Multi Level Orbital Data
Authors:
Abstract:
Many applications use vector operations by applying the single instruction to multiple data that map to different locations in conventional memory. Transferring data from memory is limited by access latency and bandwidth affecting the performance gain of vector processing. We propose a new memory system that makes all of its content available to processors in time so that processors need not access the memory; we force each location to be available to all processors at a specific time. The data moves in different orbits to become available to other processors in higher orbits at different time. We use this memory to apply parallel vector operations to data streams at first orbit level. Data processed in the first level move to upper orbit one data element at a time, allowing a processor in that orbit to apply another vector operation to deal with serial code limitations inherited in all parallel applications and interleaved it with lower level vector operations.
641
59115
Parallel Vector Processing Using Multi Level Orbital Data
Authors:
Abstract:
Many applications use vector operations by applying the single instruction to multiple data that map to different locations in conventional memory. Transferring data from memory is limited by access latency and bandwidth affecting the performance gain of vector processing. We propose a new memory system that makes all of its content available to processors in time so that processors need not access the memory; we force each location to be available to all processors at a specific time. The data moves in different orbits to become available to other processors in higher orbits at different time. We use this memory to apply parallel vector operations to data streams at first orbit level. Data processed in the first level move to upper orbit one data element at a time, allowing a processor in that orbit to apply another vector operation to deal with serial code limitations inherited in all parallel applications and interleaved it with lower level vector operations.
640
60164
Optimal Number and Placement of Vertical Links in 3D Network-On-Chip
Abstract:
3D technology can lead to a significant reduction in power and average hop-count in Networks on Chip (NoCs). It offers short and fast vertical links which copes with the long wire problem in 2D NoCs. This work proposes heuristic-based method to optimize number and placement of vertical links to achieve specified performance goals. Experiments show that significant improvement can be achieved by using a specific number of vertical interconnect.
639
60164
Optimal Number and Placement of Vertical Links in 3D Network-On-Chip
Abstract:
3D technology can lead to a significant reduction in power and average hop-count in Networks on Chip (NoCs). It offers short and fast vertical links which copes with the long wire problem in 2D NoCs. This work proposes heuristic-based method to optimize number and placement of vertical links to achieve specified performance goals. Experiments show that significant improvement can be achieved by using a specific number of vertical interconnect.
638
59918
Adverse Drug Reactions Monitoring in the Northern Region of Zambia
Abstract:
Introduction: The Copperbelt University Health Services (CBU Health) was designated by the Zambia Medicines Regulatory Authority (ZAMRA) as its agent for coordinating pharmacovigilance in Copperbelt, Luapula, Northern, North Western and Western Provinces. CBU Health’s mandate includes stimulating the reporting of adverse drug reactions (ADRs) as well collecting and collating ADR reports from health institutions in the five provinces. This report covers our experiences from May 2008. Objectives: - To monitor Adverse Drug Reactions (ADRs) in Zambian population - To create awareness amongst health care professionals about the importance of ADR reporting in Zambia - To monitor polypharmacy as well as benefit-risk profile of medicines - Generate independent, evidence based recommendations on the safety of medicines - Support the ZAMRA for formulating safety related regulatory decisions for medicines - Create a national centre of excellence at par with global drug safety monitoring standards - Communicate findings with all key stakeholders. Methodology: Beginning in early May 2008, CBU Health has been visiting on a monthly basis health institutions in the study areas. Activities include holding discussions with health workers, distribution of ADR forms and collection of ADR reports. Once collected these reports are entered into the ADR Register at CBU Health and thereafter causality assessment is done. A report is then prepared for the ZAMRA on quarterly basis. At the ZAMRA, serious ADRs are noted and recommendations made to the Ministry of Health of the Republic of Zambia. Results/Findings: Two thousand six hundred (2600) ADRs have been collected from May, 2008 to December, 2015. These reports were obtained from twenty-one (21) institutions in the Copperbelt. The reports have all been documented and assessed using the WHO Causality Method. Most of the ADRs reports were caused by antiretroviral drugs (ARVs) and some by anti-malarial drugs like Artemether/Lumefantrine – Coartem®. Five hundred reports were sent to the Uppsala Monitoring Centre Vigiflow for further analysis. Conclusion: Monitoring of adverse drug reactions is an integral component in patient safety and this should be supported by all partners in WHO programmes. As a centre for drug safety, we will ensure that we achieve our objectives to monitor ADRs in Zambia. Pharmacovigilance is the science relating to the detection, assessment, understanding and prevention of the adverse effects of drugs. It is an important public health specialty as drug safety awareness can lead to better patient outcomes and reduction in drug related morbidity. Our results show that pharmacovigilance is becoming an integral part of clinical care in Zambia for patient safety. However, erratic funding to run the programme smoothly had been our challenge.
637
58096
Quality of Life of Patients on Oral Anticoagulant Therapy in Outpatient Cardiac Department Dr. Hasan Sadikin Central General Hospital Bandung
Abstract:
Cardiovascular disease is the cause of the highest mortality rates in the world. The number of cardiovascular disease patients is increasing every year. Data obtained from World Health Organization (WHO) that 17,5 million people died from this disease. The condition of cardiovascular diseases such as atrial fibrillation, myocardial infarction, venous thromboembolism, and several other conditions need anticoagulant therapy. Results of the anticoagulant therapy are measured not only by the effectiveness of International Normalized Ratio (INR) value but also by the quality of life of the patients. The purpose of this study was to determine the quality of life of patients on oral anticoagulant therapy in outpatient cardiac department Dr. Hasan Sadikin central general hospital, Bandung, Indonesia. This is a cross-sectional study with collecting data from the quality of life questionnaire and medical record of the patients. The results of this study showed that 28 patients (46,7%) had a good quality of life, 30 patients (50%) had a moderate quality of life, and 2 patients (3,3%) had a poor quality of life with no significant differences in quality of life based on age, gender, diagnosis, and duration of drug use.
636
58099
Quality of Life of Patients on Oral Antiplatelet Therapy in Outpatient Cardiac Department Dr. Hasan Sadikin Central General Hospital Bandung
Abstract:
Health Research Data, Ministry of Health of Indonesia in 2007, showed coronary heart disease (CHD) or coronary artery disease (CAD) was the third leading cause of death in Indonesia after hypertension and stroke with 7.2% incidence rate. Antiplatelet is one of the important therapy in management of patients with CHD. In addition to therapeutic effect on patients, quality of life is one aspect of another assessment to see the success of antiplatelet therapy. The purpose of this study was to determine the quality of life of patients on oral antiplatelet therapy in outpatient cardiac department Dr. Hasan Sadikin central general hospital, Bandung, Indonesia. This research is a cross sectional by collecting data through quality of life questionnaire of patients which performed prospectively as primary data and secondary data from medical record of patients. The results of this study showed that 54.3% of patients had a good quality of life, 45% had a moderate quality of life, and 0.7% had a poor quality of life. There are no significant differences in quality of life-based on age, gender, diagnosis, and duration of drug use.
635
59242
Synergistic Effect of Eugenol Acetate with Betalactam Antibiotic on Betalactamase and Its Bioinformatics Analysis
Abstract:
Beta-lactam antibiotics are the most frequently prescribed medications in modern medicine. The antibiotic resistance by the production of enzyme beta-lactamase is an important mechanism seen in microorganisms. Resistance to beta-lactams mediated by beta-lactamases can be overcome successfully with the use of beta-lactamase inhibitors. New generations of the antibiotics contain mostly synthetic compounds, and many side effects have been reported for them. Combinations of beta-lactam and beta-lactamase inhibitors have become one of the most successful antimicrobial strategies in the current scenario of bacterial infections. Plant-based drugs are very cheap and having lesser adverse effect than synthetic compounds. The synergistic effect of eugenol acetate with beta-lactams restores the activity of beta-lactams, allowing their continued clinical use. It is reported here the enhanced inhibitory effect of phytochemical, eugenol acetate, isolated from the plant Syzygium aromaticum with beta-lactams on beta-lactamase. The compound was found to have synergistic effect with the antibiotic amoxicillin against antibiotic-resistant strain of S.aureus. The enzyme was purified from the organism and incubated with the compound. The assay showed that the compound could inhibit the enzymatic activity of beta-lactamase. Modeling and molecular docking studies indicated that the compound can fit into the active site of beta-lactamase and can mask the important residue for hydrolysis of beta-lactams. The synergistic effects of eugenol acetate with beta-lactam antibiotics may justify, the use of these plant compounds for the preparation of β-lactamase inhibitors against β-lactam resistant S.aureus.
634
58625
Near-Infrared Optogenetic Manipulation of a Channelrhodopsin via Upconverting Nanoparticles
Abstract:
Optogenetics is an innovative technology now widely adopted by researchers in different fields of the biological sciences. However, due to the weak tissue penetration capability of the short wavelengths used to activate light-sensitive proteins, an invasive light guide has been used in animal studies for photoexcitation of target tissues. Upconverting nanoparticles (UCNPs), which transform near-infrared (NIR) light to short-wavelength emissions, can help address this issue. To improve optogenetic performance, we enhance the target selectivity for optogenetic controls by specifically conjugating the UCNPs with light-sensitive proteins at a molecular level, which shortens the distance as well as enhances the efficiency of energy transfer. We tagged V5 and Lumio epitopes to the extracellular N-terminal of channelrhodopsin-2 with an mCherry conjugated at the intracellular C-terminal (VL-ChR2m) and then bound NeutrAvidin-functionalized UCNPs (NAv-UCNPs) to the VL-ChR2m via a biotinylated antibody against V5 (bV5-Ab). We observed an apparent energy transfer from the excited UCNP (donor) to the bound VL-ChR2m (receptor) by measuring emission-intensity changes at the donor-receptor complex. The successful patch-clamp electrophysiological test and an intracellular Ca2+ elevation observed in the designed UCNP-ChR2 system under optogenetic manipulation confirmed the practical employment of UCNP-assisted NIR-optogenetic functionality. This work represents a significant step toward improving therapeutic optogenetics.
633
57898
In-Silico Evaluation and Antihyperglycemic Potential of Leucas Cephalotes
Abstract:
The present study is carried out to explore the anti-hyperglycemic activity of Leucas cephalotes plant parts. A fruit, leaves, stems, and roots part of the Leucas cephalotes has been extracted in ethanol and have been evaluated for anti-hyperglycemic activity. The present study indicated that, ethanolic extract of fruit and leaves have shown significant α- amylase inhibitory activity with IC50 value of 92.86 ± 0.89 μg/mL and 98.09 ± 0.69 μg/mL respectively. Two known compounds β-sitosterol and lupeol were isolated from ethanolic extract of L. cephalotes leaves and were subjected to anti-hyperglycemic activity. Lupeol shows the best activity with IC50 55.73 ± 0.47 μg/mL and the results were verified by docking study of these compounds with mammalian α-amylase was carried out on its active site. It was concluded from the study that β-sitosterol and lupeol form one H-bond interactions with the active site residues either Asp212 or Thr21. The estimated free energy binding of β-sitosterol was found to be -9.47 kcal mol-1 with an estimated inhibition constant (Ki) of 558.94 nmol whereas the estimated free energy binding of lupeol was -11.73 kcal mol-1 with an estimated inhibition constant (Ki) of 476.71pmmol. The present study clearly showed that lupeol is more potent in comparison to β-sitosterol. The study indicates that L. cephalotes have significant potential to inhibit α-amylase enzyme.
632
60587
Anti-Angiogenic and Anti-Metastatic Effect of Aqueous Fraction from Euchelus asper Methanolic Extract.
Abstract:
Angiogenesis and metastasis are two of the most important hallmarks of cancer. Hence, most of the cancer therapies now-a-days are multi-targeted so as to reduce resistance and have better efficacy. As synthetic molecules arise with a burden of their own toxicities and side-effects, more and more research is being focused on exploiting the vast natural resources of drugs, in the form of plants and animals. Although, the idea of using marine organisms as a source of pharmaceuticals is not new, the pace at which marine drugs are being discovered, has definitely up surged! In the present study, we have assessed the anti-angiogenic and in vitro anti-metastatic activity of aqueous fraction from the extract of marine gastropod Euchelus asper. The soft body of Euchelus asper was extracted with methanol and named EAME. Partition chromatography of EAME gave three fractions EAME I, II and III. Biochemical analysis revealed the presence of proteins in EAME III. Preliminary analysis had revealed the anti-angiogenic activity was exhibited by EAME III out of the three fractions. Hereafter, EAME III (concentration 25µg/ml-400µg/ml) was tested on chick chorio-allantoic membrane (CAM) model for the detailed analysis of its potential anti-angiogenic effect. In vitro testing of the fraction (concentration 0.25µg/ml - 1µg/ml), involved cytotoxicity by SRB assay, cell cycle analysis by flow cytometry and anti-proliferative effect by scratch wound healing assay on A549 lung carcinoma cells. Apart from this, a portion of treated CAM as well as conditioned medium from treated A549 were subjected to gelatin zymography for assessment of matrix metalloproteinases MMP-2 and MMP-9 levels. Our results revealed that EAME III exhibited significant anti-angiogenic activity on CAM which was also supported by histological observations. During histological studies of CAM, it was found that EAME III caused reduction in angiogenesis by altering the extracellular matrix of the CAM membrane. In vitro analysis disclosed that EAME III exhibited moderate cytotoxic effect on A549 cells and its effect was not dose-dependent. The results of flow cytometry confirmed that EAME III caused cell cycle arrest in A549 cell line as almost all of the treated cells were found in G1 phase. Further, the migration and proliferation of A549 was significantly reduced by EAME III as observed from the scratch wound assay. Moreover, Gelatin zymography analysis revealed that EAME III caused suppression of MMP-2 in CAM membrane and reduced MMP-9 and MMP-2 expression in A549 cells. This verified that the anti-angiogenic and anti-metastatic effects of EAME III were correlated with the suppression of MMP-2 and -9. To conclude, EAME III shows dual anti-tumour action by reducing angiogenesis and exerting anti-metastatic effect on lung cancer cells, thus it has the potential to be used as an anti-cancer agent against lung carcinoma.
631
56581
Potential of Polyphenols from Tamarix Gallica towards Common Pathological Features of Diabetes and Alzheimer’s Diseases
Abstract:
Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system, respectively. It is now widely recognized that T2DM and AD share many pathophysiological features including glucose metabolism, increased oxidative stress and amyloid aggregation. Amyloid beta (Aβ) is the components of the amyloid deposits in the AD brain and while the component of the amyloidogenic peptide deposit in the pancreatic islets of Langerhans is identified as human islet amyloid polypeptide (hIAPP). These two proteins are originated from the amyloid precursor protein and have a high sequence similarity. Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-beta-spine. Add at that, extensive studies in the past years have found that like Aβ1-42, IAPP forms early intermediate assemblies as spherical oligomers, implicating that these oligomers possess a common folding pattern or conformation. These similarities can be used in the search for effective pharmacotherapy for DM, since potent therapeutic agents such as antioxidants with a catechol moiety, proved to inhibit Aβ aggregation, may play a key role in the inhibit the aggregation of hIAPP treatment of patients with DM. Tamarix gallica is one of the halophyte species having a powerful antioxidant system. Although it was traditionally used for the treatment of various liver metabolic disorders, there is no report about the use of this plant for the treatment or prevention of T2DM and AD. Therefore, the aim of this work is to investigate their protective effect towards T2DM and AD by isolation and identification of α-glucosidase inhibitors, with antioxidant potential, that play an important role in the glucose metabolism in diabetic patient, as well as, the polymerization of hIAPP and Aβ aggregation inhibitors. Structure-activity relationship study was conducted for both assays. And as for α-glucosidase inhibitors, their mechanism of action and their synergistic potential when applied with a very low concentration of acarbose were also suggesting that they can be used not only as α-glucosidase inhibitors but also be combined with established α-glucosidase inhibitors to reduce their adverse effect. The antioxidant potential of the purified substances was evaluated by DPPH and SOD assays. Th-T assay using 42-mer amyloid β-protein (Aβ42) for AD and hIAPP which is a 37-residue peptide secreted by the pancreatic β –cells for T2DM and Transmission electronic microscopy (TEM) were conducted to evaluate the amyloid aggragation of the actives substances. For α-glucosidase, p-NPG and glucose oxidase assays were performed for determining the inhibition potential and structure-activity relationship study. The Enzyme kinetic protocol was used to study the mechanism of action. From this research, it was concluded that polyphenols playing a role in the glucose metabolism and oxidative stress can also inhibit the amyloid aggregation, and that substances with a catechol and glucuronide moieties inhibiting amyloid-β aggregation, might be used to inhibit the aggregation of hIAPP.
630
57902
Comparison of β-Cell Regenerative Potentials of Selected Sri Lankan Medicinal Plant Extracts in Alloxan-Induced Diabetic Rats
Abstract:
Triggering of β-cell regeneration is a recognized therapeutic strategy for the treatment of type 1 diabetes mellitus. One such approach to foster restoration and regeneration of β-cells is from exogenous natural extracts. The aim of the present study was to investigate and compare the β-cell regenerative potentials of the extracts of Spondias pinnata (Linn. f.) Kurz, Coccinia grandis (L.) Voigt and Gmelina arborea Roxb. in alloxan induced diabetic rats. Wistar rats were divided in to six groups (n=6); healthy untreated rats, alloxan induced diabetic untreated rats (150 mg/kg, ip), diabetic rats receiving the extracts of S. pinnata (1.0 g/kg), C. grandis (0.75 g/kg), G. arobrea (1.00 g/kg) and diabetic rats receiving glibenclamide (0.5 mg/kg) for 30 days. The assessment of selected biochemical parameters, histopathology and immunohistochemistry in the pancreatic tissue were done on the 30th day. The reduction in the percentage of HbA1C was in the decreasing order of C. grandis (35%), G. arborea (31%) and S. pinnata (29%) in alloxan induced diabetic rats (p< 0.05). The concentration of serum fructosamine, insulin and C-peptide were decreased significantly in a decreasing order of C. grandis (30%, 72%, 51%), G. arborea (25%, 44%, 44%) and S. pinnata (27%, 34%, 24%) in alloxan induced diabetic rats (p < 0.05). The extent of β-cell regeneration was in the decreasing order of C. grandis, G. arborea, S. pinnata reflected through the increased percentage of insulin secreting β-cells in alloxan induced diabetic rats. The extract of C. grandis produced the highest degree of β-cell regeneration demonstrated through an increase in the number of islets and percentage of the insulin secreting β-cells (75%) in the pancreas of diabetic rats (p < 0.05). Further the C. grandis extract produced a significant increase in mean profile diameter in small (118%), average (10%), and large (13%) islets as compared with diabetic control rats respectively. However, statistically significant increase in the islet profile diameter was shown only in average (2%) and large (5%) islets in the G. arborea extract treated rats and large islets (5%) in S. pinnata extract treated diabetic rats (p < 0.05). The β-cell regeneration potency was in the decreasing order of C. grandis (0.75 g/kg), G. arborea (1.00 g/kg) and S. pinnata (1.00 g/kg) in alloxan induced diabetic rats. The three plant extracts may be useful as natural agents of triggering the β-cell regeneration in the management of type 1 diabetes mellitus.
629
60035
Formulation and Evaluation of Ethosomes of Plumeria indica Linn. Flowers
Abstract:
The number of products based on new drug delivery systems has significantly increased in the past few years, and this growth is expected to continue in the near future. These biopharmaceuticals present challenges to drug delivery scientists because of their unique nature and difficulty in delivery through conventional routes. Therefore, future research will focus on the delivery of these complex molecules through different routes, including oral, nasal, pulmonary, vaginal, rectal, etc. The aim of present study was to formulate and evaluate ethosomes of Plumeria indica flowers which may deliver the drug to targeted site more efficiently than marketed preparation and also overcome the problems related with oral administration of drug. The formulations were prepared with ethanol, lecithin, propylene glycol and were evaluated.
628
60139
Traditional Phytotherapy among Tribes of Madhya Pradesh, India Used in the Treatment of Ear, Nose and Throat Disorders
Abstract:
Madhya Pradesh, a Central State of India is rich in natural heritage due to tribal impact. Herbal harmony present either cultivated or by naturally being used by the tribes of the state in the treatment of several human and animal disorders. Diseases of ear, nose and throat (ENT) often have serious consequences including hearing impairment, and emotional strain that lower the quality of life of patients. Traditional phytotherapy have now been found to be instrumental in improving chances of discovering plants with antimicrobial activity in new drug development. The present paper enumerates the uses of ten herbs viz., garlic, eucalyptus, marigold, tulsi, euphorbia, lemon grass, haldi, bhringraj, ginger and ajwain. An attempt has also been made to reveal the method of preparation, dose, duration possible MOA of these herbs used for ENT disorders.