Displaying publications 1 - 20 of 77 in total

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  1. Transforming XML-based electronic patient records for use in medical case based reasoning systems
    Abidi SS, Manickam S
    Stud Health Technol Inform, 2000;77:709-13.
    PMID: 11187645
    Electronic patient records (EPR) can be regarded as an implicit source of clinical behaviour and problem-solving knowledge, systematically compiled by clinicians. We present an approach, together with its computational implementation, to pro-actively transform XML-based EPR into specialised Clinical Cases (CC) in the realm of Medical Case Base Systems. The 'correct' transformation of EPR to CC involves structural, terminological and conceptual standardisation, which is achieved by a confluence of techniques and resources, such as XML, UMLS (meta-thesaurus) and medical knowledge ontologies. We present below the functional architecture of a Medical Case-Base Reasoning Info-Structure (MCRIS) that features two distinct, yet related, functionalities: (1) a generic medical case-based reasoning system for decision-support activities; and (2) an EPR-CC transformation system to transform typical EPR's to CC.
  2. Extracting clinical cases from XML-based electronic patient records for use in web-based medical case based reasoning systems
    Manickam S, Abidi SS
    Stud Health Technol Inform, 2001;84(Pt 1):643-7.
    PMID: 11604816
    Development and usage of Case Based Reasoning (CBR) driven medical diagnostic system requires a large volume of clinical cases that depict the problem-solving methodology of medical experts. Successful usage of CBR based systems in healthcare is constrained by the need for a continuous supply of current and correct clinical cases (in an electronic medium) from medical experts. To address this constraint we present a strategy to pro-actively transform generic Electronic Patient Records (EPR) to Operable CBR-oriented Cases (OCC) that are compliant to specialised CBR-based medical systems. EPR-OCC transformation methodology is based on XML parse-trees, Unified Medical Language Source (UMLS) meta-thesauri and medical knowledge ontologies. The featured work involves the implementation of a Java-based computer system for the automatic transformation of XML-based EPR-originating from heterogeneous EPR repositories accessible over the Internet/WWW-to specialised OCC that can then be seamlessly incorporated within Intelligent CBR-based Medical Diagnostic Systems.
  3. State of the art and recent advances in the ultrasound-assisted synthesis, exfoliation and functionalization of graphene derivatives
    Muthoosamy K, Manickam S
    Ultrason Sonochem, 2017 Nov;39:478-493.
    PMID: 28732972 DOI: 10.1016/j.ultsonch.2017.05.019
    Sonochemistry, an almost a century old technique was predominantly employed in the cleaning and extraction processes but this tool has now slowly gained tremendous attention in the synthesis of nanoparticles (NPs) where particles of sub-micron have been produced with great stability. Following this, ultrasonication techniques have been largely employed in graphene synthesis and its dispersion in various solvents which would conventionally take days and offers poor yield. Ultrasonic irradiation allows the production of thin-layered graphene oxide (GO) and reduced graphene oxide (RGO) of up to 1nm thickness and can be produced in single layers. With ultrasonic treatment, reactions were made easy whereby graphite can be directly exfoliated to graphene layers. Oxidation to GO can also be carried out within minutes and reduction to RGO is possible without the use of any reducing agents. In addition, various geometry of graphene can be produced such as scrolled graphene, sponge or foam graphene, smooth as well as those with rough edges, each serving its own unique purpose in various applications such as supercapacitor, catalysis, biomedical, etc. In ultrasonic-assisted reaction, deposition of metal NPs on graphene was more homogeneous with custom-made patterns such as core-shell formation, discs, clusters and specific deposition at the edges of graphene sheets. Graphene derivatives with the aid of ultrasonication are the perfect catalyst for various organic reactions as well as an excellent adsorbent. Reactions which used to take hours and days were significantly reduced to minutes with exceedingly high yields. In a more recent approach, sonophotocatalysis was employed for the combined effect of sonication and photocatalysis of metal deposited graphene. The system was highly efficient in organic dye adsorption. This review provides detailed fundamental concepts of ultrasonochemistry for the synthesis of graphene, its dispersion, exfoliation as well as its functionalization, with great emphasis only based on recent publications. Necessary parameters of sonication such as frequency, power input, sonication time, type of sonication as well as temperature and dual-frequency sonication are discussed in great length to provide an overview of the resultant graphene products.
  4. Hydrodynamic cavitation assisted degradation of persistent endocrine-disrupting organochlorine pesticide Dicofol: Optimization of operating parameters and investigations on the mechanism of intensification
    Panda D, Manickam S
    Ultrason Sonochem, 2019 Mar;51:526-532.
    PMID: 30224289 DOI: 10.1016/j.ultsonch.2018.04.003
    Dicofol, a recommended Stockholm convention persistent organic pollutants (POPs) candidate is well known for its endocrine disruptive properties and has been extensively used as an organochlorine pesticide worldwide. The hydrodynamic cavitation (HC) treatment of Dicofol in aqueous media induced by a liquid whistle hydrodynamic cavitaion reactor (LWHCR) has been investigated while considering important parameters such as inlet pressure, initial concentration of Dicofol, solution temperature, pH, addition of H2O2 and radical scavenger for the extent of degradation. The pseudo-first-order degradation rate constant (k) was determined to be 0.073 min-1 with a cavitational yield of 1.26 × 10-5 mg/J at optimum operating conditions and a complete removal of Dicofol was achieved within 1 h of treatment. Considering the removal rate and energy efficiency, the optimal inlet pressure was found to be 7 bar, resulting in a cavitation number of 0.17. High performance liquid chromatography (HPLC) and Gas chromatography mass spectroscopy (GC-MS) analyses indicated a sharp decline in the concentration of Dicofol with treatment time and indicated the presence of degraded products. An 85% total organic carbon (TOC) removal was achieved within 1 h of treatment time, demonstrating successful mineralization of Dicofol. The obtained results suggest that the degradation of Dicofol followed thermal decomposition and successive recombination reactions at bubble-vapor interface. Overall, the attempted hydrodynamic cavitation demonstrated successful and rapid removal of endocrine disruptive chemicals such as Dicofol and is expected to provide efficient solution for wastewater treatment.
  5. Recent advancements in the sonophotocatalysis (SPC) and doped-sonophotocatalysis (DSPC) for the treatment of recalcitrant hazardous organic water pollutants
    Panda D, Manickam S
    Ultrason Sonochem, 2017 May;36:481-496.
    PMID: 28069236 DOI: 10.1016/j.ultsonch.2016.12.022
    Sonophotocatalysis (SPC) is considered to be one of the important wastewater treatment techniques and hence attracted the attention of researchers to eliminate recalcitrant hazardous organic pollutants from aqueous phase. In general, SPC refers to the integrated use of ultrasonic sound waves, ultraviolet radiation and the addition of a semiconductor material which functions as a photocatalyst. Current research has brought numerous improvements in the SPC based treatment by opting visible light irradiation, nanocomposite catalysts and numerous catalyst supports for better stability and performance. This review accomplishes a critical analysis with respect to the recent advancements. The efficiency of SPC based treatments has been analyzed by considering the individual methods i.e. sonolysis, photocatalysis, sonophotolysis, sono-ozone, photo-Fenton and sono-Fenton. Besides, the essential parameters such as solution temperature, concentrations of initial pollutant and catalyst, initial pH, dosages of Fenton's reagent and hydrogen peroxide (H2O2), ultrasonic power density, gas sparging, addition of radical scavenger, addition of carbon tetrachloride and methanol have been discussed with suggestions for the selection of optimum parameters. A higher synergistic pollutant removal rate has been reported during SPC treatment as compared to individual methods and the implementation of numerous doping materials and supports for the photocatalyst enhances the degradation rate of pollutants using DSPC under both visible and UV irradiation. Overall, SPC and DSPC based wastewater treatments are emerging as potential techniques as they provide effective solution in removing the recalcitrant organic pollutants and progressive research is expected to bring out superior treatment efficiency using these advanced technologies.

    IMPORTANCE OF THIS REVIEW: The review has accomplished a thorough and a critical analysis of sonophotocatalysis (SPC) based on the recently published journals. Recent advancements in the doped sonophotocatalysis (DSPC) and the mechanisms behind synergistic enhancement in the pollutant degradation rate have been discussed with justifications. Besides, the possible future works are suggested for the advancements in sonophotocatalysis based treatment. This review will be beneficial for electing a SPC based method because of the accomplished sharp comparisons among the published results. The review includes current advancements of SPC based methods which aid for a low-cost and a large-scale wastewater treatment application.

  6. Fulltext Nanomaterials for disease diagnostics
    Muthoosamy K, Manickam S
    Mikrochim Acta, 2023 Mar 18;190(4):143.
    PMID: 36933103 DOI: 10.1007/s00604-023-05724-z
  7. Fulltext Potential of chitosan-loaded nanoemulsions to control different Colletotrichum spp. and maintain quality of tropical fruits during cold storage
    Zahid N, Ali A, Manickam S, Siddiqui Y, Maqbool M
    J Appl Microbiol, 2012 Oct;113(4):925-39.
    PMID: 22805053 DOI: 10.1111/j.1365-2672.2012.05398.x
    To investigate the antifungal activity of conventional chitosan and chitosan-loaded nanoemulsions against anthracnose caused by Colletotrichum spp. isolated from different tropical fruits.
  8. Investigation of Requisites for the Optimal Mycelial Growth of the Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), on Oil Palm Biomass in Malaysia
    Sudheer S, Ali A, Manickam S
    Int J Med Mushrooms, 2016;18(10):935-943.
    PMID: 27910761
    Rigorous research has been carried out regarding the cultivation of Ganoderma lucidum using different agricultural residues. Nevertheless, large-scale cultivation and the separation of active compounds of G. lucidum are still challenges for local farmers. The objective of this study was to evaluate the use of oil palm waste fibers such as empty fruit bunch fibers and mesocarp fibers as effective substrates for the growth of G. lucidum mycelia to study the possibility of solid-state cultivation and to determine the optimum conditions necessary for the growth of mycelia of this mushroom on these waste fibers. Various parameters such as temperature, pH, humidity, and carbon and nitrogen compositions required for the optimum growth of mycelia have been determined. Oil palm fibers are a vivid source of lignocellulose, and their availability in Malaysia is high compared to that of sawdust. G. lucidum is a wood-rotting fungi that can easily decay and utilize this lignocellulose biomass, a major agricultural waste in Malaysia.
  9. Sono-nano chemistry: A new era of synthesising polyhydroxylated carbon nanomaterials with hydroxyl groups and their industrial aspects
    Afreen S, Muthoosamy K, Manickam S
    Ultrason Sonochem, 2019 Mar;51:451-461.
    PMID: 30224290 DOI: 10.1016/j.ultsonch.2018.07.015
    The main objective of this review is to derive the salient features of previously developed ultrasound-assisted methods for hydroxylating graphene and Buckminsterfullerene (C60). The pros and cons associated to ultrasound-assisted synthesis of hydroxy-carbon nanomaterials in designing the strategical methods for the industrial bulk production are also discussed. A guideline on the statistical methods has also been considered to further provide the scopes towards the application of the previously reported methods. Irrespective of many useful methods that have been developed in order to functionalize C60 and graphene by diverse oxygenated functional groups e.g. epoxide, hydroxyl, carboxyl as well as metal/metal oxide via a combination of organic chemistry and sonochemistry, there is no report dealing exclusively on the application of ultrasonic cavitation particularly to synthesising polyhydroxylated carbon nanomaterials. On this context, this review emphasizes in investigating the critical aspects of sono-nanochemistry and the statistical approaches to optimize the variables in the sonochemical process towards a large-scale synthesis of polyhydroxylated graphene and C60.
  10. Fulltext COVID-19 Vehicle Based on an Efficient Mutual Authentication Scheme for 5G-Enabled Vehicular Fog Computing
    Al-Shareeda MA, Manickam S
    Int J Environ Res Public Health, 2022 Nov 24;19(23).
    PMID: 36497709 DOI: 10.3390/ijerph192315618
    The COVID-19 pandemic is currently having disastrous effects on every part of human life everywhere in the world. There have been terrible losses for the entire human race in all nations and areas. It is crucial to take good precautions and prevent COVID-19 because of its high infectiousness and fatality rate. One of the key spreading routes has been identified to be transportation systems. Therefore, improving infection tracking and healthcare monitoring for high-mobility transportation systems is impractical for pandemic control. In order to enhance driving enjoyment and road safety, 5G-enabled vehicular fog computing may gather and interpret pertinent vehicle data, which open the door to non-contact autonomous healthcare monitoring. Due to the urgent need to contain the automotive pandemic, this paper proposes a COVID-19 vehicle based on an efficient mutual authentication scheme for 5G-enabled vehicular fog computing. The proposed scheme consists of two different aspects of the special flag, SF = 0 and SF = 1, denoting normal and COVID-19 vehicles, respectively. The proposed scheme satisfies privacy and security requirements as well as achieves COVID-19 and healthcare solutions. Finally, the performance evaluation section shows that the proposed scheme is more efficient in terms of communication and computation costs as compared to most recent related works.
  11. Functionalized fullerene (C₆₀) as a potential nanomediator in the fabrication of highly sensitive biosensors
    Afreen S, Muthoosamy K, Manickam S, Hashim U
    Biosens Bioelectron, 2015 Jan 15;63:354-364.
    PMID: 25125029 DOI: 10.1016/j.bios.2014.07.044
    Designing a biosensor for versatile biomedical applications is a sophisticated task and how dedicatedly functionalized fullerene (C60) can perform on this stage is a challenge for today and tomorrow's nanoscience and nanotechnology. Since the invention of biosensor, many ideas and methods have been invested to upgrade the functionality of biosensors. Due to special physicochemical characteristics, the novel carbon material "fullerene" adds a new dimension to the construction of highly sensitive biosensors. The prominent aspects of fullerene explain its outstanding performance in biosensing devices as a mediator, e.g. fullerene in organic solvents exhibits five stages of reversible oxidation/reduction, and hence fullerene can work either as an electrophile or nucleophile. Fullerene is stable and its spherical structure produces an angle strain which allows it to undergo characteristic reactions of addition to double bonds (hybridization which turns from sp(2) to sp(3)). Research activities are being conducted worldwide to invent a variety of methods of fullerene functionalization with a purpose of incorporating it effectively in biosensor devices. The different types of functionalization methods include modification of fullerene into water soluble derivatives and conjugation with enzymes and/or other biomolecules, e.g. urease, glucose oxidase, hemoglobin, myoglobin (Mb), conjugation with metals e.g. gold (Au), chitosan (CS), ferrocene (Fc), etc. to enhance the sensitivity of biosensors. The state-of-the-art research on fullerene functionalization and its application in sensor devices has proven that fullerene can be implemented successfully in preparing biosensors to detect glucose level in blood serum, urea level in urine solution, hemoglobin, immunoglobulin, glutathione in real sample for pathological purpose, to identify doping abuse, to analyze pharmaceutical preparation and even to detect cancer and tumor cells at an earlier stage. Employing fullerene-metal matrix for the detection of tumor and cancer cells is also possible by the inclusion of fullerene in single-walled carbon nanotubes (SWCNTs) known as peapods as well as in double-walled carbon nanotubes (DWCNTs), to augment the effectiveness of biosensors. This review discusses various approaches that have been reported for functionalizing fullerene (C60) derivatives and their application in different types of biosensor fabrication.
  12. Graphene and graphene oxide as a docking station for modern drug delivery system
    Muthoosamy K, Bai RG, Manickam S
    Curr Drug Deliv, 2014;11(6):701-18.
    PMID: 24909150
    Motivated by the success and exhaustive research on carbon nanotubes (CNTs) based drug delivery, graphene, a two-dimensional; honey-comb crystal lattice has emerged as the rising star in recent years. Graphene is a flat monolayer of carbon atoms that holds many promising properties such as unparalleled thermal conductivity, remarkable electronic properties, and most intriguingly higher planar surface and superlative mechanical strength, which are attractive in biotechnological applications. Delivery of anti-cancer drugs using graphene and its derivatives has sparked major interest in this emerging field. The anti-cancer therapies often pose a limitation of insolubility, administration problems and cell penetration ability. In addition, systemic toxicity caused by lack of selective targeting towards cancer cells and inefficient distribution limits its clinical applications. Graphene nanocomposite is a promising tool to address these drawbacks. This review will focus on various synthesis and functionalization of graphene and graphene oxide for providing better solubility and targeted drug delivery at cancer cells. A more advanced and 'smart' graphene hybrid nanostructures that have several functionalities such as stimulus-response mediated delivery, imaging at release sites as well as transfection into cancer cells are also presented. A brief description on the challenges and perspectives for future research in this field is also discussed.
  13. Fulltext Investigations on the generation of oil-in-water (O/W) nanoemulsions through the combination of ultrasound and microchannel
    Manickam S, Sivakumar K, Pang CH
    Ultrason Sonochem, 2020 Dec;69:105258.
    PMID: 32702637 DOI: 10.1016/j.ultsonch.2020.105258
    O/W nanoemulsions are isotropic colloidal systems constituted of oil droplets dispersed in continuous aqueous media and stabilised by surfactant molecules. Nanoemulsions hold applications in more widespread technological domains, more crucially in the pharmaceutical industry. Innovative nanoemulsion-based drug delivery system has been suggested as a powerful alternative strategy through the useful means of encapsulating, protecting, and delivering the poorly water-soluble bioactive components. Consequently, there is a need to generate an emulsion with small and consistent droplets. Diverse studies acknowledged that ultrasonic cavitation is a feasible and energy-efficient method in making pharmaceutical-grade nanoemulsions. This method offers more notable improvements in terms of stability with a lower Ostwald ripening rate. Meanwhile, a microstructured reactor, for instance, microchannel, has further been realised as an innovative technology that facilitates combinatorial approaches with the acceleration of reaction, analysis, and measurement. The recent breakthrough that has been achieved is the controlled generation of fine and monodispersed multiple emulsions through microstructured reactors. The small inner dimensions of microchannel display properties such as short diffusion paths and high specific interfacial areas, which increase the mass and heat transfer rates. Hence, the combination of ultrasonic cavitation with microstructures (microchannel) provides process intensification of creating a smaller monodispersed nanoemulsion system. This investigation is vital as it will then facilitate the creation of new nanoemulsion based drug delivery system continuously. Following this, the fabrication of microchannel and setup of its combination with ultrasound was conducted in the generation of O/W nanoemulsion, as well as optimisation to analyse the effect of varied operating parameters on the mean droplet diameter and dispersity of the nanoemulsion generated, besides monitoring the stability of the nanoemulsion. Scanning transmission electron microscopy (STEM) images were also carried out for the droplet size measurements. In short, the outcomes of this study are encouraging, which necessitates further investigations to be carried out to advance a better understanding of coupling microchannel with ultrasound to produce pharmaceutical-grade nanoemulsions.
  14. Enhancements in crystallinity, thermal stability, tensile modulus and strength of sisal fibres and their PP composites induced by the synergistic effects of alkali and high intensity ultrasound (HIU) treatments
    Krishnaiah P, Ratnam CT, Manickam S
    Ultrason Sonochem, 2017 01;34:729-742.
    PMID: 27773300 DOI: 10.1016/j.ultsonch.2016.07.008
    In this investigation, sisal fibres were treated with the combination of alkali and high intensity ultrasound (HIU) and their effects on the morphology, thermal properties of fibres and mechanical properties of their reinforced PP composites were studied. FTIR and FE-SEM results confirmed the removal of amorphous materials such as hemicellulose, lignin and other waxy materials after the combined treatments of alkali and ultrasound. X-ray diffraction analysis revealed an increase in the crystallinity of sisal fibres with an increase in the concentration of alkali. Thermogravimetric results revealed that the thermal stability of sisal fibres obtained with the combination of both alkali and ultrasound treatment was increased by 38.5°C as compared to the untreated fibres. Morphology of sisal fibre reinforced composites showed good interfacial interaction between fibres and matrix after the combined treatment. Tensile properties were increased for the combined treated sisal fibres reinforced PP composites as compared to the untreated and pure PP. Tensile modulus and strength increased by more than 50% and 10% respectively as compared to the untreated sisal fibre reinforced composite. It has been found that the combined treatment of alkali and ultrasound is effective and useful to remove the amorphous materials and hence to improve the mechanical and thermal properties.
  15. Inhibition and kinetic studies of cellulose- and hemicellulose-degrading enzymes of Ganoderma boninense by naturally occurring phenolic compounds
    Surendran A, Siddiqui Y, Ali NS, Manickam S
    J Appl Microbiol, 2018 Jun;124(6):1544-1555.
    PMID: 29405525 DOI: 10.1111/jam.13717
    AIM: Ganoderma sp, the causal pathogen of the basal stem rot (BSR) disease of oil palm, secretes extracellular hydrolytic enzymes. These play an important role in the pathogenesis of BSR by nourishing the pathogen through the digestion of cellulose and hemicellulose of the host tissue. Active suppression of hydrolytic enzymes secreted by Ganoderma boninense by various naturally occurring phenolic compounds and estimation of their efficacy on pathogen suppression is focused in this study.

    METHODS AND RESULTS: Ten naturally occurring phenolic compounds were assessed for their inhibitory effect on the hydrolytic enzymes of G. boninense. The enzyme kinetics (Vmax and Km ) and the stability of the hydrolytic enzymes were also characterized. The selected compounds had shown inhibitory effect at various concentrations. Two types of inhibitions namely uncompetitive and noncompetitive were observed in the presence of phenolic compounds. Among all the phenolic compounds tested, benzoic acid was the most effective compound suppressive to the growth and production of hydrolytic enzymes secreted by G. boninense. The phenolic compounds as inhibitory agents can be a better replacement for the metal ions which are known as conventional inhibitors till date. The three hydrolytic enzymes were stable in a wide range of pH and temperature.

    CONCLUSION: These findings highlight the efficacy of the applications of phenolic compounds to control Ganoderma.

    SIGNIFICANCE AND IMPACT OF THE STUDY: The study has proved a replacement for chemical controls of G. boninense with naturally occurring phenolic compounds.

  16. Tamoxifen-loaded nanostructured lipid carrier as a drug delivery system: characterization, stability assessment and cytotoxicity
    How CW, Rasedee A, Manickam S, Rosli R
    Colloids Surf B Biointerfaces, 2013 Dec 1;112:393-9.
    PMID: 24036474 DOI: 10.1016/j.colsurfb.2013.08.009
    Cancer nanotherapeutics is beginning to overwhelm the global research and viewed to be the revolutionary treatment regime in the medical field. This investigation describes the development of a stable nanostructured lipid carrier (NLC) system as carrier for Tamoxifen (TAM). The TAM-loaded NLC (TAM-NLC) developed with 200mg of TAM showed a spherical particle with the size of 46.6nm, polydispersity index of 0.267, entrapment efficiency of 99.74% and with the zeta potential of -23.78mV. Besides, the equivalent cytotoxicity of TAM and TAM-NLC to human (MCF-7) and mice (4T1) mammary breast cancer cell lines were observed. Incubating the formulation at the physiological pH resulted into reduced Ostwald ripening rate but without any significant change in the absorptivity. When coupled with the measurements of zeta potential and Ostwald ripening rate, the absorbance assay may be used to predict the long-term stability of drug-loaded nanoparticle formulations. The results of the study also suggest that TAM-NLC is a promising drug delivery system for breast cancer therapy. This is the first encouraging report on the in vitro effect of TAM-NLC against human and mouse mammary adenocarcinoma cell lines.
  17. Fulltext Growth inhibition of human gynecologic and colon cancer cells by Phyllanthus watsonii through apoptosis induction
    Ramasamy S, Abdul Wahab N, Zainal Abidin N, Manickam S, Zakaria Z
    PLoS One, 2012;7(4):e34793.
    PMID: 22536331 DOI: 10.1371/journal.pone.0034793
    Phyllanthus watsonii Airy Shaw is an endemic plant found in Peninsular Malaysia. Although there are numerous reports on the anti cancer properties of other Phyllanthus species, published information on the cytotoxicity of P. watsonii are very limited. The present study was carried out with bioassay-guided fractionation approach to evaluate the cytotoxicity and apoptosis induction capability of the P. watsonii extracts and fractions on human gynecologic (SKOV-3 and Ca Ski) and colon (HT-29) cancer cells. P. watsonii extracts exhibited strong cytotoxicity on all the cancer cells studied with IC(50) values of ≤ 20.0 µg/mL. Hexane extract of P. watsonii was further subjected to bioassay-guided fractionation and yielded 10 fractions (PW-1→PW-10). PW-4→PW-8 portrayed stronger cytotoxic activity and was further subjected to bioassay-guided fractionation and resulted with 8 sub-fractions (PPWH-1→PPWH-8). PPWH-7 possessed greatest cytotoxicity (IC(50) values ranged from 0.66-0.83 µg/mL) and was selective on the cancer cells studied. LC-MS/MS analysis of PPWH-7 revealed the presence of ellagic acid, geranic acid, glochidone, betulin, phyllanthin and sterol glucoside. Marked morphological changes, ladder-like appearance of DNA and increment in caspase-3 activity indicating apoptosis were clearly observed in both human gynecologic and colon cancer cells treated with P. watsonii especially with PPWH-7. The study also indicated that P. watsonii extracts arrested cell cycle at different growth phases in SKOV-3, Ca Ski and HT-29 cells. Cytotoxic and apoptotic potential of the endemic P. watsonii was investigated for the first time by bioassay-guided approach. These results demonstrated that P. watsonii selectively inhibits the growth of SKOV-3, Ca Ski and HT-29 cells through apoptosis induction and cell cycle modulation. Hence, P. watsonii has the potential to be further exploited for the discovery and development of new anti cancer drugs.
  18. Effect of extracts from Phyllanthus watsonii Airy Shaw on cell apoptosis in cultured human breast cancer MCF-7 cells
    Ramasamy S, Abdul Wahab N, Zainal Abidin N, Manickam S
    Exp. Toxicol. Pathol., 2013 Mar;65(3):341-9.
    PMID: 22217449 DOI: 10.1016/j.etp.2011.11.005
    Species of Phyllanthus have traditionally been used for hundreds of years for treating many ailments including diabetes, anemia, bronchitis and hepatitis. The present study aims to investigate the cytotoxic and apoptotic effects of methanol (PWM), hexane (PWH) and ethyl acetate (PWE) extracts from the leaves of the endemic plant Phyllanthus watsonii Airy Shaw (Phyllanthaceae) on MCF-7 human breast cancer cells. We observed that the PWM, PWH and PWE extracts were cytotoxic and selectively inhibited the growth and proliferation of MCF-7 cells compared to untreated control in a dose dependent manner with an IC(50) of 12.7 ± 4.65, 7.9 ± 0.60 and 7.7 ± 0.29 μg/ml, respectively. However, the extracts were not toxic at these concentrations to normal human lung fibroblast MRC-5 cells. Cell death induced by PWM, PWH and PWE extracts were mainly due to apoptosis which was characterized by apoptotic morphological changes and a nuclear DNA fragmentation. Caspase-3 activation following P. watsonii extracts treatment was also evident for apoptotic cell death which was preceded by an S phase cell cycle perturbation. The results suggested that the cytotoxic activity of P. watsonii extracts was related to an early event of cell cycle perturbation and a later event of apoptosis. Hence, P. watsonii displays potential to be further exploited in the discovery and development of new anticancer agents.
  19. Formulation development and optimization of a novel Cremophore EL-based nanoemulsion using ultrasound cavitation
    Tang SY, Manickam S, Wei TK, Nashiru B
    Ultrason Sonochem, 2012 Mar;19(2):330-45.
    PMID: 21835676 DOI: 10.1016/j.ultsonch.2011.07.001
    In the present study, response surface methodology (RSM) based on central composite design (CCD) was employed to investigate the influence of main emulsion composition variables, namely drug loading, oil content, emulsifier content as well as the effect of the ultrasonic operating parameters such as pre-mixing time, ultrasonic amplitude, and irradiation time on the properties of aspirin-loaded nanoemulsions. The two main emulsion properties studied as response variables were: mean droplet size and polydispersity index. The ultimate goal of the present work was to determine the optimum level of the six independent variables in which an optimal aspirin nanoemulsion with desirable properties could be produced. The response surface analysis results clearly showed that the variability of two responses could be depicted as a linear function of the content of main emulsion compositions and ultrasonic processing variables. In the present investigation, it is evidently shown that ultrasound cavitation is a powerful yet promising approach in the controlled production of aspirin nanoemulsions with smaller average droplet size in a range of 200-300 nm and with a polydispersity index (PDI) of about 0.30. This study proved that the use of low frequency ultrasound is of considerable importance in the controlled production of pharmaceutical nanoemulsions in the drug delivery system.
  20. Leveraging intelligent agents for knowledge discovery from heterogeneous healthcare data repositories
    Zaidi SZ, Abidi SS, Manickam S
    Stud Health Technol Inform, 2002;90:335-40.
    PMID: 15460713
    This paper presents a case for an intelligent agent based framework for knowledge discovery in a distributed healthcare environment comprising multiple heterogeneous healthcare data repositories. Data-mediated knowledge discovery, especially from multiple heterogeneous data resources, is a tedious process and imposes significant operational constraints on end-users. We demonstrate that autonomous, reactive and proactive intelligent agents provide an opportunity to generate end-user oriented, packaged, value-added decision-support/strategic planning services for healthcare professionals, manages and policy makers, without the need for a priori technical knowledge. Since effective healthcare is grounded in good communication, experience sharing, continuous learning and proactive actions, we use intelligent agents to implement an Agent based Data Mining Infostructure that provides a suite of healthcare-oriented decision-support/strategic planning services.
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