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Attenuation of Thrombosis by Crude Rice (Oryza sativa) Bran Policosanol Extract: Ex Vivo Platelet Aggregation and Serum Levels of Arachidonic Acid Metabolites

Wong WT, Ismail M, Tohit ER, Abdullah R, Zhang YD

Evid Based Complement Alternat Med, 2016;2016:7343942.
PMID: 27800004

Background. Vascular occlusion or thrombosis was often attributed to uncontrolled platelet activation. Influence of sugarcane policosanol extract on platelet was reported but little was known of rice bran policosanol, particularly its mechanisms of actions on platelet activities. Objective. Antiplatelet mechanisms of rice bran policosanol extract (RBE) were studied using hyperlipidemic Sprague Dawley rats. Ex vivo platelet aggregation, platelet count (PC), bleeding time (BT), and coagulation time were assayed. Serum eicosanoids and other aggregation-related metabolites levels were quantified. Design. Rats were divided into 6 groups for comparisons (vehicle control Tween 20/H2O, high dose policosanol 500 mg/kg, middle dose policosanol 250 mg/kg, low dose policosanol 100 mg/kg, and positive control aspirin 30 mg/kg). Results. Low dose 100 mg/kg of RBE inhibited aggregation by 42.32 ± 4.31% and this was comparable with the effect of 30 mg/kg aspirin, 43.91 ± 5.27%. Results showed that there were no significant differences in PC, BT, and coagulation time among various groups after RBE treatment. Serum thromboxane A2 was attenuated while prostacyclin level increased upon RBE treatment. Conclusions. RBE reduced ex vivo ADP-induced platelet aggregation without giving adverse effects. No changes in full blood count suggested that rice bran policosanol did not disturb biological blood cell production and destruction yet it reduced aggregation through different mechanisms.
Fulltext Thymoquinone loaded in nanostructured lipid carrier showed enhanced anticancer activity in 4T1 tumor-bearing mice

Ong YS, Saiful Yazan L, Ng WK, Abdullah R, Mustapha NM, Sapuan S, et al.

Nanomedicine (Lond), 2018 07;13(13):1567-1582.
PMID: 30028248 DOI: 10.2217/nnm-2017-0322

AIM: To investigate the enhancement of anticancer activity of thymoquinone (TQ) by the use of nanostructured lipid carrier (NLC) in 4T1 tumor-bearing female BALB/c mice.
MATERIAL & METHODS: TQ was incorporated into NLC (TQNLC) by using high pressure homogenization. TQNLC and TQ were orally administered to the mice.
RESULTS & CONCLUSION: TQNLC and TQ are potential chemotherapeutic drugs as they exhibited anticancer activity. The use of NLC as a carrier has enhanced the therapeutic property of TQ by increasing the survival rate of mice. The antimetastasis effect of TQNLC and TQ to the lungs was evidence by downregulation of MMP-2. TQNLC and TQ induced apoptosis via modulation of Bcl-2 and caspase-8 in the intrinsic apoptotic pathway.
Fulltext Evaluating the effects of electronic health records system adoption on the performance of Malaysian health care providers

Salleh MIM, Abdullah R, Zakaria N

BMC Med Inform Decis Mak, 2021 02 25;21(1):75.
PMID: 33632216 DOI: 10.1186/s12911-021-01447-4

BACKGROUND: The Ministry of Health of Malaysia has invested significant resources to implement an electronic health record (EHR) system to ensure the full automation of hospitals for coordinated care delivery. Thus, evaluating whether the system has been effectively utilized is necessary, particularly regarding how it predicts the post-implementation primary care providers' performance impact.
METHODS: Convenience sampling was employed for data collection in three government hospitals for 7 months. A standardized effectiveness survey for EHR systems was administered to primary health care providers (specialists, medical officers, and nurses) as they participated in medical education programs. Empirical data were assessed by employing partial least squares-structural equation modeling for hypothesis testing.
RESULTS: The results demonstrated that knowledge quality had the highest score for predicting performance and had a large effect size, whereas system compatibility was the most substantial system quality component. The findings indicated that EHR systems supported the clinical tasks and workflows of care providers, which increased system quality, whereas the increased quality of knowledge improved user performance.
CONCLUSION: Given these findings, knowledge quality and effective use should be incorporated into evaluating EHR system effectiveness in health institutions. Data mining features can be integrated into current systems for efficiently and systematically generating health populations and disease trend analysis, improving clinical knowledge of care providers, and increasing their productivity. The validated survey instrument can be further tested with empirical surveys in other public and private hospitals with different interoperable EHR systems.
Fulltext Induction of Apoptosis in MCF-7 Cells via Oxidative Stress Generation, Mitochondria-Dependent and Caspase-Independent Pathway by Ethyl Acetate Extract of Dillenia suffruticosa and Its Chemical Profile

Tor YS, Yazan LS, Foo JB, Wibowo A, Ismail N, Cheah YK, et al.

PLoS One, 2015;10(6):e0127441.
PMID: 26047480 DOI: 10.1371/journal.pone.0127441

Dillenia suffruticosa, which is locally known as Simpoh air, has been traditionally used to treat cancerous growth. The ethyl acetate extract of D. suffruticosa (EADs) has been shown to induce apoptosis in MCF-7 breast cancer cells in our previous study. The present study aimed to elucidate the molecular mechanisms involved in EADs-induced apoptosis and to identify the major compounds in the extract. EADs was found to promote oxidative stress in MCF-7 cells that led to cell death because the pre-treatment with antioxidants α-tocopherol and ascorbic acid significantly reduced the cytotoxicity of the extract (P<0.05). DCFH-DA assay revealed that treatment with EADs attenuated the generation of intracellular ROS. Apoptosis induced by EADs was not inhibited by the use of caspase-inhibitor Z-VAD-FMK, suggesting that the cell death is caspase-independent. The use of JC-1 dye reflected that EADs caused disruption in the mitochondrial membrane potential. The related molecular pathways involved in EADs-induced apoptosis were determined by GeXP multiplex system and Western blot analysis. EADs is postulated to induce cell cycle arrest that is p53- and p21-dependent based on the upregulated expression of p53 and p21 (P<0.05). The expression of Bax was upregulated with downregulation of Bcl-2 following treatment with EADs. The elevated Bax/Bcl-2 ratio and the depolarization of mitochondrial membrane potential suggest that EADs-induced apoptosis is mitochondria-dependent. The expression of oxidative stress-related AKT, p-AKT, ERK, and p-ERK was downregulated with upregulation of JNK and p-JNK. The data indicate that induction of oxidative-stress related apoptosis by EADs was mediated by inhibition of AKT and ERK, and activation of JNK. The isolation of compounds in EADs was carried out using column chromatography and elucidated using the nuclear resonance magnetic analysis producing a total of six compounds including 3-epimaslinic acid, kaempferol, kaempferide, protocatechuic acid, gallic acid and β-sitosterol-3-O-β-D-glucopyranoside. The cytotoxicity of the isolated compounds was determined using MTT assay. Gallic acid was found to be most cytotoxic against MCF-7 cell line compared to others, with IC50 of 36 ± 1.7 μg/mL (P<0.05). In summary, EADs generated oxidative stress, induced cell cycle arrest and apoptosis in MCF-7 cells by regulating numerous genes and proteins that are involved in the apoptotic signal transduction pathway. Therefore, EADs has the potential to be developed as an anti-cancer agent against breast cancer.
Fulltext Risk of acute kidney injury and hyponatremia in long-distance runners

Abdullah R., Wan Md Adnan W.A.H.

JUMMEC, 2018;21(2):4-9.
MyJurnal

Long-distance running has gathered some momentum among health-conscious participants. However, some
studies have revealed association between long-distance running and development of acute kidney injury.
Although the impact usually lasts only for a few days after the event, some participants have been admitted for
severe acute kidney injury, the minority of which require dialysis treatment. The mechanisms underlying the
injury may include dehydration, development of rhabdomyolysis, heat stroke and concomitant use of NSAIDS.
Unfortunately, there is no long-term follow-up study to determine the long-term effect on kidney function.
Acute hyponatremia may develop in a significant proportion of long-distance runners. Majority of them were
asymptomatic but a few fatal cases which were supposedly due to cerebral oedema have been reported.
Excessive intake of hypotonic drinks, excessive sweating and secretion of non-osmotic antidiuretic hormone
have been postulated to be the causes of hyponatremia. This mini review will discuss the pathophysiology of
the development of acute kidney injury and hyponatremia. It will also discuss the prevention and treatment
of both conditions.
A review of oxalate poisoning in domestic animals: tolerance and performance aspects

Rahman MM, Abdullah RB, Wan Khadijah WE

J Anim Physiol Anim Nutr (Berl), 2013 Aug;97(4):605-14.
PMID: 22548678 DOI: 10.1111/j.1439-0396.2012.01309.x

Published data on oxalate poisoning in domestic animals are reviewed, with a focus on tolerance and performance. Oxalic acid is one of a number of anti-nutrients found in forage. It can bind with dietary calcium (Ca) or magnesium (Mg) to form insoluble Ca or Mg oxalate, which then may lead to low serum Ca or Mg levels as well as to renal failure because of precipitation of these salts in the kidneys. Dietary oxalate plays an important role in the formation of Ca oxalate, and a high dietary intake of Ca may decrease oxalate absorption and its subsequent urinary excretion. Oxalate-rich plants can be supplemented with other plants as forage for domestic animals, which may help to reduce the overall intake of oxalate-rich plants. Non-ruminants appear to be more sensitive to oxalate than ruminants because in the latter, rumen bacteria help to degrade oxalate. If ruminants are slowly exposed to a diet high in oxalate, the population of oxalate-degrading bacteria in the rumen increases sufficiently to prevent oxalate poisoning. However, if large quantities of oxalate-rich plants are eaten, the rumen is overwhelmed and unable to metabolize the oxalate and oxalate-poisoning results. Based on published data, we consider that <2.0% soluble oxalate would be an appropriate level to avoid oxalate poisoning in ruminants, although blood Ca level may decrease. In the case of non-ruminants, <0.5% soluble oxalate may be acceptable. However, these proposed safe levels of soluble oxalate should be regarded as preliminary. Further studies, especially long-term studies, are needed to validate and improve the recommended safe levels in animals. This review will encourage further research on the relationships between dietary oxalate, other dietary factors and renal failure in domestic animals.
Increasing glucose in KSOMaa basal medium on culture Day 2 improves in vitro development of cloned caprine blastocysts produced via intraspecies and interspecies somatic cell nuclear transfer

Kwong PJ, Abdullah RB, Wan Khadijah WE

Theriogenology, 2012 Sep 1;78(4):921-9.
PMID: 22704387 DOI: 10.1016/j.theriogenology.2012.04.009

This study was conducted to evaluate the efficiency of potassium simplex optimization medium with amino acids (KSOMaa) as a basal culture medium for caprine intraspecies somatic cell nuclear transfer (SCNT) and caprine-bovine interspecies somatic cell nuclear transfer (iSCNT) embryos. The effect of increased glucose as an energy substrate for late stage development of cloned caprine embryos in vitro was also evaluated. Enucleated caprine and bovine in vitro matured oocytes at metaphase II were reconstructed with caprine ear skin fibroblast cells for the SCNT and iSCNT studies. The cloned caprine and parthenogenetic embryos were cultured in either KSOMaa with 0.2 mM glucose for 8 days (Treatment 1) or KSOMaa for 2 days followed by KSOMaa with additional glucose at a final concentration of 2.78 mM for the last 6 days (Treatment 2). There were no significant differences in the cleavage rates of SCNT (80.7%) and iSCNT (78.0%) embryos cultured in KSOMaa medium. Both Treatment 1 and Treatment 2 could support in vitro development of SCNT and iSCNT embryos to the blastocyst stage. However, the blastocyst development rate of SCNT embryos was significantly higher (P < 0.05) in Treatment 2 compared to Treatment 1. Increasing glucose for later stage embryo development (8-cell stage onwards) during in vitro culture (IVC) in Treatment 2 also improved both caprine SCNT and iSCNT embryo development to the hatched blastocyst stage. In conclusion, this study shows that cloned caprine embryos derived from SCNT and iSCNT could develop to the blastocyst stage in KSOMaa medium supplemented with additional glucose (2.78 mM, final concentration) and this medium also supported hatching of caprine cloned blastocysts.
Fulltext The effects of rainfall event and land use characteristics on river basin hydrological response: a case of Sg. Kayu Ara, Malaysia

Alaghmand, S., Abdullah, R., Abustan, I., Vosoogh, B.

Pertanika Journal of Science & Technology, 2012;20(2):205-219.
MyJurnal

As a crucial demand in urban areas, flood risk management has been considered by researchers and decision makers around the world. In this case, hydrological modelling that simulates rainfall-runoff process plays a significant role. This paper quantified the roles of three main parameters in river basin hydrological response, namely, rainfall event duration, rainfall event ARI (magnitude) and land-use development condition. The case study area of this research was Sungai Kayu Ara basin which is located in the western part of Kuala Lumpur, Malaysia. A total of twenty seven scenario were defined for this research, including three different rainfall event durations (60, 120 and 360 minutes), three different ARIs (20, 50 and 100 years) and in three different land-use conditions (existing, intermediate and ultimate). The results of this research indicate that rainfall event duration, rainfall event ARI (magnitude) and land-use development condition have considerable effects of the surface runoff hydrographs in terms of peak discharge and volume.
Therapeutic uses of epicatechin in diabetes and cancer

Abdulkhaleq LA, Assi MA, Noor MHM, Abdullah R, Saad MZ, Taufiq-Yap YH

Vet World, 2017 Aug;10(8):869-872.
PMID: 28919675 DOI: 10.14202/vetworld.2017.869-872

Epicatechin is a natural flavonoid found in green tea. It has been reported to possess an immense antioxidant effect which contributes to its therapeutic effect against a handful of ailments. In this review, we discuss its therapeutic role in the management of two of the most important human diseases; diabetes and cancer. The consumption of epicatechin has been shown to reduce blood glucose levels in diabetic patients, while is anticancer effect was attributed to its antioxidant properties, antiangiogenic and direct cytotoxicity to cancer cells. Although the exact mechanism of action of epicatechin is still being explored, there is no doubt that it is a promising candidate as an alternative. The significance of this review is to highlight the importance of the usage of natural products (in this case, epicatechin) as an alternative for the treatment of two potentially fatal diseases which is diabetes and cancer. The aim of this review is to educate the scientific community on the role of epicatechin in ameliorating the effects of diabetes and cancers on human while understanding the potential mechanisms of these aforementioned effects.
Fulltext Genetic analysis of the M2/ANXA5 haplotype as recurrent pregnancy loss predisposition in the Malay population

Ang KC, Kathirgamanathan S, Ch'ng ES, Lee YY, Roslani AL, Naidu B, et al.

J Assist Reprod Genet, 2017 Apr;34(4):517-524.
PMID: 28108842 DOI: 10.1007/s10815-017-0871-0

PURPOSE: The aim of this study was to evaluate a new predisposition factor, M2/ANXA5 (RPRGL3), in recurrent pregnancy loss (RPL) patients of Malay origin, since it was previously known that the prevalence of this condition is relatively high among the Malay population of Malaysia, where conventional hereditary thrombophilia factors have been generally ruled out.
METHODS: A total of 232 women who had experienced ≥2 unexplained RPL and 141 available male partners were recruited, with 360 healthy Malay and 166 parous female controls. Prevalence of M2 carriage and RPL odds ratios were calculated in (a) control and patient groups; (b) clinically defined subgroups in categories of pregnancy loss, primary, secondary, and tertiary; and (c) timing of pregnancy loss in early, ≤15th gestation week and "late" fetal losses, and >15th gestation week subgroups.
RESULTS: Both male and female subjects had similar M2/ANXA5 allele frequencies. The carrier rate of M2/ANXA5 for the general Malay population was 42.2 and 34.9% for parous controls. These carrier rates compared to Malay RPL subjects (52% M2 carriers) resulted in elevated odds ratios (95% confidence interval) of 1.53 (1.1 to 2.1) and 1.97 (1.3 to 3.1) accordingly for early fetal losses. Moreover, exceeding copy numbers of M2/ANXA5 alleles seemed to afflict a greater chance of RPL in couples, especially when both partners were M2 carriers.
CONCLUSION: This study confirmed the proposed role of M2/ANXA5 as embryonic, genetically associated thrombophilia predisposition factor for early RPL among ethnic Malay of Malaysia.
Fulltext Comparative aspects of microRNA expression in canine and human cancers

Sahabi K, Selvarajah GT, Abdullah R, Cheah YK, Tan GC

J Vet Sci, 2018 Mar 31;19(2):162-171.
PMID: 28927253 DOI: 10.4142/jvs.2018.19.2.162

MicroRNAs (miRNAs) have important roles in all biological pathways in multicellular organisms. Over 1,400 human miRNAs have been identified, and many are conserved among vertebrates and invertebrates. Regulation of miRNA is the most common mode of post-transcriptional gene regulation. The miRNAs that are involved in the initiation and progression of cancers are termed oncomiRs and several of them have been identified in canine and human cancers. Similarly, several miRNAs have been reported to be down-regulated in cancers of the two species. In this review, current information on the expression and roles of miRNAs in oncogenesis and progression of human and canine cancers, as well the roles miRNAs have in cancer stem cell biology, are highlighted. The potential for the use of miRNAs as therapeutic targets in personalized cancer therapy in domestic dogs and their possible application in human cancer counterparts are also discussed.
Typhonium flagelliforme induces apoptosis in CEMss cells via activation of caspase-9, PARP cleavage and cytochrome c release: its activation coupled with G0/G1 phase cell cycle arrest

Mohan S, Abdul AB, Abdelwahab SI, Al-Zubairi AS, Sukari MA, Abdullah R, et al.

J Ethnopharmacol, 2010 Oct 5;131(3):592-600.
PMID: 20673794 DOI: 10.1016/j.jep.2010.07.043

The plant Typhonium flagelliforme (TF), commonly known as 'rodent tuber' in Malaysia, is often used as traditional remedy for cancer, including leukemia.
Fulltext Cholinesterase-based biosensor for preliminary detection of toxic heavy metals in the environment and agricultural-based products

Sabullah, M. K., Khalidi, S. A. M., Abdullah, R., Sani, S. A., Gansau, J. A., Ahmad, S. A., et al.

International Food Research Journal, 2020;27(4):597-609.
MyJurnal

Heavy metals with high chemical activity from sludge and waste release, agriculture, and
mining activity are a major concern. They should be carefully managed before reaching the
main water bodies. Excessive exposure to heavy metal may cause toxic effect to any types of
organism from the biomolecular to the physiological level, and ultimately cause death. Monitoring is the best technique to ensure the safety of our environment before a rehabilitation is
needed. Nowadays, enzyme-based biosensors are utilised in biomonitoring programmes as
this technique allows for a real-time detection and rapid result. It is also inexpensive and easy
to handle. Enzyme-based biosensors are an alternative for the preliminary screening of
contamination before a secondary screening is performed using high-performance technology.
This review highlights the current knowledge on enzyme-based biosensors, focusing on
cholinesterase for toxic metal detection in the environment.
Fulltext Serum prolactin levels during pregnancy, intrapartum and postpartum periods in Malay women

Rajikin MH, Abdullah R, Arshat H, Satgunasingam N

Med J Malaysia, 1982 Mar;37(1):72-5.
PMID: 6981751

Serum human prolactin (hPRL) levels in Malay women during pregnancy, intrapartum and immediately postpartum have been invest£gated by means of a double-antibody radioimmunoassay technique. There was a progressioe rise of serum prolactin concentration from 31.9 ± 10.4 ng/ml in the first trimester to 242.0 ± 24.6 ng/ml at 36 weeks pregnancy unth. the mean values during the second and third trimester of 118.9 ± 12.7 ng/ml and 214.7 ± 10.3 ng/ml respectively. During intrapartum the concentration of hPRL was 191.9 ± 26.9 ng/ml and ithat of immediately postpartum was 178.3 ± 14.5 ng/ml. Suckling of the breast within 6 hours postpartum has resulted in a minor elevation of prolactin level, and this could have been due to the greater basal prolactin level, and/or the ineffectiveness of suckling as a potent stimulus during this period.
Fulltext Potential of fermented papaya beverage in the prevention of foodborne illness incidence

Koh, S.P., Aziz, N., Sharifudin, S.A., Abdullah, R., Hamid, N.S.A., Sarip, J.

Food Research, 2017;1(4):109-113.
MyJurnal

Foodborne illness is recognized as an emerging infectious disease. The incidence of foodborne
infections is common and the majority cases are undiagnosed or unreported. Apart from some
diarrhea or minor gastrointestinal problem, some foodborne pathogenic microbes may cause
death, particularly to those people with weakened immune system. In this study, we have
developed a new fermented papaya beverage using symbiotic culture of yeast and acetic acid
bacteria under controlled biofermentation process. An in-vitro assessment of fermented papaya
beverage against few foodborne pathogenic microorganism was conducted to determine
its minimum bactericidal concentration (MBC>99). Three types of foodborne pathogen:
Escherichia coli O157, Salmonella enterica serovar Typhimurium ATCC 53648, Salmonella
enterica serovar Enteritidis (isolated from infectious chicken) were selected. From minimum
bactericidal concentration (MBC>99) assay, both fermented papaya pulp and leaves beverages
have shown 100% killing rate against three selected foodborne pathogenic microbes. Inversely,
non-fermented papaya pulp and leaves beverages indicated no inhibition at all. In fact, further
dilution of fermented papaya pulp and leaves beverages demonstrated different degree of
MBC>99 and brix value, but the pH value remained less than 3.5. These findings indicated
the combination of soluble solid compounds presents in both fermented papaya beverage and
product acidity play an important role in the inhibition of pathogenic microorganisms. The
preliminary promising results of this work have shown that the great potential of fermented
papaya beverages as a preventive measure to reduce the incidence of foodborne illness.
Fulltext Enhanced Intrusion Detection with Data Stream Classification and Concept Drift Guided by the Incremental Learning Genetic Programming Combiner

Shyaa MA, Zainol Z, Abdullah R, Anbar M, Alzubaidi L, Santamaría J

Sensors (Basel), 2023 Apr 04;23(7).
PMID: 37050795 DOI: 10.3390/s23073736

Concept drift (CD) in data streaming scenarios such as networking intrusion detection systems (IDS) refers to the change in the statistical distribution of the data over time. There are five principal variants related to CD: incremental, gradual, recurrent, sudden, and blip. Genetic programming combiner (GPC) classification is an effective core candidate for data stream classification for IDS. However, its basic structure relies on the usage of traditional static machine learning models that receive onetime training, limiting its ability to handle CD. To address this issue, we propose an extended variant of the GPC using three main components. First, we replace existing classifiers with alternatives: online sequential extreme learning machine (OSELM), feature adaptive OSELM (FA-OSELM), and knowledge preservation OSELM (KP-OSELM). Second, we add two new components to the GPC, specifically, a data balancing and a classifier update. Third, the coordination between the sub-models produces three novel variants of the GPC: GPC-KOS for KA-OSELM; GPC-FOS for FA-OSELM; and GPC-OS for OSELM. This article presents the first data stream-based classification framework that provides novel strategies for handling CD variants. The experimental results demonstrate that both GPC-KOS and GPC-FOS outperform the traditional GPC and other state-of-the-art methods, and the transfer learning and memory features contribute to the effective handling of most types of CD. Moreover, the application of our incremental variants on real-world datasets (KDD Cup '99, CICIDS-2017, CSE-CIC-IDS-2018, and ISCX '12) demonstrate improved performance (GPC-FOS in connection with CSE-CIC-IDS-2018 and CICIDS-2017; GPC-KOS in connection with ISCX2012 and KDD Cup '99), with maximum accuracy rates of 100% and 98% by GPC-KOS and GPC-FOS, respectively. Additionally, our GPC variants do not show superior performance in handling blip drift.
Fulltext Monte Carlo dose calculation in dental amalgam phantom

Aziz MZ, Yusoff AL, Osman ND, Abdullah R, Rabaie NA, Salikin MS

J Med Phys, 2015 Jul-Sep;40(3):150-5.
PMID: 26500401 DOI: 10.4103/0971-6203.165080

It has become a great challenge in the modern radiation treatment to ensure the accuracy of treatment delivery in electron beam therapy. Tissue inhomogeneity has become one of the factors for accurate dose calculation, and this requires complex algorithm calculation like Monte Carlo (MC). On the other hand, computed tomography (CT) images used in treatment planning system need to be trustful as they are the input in radiotherapy treatment. However, with the presence of metal amalgam in treatment volume, the CT images input showed prominent streak artefact, thus, contributed sources of error. Hence, metal amalgam phantom often creates streak artifacts, which cause an error in the dose calculation. Thus, a streak artifact reduction technique was applied to correct the images, and as a result, better images were observed in terms of structure delineation and density assigning. Furthermore, the amalgam density data were corrected to provide amalgam voxel with accurate density value. As for the errors of dose uncertainties due to metal amalgam, they were reduced from 46% to as low as 2% at d80 (depth of the 80% dose beyond Zmax) using the presented strategies. Considering the number of vital and radiosensitive organs in the head and the neck regions, this correction strategy is suggested in reducing calculation uncertainties through MC calculation.
Fulltext Effectiveness of canlite and probase stabilized laterite soil

Mohd Yunus, N. Z., Wei, N. T., Yung, Y. C., Marto, A., Pakir, F., Hezmi, M. A., et al.

Journal of Advanced Research Design, 2015;5(1):17-30.
MyJurnal

Besides traditional chemical stabilizers, polymer emulsion that is considered as a nontraditional
chemical stabilizer had been introduced recently. Among polymer emulsions, Canlite and
Probase have been widely used for soil stabilization. The aim of this paper is to investigate the
effectiveness of Laterite soil stabilization treated by Canlite-liquid and Probase-liquid soil stabilizers.
A testing program, scheduled to achieve the overall objectives of this study was conducted to
determine the basic properties of Laterite soil, establish the relationship between the compaction
characteristics (maximum dry density and optimum moisture content) with the amount of polymer
emulsion and last but not least to compare the strength of the Canlite-treated and Probase-treated
Laterite soil. The effects of both polymer soil stabilizers – Canlite and Probase – were examined. The
optimum moisture content of the mixtures was used as a reference to determine the water content for
the preparation of all the specimens and later used in the unconfined compressive strength (UCS) test.
The laboratory test results showed that the additional amount of Canlite and Probase have improved
the physical properties, liquid limit and unconfined compressive strength (UCS) of the Laterite soil.
The compressive strength of the treated Laterite was found varied and depends on the type of
stabilizers, quantity of additives and curing time. From the UCS tests, it was found that Probase
improves the strength of the Laterite more than Canlite.
Fulltext Defining in vivo dose-response curves for kidney DNA adduct formation of aristolochic acid I in rat, mouse and human by an in vitro and physiologically based kinetic modeling approach

Abdullah R, Wesseling S, Spenkelink B, Louisse J, Punt A, Rietjens IMCM

J Appl Toxicol, 2020 12;40(12):1647-1660.
PMID: 33034907 DOI: 10.1002/jat.4024

Aristolochic acid I (AAI) is a well-known genotoxic kidney carcinogen. Metabolic conversion of AAI into the DNA-reactive aristolactam-nitrenium ion is involved in the mode of action of tumor formation. This study aims to predict in vivo AAI-DNA adduct formation in the kidney of rat, mouse and human by translating the in vitro concentration-response curves for AAI-DNA adduct formation to the in vivo situation using physiologically based kinetic (PBK) modeling-based reverse dosimetry. DNA adduct formation in kidney proximal tubular LLC-PK1 cells exposed to AAI was quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry. Subsequently, the in vitro concentration-response curves were converted to predicted in vivo dose-response curves in rat, mouse and human kidney using PBK models. Results obtained revealed a dose-dependent increase in AAI-DNA adduct formation in the rat, mouse and human kidney and the predicted DNA adduct levels were generally within an order of magnitude compared with values reported in the literature. It is concluded that the combined in vitro PBK modeling approach provides a novel way to define in vivo dose-response curves for kidney DNA adduct formation in rat, mouse and human and contributes to the reduction, refinement and replacement of animal testing.
Risk assessment of plant food supplements and other herbal products containing aristolochic acids using the margin of exposure (MOE) approach

Abdullah R, Diaz LN, Wesseling S, Rietjens IM

Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 2017 Feb;34(2):135-144.
PMID: 27892830 DOI: 10.1080/19440049.2016.1266098

After the incidences of induction of aristolochic acid nephropathy after consumption of herbal weight loss preparations that accidentally contained aristolochic acids (AAs), several countries defined national restrictions on the presence of AAs in food, including plant food supplements (PFS) and herbal products. This study investigates whether the risks associated with exposure to AAs via PFS and herbal products are at present indeed negligible. Data reported in literature on AA levels in PFS and other herbal products and also obtained from a new series of PFS in the present study were used to calculate the estimated daily intakes (EDIs) and corresponding margins of exposure (MOEs). Available literature data revealed that 206 out of 573 samples were found to contain aristolochic acid I (AAI) and/or aristolochic acid II (AAII). The results obtained from recently collected PFS revealed that both AAI and AAII were detected in three out of 18 analysed PFS at levels up to 594.8 and 235.3 µg g(-1), respectively, being in line with the levels reported in literature. The EDIs resulting from intake of these PFS resulted in MOEs that were generally below 10,000, corroborating the priority for risk management. Although these results refer to PFS collected by targeted sampling strategies, the data reveal that AA-containing PFS are still freely available. When considering that the use of these samples may be limited to shorter periods of time, the EDIs might be lower, but MOE values would still be lower than 10,000 for more than 50% of the AA-containing PFS and herbal products. In conclusion, the presence of AAs in PFS and herbal products even several years after instalment of the legal restrictions still raises concern, especially for people who frequently use the respective PFS and herbal products.

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