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Relationship between ABCB1 polymorphisms and serum methadone concentration in patients undergoing methadone maintenance therapy (MMT)

Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.

Am J Drug Alcohol Abuse, 2016 09;42(5):587-596.
PMID: 27284701 DOI: 10.3109/00952990.2016.1172078

BACKGROUND: Methadone is a substrate of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Large interindividual variability in serum methadone levels for therapeutic response has been reported. Genetic variations in ABCB1 gene may be responsible for the variability in observed methadone concentrations.
OBJECTIVE: This study investigated the associations of ABCB1 polymorphisms and serum methadone concentration over the 24-hour dosing interval in opioid-dependent patients on methadone maintenance therapy (MMT).
METHODS: One hundred and forty-eight male opioid-dependent patients receiving MMT were recruited. Genomic deoxyribonucleic acid (DNA) was extracted from whole blood and genotyped for ABCB1 polymorphisms [i.e. 1236C>T (dbSNP rs1128503), 2677G>T/A (dbSNP rs2032582), and 3435C>T (dbSNP rs1045642)] using the allelic discrimination real-time polymerase chain reaction (PCR). Blood samples were collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 hours after the dose. Serum methadone concentrations were measured using the Methadone ELISA Kit.
RESULTS: Our results revealed an association of CGC/TTT diplotype (1236C>T, 2677G>T/A, and 3435C>T) with dose-adjusted serum methadone concentration over the 24-hour dosing interval. Patients with CGC/TTT diplotype had 32.9% higher dose-adjusted serum methadone concentration over the 24-hour dosing interval when compared with those without the diplotype [mean (SD) = 8.12 (0.84) and 6.11 (0.41) ng ml-1mg-1, respectively; p = 0.033].
CONCLUSION: There was an association between the CGC/TTT diplotype of ABCB1 polymorphisms and serum methadone concentration over the 24-hour dosing interval among patients on MMT. Genotyping of ABCB1 among opioid-dependent patients on MMT may help individualize and optimize methadone substitution treatment.
Study site: Psychiatric Clinic, Hospital Universiti Sains Malaysia (HUSM), and other MMT clinics in Kelantan,
Malaysia

Matched MeSH terms: Methadone/pharmacokinetics
Quantitative characterization of chitosan in the skin by Fourier-transform infrared spectroscopic imaging and ninhydrin assay: application in transdermal sciences

Nawaz A, Wong TW

J Microsc, 2016 07;263(1):34-42.
PMID: 26695532 DOI: 10.1111/jmi.12371

The chitosan has been used as the primary excipient in transdermal particulate dosage form design. Its distribution pattern across the epidermis and dermis is not easily accessible through chemical assay and limited to radiolabelled molecules via quantitative autoradiography. This study explored Fourier-transform infrared spectroscopy imaging technique with built-in microscope as the means to examine chitosan molecular distribution over epidermis and dermis with the aid of histology operation. Fourier-transform infrared spectroscopy skin imaging was conducted using chitosan of varying molecular weights, deacetylation degrees, particle sizes and zeta potentials, obtained via microwave ligation of polymer chains at solution state. Both skin permeation and retention characteristics of chitosan increased with the use of smaller chitosan molecules with reduced acetyl content and size, and increased positive charge density. The ratio of epidermal to dermal chitosan content decreased with the use of these chitosan molecules as their accumulation in dermis (3.90% to 18.22%) was raised to a greater extent than epidermis (0.62% to 1.92%). A larger dermal chitosan accumulation nonetheless did not promote the transdermal polymer passage more than the epidermal chitosan. A small increase in epidermal chitosan content apparently could fluidize the stratum corneum and was more essential to dictate molecular permeation into dermis and systemic circulation. The histology technique aided Fourier-transform infrared spectroscopy imaging approach introduces a new dimension to the mechanistic aspect of chitosan in transdermal delivery.

Matched MeSH terms: Chitosan/pharmacokinetics
Liposomes in topical ophthalmic drug delivery: an update

Agarwal R, Iezhitsa I, Agarwal P, Abdul Nasir NA, Razali N, Alyautdin R, et al.

Drug Deliv, 2016 May;23(4):1075-91.
PMID: 25116511 DOI: 10.3109/10717544.2014.943336

Topical route of administration is the most commonly used method for the treatment of ophthalmic diseases. However, presence of several layers of permeation barriers starting from the tear film till the inner layers of cornea make it difficult to achieve the therapeutic concentrations in the target tissue within the eye. In order to circumvent these barriers and to provide sustained and targeted drug delivery, tremendous advances have been made in developing efficient and safe drug delivery systems. Liposomes due to their unique structure prove to be extremely beneficial drug carriers as they can entrap both the hydrophilic and hydrophobic drugs. The conventional liposomes had several drawbacks particularly their tendency to aggregate, the instability and leakage of entrapped drug and susceptibility to phagocytosis. Due to this reason, for a long time, liposomes as drug delivery systems did not attract much attention of researchers and clinicians. However, over recent years development of new generation liposomes has opened up new approaches for targeted and sustained drug delivery using liposomes and has rejuvenated the interest of researchers in this field. In this review we present a summary of current literature to understand the anatomical and physiological limitation in achieving adequate ocular bioavailability of topically applied drugs and utility of liposomes in overcoming these limitations. The recent developments related to new generation liposomes are discussed.

Matched MeSH terms: Ophthalmic Solutions/pharmacokinetics
Fulltext Improved photodynamic efficacy of Zn(II) phthalocyanines via glycerol substitution

Chin Y, Lim SH, Zorlu Y, Ahsen V, Kiew LV, Chung LY, et al.

PLoS One, 2014;9(5):e97894.
PMID: 24840576 DOI: 10.1371/journal.pone.0097894

Phthalocyanines are excellent photosensitizers for photodynamic therapy as they have strong absorbance in the near infra-red region which is most relevant for in vivo activation in deeper tissular regions. However, most phthalocyanines present two major challenges, ie, a strong tendency to aggregate and low water-solubility, limiting their effective usage clinically. In the present study, we evaluated the potential enhancement capability of glycerol substitution on the photodynamic properties of zinc (II) phthalocyanines (ZnPc). Three glycerol substituted ZnPc, 1-3, (tetra peripherally, tetra non-peripherally and mono iodinated tri non-peripherally respectively) were evaluated in terms of their spectroscopic properties, rate of singlet oxygen generation, partition coefficient (log P), intracellular uptake, photo-induced cytotoxicity and vascular occlusion efficiency. Tetrasulfonated ZnPc (ZnPcS4) was included as a reference compound. Here, we showed that 1-3 exhibited 10-100 nm red-shifted absorption peaks with higher molar absorptivity, and at least two-fold greater singlet oxygen generation rates compared to ZnPcS4. Meanwhile, phthalocyanines 1 and 2 showed more hydrophilic log P values than 3 consistent with the number of glycerol attachments but 3 was most readily taken up by cells compared to the rest. Both phthalocyanines 2 and 3 exhibited potent phototoxicity against MCF-7, HCT-116 and HSC-2 cancer cell-lines with IC50 ranging 2.8-3.2 µM and 0.04-0.06 µM respectively, while 1 and ZnPcS4 (up to 100 µM) failed to yield determinable IC50 values. In terms of vascular occlusion efficiency, phthalocyanine 3 showed better effects than 2 by causing total occlusion of vessels with diameter <70 µm of the chorioallantoic membrane. Meanwhile, no detectable vascular occlusion was observed for ZnPcS4 with treatment under similar experimental conditions. These findings provide evidence that glycerol substitution, in particular in structures 2 and 3, is able to improve the photodynamic properties of ZnPc.

Matched MeSH terms: Photosensitizing Agents/pharmacokinetics
The initial kinetics of NH3/NH4(+) efflux from L3 Teladorsagia circumcincta

Muhamad N, Walker LR, Pedley KC, Simcock DC, Brown S

Parasitol Int, 2012 Sep;61(3):487-92.
PMID: 22562002 DOI: 10.1016/j.parint.2012.04.003

The initial rate of NH(3)/NH(4)(+) accumulation in a medium containing L(3) Teladorsagia circumcincta was 0.18-0.6 pmol h(-1) larva(-1), which increased linearly with larval density. However it appeared that the larva-generated external concentration of NH(3)/NH(4)(+) did not exceed about 130 μM. The rate of NH(3)/NH(4)(+) accumulation increased with temperature between 4 °C and 37 °C, declined with increasing pH or increasing external NH(3)/NH(4)(+) concentration and was not significantly affected by the concentration of the phosphate buffer or by exsheathing the larvae. We infer from these data that the efflux of NH(3)/NH(4)(+) is a diffusive process and that the secreted or excreted NH(3)/NH(4)(+) is generated enzymatically rather than dissociating from the surface of the nematode. The enzymatic source of the NH(3)/NH(4)(+) is yet to be identified. Since the concentration of NH(3)/NH(4)(+) in the rumen and abomasum is higher than 130 μM, it is unlikely that T. circumcincta contributes to it, but NH(3)/NH(4)(+) may be accumulated from the rumen fluid by the nematode.

Matched MeSH terms: Ammonia/pharmacokinetics*
Fulltext Optimizing supercritical antisolvent process parameters to minimize the particle size of paracetamol nanoencapsulated in L-polylactide

Kalani M, Yunus R, Abdullah N

Int J Nanomedicine, 2011;6:1101-5.
PMID: 21698077 DOI: 10.2147/IJN.S18979

The aim of this study was to optimize the different process parameters including pressure, temperature, and polymer concentration, to produce fine small spherical particles with a narrow particle size distribution using a supercritical antisolvent method for drug encapsulation. The interaction between different process parameters was also investigated.

Matched MeSH terms: Acetaminophen/pharmacokinetics
Pharmacogenomics of CYP2D6: molecular genetics, interethnic differences and clinical importance

Teh LK, Bertilsson L

Drug Metab. Pharmacokinet., 2012;27(1):55-67.
PMID: 22185816

CYP2D6 has received intense attention since the beginning of the pharmacogenetic era in the 1970s. This is because of its involvement in the metabolism of more than 25% of the marketed drugs, the large geographical and inter-ethnic differences in the genetic polymorphism and possible drug-induced toxicity. Many interesting reviews have been published on CYP2D6 and this review aims to reinstate the importance of the genetic polymorphism of CYP2D6 in different populations as well as some clinical implications and important drug interactions.

Matched MeSH terms: Pharmacokinetics*
Fulltext Validation of a static Franz diffusion cell system for in vitro permeation studies

Ng SF, Rouse JJ, Sanderson FD, Meidan V, Eccleston GM

AAPS PharmSciTech, 2010 Sep;11(3):1432-41.
PMID: 20842539 DOI: 10.1208/s12249-010-9522-9

Over the years, in vitro Franz diffusion experiments have evolved into one of the most important methods for researching transdermal drug administration. Unfortunately, this type of testing often yields permeation data that suffer from poor reproducibility. Moreover, this feature frequently occurs when synthetic membranes are used as barriers, in which case biological tissue-associated variability has been removed as an artefact of total variation. The objective of the current study was to evaluate the influence of a full-validation protocol on the performance of a tailor-made array of Franz diffusion cells (GlaxoSmithKline, Harlow, UK) available in our laboratory. To this end, ibuprofen was used as a model hydrophobic drug while synthetic membranes were used as barriers. The parameters investigated included Franz cell dimensions, stirring conditions, membrane type, membrane treatment, temperature regulation and sampling frequency. It was determined that validation dramatically reduced derived data variability as the coefficient of variation for steady-state ibuprofen permeation from a gel formulation was reduced from 25.7% to 5.3% (n = 6). Thus, validation and refinement of the protocol combined with improved operator training can greatly enhance reproducibility in Franz cell experimentation.

Matched MeSH terms: Pharmacokinetics*
Formulation and in vitro evaluation of ketoprofen in palm oil esters nanoemulsion for topical delivery

Sakeena MH, Muthanna FA, Ghassan ZA, Kanakal MM, Elrashid SM, Munavvar AS, et al.

J Oleo Sci, 2010;59(4):223-8.
PMID: 20299769

The aim of the present study is to formulate and investigate the potential of nanoemulsion formulation for topical delivery of ketoprofen. In this study, Palm Oil Esters (POEs) a newly introduced oil by Universiti Putra Malaysia researchers was chosen for the oil phase of the nanoemulsion, because the oil was reported to be a good vehicle for pharmaceutical use. Oil-in-water nanoemulsion was prepared by spontaneous emulsification method. The droplets size was studied by laser scattering spectroscopy (Nanophox) and Transmission Electron Microscopy (TEM). Franz diffusion cells were used, to determine the drug release and drug transferred through methyl acetate cellulose membrane (artificial membrane). The results of droplets size analysis shows the droplets are in the range of nanoemulsion which is below than 500 nm. The in vitro release profile shows a sufficient percentage of drugs released through the methyl acetate cellulose membrane. This initial study showed that the nanoemulsion formulated using POEs has great potential for topical delivery of ketoprofen.

Matched MeSH terms: Ketoprofen/pharmacokinetics
Drug use and dosing in chronic kidney disease

Hassan Y, Al-Ramahi R, Abd Aziz N, Ghazali R

Ann Acad Med Singap, 2009 Dec;38(12):1095-103.
PMID: 20052447

One of the most important drug-related problems in patients with chronic kidney disease (CKD) is medication dosing errors. Many medications and their metabolites are eliminated through the kidney. Thus, adequate renal function is important to avoid toxicity. Patients with renal impairment often have alterations in their pharmacokinetic and pharmacodynamic parameters. The clearance of drugs eliminated primarily by renal filtration is decreased by renal disease. Therefore, special consideration should be taken when these drugs are prescribed to patients with impaired renal function. Despite the importance of dosage adjustment in patients with CKD, such adjustments are sometimes ignored. Physicians and pharmacists can work together to accomplish safe drug prescribing. This task can be complex and require a stepwise approach to ensure effectiveness, minimise further damage and prevent drug nephrotoxicity.

Matched MeSH terms: Prescription Drugs/pharmacokinetics
The oil-absorbing property of polyhydroxyalkanoate films and its practical application: a refreshing new outlook for an old degrading material

Sudesh K, Loo CY, Goh LK, Iwata T, Maeda M

Macromol Biosci, 2007 Nov 12;7(11):1199-205.
PMID: 17703476

Polyhydroxyalkanoates (PHAs) have attracted the attention of academia and industry because of their plastic-like properties and biodegradability. However, practical applications as a commodity material have not materialized because of their high production cost and unsatisfactory mechanical properties. PHAs are also believed to have high-value applications as an absorbable biomaterial for tissue engineering and drug-delivery devices because of their biocompatibility. However, research in these areas is still in its very early stages. The main problem faced by proponents of PHAs is the lack of a niche area where PHAs will be the most desired material in terms of its function during use rather than because of its eco-friendly virtues after use. Here, we report on the oil-absorbing property of PHA films and its potential applications. By comparing with some of the existing commercial products, the potential application of PHAs as cosmetic oil-blotting films is revealed for the first time. Besides having the ability to rapidly absorb and retain oil, PHA films also have a natural oil-indicator property, showing obvious changes in opacity following oil absorption. Surface analysis revealed that the surface structures such as porosity and smoothness exert great influence on the rapid oil-absorption properties of the PHA films. These newly discovered properties could be exploited to create a niche area for the practical applications of PHAs.

Matched MeSH terms: Polyhydroxyalkanoates/pharmacokinetics*
Sorption of Cr(VI), Cu(II) and Pb(II) by growing and non-growing cells of a bacterial consortium

Sannasi P, Kader J, Ismail BS, Salmijah S

Bioresour Technol, 2006 Mar;97(5):740-7.
PMID: 16324841

This paper reports the sorption of three metallic ions, namely Cr(VI), Cu(II) and Pb(II) in aqueous solution by a consortium culture (CC) comprising an acclimatised mixed bacterial culture collected from point and non-point sources. Metal sorption capability of growing and non-growing cells at initial pH of between 3 and 8 in the 1-100mg/L concentration range were studied based on Q(max) and K(f) values of the Langmuir and linearised Freundlich isotherm models, respectively. Maximal metal loading was generally observed to be dependent on the initial pH. Growing cells displayed significant maximal loading (Q(max)) for Pb(II) (238.09 mg/g) and Cu(II) (178.87 mg/g) at pH 6 and at pH 7 for Cr(VI) (90.91 mg/g) compared to non-growing cells (p < 0.05). At the pH range of 6-8, growing cells showed higher loading capacity compared to non-growing cells i.e. 38-52% for Cr, 17-28% for Cu and 3-17% for Pb. At lower metal concentrations and at more acidic pH (3-4) however, non-growing cells had higher metal loading capacity than growing cells. The metal sorption capacity for both populations were as follows: Pb(II) > Cu(II) > Cr(VI).

Matched MeSH terms: Metals, Heavy/pharmacokinetics*
Preparation, characterization, and in vitro release studies of insulin-loaded double-walled poly(lactide-co-glycolide) microspheres

Ansary RH, Rahman MM, Awang MB, Katas H, Hadi H, Doolaanea AA

Drug Deliv Transl Res, 2016 06;6(3):308-18.
PMID: 26817478 DOI: 10.1007/s13346-016-0278-y

The purpose of this study was to fabricate insulin-loaded double-walled and single-polymer poly(lactide-co-glycolide) (PLGA) microspheres using a fast degrading glucose core, hydroxyl-terminated poly(lactide-co-glycolide) (Glu-PLGA), and a moderate degrading carboxyl-terminated PLGA polymers. A modified water-in-oil-in-oil-in-water (w/o/o/w) emulsion solvent evaporation technique was employed to prepare double-walled microspheres, whereas single-polymer microspheres were fabricated by a conventional water-in-oil-in-water (w/o/w) emulsion solvent evaporation method. The effect of fabrication techniques and polymer characteristics on microspheres size, morphology, encapsulation efficiency, in vitro release, and insulin stability was evaluated. The prepared double-walled microspheres were essentially non-porous, smooth surfaced, and spherical in shape, whereas single-polymer microspheres were highly porous. Double-walled microspheres exhibited a significantly reduced initial burst followed by sustained and almost complete release of insulin compared to single-polymer microspheres. Initial burst release was further suppressed from double-walled microspheres when the mass ratio of the component polymers was increased. In conclusion, double-walled microspheres made of Glu-PLGA and PLGA can be a potential delivery system of therapeutic insulin.

Matched MeSH terms: Insulin/pharmacokinetics*
Production, Characterization and Evaluation of Kaempferol Nanosuspension for Improving Oral Bioavailability

Qian YS, Ramamurthy S, Candasamy M, Shadab M, Kumar RH, Meka VS

Curr Pharm Biotechnol, 2016;17(6):549-55.
PMID: 26813303

CONTEXT: Kaempferol has a large particle size and poor water solubility, leading to poor oral bioavailability. The present work aimed to develop a kaempferol nanosuspension (KNS) to improve pharmacokinetics and absolute bioavailability.
METHODS: A nanosuspension was prepared using high pressure homogenization (HPH) techniques. The physico-chemical properties of the kaempferol nanosuspension (KNS) were characterized using photon correlation spectroscopy (PCS), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR) and x-ray diffractometry (XRD). A reversephase high performance liquid chromatography (RP-HPLC) method for the analysis of the drug in rat plasma was developed and validated as per ICH guidelines. In vivo pharmacokinetic parameters of oral pure kaempferol solution, oral kaempferol nanosuspension and intravenous pure kaempferol were assessed in rats.
RESULTS AND DISCUSSION: The kaempferol nanosuspension had a greatly reduced particle size (426.3 ± 5.8 nm), compared to that of pure kaempferol (1737 ± 129 nm). The nanosuspension was stable under refrigerated conditions. No changes in physico-chemical characteristics were observed. In comparison to pure kaempferol, kaempferol nanosuspension exhibited a significantly (P<0.05) increased in Cmax and AUC(0-∞) following oral administration and a significant improvement in absolute bioavailability (38.17%) compared with 13.03% for pure kaempferol.
CONCLUSION: These results demonstrate enhanced oral bioavailability of kaempferol when formulated as a nanosuspension.

Matched MeSH terms: Kaempferols/pharmacokinetics*
Binding mechanism of heavy metals biosorption by Pycnoporus sanguineus

Mashitah, Zulfadhly Z, Bhatia S

Artif Cells Blood Substit Immobil Biotechnol, 1999 Sep-Nov;27(5-6):441-5.
PMID: 10595446

Non-living biomass of Pycnoporus sanguineus has an ability to take up lead,copper and cadmium ions from an aqueous solution. The role played by various functional groups in the cell wall and the mechanism uptake of lead, copper and cadmium by Pycnoporus sanguineus were investigated. Modification of the functional groups such as lipids, carboxylic and amino was done through chemical pretreatment in order to study their role in biosorption of metal ions. Results showed that the chemical modification of these functional groups has modified the ability of biomass to remove lead, copper and cadmium ions from the solution. Scanning electron microscopy was also used to study the morphological structure of the biomass before and after adsorption. The electron micrograph indicated that the structure of biomass changed due to the adsorption of the metals onto the cell walls. Furthermore, the X-ray energy dispersion analysis (EDAX) showed that the calcium ion present in the cell wall of biomass was released and replaced by lead ions. This implied that an ion exchange is one of the principal mechanisms for metal biosorption.

Matched MeSH terms: Metals, Heavy/pharmacokinetics*
The effect of morphine on the biosynthesis of catecholamines in the rat brain

Malini M, Kwan TK, Perumal R

Biochem. Mol. Biol. Int., 1994 Feb;32(2):279-90.
PMID: 8019433

In vivo studies involved monitoring the effect of morphine administration on catecholamine biosynthesis by the brain while in vitro studies involved studying the effect of morphine on the uptake of tritiated tyrosine by synaptosomes and its subsequent incorporation into the catecholamines. The extremely low levels of these endogenous compounds required the use of High Performance Liquid Chromatography with electrochemical detection. Intra-peritoneal injection of morphine at a dosage of 10 mg/kg did not produce appreciable changes in the catecholamine levels but a dosage of 30 mg/kg morphine was found to elevate dihydroxy phenylacetic acid content. At a dosage of 60 mg/kg, dopamine levels were elevated while noradrenaline was depleted. Morphine, at a concentration of 1 x 10(-5)M increases the incorporation of tritiated tyrosine into dopamine and dihydroxy phenylacetic acid in synaptosomal preparations.

Matched MeSH terms: Tyrosine/pharmacokinetics
Estimation of population pharmacokinetics for carbamazepine in Malaysian patients using the OPT computer program

Ismail R, Rahman AF

J Clin Pharm Ther, 1993 Feb;18(1):55-8.
PMID: 8473361

We used OPT to estimate individual and population pharmacokinetics for carbamazepine (CBZ) in Malaysian epileptic patients attending our Neurology Clinic. We noted that plasma CBZ concentrations and clearances correlated poorly with daily doses and body weights respectively but we found the values for clearance, volumes of distribution, elimination rate constants and half lives to be in good agreement with earlier reports. We conclude that OPT is a simple yet useful program to derive individual and population pharmacokinetic parameters for CBZ for use in dosage adjustments. We also conclude that although the Malaysian population do not differ substantially in handling CBZ, available data for the pharmacokinetic parameters must be used cautiously in applying it to the therapeutic drug monitoring for CBZ in our patients.

Matched MeSH terms: Carbamazepine/pharmacokinetics*
Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine

Gunawardena TNA, Rahman MT, Abdullah BJJ, Abu Kasim NH

J Tissue Eng Regen Med, 2019 04;13(4):569-586.
PMID: 30644175 DOI: 10.1002/term.2806

Recent studies suggest that the main driving force behind the therapeutic activity observed in mesenchymal stem cells (MSCs) are the paracrine factors secreted by these cells. These biomolecules also trigger antiapoptotic events to prevent further degeneration of the diseased organ through paracrine signalling mechanisms. In comparison with the normal physiological conditions, an increased paracrine gradient is observed within the peripheral system of diseased organs that enhances the migration of tissue-specific MSCs towards the site of infection or injury to promote healing. Thus, upon administration of conditioned media derived from mesenchymal stem cell cultures (MSC-CM) could contribute in maintaining the increased paracrine factor gradient between the diseased organ and the stem cell niche in order to speed up the process of recovery. Based on the principle of the paracrine signalling mechanism, MSC-CM, also referred as the secretome of the MSCs, is a rich source of the paracrine factors and are being studied extensively for a wide range of regenerative therapies such as myocardial infarction, stroke, bone regeneration, hair growth, and wound healing. This article highlights the current technological applications and advances of MSC-CM with the aim to appraise its future potential as a regenerative therapeutic agent.

Matched MeSH terms: Culture Media, Conditioned/pharmacokinetics
Comparative analysis of antioxidant and antiproliferative activities of Rhodomyrtus tomentosa extracts prepared with various solvents

Abd Hamid H, Mutazah R, Yusoff MM, Abd Karim NA, Abdull Razis AF

Food Chem Toxicol, 2017 Oct;108(Pt B):451-457.
PMID: 27725206 DOI: 10.1016/j.fct.2016.10.004

Rhodomyrtus tomentosa (Aiton) Hassk. has a wide spectrum of pharmacological effects and has been used to treat wounds, colic diarrhoea, heartburns, abscesses and gynaecopathy. The potential antiproliferative activities of R. tomentosa extracts from different solvents were evaluated in vitro on HepG2, MCF-7 and HT 29 cell lines while antioxidant activity was monitored by radical scavenging assay (DPPH), copper reducing antioxidant capacity (CUPRAC) and β-carotene bleaching assay. Extracts from R. tomentosa show the viability of the cells in concentration-dependent manner. According to the IC50 obtained, the ethyl acetate extracts showed significant antiproliferative activity on HepG2 (IC50 11.47 ± 0.280 μg/mL), MCF-7 (IC50 2.68 ± 0.529 μg/mL) and HT 29 (IC50 16.18 ± 0.538 μg/mL) after 72 h of treatment. Bioassay guided fractionation of the ethyl acetate extract led to the isolation of lupeol. Methanol extracts show significant antioxidant activities in DPPH (EC50 110.25 ± 0.005 μg/ml), CUPRAC (EC50 53.84 ± 0.004) and β-carotene bleaching (EC50 58.62 ± 0.001) due to the presence of high total flavonoid and total phenolic content which were 110.822 ± 0.017 mg butylated hydroxytoluene (BHT)/g and 190.467 ± 0.009 mg gallic acid (GAE)/g respectively. Taken together, the results extracts show the R. tomentosa as a potential source of antioxidant and antiproliferative efficacy.

Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacokinetics*
An evaluation of the significance of mouth and hand contamination for lead absorption in lead-acid battery workers

Far HS, Pin NT, Kong CY, Fong KS, Kian CW, Yan CK

Int Arch Occup Environ Health, 1993;64(6):439-43.
PMID: 8458660

The present study was conducted to evaluate the role of ingestion through hand and mouth contamination in the absorption of lead in 25 lead-acid battery workers. Levels of personal exposure to airborne lead ranged from 0.004 to 2.58 mg/m3 [geometric mean 0.098, with 25% of samples exceeding threshold limit values (ACGIH) of 0.15 mg/m3]; the mean (SD) blood lead level was 48.9 (10.8) micrograms/dl. Mean hand lead contents increased 33-fold from preshift levels on Monday mornings (33.5 micrograms/500 ml) to midshift levels on Thursday afternoons (1121 micrograms/500 ml). Mouth lead contents increased 16-fold from 0.021 micrograms/50 ml on Mondays to 0.345 micrograms/50 ml on Thursdays. The typical Malay racial habit of feeding with bare hands and fingers without utensils (closely associated with mouth and hand lead levels on Mondays) explained the bulk of the variance in blood lead levels (40%), with mouth lead on Thursdays (closely associated with poor personal hygiene) explaining a further 10%. Air lead was not a significant explanatory variable. The implementation of a programme of reinforcing hand-washing and mouth-rinsing practices resulted in a reduction of the blood lead level by 11.5% 6 months later. These results indicate that parenteral intake from hand and mouth contamination is an important cause of lead absorption in lead-exposed workers.

Matched MeSH terms: Lead/pharmacokinetics

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