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Displaying publications 21 - 40 of 831 in total

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In vitro genotoxicity tests for polyhydroxybutyrate--a synthetic biomaterial

Ali AQ, Kannan TP, Ahmad A, Samsudin AR

Toxicol In Vitro, 2008 Feb;22(1):57-67.
PMID: 17892925

The aims of this study are to determine the mutagenicity of a locally produced polyhydroxybutyrate (PHB) using Salmonella mutagenicity test and to find out if PHB altered the expression of p53 and c-myc proto-oncogenes and bcl-xl and bcl-xs anti-apoptotic genes in the human fibroblast cell line, MRC-5. Different concentrations of PHB were incubated with special genotypic variants of Salmonella strains (TA1535, TA1537, TA1538, TA98 and TA100) carrying mutations in several genes both with and without metabolic activation (S9) and the test was assessed based on the number of revertant colonies. The average number of revertant colonies per plate treated with PHB was less than double as compared to that of negative control. For the gene expression analyses, fibroblast cell lines were treated with PHB at different concentrations and incubated for 1, 12, 24 and 48 h separately. The total RNA was isolated and analysed for the expression of p53, c-myc, bcl-xl and bcl-xs genes. The PHB did not show over or under expression of the genes studied. The above tests indicate that the locally produced PHB is non-genotoxic and does not alter the expression of the proto-oncogenes and anti-apoptotic genes considered in this study.

Matched MeSH terms: Dose-Response Relationship, Drug
Lineage-related cytotoxicity and clonogenic profile of 1,4-benzoquinone-exposed hematopoietic stem and progenitor cells

Chow PW, Abdul Hamid Z, Chan KM, Inayat-Hussain SH, Rajab NF

Toxicol Appl Pharmacol, 2015 Apr 1;284(1):8-15.
PMID: 25645895 DOI: 10.1016/j.taap.2015.01.016

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) are sensitive targets for benzene-induced hematotoxicity and leukemogenesis. The impact of benzene exposure on the complex microenvironment of HSCs and HPCs remains elusive. This study aims to investigate the mechanism linking benzene exposure to targeting HSCs and HPCs using phenotypic and clonogenic analyses. Mouse bone marrow (BM) cells were exposed ex vivo to the benzene metabolite, 1,4-benzoquinone (1,4-BQ), for 24h. Expression of cellular surface antigens for HSC (Sca-1), myeloid (Gr-1, CD11b), and lymphoid (CD45, CD3e) populations were confirmed by flow cytometry. The clonogenicity of cells was studied using the colony-forming unit (CFU) assay for multilineage (CFU-GM and CFU-GEMM) and single-lineage (CFU-E, BFU-E, CFU-G, and CFU-M) progenitors. 1,4-BQ demonstrated concentration-dependent cytotoxicity in mouse BM cells. The percentage of apoptotic cells increased (p < 0.05) following 1,4-BQ exposure. Exposure to 1,4-BQ showed no significant effect on CD3e(+) cells but reduced the total counts of Sca-1(+), CD11b(+), Gr-1(+), and CD45(+) cells at 7 and 12 μM (p < 0.05). Furthermore, the CFU assay showed reduced (p < 0.05) clonogenicity in 1,4-BQ-treated cells. 1,4-BQ induced CFU-dependent cytotoxicity by significantly inhibiting colony growth for CFU-E, BFU-E, CFU-G, and CFU-M starting at a low concentration of exposure (5μM); whereas for the CFU-GM and CFU-GEMM, the inhibition of colony growth was remarkable only at 7 and 12μM of 1,4-BQ, respectively. Taken together, 1,4-BQ caused lineage-related cytotoxicity in mouse HPCs, demonstrating greater toxicity in single-lineage progenitors than in those of multi-lineage.

Matched MeSH terms: Dose-Response Relationship, Drug
Single-walled carbon nanotubes (SWCNTs) inhibit heat shock protein 90 (HSP90) signaling in human lung fibroblasts and keratinocytes

Ong LC, Tan YF, Tan BS, Chung FF, Cheong SK, Leong CO

Toxicol Appl Pharmacol, 2017 08 15;329:347-357.
PMID: 28673683 DOI: 10.1016/j.taap.2017.06.024

Single-walled carbon nanotubes (SWCNTs) are carbon-based nanomaterials that possess immense industrial potential. Despite accumulating evidence that exposure to SWCNTs might be toxic to humans, our understanding of the mechanisms for cellular toxicity of SWCNTs remain limited. Here, we demonstrated that acute exposure of short (1-3μm) and regular-length (5-30μm) pristine, carboxylated or hydroxylated SWCNTs inhibited cell proliferation in human somatic and human stem cells in a cell type-dependent manner. The toxicity of regular-length pristine SWCNT was most evidenced in NP69>CYT00086>MCF-10A>MRC-5>HaCaT > HEK-293T>HepG2. In contrast, the short pristine SWCNTs were relatively less toxic in most of the cells being tested, except for NP69 which is more sensitive to short pristine SWCNTs as compared to regular-length pristine SWCNTs. Interestingly, carboxylation and hydroxylation of regular-length SWCNTs, but not the short SWCNTs, significantly reduced the cytotoxicity. Exposure of SWCNTs also induced caspase 3 and 9 activities, mitochondrial membrane depolarization, and significant apoptosis and necrosis in MRC-5 embryonic lung fibroblasts. In contrast, SWCNTs inhibited the proliferation of HaCaT human keratinocytes without inducing cell death. Further analyses by gene expression profiling and Connectivity Map analysis showed that SWCNTs induced a gene expression signature characteristic of heat shock protein 90 (HSP90) inhibition in MRC-5 cells, suggesting that SWCNTs may inhibit the HSP90 signaling pathway. Indeed, exposure of MRC-5 cells to SWCNTs results in a dose-dependent decrease in HSP90 client proteins (AKT, CDK4 and BCL2) and a concomitant increase in HSP70 expression. In addition, SWCNTs also significantly inhibited HSP90-dependent protein refolding. Finally, we showed that ectopic expression of HSP90, but not HSP40 or HSP70, completely abrogated the cytotoxic effects of SWCNTs, suggesting that SWCNT-induced cellular toxicity is HSP90 dependent. In summary, our findings suggest that the toxic effects of SWCNTs are mediated through inhibition of HSP90 in human lung fibroblasts and keratinocytes.

Matched MeSH terms: Dose-Response Relationship, Drug
Anti-allergic activity of 2,4,6-trihydroxy-3-geranylacetophenone (tHGA) via attenuation of IgE-mediated mast cell activation and inhibition of passive systemic anaphylaxis

Tan JW, Israf DA, Harith HH, Md Hashim NF, Ng CH, Shaari K, et al.

Toxicol Appl Pharmacol, 2017 03 15;319:47-58.
PMID: 28167223 DOI: 10.1016/j.taap.2017.02.002

tHGA, a geranyl acetophenone compound originally isolated from a local shrub called Melicope ptelefolia, has been previously reported to prevent ovalbumin-induced allergic airway inflammation in a murine model of allergic asthma by targeting cysteinyl leukotriene synthesis. Mast cells are immune effector cells involved in the pathogenesis of allergic diseases including asthma by releasing cysteinyl leukotrienes. The anti-asthmatic properties of tHGA could be attributed to its inhibitory effect on mast cell degranulation. As mast cell degranulation is an important event in allergic responses, this study aimed to investigate the anti-allergic effects of tHGA in cellular and animal models of IgE-mediated mast cell degranulation. For in vitro model of IgE-mediated mast cell degranulation, DNP-IgE-sensitized RBL-2H3 cells were pre-treated with tHGA before challenged with DNP-BSA to induce degranulation. For IgE-mediated passive systemic anaphylaxis, Sprague Dawley rats were sensitized by intraperitoneal injection of DNP-IgE before challenged with DNP-BSA. Both in vitro and in vivo models showed that tHGA significantly inhibited the release of preformed mediators (β-hexosaminidase and histamine) as well as de novo mediators (interleukin-4, tumour necrosis factor-α, prostaglandin D2 and leukotriene C4). Pre-treatment of tHGA also prevented IgE-challenged RBL-2H3 cells and peritoneal mast cells from undergoing morphological changes associated with mast cell degranulation. These findings indicate that tHGA possesses potent anti-allergic activity via attenuation of IgE-mediated mast cell degranulation and inhibition of IgE-mediated passive systemic anaphylaxis. Thus, tHGA may have the potential to be developed as a mast cell stabilizer for the treatment of allergic diseases in the future.

Matched MeSH terms: Dose-Response Relationship, Drug
The selective cytotoxicity of the alkenyl glucosinolate hydrolysis products and their presence in Brassica vegetables

Kadir NH, David R, Rossiter JT, Gooderham NJ

Toxicology, 2015 Aug 6;334:59-71.
PMID: 26066520 DOI: 10.1016/j.tox.2015.06.002

Cruciferous vegetable consumption correlates with reduced risk of cancer. This chemopreventative activity may involve glucosinolates and their hydrolysis products. Glucosinolate-derived isothiocyanates have been studied for their toxicity and chemopreventative properties, but other hydrolysis products (epithionitriles and nitriles) have not been thoroughly examined. We report that these hydrolysis products differ in their cytotoxicity to human cells, with toxicity most strongly associated with isothiocyanates rather than epithionitriles and nitriles. We explored mechanisms of this differential cytotoxicity by examining the role of oxidative metabolism, oxidative stress, mitochondrial permeability, reduced glutathione levels, cell cycle arrest and apoptosis. 2-Propenylisothiocyanate and 3-butenylisothiocyanate both inhibited cytochome P450 1A (CYP1A) enzyme activity in CYP expressing MCL-5 cells at high cytotoxic doses. Incubation of MCL-5 cells with non-cytotoxic doses of 2-propenylisothiocyanate for 24h resulted in a dose-dependent inhibition of ethoxyresorufin O-deethylase, yet failed to affect CYP1A1 mRNA expression indicating interference with enzyme activity rather than inhibition of transcription. Increased reactive oxygen species (ROS) production was observed only for 2-propenylisothiocyanate treatment. 2-Propenylisothiocyanate treatment lowered reduced glutathione levels whereas no changes were noted with 3,4-epithiobutylnitrile. Cell cycle analysis showed that 2-propenylisothiocyanate induced a G2/M block whereas other hydrolysis products showed only marginal effects. We found that 2-propenylisothiocyanate and 3-butenylisothiocyanate induced cell death predominantly via necrosis whereas, 3,4-epithiobutylnitrile promoted both necrosis and apoptosis. Thus the activity of glucosinolate hydrolysis products includes cytotoxicity that is compound-class specific and may contribute to their putative chemoprotection properties.

Matched MeSH terms: Dose-Response Relationship, Drug
Fulltext Goniothalamin induces coronary artery smooth muscle cells apoptosis: the p53-dependent caspase-2 activation pathway

Chan KM, Rajab NF, Siegel D, Din LB, Ross D, Inayat-Hussain SH

Toxicol. Sci., 2010 Aug;116(2):533-48.
PMID: 20498002 DOI: 10.1093/toxsci/kfq151

Goniothalamin (GN), a styryl-lactone isolated from Goniothalamus andersonii, has been demonstrated to possess antirestenostic properties by inducing apoptosis on coronary artery smooth muscle cells (CASMCs). In this study, the molecular mechanisms of GN-induced CASMCs apoptosis were further elucidated. Apoptosis assessment based on the externalization of phosphatidylserine demonstrated that GN induces CASMCs apoptosis in a concentration-dependent manner. The GN-induced DNA damage occurred with concomitant elevation of p53 as early as 2 h, demonstrating an upstream signal for apoptosis. However, the p53 elevation in GN-treated CASMCs was independent of NAD(P)H: quinone oxidoreductase 1 and Mdm-2 expression. An increase in hydrogen peroxide and reduction in free thiols confirmed the role for oxidative stress in GN treatment. Pretreatment with the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-FMK) that significantly abrogated GN-induced CASMCs apoptosis suggested the involvement of caspase(s). The role of apical caspase-2, -8, and -9 was then investigated, and sequential activation of caspase-2 and -9 but not caspase-8 leading to downstream caspase-3 cleavage was observed in GN-treated CASMCs. Reduction of ATP level and decrease in oxygen consumption further confirmed the role of mitochondria in GN-induced apoptosis in CASMCs. The mitochondrial release of cytochrome c was seen without mitochondrial membrane potential loss and was independent of cardiolipin. These data provide insight into the mechanisms of GN-induced apoptosis, which may have important implications in the development of drug-eluting stents.

Matched MeSH terms: Dose-Response Relationship, Drug
Cost-effectiveness analysis of pharmacogenetic-guided warfarin dosing in Thailand

Chong HY, Saokaew S, Dumrongprat K, Permsuwan U, Wu DB, Sritara P, et al.

Thromb Res, 2014 Dec;134(6):1278-84.
PMID: 25456732 DOI: 10.1016/j.thromres.2014.10.006

Pharmacogenetic (PGx) test is a useful tool for guiding physician on an initiation of an optimal warfarin dose. To implement of such strategy, the evidence on the economic value is needed. This study aimed to determine the cost-effectiveness of PGx-guided warfarin dosing compared with usual care (UC).

Matched MeSH terms: Dose-Response Relationship, Drug
Double-blind randomised controlled trial of vitamin D3 supplementation for the prevention of acute respiratory infection in older adults and their carers (ViDiFlu)

Martineau AR, Hanifa Y, Witt KD, Barnes NC, Hooper RL, Patel M, et al.

Thorax, 2015 Oct;70(10):953-60.
PMID: 26063508 DOI: 10.1136/thoraxjnl-2015-206996

RATIONALE: Low-dose vitamin D supplementation is already recommended in older adults for prevention of fractures and falls, but clinical trials investigating whether higher doses could provide additional protection against acute respiratory infection (ARI) are lacking.
OBJECTIVE: To conduct a clinical trial of high-dose versus low-dose vitamin D3 supplementation for ARI prevention in residents of sheltered-accommodation housing blocks ('schemes') and their carers in London, UK.
MEASUREMENTS AND METHODS: Fifty-four schemes (137 individual participants) were allocated to the active intervention (vitamin D3 2.4 mg once every 2 months +10 μg daily for residents, 3 mg once every 2 months for carers), and 54 schemes with 103 participants were allocated to control (placebo once every 2 months +vitamin D3 10 μg daily for residents, placebo once every 2 months for carers) for 1 year. Primary outcome was time to first ARI; secondary outcomes included time to first upper/lower respiratory infection (URI/LRI, analysed separately), and symptom duration.
MAIN RESULTS: Inadequate vitamin D status was common at baseline: 220/240 (92%) participants had serum 25(OH)D concentration <75 nmol/L. The active intervention did not influence time to first ARI (adjusted HR (aHR) 1.18, 95% CI 0.80 to 1.74, p=0.42). When URI and LRI were analysed separately, allocation to the active intervention was associated with increased risk of URI (aHR 1.48, 95% CI 1.02 to 2.16, p=0.039) and increased duration of URI symptoms (median 7.0 vs 5.0 days for active vs control, adjusted ratio of geometric means 1.34, 95% CI 1.09 to 1.65, p=0.005), but not with altered risk or duration of LRI.
CONCLUSIONS: Addition of intermittent bolus-dose vitamin D3 supplementation to a daily low-dose regimen did not influence risk of ARI in older adults and their carers, but was associated with increased risk and duration of URI.
TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT01069874.

Matched MeSH terms: Dose-Response Relationship, Drug
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.

Matched MeSH terms: Dose-Response Relationship, Drug
Variability of plasma phenobarbitone concentration in Asian children in Singapore

Lee HS

Ther Drug Monit, 1984;6(2):182-8.
PMID: 6740737

In a study with 113 Asian children in which phenobarbitone was used as the sole antiepileptic drug in 75 children, including Chinese, Malays, and Indians, the mean phenobarbitone dosage required to produce a plasma level of 15 micrograms/ml was 5.2 mg/kg/day. While the mean plasma level/dose ratio varied, the differences between the three ethnic groups were not statistically significant. Also of little difference were the ratios between the male and female groups. For those patients with poor seizure control, however, the mean plasma level/dose ratio was significantly lower than in those whose seizures were controlled. Using additional anticonvulsant drugs concurrently with phenobarbitone in 40 children raised the mean plasma level/dose ratios significantly in each ethnic group. Further, the greater age level in those given additional antiepileptic drugs might have contributed slightly to a higher mean plasma level/dose ratio.

Matched MeSH terms: Dose-Response Relationship, Drug
Slow carbamazepine clearance in a nonadherent Malay woman with epilepsy and thyrotoxicosis

Yeap LL, Lim KS, Ng CC, Hui-Ping Khor A, Lo YL

Ther Drug Monit, 2014 Feb;36(1):3-9.
PMID: 24342894 DOI: 10.1097/FTD.0000000000000024

The authors describe a case of a 37-year-old Malay lady with an unusually slow carbamazepine clearance, which may be related to genetic polymorphisms of drug metabolizing enzymes and transporters. When given a small daily dose of 200 mg immediate-release carbamazepine, this patient experienced drowsiness. Subsequently, she reduced her carbamazepine dose to 200 mg twice a week (on Mondays and Fridays), resulting in poor seizure control. At the same time, the patient was diagnosed with hyperthyroidism and was given carbimazole and propranolol. Hyperthyroidism and the concurrent use of these antihyperthyroid agents may have further slowed down the metabolism of carbamazepine. Therapeutic drug monitoring of carbamazepine was carried out, and a slow carbamazepine clearance of 1.45 L·h⁻¹ per 70 kg was observed. Genotyping of selected genetic variants in CYP3A4, CYP3A5, EPHX1, ABCB1, and ABCC2 revealed that she has CYP3A5*3/*3 and ABCB1 3435-CC genotypes. Both genotypes have been shown to be associated with higher adjusted mean serum carbamazepine concentration in Chinese and Korean patients with epilepsy. Physicians should be vigilant about the risk of adverse effects among patients with a slow carbamazepine clearance, especially in Malays. Simulations of carbamazepine dosing regimen based on the pharmacokinetic parameters of this patient were performed to allow individualization of drug therapy.

Matched MeSH terms: Dose-Response Relationship, Drug
Fulltext Influence of cytokinins in combination with GA₃ on shoot multiplication and elongation of tea clone Iran 100 (Camellia sinensis (L.) O. Kuntze)

Gonbad RA, Rani Sinniah U, Aziz MA, Mohamad R

ScientificWorldJournal, 2014;2014:943054.
PMID: 24605069 DOI: 10.1155/2014/943054

The use of in vitro culture has been accepted as an efficient technique for clonal propagation of many woody plants. In the present research, we report the results of a number of experiments aimed at optimizing micropropagation protocol for tea (Camellia sinensis (L.) O. Kuntze) (clone Iran 100) using nodal segments as the explant. The effect of different combinations and concentrations of plant growth regulators (PGR) (BAP, TDZ, GA₃) on shoot multiplication and elongation was assessed. The influence of exposure to IBA in liquid form prior to transfer to solid media on rooting of tea microshoots was investigated. The results of this study showed that the best treatment for nodal segment multiplication in terms of the number of shoot per explant and shoot elongation was obtained using 3 mg/L BAP in combination with 0.5 mg/L GA₃. TDZ was found to be inappropriate for multiplication of tea clone Iran 100 as it resulted in hyperhydricity especially at concentrations higher than 0.05 mg/L. Healthy shoots treated with 300 mg/L IBA for 30 min followed by transfer to 1/2 strength MS medium devoid of PGR resulted in 72.3% of shoots producing roots and upon transferring them to acclimatization chamber 65% survival was obtained prior to field transfer.

Matched MeSH terms: Dose-Response Relationship, Drug
Fulltext Allocation of secondary metabolites, photosynthetic capacity, and antioxidant activity of Kacip Fatimah (Labisia pumila Benth) in response to CO2 and light intensity

Ibrahim MH, Jaafar HZ, Karimi E, Ghasemzadeh A

ScientificWorldJournal, 2014;2014:360290.
PMID: 24683336 DOI: 10.1155/2014/360290

A split plot 3 by 4 experiment was designed to investigate and distinguish the relationships among production of secondary metabolites, soluble sugar, phenylalanine ammonia lyase (PAL; EC 4.3.1.5) activity, leaf gas exchange, chlorophyll content, antioxidant activity (DPPH), and lipid peroxidation under three levels of CO2 (400, 800, and 1200 μ mol/mol) and four levels of light intensity (225, 500, 625, and 900 μ mol/m(2)/s) over 15 weeks in Labisia pumila. The production of plant secondary metabolites, sugar, chlorophyll content, antioxidant activity, and malondialdehyde content was influenced by the interactions between CO2 and irradiance. The highest accumulation of secondary metabolites, sugar, maliondialdehyde, and DPPH activity was observed under CO2 at 1200 μ mol/mol + light intensity at 225 μ mol/m(2)/s. Meanwhile, at 400 μ mol/mol CO2 + 900 μ mol/m(2)/s light intensity the production of chlorophyll and maliondialdehyde content was the highest. As CO2 levels increased from 400 to 1200 μ mol/mol the photosynthesis, stomatal conductance, f v /f m (maximum efficiency of photosystem II), and PAL activity were enhanced. The production of secondary metabolites displayed a significant negative relationship with maliondialdehyde indicating lowered oxidative stress under high CO2 and low irradiance improved the production of plant secondary metabolites that simultaneously enhanced the antioxidant activity (DPPH), thus improving the medicinal value of Labisia pumila under this condition.

Matched MeSH terms: Dose-Response Relationship, Drug
Fulltext Diverse effects of lead nitrate on the proliferation, differentiation, and gene expression of stem cells isolated from a dental origin

Abdullah M, Rahman FA, Gnanasegaran N, Govindasamy V, Abu Kasim NH, Musa S

ScientificWorldJournal, 2014;2014:235941.
PMID: 24616615 DOI: 10.1155/2014/235941

Lead (Pb(2+)) exposure continues to be a significant public health problem. Therefore, it is vital to have a continuous epidemiological dataset for a better understanding of Pb(2+) toxicity. In the present study, we have exposed stem cells isolated from deciduous and permanent teeth, periodontal ligament, and bone marrow to five different types of Pb(2+) concentrations (160, 80, 40, 20, and 10 µM) for 24 hours to identify the adverse effects of Pb(2+) on the proliferation, differentiation, and gene expression on these cell lines. We found that Pb(2+) treatment altered the morphology and adhesion of the cells in a dose-dependent manner. There were no significant changes in terms of cell surface phenotypes. Cells exposed to Pb(2+) continued to differentiate into chondrogenesis and adipogenesis, and a severe downregulation was observed in osteogenesis. Gene expression studies revealed a constant expression of key markers associated with stemness (Oct 4, Rex 1) and DNA repair enzyme markers, but downregulation occurred with some ectoderm and endoderm markers, demonstrating an irregular and untimely differentiation trail. Our study revealed for the first time that Pb(2+) exposure not only affects the phenotypic characteristics but also induces significant alteration in the differentiation and gene expression in the cells.

Matched MeSH terms: Dose-Response Relationship, Drug
Proliferation potential of 18-month-old callus of Ananas comosus L. cv. Moris

De Silva AE, Kadir MA, Aziz MA, Kadzimin S

ScientificWorldJournal, 2006 Feb 17;6:169-75.
PMID: 16493521

Differential effect of plant growth regulators and additives in proliferation of 18-month-old calli of Ananas comosus L. cv. Moris were assessed in vitro. The proliferation of callus relied on the growth regulators and additives. Of the different auxins supplemented in the Murashige and Skoog (MS) media, 32.22 microM alpha-naphthaleneacetic acid (NAA) gave the highest mean fresh weight of callus (46.817 g). Medium supplemented with 2,4-dichlorophenoxyacetic acid (2,4-D) was inferior to NAA, while b-naphthoxy acetic acid (BNOA) and p-chlorophenoxy acetic acid (4-CPA) were not effective in proliferating 18-months old callus. Addition of casein hydrolysate and coconut water to NAA supplemented medium showed better proliferation and production of callus. However, in terms of callus production, NAA at 32.22 microM was economically better.

Matched MeSH terms: Dose-Response Relationship, Drug
Fulltext Development of Novel Protocol to Al3+ Stress Tolerance at Germination Stage in Indica Rice through Statistical Approaches

Jahan N, Abd Manan F, Mansoor A, Zaidi MA, Shahwani MN, Javed MA

ScientificWorldJournal, 2018;2018:8180174.
PMID: 30356418 DOI: 10.1155/2018/8180174

Rice production is decreasing by abiotic stresses like heavy metals. In such circumstances, producing food for growing human population is a challenge for plant breeders. Excess of Al3+ in soil has become threat for high yield of rice. Improvement of crop is one of potential solution for high production. The aim of this study was to develop the new method for optimization of Al3+ toxicity tolerance in indica rice at germination stag using two-way ANOVA and Duncan's multiple-range test (DMRT). Seeds of two indica rice cultivars (Pokkali and Pak Basmati) were exposed in different concentrations (control, 5 mM, 15 mM, and 20 mM) of Al3+ toxicity at pH 4 ±0.2 for two weeks. Germination traits such as final germination percentage (FG%), germination energy (GE), germination speed (GS), germination index (GI), mean time of germination (MGT), germination value (GV), germination velocity (GVe), peak value of germination (GPV), and germination capacity (GC) and growth traits such as root length (RL), shoot length (SL), total dry biomass (TDB), and germination vigour index (GVI) were measured. To obtain the maximum number of significance (≤ 0.01%) parameters in each concentration of Al3+ toxicity with control, two-way ANOVA was established and comparison of mean was done using DMRT. The results showed that 5 mM, 10 mM, and 15 mM have less significant effects on the above-mentioned parameters. However, 20 mM concentration of Al3+ produced significant effects (≤ 0.01%). Therefore, 20 mM of Al3+ is considered optimized limit for indica cultivars (Pokkali and Pak Basmati).

Matched MeSH terms: Dose-Response Relationship, Drug
Fulltext Physiochemical and phytochemical properties of wax apple (Syzygium samarangense [Blume] Merrill & L. M. Perry var. Jambu Madu) as affected by growth regulator application

Moneruzzaman Khandaker M, Nasrulhaq Boyce A, Osman N, Sharif Hossain A

ScientificWorldJournal, 2012;2012:728613.
PMID: 22701370 DOI: 10.1100/2012/728613

This study represents the first paper of the effects of growth regulators on the physiochemical and phytochemical properties of the wax apple fruit, a widely cultivated fruit tree in southeast Asia. Net photosynthesis, sucrose phosphate synthase (SPS) activity, peel color, fruit firmness, juice content, pH value, total soluble solids (TSSs), and the sugar acid ratio were all significantly increased in growth regulators (PGRs) treated fruits. The application of gibberellin (GA(3)), naphthalene acetic acid (NAA), and 2,4-dichlorophenoxy acetic acid (2,4-D) significantly reduced titratable acidity and increased total sugar and carbohydrate content compared to the control. The 50 mg/L GA₃, 10 mg/L NAA, and 5 mg/L 2,4-D treatments produced the greatest increases in phenol and flavonoid content; vitamin C content was also higher for these treatments. PGR treatment significantly affected chlorophyll, anthocyanin, and carotene content and produced higher phenylalanine ammonia lyase (PAL) and antioxidant activity levels. There was a positive correlation between peel color and TSS and antioxidant activity and both phenol and flavonoid content and PAL activity and anthocyanin formation. A taste panel assessment was also performed, and the highest scores were given to fruits that had been treated with GA₃ or auxin. The study showed that application of 50 mg/L GA₃, 10 mg/L NAA, and 5 mg/L 2,4-D once a week from bud development to fruit maturation increased the physiochemical and phytochemical properties of wax apple fruits.

Matched MeSH terms: Dose-Response Relationship, Drug
Fulltext Toxicity of metals to a freshwater snail, Melanoides tuberculata

Shuhaimi-Othman M, Nur-Amalina R, Nadzifah Y

ScientificWorldJournal, 2012;2012:125785.
PMID: 22666089 DOI: 10.1100/2012/125785

Adult freshwater snails Melanoides tuberculata (Gastropod, Thiaridae) were exposed for a four-day period in laboratory conditions to a range of copper (Cu), cadmium (Cd), zinc (Zn), lead (Pb), nickel (Ni), iron (Fe), aluminium (Al), and manganese (Mn) concentrations. Mortality was assessed and median lethal times (LT₅₀) and concentrations (LC₅₀) were calculated. LT₅₀ and LC₅₀ increased with the decrease in mean exposure concentrations and times, respectively, for all metals. The LC(50) values for the 96-hour exposures to Cu, Cd, Zn, Pb, Ni, Fe, Al, and Mn were 0.14, 1.49, 3.90, 6.82, 8.46, 8.49, 68.23, and 45.59 mg L⁻¹, respectively. Cu was the most toxic metal to M. tuberculata, followed by Cd, Zn, Pb, Ni, Fe, Mn, and Al (Cu > Cd > Zn > Pb > Ni > Fe > Mn > Al). Metals bioconcentration in M. tuberculata increases with exposure to increasing concentrations and Cu has the highest accumulation (concentration factor) in the soft tissues. A comparison of LC₅₀ values for metals for this species with those for other freshwater gastropods reveals that M. tuberculata is equally sensitive to metals.

Matched MeSH terms: Dose-Response Relationship, Drug
Female sexual dysfunction in patients treated with antidepressant-comparison between escitalopram and fluoxetine

Sidi H, Asmidar D, Hod R, Guan NC

J Sex Med, 2012 May;9(5):1392-9.
PMID: 21477024 DOI: 10.1111/j.1743-6109.2011.02256.x

Selective serotonin reuptake inhibitor is one of the most widely used antidepressant and commonly associated with female sexual dysfunction (FSD).

Matched MeSH terms: Dose-Response Relationship, Drug
Anxiolytic-like effects of mitragynine in the open-field and elevated plus-maze tests in rats

Hazim AI, Ramanathan S, Parthasarathy S, Muzaimi M, Mansor SM

J Physiol Sci, 2014 May;64(3):161-9.
PMID: 24464759 DOI: 10.1007/s12576-014-0304-0

The effects of mitragynine on anxiety-related behaviours in the open-field and elevated plus-maze tests were evaluated. Male Sprague-Dawley rats were orally treated with mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) 60 min before behavioural testing. Mitragynine doses used in this study were selected on the basis of approximately human equivalent doses with reference to our previous literature reports. Acute administration of mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) increased central zone and open arms exploration in the open-field and elevated plus-maze tests respectively. These anxiolytic-like effects of mitragynine were effectively antagonized by intraperitoneal administration of naloxone (2 mg/kg), flumazenil (10 mg/kg), sulpiride (0.5 mg/kg) or SCH 23390 (0.02 mg/kg) 15 min before mitragynine treatments. These findings reveal that the acute administration of mitragynine produces anxiolytic-like effects and this could be possibly attributed to the interactions among opioidergic, GABAergic and dopaminergic systems in brain regions involved in anxiety.

Matched MeSH terms: Dose-Response Relationship, Drug

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