Displaying publications 81 - 100 of 831 in total

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  1. Vijayarathna S, Sasidharan S
    Asian Pac J Trop Biomed, 2012 Oct;2(10):826-9.
    PMID: 23569855 DOI: 10.1016/S2221-1691(12)60237-8
    To investigate the cytotoxic effect of Elaeis guineensis methanol extract on MCF-7 and Vero cell.
    Matched MeSH terms: Dose-Response Relationship, Drug
  2. Vijayapandi P, Annabathina V, SivaNagaSrikanth B, Manjunath V, Boggavarapu P, Mohammed P AK, et al.
    PMID: 24082330
    The present investigation was aimed at determining the effects of hexane, acetone, methanol and aqueous extracts of Acorus calamus leaves (ACHE, ACAE, ACME and ACAQE) on cholinergic and histaminic system using isolated frog rectus abdominis muscle and guinea pig ileum. A dose dependent potentiation of Ach response (anticholinesterase like effect) was found with ACAE and ACME at 0.25, 0.5, 0.75 and 1 mg/ml, but at higher dose of ACAE, ACME, ACAQE and ACHE (5, 20 mg/ml) inhibit the Ach response (antinicotinic effect). These results revealed biphasic effect of Acorus calamus leaves extracts on acetylcholine induced contractile response in isolated frog rectus abdominis muscle preparation (i.e. potentiation effect at lower dose and inhibitory effect at higher dose). Studies on isolated guinea pig ileum demonstrated antihistaminic effect in a dose dependent manner (100-1000 µg/ml) with ACAE, ACME and ACAQE. In addition, the dose dependent inhibition of Ach response (antimuscarinic effect) was observed with ACAE and ACME. In conclusion, Acorus calamus leaves extracts exerts antinicotinic, anticholinesterase like activities in isolated frog rectus abdominis muscle and antihistaminic, antimuscarinic effect in guinea pig ileum. It has been suggested that these observed activities can be further studied for therapeutic potential of Acorus calamus leaves in the treatment of cognitive disorders and asthma.
    Matched MeSH terms: Dose-Response Relationship, Drug
  3. Vijayanathan Y, Lim FT, Lim SM, Long CM, Tan MP, Majeed ABA, et al.
    Neurotox Res, 2017 Oct;32(3):496-508.
    PMID: 28707266 DOI: 10.1007/s12640-017-9778-x
    Conventional mammalian models of neurodegeneration are often limited by futile axonogenesis with minimal functional recuperation of severed neurons. The emergence of zebrafish, a non-mammalian model with excellent neuroregenerative properties, may address these limitations. This study aimed to establish an adult zebrafish-based, neurotoxin-induced Parkinson's disease (PD) model and subsequently validate the regenerative capability of dopaminergic neurons (DpN). The DpN of adult male zebrafish (Danio rerio) were lesioned by microinjecting 6-hydroxydopamine (6-OHDA) neurotoxin (6.25, 12.5, 18.75, 25, 37.5, 50 and 100 mg/kg) into the ventral diencephalon (Dn). This was facilitated by an optimised protocol that utilised 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate (DiI) dye to precisely identify the injection site. Immunostaining was utilised to identify the number of tyrosine hydroxylase immunoreactive (TH-ir) DpN in brain regions of interest (i.e. olfactory bulb, telencephalon, preoptic area, posterior tuberculum and hypothalamus). Open tank video recordings were performed for locomotor studies. The Dn was accessed by setting the injection angle of the microinjection capillary to 60° and injection depth to 1200 μm (from the exposed brain surface). 6-OHDA (25 mg/kg) successfully ablated >85% of the Dn DpN (preoptic area, posterior tuberculum and hypothalamus) whilst maintaining a 100% survival. Locomotor analysis of 5-min recordings revealed that 6-OHDA-lesioned adult zebrafish were significantly (p 
    Matched MeSH terms: Dose-Response Relationship, Drug
  4. Vijayan V, Shalini K, Yugesvaran V, Yee TH, Balakrishnan S, Palanimuthu VR
    Curr Pharm Des, 2018;24(28):3366-3375.
    PMID: 30179118 DOI: 10.2174/1381612824666180903110301
    BACKGROUND: Triple-Negative Breast Cancer is an aggressive type of breast cancer, which is not treatable by chemotherapy drugs, due to the lack of Estrogen Receptor (ER), Progesterone Receptor (PR) expression and Human Epidermal Growth Factor Receptor 2 (HER2) on the cell surface.

    OBJECTIVE: The aim of this study was to compare the effect of paclitaxel loaded PLGA nanoparticle (PTX-NPs) on the cytotoxicity and apoptosis of the different MDA-MB type of cell lines.

    METHOD: PTX-NPs were prepared by nanoprecipitation method and characterized earlier. The cytotoxicity of PTX-NPs was evaluated by MTT and LDH assay, later apoptosis was calculated by flow cytometry analysis.

    RESULTS: The prepared NP size of 317.5 nm and zetapontial of -12.7 mV showed drug release of 89.1 % at 48 h. MDA-MB-231 type cell showed significant cytotoxicity by MTT method of 47.4 ± 1.2 % at 24 h, 34.6 ± 0.8 % at 48 h and 23.5 ± 0.5 % at 72 h and LDH method of 35.9 ± 1.5 % at 24 h, 25.4 ± 0.6 % at 48 h and 19.8 ± 2.2 % at 72 h with apoptosis of 47.3 ± 0.4 %.

    CONCLUSION: We have found that PTX-NPs showed the cytotoxic effect on all the MDA-MB cancer cell lines and showed potent anticancer activities against MDA-MB-231 cell line via induction of apoptosis.

    Matched MeSH terms: Dose-Response Relationship, Drug
  5. Venugopalan SK, T S S, V N, S M M, S R
    Biomed Pharmacother, 2016 Oct;83:1485-1492.
    PMID: 27619103 DOI: 10.1016/j.biopha.2016.08.068
    Thymus mitochondria play a crucial role in immune function. This study identifies the novel protective role of N-Acetylglucosamine (NAG) in dexamethasone (DEX) induced mitochondrial perturbations in mice thymus. Mice were induced with DEX (5mg/kg) and treated with NAG i.p. (266μg/kg, 400μg/kg and 800μg/kg) for 14 days, Withanolide A (800μg/kg) has been used as positive control. Dose dependent treatment of NAG against DEX significantly restored the mitochondrial enzyme levels (ICDH, KDH, SDH and MDH) and elevated the mitochondrial glutathione antioxidants defense (GSH, SOD, GPX and GST) thus improving the ATP status which was confirmed by ultrastructural alterations in mitochondria and nucleus using TEM studies. Further histopathological studies also revealed that NAG attenuate DEX induced thymotoxicity. Finally, the study concludes that dose dependent treatment of NAG supports a potential role in preventing DEX induced thymotoxicity and NAG acts as a beneficial pharmacological intervention in the DEX induced thymic repercussions.
    Matched MeSH terms: Dose-Response Relationship, Drug
  6. Venugopala KN, Chandrashekharappa S, Pillay M, Abdallah HH, Mahomoodally FM, Bhandary S, et al.
    PLoS One, 2019;14(6):e0217270.
    PMID: 31163040 DOI: 10.1371/journal.pone.0217270
    Indolizines are heteroaromatic compounds, and their synthetic analogues have reportedly showed promising pharmacological properties. In this study, a series of synthetic 7-methoxy-indolizine derivatives were synthesised, characterised and evaluated for in vitro whole-cell anti-tuberculosis (TB) screening against susceptible (H37Rv) and multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) using the resazurin microplate assay method. The cytotoxicity was evaluated using the MTT assay. In silico molecular-docking study was conducted for compounds 5a-j against enoyl-[acyl-carrier] protein reductase, a key enzyme of the type II fatty acid synthesis that has attracted much interest for the development of novel anti-TB compounds. Thereafter, molecular dynamic (MD) simulation was undertaken for the most active inhibitors. Compounds 5i and 5j with the methoxy functional group at the meta position of the benzoyl group, which was at the third position of the indolizine nucleus, demonstrated encouraging anti-TB activity against MDR strains of MTB at 16 μg/mL. In silico studies showed binding affinity within the range of 7.07-8.57 kcal/mol, with 5i showing the highest binding affinity. Hydrogen bonding, π-π- interactions, and electrostatic interactions were common with the active site. Most of these interactions occurred with the catalytic amino acids (Pro193, Tyr158, Phe149, and Lys165). MD simulation showed that 5j possessed the highest binding affinity toward the enzyme, according to the two calculation methods (MM/PBSA and MM/GBSA). The single-crystal X-ray studies of compounds 5c and 5d revealed that the molecular arrangements in these two structures were mostly guided by C-H···O hydrogen-bonded dimeric motifs and C-H···N hydrogen bonds, while various secondary interactions (such as π···π and C-H···F) also contributed to crystal formation. Compounds 5a, 5c, 5i, and 5j exhibited no toxicity up to 500 μg/mL. In conclusion, 5i and 5j are promising anti-TB compounds that have shown high affinity based on docking and MD simulation results.
    Matched MeSH terms: Dose-Response Relationship, Drug
  7. Venugopal Y, Hatta SFWM, Musa N, Rahman SA, Ratnasingam J, Paramasivam SS, et al.
    Asia Pac J Clin Nutr, 2017 May;26(3):412-420.
    PMID: 28429905 DOI: 10.6133/apjcn.042016.10
    BACKGROUND AND OBJECTIVES: Vitamin D3 (cholecalciferol) dose required to maintain sufficiency in non- Caucasian women with postmenopausal osteoporosis (PMO) inthe tropics has not been well studied. Some guidelines mandate 800-1000 IU vitamin D/day but the Endocrine Society (US) advocates 1500-2000 IU/day to maintain 25-hydroxyvitamin-D (25(OH)D) concentration at >75 nmol/L. We aimed to establish oral cholecalciferol dose required to maintain 25(OH)D concentration at >75 nmol/L in PMO Chinese Malaysian women, postulating lower dose requirements amongst light-skinned subjects in the tropics.

    METHODS AND STUDY DESIGN: 90 Chinese Malaysian PMO women in Kuala Lumpur, Malaysia (2°30'N) with baseline serum 25(OH)D levels >=50 nmol/L were recruited. Prior vitamin D supplements were discontinued and subjects randomized to oral cholecalciferol 25,000 IU/4-weekly (Group-A) or 50,000 IU/4-weekly (Group- B) for 16 weeks, administered under direct observation. Serum 25(OH)D, PTH, serum/urinary calcium were measured at baseline, 8 and 16 weeks.

    RESULTS: Baseline characteristics, including osteoporosis severity, sun exposure (~3 hours/week), and serum 25(OH)D did not differ between treatment arms. After 16 weeks, 91% of women sufficient at baseline, remained sufficient on 25,000 IU/4-weekly compared with 97% on 50,000 IU/4-weekly with mean serum 25(OH)D 108.1±20.4 and 114.7±18.4 SD nmol/L respectively (p=0.273). At trial's end, 39% and 80% of insufficient women at baseline attained sufficiency in Group A and Group B (p=0.057). Neither dose was associated with hyperparathyroidism or toxicity.

    CONCLUSIONS: Despite pretrial vitamin D supplementation and adequate sun exposure, 25.6% Chinese Malaysian PMO women were vitamin D insufficient indicating sunshine alone cannot ensure sufficiency in the tropics. Both ~900 IU/day and ~1800 IU/day cholecalciferol can safely maintain vitamin D sufficiency in >90% of Chinese Malaysian PMO women. Higher doses are required with baseline concentration <75 nmol/L.
    Matched MeSH terms: Dose-Response Relationship, Drug
  8. Vedamanikam VJ, Shazilli NA
    Bull Environ Contam Toxicol, 2008 Jun;80(6):516-20.
    PMID: 18414763 DOI: 10.1007/s00128-008-9413-x
    A study was conducted to determine the suitability of using selected aquatic dipterian larvae for biomonitoring bioassays. The organisms included a member of the biting midge family that was identified as Culicoides furens and a member of the non-biting midge family, identified as Chironomus plumosus. Median lethal toxicity tests were conducted to observe the variation between metal sensitivities between the two larval forms and how variations in temperature could affect the experimental setup. Nine heavy metals were used in the study. It was observed that the 96 h LC(50) (in mg/L) for the different metals was found to be Zn-16.21 (18.55 +/- 13.87); Cr-0.96 (1.08 +/- 0.84); Ag-4.22 (6.87 +/- 1.57); Ni-0.42 (0.59 +/- 0.25); Hg-0.42 (0.59 +/- 0.25); Pb-16.21 (18.31 +/- 14.11); Cu-42.24 (45.18 +/- 39.30); Mn-4.22 (7.19 +/- 1.25); Cd-0.42 (0.59 +/- 0.25) for the Chironomus plumosus and Zn-4.22 (6.56 +/- 1.88); Cr-0.42 (0.54 +/- 0.30); Ag-0.42 (0.54 +/- 0.30); Ni-0.42 (0.54 +/- 0.30); Hg-0.04 (0.07 +/- 0.01); Pb-0.42 (0.54 +/- 0.30); Cu-42.24 (45.18 +/- 39.30); Mn-4.22 (6.56 +/- 1.88); Cd-0.42 (0.54 +/- 0.30) in the case of the Culicoides furens. With temperature as a variable the LC(50) values were observed to increase from 2.51 mg/L at 10 degrees C to 4.22 ppm at 30 degrees C and to reduce slightly to 3.72 mg/L at 35 degrees C as seen in the case of Zn. It was also observed that at 40 degrees C thermal toxicity and chemical toxicity overlapped as 100% mortality was observed in the controls. This trend was observed in all metals for both C. plumosus and C. furens. Thus indicating temperature played an important role in determining LC(50) values of toxicants.
    Matched MeSH terms: Dose-Response Relationship, Drug
  9. Vattam KK, Raghavendran H, Murali MR, Savatey H, Kamarul T
    Hum Exp Toxicol, 2016 Aug;35(8):893-901.
    PMID: 26429928 DOI: 10.1177/0960327115608246
    In the present study, thirty six male Sprague Dawley rats were randomly divided into six groups and were injected with varying doses of alloxan (Ax) and nicotinamide (NA). The serum levels of glucose, insulin, and adiponectin were measured weekly up to 4 weeks.
    Matched MeSH terms: Dose-Response Relationship, Drug
  10. Van Kriekinge G, Sohn WY, Aljunid SM, Soon R, Yong CM, Chen J, et al.
    Asian Pac J Cancer Prev, 2018 Apr 25;19(4):933-940.
    PMID: 29693347
    Purpose: To comparatively evaluate the results of a 2-dose human papillomavirus (HPV) vaccination programme
    with the AS04-adjuvanted HPV16/18 vaccine (AS04-HPV-16/18v) or HPV-6/11/16/18 vaccine (4vHPVv), in addition
    to cervical cancer (CC) screening, in Malaysia. Methods: A lifetime Markov model replicating the natural history of
    HPV in 13-year-old girls was adapted to Malaysia to assess the impact of vaccination on pre-cancerous lesions, genital
    warts and CC cases, CC deaths, quality-adjusted life years (QALYs), and costs from the perspective of the Malaysian
    Ministry of Health. Vaccine effectiveness was based on efficacy and HPV type distribution. Both vaccines were assumed
    to have equal efficacy against vaccine-type HPV but differed for protection against non-vaccine types. Vaccine price
    parity was used and health and cost outcomes were discounted at 3%/annum. Sensitivity analyses tested the robustness
    of the results. Results: The model predicted that AS04-HPV-16/18v would result in 361 fewer CC cases and 115 fewer
    CC deaths than 4vHPVv, whereas 4vHPVv averted 4,241 cases of genital warts over the cohort’s lifetime. Discounted
    total costs showed savings of 18.50 million Malaysian Ringgits and 246 QALYs in favour of AS04-HPV-16/18v. In
    one-way sensitivity analyses, the discount rate was the most influential variable for costs and QALYs, but AS04-HPV-
    16/18v remained dominant throughout. A two-way sensitivity analysis to assess the longevity of cross-protection for both
    vaccines confirmed the base-case. Conclusions: In Malaysia, the use of AS04-HPV-16/18v, in addition to screening,
    was modelled to be dominant over 4vHPVv, with greater estimated CC benefits and lower costs.
    Matched MeSH terms: Dose-Response Relationship, Drug
  11. Vamsi K, Siddiqui F
    J Contemp Dent Pract, 2018 Jul 01;19(7):824-829.
    PMID: 30066686
    AIM: To study the antimicrobial effect of chlorhexidine diacetate (CHX-D)-modified type II glass ionomer cement (GIC) against the two predominant deep caries microorganisms, namely Lactobacillus casei and Actinomyces viscosus.

    MATERIALS AND METHODS: An experimental GIC (ex-GIC) was prepared by mixing CHX-D powder with the powder of type II GIC to obtain 1% (w/w) concentration of CHX-D in the GIC. Antibacterial activity of this ex-GIC was tested against L. casei and A. viscosus using the agar diffusion method. The ex-GIC specimens were tested in their unset and set forms for each bacterium. For the unset group, specimens were placed in each agar plate immediately after manipulation and for the set group, specimens were placed in each agar plate, 1 hour after manipulation. The inhibition zones on the agar plate were recorded in millimeters immediately on placement of the specimen in the agar plate and after 48 hours. The reading was recorded and statistically analyzed for significant difference.

    RESULTS: Mann-Whitney U test showed statistically significant difference in the inhibition zones produced by ex-GIC against L. casei and A. viscosus when both were compared in unset (p-value = 0.002) and set (p-value = 0.031) groups. For both the groups, the zone of inhibition against L. casei was greater. Though the unset group recorded wider zone of inhibition, the difference was not significant when compared with the respective set group. This was true for both the bacterial groups.

    CONCLUSION: The 1% CHX-D-modified type II GIC showed antibacterial property against L. casei and A. viscosus and significantly higher activity against L. casei.

    CLINICAL SIGNIFICANCE: Addition of 1% CHX-D to type II GIC showed evidence of antibacterial activity against organisms found in deep carious lesion and therefore may exhibit superior antimicrobial efficiency when used as an intermediate therapeutic restoration in deep cavities.

    Matched MeSH terms: Dose-Response Relationship, Drug
  12. Utar Z, Majid MI, Adenan MI, Jamil MF, Lan TM
    J Ethnopharmacol, 2011 Jun 14;136(1):75-82.
    PMID: 21513785 DOI: 10.1016/j.jep.2011.04.011
    ETHNOPHARMACOLOGICAL RELEVANCE: [corrected] Mitragyna speciosa Korth (Rubiaceae) is one of the medicinal plants used traditionally to treat various types of diseases especially in Thailand and Malaysia. Its anti-inflammatory and analgesic properties in its crude form are well documented. In this study, the cellular mechanism involved in the anti-inflammatory effects of mitragynine, the major bioactive constituent, was investigated.

    MATERIALS AND METHODS: The effects of mitragynine on the mRNA and protein expression of COX-1 and COX-2 and the production of prostaglandin E(2) (PGE(2)) were investigated in LPS-treated RAW264.7 macrophage cells. Quantitative RT-PCR was used to assess the mRNA expression of COX-1 and COX-2. Protein expression of COX-1 and COX-2 were assessed using Western blot analysis and the level of PGE(2) production was quantified using Parameter™ PGE(2) Assay (R&D Systems).

    RESULTS: Mitragynine produced a significant inhibition on the mRNA expression of COX-2 induced by LPS, in a dose dependent manner and this was followed by the reduction of PGE(2) production. On the other hand, the effects of mitragynine on COX-1 mRNA expression were found to be insignificant as compared to the control cells. However, the effect of mitragynine on COX-1 protein expression is dependent on concentration, with higher concentration of mitragynine producing a further reduction of COX-1 expression in LPS-treated cells.

    CONCLUSIONS: These findings suggest that mitragynine suppressed PGE(2) production by inhibiting COX-2 expression in LPS-stimulated RAW264.7 macrophage cells. Mitragynine may be useful for the treatment of inflammatory conditions.

    Matched MeSH terms: Dose-Response Relationship, Drug
  13. Utami R, Khalid N, Sukari MA, Rahmani M, Abdul AB, Dachriyanus
    Pak J Pharm Sci, 2013 Mar;26(2):245-50.
    PMID: 23455191
    Elaeocarpus floribundus is higher plant that has been used as traditional medicine for treating several diseases. There is no previous report on phytochemicals and bioactivity studies of this species. In this investigation, triterpenoids friedelin, epifriedelanol and β-sitosterol were isolated from its leaves and stem bark. Determination of total phenolic content of methanolic extract of leaves and stem bark was carried out using Folin-Ciocalteu reagent. All extracts and isolated compounds were subjected to screening of antioxidant activity using DPPH free radical scavenging method and cytotoxic activities by MTT assay towards human T4 lymphoblastoid (CEM-SS) and human cervical (HeLa) cancer cells. In the total phenolic content determination, methanolic extract of leaves gave higher value of 503.08±16.71 mg GAE/g DW than stem bark with value of 161.5±24.81 mg GAE/g DW. Polar extracts of leaves and stem bark possessed promising antioxidant activity with methanol extract of stem bark exhibited strongest activity with IC50 value of 7.36±0.01 μg/ml. In the cytotoxic activity assay, only chloroform extract of leaves showed significant activity with IC50 value of 25.6±0.06 μg/ml against CEM-SS cancer cell, while friedelin and epifriedelanol were found to be active against the two cancer cells with IC50 values ranging from 3.54 to 11.45 μg/ml.
    Matched MeSH terms: Dose-Response Relationship, Drug
  14. Upadhyay N, Tilekar K, Safuan S, Kumar AP, Schweipert M, Meyer-Almes FJ, et al.
    Bioorg Chem, 2021 11;116:105350.
    PMID: 34547645 DOI: 10.1016/j.bioorg.2021.105350
    In the present study, two novel series of compounds incorporating naphthyl and pyridyl linker were synthesized and biological assays revealed 5-((6-(2-(5-(2-chlorophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethoxy) naphthalene-2-yl)methylene)thiazolidine-2,4-dione (14b) as the most potent dual inhibitors of vascular endothelial growth factors receptor-2 (VEGFR-2) and histone deacetylase 4 (HDAC4). Compounds 13b, 14b, 17f, and 21f were found to stabilize HDAC4; where, pyridyl linker swords were endowed with higher stabilization effects than naphthyl linker. Also, 13b and 14b showed best inhibitory activity on VEGFR-2 as compared to others. Compound 14b was most potent as evident by in-vitro and in-vivo biological assessments. It displayed anti-angiogenic potential by inhibiting endothelial cell proliferation, migration, tube formation and also suppressed new capillary formation in the growing chick chorioallantoic membranes (CAMs). It showed selectivity and potency towards HDAC4 as compared to other HDAC isoforms. Compound 14b (25 mg/kg, i.p.) also indicated exceptional antitumor efficacy on in-vivo animal xenograft model of human colorectal adenocarcinoma (HT-29). The mechanism of action of 14b was also confirmed by western blot.
    Matched MeSH terms: Dose-Response Relationship, Drug
  15. Umar MI, Asmawi MZ, Sadikun A, Abdul Majid AM, Atangwho IJ, Khadeer Ahamed MB, et al.
    Pharm Biol, 2014 Nov;52(11):1411-22.
    PMID: 25026347 DOI: 10.3109/13880209.2014.895017
    Azadirachta indica A. Juss. (Meliaceaes) leaves have been used traditionally to treat swelling and rheumatism in Indian cultures.
    Matched MeSH terms: Dose-Response Relationship, Drug
  16. Ullah H, Rahim F, Taha M, Uddin I, Wadood A, Shah SAA, et al.
    Bioorg Chem, 2018 08;78:58-67.
    PMID: 29533215 DOI: 10.1016/j.bioorg.2018.02.020
    We have synthesized oxadiazole derivatives (1-16), characterized by 1H NMR, 13C NMR and HREI-MS and screened for thymidine phosphorylase inhibitory potential. All derivatives display varied degree of thymidine phosphorylase inhibition in the range of 1.10 ± 0.05 to 49.60 ± 1.30 μM when compared with the standard inhibitor 7-Deazaxanthine having an IC50 value 38.68 ± 1.12 μM. Structure activity relationships (SAR) has been established for all compounds to explore the role of substitution and nature of functional group attached to the phenyl ring which applies imperious effect on thymidine phosphorylase activity. Molecular docking study was performed to understand the binding interaction of the most active derivatives with enzyme active site.
    Matched MeSH terms: Dose-Response Relationship, Drug
  17. Ullah A, Ashraf M, Javeed A, Anjum AA, Attiq A, Ali S
    Environ Toxicol Pharmacol, 2016 Jul;45:227-34.
    PMID: 27327526 DOI: 10.1016/j.etap.2016.05.017
    Pathophysiological changes in diabetes like hyperglycemia, oxidative stress, insulin resistance and compensatory hyperinsulinemia predispose cells to malignant transformation and damage DNA repair mechanism. This study was designed to explore the potential synergistic toxic effects of anti-diabetic drug (Metformin), and an analgesic drug (Celecoxib) at cellular level. MTT assay run on Vero cell line revealed that the combinations of Metformin and Celecoxib augment the anti-proliferative effects, whereas Single cell gel electrophoresis spotlighted that Metformin produce non-significant DNA damage with the threshold concentration of 400μg/ml in peripheral blood mononuclear cells (lymphocytes and monocytes), while Celecoxib produced significant (P<0.05) DNA damage (class III comets) above the concentration of 75μg/ml, however the DNA damage or DNA tail protrusions by combinations of both drugs were less than what was observed with Celecoxib alone. Metformin or Celecoxib did not appear mutagenic against any mutant strains (TA 100 and TA 98) but their combination exhibited slight mutagenicity at much higher concentration. The results obtained at concentrations higher than the therapeutic level of drugs and reflect that Metformin in combination with Celecoxib synergistically inhibits the cell proliferation in a concentration dependent pattern. Since, this increase in cytotoxicity did not confer an increase in DNA damage; this combination could be adopted to inhibit the growth of malignant cell without producing any genotoxic or mutagenic effects at cellular level.
    Matched MeSH terms: Dose-Response Relationship, Drug
  18. Tubesha Z, Imam MU, Mahmud R, Ismail M
    Molecules, 2013 Jun 26;18(7):7460-72.
    PMID: 23803717 DOI: 10.3390/molecules18077460
    Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE) has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ)/kg. TQRFNE and distilled water (DW) as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW) group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure.
    Matched MeSH terms: Dose-Response Relationship, Drug
  19. Tsai IH, Chen YH, Wang YM, Liau MY, Lu PJ
    Arch Biochem Biophys, 2001 Mar 15;387(2):257-64.
    PMID: 11370849
    To investigate the geographic variations in venoms of two medically important pitvipers, we have purified and characterized the phospholipases A2 (PLA2s) from the pooled venoms of Calloselasma rhodostoma from Malaysia, Thailand, Indonesia, and Vietnam, as well as the individual venom of Trimeresurus mucrosquamatus collected from both North and South Taiwan. Enzymatic and pharmacological activities of the purified PLA2s were also investigated. The complete amino acid sequences of the purified PLA2s were determined by sequencing the corresponding cDNAs from the venom gland and shown to be consistent with their molecular weight data and the N-terminal sequences. All the geographic venom samples of C. rhodostoma contain a major noncatalytic basic PLA2-homolog and two or three acidic PLA2s in different proportions. These acidic PLA2s contain Glu6-substitutions and show distinct inhibiting specificities toward the platelets from human and rabbit. We also found that the T. mucrosquamatus venoms from North Taiwan but not those from South Taiwan contain an Arg6-PLA2 designated as TmPL-III. Its amino acid sequence is reported for the first time. This enzyme is structurally almost identical to the low- or nonexpressed Arg6-PLA2 from C. rhodostoma venom gland, and thus appears to be a regressing venom component in both of the Asian pitvipers.
    Matched MeSH terms: Dose-Response Relationship, Drug
  20. Topkaya D, Ng SY, Bretonnière Y, Lafont D, Chung LY, Lee HB, et al.
    Photodiagnosis Photodyn Ther, 2016 Dec;16:12-14.
    PMID: 27475243 DOI: 10.1016/j.pdpdt.2016.07.008
    Matched MeSH terms: Dose-Response Relationship, Drug
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