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  1. Fulltext The use of surgical antibiotic prophylaxis in seven Malaysian hospitals
    Lim VK, Cheong YM, Suleiman AB
    Southeast Asian J. Trop. Med. Public Health, 1994 Dec;25(4):698-701.
    PMID: 7667716
    A survey on the use of antibiotics in surgical prophylaxis was carried out in seven Malaysian hospitals. Details of antibiotic prescriptions were obtained through questionnaires completed by the prescriber. A total of 430 such prescriptions was analysed. A large number of different antibiotic regimens were used for a variety of surgical procedures. The majority of prescriptions (70%) were issued for procedures where such prophylaxis was probably not necessary. Antibiotics were also often prescribed for durations that were longer than necessary. There is an urgent need to educate surgeons and standardize surgical prophylactic regimens in order to reduce cost and combat the emergence of antibiotic resistance.
    Matched MeSH terms: Dose-Response Relationship, Drug
  2. 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
  3. The relationship between trough concentration of vancomycin and effect on methicillin-resistant Staphylococcus aureus in critically ill patients
    Cheong JY, Makmor-Bakry M, Lau CL, Abdul Rahman R
    S. Afr. Med. J., 2012 Jul;102(7):616-9.
    PMID: 22748440
    The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections in intensive care units in Malaysia is significant. Invasive MRSA infections are commonly treated with vancomycin. In clinical practice, the serum vancomycin trough concentration is used as a surrogate marker of vancomycin efficacy. A low concentration of vancomycin may result in less effective therapy and increase the risk of bacterial resistance. We evaluated the relationship between the resolution of MRSA infections and trough concentrations of vancomycin.
    Matched MeSH terms: Dose-Response Relationship, Drug
  4. The properties of red seaweed (Kappaphycus alvarezii) and its effect on mammary carcinogenesis
    Chang VS, Okechukwu PN, Teo SS
    Biomed Pharmacother, 2017 Mar;87:296-301.
    PMID: 28063411 DOI: 10.1016/j.biopha.2016.12.092
    The edible red seaweed (Kappaphycus alvarezii) is one of the algae species which was found to be rich in nutrients and nutraceutical. Hence, K. alvarezii may have the ability to suppress cancer through its antiproliferative properties. The aim of this study was to investigate the potential compounds of K. alvarezii, cytotoxicity properties of K. alvarezii extract on breast cancer cell line (MCF-7), investigated toxicity effect of high dosage K. alvarezii extract in rats and determined the effect of K. alvarezii on 7, 12-dimethylbenz[a]anthracene (DMBA) mammary carcinogenesis in rats. The method of LCMS/MS and MTT assay were used. For animal study, sub-chronic toxicity method was used, the rats were supplemented with 2000mg/kg body weight daily of K. alvarezii crude extracts by oral gavage. For the anticancer effect of K. alvarezii crude extracts, this study consisted of three groups of the experimental, untreated and normal group of rats. The experimental and untreated groups of rats were induced with mammary tumour with DMBA. The experimental group of rats was given with K. alvarezii crude extracts orally. The results were being used to compare with the untreated group of rats and normal group of rats. All the rats were fed with standard diet and water ad libitum. Mortality, behavior changes and tumour sizes were observed specifically. The differences between the three groups of rats were evaluated by using the ANOVA test. By using LCMS/MS method, six unknown compounds were analysed. K. alvarezii crude extract reduced the cell viability of MCF-7 from 84.91% to 0.81% and the IC50 value is 4.1±0.69mg/mL. For sub-chronic and heavy metal toxicity studies, no significant difference was found in haematological and biochemical values of the control group and experimental group. The growth rate of tumours in the untreated group of rats was found significantly higher than the experimental group of rats. Besides that, the white blood cells level in untreated group was found significantly higher than the experimental group and the normal group. In conclusion, K. alvarezii extract might able to slow down the growth rate of the tumour cells, therefore, identification of an active compound of inhibition growth rate of the tumour cells can be positively carried out in the future.
    Matched MeSH terms: Dose-Response Relationship, Drug
  5. The potential use of a layer-by-layer strategy to develop LDPE antimicrobial films coated with silver nanoparticles for packaging applications
    Azlin-Hasim S, Cruz-Romero MC, Cummins E, Kerry JP, Morris MA
    J Colloid Interface Sci, 2016 Jan 01;461:239-248.
    PMID: 26402783 DOI: 10.1016/j.jcis.2015.09.021
    Commercial low-density polyethylene (LDPE) films were UV/ozone treated and coated using a layer-by-layer (LbL) technique by alternating the deposition of polyethyleneimine (PEI) and poly(acrylic acid) (PAA) polymer solutions and antimicrobial silver (Ag). The effects of the initial pH of the PEI/PAA polymer solutions alternating layers (pH 10.5/4 or 9/6.5) on the antimicrobial activity of the developed LbL coatings combined with Ag against Gram-negative and Gram-positive bacteria were investigated. The results from fourier transform infrared spectroscopy and toluidine blue O assay showed that LDPE LbL coated using PEI/PAA polymer solutions with initial pH of 10.5/4 significantly increased the presence of carboxylic acid groups and after Ag attachment the coating had higher antimicrobial activity against both Gram-negative and Gram-positive bacteria compared to the LDPE LbL coated using PEI/PAA polymer solutions with initial pH of 9/6.5. The LDPE LbL coated films using non-modified pH PEI/PAA polymer solutions decreased the water contact-angle indicating an increased hydrophilicity of the film, also increased the tensile strength and roughness of LDPE LbL coated films compared to uncoated LbL samples. The LDPE LbL coated films attached with Ag(+) were UV/ozone treated for 20 min to oxidise Ag(+) to Ag(0). The presence of Ag(0) (Ag nanoparticles (NPs)) on the LDPE LbL coated films was confirmed by XRD, UV-vis spectrophotometer and colour changes. The overall results demonstrated that the LbL technique has the potential to be used as a coating method containing antimicrobial Ag NPs and that the manufactured films could potentially be applied as antimicrobial packaging.
    Matched MeSH terms: Dose-Response Relationship, Drug
  6. Fulltext The potential protective effect of Commelina nudiflora L. against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats, mediated by suppression of oxidative stress and inflammation
    Shah MD, D'Souza UJA, Iqbal M
    Environ Health Prev Med, 2017 Sep 11;22(1):66.
    PMID: 29165163 DOI: 10.1186/s12199-017-0673-0
    BACKGROUND: This study aims to assess the hepatoprotective potential of Commelina nudiflora against CCl4-induced hepatic injury in rats.

    METHOD: Antioxidant activities were determined. Phytochemical analysis was performed by gas chromatography mass spectrometry (GCMS). In the in vivo study, Sprague Dawley rats were pretreated with C. nudiflora (150, 300, and 450 mg kg body weight (b.wt.)) once daily for 14 days followed by two doses of CCl4 (1 ml/kg b.wt.). After 2 weeks, the rats were sacrificed and hepatoprotective analysis was performed.

    RESULTS: In vitro studies have shown that the extract possessed strong antioxidant activity and has ability to scavenge 2,2-diphenyl-2-picrylhydrazyl-free radicals effectively. GCMS analysis of the C. nudiflora extract revealed the presence of various bioactive compounds. Administration of C. nudiflora significantly reduced the impact of CCl4 toxicity on serum markers of liver damage, serum aspartate transaminase (AST), and alanine transaminase (ALT). C. nudiflora also increased antioxidant levels of hepatic glutathione (GSH) and antioxidant enzymes and ameliorated the elevated hepatic formation of malondialdehyde (MDA) induced by CCl4 in rats. Histopathological examination indicated that C. nudiflora protect the liver from the toxic effect of CCl4 and healed lesions such as necrosis, fatty degeneration, and hepatocyte injury as irregular lamellar organization and dilations in the endoplasmic reticulum. The immunohistochemical studies revealed that pretreatment of C. nudiflora decreased the formation of 4-hydroxy-2-nonenal (HNE)-modified protein adducts and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Furthermore, overexpression of the proinflammatory cytokines TNF-α, IL-6, and prostaglandin E2 is also reduced.

    CONCLUSION: These findings exhibited the potential prospect of C. nudiflora as functional ingredients to prevent ROS-related liver damage.

    Matched MeSH terms: Dose-Response Relationship, Drug
  7. The oral and intratracheal toxicities of ROUNDUP and its components to rats
    Adam A, Marzuki A, Abdul Rahman H, Abdul Aziz M
    Vet Hum Toxicol, 1997 Jun;39(3):147-51.
    PMID: 9167243
    The toxicities of ROUNDUP and its component chemicals, glyphosate (N-phosphonomethylglycine) and polyoxyethyleneamine (POEA), were determined at 0, 1, 3, 6 and 24 h following administration to rats. The intratracheal administration of glyphosate (0.2 g/kg), POEA (0.1 g/kg), a mixture of glyphosate (0.2 g/kg) + POEA (0.1 g/kg), or ROUNDUP (containing 0.2 g/kg glyphosate and 0.1 g/kg POEA) elicited immediate respiratory effects which were more severe and which lasted longer in the groups receiving the POEA-containing preparations than in the glyphosate alone group. By 1 h, all test preparations had caused deaths, but more occurred from the POEA-containing preparations than from glyphosate. The po administration of POEA (1 g/kg), the mixture of glyphosate (2 g/kg) +POEA (1 g/kg), or ROUNDUP (containing 2 g/kg glyphosate and 1 g/kg POEA) produced diarrhea and blood-stained weeping from noses. Death was only seen from POEA at 24 h. Glyphosate (2 g/kg po) produced transient diarrhea without nose bleeds; POEA caused diarrhea at 1 h; and the mixture of POEA + glyphosate produced diarrhea later that increased in severity with time. Bloody nose secretions were seen only with the preparations that contained POEA. No deaths, respiratory effects or bloody nose secretions occurred in controls given saline. Both POEA and glyphosate caused lung hemorrhages and lung epithelial cell damage with po or intratracheal exposures. These results indicate POEA and preparations that contained POEA were more toxic than glyphosate.
    Matched MeSH terms: Dose-Response Relationship, Drug
  8. The influences of temperature and naloxone on the antinociceptive activity of Corchorus olitorius L. in mice
    Zakaria ZA, Safarul M, Valsala R, Sulaiman MR, Fatimah CA, Somchit MN, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2005 Jul;372(1):55-62.
    PMID: 16133487
    A series of preliminary studies was carried out to evaluate the antinociceptive (pain relief) activity of the aqueous extract of Corchorus olitorius L. leaves (COAE) and to determine the influence of temperature and opioid receptors on COAE activity using the abdominal constriction and hot plate tests in mice. COAE, at concentrations of 10, 25, 50, 75, and 100%, showed both peripheral and central antinociception that are non-concentration- and concentration-dependent respectively. The peripheral activity was clearly observed at a concentration of 25% and diminished at a concentration of 100%, while the central activity was observed at all the concentrations of COAE used. Furthermore, the insignificant results obtained indicated that this peripheral activity (at concentrations of 25 and 50%) was comparable to that of morphine (0.8 mg/kg). Pre-heating COAE at a temperature of 80 degrees C and 100 degrees C, or 60 degrees C and 80 degrees C was found to enhance its peripheral and central antinociception respectively. Pre-treatment with naloxone (10 mg/kg), a general opioid receptor antagonist, for 5 min, followed by COAE, was found to completely block its peripheral, but not central, antinociceptive activity. Based on this observation, we conclude that the antinociceptive activity exhibited by C. olitorius is enhanced by the increase in temperature and may be mediated peripherally, but not centrally, at least in part, via an opioid receptor.
    Matched MeSH terms: Dose-Response Relationship, Drug
  9. The influence of metformin on IGF-1 levels in humans: A systematic review and meta-analysis
    Yang X, Kord-Varkaneh H, Talaei S, Clark CCT, Zanghelini F, Tan SC, et al.
    Pharmacol Res, 2020 01;151:104588.
    PMID: 31816435 DOI: 10.1016/j.phrs.2019.104588
    BACKGROUND: A meta-analysis is needed to comprehensively consolidate findings from the influence of metformin on IGF-1 levels. The present study was conducted with the objective to accurately evaluate the influence of metformin intake on IGF-1 levels via a meta-analysis of randomized controlled trials.

    METHODS: A comprehensive systematic search was carried out in PubMed/MEDLINE, Web of Science, SCOPUS and Embase from inception until June 2019. Weighted mean difference (WMD) with the 95 % CI were applied for estimating the effects of metformin on serum IGF-1 levels.

    RESULTS: 11 studies involving a total of 569 individuals reported changes in IGF-1 plasma concentrations as an outcome measure. Pooled results demonstrated an overall non-significant decline in IGF-1 following metformin intake (WMD: -8.292 ng/ml, 95 % CI: -20.248, 3.664, p = 0.174) with heterogeneity among (p = 0.000,I2 = 87.1 %). The subgroup analyses displayed that intervention duration <12 weeks on children (WMD:-55.402 ng/ml, 95 % CI: -79.845, -30.960, I2 = 0.0 %) significantly reduced IGF-1. Moreover, in age 18 < years older metformin intake (WMD: 15.125 ng/ml, 95 % CI: 5.522, 24.729, I2 = 92.5 %) significantly increased IGF-1 than 18 ≤ years older (WMD:-1.038 ng/ml, 95 % CI: -3.578,1.502,I2 = 78.0 %). Following dose-response evaluation, metformin intake reduced IGF-1 (coefficient for dose-response analysis= -13.14, P = 0.041 and coefficient for liner analysis= -0.066, P = 0.038) significantly based on treatment duration.

    CONCLUSION: We found in children, intervention duration <12 weeks yielded significant reductions in IGF-1, whilst paradoxically, in participants >18 years old, metformin intake significantly increased IGF-1. We suggest that caution be taken when interpreting the findings of this review, particularly given the discordant supplementation practices between children and adults.

    Matched MeSH terms: Dose-Response Relationship, Drug
  10. The influence of CYP3A gene polymorphisms on cyclosporine dose requirement in renal allograft recipients
    Eng HS, Mohamed Z, Calne R, Lang CC, Mohd MA, Seet WT, et al.
    Kidney Int, 2006 May;69(10):1858-64.
    PMID: 16612333
    Cyclosporine is a substrate of cytochrome P-450 3A (CYP3A) subfamily of enzymes and characterized by a narrow therapeutic range with wide interindividual variation in pharmacokinetics. A few single-nucleotide polymorphisms detected in CYP3A genes have been shown to correlate significantly with the CYP3A protein expression and activity. We therefore postulated that these polymorphisms could be responsible for some of the interindividual variation in cyclosporine pharmacokinetics. The objective of our study is to determine correlation if any between single-nucleotide polymorphisms of CYP3A5 and CYP3AP1 on cyclosporine dose requirement and concentration-to-dose ratio in renal allograft recipients. Cyclosporine-dependent renal allograft recipients were genotyped for CYP3A5 A6986G and CYP3AP1 G-44A. The cyclosporine dosages prescribed and the corresponding cyclosporine trough levels for each patient were recorded so that cyclosporine dose per weight (mg/kg/day) and concentration-to-dose ratio (C(0)/D, whereby C(0) is trough level and D is daily dose per weight) could be calculated. A total of 67 patients were recruited for our study. The dose requirement for 1, 3, and 6 months post-transplantation ranged 2.3-11.4, 1.0-9.0, and 1.4-7.2 mg/kg/day, respectively. Patients with *1*1*1*1 (n=5) CYP3A5- and CYP3AP1-linked genotypes needed higher dose of cyclosporine compared to patients with *1*3*1*3 (n = 27) and *3*3*3*3 (n = 33) linked genotypes in months 3 and 6 post-transplantation (P < 0.016). The identification of patients with *1*1*1*1 by CYP3A5 and CYP3AP1 genotyping may have a clinically significant and positive impact on patient outcome with reduced rejection rate by providing pretransplant pharmacogenetic information for optimization of cyclosporine A dosing.
    Matched MeSH terms: Dose-Response Relationship, Drug
  11. Fulltext The in vivo rodent micronucleus assay of Kacip Fatimah (Labisia pumila) extract
    Zaizuhana S, Puteri J Noor MB, Noral'ashikin Y, Muhammad H, Rohana AB, Zakiah I
    Trop Biomed, 2006 Dec;23(2):214-9.
    PMID: 17322824 MyJurnal
    Kacip Fatimah also known as Labisia pumila (Myrsinaceae), is a traditional herbal medicine with a long history in the Malay community. It has been used by many generations of Malay women to induce and facilitate childbirth as well as a post-partum medicine. We tested the genotoxic potential of Kacip Fatimah in bone marrow cells obtained from Sprague-Dawley rats using micronuclei formation as the toxicological endpoints. Five groups of five male rats each were administered orally for two consecutive days with doses of 100, 700 and 2000 mg/kg body weight of Kacip Fatimah extract dissolved in distilled water. Micronucleus preparation was obtained from bone marrow cells of the animals following standard protocols. No statistically significant increase in micronucleated polychromatic erythrocytes (MNPCEs) was observed at any dose level and sacrifice/harvest time point (24, 48 and 72h). However, a significant decrease in polychromatic erythrocytes/normochromatic erythrocytes (PCE:NCE) ratio was observed from the highest dose level (2000 mg/kg of body weight) at 48h harvest time point. In this study, we investigated the effect of Kacip Fatimah on mammalian bone marrow cells using micronuclei formation to assess the genotoxicity of the herb.
    Matched MeSH terms: Dose-Response Relationship, Drug
  12. The impact of capsaicin intake on risk of developing gastric cancers: a meta-analysis
    Pabalan N, Jarjanazi H, Ozcelik H
    J Gastrointest Cancer, 2014 Sep;45(3):334-41.
    PMID: 24756832 DOI: 10.1007/s12029-014-9610-2
    BACKGROUND: Reported associations of capsaicin with gastric cancer development have been conflicting. Here, we examine 10 published articles that explore these associations using 2,452 cases and 3,996 controls.

    METHODS: We used multiple search strategies in MEDLINE through PubMed to seek for suitable articles that had case-control design with gastric cancer as outcome.

    RESULTS: The outcomes of our study shows protection (odds ratio [OR] 0.55, P = 0.003) and susceptibility (OR 1.94, P = 0.0004), both significant with low and medium-high intake of capsaicin, respectively, although under relatively heterogeneous conditions (P(heterogeneity) = <0.0001). Outlier analysis resulted in loss of overall heterogeneity (P = 0.14) without affecting the pooled ORs. Among the subgroups, low intake elicited protection in both Korean (OR 0.37) and Mexican (OR 0.63) populations while high intake rendered these subgroups susceptible (OR 2.96 and OR 1.57, respectively). These subgroup values were highly significant (P = 0.0001-0.01) obtained in heterogeneous conditions (P(heterogeneity) 

    Matched MeSH terms: Dose-Response Relationship, Drug
  13. Fulltext The hexane fraction of Ardisia crispa Thunb. A. DC. roots inhibits inflammation-induced angiogenesis
    Hamsin DE, Hamid RA, Yazan LS, Taib CN, Ting YL
    BMC Complement Altern Med, 2013;13:5.
    PMID: 23298265 DOI: 10.1186/1472-6882-13-5
    Ardisia crispa (Myrsinaceae) is used in traditional Malay medicine to treat various ailments associated with inflammation, including rheumatism. The plant's hexane fraction was previously shown to inhibit several diseases associated with inflammation. As there is a strong correlation between inflammation and angiogenesis, we conducted the present study to investigate the anti-angiogenic effects of the plant's roots in animal models of inflammation-induced angiogenesis.
    Matched MeSH terms: Dose-Response Relationship, Drug
  14. Fulltext The gastroprotective effects of hydroalcoholic extract of Monolluma quadrangula against ethanol-induced gastric mucosal injuries in Sprague Dawley rats
    Ibrahim IA, Abdulla MA, Hajrezaie M, Bader A, Shahzad N, Al-Ghamdi SS, et al.
    Drug Des Devel Ther, 2016;10:93-105.
    PMID: 26766904 DOI: 10.2147/DDDT.S91247
    Monolluma quadrangula (Forssk.) Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE) was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg) to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg) orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid-Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the experimental rats pretreated with MHAE compared to the ulcer control group. Immunohistochemistry staining revealed an upregulation of the Hsp70 protein and a downregulation of the Bax protein in rats pretreated with MHAE compared with the control rats. Gastric homogenate showed significantly increased catalase and superoxide dismutase, and the level of malondialdehyde (MDA) was reduced in the rats pretreated with MHAE compared to the control group. In conclusion, MHAE exhibited a gastroprotective effect against ethanol-induced gastric mucosal injury in rats. The mechanism of this gastroprotection included an increase in pH and gastric wall mucus, an increase in endogenous enzymes, and a decrease in the level of MDA. Furthermore, protection was given through the upregulation of Hsp70 and the downregulation of Bax proteins.
    Matched MeSH terms: Dose-Response Relationship, Drug
  15. Fulltext The gastro protective effects of Cibotium barometz hair on ethanol-induced gastric ulcer in Sprague-Dawley rats
    Al-Wajeeh NS, Hajerezaie M, Noor SM, Halabi MF, Al-Henhena N, Azizan AH, et al.
    BMC Vet Res, 2017 Jan 19;13(1):27.
    PMID: 28103938 DOI: 10.1186/s12917-017-0949-z
    Cibotium barometz is a medical herb used traditionally in the Malaysian peninsula for several ailments, including gastric ulcer. The aim of this study was assessment the anti-ulcer effects of C. barometz hair on ethanol-induced stomach hemorrhagic abrasions in animals. Seven groups of Sprague Dawley (SD) rats were administered 10% Tween 20 in the normal control and ulcer control groups, and omeprazole 20 mg/kg and 62.5, 125, 250, and 500 mg/kg of C. barometz hair extract in the experimental groups. After 60 min, the normal control group of rats was orally administered 10% Tween 20, while absolute ethanol was orally administered to the groups of ulcer control, omeprazole and experimental groups. Stomachs of the rats were examined macroscopically and histologically. Homogenates of stomachs were used to evaluate endogenous antioxidant enzyme activities.
    Matched MeSH terms: Dose-Response Relationship, Drug
  16. Fulltext The ethyl acetate fraction of a methanolic extract of unripe noni (Morinda citrifolia Linn.) fruit exhibits a biphasic effect on the dopaminergic system in mice
    Pandy V, Narasingam M, Vijeepallam K, Mohan S, Mani V, Mohamed Z
    Exp Anim, 2017 Aug 05;66(3):283-291.
    PMID: 28450692 DOI: 10.1538/expanim.16-0105
    In earlier ex vivo studies, we reported the biphasic effect of a methanolic extract of unripe Morinda citrifolia fruit (MMC) on dopamine-induced contractility in isolated rat vas deferens preparations. The present in vivo study was designed and undertaken to further explore our earlier ex vivo findings. This study examined the effect of the ethyl acetate fraction of a methanolic extract of unripe Morinda citrifolia Linn. fruit (EA-MMC; 5-100 mg/kg, p.o.) on the dopaminergic system using mouse models of apomorphine-induced climbing time and climbing behavior, methamphetamine-induced stereotypy (sniffing, biting, gnawing, and licking) and haloperidol-induced catalepsy using the bar test. Acute treatment with EA-MMC at a low dose (25 mg/kg, p.o.) significantly attenuated the apomorphine-induced climbing time and climbing behavior in mice. Similarly, EA-MMC (5 and 10 mg/kg, p.o.) significantly inhibited methamphetamine-induced stereotyped behavior in mice. These results demonstrated that the antidopaminergic effect of EA-MMC was observed at relatively lower doses (<25 mg/kg, p.o.). On the other hand, EA-MMC showed dopaminergic agonistic activity at a high dose (3,000 mg/kg, p.o.), which was evident from alleviation of haloperidol (a dopamine D2 blocker)-induced catalepsy in mice. Therefore, it is concluded that EA-MMC might possess a biphasic effect on the dopaminergic system, i.e., an antagonistic effect at lower doses (<25 mg/kg, p.o.) and an agonistic effect at higher doses (>1,000 mg/kg, p.o.). However, further receptor-ligand binding assays are necessary to confirm the biphasic effects of M. citrifolia fruit on the dopaminergic system.
    Matched MeSH terms: Dose-Response Relationship, Drug
  17. Fulltext The effects of α-tocopherol on bone: a double-edged sword?
    Chin KY, Ima-Nirwana S
    Nutrients, 2014 Apr 10;6(4):1424-41.
    PMID: 24727433 DOI: 10.3390/nu6041424
    Recent studies have found conflicting evidence on the role of α-tocopherol (αTF) on bone health. This nonsystematic review aimed to summarize the current evidence on the effects of αTF on bone health from cell culture, animal, and human studies in order to clarify the role of αTF on bone health. Our review found that αTF exerted beneficial, harmful or null effects on bone formation cells. Animal studies generally showed positive effects of αTF supplementation on bone in various models of osteoporosis. However, high-dose αTF was possibly detrimental to bone in normal animals. Human studies mostly demonstrated a positive relationship between αTF, as assessed using high performance liquid chromatography and/or dietary questionnaire, and bone health, as assessed using bone mineral density and/or fracture incidence. Three possible reasons high dosage of αTF can be detrimental to bone include its interference with Vitamin K function on bone, the blocking of the entry of other Vitamin E isomers beneficial to bone, and the role of αTF as a prooxidant. However, these adverse effects have not been shown in human studies. In conclusion, αTF may have a dual role in bone health, whereby in the appropriate doses it is beneficial but in high doses it may be harmful to bone.
    Matched MeSH terms: Dose-Response Relationship, Drug
  18. The effects of intramuscular and intraperitoneal injections of benzo[a]pyrene on selected biomarkers in Clarias gariepinus
    Karami A, Christianus A, Ishak Z, Syed MA, Courtenay SC
    Ecotoxicol Environ Saf, 2011 Sep;74(6):1558-66.
    PMID: 21636131 DOI: 10.1016/j.ecoenv.2011.05.012
    This study investigated the dose-dependent and time-course effects of intramuscular (i.m.) and intraperitoneal (i.p.) injection of benzo[a]pyrene (BaP) on the biomarkers EROD activity, GST activity, concentrations of BaP metabolites in bile, and visceral fat deposits (Lipid Somatic Index, LSI) in African catfish (Clarias gariepinus). Intraperitoneal injection resulted in 4.5 times higher accumulation of total selected biliary FACs than i.m. injection. Hepatic GST activities were inhibited by BaP via both injection methods. Dose-response relationships between BaP injection and both biliary FAC concentrations and hepatic GST activities were linear in the i.p. injected group but nonlinear in the i.m. injected fish. Hepatic EROD activity and LSI were not significantly affected by BaP exposure by either injection route. We conclude that i.p. is a more effective route of exposure than i.m. for future ecotoxicological studies of PAH exposure in C. gariepinus.
    Matched MeSH terms: Dose-Response Relationship, Drug
  19. The effects of angiotensin II on pulse wave velocity in healthy humans
    Rehman A, Rahman AR, Rasool AH, Naing NN
    Int J Clin Pharmacol Ther, 2001 Oct;39(10):423-30.
    PMID: 11680667
    To examine the dose response relationship between Ang II and pulse wave velocity (an index of arterial stiffness) in healthy human volunteers.
    Matched MeSH terms: Dose-Response Relationship, Drug
  20. The effects of Naja sumatrana venom cytotoxin, sumaCTX on alteration of the secretome in MCF-7 breast cancer cells following membrane permeabilization
    Hiu JJ, Yap MKK
    Int J Biol Macromol, 2021 Aug 01;184:776-786.
    PMID: 34174307 DOI: 10.1016/j.ijbiomac.2021.06.145
    Naja sumatrana venom cytotoxin (sumaCTX) is a basic protein which belongs to three-finger toxin family. It has been shown to induce caspase-dependent, mitochondrial-mediated apoptosis in MCF-7 cells at lower concentrations. This study aimed to investigate the alteration of secretome in MCF-7 cells following membrane permeabilization by high concentrations of sumaCTX, using label-free quantitative (LFQ) approach. The degree of membrane permeabilization of sumaCTX was determined by lactate dehydrogenase (LDH) assay and calcein-propidium iodide (PI) assays. LDH and calcein-PI assays revealed time-dependent membrane permeabilization within a narrow concentration range. However, as toxin concentrations increased, prolonged exposure of MCF-7 cells to sumaCTX did not promote the progression of membrane permeabilization. The secretome analyses showed that membrane permeabilization was an event preceding the release of intracellular proteins. Bioinformatics analyses of the LFQ secretome revealed the presence of 105 significantly distinguished proteins involved in metabolism, structural supports, inflammatory responses, and necroptosis in MCF-7 cells treated with 29.8 μg/mL of sumaCTX. Necroptosis was presumably an initial stress response in MCF-7 cells when exposed to high sumaCTX concentration. Collectively, sumaCTX-induced the loss of membrane integrity in a concentration-dependent manner, whereby the cell death pattern of MCF-7 cells transformed from apoptosis to necroptosis with increasing toxin concentrations.
    Matched MeSH terms: Dose-Response Relationship, Drug
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