Displaying publications 21 - 40 of 831 in total

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  1. Chen HJ, Dai FJ, Chang CR, Lau YQ, Chew BS, Chau CF
    J Food Drug Anal, 2019 10;27(4):869-875.
    PMID: 31590758 DOI: 10.1016/j.jfda.2019.06.005
    In the present study, the influences of diets (i.e. chow and AIN-93 diets) on the interpretation of various fecal parameters including viable microbiota, moisture, weight, and short-chain fatty acids in rats fed different amounts of inulin (0.5-2 g/kg). Eight groups of rats (n = 8/group) were fed, for 4 weeks, chow or AIN-93 diets with or without inulin supplementation. Fecal samples were analyzed for different fecal parameters. After a 2-week adaptation, apparent differences in some fecal parameters were observed between the chow and AIN-93 diet groups. Throughout the 4-week intervention period, significantly (p dose (0.5 g/kg) of inulin in chow diet groups, while most of these changes could merely be seen at medium-dose (1 g/kg) in AIN-93 diet groups. These results demonstrated that the choice of experimental diets would affect the comparison of fecal parameters as well as the interpretation of effective dosage of prebiotic in intestinal health assessments.
    Matched MeSH terms: Dose-Response Relationship, Drug
  2. 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
  3. 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
  4. Zia A, Kamaruzzaman SB, Tan MP
    Postgrad Med, 2015 Mar;127(2):186-93.
    PMID: 25622817 DOI: 10.1080/00325481.2015.996505
    Hypertension is a highly prevalent condition among older people, but many physicians avoid aggressive treatment in this age group due to concerns about adverse effects such as orthostatic hypotension and falls. Orthostatic hypotension, which also increases in prevalence with increasing age, has been considered to be associated with antihypertensive therapy. Both orthostatic hypotension and antihypertensive medications are considered independent yet closely related predictors for falls among older people. The prescription of antihypertensive therapy among the elderly remains a long-standing controversy in geriatric medicine due to ongoing concerns about potential complications such as falls, despite conclusive evidence supporting the treatment of hypertension even among the very elderly. However, recent evidence suggests a dose-dependent relationship between blood pressure lowering therapy and falls among older individuals with preexisting risk factors for falls. In response to the spate of revisions in hypertension treatment targets for older patients in international guidelines and the recent evidence on antihypertensive therapy and falls, this review article examines the complex relationship between hypertension, antihypertensives, orthostatic hypotension, and falls among older patients.
    Matched MeSH terms: Dose-Response Relationship, Drug
  5. Taha M, Ismail NH, Lalani S, Fatmi MQ, Atia-Tul-Wahab, Siddiqui S, et al.
    Eur J Med Chem, 2015 Mar 6;92:387-400.
    PMID: 25585009 DOI: 10.1016/j.ejmech.2015.01.009
    In an effort to design and synthesize a new class of α-glucosidase inhibitor, we synthesized benzothiazole hybrid having benzohydrazide moiety (5). Compound 5 was reacted with various substituted aryl aldehyde to generate a small library of compounds 6-35. Synthesis of compounds was confirmed by the spectral information. These compounds were screened for their α-glucosidase activity. They showed a varying degree of α-glucosidase inhibition with IC50 values ranging between 5.31 and 53.34 μM. Compounds 6, 7, 9-16, 19, 21-30, 32-35 showed superior activity as compared to standard acarbose (IC50 = 906 ± 6.3 μM). This has identified a new class of α-glucosidase inhibitors. The predicted physico-chemical properties indicated the drug appropriateness for most of these compounds, as they obey Lipinski's rule of five (RO5). A hybrid B3LYP density functional theory (DFT) was employed for energy, minimization of 3D structures for all synthetic compounds using 6-311 + G(d,p) basis sets followed by molecular docking to explore their interactions with human intestinal C- and N-terminal domains of α-glucosidase. All compounds bind to the prospective allosteric site of the C- terminal domain, and consequently, may be considered as mixed inhibitors. It was hypothesized that both the dipole moment and H-bond interactions govern the biological activation of these compounds.
    Matched MeSH terms: Dose-Response Relationship, Drug
  6. Somchit MN, Mohamed NA, Ahmad Z, Zakaria ZA, Shamsuddin L, Omar-Fauzee MS, et al.
    Pak J Pharm Sci, 2014 Sep;27(5):1277-80.
    PMID: 25176383
    Spirulina spp. is a blue-green algae belongs to the family of Oscillatoriaceae, which having diverse biological activity. The aim of this current study was to evaluate and compare the anti-pyretic and anti-inflammatory activity of Spirulina platensis/SP and Spirulina lonar/SL extracts. In the anti-pyretic study, the ability to reduce the rectal temperature of rats induced pyrexia with 2g/kg Brewer's Yeast (BY) was performed. Rats were dosed either 2 or 4 mg/kg SP or SL. Rectal temperature was taken every hour for 8 hours. Results shown that there were significant dose-dependent (p<0.05) reduction of both treatments. However, SP treatment revealed faster reduction in rectal temperature. For anti-inflammatory activity, the reduction in the volume of paw edema induced by Prostaglandin E2 (100 IU/rat intraplantar) was measured. Rats were dosed orally with 2 or 4 mg/kg SP or SL. The paw edema was measured every 30 minutes for 4 hours using plethysmometer. Results had shown a significant dose dependent reduction in diameter of paw edema (p<0.05). The finding suggests that SP and SL extracts have anti-pyretic and anti-inflammatory properties. However, SP was found to be more effective than SL as anti-pyretic and anti-inflammatory agent.
    Matched MeSH terms: Dose-Response Relationship, Drug
  7. 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
  8. Khan KM, Saad SM, Shaikh NN, Hussain S, Fakhri MI, Perveen S, et al.
    Bioorg Med Chem, 2014 Jul 1;22(13):3449-54.
    PMID: 24844756 DOI: 10.1016/j.bmc.2014.04.039
    2-Arylquinazolin-4(3H)-ones 1-25 were synthesized by reacting anthranilamide with various benzaldehydes using CuCl2·2H2O as a catalyst in ethanol under reflux. Synthetic 2-arylquinazolin-4(3H)-ones 1-25 were evaluated for their β-glucuronidase inhibitory potential. A trend of inhibition IC50 against the enzyme in the range of 0.6-198.2μM, was observed and compared with the standard d-saccharic acid 1,4-lactone (IC50=45.75±2.16μM). Compounds 13, 19, 4, 12, 14, 22, 23, 25, 15, 8, 17, 11, 21, 1, 3, 18, 9, 2, and 24 with the IC50 values within the range of 0.6-44.0μM, indicated that the compounds have superior activity than the standard. The compounds showed no cytotoxic effects against PC-3 cells. A structure-activity relationship is established.
    Matched MeSH terms: Dose-Response Relationship, Drug
  9. Khan KM, Rahim F, Wadood A, Kosar N, Taha M, Lalani S, et al.
    Eur J Med Chem, 2014 Jun 23;81:245-52.
    PMID: 24844449 DOI: 10.1016/j.ejmech.2014.05.010
    In our effort directed toward the discovery of new anti-diabetic agent for the treatment of diabetes, a library of biscoumarin derivative 1-18 was synthesized and evaluated for α-glucosidase inhibitory potential. All eighteen (18) compounds displayed assorted α-glucosidase activity with IC50 values 16.5-385.9 μM, if compared with the standard acarbose (IC50 = 906 ± 6.387 μM). In addition, molecular docking studies were carried out to explore the binding interactions of biscoumarin derivatives with the enzyme. This study has identified a new class of potent α-glucosidase inhibitors.
    Matched MeSH terms: Dose-Response Relationship, Drug
  10. Antony JJ, Keng CL, Mahmood M, Subramaniam S
    Appl Biochem Biotechnol, 2013 Sep;171(2):315-29.
    PMID: 23832189 DOI: 10.1007/s12010-013-0369-x
    Regrowth of the cryopreserved protocorm-like bodies (PLBs) of Dendrobium Bobby Messina was assessed based on the plant vitrification solution 2 (PVS2) optimisation conditions. The optimized protocol obtained based on TTC spectrophotometrical analysis and growth recovery were 3-4 mm of PLBs size precultured in 0.2 M sucrose for 1 day, treated with a mixture of 2 M glycerol and 0.4 M sucrose supplemented with half-strength liquid MS media at 25 °C for 20 min and subsequently dehydrated with PVS2 at 0 °C for 20 min prior to storage in liquid nitrogen. Following rapid warming in a water bath at 40 °C for 90 s, PLBs were treated with unloading solution containing half-strength liquid MS media supplemented with 1.2 M sucrose. Subsequently, the PLBs were cultured on half-strength semi-solid MS media supplemented with 2 % (w/v) sucrose without any growth regulators and resulted in 40 % growth recovery. In addition, ascorbic acid treatment was used to evaluate the regeneration process of cryopreserved PLBs. However, growth recovery rates of non-cryopreserved and cryopreserved PLBs were 30 and 10 % when 0.6 mM ascorbic acid was added. Scanning electron microscopy analysis indicates that there are not much damages observed on both cryopreserved and non-cryopreserved PLBs in comparison to PLBs stock culture.
    Matched MeSH terms: Dose-Response Relationship, Drug
  11. Yoon YK, Ali MA, Wei AC, Choon TS, Khaw KY, Murugaiyah V, et al.
    Bioorg Chem, 2013 Aug;49:33-9.
    PMID: 23886696 DOI: 10.1016/j.bioorg.2013.06.008
    Two series of novel acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors containing benzimidazole core structure were synthesized by a four-step reaction pathway starting from 4-fluoro-3-nitrobenzoic acid as the basic compound. The structure of the novel benzimidazoles was characterized and confirmed by the elemental and mass spectral analyses as well as (1)H NMR spectroscopic data. Of the 34 novel synthesized compounds, three benzimidazoles revealed AChE inhibition with IC50<10 μM. The highest inhibitory activity (IC50=5.12 μM for AChE and IC50=8.63 μM for BChE) corresponds to the compound 5IIc (ethyl 1-(3-(1H-imidazol-1-yl)propyl)-2-(4-nitrophenyl)-1H-benzo[d]imidazole-5-carboxylate). The relationship between lipophilicity and the chemical structures as well as their limited structure-activity relationship was discussed.
    Matched MeSH terms: Dose-Response Relationship, Drug
  12. Basiri A, Murugaiyah V, Osman H, Kumar RS, Kia Y, Awang KB, et al.
    Eur J Med Chem, 2013 Sep;67:221-9.
    PMID: 23871902 DOI: 10.1016/j.ejmech.2013.06.054
    Series of hitherto unreported piperidone grafted pyridopyrimidines synthesized through ionic liquid mediated multi-component reaction. These compounds were evaluated for their inhibitory activities against AChE and BChE enzymes. All the compounds displayed considerable potency against AChE with IC50 values ranging from 0.92 to 9.11 μM, therein compounds 6a, 6h and 6i displayed superior enzyme inhibitory activities compared to standard drug with IC50 values of 0.92, 1.29 and 2.07 μM. Remarkably, all the compounds displayed higher BChE inhibitory activity compared to galantamine with IC50 values of 1.89-8.13 μM. Molecular modeling, performed for the most active compounds using three dimensional crystal structures of TcAChE and hBChE, disclosed binding template of these inhibitors into the active site of their respective enzymes.
    Matched MeSH terms: Dose-Response Relationship, Drug
  13. 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
  14. Siew BTT, Wong JL, Beniyamin A, Ho A, Kannan SKK, Jamalul Azizi AR
    Med J Malaysia, 2012 Apr;67(2):204-6.
    PMID: 22822644 MyJurnal
    INTRODUCTION: Patients with asthma-like symptoms pose a diagnostic dilemma when physical examination is normal. The usual practice in Malaysia would be to give empirical asthma treatment. Bronchial challenge test (BCT) is widely used in many countries to diagnose asthma objectively but it is not widely available in Malaysia.
    OBJECTIVE: To describe our experience with BCT using methacholine at Queen Elizabeth Hospital as a supporting tool in the investigation of patients with asthma-like symptoms.
    METHODOLOGY: Review of case notes of patients who underwent BCT from July 2008 till April 2009. BCT was performed via dosimeter technique. Results were classified as high hyper responsiveness if the provocative dose of methacholine required to achieve 20% fall in FEV1 (PD20) was less than or equal to 0.125 micromol, moderate hyper responsiveness if PD20 was between 0.125 to 1.99 micromol or mild hyper responsiveness if PD20 was between 2.00 to 6.6 micromol. PD20 of more than 6.6 micromol constitutes a negative MCT.
    RESULTS: 29 patients had BCT during the study period. 19 cases were included in this review. The age ranged from 13 to 70 years old. There were 12 males and 7 females. Duration of symptoms ranged from 2 weeks to 23 years. BCT was positive (mild or moderate hyper responsiveness) in 10 out of 19 patients. No patient had high bronchial hyper responsiveness.
    CONCLUSIONS: BCT is a useful adjunctive tool in the investigation of patients presenting with asthma-like symptoms. This test obviates empirical asthma treatment. BCT should be made available in all major hospitals in Malaysia.
    Matched MeSH terms: Dose-Response Relationship, Drug
  15. Piaru SP, Mahmud R, Abdul Majid AM, Mahmoud Nassar ZD
    Asian Pac J Trop Med, 2012 Apr;5(4):294-8.
    PMID: 22449521 DOI: 10.1016/S1995-7645(12)60042-X
    OBJECTIVE: Toinvestigate the anti-angiogenic activity and antioxidant properties of Myristica fragrans (M. fragrans) (nutmeg) and Morinda citrifolia (M. citrifolia)(mengkudu) oils.

    METHODS: The nutmeg and megkudu essential oils were obtained by steam distillation. The antioxidant activities of both essential oils were determined by beta-carotene/linoleic acid bleaching assay and reducing power while the anti-angiogenic activity was investigated using rat aortic ring assay using various concentrations.

    RESULTS: The results showed that nutmeg oil has higher antioxidant activity than mengkudu oil. The nutmeg oil effectively inhibited the oxidation of linoleic acid with (88.68±0.1)% while the inhibition percentage of oxidation of linoleic acid of the mengkudu oil is (69.44±0.4)%. The nutmeg oil and mengkudu oil showed reducing power with an EC(50) value of 181.4 μg/mL and 3 043.0 μg/mL, respectively. The antiangiogenic activity of nutmeg oil showed significant antiangiogenic activity with IC(50) of 77.64 μg/mL comparing to mengkudu oil which exhibits IC(50) of 109.30 μg/mL.

    CONCLUSIONS: Bioactive compound(s) will be isolated from the nutmeg essential oil to be developed as antiangiogenic drugs.

    Matched MeSH terms: Dose-Response Relationship, Drug
  16. Pour BM, Sasidharan S
    Asian Pac J Trop Biomed, 2011 Jun;1(3):230-2.
    PMID: 23569765 DOI: 10.1016/S2221-1691(11)60033-6
    To investigate the toxicity of methanol extract of various parts (Root, Stem, Leaf, Flower and Fruit) of Lantana camara (L. Camara) in Artemia salina.
    Matched MeSH terms: Dose-Response Relationship, Drug
  17. Al-Najjar BO, Wahab HA, Tengku Muhammad TS, Shu-Chien AC, Ahmad Noruddin NA, Taha MO
    Eur J Med Chem, 2011 Jun;46(6):2513-29.
    PMID: 21482446 DOI: 10.1016/j.ejmech.2011.03.040
    Peroxisome Proliferator-Activated Receptor γ (PPARγ) activators have drawn great recent attention in the clinical management of type 2 diabetes mellitus, prompting several attempts to discover and optimize new PPARγ activators. With this in mind, we explored the pharmacophoric space of PPARγ using seven diverse sets of activators. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of pharmacophoric models and 2D physicochemical descriptors capable of accessing self-consistent and predictive quantitative structure-activity relationship (QSAR) (r2(71)=0.80, F=270.3, r2LOO=0.73, r2PRESS against 17 external test inhibitors=0.67). Three orthogonal pharmacophores emerged in the QSAR equation and were validated by receiver operating characteristic (ROC) curves analysis. The models were then used to screen the national cancer institute (NCI) list of compounds. The highest-ranking hits were tested in vitro. The most potent hits illustrated EC50 values of 15 and 224 nM.
    Matched MeSH terms: Dose-Response Relationship, Drug
  18. Basma AA, Zakaria Z, Latha LY, Sasidharan S
    Asian Pac J Trop Med, 2011 May;4(5):386-90.
    PMID: 21771682 DOI: 10.1016/S1995-7645(11)60109-0
    OBJECTIVE: To assess antioxidant activities of different parts of Euphorbia hirta (E. hirta), and to search for new sources of safe and inexpensive antioxidants.

    METHODS: Samples of leaves, stems, flowers and roots from E. hirta were tested for total phenolic content, and flavonoids content and in vitro antioxidant activity by diphenyl-1-picrylhydrazyl (DPPH) assay and reducing power was measured using cyanoferrate method.

    RESULTS: The leaves extract exhibited a maximum DPPH scavenging activity of (72.96±0.78)% followed by the flowers, roots and stems whose scavenging activities were (52.45±0.66)%, (48.59±0.97)%, and (44.42±0.94)%, respectively. The standard butylated hydroxytoluene (BHT) was (75.13±0.75)%. The IC(50) for leaves, flowers, roots, stems and BHT were 0.803, 0.972, 0.989, 1.358 and 0.794 mg/mL, respectively. The reducing power of the leaves extract was comparable with that of ascorbic acid and found to be dose dependent. Leaves extract had the highest total phenolic content [(206.17±1.95) mg GAE/g], followed by flowers, roots and stems extracts which were (117.08±3.10) mg GAE/g, (83.15±1.19) mg GAE/g, and (65.70±1.72) mg GAE/g, respectively. On the other hand, total flavonoids content also from leave had the highest value [(37.970±0.003) mg CEQ/g], followed by flowers, roots and stems extracts which were (35.200±0.002) mg CEQ/g, (24.350±0.006) mg CEQ/g, and (24.120±0.004) mg CEQ/g, respectively. HPTLC bioautography analysis of phenolic and antioxidant substance revealed phenolic compounds. Phytochemical screening of E. hirta leaf extract revealed the presence of reducing sugars, terpenoids, alkaloids, steroids, tannins, flavanoids and phenolic compounds.

    CONCLUSIONS: These results suggeste that E. hirta have strong antioxidant potential. Further study is necessary for isolation and characterization of the active antioxidant agents, which can be used to treat various oxidative stress-related diseases.

    Matched MeSH terms: Dose-Response Relationship, Drug
  19. Tan HP, Wong DZ, Ling SK, Chuah CH, Kadir HA
    Fitoterapia, 2012 Jan;83(1):223-9.
    PMID: 22093753 DOI: 10.1016/j.fitote.2011.10.019
    The galloylated cyanogenic glucosides based on prunasin (1-7), gallotannins (8-14), ellagitannins (15-17), ellagic acid derivatives (18, 19) and gallic acid (20) isolated from the leaves of Phyllagathis rotundifolia (Melastomataceae) were investigated for their neuroprotective activity against hydrogen peroxide (H(2)O(2))-induced oxidative damage in NG108-15 hybridoma cell line. Among these compounds, the gallotannins and ellagitannins exhibited remarkable neuroprotective activities against oxidative damage in vitro as compared to galloylated cyanogenic glucosides and ellagic acid derivatives in a dose-dependent manner. They could be explored further as potential natural neuroprotectors in various remedies of neurodegenerative diseases.
    Matched MeSH terms: Dose-Response Relationship, Drug
  20. Wong NL, Achike FI
    Regul. Pept., 2010 Aug 9;163(1-3):113-9.
    PMID: 20434492 DOI: 10.1016/j.regpep.2010.04.003
    Hyperglycaemia initiates endothelial dysfunction causing diabetic macro- and micro-vasculopathy, the main causes of morbidity and mortality in diabetes mellitus. The vasculopathy exhibits gender peculiarities. We therefore explored gender differences in comparing the effects of hyperglycaemia (50 mM) per se with its hyperosmolar (50 mM) effects on vascular tissue responses to insulin. Endothelium-intact or denuded thoracic aortic rings from age-matched male and female Sprague-Dawley rats were incubated for 10 min or 6 h (acute versus chronic exposure) in normal, hyperglycaemic or hyperosmolar Krebs solution. Relaxant responses to insulin (6.9x10(-7)-6.9x10(-5) M) of the phenylephrine-contracted tissues were recorded. Endothelium denudation in both genders inhibited relaxation to insulin in all conditions, more significantly in female than in male tissues, suggesting the female response to insulin is more endothelium-dependent than the male. Acutely and chronically exposed normoglycemic endothelium-intact or -denuded tissues responded similarly to insulin. Chronic hyperglycemic or hyperosmolar exposure did not alter the endothelium-denuded tissue responses to insulin, whereas the responses of the endothelium-intact male and female hyperosmolar, and male hyperglycemic tissues were enhanced. The results show that insulin exerts an endothelium-dependent and independent relaxation with the female tissue responses more endothelium-dependent than the male. The data also suggest that hyperosmolarity per se enhances aortic tissue relaxant responses to insulin whereas hyperglycemia per se inhibits the same and more so in female than male tissues. These effects are endothelium-dependent.
    Matched MeSH terms: Dose-Response Relationship, Drug
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