Displaying publications 41 - 60 of 66 in total

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  1. Shastri MD, Chong WC, Dua K, Peterson GM, Patel RP, Mahmood MQ, et al.
    Inflammopharmacology, 2021 Feb;29(1):15-33.
    PMID: 33152094 DOI: 10.1007/s10787-020-00770-y
    Asthma is a common, heterogeneous and serious disease, its prevalence has steadily risen in most parts of the world, and the condition is often inadequately controlled in many patients. Hence, there is a major need for new therapeutic approaches. Mild-to-moderate asthma is considered a T-helper cell type-2-mediated inflammatory disorder that develops due to abnormal immune responses to otherwise innocuous allergens. Prolonged exposure to allergens and persistent inflammation results in myofibroblast infiltration and airway remodelling with mucus hypersecretion, airway smooth muscle hypertrophy, and excess collagen deposition. The airways become hyper-responsive to provocation resulting in the characteristic wheezing and obstructed airflow experienced by patients. Extensive research has progressed the understanding of the underlying mechanisms and the development of new treatments for the management of asthma. Here, we review the basis of the disease, covering new areas such as the role of vascularisation and microRNAs, as well as associated potential therapeutic interventions utilising reports from animal and human studies. We also cover novel drug delivery strategies that are being developed to enhance therapeutic efficacy and patient compliance. Potential avenues to explore to improve the future of asthma management are highlighted.
    Matched MeSH terms: Muscle, Smooth
  2. Ajay M, Gilani AU, Mustafa MR
    Life Sci, 2003 Dec 19;74(5):603-12.
    PMID: 14623031
    The potency, structure-activity relationship, and mechanism of vasorelaxation of a series of flavonoids, representing different subclasses (flavonols: fisetin, rutin, quercetin; flavones: chrysin, flavone, baicalein; flavanones: naringenin, naringin; isoflavones: diadzein and flavanes: epigallo catechin gallate), were examined in the isolated rat aorta. Most of the flavonoids tested showed concentration dependent relaxant effects against K+ (80 mM) and phenylephrine (PE, 0.1 microM)-induced contractions with a greater inhibition of the responses to the alpha1-adrenoceptor agonist. The relaxant effects of most of the flavonoids involve in part the release of nitric oxide and prostaglandins from the endothelium as pretreatment with L-NAME and indomethacin attenuated the responses. In addition, the relaxant action of the flavonoids includes inhibition of Ca+2 influx and release of Ca+2 from intracellular stores. A structure-activity relationship amongst the flavonoids was suggested.
    Matched MeSH terms: Muscle, Smooth, Vascular/drug effects*
  3. Nabishah BM, Morat PB, Kadir BA, Khalid BA
    Gen. Pharmacol., 1991;22(2):389-92.
    PMID: 1647349
    1. Glucocorticosteroid may relieve bronchospasm by mediating changes in the muscarinic receptor concentration and/or its affinity. 2. Cholinergic muscarinic receptors were determined by using Scatchard's plots from radioligand binding assays of 0.13-3.2 nM [3H]quinuclidinyl benzylate binding to the membrane fraction of bronchial smooth muscle (BSM). 3. The concentration of muscarinic receptor in BSM of normal rat was 57 +/- 3 fmol mg protein and the dissociation constant was 0.07 +/- 0.02 nM. Dexamethasone and corticosterone reduced muscarinic receptor concentration to 50-60% of basal with no changes in receptor affinity. No changes were found in rat treated with deoxycorticosterone. 4. These findings suggest that glucocorticoids but not mineralocorticoid relieve bronchospasm at least partly by reducing the cholinergic hypersensitivity.
    Matched MeSH terms: Muscle, Smooth/drug effects*; Muscle, Smooth/metabolism
  4. Balkis Budin S, Othman F, Louis SR, Abu Bakar M, Radzi M, Osman K, et al.
    Rom J Morphol Embryol, 2009;50(1):23-30.
    PMID: 19221642
    PREMISES AND OBJECTIVES: Antioxidant plays an important role in preventing the progression of diabetes mellitus (DM) complications. The aim of the present study was to investigate the effect of alpha lipoic acid (ALA) supplementation on plasma lipid, oxidative stress and vascular changes in diabetic rats.
    Matched MeSH terms: Muscle, Smooth, Vascular/drug effects; Muscle, Smooth, Vascular/pathology; Muscle, Smooth, Vascular/physiopathology*; Muscle, Smooth, Vascular/ultrastructure
  5. Nabishah BM, Morat PB, Khalid BA, Kadir BA
    Clin Exp Pharmacol Physiol, 1990 Dec;17(12):841-7.
    PMID: 2092952
    1. The effects of corticosteroid pretreatment on acetylcholine (ACH)-induced contraction of bronchial smooth muscle (BSM) were studied. 2. ACH dose-response curves for dexamethasone (DM)- and corticosterone (B)-treated but not deoxycorticosterone (DOC)-treated BSM were significantly shifted to the right; this provides evidence that glucocorticoid treatment reduced the sensitivity of BSM to ACH. 3. Morphine enhanced BSM contraction in response to ACH by 20%. DM suppressed this enhancement. 4. These findings correlated well with the reduction of muscarinic receptor numbers in BSM by glucocorticoids in our previous study. In addition, glucocorticoids reduced the sensitivity of BSM to opioids.
    Matched MeSH terms: Muscle, Smooth/drug effects*; Muscle, Smooth/physiology
  6. Devi RC, Sim SM, Ismail R
    PMID: 22675383 DOI: 10.1155/2012/539475
    Cymbopogon citratus has been shown to have antioxidant, antimicrobial, antispasmodic and chemo-protective properties. Citral, is the major constituent of C. citratus. This study investigated the effects of methanolic extracts of leaves (LE), stems (SE), and roots (RE) of C. citratus and citral on vascular smooth muscle and explored their possible mechanisms of action. The experiment was conducted using isolated tissue preparations, where citral, LE, SE, and RE were added separately into a tissue bath that contained aortic rings, which were pre-contracted with phenylephrine (PE). Citral, LE, and RE exhibited a dose-dependent relaxant effect on the PE-induced contractions. Citral appeared to partially act via NO as its vasorelaxant effect was attenuated by L-NAME. However, the effect of LE may involve prostacyclin as indomethacin reversed the relaxant effect of LE on the PE-induced contraction. Furthermore, citral, LE, and RE abolished the restoration of PE-induced contraction caused by the addition of increasing doses of calcium in both endothelium intact and denuded rings. These findings suggest that the relaxation effect of citral, LE, and RE is endothelium-independent and may be mainly by affecting the intracellular concentration of calcium. Citral may partially act through the NO pathway while a vasodilator prostaglandin may mediate the effect of LE.
    Matched MeSH terms: Muscle, Smooth, Vascular
  7. Ajay M, Achike FI, Mustafa AM, Mustafa MR
    Clin Exp Pharmacol Physiol, 2006 Apr;33(4):345-50.
    PMID: 16620299
    1. There is a growing interest in the anti-oxidant characteristics and use of flavonoids in the management of cardiovascular diseases. The cardiovascular mechanism of action of these plant derivatives remains controversial. This study compared the effects of the flavonoid quercetin with those of the anti-oxidant vitamin ascorbic acid (vitamin C) on the reactivity of aortic rings from spontaneously hypertensive rats (SHR). 2. The phenylephrine (PE)-induced contractile and the endothelium-dependent and independent relaxant responses of aortic rings from 21 to 22 week old SHR and age-matched normotensive Wistar (WKY) rats were observed in the presence of quercetin or ascorbic acid. All the experiments were performed in the presence of the cyclooxygenase inhibitor, indomethacin (10 micromol/L). 3. The endothelium-dependent and independent relaxations to acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were significantly lesser in the SHR compared to the WKY tissues whereas the contractile responses to PE were similar in both tissues. Pretreatment of WKY rings with quercetin or ascorbic acid had no effect on the responses to ACh or PE. In the SHR tissues, however, quercetin or ascorbic acid significantly improved the relaxation responses to ACh and reduced the contractions to PE with greater potency for quercetin. Both compounds lacked any effects on the responses to SNP in either aortic ring types. N(omega)-nitro-L-arginine methyl ester (l-NAME, 10 micromol/L) significantly attenuated the vasodepressor effects of quercetin and ascorbic acid, raising the responses to PE to a level similar to that observed in the control SHR tissues. In l-NAME pretreated aortic rings, quercetin and ascorbic acid inhibited the contractile responses to PE with the same magnitude in WKY and SHR tissues. 4. The present results suggest that acute exposure to quercetin improves endothelium-dependent relaxation and reduces the contractile responses of hypertensive aortae with a greater potency than ascorbic acid. This suggests a better vascular protection with this flavonoid than ascorbic acid in the SHR model of hypertension and possibly in human cardiovascular diseases.
    Matched MeSH terms: Muscle, Smooth, Vascular/drug effects
  8. Mustafa MR, Achike FI
    Acta Pharmacol Sin, 2000 Dec;21(12):1165-8.
    PMID: 11603294
    Dicentrine is a known alpha 1-adrenoceptor antagonist, but its alpha 1-adrenoceptor subtype selectivity has not yet been determined. We therefore, investigated the putative alpha 1-adrenoceptor subtype selectivity of this agent.
    Matched MeSH terms: Muscle, Smooth/drug effects; Muscle, Smooth, Vascular/drug effects
  9. Wong CY, Chang YM, Tsai YS, Ng WV, Cheong SK, Chang TY, et al.
    BMC Genomics, 2020 Jul 07;21(1):467.
    PMID: 32635896 DOI: 10.1186/s12864-020-06868-5
    BACKGROUND: Mesangial cells play an important role in the glomerulus to provide mechanical support and maintaine efficient ultrafiltration of renal plasma. Loss of mesangial cells due to pathologic conditions may lead to impaired renal function. Mesenchymal stem cells (MSC) can differentiate into many cell types, including mesangial cells. However transcriptomic profiling during MSC differentiation into mesangial cells had not been studied yet. The aim of this study is to examine the pattern of transcriptomic changes during MSC differentiation into mesangial cells, to understand the involvement of transcription factor (TF) along the differentiation process, and finally to elucidate the relationship among TF-TF and TF-key gene or biomarkers during the differentiation of MSC into mesangial cells.

    RESULTS: Several ascending and descending monotonic key genes were identified by Monotonic Feature Selector. The identified descending monotonic key genes are related to stemness or regulation of cell cycle while ascending monotonic key genes are associated with the functions of mesangial cells. The TFs were arranged in a co-expression network in order of time by Time-Ordered Gene Co-expression Network (TO-GCN) analysis. TO-GCN analysis can classify the differentiation process into three stages: differentiation preparation, differentiation initiation and maturation. Furthermore, it can also explore TF-TF-key genes regulatory relationships in the muscle contraction process.

    CONCLUSIONS: A systematic analysis for transcriptomic profiling of MSC differentiation into mesangial cells has been established. Key genes or biomarkers, TFs and pathways involved in differentiation of MSC-mesangial cells have been identified and the related biological implications have been discussed. Finally, we further elucidated for the first time the three main stages of mesangial cell differentiation, and the regulatory relationships between TF-TF-key genes involved in the muscle contraction process. Through this study, we have increased fundamental understanding of the gene transcripts during the differentiation of MSC into mesangial cells.

    Matched MeSH terms: Muscle, Smooth, Vascular/physiology
  10. Nabishah BM, Morat PB, Alias AK, Kadir BA, Khalid BA
    Clin Exp Pharmacol Physiol, 1992 Dec;19(12):839-42.
    PMID: 1335381
    1. Male Sprague-Dawley rats were made either hyper- or hypothyroid with thyroxine or 4-methyl-2-thiouracil, respectively. Bronchial smooth muscle (BSM) contractility and lung cyclic adenosine 3',5'-monophosphate (cAMP) content were measured in both conditions. 2. Bronchial smooth muscle contractility was significantly weaker in hyperthyroid rats, while the BSM contractility of hypothyroid rats was the same as controls. 3. The cAMP content of hyperthyroid rat lungs was similar to controls but was decreased in hypothyroid rats. 4. These studies demonstrated that both the hyper- and hypothyroid states affect respiration, although the mechanisms involved with different for each condition.
    Matched MeSH terms: Muscle, Smooth/physiology*
  11. Loong BJ, Tan JH, Lim KH, Mbaki Y, Ting KN
    Naunyn Schmiedebergs Arch Pharmacol, 2015 Oct;388(10):1061-7.
    PMID: 26051407 DOI: 10.1007/s00210-015-1140-3
    The functional responses of different overnight-stored in vitro tissues are not clearly described in any animal model. The influence of overnight storage in an animal model may vary between tissue types. We employed Sprague-Dawley rat as our animal model and investigated the functional changes of rat aorta, trachea, bronchus and bladder that were used (i) immediately after surgical removal (denoted as fresh) and (ii) after storage in aerated (95% O2, 5% CO2) Krebs-Ringer bicarbonate solution at 4 °C for 24 h (denoted as stored). The aorta ring was pre-contracted with phenylephrine, and the functional response of the tissue was investigated using isoprenaline, forskolin and carbachol. Carbachol was also used to increase the tone in trachea, bronchus rings and bladder strips. A clear reduced function of endothelium, with a minor if any effect in the smooth muscle function in rat aorta was observed after overnight storage. The contractile response of overnight-stored rat airway (trachea and bronchus) and bladder smooth muscles remained unchanged. Among all tested tissues, only bronchus showed a reduced response rate (only 40% responded) after storage. In vitro rat tissues that are stored in Krebs solution at 4 °C for 24 h can still be used to investigate smooth muscle responses, however, not endothelium-mediated responses for aorta. The influence of overnight storage on different tissues from an animal model (Sprague-Dawley rat in our study) also provides an insight in maximising the use of sacrificed animals.
    Matched MeSH terms: Muscle, Smooth/drug effects*; Muscle, Smooth/metabolism; Muscle, Smooth, Vascular/drug effects*; Muscle, Smooth, Vascular/metabolism
  12. Ajura Abdul Jalil, Lukman Md Auzair, Hin, Lau Shin
    MyJurnal
    Congenital epulis is a fairly rare soft tissue tumour occurring exclusively on the alveolar ridge of newborns. The exact origin of congenital epulis is still debatable. The objective of the study is to determine the clinicopathological features and immunohistochemical findings of congenital epulis. A retrospective study was carried out to determine the clinicopathological features of congenital epulis, diagnosed histologically in the main oral histopathology laboratory in Malaysia from 1967 to 2014. Immunostaining using vimentin, muscle specific actin, smooth muscle antigen, desmin, S100, CD34, CD68 and CD1a was carried out. Twelve cases of congenital epulis were reviewed. All of the patients were females and the presentation age ranged from 2 to 90 days. The patients comprised of 6 Malays, 3 Chinese, 2 Indians and 1 Orang Asli. Most of the cases (n=7) involved the maxillary ridge and presented as pedunculated well-defined lumps (n=8). Excisional biopsy was performed in all cases. Via immunohistochemistry, vimentin expression was observed in all cases; but negative for CD34, muscle specific actin, smooth muscle antigen, and desmin. CD1a and S100 positivity was seen in five cases. The interstitial cells were highlighted by CD68. Although congenital epulis has been first described 130 years ago, the exact nature of its histogenesis remains a mystery.
    Matched MeSH terms: Muscle, Smooth
  13. AlMatar M, Makky EA
    3 Biotech, 2016 Jun;6(1):4.
    PMID: 28330073 DOI: 10.1007/s13205-015-0323-4
    Fungi are important natural product sources that have enormous potential for the production of novel compounds for use in pharmacology, agricultural applications and industry. Compared with other natural sources such as plants, fungi are highly diverse but understudied. However, research on Cladosporium cladosporioides revealed the existence of bioactive products such as p-methylbenzoic acid, ergosterol peroxide (EP) and calphostin C as well as enzymes including pectin methylesterase (PME), polygalacturonase (PG) and chlorpyrifos hydrolase. p-Methylbenzoic acid has ability to synthesise 1,5-benzodiazepine and its derivatives, polyethylene terephthalate and eicosapentaenoic acid. EP has anticancer, antiangiogenic, antibacterial, anti-oxidative and immunosuppressive properties. Calphostin C inhibits protein kinase C (PKC) by inactivating both PKC-epsilon and PKC-alpha. In addition, calphostin C stimulates apoptosis in WEHI-231 cells and vascular smooth muscle cells. Based on the stimulation of endoplasmic reticulum stress in some types of cancer, calphostin C has also been evaluated as a potential photodynamic therapeutic agent. Methylesterase (PME) and PG have garnered attention because of their usage in the food processing industry and significant physiological function in plants. Chlorpyrifos, a human, animal and plant toxin, can be degraded and eliminated by chlorpyrifos hydrolase.
    Matched MeSH terms: Muscle, Smooth, Vascular
  14. Achike FI, Kwan CY
    Acta Pharmacol Sin, 2002 Aug;23(8):698-704.
    PMID: 12147191
    In an attempt to pharmacologically characterize the Chinese antihypertensive drug, tetrandrine, we observed in rat-tail arteries, an unusual contraction in tissues that were stimulated with high [KCl] and not those stimulated with phenylephrine. The characteristics of this contraction were studied.
    Matched MeSH terms: Muscle, Smooth, Vascular/drug effects*; Muscle, Smooth, Vascular/physiology
  15. Loh LC
    Family Physician, 2005;13(3):0-0.
    MyJurnal
    Significant changes have occurred in relation to how chronic asthma is being treated. Emphasis has now shifted from viewing asthma as a condition of smooth muscle dysfunction to one of chronic inflammation. As such, anti-inflammatory therapy forming the cornerstone of treatment represents the first important milestone in the evolution of asthma treatment. For this purpose, inhaled corticosteroid (ICS) is by far the most effective anti-inflammatory therapy. Another important milestone is the recognition of the superiority of adding long-acting β2-agonist (LABA) to ICS over escalating ICS dose alone or other forms of add-on therapies in treating asthmatic patients not responding to regular ICS alone. The effectiveness of adding LABA to ICS in treating asthma logically led to combining the two drugs into one single inhaler (salmeterol/fluticasone and budesonide/formoterol) that has the attractiveness of being user-friendly and ensuring that ICS is not missed out. The unique property of formoterol that allows for repetitive flexible dosing paved way to the concept of using Symbicort for both regular maintenance dosing and as required rescue medication. This revolutionary approach has been recently shown to provide improved asthma outcome, achieved at an overall lower or at least comparable corticosteroid intake, and may represent another evolutionary step in the treatment strategy of chronic asthma.
    Matched MeSH terms: Muscle, Smooth
  16. Ameer OZ, Salman IM, Siddiqui MJ, Yam MF, Sriramaneni RN, Sadikun A, et al.
    Braz. J. Med. Biol. Res., 2010 Feb;43(2):186-94.
    PMID: 20084331
    We investigated the vascular responses and the blood pressure reducing effects of different fractions obtained from the methanol extract of Loranthus ferrugineus Roxb. (F. Loranthaceae). By means of solvent-solvent extraction, L. ferrugineus methanol extract (LFME) was successively fractionated with chloroform, ethyl acetate and n-butanol. The ability of these LFME fractions to relax vascular smooth muscle against phenylephrine (PE)- and KCl-induced contractions in isolated rat aortic rings was determined. In another set of experiments, LFME fractions were tested for blood pressure lowering activity in anesthetized adult male Sprague-Dawley rats (250-300 g, 14-18 weeks). The n-butanol fraction of LFME (NBF-LFME) produced a significant concentration-dependent inhibition of PE- and KCl-induced aortic ring contractions compared to other fractions. Moreover, NBF-LFME had a significantly higher relaxant effect against PE- than against high K+-induced contractions. In anesthetized Sprague-Dawley rats, NBF-LFME significantly lowered blood pressure in a dose-dependent manner and with a relatively longer duration of action compared to the other fractions. HPLC, UV and IR spectra suggested the presence of terpenoid constituents in both LFME and NBF-LFME. Accordingly, we conclude that NBF-LFME is the most potent fraction producing a concentration-dependent relaxation in vascular smooth muscle in vitro and a dose-dependent blood pressure lowering activity in vivo. The cardiovascular effects of NBF-LFME are most likely attributable to its terpenoid content.
    Matched MeSH terms: Muscle, Smooth, Vascular/drug effects*
  17. Sakihama H, Lee GR, Chin BY, Csizmadia E, Gallo D, Qi Y, et al.
    Arterioscler Thromb Vasc Biol, 2021 Jun;41(6):1915-1927.
    PMID: 33853347 DOI: 10.1161/ATVBAHA.120.315558
    [Figure: see text].
    Matched MeSH terms: Muscle, Smooth, Vascular/drug effects*; Muscle, Smooth, Vascular/enzymology; Muscle, Smooth, Vascular/pathology
  18. Vadivelu RK, Yeap SK, Ali AM, Hamid M, Alitheen NB
    PMID: 23056140 DOI: 10.1155/2012/251362
    Betulinic acid is a widely available plant-derived triterpene which is reported to possess selective cytotoxic activity against cancer cells of neuroectodermal origin and leukemia. However, the potential of betulinic acid as an antiproliferative and cytotoxic agent on vascular smooth muscle (VSMC) is still unclear. This study was carried out to demonstrate the antiproliferative and cytotoxic effect of betulinic acid on VSMCs using 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry cell cycle assay, BrdU proliferation assay, acridine orange/propidium iodide staining, and comet assay. Result from MTT and BrdU assays indicated that betulinic acid was able to inhibit the growth and proliferation of VSMCs in a dose-dependent manner with IC(50) of 3.8 μg/mL significantly (P < 0.05). Nevertheless, betulinic acid exhibited G(1) cell cycle arrest in flow cytometry cell cycle profiling and low level of DNA damage against VSMC in acridine orange/propidium iodide and comet assay after 24 h of treatment. In conclusion, betulinic acid induced G(1) cell cycle arrest and dose-dependent DNA damage on VSMC.
    Matched MeSH terms: Muscle, Smooth, Vascular
  19. Duangjai A, Parseatsook K, Sajjapong W, Saokaew S
    J Med Food, 2020 Nov;23(11):1169-1175.
    PMID: 32976072 DOI: 10.1089/jmf.2020.4769
    Vietnamese coriander (Polygonum odoratum Lour.) is a plant native to northern Thailand. The biological activities of P. odoratum Lour. extract (POE) include antibacterial, antiviral, and expectorant. However, the effect of POE on intestinal smooth muscle motility is unclear. The aim of this study was to evaluate the relaxant effects of POE on isolated rat ileum. Propranolol (1 μM), calcium chloride (1-20 mM), and Nω-nitro-l-arginine methylester (l-NAME, 100 μM) were used to investigate the mechanisms of action. The results showed that POE (0.01-5 mg/mL) reduced KCl-induced contraction. In addition, POE (1 mg/mL) reduced the contraction by propranolol and l-NAME and attenuated CaCl2-induced contractions. Our results indicate that the relaxation effect of POE on ileum contractions seems to involve nitric oxide and β-adrenergic pathways, and blockade of calcium influx. These findings provide a pharmacological basis for the traditional use of POE to treat gastrointestinal disorders such as irritable bowel syndrome or diarrhea.
    Matched MeSH terms: Muscle, Smooth/drug effects*
  20. Azizah MR, Shahnaz M, Zulkifli MN, Nasuruddin BA
    Malays J Pathol, 1995 Dec;17(2):83-6.
    PMID: 8935131
    A study of 101 sera from 69 Malay, 14 Chinese and 18 Indian healthy adult Malaysians was undertaken to determine the frequency of antinuclear antibodies (ANA), antimitochondrial antibodies (AMA), antismooth muscle antibodies (SMA) and antiparietal cell antibodies (APCA). There were 67 females and 34 males with a mean age of 31.7 years (+/-8.6). ANA was assayed by immunofluorescence (IF) using both mouse liver and HEp-2 cell substrates. AMA, SMA and APCA were also tested by IF using composite sections from mouse liver, kidney and stomach substrates. Analysis showed 6.9% were positive for ANA at a titre of 1:40 with HEp-2 while only 1.9% were detected using mouse liver. 9.9% had detectable AMA from titres 1:10 to 1:90. None of them had detectable SMA and only 1 (0.09%) had APCA at a titre of 1:80. This study suggests that a diagnosis of an autoimmune disorder has to be cautiously made taking into consideration that autoantibodies are present in low titres in the healthy population.
    Matched MeSH terms: Muscle, Smooth/immunology*
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