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Inhibitory Effects (inhibitory + effects)
Kinds of Inhibitory Effects Selected AbstractsIN VITRO INHIBITORY EFFECTS OF ATORVASTATIN ON CARDIAC FIBROBLASTS: IMPLICATIONS FOR VENTRICULAR REMODELLINGCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2005Jennifer Martin SUMMARY 1.,Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) reduce mortality after myocardial infarction (MI). Although this may be predominantly due to their known anti-ischaemic actions, these drugs are known to have other beneficial effects. 2.,Because pathological deposition of extracellular matrix (ECM) material is a key component of remodelling after MI, we sought to determine whether atorvastatin could inhibit ECM production in vitro. 3.,The addition of atorvastatin to rat cardiac fibroblasts stimulated with either transforming growth factor (TGF)-,1 (TGF-,1) or angiotensin (Ang) II reduced collagen synthesis in a dose-dependent manner (3.7-fold reduction (95% confidence interval (CI) 1.8,15; P < 0.01) and 5.3-fold reduction (95% CI 1.8,7.7; P < 0.01), respectively, compared with stimulant alone). Similar observations were made in human cardiac fibroblast cell culture. Atorvastatin also dose-dependently reduced TGF-,1 and AngII-induced increases in ,(I)-procollagen mRNA (P < 0.01 for both), as well as gene expression of the profibrotic peptide connective tissue growth factor. 4.,Atorvastatin appears to directly inhibit collagen production by cardiac fibroblasts. This antifibrotic action may contribute to the antiremodelling effect of statins. [source] Dual Excitatory and Inhibitory Effects of Stimulation of Intrinsic Innervation of the Anterior Pituitary on Adrenocorticotropic Hormone Release in the RatJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2004L.-Z. Gao Abstract The gland cells of the mammalian anterior pituitary are innervated by substantial amounts of nerve fibres, and there is evidence that the nerve fibres are functionally active. In the rat, the nerve fibres make typical excitatory synapses with corticotropes. The physiological significance of this synaptic relationship was investigated in the present study. The anterior pituitary of the rat was sliced and stimulated with electrical field in a chamber. The perfusate was continuously collected and immunoradioassayed for adrenocorticotropic hormone (ACTH). When the gland slices were stimulated at a high frequency of 10 Hz, there was a significant inhibition of ACTH secretion. Stimulation at a low frequency of 2 Hz resulted in a quick and transient excitation of ACTH release. The results indicate that stimulation of the nerve fibres in the anterior pituitary has dual excitatory and inhibitory effects on ACTH secretion. [source] Inhibitory Effects of Ethanol on Rat Mesangial Cell Proliferation via Protein Kinase C PathwayALCOHOLISM, Issue 3 2002Kayoko Segawa A large body of evidence has shown that ethanol inhibits the cell growth and cell proliferation in a variety of cell types. However, it has not been studied whether ethanol inhibits the proliferation of mesangial cells (MC) in the kidney. We examined the effects of ethanol on cell proliferation in cultured rat MC. Treatment with ethanol (10,200 mM) for 48 hr inhibited [3H]thymidine incorporation into MC in a concentration-dependent manner. The same concentrations of ethanol also inhibited the increase in cell number of MC. GF109203X and chelerythrine chloride, inhibitors for protein kinase C, eliminated the inhibitory effects of ethanol; and protein kinase C activator, PMA, mimicked the effects of ethanol. In contrast, neither the protein kinase A inhibitor H-89 nor the protein kinase G inhibitor KT5823 had any effect. These findings suggest that ethanol has inhibitory effects on the proliferation of MC, probably via activation of the protein kinase C pathway. [source] Are the Inhibitory Effects of Nicotine on Erectile Response in Nonsmokers Generalizable to Long-Term Smokers?THE JOURNAL OF SEXUAL MEDICINE, Issue 8 2008A Reply [source] Differential Inhibitory Effects of the Polyphenol Ellagic Acid on Inflammatory Mediators NF-,B, iNOS, COX-2, TNF-,, and IL-6 in 1,2-Dimethylhydrazine-Induced Rat Colon CarcinogenesisBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2010Syed Umesalma We investigated the effect of ellagic acid on colon cancer induced by 1,2-dimethylhydrazine in rats. Male Wistar albino rats were divided into four groups. Group 1 served as control, group 2 rats received ellagic acid 60 mg/kg bodyweight/every day p.o. throughout the experiment. Rats from groups 3 and 4 were given subcutaneous (s.c.) injections of 1,2-dimethylhydrazine (20 mg/kg body weight) once a week for the first 15 weeks; rats in group 4 received ellagic acid as in group 2 after the last injection of 1,2-dimethylhydrazine and continued till the end of the experimental period of 30 weeks. 1,2-dimethylhydrazine-induced rats exhibited alterations in cancer tumour markers [5,-nucleotidase (5,-ND), gamma glutamyl transpeptidase (,-GT), carcinoembryonic antigen (CEA), alphafetoprotein (AFP) and cathepsin-D (CD)]; pathophysiological markers [alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)] and oral administration of ellagic acid restored the levels of these marker enzymes. Nuclear factor-kappa B (NF-,B) actively involved in the regulation of both pro-inflammatory proteins [inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)] and pro-inflammatory cytokines [tumour necrosis factor (TNF)-, and interleukin (IL)-6] and in our study 1,2-dimethylhydrazine-induced group exhibited elevated expressions of all these inflammatory proteins. Ellagic acid administration reduced the expressions of NF-,B, COX-2, iNOS, TNF-, and IL-6 as confirmed by immunohistochemical, immunoblot and immunofluorescence analysis during 1,2-dimethylhydrazine-induced colon carcinogenesis. In conclusion, ellagic acid demonstrates anti-inflammatory property by iNOS, COX-2, TNF-, and IL-6 down-regulation due to inhibition of NF-,B and exerts its chemopreventive effect on colon carcinogenesis. [source] Inhibitory Effects of Silibinin on Cytochrome P-450 Enzymes in Human Liver MicrosomesBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2000Svane Beckmann-Knopp Silibinin, the main constituent of silymarin, a flavonoid drug from silybum marianum used in liver disease, was tested for inhibition of human cytochrome P-450 enzymes. Metabolic activities were determined in liver microsomes from two donors using selective substrates. With each substrate, incubations were carried out with and without silibinin (concentrations 3.7,300 ,M) at 37° in 0.1 M KH2PO4 buffer containing up to 3% DMSO. Metabolite concentrations were determined by HPLC or direct spectroscopy. First, silibinin IC50 values were determined for each substrate at respective KM concentrations. Silibinin had little effect (IC50>200 ,M) on the metabolism of erythromycin (CYP3A4), chlorzoxazone (CYP2E1), S(+)-mephenytoin (CYP2C19), caffeine (CYP1A2) or coumarin (CYP2A6). A moderate effect was observed for high affinity dextromethorphan metabolism (CYP2D6) in one of the microsomes samples tested only (IC50=173 ,M). Clear inhibition was found for denitronifedipine oxidation (CYP3A4; IC50=29 ,M and 46 ,M) and S(,)-warfarin 7-hydroxylation (CYP2C9; IC50=43 ,M and 45 ,M). When additional substrate concentrations were tested to assess enzyme kinetics, silibinin was a potent competitive inhibitor of dextromethorphan metabolism at the low affinity site, which is not CYP2D6 (Ki,c=2.3 ,M and 2.4 ,M). Inhibition was competitive for S(,)-warfarin 7-hydroxylation (Ki,c=18 ,M and 19 ,M) and mainly non-competitive for denitronifedipine oxidation (Ki,n=9 ,M and 12 ,M). With therapeutic silibinin peak plasma concentrations of 0.6 ,M and biliary concentrations up to 200 ,M, metabolic interactions with xenobiotics metabolised by CYP3A4 or CYP2C9 cannot be excluded. [source] ChemInform Abstract: Synthesis of 3-Substituted Isocoumarins and Their Inhibitory Effects on Degranulation of RBL-2H3 Cells Induced by Antigen.CHEMINFORM, Issue 9 2009Ai Kurume Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Inhibitory Effects Of Angiotensin Ii On Barosensitive Rostral Ventrolateral Medulla Neurons Of The RatCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2001Delphine Bertram SUMMARY 1. The brain renin,angiotensin system can influence arterial baroreceptor reflex control of blood pressure (BP) through both direct and indirect effects on sympathetic premotor neurons of the rostral ventrolateral medulla (RVLM). The present study examined the direct effect of angiotensin (Ang) II applied by microiontophoresis on the ongoing activity of single RVLM neurons. 2. In 26 urethane-anaesthetized Wistar rats, recordings of single unit activities of barosensitive RVLM neurons were made from one barrel of a six-barrel micropipette assembly. The other five barrels were filled with either L -glutamate, AngII, valsartan (an AT1 receptor antagonist), PD 123177 (an AT2 receptor antagonist) and saline. All drugs were applied by microiontophoresis. 3. Mean BP was 83 ± 3 mmHg. Application of AngII inhibited the ongoing activity of RVLM neurons, identified as barosensitive because their activity was inhibited by a phenylephrine- induced increase in BP, from 12.6 ± 1.5 to 5.4 ± 1.1 Hz (n = 24; P < 0.001). Angiotensin II also inhibited the glutamate-evoked excitation of barosensitive RVLM neurons from 15 ± 3 to 5.8 ± 2.0 Hz (n = 6; P < 0.001). Valsartan significantly increased neuronal activity from 9.5 ± 2.3 to 13.5 ± 3.2 Hz (n = 7, P < 0.01), whereas PD 123177 significantly decreased neuronal activity from 13.5 ± 3.5 to 9.9 ± 2.8 Hz (n = 13; P < 0.01). 4. The results suggest that AngII exerts a tonic inhibitory effect on barosensitive RVLM neurons, which is presumably mediated through AT1 receptor stimulation. [source] Effects of the herbicide hexazinone on nutrient cycling in a low-pH blueberry soilENVIRONMENTAL TOXICOLOGY, Issue 2 2004D. M. Vienneau Abstract The herbicide hexazinone was applied as the commercial formulation Velpar® L at field-rate (FR) concentrations of FR (14.77 ,g ai g,1), FR×5 (73.85 ,g ai g,1), FR×10 (147.70 ,g ai g,1), FR×50 (738.50 ,g ai g,1), and FR×100 (1477.00 ,g ai g,1) to acidic soil, pH 4.12, taken from a lowbush blueberry field. Hexazinone was tested for inhibitory effects on various transformations of the nitrogen cycle and soil respiration. Nitrogen fixation was unaffected by hexazinone levels up to FR×100 following a 4-week incubation period. Ammonification was initially inhibited by all levels of hexazinone, but after 4 weeks, ammonification in all treatment systems was equal to or greater than the control. Nitrification was more sensitive to hexazinone; however, application at a field-rate level caused no inhibition. Inhibitory effects were noted above FR after a 2-month endpoint analysis and above FR×5 after a 6-month endpoint analysis. Hexazinone concentrations up to and including FR×100 stimulated denitrification. Soil respiration was also stimulated over a 3-week period when applied at a level up to 100 times the recommended field rate. In general, it was found that when applied at the recommended field application rate, hexazinone does not adversely affect the nitrogen cycle or soil respiration in acidic lowbush blueberry soils. © 2004 Wiley Periodicals, Inc. Environ Toxicol 19: 115,122, 2004 [source] Inhibitory effects of gallic acid ester derivatives on Saccharomyces cerevisiae multidrug resistance protein Pdr5pFEMS YEAST RESEARCH, Issue 3 2010Luciana Pereira Rangel Abstract Overexpression of the Saccharomyces cerevisiae ABC transporter Pdr5p confers resistance to a range of structurally unrelated xenobiotics. This property allows Pdr5p to be used as a target for novel multidrug resistance reversal reagents or chemosensitizers. Herein, we report the effects of gallic acid derivatives with substitutions either on the ester moiety or in the benzene ring on the activity of Pdr5p. Compounds with a longer side chain (8,16 carbons) resulted in greater inhibition of Pdr5p ATPase. Derivatives with side chains of 8,12 carbons that retained hydroxyl groups on the benzene ring extensively inhibited Pdr5p ATPase activity. These compounds almost completely inhibited the efflux of the Pdr5p fluorescent substrate Rhodamine 6G and at 25 ,M chemosensitized the Pdr5p-overexpressing strain AD124567 to fluconazole (0.4 mg mL,1). Gallic acid derivatives may be a new class of Pdr5p inhibitors. [source] Advanced oxidation protein products inhibit differentiation and activate inflammation in 3T3-L1 preadipocytes,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2010Qiu Gen Zhou Accumulation of advanced oxidation protein products (AOPPs) is prevalent in metabolic syndromes, a condition with impaired preadipocytes differentiation. In the present study, we tested the hypothesis that AOPPs disturb preadipocyte differentiation. Exposure of 3T3-L1 preadipocytes to increased levels of AOPPs inhibited accumulation of intracellular triglyceride and decreased the expression of the essential markers of matured adipocytes, such as adipocyte fatty-acid-binding protein (aP2), CAAT/enhancer-binding protein (C/EBP)-,, and peroxisome proliferator-activated receptor (PPAR)-,, in response to standard adipogenic induction. Inhibitory effects of AOPPs on preadipocytes differentiation was time sensitive, which occurred at the early stage of differentiation. In the presence of AOPPs, induction of preadipocytes differentiation resulted in upregulated expression of C/EBP homologous protein (CHOP) and CUG-Triplet repeat-binding protein (CUGBP), two important inhibitors of preadipocytes differentiation. In addition, treatment with AOPPs increased abundance of C/EBP-,-liver enriched inhibitory protein (C/EBP-,-LIP), a truncated C/EBP-, isoform without adipogenic activity. Moreover, AOPPs-treated preadipocytes expressed a macrophage marker F4/80 and overexpressed tumor necrosis factor-, and interleukin-6 via nuclear factor-,B (NF-,B)-dependent pathway. However, blocking inflammation with NF-,B inhibitor failed to improve AOPPs-induced inhibition of preadipocytes differentiation. These data suggest that accumulation of AOPPs may inhibit differentiation of preadipocytes and activate inflammation in these cells. This information might have implication for understanding the impairment of preadipocytes differentiation and fat inflammation seen in metabolic syndrome. J. Cell. Physiol. 225: 42,51, 2010. © 2010 Wiley-Liss, Inc. [source] Inhibitory effects of Cu, Zn, Ni and Co on nitrification and relevance of speciationJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 4 2010Ferhan Çeçen Abstract BACKGROUND: The speciation of metals is often overlooked in understanding their observed inhibitory effect in biological systems, in particular in nitrification systems. This study examines the effects of Cu, Zn, Ni and Co on a nitrifying sludge, where the aim is to relate inhibition to speciation. RESULTS: Nitrification inhibition was monitored by O2 and CO2 measurements, an approach rarely followed to date. The IC50 value of each metal was expressed in terms of total, free and labile metal. Zn and Cu formed similar species, but had different free and labile fractions. Although free and labile fractions of Cu were much lower than the others, it was the most inhibitory metal. Ni and Co exhibited quite different inhibitory effects on nitrification despite the formation of similar metal species. Co was the least inhibitory metal and exhibited its effect very slowly. CONCLUSION: The study is among the few which examine inhibition and speciation of several metals in a comparative way. In the same nitrification medium each metal formed different species, which is a factor to be considered in interpretation of inhibition. The results may be projected to nitrifying systems to clarify the underlying factors in inhibition. Copyright © 2009 Society of Chemical Industry [source] Effect of inhibitory compounds on the anaerobic digestion performance of diluted wastewaters from the alimentary industryJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 11 2009Rafael Camarillo Abstract BACKGROUND: Up to now the effect of inhibitory compounds on the anaerobic digestion performance of urban and industrial wastewaters has been mostly studied in fluidized bed and upflowing anaerobic sludge blanket (UASB) bioreactors but not in upflow packed-bed biodigesters. RESULTS: In this paper, response surface methodology (RSM) was used to quantify the effect of various inhibitory compounds (olive oil, ethanol and phenol) on chemical oxygen demand (COD) removal and biogas production rate from synthetic solutions and real industrial wastewaters by anaerobic digestion. The synthetic solutions possessed the same composition in these inhibitory compounds as diluted effluents from olive oil mill and winery industries. The process was performed in a laboratory scale digester containing anaerobic sludge from the Urban Reclamation Station of Toledo (Spain). The comparison of both individual factors and interactions between factors showed that the addition of olive oil at moderate concentrations (up to 0.5% w/w) did not change the performance of the process in comparison with that observed when feeding to the system a model solution (51.5% COD removal, 0.65 L biogas day,1). However, low concentrations of ethanol or phenol (250 and 150 mg L,1, respectively) almost completely inhibited the methanogenic phase. Moreover, a strong interaction between ethanol and phenol concentrations on COD removal was observed. CONCLUSION: The experimental results showed quantitatively the importance of some inhibitory compounds on anaerobic treatment of both synthetic solutions and real wastewaters from olive oil mill and winery industries. Inhibitory effects are closely related to both the organic loads and the anaerobic bioreactor used. Copyright © 2009 Society of Chemical Industry [source] Inhibitory effects of aspirin and indometacin on the growth of Helicobacter pylori in vitroJOURNAL OF DIGESTIVE DISEASES, Issue 4 2002Wei Hong WANG OBJECTIVE: The interactions between non-steroidal anti-inflammatory drugs and Helicobacter pylori have not been sufficiently documented to date. The aim of this study was to investigate the possible effects of aspirin and indometacin on the growth of H. pylori and to determine the effects of aspirin on the susceptibility of H. pylori to some antimicrobials. METHODS: Kinetic studies were performed by inoculating strains of H. pylori in brucella broth with different concentrations of aspirin and indometacin. Growth of bacteria in the broth was assessed spectrophotometrically and by viable colony counts after incubation for 24 and 48 h. Bacterial morphology was determined by Gram stain under light microscopy. The minimal inhibitory concentration (MIC) of aspirin and indometacin was determined by the standard agar dilution method. The MIC of amoxicillin, clarithromycin and metronidazole was measured in the presence and absence of aspirin by the E -test method. RESULTS: Kinetic studies revealed that aspirin and indometacin inhibited the growth of H. pylori in a dose-dependent manner. The bactericidal activity of these agents was expressed by cell lysis. Aspirin at 400 µg/mL produced an almost 2-log decrease in the number of CFU/mL at 48 h. Similar inhibitory effects were obtained when 100 µg/mL indometacin was tested. The MIC at which 90% of H. pylori was inhibited was 512 µg/mL and 128 µg/mL for aspirin and indometacin, respectively. Increased susceptibility of H. pylori to amoxicillin, clarithromycin and metronidazole was found in the presence of aspirin. CONCLUSIONS: Aspirin and indometacin could significantly inhibit the growth of H. pylori when incubated in brucella broth in vitro. A subinhibitory concentration of aspirin enhanced the susceptibility of H. pylori to some antimicrobial agents. [source] Inhibitory effects of a monoclonal antibody (MAb-001) on in vitro oxygen consumption and multiplication of the pathogenic haemoflagellate, Cryptobia salmositica KatzJOURNAL OF FISH DISEASES, Issue 7 2001N Hontzeas A monoclonal antibody (MAb-001), against a surface glycoprotein on Cryptobia salmositica inhibited the multiplication and oxygen consumption of both virulent and avirulent strains of the parasite. The classical cysteine proteinase inhibitor (E-64) and a cysteine proteinase activator (EDTA) affected the in vitro multiplication of C. salmositica. Concentrations of E-64 higher than 10 ,M reduced the multiplication of C. salmositica while 5 mM of EDTA enhanced its multiplication. We propose that the cysteine proteinase is an important metabolic enzyme in C. salmositica and that binding of MAb-001 to the enzyme inhibited parasite multiplication and reduced oxygen consumption. [source] Inhibitory effects of N -acetylcysteine on scavenger receptor class A expression in human macrophagesJOURNAL OF INTERNAL MEDICINE, Issue 5 2002L. SVENSSON Abstract.,Svensson L, Norén K, Wiklund O, Lindmark H, Ohlsson B, Mattsson Hultén L (Wallenberg Laboratory for Cardiovascular Research, The Sahlgrenska Academy at Göteborg University, Göteborg; and AstraZeneca, Mölndal, Sweden). Inhibitory effects of N -acetylcysteine on scavenger receptor class A expression in human macrophages. J Intern Med 2002; 251:. Objective.,The formation of foam cells from monocyte-derived macrophages involves the uptake of modified lipoproteins by scavenger receptors. Antioxidants inhibit lipoprotein oxidation and may also modulate gene expression. We investigated the effect of the antioxidant N -acetylcysteine on the expression of the class A scavenger receptor (SR-A) types I and II in human macrophages. Design.,Monocytes and macrophages from healthy blood donors and plaque-derived macrophages from patients undergoing carotid endartherectomy were used for experiments. SR-A mRNA was analysed with quantitative and semiquantitative reverse transcription-polymerase chain reaction, and ligand binding and uptake were assessed with 125I-labelled acetylated low-density lipoprotein (LDL). Results.,Incubation of monocytes and monocyte-derived macrophages with N -acetylcysteine decreased both SR-A I and II mRNA expression. N -Acetylcysteine also reduced SR-A mRNA in lesion-derived cells. Binding and uptake of 125I-acetylated LDL was decreased after brief incubation with N -acetylcysteine. After longer periods of incubation with N -acetylcysteine we observed an increased degradation of lipoproteins. Conclusions.,Our results imply that N -acetylcysteine leads to a decrease in SR-A mRNA and initially also to an attenuated uptake of modified lipoproteins. This adds more to the knowledge about the cellular actions of this drug. [source] Inhibitory effects of a new bisphosphonate, minodronate, on proliferation and invasion of a variety of malignant bone tumor cellsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2006Tadahiko Kubo Abstract Little is known about the biological effects of bisphosphonates on primary malignant bone tumors. The purpose of this study was to investigate the antitumor effects of newly developed minodronate (MIN) on a variety of human malignant bone tumors. We examined the effects of MIN and clinically relevant incadronate (INC) on the proliferation, apoptosis, and cell cycle of two osteosarcoma (Saos-2, MG-63), two chondrosarcoma (SW1353, OUMS27), and two Ewing's sarcoma (RD-ES, SK-ES-1) cell lines. Furthermore, we investigated the anti-invasion effects of MIN on sarcoma cells and the effects of MIN on tumor growth in nude mice. MIN inhibited the viability of all six cell lines in a dose-dependent manner with IC50 values of 2.7 to 5.0 µM, which were significantly lower than those of INC. Importantly, both bisphosphonates affected the viability of normal bone marrow stromal cells much less than sarcoma cells. Both bisphosphonates induced cell cycle perturbation in all sarcoma cells tested and apoptosis in Saos-2 and SW1353 cells, although they failed to induce apoptosis in RD-ES and SK-ES-1 cells. MIN significantly suppressed invasion, even at a low concentration of 1 µM (p,<,0.01). Daily injection of 5 µg of MIN inhibited the growth of SK-ES-1 xenograft sarcoma in nude mice without loss of body weight. These findings suggest that MIN may have a beneficial adjuvant role in the treatment of patients with malignant bone tumors. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1138,1144, 2006 [source] Inhibitory effects of green tea polyphenol (,)-epigallocatechin gallate on the expression of matrix metalloproteinase-9 and on the formation of osteoclastsJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2004Jeong-Ho Yun Background:, Alveolar bone resorption is a characteristic feature of periodontal diseases and involves the removal of both the mineral and organic constituents of the bone matrix, which is caused by either multinucleated osteoclast cells or matrix metalloproteinases (MMPs). The gram-negative bacterium, Porphyromonas gingivalis has been reported to stimulate the activity and expression of several groups of MMPs, whereas (,)-epigallocatechin gallate (EGCG), the main constituent of green tea polyphenols, has been reported to have inhibitory effects on the activity and expression of MMPs. Objectives:, In the present study, we investigated the effects of the green tea polyphenol, EGCG, on the gene expression of osteoblast-derived MMP-2, -9 and -13, stimulated by P. gingivalis, and on the formation of osteoclasts. Methods:, The effect of EGCG on the gene expression of MMPs was examined by treating mouse calvarial primary osteoblastic cells with EGCG (20 µm) in the presence of sonicated P. gingivalis extracts. The transcription levels of MMP-2, -9 and -13 were assessed by reverse transcription-polymerase chain reaction (RT-PCR). The effect of EGCG on osteoclast formation was confirmed by tartrate-resistant acid phosphatase (TRAP) staining in a co-culture system of mouse bone marrow cells and calvarial primary osteoblastic cells. Results:, Treatment with the sonicated P. gingivalis extracts stimulated the expression of MMP-9 mRNA and this effect was significantly reduced by EGCG, whereas the transcription levels of MMP-2 and MMP-13 were not affected by either the sonicated P. gingivalis extracts or EGCG. In addition, EGCG significantly inhibited osteoclast formation in the co-culture system at a concentration of 20 µm. Conclusions:, These findings suggest that EGCG may prevent the alveolar bone resorption that occurs in periodontal diseases by inhibiting the expression of MMP-9 in osteoblasts and the formation of osteoclasts. [source] Inhibitory effects of 5-chloroacetyl-2-piperidino-1,3-selenazole, a novel selenium-containing compound, on skin melanin biosynthesisJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2010Eunjoo H. Lee Abstract Objectives Increased production and accumulation of melanin leads to many hyperpigmentation disorders such as melasma, freckles and geriatric pigment spots. Thus, there is a need for the development of depigmenting agents. Based on our previous reports, selenium derivatives as anti-melanogenic lead compounds could be very important. The aim of this study was to investigate the depigmenting effect of novel selenium-containing compounds. Methods The inhibitory effects of 5-chloroacetyl-2-piperidino-1,3-selenazole (CS1), a novel selenium-containing compound, on melanogenesis were investigated in B16F10 melanoma cells and cultured brownish guinea pig skin tissue with ,-melanocyte-stimulating hormone stimulation. Key findings We found that CS1 inhibited melanin production in B16F10 cells by suppressing tyrosinase activity and its protein expression. In addition, Western blotting analysis revealed that CS1 suppressed the expression of tyrosinase-related protein (TRP)-1 and TRP-2. Therefore, the depigmenting effect of CS1 might have been due to inhibition of tyrosinase activity and expression of melanogenic enzymes. Furthermore, CS1 had inhibitory effects on melanin biosynthesis of primary cultured skin of brownish guinea pig. Conclusions The results suggested that CS1 could be a useful candidate for the treatment of skin hyperpigmentation. [source] Inhibitory effects of 1,3-thiazine derivatives on melanogenesisJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2009Sang Keun Ha Abstract Objectives The aim of this study was to identify a novel skin-depigmenting agent from synthetic 1,3-thiazine derivatives. Methods We investigated the inhibitory effects of six kinds of 1,3-thiazine derivative on melanogenesis by examining their effects on tyrosinase activity and melanin biosynthesis in melan-a cells and the zebrafish model. Key findings Of the six compounds, 4-hydroxy-2,6-dimethyl-5,6-dihydro-4H -1,3-thiazine (TZ-6) had the strongest anti-melanogenic effects in cultured melan-a cells (30.4% inhibition at 100 ,M). In addition, TZ-6 exhibited an inhibitory effect on mushroom and cellular tyrosinase. Based on the results of Western blotting, TZ-6 reduced the expression of tyrosinase at 100 mM. Additionally, TZ-6 reduced body pigmentation and inhibited tyrosinase activity in the zebrafish model. Conclusions The results have provided useful information for the development of a skin whitening agent. [source] Environmental Modulation of Alcohol Intake in Hamsters: Effects of Wheel Running and Constant Light ExposureALCOHOLISM, Issue 9 2010Steven B. Hammer Background:, Alcohol abuse leads to marked disruptions of circadian rhythms, and these disturbances in themselves can increase the drive to drink. Circadian clock timing is regulated by light, as well as by nonphotic influences such as food, social interactions, and wheel running. We previously reported that alcohol markedly disrupts photic and nonphotic modes of circadian rhythm regulation in Syrian hamsters. As an extension of this work, we characterize the hedonic interrelationship between wheel running and ethanol (EtOH) intake and the effects of environmental circadian disruption (long-term exposure to constant light [LL]) on the drive to drink. Methods:, First, we tested the effect of wheel running on chronic free-choice consumption of a 20% (v/v) EtOH solution and water. Second, the effect of this alcohol drinking on wheel running in alcohol-naive animals was investigated. Third, we assessed the influence of LL, known to suppress locomotor activity and cause circadian rhythm disruption, on EtOH consumption and wheel-running behavior. Results:, Inhibitory effects of wheel running on EtOH intake and vice versa were observed. Exposure to LL, while not affecting EtOH intake, induced rhythm splitting in 75% of the animals. Notably, the splitting phenotype was associated with lower levels of EtOH consumption and preference prior to, and throughout, the period of LL exposure. Conclusions:, These results are evidence that exercise may offer an efficacious clinical approach to reducing EtOH intake. Also, predisposition for light-induced (or other) forms of circadian disruption may modulate the drive to drink. [source] Inhibitory effects of urinary metabolites on platelet aggregation after orally administering Shimotsu-To, a traditional Chinese medicine, to ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2003Takaaki Yasuda ABSTRACT Shimotsu-To, which consists of four herbal extracts, has been used clinically for improving abnormal blood coagulation, fibrinolysis, atherosclerosis and chronic inflammation in Japan and China. We have investigated the pharmacological relationship between the effects and chemical components of Shimotsu-To after oral administration to rats. The urinary constituents were separated and identified by three dimensional (3D-) HPLC equipped with a photodiode array detector as a new tool and the chemical structures were determined by spectroscopic methods to be trans -ferulic acid-3- O -sulfate (1), vanillic acid (2), m -hydroxyphenylpropionic acid (3), trans -ferulic acid (4) and cis -ferulic acid (5). Of these compounds, 2,5 strongly inhibited platelet aggregation induced by ADP and arachidonic acid. Compound 1, the sulfate conjugate of 4, did not show any inhibitory effect, which suggested that the inhibitory effect on platelet aggregation was inactivated by sulfate conjugation. These results indicated that compounds 2,5 partly contributed to the anti-Oketsu effect of Shimotsu-To through the inhibition of platelet aggregation. [source] Inhibitory effects of Hibiscus sabdariffa L extract on low-density lipoprotein oxidation and anti-hyperlipidemia in fructose-fed and cholesterol-fed ratsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 15 2004Chang-Che Chen Abstract Hibiscus sabdariffa L extract (HSE) is an aqueous extract of Hibiscus sabdariffa L flowers that is used as a local soft drink and medical herb in Taiwan. Oxidation of low-density lipoprotein (LDL) has been shown to increase the incidence of atherosclerosis. In this study, we determined the antioxidative activity of HSE on LDL oxidation by examining relative electrophoretic mobilities (REM) and thiobarbituric acid-reactive substances (TBARS). The data revealed an inhibitory effect of HSE on Cu2+ -mediated REM and TBARS. HSE exhibited a remarkable ability to reduce cholesterol degradation and ApoB fragmentation. Overall, HSE showed a high potency to inhibit the production of oxidized LDL induced by copper and, specifically, to reduce serum triglycerides in high-fructose diet (HFD) fed rats and serum cholesterol in high-cholesterol diet (HCD) fed animals. The levels of LDL and the ratio of LDL-cholesterol (LDL-C) to HDL-cholesterol (HDL-C) were reduced by HSE in both hyperlipidaemia models. Based on these findings, we suggest that HSE may be used to inhibit LDL oxidation and to prevent various types of hyperlipidaemia in HFD- or HCD-fed rats. Copyright © 2004 Society of Chemical Industry [source] Inhibitory effects of desflurane and sevoflurane on oxytocin-induced contractions of isolated pregnant human myometriumACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2005K. Yildiz Background:, In this study, we investigated the inhibitory effects of desflurane and sevoflurane on oxytocin-induced contractions of isolated human myometrium. Methods:, Following delivery of the infant and placenta, a small segment of myometrium was excised from the upper incisional surface of the lower uterine segment and 20 strips, randomly assigned into two groups (n = 10), were obtained from 20 non-laboring term parturients. The study protocol consisted of a 60-min period of spontaneous contractions, control recording with oxytocin 2 × 109 m (10-min period), washout interval of 10 min, volatile administration (three times per 15-min period) of 0.5, 1 and 2 minimum alveolar concentration (MAC), response to oxytocin (10-min period), a further washout interval (10-min period) and subsequent control recording with oxytocin without anesthetics. Results:, After oxytocin administration, the frequency and amplitude of contractions increased (P < 0.05) and the duration decreased (P < 0.05). The frequency and amplitude of contractions induced with oxytocin decreased significantly at 0.5, 1 and 2 MAC of desflurane and sevoflurane (P < 0.05). The amplitude of contractions was significantly different at 1 MAC between the two groups (P < 0.05). The duration of contractions at 2 MAC decreased in both groups (P < 0.05). Conclusions:, Desflurane and sevoflurane at 0.5, 1 and 2 MAC inhibit the frequency and amplitude of myometrial contractions induced with oxytocin in a dose-dependent manner. However, desflurane inhibits the amplitude less than sevoflurane at 1 MAC. We suggest that 0.5 MAC of both agents and 1 MAC of desflurane may be safely used in the presence of oxytocin following delivery of the infant and placenta during Cesarean section without fear of uterine atony and hemorrhage. [source] Inhibitory effects of soluble MD-2 and soluble CD14 on bacterial growthMICROBIOLOGY AND IMMUNOLOGY, Issue 2 2010Takahiro Ohnishi ABSTRACT The effects of the soluble forms of the endotoxin receptor molecules sMD-2 and sCD14 on bacterial growth were studied. When Escherichia coli and Bacillus subtilis were incubated at 37°C for 18 hr with either sMD-2 or sCD14, growth of these bacteria was significantly inhibited as evaluated by viable cell counts and NADPH/NADH activity. A mutant of sCD14 (sCD14d57-64) lacking a region essential for LPS binding did not inhibit the growth of E. coli, whereas this mutant did inhibit the growth of B. subtilis. Addition of excess PG to the bacterial culture reversed the inhibitory effect of sMD-2 on the growth of B. subtilis, but not on the growth of E. coli. Furthermore, when evaluated by ELISA, both sMD-2 and sCD14 bound specifically to PG. Taken together, these results indicate that sMD-2 and sCD14 inhibit the growth of both Gram-positive and Gram-negative bacteria and further suggest that binding to PG and LPS is involved in the inhibitory effect of sMD-2 on Gram-positive bacteria and of sCD14 on Gram-negative bacteria, respectively. [source] Cover Picture , Mol.MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 5 2008Nutr. Cancer chemoprevention and hemotherapy: dietary polyphenols and signalling pathways Inhibitory effects of trans-resveratrol analogues on human colon tumoral cells Potential of sphingomyelin as a chemopreventive gent in colon cancer Unsaturated fatty acids liberated from VLDL cause apoptosis in endothelial cells [source] Inhibitory effects of cranberry juice on attachment of oral streptococci and biofilm formationMOLECULAR ORAL MICROBIOLOGY, Issue 3 2004A. Yamanaka Cranberry juice is known to inhibit bacterial adhesion. We examined the inhibitory effect of cranberry juice on the adhesion of oral streptococci strains labeled with [3H]-thymidine to saliva-coated hydroxyapatite beads (s-HA). When the bacterial cells were momentarily exposed to cranberry juice, their adherence to s-HA decreased significantly compared with the control (P < 0.01). Their hydrophobicity also decreased dependently with the concentration of cranberry juice. We also evaluated the inhibitory effect of cranberry juice on biofilm formation. By using a microplate system, we found that the high molecular mass constituents of cranberry juice inhibited the biofilm formation of the tested streptococci. The inhibitory activity was related to the reduction of the hydrophobicity. The present findings suggest that cranberry juice component (s) can inhibit colonization by oral streptococci to the tooth surface and can thus slow development of dental plaque. [source] Expression and localization of the µ-opioid receptor (MOR) in the equine cumulus,oocyte complex and its involvement in the seasonal regulation of oocyte meiotic competence,MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 8 2008Maria Elena Dell'Aquila Abstract The µ-opioid receptor (MOR) was identified in equine oocytes, cumulus and granulosa cells. By RT-PCR, a 441bp fragment was observed. By immunoblotting, a 65 kDa band was detected in samples of winter anestrous whereas in cells recovered in breeding season, two bands, 65 and 50 kDa, were found. The 65 kDa band was significantly more intense in winter anestrous specimens. In samples recovered in the breeding season, this band significantly decreased with the raise of follicle size and was heavier in compact oocytes and cumulus cells. The protein was localized on the oolemma and within the cytoplasm of oocytes and cumulus cells. In vitro oocyte maturation rate (MR), analyzed by confocal microscopy for nuclear chromatin, microfilaments and microtubules, was reduced after the addition of 3,×,10,8 M ,-endorphin in medium without additional hormones. Inhibitory effects of 10,3 M Naloxone in oocytes collected in anestrous and spring transition were observed, both in presence and absence of hormones added to culture medium. Increased MRs were observed in oocytes collected in anestrous and cultured in presence of 10,8 M Naloxone. The exposure to 10,3 M Naloxone induced significant intracellular calcium increases in cumulus cells recovered all over the year. ,-Endorphin 3,×,10,8 M induced significant calcium increases only in cumulus cells recovered in fall transition and anestrous. Naloxone 10,8 M did not induce intracellular calcium modifications. We conclude that the MOR is differentially expressed in equine cumulus,oocyte complexes in the different seasons of the year and plays a role in the seasonal regulation of meiotic competence of equine oocytes. Mol. Reprod. Dev. 75: 1229,1246, 2008. © 2008 Wiley-Liss, Inc. [source] Prostaglandin E1 at clinically relevant concentrations inhibits aggregation of platelets under synergic interaction with endothelial cellsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2002T. Koga Background: The inhibitory effect of prostaglandin E1 (PGE1) on platelet aggregation is considered an important characteristic of this agent. However, the concentration of PGE1 to inhibit aggregation in vitro is higher than those of clinical use (1 ng/ml). To clarify whether PGE1 at clinically relevant concentrations inhibits aggregation under synergic action with endothelial cell-derived factors (nitric oxide and prostacyclin), we evaluated the minimum effective concentration of PGE1 to enhance the anti-aggregating activity of endothelial cells. Methods: Inhibitory effects of PGE1 and/or the incubation buffer from cultured porcine aortic endothelial (PAE) cells on human platelet aggregation induced by 2 µg/ml collagen were examined by turbidimetry. Results: PGE1 concentration-dependently (>3 ng/ml) inhibited aggregation: the incubation buffer from PAE cells stimulated by bradykinin also inhibited aggregation. Bradykinin concentration-dependently increased the anti-aggregating activity of the PAE incubation buffer. The half-maximum effective concentration of bradykinin to inhibit aggregation (95.4±22.3 nM) was significantly decreased to 10.3±2.5 nM by 0.1 ng/ml PGE1 and to 0.9±0.5 nM by 1 ng/ml PGE1, respectively. These indicated that PGE1 (=0.1 ng/ml) inhibits aggregation through synergism with endothelial cells. The synergic effect of PGE1 and the anti-aggregating activity of the PAE cells preincubated with 10 µM indomethacin for 30 min was more potent than that of these cells preincubated with 1 mM NG -nitro-L-arginine methyl ester. This suggested that the interaction of PGE1 with endothelial cell-derived nitric oxide is more powerful than that with endothelial cell-derived prostacyclin. Conclusion: Prostaglandin E1 (=0.1 ng/ml) inhibited platelet aggregation under synergic interaction with endothelial cells. [source] Inhibitory effects of antisense oligonucleotides on the expression of procollagen type III gene in mouse hepatic stellate cells transformed by simian virus 40PATHOLOGY INTERNATIONAL, Issue 12 2000Satoshi Horie The effects of phosphorothioate antisense oligonucleotides (ASO), complementary to the AUG start region, the junctional region of the intron and exon, and to exon of the procollagen type III gene, were investigated in a mouse hepatic stellate cell (HSC) line transformed by the simian virus 40 gene, SV68c-IS cells. ASO were transfected by lipofection. Immunohistochemistry, western and northern blotting showed inhibitory effects on procollagen type III gene expression by ASO that were complementary to the AUG start region and the junctional region of the intron and exon 2. However, ASO complementary to the exon 2 and 3, junctional region of the intron and exon 3, and sense oligonucleotides complementary to each ASO did not show any inhibitory effects. The effects of ASO complementary to the AUG start region were greater than those of ASO complementary to the junctional region. The effects of ASO were transient and a large amount of ASO was required to induce inhibitory effects without lipofection. ASO were effective in inhibiting the expression of the procollagen type III gene in the HSC which is well known to play a critical role in liver fibrosis. [source] | |||||||||||||||||||||||||||||||||||||