Biomedical subjects

S H Tsai

Publications and source records attributed to S H Tsai.

At least 19 recordsLinked to original sources

PubMed2004

Microfluidic flow switching design using volume of fluid model.

In this study, a volume of fluid (VOF) model was employed for microfluidic switch design. The VOF model validity in predicting the interface between fluid streams with different viscosities co-flowing in a microchannel was first verified by experimental observation. It was then extended to microfluidic flow switch design. Two specific flow switches, one with a guided fluid to one of five desired outlet ports, and another with a guided fluid flows into one, two, or three outlet ports equally distributed along the outlet channel of a Y-shaped channel. The flow switching was achieved by controlling the flow rate ratios between tested and buffer fluids. The numerical results showed that the VOF model could successfully predict the flow switching phenomena in these flow switches. The numerical results also showed that the flow rate ratio required for flow switching depends on the viscosity ratio between the tested and buffer fluids. The numerical simulation was verified by experimental study and the agreement was good.

Computer Simulation↗

PubMed2003

Stenotrophomonas maltophilia septicemia with pyomyositis in a chemotherapy-treated patient.

Pyomyositis is a rare complication of chemotherapy. A 35-year-old male patient with myelodysplastic syndrome developed Stenotrophomonas maltophilia bacteremia shortly after chemotherapy, and Stenotrophomonas maltophilia-related pyomyositis was encountered after recovery from neutropenia. He recovered completely after surgical drainage and a protracted course of antibiotic treatment. It is postulated that subclinical myopathy, immunosuppression secondary to the malignancy, or chemotherapeutic drugs may predispose to pyomyositis. Early recognition of this unusual complication in a cancer patient undergoing chemotherapy can prevent further catastrophes.

Adult↗

PubMed2002

A preliminary study on electrically enhanced crossflow microfiltration of CMP (chemical-mechanical polishing) wastewater.

Chemical-mechanical polishing (CMP) is currently one of the main technologies used by wafer plants in the semiconductor industry. Normally, a large amount of de-ionized water should be used to wash out the abrasives adhered to the surface of wafers during the grinding process. Therefore, CMP wastewater not only has a great quantity but also contains very small size of suspended solids. Generally, these suspended solids would not settle. This phenomenon results in a low visibility of CMP wastewater. To solve this problem, a study on electrically enhanced crossflow microfiltration of CMP wastewater was conducted. Normally, the membrane of traditional dead-end filtration is easily blocked by the filter cake resulting in a small flux of filtrate. Therefore, the form of crossflow filtration (CFF) is used to reduce the blocking of the membrane. Furthermore, if CFF is accompanied by an external electric field, the negatively charged suspended solids in wastewater would move toward the positive electrode. Meanwhile, the flux of filtrate would increase. In this investigation, CMP wastewater was obtained from a wafer plant and characterized by various standard methods. Before testing, the CMP wastewater was pre-filtered using a 1.2 microm pore size filter. Then it was operated by a crossflow microfiltration (0.1 microm pore size) system under an appropriate crossflow velocity, filtration pressure, and electric potential. The filtrate was also characterized by various standard methods. Experimental results show that the filtrate has a turbidity of zero value. Thus, the filtrate could be reused for other purposes. However, the suspended solids of the CMP wastewater would be concentrated by this method. Therefore, the recovery of the suspended solids would be worth considering.

Electricity↗

PubMed2001

Suppression of Fas ligand expression on endothelial cells by arsenite through reactive oxygen species.

Chronic exposure to arsenite is associated with vascular disease, such as arteriosclerosis. However, the cellular mechanisms for vascular disease in response to arsenic are not well known. The present study has demonstrated that arsenite not arsenate decreased the Fas ligand (FasL) expression on ECV304 cells through reactive oxygen species. Incubation of ECV304 cells with arsenite decreased the FasL expression and increased the intracellular peroxide levels. In addition, hydrogen peroxide was found to suppress FasL expression in a dose-dependent manner. The antioxidant, N-acetyl-cysteine, blocked the suppression of FasL expression in response to arsenite. These data suggested that arsenite initiates endothelium dysfunction, at least partly, by suppressing the FasL expression through activating reactive oxygen species sensitive endothelial cell signaling.

Acetylcysteine↗

PubMed2001

Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferator-activated receptor-gamma by flavonoids in mouse macrophages.

Peroxisome proliferator-activated receptor (PPAR)gamma transcription factor has been implicated in anti-inflammatory response. Of the compounds tested, apigenin, chrysin, and kaempferol significantly stimulated PPAR gamma transcriptional activity in a transient reporter assay. In addition, these three flavonoids strongly enhanced the inhibition of inducible cyclooxygenase and inducible nitric oxide synthase promoter activities in lipopolysaccharide-activated macrophages which contain the PPAR gamma expression plasmids. However, these three flavonoids exhibited weak PPAR gamma agonist activities in an in vitro competitive binding assay. Limited protease digestion of PPAR gamma suggested these three flavonoids produced a conformational change in PPAR gamma and the conformation differs in the receptor bound to BRL49653 versus these three flavonoids. These results suggested that these three flavonoids might act as allosteric effectors and were able to bind to PPAR gamma and activate it, but its binding site might be different from the natural ligand BRL49653.

Animals↗

PubMed2001

Inhibition of melanoma growth and metastasis by combination with (-)-epigallocatechin-3-gallate and dacarbazine in mice.

(-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, was shown to have cancer chemopreventive activity. In this study, we examined the antimetastatic effects of EGCG or the combination of EGCG and dacarbazine on B16-F3m melanoma cells in vitro and in vivo. First, the antimetastatic potentials of five green tea catechins were examined by soft agar colony formation assay, and the results show that EGCG was more effective than the other catechins in inhibiting soft agar colony formation. Second, EGCG dose-dependently inhibited B16-F3m cell migration and invasion by in vitro Transwell assay. Third, EGCG significantly inhibited the spread of B16-F3m cells on fibronectin, laminin, collagen, and Matrigel in a dose-dependent manner. In addition, EGCG significantly inhibited the tyrosine phosphorylation of focal adhesion kinase (FAK) and the activity of matrix metalloproteinase-9 (MMP-9). In animal experiments, EGCG alone reduced lung metastases in mice bearing B16-F3m melanomas. However, a combination of EGCG and dacarbazine was more effective than EGCG alone in reducing the number of pulmonary metastases and primary tumor growths, and increased the survival rate of melanoma-bearing mice. These results demonstrate that combination treatment with EGCG and dacarbazine strongly inhibits melanoma growth and metastasis, and the action mechanisms of EGCG are associated with the inhibition of cell spreading, cell-extracellular matrix and cell-cell interactions, MMP-9 and FAK activities.

Animals↗

PubMed2001

Alternative activation of extracellular signal-regulated protein kinases in curcumin and arsenite-induced HSP70 gene expression in human colorectal carcinoma cells.

We have investigated the regulation mechanism of chemical stress-induced HSP70 gene expression in human colorectal carcinoma cells (COLO205 and HT29). Our data show that chemical treatments including sodium arsenite and curcumin, induced significant synthesis of HSP70 and its mRNA. The induced HSP70 gene expression appears to be increased at the transcriptional level. The increase in HSP70 gene expression by both chemicals is associated with an increase in HSF binding to HSE and induction of HSF1 di- or trimerization. Phosphorylation and activation of extracellular signal-regulated proteins (ERK1/2) were detected in sodium arsenite-treated COLO205 and HT29 cells, and the free radical scavenger N-acetyl-L-cysteine (NAC) was able to inhibit this ERK1/2 activation and HSP70 gene expression. MAPK blockade by the specific MEK1 inhibitor (PD98059) decreased the ability of sodium arsenite to increase HSP70 gene expression in a dose-dependent manner along with dephosphorylation of ERK1/2 proteins. In contrast to arsenite treatment, activation of ERK1/2 was not detected in curcumin-treated colorectal carcinoma cells, and NAC and PD98059 did not show any inhibitory effect on HSP70 gene expression induced by curcumin. Overexpression of a dominant negative mutant of mitogen-activated protein kinase kinase kinase 1 (MEKK1-DN) prevents arsenite-induced ERK1/2 phosphorylation and HSP70 protein synthesis. These results indicated that the ERK signaling pathway can participate in HSP70 gene expression induced by the prooxidant sodium arsenite, but not by the antioxidant curcumin.

Acetylcysteine↗

PubMed2001

Metallo-beta-lactamases in clinical Pseudomonas isolates in Taiwan and identification of VIM-3, a novel variant of the VIM-2 enzyme.

A total of 209 clinical isolates of Pseudomonas (193 Pseudomonas aeruginosa, 10 P. putida, 4 P. stutzeri, and 2 P. fluorescens isolates) with reduced susceptibilities to imipenem and/or ceftazidime were subjected to PCR assays with primers specific for bla(IMP-1), bla(IMP-2), bla(VIM-1), and bla(VIM-2) and sequence analysis to identify the metallo-beta-lactamases (MBLs) prevalent among these organisms in Taiwan; and 21 isolates gave positive results. Five isolates including two P. putida and three P. stutzeri isolates were found to carry bla(IMP-1), and six isolates including five P. putida and one P. stutzeri isolates harbored bla(VIM-2). The remaining 10 isolates were P. aeruginosa, and all were found to carry a novel variant of bla(VIM-2), designated bla(VIM-3). There are only two nucleotide differences between bla(VIM-2) and bla(VIM-3), leading to two amino acid alterations. Our findings indicate that VIM-2 and its variant have become the most prevalent metalloenzymes in Pseudomonas in Taiwan. Southern hybridization with the bla(VIM-2)-, bla(VIM-3)-, and bla(IMP-1 )-specific probes revealed that only two VIM-2-producing P. putida isolates appeared to carry the MBL gene on plasmids. Pulsed-field gel electrophoresis showed that six VIM-3-producing P. aeruginosa isolates and two IMP-1-producing P. stutzeri isolates were genetically related, suggesting that the spread of these MBL genes in Taiwan could be due to clonal dissemination as well as genetic exchange between different clones.

DNA Primers↗

PubMed2001

Outbreak of infection with multidrug-resistant Klebsiella pneumoniae carrying bla(IMP-8) in a university medical center in Taiwan.

Klebsiella pneumoniae strains with the transferable carbapenem-hydrolyzing metallo-beta-lactamases, which include IMP- and VIM-type enzymes, remain extremely rare. To investigate whether IMP- or VIM-producing K. pneumoniae isolates had spread at a university medical center in Taiwan, a total of 3,458 clinical isolates of K. pneumoniae consecutively collected in 1999 and 2000 were tested by the agar diffusion method, colony hybridization, PCR, and nucleotide sequencing. A total of 40 isolates (1.2%), or 17 nonrepetitive isolates, from 16 patients were found to carry bla(IMP-8), a metallo-beta-lactamase gene recently identified from a K. pneumoniae strain in Taiwan. Carriage of bla(VIM) or other bla(IMP) genes was detected in none of the remaining isolates. Of the 17 nonrepetitive bla(IMP-8)-positive isolates, 15 isolates (88.2%) appeared susceptible to imipenem (MICs, <or=4 microg/ml) and meropenem (MICs, <or=1 microg/ml), indicating the difficulty in detecting bla(IMP-8) in K. pneumoniae by routine susceptibility tests; 14 isolates (82.4%) produced SHV-12 as well; and 14 isolates (82.4%) were also resistant to fluoroquinolones. The organisms caused wound infections in eight patients and bloodstream infections in three patients. They were not directly associated with the death of nine patients. Before the recovery of the bla(IMP-8)-positive isolates, all 16 patients had undergone various surgical procedures, and 15 patients had been admitted to the surgical intensive care unit, suggesting a nosocomial outbreak. Two major patterns were observed by pulsed-field gel electrophoresis for 14 of the 17 nonrepetitive isolates, indicating that the clonal spread was mainly responsible for the outbreak.

Adult↗

PubMed2001

Choroidal masses: a fourteen-year analysis.

BACKGROUND: Choroidal masses present much diversification in clinical features and incidence. The purpose of this study is to investigate the epidemiological and clinicopathological manifestations of different choroidal tumors in order to tabulate appropriate diagnostic approaches. METHODS: A retrospective analysis of patients with choroidal masses was conducted, the analysis being based upon the review of our medical records from January 1986 to December 1999 inclusively. A definite diagnosis of choroidal mass was confirmed by at least two experienced ophthalmologists. For patients who were enrolled in this study, an ophthalmic examination was conducted and medical history was recorded. Some ancillary tests, such as indirect ophthalmoscopy, ultrasonography, fluorescein angiography, computed tomography, and magnetic resonance imaging, were used to support the accuracy of our diagnoses. RESULTS: A total of 149 patients were enrolled in this study, of which 103 cases were excluded due to a loss of follow-up or incomplete medical records. Forty-six patients (51 eyes) included 12 cases (26%) of malignant metastases, 10 cases (22%) of hemangiomas, 2 cases (4%) of osteomas, 5 cases (11%) of melanocytomas, 8 cases (17%) of melanomas, and 9 cases (20%) of other melanocytic lesions. The male to female ratio was 21:25. The average length of follow-up was 20.5 months, and the average age of these patients was 42.8 years. Presenting with varied clinical incidence and pictures, each category of choroidal mass was investigated thoroughly. CONCLUSION: With more clinical experience and a better understanding of choroidal masses, we are able to propose an early differential diagnosis and therapeutic approach to the effective management of them in order to minimize ocular morbidity and improve patients' survival and quality of life.

Adult↗

PubMed2001

Results of 12-year clinical study of giant retinal tear.

BACKGROUND: To evaluate the surgical results of scleral buckling alone on eyes with retinal detachment with giant retinal tears of less than 120 degrees, without inverted flap or proliferative vitreoretinopathy, and vitrectomy combined with scleral buckling with or without intraoperative usage of perfluorocarbon liquid (PFCL) in complicated cases. METHODS: Retrospectively, we reviewed giant retinal tear cases treated at Chang Gung Memorial Hospital, Kaohsiung, Taiwan between January 1, 1989 and August 31,2000. The surgical techniques consisted of standard three-port pars plana vitrectomy combined with scleral buckling in complicated cases, PFCL used intraoperatively in later cases, and scleral buckling alone in minor cases. RESULTS: A total of 47 consecutive eyes with giant retinal tears with retinal detachment in 45 patients with no previous history of ocular penetrating injury or vitreoretinal operations were enrolled in this study. The follow-up period was at least three months for all patients. Thirty-four eyes (72.3%) had giant retinal tears of less than 180 degrees, 12 eyes (25.5%) had tears between 180 degrees and 270 degrees, and one eye had two giant retinal tears. Scleral buckling combined with vitrectomy was performed in 36 complicated eyes (76.6%), PFCL was used intraoperatively later in 24 eyes, and scleral buckling was used alone in 11 minor cases (23.4%). Thirty eyes (63.8%) gained reattachment after the first surgery. Altogether, the retinas of 38 of 47 eyes (80.9%) remained attached at the last follow-up examination. CONCLUSION: In minor cases of giant retinal tear, scleral buckling alone without vitrectomy may be considered the primary surgical procedure. In complicated cases, using PFCL intraoperatively not only affords many advantages during surgery, but also raises the retinal reattachment rate.

Adolescent↗

PubMed2000

Comparison of the MB/BacT and BACTEC MGIT 960 system for recovery of mycobacteria from clinical specimens.

A total of 543 specimens were cultured in parallel with the MB/BacT and BACTEC MGIT 960 systems and on the conventional solid media. Mycobacteria were identified from 95 (17.5%) specimens, including 63 (66.3%) Mycobacterium tuberculosis and 32 (33.7%) nontuberculous mycobacteria. The recovery rates for the MB/BacT, MGIT 960, and solid media were 91.6, 87.4, and 54.7%, respectively, for all mycobacteria; the recovery rates were 93.6, 88.9, and 63.4%, respectively, for M. tuberculosis complex alone, and 87.5, 84.4, and 37.5%, respectively, for all nontuberculous mycobacteria. The mean times to detection of all mycobacteria by individual systems were 13. 9, 8.7, 31.7 days for the MB/BacT, MGIT 960 and solid media, respectively, 13.9, 9.3, 32.9 days for M. tuberculosis alone, and 14. 1, 8.1, 27.2 days for all nontuberculous mycobacteria. The contamination rates of the MB/BacT and MGIT 960 were 10.2 and 5.4%, respectively. With regard to detection times and recovery rates, both automated systems are superior to the conventional media (all p < 0.005). As compared to the MB/BacT, the MGIT 960 detected mycobacterial growth more rapidly (p < 0.001), and had a lower contamination rate (p = 0.003); however, there was no statistically significant difference in recovery rates between these two systems. These results indicate that both MGIT 960 and MB/BacT systems are rapid, sensitive, and efficient methods for the recovery of mycobacteria from clinical specimens.

Humans↗

PubMed2000

Prevalence of SHV-12 among clinical isolates of Klebsiella pneumoniae producing extended-spectrum beta-lactamases and identification of a novel AmpC enzyme (CMY-8) in Southern Taiwan.

Twenty (8.5%) of 234 nonrepetitive clinical isolates of Klebsiella pneumoniae from southern Taiwan were found to produce extended-spectrum beta-lactamases (ESBLs): 10 strains produced SHV-12, 4 produced SHV-5, 2 produced a non-TEM non-SHV ESBL with a pI of 8.3, 3 produced a novel AmpC beta-lactamase designated CMY-8 with a pI of 8.25, and 1 produced SHV-12 and an unidentified AmpC enzyme with a pI of 8.2. The CMY-8 enzyme confers a resistance phenotype similar to CMY-1 and MOX-1, and sequence comparisons showed high homologies (>95%) of nucleotide and amino acid sequences among these three enzymes. Plasmid and pulse-field gel electrophoresis analyses revealed that all isolates harboring an SHV-derived ESBL were genetically unrelated, indicating that dissemination of resistance plasmids is responsible for the spread of SHV ESBLs among K. pneumoniae in this area. All three isolates carrying CMY-8 had identical genotypic patterns, suggesting the presence of an epidemic strain.

Amino Acid Sequence↗

PubMed2000

Dissemination of CTX-M-3 and CMY-2 beta-lactamases among clinical isolates of Escherichia coli in southern Taiwan.

A total of 1,210 clinical isolates of Escherichia coli collected from a university hospital in southern Taiwan were screened for production of extended-spectrum beta-lactamases (ESBLs). Expression of classical ESBLs (resistant to extended-spectrum beta-lactam agents and susceptible to beta-lactam inhibitors) was inferred in 18 isolates by the phenotypic confirmatory test. These included 10 isolates producing CTX-M-3, 2 strains carrying SHV-12, 1 strain harboring SHV-5, 1 strain expressing TEM-10, and 4 strains producing unidentifiable ESBLs with a pI of 8.05, 8.0, or 7.4. Eighteen isolates that showed decreased susceptibilities to ceftazidime and/or cefotaxime, negative results for the confirmatory test, and high-level resistance to cefoxitin (MICs of >/=128 microg/ml) were also investigated. Five isolates were found to produce CMY-2 AmpC enzymes, one isolate carried both CTX-M-3 and CMY-2, and the remaining three and nine isolates expressed putative AmpC beta-lactamases with pIs of >9.0 and 8.9, respectively. Thus, together with the isolate producing CTX-M-3 and CMY-2, 19 (1.6%) isolates produced classical ESBLs. Pulsed-field gel electrophoresis revealed that all isolates carrying CTX-M-3 and/or CMY-2 were genetically unrelated, indicating that dissemination of resistance plasmids was responsible for the spread of these two enzymes among E. coli in this area. Among the 16 isolates expressing CTX-M-3 and/or CMY-2, 5 might have colonized outside the hospital environment. Our data indicate that CTX-M-3 and CMY-2, two beta-lactamases initially identified in Europe, have been disseminated to and are prevalent in Taiwan.

Adult↗

PubMed1999

Suppression of TNFalpha-mediated NFkappaB activity by myricetin and other flavonoids through downregulating the activity of IKK in ECV304 cells.

Flavonoids are a group of naturally-occurring phenolic compounds in the plant kingdom, and many flavonoids are found with vascular protective properties. Nevertheless how the protective response is exerted by flavonoids is not well characterized. In view of the nuclear factor-kappaB (NFkappaB) may play a central role in the initiation of atherosclerosis, prevention of the activation of NFkappaB represents an important role in protecting vascular injury. In this study, the effects of flavonoids on NFkappaB/inhibitor-kappaB (IkappaB) system in ECV304 cells activated with tumor necrosis factor-alpha (TNFalpha) were examined. We investigated the inhibitory action of six flavonoids on IkappaB kinase (IKK) activity, an enzyme recently found to phosphorylate critical serine residues of IkappaB for degradation. Of six flavonoids tested, myricetin was found to strongly inhibit IKK kinase activity, and prevent the degradation of IkappaBalpha and IkappaBbeta in activated endothelial cells. Furthermore, myricetin was also found to inhibit NFkappaB activity correlated with suppression of monocyte adhesion to ECV304 cells. Therefore we conclude that flavonoids may be of therapeutic value for vascular disease through down regulation of NFkappaB/IkappaB system.

Base Sequence↗

PubMed1999

Theaflavin-3,3'-digallate from black tea blocks the nitric oxide synthase by down-regulating the activation of NF-kappaB in macrophages.

Nitric oxide (NO) plays an important role in inflammation and also in multiple stages of carcinogenesis. We investigated the effects of various tea polyphenols, including theaflavin, a mixture of theaflavin-3-gallate and theaflavin-3'-gallate, theaflavin-3,3'-digallate, thearubigin, and (-)-epigallocatechin-3-gallate on the induction of NO synthase in lipopolysaccharide-activated murine macrophages, RAW 264.7 cells. Theaflavin-3,3'-digallate was found to be stronger than (-)-epigallocatechin-3-gallate in inhibiting NO generation and inducible NO synthase protein in activated macrophages, while theaflavin, a mixture of theaflavin-3-gallate and theaflavin-3'-gallate and thearubigin were less effective. Inhibition of NO production was observed when cells were cotreated with theaflavin-3,3'-digallate and lipopolysaccharide. Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses demonstrated that significantly reduced 130-kDa protein and mRNA levels of inducible NO synthase were expressed in lipopolysacchride-activated macrophages with theaflavin-3,3'-digallate, compared to those without theaflavin-3,3'-digallate. Electrophoretic mobility shift assay (EMSA) indicated that theaflavin-3,3'-digallate blocked the activation of nuclear factor kappaB (NF-kappaB), a transcription factor necessary for inducible NO synthase induction. Theaflavin-3,3'-digallate also blocked phosphorylation of IkappaB from cytosolic fraction and reduced lipopolysacchride-induced nuclear accumulation of transcription factor NF-kappaB p65 and p50 subunits. These results suggest that theaflavin-3,3'-digallate decreases the protein levels of inducible NO synthase by reducing the expression of inducible NO synthase mRNA, and the reduction could be via preventing the activation of NF-kappaB, thereby inhibiting the induction of inducible NO synthase transcription. It was also demonstrated that the gallic acid moiety of theaflavin-3,3'-digallate is essential for their potent anti-inflammation activity.

Animals↗

PubMed1999

Elevation of apoptotic potential by anoxia hyperoxia shift in NIH3T3 cells.

Apoptosis has been hypothesized to be mediated through the induction of free radicals via oxidative pathway. In this study, we demonstrated the induction of cellular apoptosis by anoxia-hyperoxia shift, but not by anoxia or hyperoxia alone in NIH3T3 cells. The decrement of ROS by anoxia thus appears to be an essential early event leading to apoptosis. G1 arrest was detected in anoxia-treated cells, and postanoxic oxygen recovery could reverse this effect, and induce apoptosis. On analysis of the binding activity of AP-1, we found biphasic induction of binding ability in cells undergoing anoxia-hyperoxia shift. In the early stage of anoxia, a transitional increase of AP-1 binding activity was detected, which was reduced to the minimal levels after 24 h of anoxia. During the period of postanoxic hyperoxia treatment, the binding activity of AP-1 was reinduced and increased remarkably with time up to 24 h. These results were in accordance with the expressions of c-jun and c-fos proteins. Enhancement of poly(ADP-ribosyl)ation activities, especially ADP-ribosylation of histone H1 was detected in post-anoxic hyperoxia-treated cells, and cleavage of PARP and activation of caspase 3 were also observed in post-anoxic hyperoxia (recovery) treated cells, but not in anoxia-treated cells. We propose that the differential induction of c-jun/c-fos (AP-1) gene expressions and sequential activation of PARP activity are essential in anoxia/hyperoxia-induced apoptosis.

3T3 Cells↗

PubMed1999

Suppression of nitric oxide synthase and the down-regulation of the activation of NFkappaB in macrophages by resveratrol.

Resveratrol, naringenin and naringin are naturally occurring flavonoids in grapes and grapefruits. The anti-inflammatory effects of these flavonoids have been well documented, but the mechanism is poorly characterized. High concentration of NO are produced by inducible NO synthase (iNOS) in inflammation, and the prevention of the expression of iNOS may be an important anti-inflammatory mechanism. In this study, the effects of these flavonoids on the induction of NO synthase (NOS) in RAW 264.7 cells activated with bacterial lipopolysaccharide (LPS, 50 ng ml(-1)) were investigated. Resveratrol was found strongly to inhibit NO generation in activated macrophages, as measured by the amount of nitrite released into the culture medium, and resveratrol strongly reduced the amount of cytosolic iNOS protein and steady state mRNA levels. However, the inhibitory abilities of naringenin were lower, and the inhibitory abilities of naringin were almost negligible. In electrophoretic mobility shift assays, the activation of NFkappaB induced by LPS for 1 h was inhibited by resveratrol (30 microM). Furthermore, in immunoblotting analysis, cells treated with LPS plus resveratrol showed an inhibition of phosphorylation as well as degradation of IkappaBalpha, and a reduced nuclear content of NFkappaB subunits. The flavonoids may be of value for inhibiting the enhanced expression of iNOS in inflammation through down-regulation of NFkappaB binding activity.

Animals↗