Biomedical subjects

T W Wu

Publications and source records attributed to T W Wu.

At least 19 recordsLinked to original sources

PubMed2002

A direct mixed-body boundary element method for packed silencers.

Bulk-reacting sound absorbing materials are often used in packed silencers to reduce broadband noise. A bulk-reacting material is characterized by a complex mean density and a complex speed of sound. These two material properties can be measured by the two-cavity method or calculated by empirical formulas. Modeling the entire silencer domain with a bulk-reacting lining will involve two different acoustic media, air and the bulk-reacting material. Traditionally, the interior silencer domain is divided into different zones and a multi-domain boundary element method (BEM) may be applied to solve the problem. However, defining different zones and matching the elements along each interface is tedious, especially when the zones are intricately connected. In this paper, a direct mixed-body boundary element method is used to model a packed silencer without subdividing it into different zones. This is achieved by summing up all the integral equations in different zones and then adding the hypersingular integral equations at interfaces. Several test cases, including a packed expansion chamber with and without an absorbing center bullet, and a parallel baffle silencer, are studied. Numerical results for the prediction of transmission loss (TL) are compared to experimental data.

Journal Article↗

PubMed2000

MCI-186: further histochemical and biochemical evidence of neuroprotection.

The bioactivity of 3-methyl-1-phenyl-pyrazolin-5-one (MCI-186) was examined based on histochemical changes in drastic global ischemic rat brains. Rats with mean arterial blood pressure reduction were subjected to 60 min cerebral ischemia/80 min reperfusion. Infusion of MCI-186 at 3.0 mg/Kg reduced brain infarction from 21 +/- 4% (saline control, n= 15) to 11 +/- 3% (n=16, p<0.05). By comparison, infusion of up to 20 mg/Kg propyl galalate (PG)--a well documented antioxidant--produced an infarct percentage of 14 +/- 5% (n=8), close to the saline control. Biochemically, the neuroprotective effect of MCI-186 was demonstrated by diminishing the release of creatine kinase (CK) in serum from 3363 +/- 608 U/L (n=14) in saline control to 1989 +/- 293 U/L (n= 15) in MCI group (p<0.05), while PG did not lower the activity of CK significantly. MCI-186 behaves as a free radical scavenger by suppressing the formation of superoxide anion in xanthine oxidase (XO)-hypoxanthine (HP) system (p<0.05). Our data supported our contention that MCI-186 has potent anti-stroke effect with antioxidant activities.

Animals↗

PubMed2000

Morin hydrate: a potential antioxidant in minimizing the free-radicals-mediated damage to cardiovascular cells by anti-tumor drugs.

The co-incubation of morin hydrate with either doxorubicin or mitomycin C could minimize the toxicity of these anti-tumor drugs on cardiovascular cells, such as red blood cells, human umbilical vein endothelial cells (ECV304) and primary mouse cardiomyocytes, whereas morin hydrate did not lower the cytotoxicity of the drugs on human hepatocellular carcinoma cells (HepG2). Morin hydrate may not exert its antioxidant effect by enhancing the antioxidant enzymatic activity because it did not cause any induction on the mRNA levels of manganese superoxide dismutase expression in ECV304 cells and HepG2 cells.

Animals↗

PubMed1999

CpABC, a Cryptosporidium parvum ATP-binding cassette protein at the host-parasite boundary in intracellular stages.

The intracellular parasite Cryptosporidium parvum develops inside a vacuole at the apex of its epithelial host cell. The developing parasite is separated from the host cell cytoplasm by a zone of attachment that consists of an extensively folded membranous structure known as the feeder organelle. It has been proposed that the feeder organelle is the site of regulation of transport of nutrients and drugs into the parasite. In this report, we localize an approximately 200-kDa integral membrane protein, CpABC, from Cryptosporidium parvum to the host-parasite boundary, possibly the feeder organelle. The predicted amino acid sequence of CpABC has significant structural similarity with the cystic fibrosis conductance regulator and the multidrug resistance protein subfamily of ATP-binding cassette proteins. This is an example of a parasite-encoded transport protein localized at the parasite-host interface of an intracellular protozoan.

ATP-Binding Cassette Transporters↗

PubMed1999

Targeting of aminopeptidase N to bile canaliculi correlates with secretory activities of the developing canalicular domain.

We have used human hepatoma cell lines as an in vitro model to study the development of hepatic bile canaliculi (BC). Well-differentiated hepatoma cells cultured for 72 hours could develop characteristic spheroid structures at sites of cell-cell contact that contained tight junctions and various membrane protein markers, resembling BC found in vivo. Intact cytoskeleton was essential for this differentiation process. In the coculture experiments in which cells of different origins were populated together, BC only formed between hepatic cells and preferentially among well-differentiated cells. Poorly differentiated hepatoma cells never formed BC among themselves, but could be induced to undergo canalicular differentiation by interacting with well-differentiated cells. During BC morphogenesis, integral canalicular membrane proteins were gradually delivered and accumulated at the developing BC. Among them, targeting of aminopeptidase N (APN) seemed to correlate with activation of certain secretory functions. Specifically, only APN-positive BC supported excretion of fluorescein diacetate (FDA) and 70-kd dextran, but had no relationship with secretion of horseradish peroxidase (HRP). Targeting of another BC protein, dipeptidyl peptidase IV (DPPIV), on the other hand, bore no association with any secretory activity examined. In addition, inhibition of enzymatic activity of APN could perturb canalicular differentiation without affecting cell proliferation. Our results suggest that targeting of APN proteins may reflect or even play an important role in the development and functional maturation of the canalicular structures.

Bile Canaliculi↗

PubMed1999

Aortic endothelial cells damaged by a nitric oxide donor and protected by flavonoids.

Cultured porcine aortic endothelial cells (PAEC) were exposed to four concentrations (0.00 mM - 5.00 mM) of 3-Morpholino-sydnonimine-hydrochloride (SIN-1, a nitric oxide donor). SIN-1 demonstrated a dose dependent cytotoxicity against PAEC as indicated by the thiobarbituric acid (TBA) assay. Morphologically and biochemically, the presence of selected flavonoids (morin, quercetin, or catechin) was shown to protect the PAEC from SIN-1 toxicity. Protection levels determined from the TBA assay were significant (p<0.05) for all flavonoids, with morin at 72+/-8%. Quercetin and catechin had comparable protective activities of 54+/-6% and 43+/-3%, respectively. This study supports the contention that SIN-1 is cytotoxic to PAEC and that antioxidants such as flavonoids may attenuate such toxicity.

Animals↗

PubMed1998

Morin hydrate: a better protector than purpurogallin of corneal endothelial cell damage induced by xanthine oxidase and SIN-1.

PURPOSE: Free radicals are responsible for tissue injury in corneal preservation and transplantation. Morin hydrate, a flavonoid from Brazil wood, has been shown to be cytoprotective in several types of cells. The aim of this study was to investigate the effectiveness of morin hydrate on rabbit corneal endothelial cells against damage induced by oxyradicals and nitric oxide. METHODS: Corneal endothelial cell cultures were prepared from New Zealand white rabbits, using standard microcarrier technique. Two free-radical-generating systems were used-17 IU/L xanthine oxidase/1 mM hypoxanthine and 5 mM 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1, a nitric oxide-donating agent). RESULTS: Over 95% of cultured corneal endothelial cells necrosed within 3.6 +/- 1.5 min after exposure to xanthine oxidase/hypoxanthine. Adding morin hydrate delayed cell necrosis to 5.8 +/- 0.3 min (0.25 mM morin hydrate), 13.3 +/- 5.0 min (0.5 mM), and 41.5 +/- 8.6 min (1.0 mM). Exposed to nitric oxide generated by SIN-1, cells necrosed by 9.5 +/- 2.5 min, versus 14.1 +/- 1.3 min (0.25 mM morin hydrate), 27.2 +/- 2.0 min (0.5 mM), and 43.3 +/- 5.4 min (1.0 mM). Morin hydrate significantly prolonged survival of cells compared to equimolar concentrations of purpurogallin, Trolox, or ascorbate (P < 0.01). CONCLUSION: This study demonstrates that morin hydrate behaves as a broad-spectrum antioxidant: it scavenges not only xanthine oxidase/hypoxanthine-generated oxyradicals, but also nonenzymatic, nitrogen-derived radicals, better than those above mentioned antioxidants. This property of morin hydrate may help prevent free radical damage in corneal preservation solutions.

Animals↗

PubMed1998

Cyclosporin analogs inhibit in vitro growth of Cryptosporidium parvum.

Cyclosporine and nonimmunosuppressive cyclosporin (CS) analogs were demonstrated to be potent inhibitors of the growth of the intracellular parasite Cryptosporidium parvum in short-term (48-h) in vitro cultures. Fifty-percent inhibitory concentrations (IC50s) were 0.4 microM for SDZ 033-243, 1.0 microM for SDZ PSC-833, and 1.5 microM for cyclosporine. Two other analogs were less effective than cyclosporine: the IC50 of SDZ 205-549 was 5 microM, and that of SDZ 209-313 was 7 microM. These were much lower than the IC50 of 85 microM of paromomycin, a standard positive control for in vitro drug assays for this parasite. In addition, intracellular growth of excysted sporozoites that had been incubated for 1 h in cyclosporine was significantly reduced, suggesting that the drug can inhibit sporozoite invasion. The cellular activities of the CS analogs used have been characterized for mammalian cells and protozoa. The two analogs that were most active in inhibiting C. parvum, SDZ PSC-833 and SDZ 033-243, bind weakly to cyclophilin, a peptidyl proline isomerase which is the primary target of cyclosporine and CS analogs. However, they are potent modifiers of the activity of the P glycoproteins/ multidrug resistance (MDR) transporters, members of the ATP-binding cassette (ABC) superfamily. Hence, both cyclophilin and some ABC transporters may be targets for this class of drugs, although drugs that preferentially interact with the latter are more potent. Cyclosporine (0.5 microM) had no significant chemosensitizing activity. That is, it did not significantly increase sensitivity to paromomycin, suggesting that an ABC transporter is not critical in the efflux of this drug. Cyclosporine at concentrations up to 50 microM was not toxic to host Caco-2 cells in the CellTiter 96 assay. The results of this study complement those of studies of the inhibitory effect of cyclosporine and CS analogs on other apicomplexan parasites, Plasmodium falciparum, Plasmodium vivax, and Toxoplasma gondii.

Animals↗

PubMed1998

Evidence of Trolox and some gallates as synergistic protectors of erythrocytes against peroxyl radicals.

The peroxidation of human erythrocytes induced by peroxyl radical initiator and its inhibition by several gallate esters (e.g., propyl, methyl, ethyl) and Trolox (a more polar analogue of vitamin E) have been studied. The antioxidant activity was determined on erythrocytes against hemolysis generated by a thermal activator, 2,2'-azobis-(2-amidinopropane)dihydrogenchloride. It was found that propyl gallate and its two analogues were more effective than Trolox in preventing cell lysis. However, the combination of gallate esters and Trolox produced a protective effect exceeding the arithmetic sum of their individual contributions. These perceived synergisms occur at more than one level of Trolox at a given level of a gallate ester.

Antioxidants↗

PubMed1997

Ribosomal RNA gene organization in Cryptosporidium parvum.

The cytoplasmic ribosomal RNA (rRNA) genes of the Apicomplexan protozoan parasite Cryptosporidium parvum have been analyzed with respect to size, copy number, organization and structure. The small and large subunit rRNAs are 1.7 and 3.6 kb, respectively. A 151 bp putative 5.8S rRNA gene was identified. The rDNA unit is 5' small subunit rRNA internal transcribed spacer 1-5.8S rRNA-internal transcribed spacer 2-large subunit rRNA 3'. There are five copies of the rDNA unit per haploid genome and they are not organized in a conventional head to tail tandem array with a conserved external transcribed spacer. The rDNA units are dispersed through the genome to at least three chromosomes. At least two of the rDNA units are single unlinked copies on different chromosomes. There are two structurally distinct types of rDNA unit, Type A and B, with marked differences in the internal transcribed spacer regions. There are four copies of the Type A rDNA unit and one copy of the Type B rDNA unit.

Animals↗

PubMed1997

Comparative protection against oxyradicals by three flavonoids on cultured endothelial cells.

Oxygen-derived free radicals are known to injure the endothelium of aorta in diverse disorders. In this study we compared the cytoprotective effects of three flavonoids against oxyradical damage to porcine aortic endothelial cells in vitro. Cultured porcine aortic endothelial cells were exposed to oxyradicals generated by xanthine oxidase--hypoxanthine (XO-HP). The cytoprotective activities of morin, quercetin, and catechin on these systems were compared using established morphologic criteria. The results in the XO-HP system showed that morin at 0.125, 0.25, and 0.5 mM delayed cell necrosis to 27.4 +/- 1.3, 46.8 +/- 1.8, and longer than 70 min, respectively, compared with 12.0 +/- 1.3 min in the control group. These degrees of protection were significantly stronger than those provided by quercetin and catechin at corresponding concentrations (p < 0.01). Morin and quercetin were moderate inhibitors of xanthine oxidase on the basis of the oxygen consumption rate, whereas catechin at the same concentrations had little inhibitory effect. The data from uric acid formation and cytochrome c reduction were consistent with the oxygen consumption measurement for the three flavonoids.

Animals↗

PubMed1996

Molecular structure and antioxidant specificity of purpurogallin in three types of human cardiovascular cells.

Purpurogallin (PPG) in an active cytoprotector found in certain oak barks. We have shown that PPG prolongs the survival of cultured cardiocytes from rats and rabbits against different oxidants better than do antioxidants such as Trolox (a hydrophilic analogue of vitamin E) in a morphometric assay system. First, we verified by X-ray crystallography that PPG is a bicyclic molecule comprising a phenolic ring fused with a seven-membered ring in a highly planar conformation. In analogues of PPG wherein the two double bonds in the seven membered ring of the parent molecule are saturated or where the four OH groups of the parent compound are substituted by four OCH3 groups, the derivatives are less planar and less protective of the human cells than native PPG. Second, PPG in a concentration-dependent manner protected myocytes and endothelial cells of humans against oxyradicals generated with any one of the following oxyradical generators: (a) xanthine oxidase plus hypoxanthine, (b) menadione, or (c) paraquat. In each case, PPG was more cytoprotective than comparative antioxidants. Also, PPG protected erythrocytes against peroxyl radicals better than the two PPG derivatives mentioned. Third, the cytoprotective action of PPG detected in vitro was accompanied by declines of malondialdehyde. Finally, we observed that PPG chelated ferrous ions and, therefore, can suppress the formation of radicals in the Fenton reaction. Thus, PPG with its molecular architecture and presumably its affinity for ferrous ions protects multiple types of cardiovascular cells against oxyradicals.

Animals↗

PubMed1996

Antioxidation of human low density lipoprotein by unconjugated and conjugated bilirubins.

We demonstrate here that both unconjugated bilirubin (Bu) and conjugated bilirubin (Bc) can protect human low density lipoprotein(LDL) against oxidation by oxyradicals generated by 2,2'-azo-bis (2 amidinopropane) dihydrochloride at 37 degrees. The oxidation was assessed by agarose gel electrophoresis and was further corroborated by assaying the malondialdehydes and lipid peroxides formed throughout oxidation. On a per mole basis, Bu and less so Bc was more effective than ascorbate in preventing LDL oxidation. Since oxidative modification of human LDL was implicated in plaque formation in blood vessels leading to atherogenesis, the data suggested that either bile pigment may help reduce the risk of atherogenesis.

Amidines↗

PubMed1996

Morin hydrate inhibits azo-initiator induced oxidation of human low density lipoprotein.

We demonstrated that the flavonoid morin hydrate at 75-100 microM protects against the oxidation of low density lipoprotein (LDL) by free radicals produced by 2,2'-azo-bis(2-amidinopropane) dihydrochloride. Morin hydrate reduces the relative electrophoretic mobility, malondialdehyde equivalents and lipid peroxide level of oxidized LDL. On the other hand, Trolox (an analogue of vitamin E) showed less protective effect in the present system. Since free radical mediated oxidation of LDL is implicated to be a cause of atherogenesis, morin hydrate may be a candidate chemotherapeutic agent herein.

Amidines↗

PubMed1995

Molecular properties and myocardial salvage effects of morin hydrate.

Morin hydrate is a bioactive pigment found in yellow Brazil wood. Recently, we reported that morin hydrate prolongs the survival of three types of cells from the human circulatory system against oxyradicals generated in vitro. The protection excels that given by equimolar concentrations of ascorbate, mannitol, and Trolox. Here, we demonstrate that, in vivo, morin hydrate at 5 mumol/kg actually reduced by > 50% the tissue necrosis in post-ischemic and reperfused rabbit hearts. Mechanistically, morin hydrate not only scavenges oxyradicals, but also moderately inhibits xanthine oxidase, a free-radical generating enzyme from the ischemic endothelium. Among other possibilities, morin hydrate appears to chelate some metal ions (e.g. Fe2+) in oxyradical formation, although this needs to be examined further. Nuclear magnetic resonance (at 500 mHz) and electron-impact mass spectrometry also supported a molecular formula of C15H10O7 for morin hydrate. Only by X-ray crystallography was it clearly revealed that there are two water molecules attached by intermolecular hydrogen bonds to a morin molecule. Also, the three rings of morin hydrate approach coplanarity. This conformation favours a delocalization of electrons after oxyradical reduction, making morin an effective antioxidant. Thus, we have documented some of the molecular properties and myocardial salvage effects of morin hydrate.

Animals↗

PubMed1995

Antioxidation of human low density lipoprotein by morin hydrate.

Oxidative modification of low density lipoprotein (LDL) has been suggested to be a risk factor for the development of atherosclerosis. Agents which can protect LDL from oxidation may be useful in preventing atherogenesis. Here, we found that morin hydrate, at 100 microM concentration, effectively inhibits Cu(2+)-induced oxidation of LDL. The oxidation of LDL was assessed by agarose gel electrophoresis. This was further studied by measuring the increased values of the malondialdehyde equivalents and the decreased numbers of reactive amino groups on oxidized LDL. Trolox, at equimolar concentrations, exhibit similar effects in preventing oxidation of LDL.

Antioxidants↗

PubMed1995

Comparative cytoprotection of cultured corneal endothelial cells by water-soluble antioxidants against free-radical damage.

We reported previously that purpurogallin (PPG) markedly protects the cultured rabbit corneal endothelial cells (RCEC) against oxyradical damage generated with hypoxanthine (HX) and xanthine oxidase (XO)(1). In this study, we further compared the cytoprotective activities of PPG versus Trolox (TX, alpha-tocopherol, a water-soluble analogue of vitamin E) and ascorbate (Asc) in confluent cultured RCEC with phase contrast microscopy and confirmed by transmission electron microscopy. PPG prolonged survival of the oxyradical damaged cells longer than those without PPG present (18.6 +/- 1.4 min at 1.0 mM and 11.2 +/- 1.0 at 0.25 mM respectively vs. 7.3 +/- 0.8 min in control). At levels equimolar to PPG, TX, and Asc were less effective in delaying cell necrosis caused by HX and XO (p < 0.01). When exposed to superoxide radicals generated by menadione, RCEC necrosed at 29.8 +/- 1.5 min compared to PPG 47.2 +/- 1.0 min at 1.0 mM and 38.9 +/- 1.0 min at 0.25 mM. This was significantly different from TX and Asc at corresponding concentrations (p < 0.01). PPG scavenges not only HX-XO-generated oxyradicals, but also nonenzymatically produced superoxide radicals, more actively than two well known antioxidants--TX and Asc.

Animals↗

PubMed1994

Propyl gallate as a hepatoprotector in vitro and in vivo.

Recently, there has been renewed interest in propyl gallate, a preservative in foods and fuels. This compound, which exhibits antimicrobial activity, has been found to be toxicologically safe after almost 30 years of evaluation. In the present study, we examined whether propyl gallate is a hepatoprotective antioxidant, and investigated some of its bases of action vis-à-vis Trolox, a vitamin E analogue. In isolated rat hepatocytes, propyl gallate prolonged substantially cell survival against oxyradicals generated with xanthine oxidase-hypoxanthine. The protection was dose dependent and excelled that of Trolox, mannitol, or ascorbate, each at or near its optimum level in the same system. In rats undergoing an 80-min partial hepatic ischemia, infusion of propyl gallate at 20 mumol/kg body weight just before a 24-hr reperfusion salvaged the organ by 80.0 +/- 11.5%, an extent comparable to that with Trolox. Mechanistically, we found that propyl gallate (a) protected hepatocytes against the cascade of oxyradicals produced by xanthine oxidase-hypoxanthine; (b) protected hepatocytes against superoxide radicals generated specifically by menadione; (c) protected the functionally important hepatic vascular endothelial cells more effectively than Trolox against xanthine oxidase-hypoxanthine, and (d) approximately halved the amount of lipid conjugated dienes (a more specific marker of oxyradical damage than malondialdehyde) formed in tissues after oxidant damage. Therefore, there are fundamental reasons why propyl gallate is an effective antioxidant-based hepatoprotector, both in vitro and in vivo.

Animals↗