Biomedical subjects

R M Wu

Publications and source records attributed to R M Wu.

At least 19 recordsLinked to original sources

PubMed2006

3D simulations of hydrodynamic drag forces on two porous spheres moving along their centerline.

This paper numerically evaluates the hydrodynamic drag force exerted on two highly porous spheres moving steadily along their centerline through a quiescent Newtonian fluid over a Reynolds number ranging from 0.1 to 40. At creeping-flow limit, the drag forces exerted on both spheres were approximately identical. At higher Reynolds numbers the drag force on the leading sphere (sphere #1) was higher than the following sphere (sphere #2), revealing the shading effects produced by sphere #1 on sphere #2. At dimensionless diameter beta<2 (beta=d(f)/2k(0.5), d(f) and k are sphere diameter and interior permeability, respectively), the spheres can be regarded as "no-spheres" limit. At increasing beta for both spheres, the drag force on sphere #2 was increased because of the more difficult advective flow through its interior, and at the same time the drag was reduced owing to the stronger wake flow produced by the denser sphere #1. The competition between these two effects leads to complicated dependence of drag force on sphere #2 on beta value. These effects were minimal when beta became low.

Journal Article↗

PubMed2004

DNA haplotype analysis of CAG repeat in Taiwanese Huntington's disease patients.

We studied the expanded CAG repeat and adjacent CCG repeat in 53 Huntington's disease (HD) patients and 172 unrelated normal subjects matched to the patients for ethnic origin. The range of the CAG repeat varied from 38 to 109 in the HD patients and from 10 to 29 in the control group. A significant negative correlation was found between the age at onset and the CAG expansion, with no significant influence of the adjacent CCG repeat on the age at onset by multiple regression analysis. Allelic association using CCG repeat and 2 flanking dinucleotide repeat markers within 150 kb of the HD gene revealed linkage disequilibrium for 2 of 3 markers. Haplotype analysis of 24 HD families using these markers identified 3 major haplotypes underlying 87.5% of HD chromosomes. The data suggested frequent haplotypes in the Taiwanese population on which one or more mutational events leading to the disease occurred.

Alleles↗

PubMed2004

Blanket dynamics in upflow suspended bed.

A one-dimensional model for the spatio-temporal variation of solids fraction in the blanket considering both the hydrodynamic dispersion and the convection effects was proposed in this study. The model equation was a wave equation whose solution presented shock-wave like characteristic. The model output predicted that the distribution of the solids fraction in the blanket would, firstly, evolve to a uniform distribution at a lower solids fraction. Afterward, the blanket would compact itself to another uniform distribution at a higher solids fraction. Experimental works with synthetic raw water coagulated with PACl suspended in a lab-scale suspended bed confirmed the theoretical predictions. The solids flux plot was constructed with underdosed, optimal and overdosed suspensions. Change in coagulant dose would affect the blanket height and the response time. The solids flux curve was shifted accordingly. The "optimal' operational condition for the upflow suspended bed that produced the lowest effluent turbidity was identified and discussed.

Flocculation↗

PubMed2002

Multilevel structure of sludge flocs.

In this work, the structure of two kaolin sludges and a waste activated sludge are investigated using both light-scattering and free-settling methods. Fractal dimensions estimated by the light-scattering and free-settling techniques (D(S) and D(F) respectively) differ significantly and support the hypothesis that naturally occurring aggregates possess a multilevel structure. A two-level floc structural model comprised of (i) a primary floc (of fractal dimension D(S)) consisting of primary particles and (ii) a secondary floc (of fractal dimension D(F)) consisting of the microflocs is proposed to interpret the experimental findings. The structural changes of sludge flocs before and after cationic flocculation are interpreted using the proposed two-level model.

Journal Article↗

PubMed2002

Advective flow and floc permeability.

This work monitored advection flow through a floc by bubble tracking. Close examination of the motion of a swarm of hydrogen bubbles that passed over a free-falling floc allowed the extent of advection flow to be estimated at 53% for the original activated sludge floc, and 12% for the flocculated floc. The interior permeability of the sludge flocs was estimated from this information. The fluid force exerted on the falling floc was also considered.

Journal Article↗

PubMed2002

Genetic polymorphism of the CYP2E1 gene and susceptibility to Parkinson's disease in Taiwanese.

Cytochrome p450IIE1 (CYP2E1), an ethanol-inducible cytochrome p450 enzyme, is expressed in the basal ganglia and is probably involved in the activation of neurotoxicants, producing free radical metabolites and resulting in oxidative stress. To examine the association between CYP2E1 polymorphism and the risk of Parkinson's disease (PD), we performed a case-control study on a large population of Taiwanese PD patients, focusing especially on early-onset PD patients (onset at, or before, the age of 50). Two hundred and thirty-four PD patients and 251 age- and sex-matched controls were recruited. A much higher frequency of the uncommon c2 allele was seen in our control subjects than in Caucasians (0.23 vs. 0.02). There were no significant differences between PD patients and controls in the distribution of either allelic or genotype frequencies. Our results suggest that CYP2E1 is not a major or independent determinant in the occurrence of PD in Taiwanese.

Age of Onset↗

PubMed2001

The COMT L allele modifies the association between MAOB polymorphism and PD in Taiwanese.

OBJECTIVE: Reports suggest that catechol-O-methyltransferase (COMT(L/L)) (Val(158)/Met) and monoamine oxidase B (MAOB) intron 13 genotype polymorphism is associated with PD. To understand the ethnicity-specific effects of genetic polymorphism, we performed a case-control study of the association between PD susceptibility and polymorphism of MAOB and COMT, both separately and in combination, in Taiwanese. METHODS: Two hundred twenty-four patients with PD and 197 controls, matched for age, sex, and birthplace, were recruited. MAOB and COMT polymorphism genotyping was performed by using PCR-based restriction fragment length polymorphism (RFLP) analyses. chi(2), OR, and Fisher's exact tests were used to compare differences in allelic frequencies and genotypes. RESULTS: The MAOB G genotype (G in men and G:/G in women) was associated with a 2.07-fold increased relative risk of PD. COMT polymorphism, considered alone, showed no correlation with PD risk; however, a significant synergistic enhancement was found in PD patients harboring both the COMT(L) and MAOB G genotypes. CONCLUSIONS: These results suggest that, in Taiwanese, PD risk is associated with MAOB G intron 13 polymorphism, and this association is augmented in the presence of the COMT(L) genotype, indicating an interaction of these two dopamine-metabolizing enzymes in the pathogenesis of sporadic PD. However, the relatively low frequencies of these combined genotypes in our study necessitates confirmation with a larger sample size.

Aged↗

PubMed2001

Novel cake characteristics of waste-activated sludge.

Breaking down the time limit constraints for conventional compression-permeation (C-P) cell test, this work has, for the first time, experimentally evaluated the cake characteristics of viable waste-activated sludge subject to polyelectrolyte flocculation and to freeze/thaw treatment under a pressure range of 25-200 kPa. There exists a threshold pressure exceeding which the cake structure would significantly deteriorate. Also, the present biological sludge is a "super-compactible" sludge, whose compactibility is greater than most data ever reported in open literature. The information presented herein has implications to filter design/operation and can be used as a reference data set for examining the existing filtration theories.

Bacteria↗

PubMed2001

Hydrodynamic drag on non-spherical floc and free-settling test.

This work numerically investigates the hydrodynamic drag force exerted on a porous spheroid floc moving steadily through a quiescent Newtonian fluid over a wide range of the Reynolds number. The flow patterns for a highly porous spheroid moving at an elevated Reynolds number are basically the same as those at a low Reynolds number, which extends the applicable range of a creeping-flow based correlation to the higher Reynolds number regime. The shape effect becomes more prominent as the spheroid becomes more porous. Using the equivalent diameter, defined as the geometric mean diameter of the principal axes, leads to a universal correlation relating to the drag force, aspect ratio, and interior permeability. In addition, free-settling experiments are performed to estimate how the non-spherical shape affects the three sludge samples. The possible errors in data reduction for the free-settling test are attributed to the a/b ratio and the internal permeability. The errors range from 16-34% for a/b = 0.6-2.0.

Flocculation↗

PubMed2000

Effect of MAO-B inhibitors on MPP+ toxicity in Vivo.

l-Deprenyl (Selegiline), a selective and irreversible type B monoamine oxidase inhibitor, has been used as an adjunct to levodopa therapy in Parkinson's disease. Recently, it is proposed as a putative neuroprotective agent in delaying the progression of cell death based on its capability of reducing the oxidative stress derived from the MAO-B dependent metabolism of dopamine, and blocking the development of MPTP-parkinsonism. However, a variety of experimental models suggest that l-deprenyl provides neuroprotection through multiple modes of mechanism other than the inhibition of MAO-B. We have previously shown that l-deprenyl protects midbrain dopamine neurons from MPP+ toxicity by a novel antioxidant effect. In the present study we examined whether the protection against MPP+ toxicity is also shared by other reversible or irreversible MAO-B inhibitors including (+)-deprenyl, Ro16-6491 and pargyline. Our data show that non of these MAO-B inhibitors changes the dopamine loss in the striatum induced by intranigral injection of MPP+. Our result suggests that l-deprenyl may possess a unique neuroprotective action on nigral neuron against MPP+ toxicity independent of the MAO-B inhibition.

1-Methyl-4-phenylpyridinium↗

PubMed2000

Monitoring of the levodopa concentration-response relationship in Parkinson's disease.

Motor fluctuations and abnormal involuntary movements are common complications encountered in advanced Parkinson's disease (PD) patients with long-term levodopa therapy. Monitoring of plasma levodopa concentrations and clinical effects has been reported to benefit the management of these complications. However, to our knowledge, there is no data available in Taiwan concerning the correlation between the plasma levodopa levels and motor fluctuations. In this study, we developed the laboratory methodology for plasma levodopa determination by using the aluminum extraction procedure and HPLC-ED. Serial blood samples and motor scores were obtained from 7 PD patients, and the correlation between plasma levodopa levels and motor responses were studied individually. In three patients with wearing-off phenomenon, plasma levodopa concentrations are compatible with the clinical "on" and "off" states. In the other four patients with complex fluctuating responses, their levodopa dosages were adjusted by the results of monitoring. Better motor responses were achieved by optimization of the levodopa pharmacokinetics in these patients. Our preliminary data suggest that simultaneous monitoring of plasma levodopa concentrations and clinical effects might be helpful to improve the therapeutic strategy in some of the parkinsonian patients with fluctuating responses to levodopa.

Adult↗

PubMed1999

CPP antagonizes hypoxia-induced changes in dopamine metabolism in the striatum of newborn rat.

Treatment with 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a potent and competitive N-methyl-D-aspartate antagonist, is able to reduce the hypoxia-induced increase in striatal dopamine level by 26% even after the hypoxic insult has occurred. The hypoxia-induced decrease of the striatal 3,4-dihydroxyphenylacetic acid level can also be reversed by CPP. This study demonstrates that CPP can antagonize the hypoxia-induced changes in the dopamine metabolism in the striatum of the newborn rat.

Animals↗

PubMed1998

Sleep disturbances in the Vietnam generation: findings from a nationally representative sample of male Vietnam veterans.

OBJECTIVE: This study analyzed questionnaire items that address complaints about sleep from the National Vietnam Veterans Readjustment Study, a nationally representative sample of the 3.1 million men and women who served in Vietnam. This study compared the frequency of nightmares and difficulties with sleep onset and sleep maintenance in male Vietnam theater veterans with male Vietnam era veteran and male civilian comparison subjects. It focused on the role of combat exposure, nonsleep posttraumatic stress disorder (PTSD) symptoms, comorbid psychiatric and medical disorder, and substance abuse in accounting for different domains of sleep disturbance. METHOD: The authors undertook an archival analysis of the National Vietnam Veterans Readjustment Study database using correlations and linear statistical models. RESULTS: Frequent nightmares were found exclusively in subjects diagnosed with current PTSD at the time of the survey (15.0%). In the sample of veterans who served in Vietnam (N = 1,167), combat exposure was strongly correlated with frequency of nightmares, moderately correlated with sleep onset insomnia, and weakly correlated with disrupted sleep maintenance. A hierarchical multiple regression analysis showed that in Vietnam theater veterans, 57% of the variance in the frequency of nightmares was accounted for by war zone exposure and non-sleep-related PTSD symptoms. Alcohol abuse, chronic medical illnesses, panic disorder, major depression, and mania did not predict the frequency of nightmares after control for nonsleep PTSD symptoms. CONCLUSIONS: Frequent nightmares appear to be virtually specific for PTSD. The nightmare is the domain of sleep disturbance most related to exposure to war zone traumatic stress.

Combat Disorders↗

PubMed1996

Suppression of hydroxyl radical formation and protection of nigral neurons by l-deprenyl (selegiline).

The present study clearly demonstrated that l-deprenyl confers a substantial protective effect against MPP+ in the substantia nigra zona compacta in vivo. 32.39. The protection provided by l-deprenyl may not depend on its inhibition of type B monoamine oxidase. A unique antioxidant property of l-deprenyl by suppression of cycotoxic. OH formation and associated oxidative damage induced by MPP+ in the A9 melanized nigral neurons may contribute to the protection against MPP+ toxicity in the nigrostriatal system. The likelihood that l-deprenyl may confer neuroprotection against MPP+ toxicity through antioxidant effect is further strongly supported by our recent data that U-78517F (2-methlaminochromans) a potent inhibitor of ironcatalyzed lipid peroxidation, and DMSO an effective. OH scavenger also protect nigral neurons against MPP(+)-induced severe oxidative injury in the substantia nigra. This putative antioxidant effect of deprenyl may explore another mechanism which may in part contribute to its overt neuroprotection against several toxins, including 6-OHDA, DSP-4, and MPTP, and the possible clinical effects on slowing the neuronal degeneration in early Parkinson's disease, Alzheimer's disorder and even senescent changes.

1-Methyl-4-phenylpyridinium↗

PubMed1995

Neuronal protective and rescue effects of deprenyl against MPP+ dopaminergic toxicity.

Intranigral infusion of 1-Methyl-4-phenylpyridinium ion (MPP+, 2.1-16.8 nmol) dose-dependently injured nigral neurons as reflected by reduced dopamine levels in the ipsilateral striatum four days after the infusion of this toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Coadministration of deprenyl (4.2 nmol) with MPP+ into the substantia nigra protected against MPP(+)-induced moderate (20-50%) but not severe (over 70%) nigral injury as reflected in striatal dopamine reductions. However, supplementary treatment with deprenyl (0.25 mg/kg, s.c., twice daily for 4 days) after intranigral infusion of MPP+ significantly rescued nigral neurons from more severe damage caused by a higher MPP+ does (8.4 nmol) manifested by a lesser striatal dopamine decrease (-31%) compared to the non-deprenyl treated group (-70%). Thus, in addition to the blockade of bioactivation of MPTP, deprenyl can protect and/or rescue nigral neurons from MPP(+)-induced dopaminergic neurotoxicity. These in vivo data add further evidence to suggest that deprenyl, a putative and clinically unproven neuroprotective agent, may be of value in slowing the progressive nigral degeneration in "early" Parkinson's disease, but may prove to be less so in its terminal stages.

1-Methyl-4-phenylpyridinium↗

PubMed1994

In vivo generation of hydroxyl radicals and MPTP-induced dopaminergic toxicity in the basal ganglia.

The in vivo generation of .OH free radicals in specific brain regions can be measured by intracerebral microdialysis perfusion of salicylate, avoiding many of the pitfalls inherent in systemic administration of salicylate. Direct infusion of salicylate into the brain can minimize the hepatic hydroxylation of salicylate and its contribution to brain levels of 2,5-DHBA. Levels of 2,5-DHBA detected in the brain dialysate may reflect the .OH adduct plus some enzymatic hydroxylation of salicylate in the brain. After minimizing the contribution of enzyme and/or blood-borne 2,5-DHBA, the present data demonstrate the validity of the use of 2,3-DHBA and apparently 2,5-DHBA as indices of .OH formation in the brain. Therefore, intracranial microdialysis of salicylic acid and measurement of 2,3-DHBA appears to be a useful .OH trapping procedure for monitoring the time course of .OH generation in the extracellular fluid of the brain. These results indicate that nonenzymatic and/or enzymatic oxidation of the dopamine released by MPTP analogues in the extracellular fluid may play a key role in the generation of .OH free radicals in the iron-rich basal ganglia. Moreover, a site-specific generation of cytotoxic .OH free radicals and quinone/semiquinone radicals in the striatum may cause the observed lipid peroxidation, calcium overload, and retrograde degeneration of nigrostriatal neurons. This free-radical-induced nigral injury can be suppressed by antioxidants (i.e., U-78517F, DMSO, and deprenyl) and possibly hypothermia as well. In the future, this in vivo detection of .OH generation may be useful in answering some of the fundamental questions concerning the relevance of oxidants and antioxidants in neurodegenerative disorders during aging. It could also pave the way for the research and development of novel neuroprotective antioxidants and strategies for the early or preventive treatment of neurodegenerative disorders, such as Parkinson's disease (Wu et al., this issue), amyotrophic lateral sclerosis, head trauma, and possibly Alzheimer's cognitive dysfunction as well. In conclusion, this in vivo free-radical trapping procedure provides evidence to support a current working hypothesis that a site-specific formation of cytotoxic .OH free radicals in the basal ganglia may be one of the neurotoxic mechanisms underlying nigrostriatal degeneration and Parkinsonism caused by the dopaminergic neurotoxin MPTP. Addendum added in proof: The controversy concerning possible neurotoxic and/or neuroprotective roles of NO. in cell cultures was discussed and debated at the symposium (Wink et al., this issue; Dawson et al., this issue; Lipton et al., this issue).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Antioxidant mechanism and protection of nigral neurons against MPP+ toxicity by deprenyl (selegiline).

The current research has demonstrated that MPP+ can induce lipid peroxidation in the nigrostriatal system of rat in vivo. Antioxidant agent U-78517F and .OH scavenger DMSO may protect against MPP+ toxicity through the inhibition of .OH radical-mediated oxidative injury in the substantia nigra. These findings indicate that the cytotoxic hydroxyl radical generated from dopamine oxidation in the iron-rich basal ganglia may contribute to the mechanism underlying the selective A9 melanized nigral degeneration in MPTP-Parkinsonism and possibly in idiopathic Parkinson's disease. In addition, the present studies also clearly demonstrate that deprenyl can substantially protect dopaminergic neurons against MPP+ toxicity in the substantia nigra zona compacta in vivo. The neuroprotective effect provided by deprenyl may not be the consequence of its inhibition of MAO-B activity or prevention of the uptake of MPP+ by dopaminergic neurons. A unique antioxidant property of deprenyl by suppressing .OH formation and associated oxidative injury induced by MPP+ may contribute to the apparent neuroprotective action. In perspective, this putative antioxidant effect of deprenyl may provide another mechanism to its overt neuroprotective effects against oxygen radical-mediated oxidative injury in some neurotoxic chemicals, such as 6-OHDA and DSP-4, and probably in Alzheimer's disease and senescent changes. Finally, based on the present data, a possible neuroprotective therapeutic window of deprenyl in the treatment of early Parkinson's disease has been proposed. It is suggested that deprenyl should be introduced as early as possible in de novo Parkinsonian patients to achieve its full neuroprotective effect on nigral degeneration. Moreover, a combination of early detection of individuals at risk of developing Parkinson's disease and early intervention of deprenyl and/or other centrally active antioxidants to these patients may provide a new preventive therapeutic strategy in the future, in addition to the current conventional levodopa treatment of Parkinson's disease.

1-Methyl-4-phenylpyridinium↗

PubMed1994

Ferrous-citrate complex and nigral degeneration: evidence for free-radical formation and lipid peroxidation.

Increased nigral iron content in the parkinsonian brain is now well documented and is implicated in the pathogenesis of this movement disorder. Free iron in the pigmented DA-containing neurons catalyze DA autoxidation and Fenton reaction to produce cytotoxic .OH, initiating lipid peroxidation and consequent cell damage. The present results clearly demonstrate that a regional increase in the levels of the "labile iron pool" can result in the degeneration of dopaminergic nigral neurons as reflected by a significant inhibition in the expression of tyrosine hydroxylase mRNA and DA depletion. Iron-complex-induced damage of dopaminergic neurons in the substantia nigra, might have resulted from a sequence of cytotoxic events including the .OH generation and lipid peroxidation as demonstrated in this study. This free-radical-induced oxidative nigral injury may be a reliable free-radical model for studying parkinsonism and may be relevant to idiopathic Parkinson's disease. This apparent nigral injury stimulated by Fe(2+)-citrate is more severe than that produced by ferric iron and its citrate complex. Moreover, these data indicate that Fe(2+)-citrate is as potent as MPP+ in causing oxidative injury to the substantia nigral neurons. However, the nigral toxicity of MPTP and its congeners are not progressive, while Fe(2+)-citrate complex may produce a progressive degeneration of the nigrostriatal neurons which is similar to the progression of ideopathic Parkinson's disease. Thus, this unique Fe(2+)-citrate complex animal model could be used for studying neuroprotective treatments for retarding or halting the progressive nigrostriatal degeneration caused by free radicals in the iron-rich basal ganglia.

3,4-Dihydroxyphenylacetic Acid↗