Biomedical subjects

W R Wu

Publications and source records attributed to W R Wu.

17 recordsLinked to original sources

PubMed2001

Exposure to repeated low-level formaldehyde in rats increases basal corticosterone levels and enhances the corticosterone response to subsequent formaldehyde.

Low-level exposure to volatile organic compounds may produce symptoms in humans reporting multiple chemical sensitivity (MCS) through altered hypothalamic-pituitary-adrenal (HPA) axis functioning. We determined whether repeated formaldehyde (Form) exposure would alter corticosterone (CORT) levels in a rat model of MCS. Male Sprague-Dawley rats were given acute chamber exposures to Air or Form (0.7 or 2.4 ppm), and trunk blood was collected 20 or 60 min later. All groups showed increased CORT levels above naïve basal levels at 20 min and a return to baseline by 60 min, with no differences between treatment groups. The second experiment examined the effect of repeated Form exposure (1 h/day x 5 days/week x 2 or 4 weeks) on basal CORT levels and after a final challenge. Basal CORT was increased above naïve values after 2 week exposure to Air or 0.7 ppm Form. By 4 week, CORT levels in the Air group returned to naïve values, but remained elevated in the 0.7 ppm Form group. There were no differences in basal CORT levels among either 2.4 ppm exposed groups. After a final Air or Form challenge, the 2 and 4 week Air and 0.7 ppm Form groups had elevated CORT levels similar to their acute response, while the 2 and 4 week 2.4 ppm Form groups had elevated CORT levels compared to their acute response, indicating enhanced reactivity of the HPA axis to subsequent Form. These findings suggest that altered HPA axis functioning occurs after repeated low-level Form exposure, and may have implications for mechanisms mediating MCS in humans.

Animals↗

PubMed2001

Dopamine D1 receptor activation in the medial prefrontal cortex prevents the expression of cocaine sensitization.

This study examined whether microinjection of the full D1 agonist, SKF 81297, or the D1 antagonist, SCH 23390, into the medial prefrontal cortex (mPFC) would alter the expression phase of cocaine sensitization. Male Sprague-Dawley rats were administered saline or cocaine (15 mg/kg, i.p.) once per day for seven consecutive days. After 8 to 17 days withdrawal, rats received a bilateral intra-mPFC microinjection of SKF 81297: either 0, 0.03, 0.1, or 0.3 microg/side; SCH 23390: either 0, 0.1, 0.3, or 1.0 microg/side; or a combination of 0.1 microg of SKF 81297 + 0.3 microg of SCH 23390, followed by an i.p. saline or cocaine (15 mg/kg, i.p.) injection. In naïve rats, vertical activity was elevated by the two lower doses of SKF 81297. A similar enhancement of cocaine-induced activity was observed in daily saline rats at the highest dose tested. In contrast, SKF 81297 suppressed the expression of sensitization to cocaine. This blockade of sensitization was prevented by coinfusion of SCH 23390. Infusion of SCH 23390 alone into the mPFC in daily saline and cocaine-pretreated rats demonstrated a suppression of cocaine-induced locomotion in daily saline-pretreated rats after the highest dose, but a slight augmentation of activity after the lowest dose in daily cocaine-pretreated rats. These results demonstrate a contribution by mPFC D1 receptors in the expression of cocaine sensitization and further suggest that the effects of D1 receptor activation in the mPFC occur in opposite directions in daily saline versus daily cocaine-pretreated rats.

Animals↗

PubMed2000

Differential effects of L-deprenyl on MPP+- and MPTP-induced dopamine overflow in microdialysates of striatum and nucleus accumbens.

The present studies investigated the effects of L-deprenyl, 1-methyl-4-phenylpyridinium ion (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the efflux of dopamine and its metabolites in microdialysates of striatum and nucleus accumbens in rats. L-Deprenyl or L-amphetamine perfusion into striatum had no effects on basal dopamine efflux, though L-deprenyl reduced the basal efflux of dihydroxyphenylacetic acid and homovanillic acid. MPP+ or MPTP perfusion into striatum significantly increased the dopamine efflux, and the action of MPTP was more potent than that of MPP+. Pretreatment with L-deprenyl antagonized the actions of MPP+ and MPTP. The striatal dopamine efflux of rats was gradually restored by itself after the overflow caused by 2-h perfusion of the dopaminergic neurotoxins, while L-deprenyl could not accelerate the recovery. Perfusion with L-deprenyl or L-amphetamine, but not pargyline, into nucleus accumbens increased the dopamine efflux in a dose-dependent fashion, which could be antagonized by haloperidol pretreatment. MPP+ or MPTP perfusion into nucleus accumbens also increased the dopamine efflux, and the action of MPTP was also more potent than that of MPP+. Pretreatment with L-deprenyl could not antagonize the actions of MPP+ and MPTP. These findings suggest that L-deprenyl, MPP+ and MPTP induce differential effects on nigrostriatal and mesolimbic dopaminergic pathways in vivo. L-Deprenyl has neuroprotective rather than neurorestorative action against MPP+- and MPTP-induced dopamine overflow from striatum. Further, L-deprenyl-induced dopamine overflow from nucleus accumbens may explain the amphetamine-like reinforcing property of L-deprenyl.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2000

I-stepholidine facilitates inhibition of mPFC DA receptors on subcortical NAc DA release.

AIM: To determine whether the D1 agonistic action of (-)-stepholidine (SPD) on the medial prefrontal cortex (mPFC) neuron is involved in the modulation of evoked subcortical dopamine (DA) release from nucleus accumbens (NAc) of rats. METHODS: With the microinjection of SPD into the mPFC, the ventral tegmental area (VTA)-stimulated or amphetamine (AMP)-evoked DA efflux in the NAc was detected by microdialysis + HPLC-ECD in the 6-hydroxydopamine (6-OHDA)-lesioned and intact rats. RESULTS: The depletion of DA in the mPFC did not modify both the basal level and the VTA-stimulated DA efflux in the NAc, but significantly facilitated the AMP (20 mumol.L-1)-evoked DA efflux within the NAc. It indicates that the mPFC DA system is involved in the regulation of evoked DA release in the NAc. Besides, the AMP-evoked increase of the extracellular DA release in the NAc was significantly attenuated by SPD (10, 30 mmol.L-1) microinjection into the mPFC, though this injection of SPD could not alter the response of DA release by the stimulation of the VTA. Furthermore, the inhibitory effect of SPD on the AMP-evoked DA efflux could be partially reversed by intravenous administration of D1 antagonist Sch-23390 (1 mg.kg-1), but not by D2 antagonist spiperone. CONCLUSION: SPD is capable of enhancing the function of D1 receptors in the mPFC, by which it facilitates the inhibition of DA release in the NAc.

Animals↗

PubMed1999

Immunosuppressive effects of dihydroetorphine, a potent narcotic analgesic, in dihydroetorphine-dependent mice.

The immunomodulatory effects of dihydroetorphine were systematically investigated in subchronically treated mice. In a dose-dependent fashion, dihydroetorphine (total doses at 444.5, 889 and 1778 microg/kg) lowered the increase of body weight, decreased the weight of the spleen and thymus, weakened the delayed-type hypersensitivity, reduced the generation of antibody-forming cells, inhibited splenic lymphocyte proliferation induced by concanavalin A and lipopolysaccharide, suppressed the production of interleukin-2 in the supernatant of splenocytes induced by concanavalin A, and depleted the ratio of CD4+ and CD8+ subpopulations. Moreover, the physical dependence on dihydroetorphine was also evaluated to confirm that the immunosuppression was concomitant with the addiction to the drug. These results demonstrate that subchronic treatment with dihydroetorphine dose dependently suppresses both humoral and cell-mediated immune function, and that the immunosuppressive effects of dihydroetorphine are much more potent than those of morphine.

Analgesics, Opioid↗

PubMed1999

The amphetamine-like reinforcing effect and mechanism of L-deprenyl on conditioned place preference in mice.

The present study investigated the reinforcing effect of L-deprenyl on conditioned place preference in mice and its mechanism. Conditioned place preference was induced by 10 and 25 mg/kg L-deprenyl in a dose-dependent fashion during five consecutive conditioning days, and its reinforcing property was about five-fold less potent than that of L-amphetamine. Pretreatment with the dopamine antagonist, haloperidol (1 mg/kg i.p.), effectively blocked the place preference produced by L-deprenyl (10 and 25 mg/kg i.p.) and L-amphetamine (2 and 5 mg/kg i.p.), but haloperidol itself produced no place aversion. The neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 30 mg/kg did not modify the place preference induced by both L-deprenyl and L-amphetamine, though the dopamine concentration in striata assayed by high performance liquid chromatography with electrochemical detection (HPLC-EC) was significantly reduced. These results suggest that L-deprenyl has amphetamine-like reinforcing properties. The reinforcing effect of L-deprenyl may be mediated by central dopaminergic neuronal systems, while the nigrostriatal dopaminergic pathway is not involved.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1999

Involvement of monoamine oxidase inhibition in neuroprotective and neurorestorative effects of Ginkgo biloba extract against MPTP-induced nigrostriatal dopaminergic toxicity in C57 mice.

The present study investigated the neuroprotective and neurorestorative effects of Ginkgo biloba extract (EGb 761) and its two components ginkgolides A (BN52020) and B (BN52021) in mice. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg/d i.p. for six days) significantly reduced striatal dopamine (DA) levels in C57 mice measured by high performance liquid chromatography with electrochemical detection (HPLC-EC). When C57 mice were pretreated with EGb 761 (20, 50, 100 mg/kg/d i.p.) for 7 days and then treated with the same extract 30 min before MPTP injection for 6 days, the neurotoxic effect of MPTP was antagonized in a dose-dependent fashion. Similar treatment with ginkgolides A and B (5, 10, 50 mg/kg/d i.p.) showed no protective effect. When C57 mice were treated with EGb 761 (50 mg/kg/d i.p.) after MPTP-lesion, the recovery of striatal dopamine (DA) levels was accelerated. However, similar treatment with ginkgolides A or B (10 mg/kg/d i.p.) did not show any effect. EGb 761, but not ginkgolides A and B, nonselectively inhibited mouse brain MAO activity in vitro (IC50 = 36.45 +/- 1.56 microg/ml) tested by an improved fluorimetric assay. The results demonstrate that EGb 761 administered before or after MPTP treatment effectively protects against MPTP-induced nigrostriatal dopaminergic neurotoxicity and that the inhibitory effect of EGb 761 on brain MAO may be involved in its neuroprotective effect.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1999

Time-related mapping of quantitative trait loci underlying tiller number in rice.

Using time-related phenotypic data, methods of composite interval mapping and multiple-trait composite interval mapping based on least squares were applied to map quantitative trait loci (QTL) underlying the development of tiller number in rice. A recombinant inbred population and a corresponding saturated molecular marker linkage map were constructed for the study. Tiller number was recorded every 4 or 5 days for a total of seven times starting at 20 days after sowing. Five QTL were detected on chromosomes 1, 3, and 5. These QTL explained more than half of the genetic variance at the final observation. All the QTL displayed an S-shaped expression curve. Three QTL reached their highest expression rates during active tillering stage, while the other two QTL achieved this either before or after the active tillering stage.

Chromosome Mapping↗

PubMed1999

Neuroprotective rather than neurorescue or neurorestorative effect of selegiline against MPTP-induced dopaminergic toxicity.

AIM: To study the neuroprotective, neurorescue, neurorestorative effects of selegiline (Sel) on nigrostriatal dopaminergic neuronal system and its inhibition of brain monoamine oxidase B (MAO-B). METHODS: The striatal levels of dopamine and its metabolites were measured using HPLC with electrochemical detection (HPLC-EC). The inhibition of MAO-B was tested by an improved fluorimetric assay. RESULTS: 1-Methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) (30 mg.kg-1 i.p.) reduced the striatal dopamine level by 73% in mice. Selegiline (Sel, 10 mg.kg-1 i.p.) before, but not after, MPTP treatment protected against MPTP-induced nigrostriatal dopaminergic neurotoxicity. There were no differential effects between Sel and saline treatments on the recovery of striatal dopamine levels, which were partially restored during 2 wk. 1-Methyl-4-phenylpyridinium (MPP+) (5 mg.kg-1 i.p.) produced no dopaminergic neurotoxicity. Furthermore, Sel selectively and irreversibly inhibited mouse brain MAO-B in vitro (IC50 = 17 nmol.L-1, 95% confidence limits = 14-20 nmol.L-1). CONCLUSION: Selegiline has neuroprotective rather than neurorescue or neurorestorative effects on MPTP-induced nigrostriatal dopaminergic neuronal degeneration, which is directly pertinent to its selective and irreversible inhibition of brain MAO-B activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1998

Involvement of mu-opioid receptors and alpha-adrenoceptors in the immunomodulatory effects of dihydroetorphine.

The present study investigated the effects of acutely administered dihydroetorphine on mitogen-stimulated lymphocyte proliferation and lymphokine production in mice. These immune functions were significantly suppressed by dihydroetorphine at 24 microg/kg and 128 microg/kg in a dose-dependent fashion. This study further examined the involvement of micro-opioid receptors and alpha-adrenoceptors in the immunomodulatory effects of dihydroetorphine. The micro-opioid receptor antagonist, naloxone (4 mg/kg), and alpha-adrenoceptor antagonist, phentolamine (10 mg/kg), but not the beta-adrenoceptor antagonist, propranolol (10 mg/kg), effectively blocked dihydroetorphine-induced suppression of splenic lymphocyte proliferation and lymphokine production. These results demonstrate that dihydroetorphine has significant immunosuppressive effects in mice and the mechanisms of these effects may lie in its interactions with opioid receptors and adrenergic pathways.

Adjuvants, Immunologic↗

PubMed1998

Image contrast enhancement based on a histogram transformation of local standard deviation.

The adaptive contrast enhancement (ACE) algorithm, which uses contrast gains (CG's) to adjust the high-frequency components of images, is a well-known technique for medical image processing. Conventionally, the CG is either a constant or inversely proportional to the local standard deviation (ILSD). However, it is known that conventional approaches entail noise overenhancement and ringing artifacts. In this paper, we present a new ACE algorithm that eliminates these problems. First, a mathematical model for the LSD distribution is proposed by extending Hunt's image model. Then, the CG is formulated as a function of the LSD. The function, which is nonlinear, is determined by the transformation between the LSD histogram and a desired LSD distribution. Using our formulation, it can be shown that conventional ACE's use linear functions to compute the new CG's. It is the proposed nonlinear function that produces an adequate CG resulting in little noise overenhancement and fewer ringing artifacts. Finally, simulations using some X-ray images are provided to demonstrate the effectiveness of our new algorithm.

Algorithms↗

PubMed1998

Immunosuppressive effects of intravenous self administration of dihydroetorphine on lymphocyte functions in rats.

AIM: To study the effects of dihydroetorphine (DHE) on lymphocyte functions in rats and to further assess the abuse potential of DHE. METHODS: An intravenous self administration (SA) procedure in rats was used to determine the SA liability of DHE. Concanavalin A (Con A)-stimulated lymphocyte proliferation and lymphokine production of rat splenocytes were measured. RESULTS: DHE 178 +/- 13 micrograms established a stable and typical rat model of psychological dependence, suppressed lymphocyte proliferation (129 +/- 11 Bq) compared with control group (620 +/- 36 Bq), and inhibited the activity of interleukin-2 (IL-2) (A570 = 0.28 +/- 0.06) compared with control group (A570 = 0.51 +/- 0.03). CONCLUSION: DHE had a high abuse potential and inhibited the Con A-induced lymphocyte proliferation and interleukin-2 production in rats.

Animals↗

PubMed1984