Biomedical subjects

D Wu

Publications and source records attributed to D Wu.

At least 199 records · Page 11Linked to original sources

PubMed1999

An evaluation of thermal and epithermal neutron activation analysis compton suppression methods for biological reference materials.

For neutron activation analysis (NAA), the usual matrix problems of sodium, chlorine, and bromine are well known to give rise to high backgrounds that inhibit the determination of several trace elements for short-lived or medium-lived NAA. For long counting times in long-lived NAA, very low backgrounds are required to achieve good sensitivities. We have investigated the use of thermal and epithermal NAA in conjunction with Compton suppression to determine several elements such as arsenic, antimony, cadmium, and mercury, at the level of a few nanograms. The values of these techniques are discussed in contrast to the standard radiochemical methods.

Biological Assay↗

PubMed1999

Cardiovascular effects of a mu-selective opioid agonist (tyrosine-D-arginine-phenylalanine-lysine-NH2) in fetal sheep: sites and mechanisms of action.

OBJECTIVE: We investigated the effects of DALDA (tyrosine-D-arginine-phenylalanine-lysine-NH2), a mu-selective opioid peptide, on heart rate and blood pressure in fetal sheep with long-term instrument implantation. STUDY DESIGN: DALDA was given as an intravenous bolus in doses ranging from 0.15 to 0.5 mg/kg. A 0.5 mg/kg dose of DALDA was given in the presence of the opioid antagonist naloxone and its quaternary analog naloxone methiodide (6 mg/h); it was also given in conjunction with the beta-adrenergic antagonist propranolol (2 mg/h). Statistical analyses were performed by 1-way and 2-way analysis of variance. RESULTS: The fetus responded to DALDA with an increase in heart rate with all doses (P <.01) but without any change in blood pressure. This response was abolished by naloxone (P <.001), naloxone methiodide (P =.003), and propranolol (P <.001). CONCLUSIONS: In the fetus intravenous DALDA increases heart rate without any change in blood pressure by way of the mu receptor and through central sympathetic activation. These effects of DALDA are different from those seen in the adult, suggesting different sites and mechanisms of action.

Adrenergic beta-Antagonists↗

PubMed1999

Effect of vitamin E on human aortic endothelial cell production of chemokines and adhesion to monocytes.

Epidemiological and clinical studies indicate that vitamin E may reduce the risk of cardiovascular disease (CVD). Modulation of adhesion molecule expression and chemokine production by vitamin E may contribute to its beneficial effect. In this study we found that the enrichment of confluent human aortic endothelial cells (HAEC) or U937 monocytic cells with increasing doses of vitamin E (d-alpha-tocopherol, 20, 40, and 60 micromol/l for 20 h) inhibited their adhesion when either or both cell types were stimulated with interleukin (IL)-1beta. Enrichment of HAEC with the same doses of vitamin E suppressed IL-1beta-stimulated expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin). Supplementation with increasing doses of vitamin E up to 60 micromol/l was not effective in preventing spontaneous production of monocyte chemoattractant protein-1 (MCP-1), but supplementation with vitamin E at 60 micromol/l reduced IL-8 production significantly. However, IL-1beta-induced productions of both MCP-1 and IL-8 were dose-dependently suppressed by enrichment of cells with vitamin E. Vitamin E, at the doses used, did not significantly change the spontaneous production but dose-dependently inhibited the IL-1beta-induced production of inflammatory cytokine IL-6. We concluded that vitamin E could inhibit production of chemokines and inflammatory cytokines, in addition to inhibiting adhesion of HAEC to monocytes by reducing expression of adhesion molecules when cells were activated with an inflammatory cytokine. These mediators are actively involved in the pathogenesis of atherosclerosis. Therefore, their inhibition by vitamin E may contribute to vitamin E's reported reduction in risk of CVD.

Analysis of Variance↗

PubMed1999

In vivo upregulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived peptides.

Glucose is the critical metabolic fluid for the brain, and the transport of this nutrient from blood to brain is limited by the blood-brain barrier (BBB) GLUT1 glucose transporter. The expression of the BBB-GLUT1 gene is augmented in brain endothelial cultured cells incubated with brain-derived trophic factors and the brain-derived peptide preparation Cerebrolysin (C1, EBEWE, Austria). The aim of the present investigation was to determine if C1 induces similar changes in the expression of the BBB-GLUT1 gene following its administration to rats in vivo. The BBB glucose transporter activity was investigated with the intracarotid artery perfusion technique using [3H]diazepam as cerebral blood flow marker. The acute or chronic administration of C1 markedly increased the brain permeability surface area of D-[14C]glucose compared to controls (D-[14C]glucose/[3H]diazepam ratio, 1.6- to 1.9-fold increase in frontal cortex, P < 0.05). Increased activity of the BBB glucose transporter was correlated with a significant rise in the abundance of the BBB-GLUT1 protein measured by both Western blot analysis and immunocytochemistry, and with a decrease in the transcript levels of this transporter. Data presented here demonstrate that the in vivo administration of Cl increases the transport of glucose from blood to brain via BBB-GLUT1 gene expression.

Amino Acids↗

PubMed1999

Respiratory depression after intravenous administration of delta-selective opioid peptide analogs.

We compared the effects of three micro-(DAMGO, DALDA, TNPO) and three delta-(DPDPE, DELT, SNC-80) opioid agonists on arterial blood gas after IV administration in awake sheep. None of the mu agonists altered pO2, pCO2 or pH. All three mu agonists decreased pO2 increased pCO2 and decreased pO2, and this effect was not sensitive to naloxone or TIPPpsi, a delta-antagonist, suggesting that it is not mediated by beta-opioid receptors. When administered to pregnant animals, there were significant changes in fetal pCO2 and pH. It may be possible to develop delta-selective opioid agonists which do not produce respiratory depression.

Analgesics↗

PubMed1999

Nociceptin/orphanin FQ increases blood pressure and heart rate via sympathetic activation in sheep.

This study was undertaken to examine the cardiovascular effects of nociceptin/Orphanin FQ (OFQ). Nociceptin/OFQ (10-300 nmol/kg, IV) stimulates an increase in mean blood pressure (MBP) and heart rate (HR) in chronically catheterized sheep. Pretreatment with phenoxybenzamine (5 mg/kg) attenuated the pressor response, consistent with sympathetically mediated vasoconstriction. Furthermore, the lack of a reflex bradycardia suggests either blunting of the baroreflex by nociceptin/OFQ or direct beta-adrenergic activation. The bradycardic response to norepinephrine (0.6 microg/kg, IV) remained intact after nociceptin/OFQ administration, demonstrating that nociceptin/OFQ does not blunt the baroreflex. Additionally, the increase in HR was completely reversed by pretreatment with propranolol. These data suggest that nociceptin/OFQ plays a role in cardiovascular regulation via sympathetic activation.

Adrenergic beta-Antagonists↗

PubMed1999

Quantification of cholinergic and select non-cholinergic mesopontine neuronal populations in the human brain.

The pars compacta and pars dissipata of the pedunculopontine nucleus contain cholinergic cell group Ch5, and the laterodorsal tegmental nucleus contains cholinergic cell group Ch6. The pedunculopontine nucleus has been implicated in a variety of functions, including mediation of rapid eye movement sleep and in extrapyramidal motor function, although the role of cholinergic and non-cholinergic neurons is unclear. Quantitative neuroanatomical techniques were used to map the distribution of cholinergic neurons in the mesopontine nuclei of the adult human brain. In addition, the number and distribution of comparably sized non-cholinergic neurons at selected anatomical levels were compared. An antibody raised against human choline acetyltransferase was used to stain immunohistochemically the mesopontine neurons in six brains, ranging in age from 28 to 60 years. The rostrocaudal length of the Cb5/Ch6 cell complex was approximately 10 mm. The estimated total number of cells was similar for all brains, and varied by less than 7%. The estimated average number of cholinergic cells in the combined pedunculopontine and laterodorsal tegmental nuclei was approximately 20,000, with 30% of the cells in the pedunculopontine nucleus pars compacta, 57% in the pedunculopontine nucleus pars dissipata and 13% in the laterodorsal tegmental nucleus. There was no correlation between cell number and age. Within areas of mesopontine tegmentum occupied by the Ch5 cholinergic neurons, there were often more noncholinergic neurons than comparably sized cholinergic neurons. The present study provides detailed maps of the distribution and number of mesopontine cholinergic neurons in the normal human brain. Many non-cholinergic neurons are intermixed with the cholinergic pedunculopontine neurons. One region of the pedunculopontine nucleus pars dissipata containing few cholinergic neurons, located adjacent to the ventral border of the pedunculopontine nucleus pars compacta, may correspond to the midbrain-extrapyramidal area as defined previously in rodent and in non-human primate. These data will be useful for quantitative neuropathological studies concerning the role of both cholinergic and non-cholinergic mesopontine neurons in diseases proposed to affect these neurons, including Parkinson's disease, schizophrenia and progressive supranuclear palsy.

Acetylcholine↗

PubMed1999

Mesopontine cholinergic and non-cholinergic neurons in schizophrenia.

Mesopontine cholinergic neurons influence midbrain dopaminergic neurons, and thalamic and cerebellar structures which have been implicated in the neuroanatomy of schizophrenia. It has been reported that there are approximately twice as many mesopontine cholinergic neurons in schizophrenics than in normals, using nicotinomide adenosine dinucleotide phosphatediaphorase histochemistry to identify the cholinergic neurons. The present study sought to replicate this finding by analysing mesopontine cholinergic neurons using an antibody against choline acetyltransferase. The mesopontine cholinergic neurons are located in the pars compacta and pars dissipata of the pedunculopontine nucleus, and in the laterodorsal tegmental nucleus. Quantitative computer imaging techniques were used to map the distribution of mesopontine cholinergic neurons. In addition, all medium-sized and large neurons in a region of interest containing the middle portion of the pedunculopontine nucleus pars compacta were counted in Nissl-stained sections. There was no difference between schizophrenic and normal brains in terms of: (i) the rostral-caudal length of the cholinergic cell complex, approximately 10 mm; (ii) the estimated total number of cholinergic neurons in the combined pedunculopontine nucleus and laterodorsal tegmental nucleus, approximately 20,000 cells unilaterally; and (iii) the combined number of cholinergic and non-cholinergic Nissl-stained neurons in the middle portion of the pedunculopontine nucleus. The present data do not support the previous observation of increased numbers of mesopontine cholinergic neurons in schizophrenia.

Acetylcholine↗

PubMed1999

Quantitative determination of an extremely polar compound allantoin in human urine by LC-MS/MS based on the separation on a polymeric amino column.

Quantitative determination of allantoin in biological matrix poses a challenge to bioanalysis due to the extreme polarity of allantoin. The molecule exhibits virtually no retention on any of the available hydrophobic HPLC packing materials. In this study, an assay was developed for the LC-MS/MS quantitation of allantoin in human urine using a polymeric amino column to achieve the necessary separation. The urine samples were prepared by a single-step solid phase extraction (SPE) procedure. The extracted samples were analyzed on a jordi-gel DVB polyamine column (operated under an acetonitrile/water gradient with water as the stronger mobile phase) interfaced with a Finnigan TSQ 7,000 mass spectrometer. Negative electrospray ionization (ESI) was employed as the ionization source. Allantoin and its internal standard (13C1, 15N1-allantoin) were detected by use of single reaction monitoring (SRM) mode. The method was validated in the concentration range of 14.6-213 microg/ml(-1), with within and between run accuracy and precision both < 7%. The method has been successfully applied to clinical sample analysis.

Acetonitriles↗

PubMed1999

Peak fronting in reversed-phase high-performance liquid chromatography: a study of the chromatographic behavior of oxycodone hydrochloride.

Severe peak asymmetry--fronting--was observed for oxycodone during elution at 30 degrees C from a C18 HPLC column using a mobile phase consisting of 14.9% MeOH, 84.5% 0.05 M KH2PO4 (pH 3.0), 0.5% MTBE, and 0.1% TEA. Investigation using deuterium-labeled oxycodone and analysis by LC/MS showed that gem diol and hemiketal adducts of oxycodone formed as a result of the equilibrium addition of water and methanol to the C-6 ketone on oxycodone. As a result of slow equilibrium kinetics at room temperature in aqueous solution, the gem-diol and methyl hemiketal eluted as an unresolved broad band in front of the oxycodone peak. Decreasing the column temperature to 0 degrees C decreased the rates of interconversion and allowed the resolution and separation of these species from each other and from oxycodone. Increasing the column temperature to 60 degrees C increased the rates of interconversion with the result that the three species eluted as a single, homogenous peak with greatly improved peak symmetry.

Analgesics, Opioid↗

PubMed1999

Variation of P-QRS relation during atrioventricular node reentry tachycardia.

OBJECTIVES: The main objective of this study was to characterize the phenomenon of variation in the P-QRS relation during atrioventricular node reentry tachycardia. BACKGROUND: Variation of P-QRS relation during tachycardia has been observed occasionally in atrioventricular node reentry tachycardia. However, the incidence, the characteristics and the mechanisms of this phenomenon have not been investigated previously. METHODS: Retrospective analysis was performed in 311 consecutive patients with slow-fast form and 108 patients with atypical or multiple form of atrioventricular node reentry tachycardia to examine whether variation of P-QRS relation with changes in AH, HA and AH/HA (A = atria; H = His bundle) ratio occurred during tachycardia. RESULTS: A total of 28 patients, 8 with slow-fast and 20 with atypical or multiple tachycardias, were found to manifest this phenomenon. There were 6 males and 22 females, with an average age of 38+/-16 years. In 10 patients, this phenomenon occurred transiently following electrical induction of the tachycardia. In 15 patients, changes in AH, HA and AH/HA ratio were associated with the occurrence of Wenckebach or 2:1 block proximal to the His bundle (H) recording site without interruption of the tachycardia. In nine patients, three with nonsustained tachycardia and six after administration of adenosine triphosphate, this phenomenon was observed at the termination of the tachycardia. This phenomenon was usually accompanied by a mild lengthening of the tachycardia cycle length. CONCLUSIONS: Variation of P-QRS relation with or without block may occur during atrioventricular node reentry tachycardia, especially in atypical or multiple-form tachycardias. It was postulated that decremental conduction in the distal common pathway, which exists between the distal link of the reentry circuit and the H, is primarily responsible for this phenomenon.

Adenosine Triphosphate↗

PubMed1999

Mechanisms and clinical significance of transient atrioventricular block during dobutamine stress echocardiography.

OBJECTIVES: The purpose of this study was to investigate the possible mechanism and the clinical significance of transient atrioventricular block (AVB) during dobutamine stress echocardiography (DSE). BACKGROUND: Transient AVB occurs rarely during DSE; however, the mechanisms responsible for blocks are unclear. METHODS: A retrospective analysis of clinical, echocardiographic, catheterization, revascularization and head-up tilting test data was conducted in patients who developed transient AVB during DSE. RESULTS: A total of 302 patients with known or suspected coronary artery disease (CAD) underwent DSE before coronary angiography between November 1997 and August 1998. Transient AVB developed in 12 patients during the test. Mobitz I block was noted in six patients and Mobitz II block in the other six patients. Nine of these 12 patients were subsequently shown to have CAD and three had no significant coronary artery stenosis. Mobitz II block was observed only in patients with CAD, while Mobitz I block occurred in three patients with and three patients without CAD (p < 0.05). Eight of the nine patients with CAD underwent a successful coronary angioplasty with or without stenting and a repeat DSE revealed no recurrence of heart block except in one patient. Head-up tilting test in the 12 patients revealed a positive response in three of the nine patients with and all three patients without CAD. A negative head-up tilting test was likely to be observed in patients with, as compared with those without, CAD in this study population (p < 0.05). CONCLUSIONS: Transient AVB is not an infrequent manifestation during DSE. Both myocardial ischemia and neurally mediated vagal reflex may be responsible for this phenomenon. The development of Mobitz II block during DSE is indicative of the presence of CAD. A successful revascularization in patients with CAD who develop transient AVB may abolish this phenomenon.

Adult↗

PubMed1999

Two novel azadirachtin derivatives from azadirachta indica

Two novel compounds, the first 29-oxymethylene azadirachtin analogue, 29-oxymethylene-11- demethoxycarbonyl-11alpha-hydroxyazadirachtin (azadirachtin M) (1) and 22, 23-dihydro-23alpha-hydroxy-3-tigloyl-11-deoxyazadirachtinin (azadirachtin N) (2), together with known compound 11-epi-azadirachtin H were isolated from a methanolic extract of the seed kernels of Azadirachta indica. The structures of 1 and 2 were elucidated on the basis of spectral methods.

Journal Article↗

PubMed1999

Blood-brain barrier transport of reduced folic acid.

PURPOSE: The brain is relatively resistant to folic acid deficiency, indicating specialized transport systems may exist for this vitamin localized within the brain capillary endothelial wall, which makes up the blood-brain barrier (BBB) in vivo. The present studies quantify the BBB transport of [3H]-methyltetrahydrofolic acid (MTFA) in vivo and in isolated human brain capillaries in vitro. METHODS: BBB transport of [3H]-MTFA was compared to that of 14C]-sucrose, a plasma volume marker, following either intravenous injection or intracarotid perfusion in anesthetized rats. Competition by 10 microM MTFA or 10 microM folic acid was examined to determine whether folic acid is also transported by the MTFA uptake system. RESULTS: The BBB permeability-surface area (PS) product of [3H]-MTFA, 1.1 +/- 0.3 microL/min/g, was 6-fold greater than that of [14C]-sucrose following intravenous injection. The BBB PS product determined by intracarotid arterial perfusion was not significantly different from the BBB PS product calculated following intravenous injection. A time- and temperature- dependent uptake of [3H]-MTFA in human brain capillaries was observed. The uptake of [3H]-MTFA by either rat brain in vivo or by human brain capillaries in vitro was equally inhibited by 10 microM concentrations of either unlabeled MTFA or unlabeled folic acid. CONCLUSIONS: (1) A saturable transport system exists at the BBB for folic acid derivatives and since this transport is equally inhibited by either folic acid or MTFA, it is inferred that this transport system is the folic acid receptor, and not the reduced folic acid carrier. (2) The presence of a folate transport system at the BBB may offer an endogenous transport system for brain drug delivery of conjugates of folates and drugs that do not normally cross the BBB in vivo.

Animals↗

PubMed1999

Pteridine fluorescence for age determination of Anopheles mosquitoes.

The age structure of mosquito populations is of great relevance to understanding the dynamics of disease transmission and in monitoring the success of control operations. Unfortunately, the ovarian dissection methods currently available for determining the age of adult mosquitoes are technically difficult, slow and may be of limited value, because the proportion of diagnostic ovarioles in the ovary declines with age. By means of reversed-phase HPLC this study investigated the malaria vectors Anopheles gambiae and An. stephensi to see if changes in fluorescent pteridine pigments, which have been used in other insects to determine the age of field-caught individuals, may be useful for age determination in mosquitoes. Whole body fluorescence was inversely proportional to age (P < 0.001, r2 > 91%) up to 30 days postemergence, with the regression values: y = 40580-706x for An. gambiae, and y = 52896-681x for An. stephensi. In both species the main pteridines were 6-biopterin, pterin-6-carboxylic acid and an unidentified fluorescent compound. An. gambiae had only 50-70% as much fluorescence as An. stephensi, and fluorescent compounds were relatively more concentrated in the head than in the thorax (ratios 1:0.8 An. gambiae; 1:0.5 An. stephensi). The results of this laboratory study are encouraging. It seems feasible that this simpler and faster technique of fluorescence quantification could yield results of equivalent accuracy to the interpretation of ovarian dissection. A double-blind field trial comparing the accuracy of this technique to marked, released and recaptured mosquitoes is required to test the usefulness of the pteridine method in the field.

Age Factors↗

PubMed1999

Volume-pressure properties of the upper airway in normal subjects and patients with obstructive sleep apnoea.

The aim of this study was to examine the volume-pressure (V-P) characteristics of isolated upper airways in normal subjects and patients with obstructive sleep apnoea (OSA) and to ascertain whether an increase in upper airway muscle activity affects these characteristics. We studied upper airway pressure changes during volume changes by inflation and deflation of air volumes of 5, 10, 15 and 20 mL without and with submental electrical stimulation, during voluntary closing of the glottis, in seven normal subjects and 13 OSA patients. Volume-pressure properties of the upper airway were assessed by elastance (Euaw) which was obtained from the slope of the regression line of the V-P relationships. Euaw in OSA patients was 0.52 +/- 0.08 cmH2O/mL, which was greater than in normal subjects (0.26 +/- 0.06 cmH2O/mL). Submental stimulation increased Euaw in both OSA patients and normal subjects (0.70 +/- 0.11 cmH2O/mL and 0.41 +/- 0.11 cmH2O/mL, respectively). These results suggest that upper airways of OSA patients during wakefulness are less collapsible than those of normal subjects, and that, in both groups, submental stimulation may stiffen the upper airway.

Adult↗

PubMed1999

Distribution of T-lymphocyte subpopulation in blood and spleen of normal cattle and cattle with enzootic bovine leukosis.

Immunocytochemical and flow cytometry techniques were used to examine T-lymphocyte subpopulations in peripheral blood lymphocytes (PBLs) and spleen from cases of enzootic bovine leukosis (EBL) in adult cattle, and from normal cattle (adult and young), with a panel of monoclonal antibodies against bovine leucocyte differentiation molecules. Both in PBLs and spleen, the percentages of T-lymphocyte subpopulations (CD3+, CD4+, CD8+, and WC1 + gamma delta T lymphocytes) of EBL-affected and normal adult cattle were significantly lower than those of normal young cattle. The percentages of these T-lymphocyte subpopulations in the PBLs of adult cattle with EBL were lower than those of normal adult cattle, but the converse was true in the spleen. It is suggested that tumour immunity occurred in the spleen. Histological examination revealed no follicular hyperplasia in the spleen, and the proliferation of neoplastic cells began in the red pulp. It is concluded that the spleen is not the organ initially responsible for the transformation of EBL lymphoma and that neoplastic cells migrating from peripheral blood are metastatic.

Age Factors↗

PubMed1999

Effect of dietary supplementation with black currant seed oil on the immune response of healthy elderly subjects.

BACKGROUND: We have shown that the age-associated increase in prostaglandin E(2) production contributes to the decline in T cell-mediated function with age. Black currant seed oil (BCSO), rich in both gamma-linolenic (18:3n-6) and alpha-linolenic (18:3n-3) acids, has been shown to modulate membrane lipid composition and eicosanoid production. OBJECTIVE: Our objectives were to 1) test whether dietary supplementation with BCSO can improve the immune response of healthy elderly subjects, and 2) determine whether the altered immune response is mediated by a change in the factors closely associated with T cell activation. DESIGN: A randomized, double-blind, placebo-controlled (soybean oil) study was conducted to examine the effect of 2 mo of BCSO supplementation on the immune response of 40 healthy subjects aged >/=65 y. In vivo immune function was determined by delayed-type hypersensitivity skin response. Peripheral blood mononuclear cells (PBMCs) were tested for in vitro immune response. RESULTS: In subjects supplemented with BCSO, the total diameter of induration at 24 h and individual responses to tetanus toxoid and Trichophyton mentagrophytes were significantly higher than their baseline values. The change in response to tetanus toxoid was significantly different from that of the placebo group. The BCSO group showed a significant increase in proliferative response of PBMCs to the T cell mitogen phytohemagglutinin that was not significantly different from that observed in the placebo group. BCSO had no effect on concanavalin A-induced mitogenic response, interleukin 2 and -1beta production, and PBMC membrane fluidity. Prostaglandin E(2) production was significantly reduced in the BCSO-supplemented group, and this change was significantly different from that of the placebo group. CONCLUSION: BCSO has a moderate immune-enhancing effect attributable to its ability to reduce prostaglandin E(2) production.

Aged↗