Biomedical subjects

J Pang

Publications and source records attributed to J Pang.

At least 19 recordsLinked to original sources

PubMed2003

Physiological aspects of vetiver grass for rehabilitation in abandoned metalliferous mine wastes.

Physiological aspects of why vetiver grass (Vetiveria zizanioides L.) can be tolerant to heavy metals and be used as an alternative method for rehabilitation of abandoned metalliferous mine wastelands have been investigated. The results showed that high proportions of lead and zinc (Pb/Zn) tailing greatly inhibited the leaf growth, dry matter accumulation, and photosynthesis of leaves, but stimulated the accumulation of proline and abscisic acid (ABA), and enhanced the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), implying that different mechanisms to detoxify active oxygen species (AOS) existed in different parts of plants. Physiological responses to heavy metal treatments differed greatly between roots and shoots. Nitrogen fertilizer application could greatly alleviate the adverse effects of high proportions of Pb/Zn tailing on vetiver grass growth.

Abscisic Acid↗

PubMed2003

Alfentanil infusion as a component of intravenous anaesthesia for coronary artery bypass surgery with "fast-track" recovery.

Alfentanil and propofol total intravenous anaesthesia was assessed in 25 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). A manually controlled alfentanil infusion, calculated from estimated lean body mass and published pharmacokinetic data, was effective in achieving target plasma concentrations, while the "Diprifusor" system was used to vary propofol target concentrations according to changes in haemodynamics and anaesthetic requirement. The effects of CPB on alfentanil plasma concentrations were offset by changes in protein binding and free-fraction of the drug. With the use of only two target plasma concentrations for alfentanil (changed after CPB), a pre-determined infusion profile ensured effective plasma concentrations during surgery and concentrations unlikely to inhibit extubation within six hours of sternal closure.

Alfentanil↗

PubMed2002

Subluminous phase velocity of a focused laser beam and vacuum laser acceleration.

It has been found that for a focused laser beam propagating in free space, there exists, surrounding the laser beam axis, a subluminous wave phase velocity region. Relativistic electrons injected into this region can be trapped in the acceleration phase and remain in phase with the laser field for sufficiently long times, thereby receiving considerable energy from the field. Optics placed near the laser focus are not necessary, thus allowing high intensities and large energy gains. Important features of this process are examined via test particle simulations. The resulting energy gains are in agreement with theoretical estimates based on acceleration by the axial laser field.

Journal Article↗

PubMed2001

Cloning and characterization of Ginkgo biloba levopimaradiene synthase which catalyzes the first committed step in ginkgolide biosynthesis.

Levopimaradiene synthase, which catalyzes the initial cyclization step in ginkgolide biosynthesis, was cloned and functionally characterized. A Ginkgo biloba cDNA library was prepared from seedling roots and a probe was amplified using primers corresponding to conserved gymnosperm terpene synthase sequences. Colony hybridization and rapid amplification of cDNA ends yielded a full-length clone encoding a predicted protein (873 amino acids, 100,289 Da) similar to known gymnosperm diterpene synthases. The sequence includes a putative N-terminal plastid transit peptide and three aspartate-rich regions. The full-length protein expressed in Escherichia coli cyclized geranylgeranyl diphosphate to levopimaradiene, which was identical to a synthetic standard by GC/MS analysis. Removing 60 or 79 N-terminal residues increased levopimaradiene production, but a 128-residue N-terminal deletion lacked detectable activity. This is the first cloned ginkgolide biosynthetic gene and the first in vitro observation of an isolated ginkgolide biosynthetic enzyme.

Alkyl and Aryl Transferases↗

PubMed2001

Pharmacokinetics and pharmacodynamic effects of 5-fluorouracil given as a one-hour intravenous infusion.

PURPOSE: Clinical toxicity associated with 5-fluorouracil (5-FU) is related to the area under the plasma concentration-time curve (AUC). Recently, short-term infusions of 5-FU given over 30 or 60 min have been substituted for conventional "bolus" 5-FU given over 3-5 min in randomized clinical trials, but there are only limited pharmacokinetic data for these altered infusion durations. We therefore wished to determine the pharmacokinetics and toxicity associated with 5-FU given as a 1-h intravenous (i.v.) infusion. METHODS: A group of 22 adults with advanced gastrointestinal tract cancers and no prior systemic chemotherapy for advanced disease received interferon alpha-2a (5 MU/m2 s.c., days 1-7), leucovorin (500 mg/m2 i.v. over 30 min, days 2-6) and 5-FU (370 mg/m2 i.v. over 1 h, days 2-6). The doses of 5-FU and interferon-alpha were adjusted according to individual tolerance. The pharmacokinetics and clinical toxicity were retrospectively compared with patients receiving the same regimen under the same treatment guidelines except that 5-FU was given over 5 min. RESULTS: The regimen was well tolerated, and 41% of the patients tolerated 5-FU dose escalations to 425-560 mg/m2 per day. Grade 3 or worse diarrhea and fatigue ultimately occurred in 14% of the patients each. Granulocytopenia, mucositis, and diarrhea appeared to be appreciably milder in the present trial compared with our prior phase II experience in colorectal cancer. The peak 5-FU plasma levels and AUC with 370 mg/m2 5-FU given over 1 h were 7.3-fold and 2.4-fold lower than previously measured in 31 patients who received 5-FU over 5 min. CONCLUSION: Increasing the length of 5-FU infusion to 1 h seemed to substantially reduce the clinical toxicity with this modulated 5-FU regimen, likely due to markedly lower peak 5-FU plasma levels and AUC. Changes in the duration of a short infusion of 5-FU clearly affects the clinical toxicity, but raises the concern of a potentially adverse impact on its antitumor activity. These results suggest the importance of including precise guidelines concerning the time over which 5-FU is given in clinical trials. Having a specified duration of 5-FU infusion is also important if 5-FU dose escalation is considered.

Adult↗

PubMed2001

Blue light-induced apoptosis in cultured retinal pigment epithelium cells of the rat.

BACKGROUND: We previously demonstrated that phagosome-free retinal pigment epithelium (RPE) cells in culture can be damaged directly by blue light (wavelength 440+/-10 nm) as observed by electron microscope. A low intensity (1.0 mW/cm2) of light induced only swelling of mitochondria, while a high intensity (4.0 mW/cm2) induced necrosis in the RPE. The aim of the present study was to investigate what intensity of blue light could induce apoptosis in cultured phagosome-free RPE. METHODS: Primary cultured RPE cells, harvested from Long-Evans rats, that contained no phagosomes were exposed to a cool blue light (wavelength 440+/-10 nm). After exposure, transmission electron microscopy (TEM) and TdT-mediated dUTP nick-end labeling (TUNEL) staining were used to detect apoptosis in the RPE cells. To assess the relationship of oxidation to apoptosis by blue light, we added N-acetylcysteine (NAC) as a free radical scavenger and investigated its inhibitory effect on apoptosis. RESULTS: In RPE cells exposed to blue light of 2.7 mW/cm2 for 24 h, apoptotic bodies were found by TEM. In RPE cells exposed to blue light of 2.0 mW/cm2 for 60 h, apoptotic bodies, nuclear condensation and nuclear segmentation were observed by TEM and some RPE cells showed positive TUNEL staining. When 30 mM of NAC was added, TUNEL staining was negative. CONCLUSION: Our findings demonstrate that apoptotic cell death is induced by blue light exposure in cultured RPE cells in vitro. The findings of our previous experiments and those of the present study suggest that a higher intensity of blue light could induce necrosis, and moderately intense blue light could induce non-necrotic cell death or apoptosis, in RPE cells. Furthermore, it is suggested that blue light caused cell death by a free-radical-associated mechanism.

Acetylcysteine↗

PubMed2001

Do antenatal corticosteroids help in the setting of preterm rupture of membranes?

OBJECTIVE: It is now accepted that corticosteroid administration before preterm delivery reduces neonatal mortality and morbidity. However, corticosteroid use in the setting of rupture of membranes remains controversial. STUDY DESIGN: We reviewed data from the first and largest randomized trial in this area and included them in a new meta-analysis. RESULTS: Data from 318 women with rupture of membranes in the Auckland Trial showed that there was a trend toward reduction of the risk of respiratory distress syndrome with corticosteroids but that this trend did not reach statistical significance. There was little effect on the risks of neonatal death, intraventricular hemorrhage, and fetal, neonatal, or maternal infection. Combined data from 15 controlled trials involving >1400 women with rupture of membranes confirmed that corticosteroids reduce the risks of respiratory distress syndrome (relative risk, 0.56; 95% confidence interval, 0.46-0.70), intraventricular hemorrhage (relative risk, 0.47; 95% confidence interval, 0.31-0.70), and necrotizing enterocolitis (relative risk, 0.21; 95% confidence interval, 0.05-0.82). They also may reduce the risk of neonatal death (relative risk, 0.68; 95% confidence interval, 0.43-1.07). They do not appear to increase the risk of infection in either mother (relative risk, 0.86; 95% confidence interval, 0.61-1.20) or baby (relative risk, 1.05; 95% confidence interval, 0.66-1.68). The duration of rupture of membranes does not alter these outcomes. CONCLUSION: The available data indicate that corticosteroid administration is beneficial in the setting of rupture of membranes. In our opinion further trials to address this question cannot be justified.

Adrenal Cortex Hormones↗

PubMed2001

Effects of alcohol on blood pressure and production of vascular aldosterone and corticosterone.

AIMS: The aims of this study were to search for the role of alcohol in blood pressure regulation in rats and to investigate the effects of alcohol on the production of vascular aldosterone and corticosterone. METHODS: Male Wistar rats received alcohol 0.7 g x kg(-1) x day(-1) (alcohol-treated group 1) or 1.4 g x kg(-1) x day(-1) (alcohol-treated group 2) or 2.1 g x kg(-1) x day(-1) (alcohol-treated group 3), orally, for 3 months, and blood pressure was monitored by a pressure transducer. Systolic blood pressure increased in Wistar rats treated with alcohol compared to control rats. Mesenteric artery perfusion ex vivo was performed and pressor responses to norepinephrine were determined. The pressor responses to norepinephrine in mesenteric arteries treated with alcohol were significantly increased. The perfusate from the mesenteric arteries was collected and applied to a Sep-Pak C 18 cartridge column for reverse-phase high-performance liquid chromatography and aldosterone and corticosterone levels were determined by radioimmunoassay, aldosterone was decreased but corticosterone was increased in the perfusate from arteries treated with alcohol. RESULTS: Reverse transcriptase polymerase chain reaction showed that alcohol inhibited the expression of 11beta-HSD2 and CYP11B2 mRNA in mesenteric arteries. CONCLUSIONS: These results reveal that alcohol is able to induce hypertension and provide evidence that alcohol inhibits the transcriptions of both 11beta-HSD2 and CYP11B2 in the vasculature, leading to lower aldosterone and higher corticosterone production in vessels, and increased vasoconstrictor responses to norepinephrine.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

PubMed2001

Sterols in blood of normal and Smith-Lemli-Opitz subjects.

Smith-Lemli-Opitz syndrome (SLOS) is a hereditary disorder in which a defective gene encoding 7-dehydrocholesterol reductase causes the accumulation of noncholesterol sterols, such as 7- and 8-dehydrocholesterol. Using rigorous analytical methods in conjunction with a large collection of authentic standards, we unequivocally identified numerous noncholesterol sterols in 6 normal and 17 SLOS blood samples. Plasma or erythrocytes were saponified under oxygen-free conditions, followed by multiple chromatographic separations. Individual sterols were identified and quantitated by high performance liquid chromatography (HPLC), Ag(+)-HPLC, gas chromatography (GC), GC-mass spectrometry, and nuclear magnetic resonance. As a percentage of total sterol content, the major C(27) sterols observed in the SLOS blood samples were cholesterol (12;-98%), 7-dehydrocholesterol (0.4;-44%), 8-dehydrocholesterol (0.5;-22%), and cholesta-5,7,9(11)-trien-3beta-ol (0.02;-5%), whereas the normal blood samples contained <0.03% each of the three noncholesterol sterols. SLOS and normal blood contained similar amounts of lathosterol (0.05;-0.6%) and cholestanol (0.1;-0.4%) and approximately 0.003;-0.1% each of the Delta(8), Delta(8(14)), Delta(5,8(14)), Delta(5,24), Delta(6,8), Delta(6,8(14)), and Delta(7,24) sterols. The results are consistent with the hypothesis that the Delta(8(14)) sterol is an intermediate of cholesterol synthesis and indicate the existence of undescribed aberrant pathways that may explain the formation of the Delta(5,7,9(11)) sterol. 19-Norcholesta-5,7,9-trien-3beta-ol was absent in both SLOS and normal blood, although it was routinely observed as a GC artifact in fractions containing 8-dehydrocholesterol. The overall findings advance the understanding of SLOS and provide a methodological model for studying other metabolic disorders of cholesterol synthesis.

Adult↗

PubMed2001

[Effect of unprepared and prepared "he zi" on contraction of isolated trachea smooth muscle in rabbits].

Isolated trachea smooth muscle in rabbits induced by Ach or KCl was adopted to study the effect of unprepared and prepared "He Zi". The results showed that unprepared "He Zi" couldn't affect the contraction of isolated trachea smooth muscle in rabbit induced by Ach or KCl, and that prepared "He Zi" couldn't affect the contraction of isolated trachea smooth muscle in rabbit induced by KCl. The results also showed that prepared "He Zi" could significantly inhibit the contraction induced by Ach. The inhibition effect may not be associated with cGMP, adrenergic receptor, and release of NO and prostaglandin, and was epithelium independent. Maybe the different content of tannic acid contributed to the different effect between unprepared and prepared "He Zi".

Acetylcholine↗

PubMed2001

[Study on the role of human papillomavirus in carcinogenesis of oral papillomas by in situ hybridization].

OBJECTIVE: To explore the role of human papillomavirus (HPV) infection on carcinogenesis of oral squamous cell papillomas (SCP). METHODS: By using digoxin labelled HPV 6/11 and HPV 16/18 probes, through hybridization in situ technique, the HPV DNA sequence in 30 cases of oral SCP were detected. RESULTS: Among them, 16 cases (53.3%) were positive for HPV 6/11 DNA. None of cases of SCP were positive for HPV 16/18 DNA. CONCLUSION: Our results show that the frequent finding of HPV 6/11 DNA in oral SCP had close association between oral papillomas and HPV 6/11 infection.

Adolescent↗

PubMed2000

High glucose inhibits glucose-6-phosphate dehydrogenase via cAMP in aortic endothelial cells.

Recent studies have shown that hyperglycemia is a principal cause of cellular damage in patients with diabetes mellitus. A major consequence of hyperglycemia is increased oxidative stress. Glucose-6-phosphate dehydrogenase (G6PD) plays an essential role in the regulation of oxidative stress by primarily regulating NADPH, the main intracellular reductant. In this paper we show that increased glucose (10-25 mm) caused inhibition of G6PD resulting in decreased NADPH levels in bovine aortic endothelial cells (BAEC). Inhibition was seen within 15 min. High glucose-induced inhibition of G6PD predisposed cells to cell death. High glucose via increased activity of adenylate cyclase also stimulated an increase in cAMP levels in BAEC. Agents that increased cAMP caused a decrease in G6PD activity. Inhibition of cAMP-dependent protein kinase A ameliorated the high glucose-induced inhibition of G6PD. Finally, high glucose stimulated phosphorylation of G6PD. These results suggest that, in BAEC, high glucose stimulated increased cAMP, which led to increased protein kinase A activity, phosphorylation of G6PD, and inhibition of G6PD activity. We conclude that these changes in G6PD activity play an important role in high glucose-induced cell damage/death.

Animals↗

PubMed2000

Steric bulk at cycloartenol synthase position 481 influences cyclization and deprotonation.

Cycloartenol synthase converts oxidosqualene to the pentacyclic sterol precursor cycloartenol. An Arabidopsis thaliana cycloartenol synthase Ile481Val mutant was previously shown to produce lanosterol and parkeol in addition to its native product cycloartenol. Experiments are described here to construct Phe, Leu, Ala, and Gly mutants at position 481 and to determine their cyclization product profiles. The Phe mutant was inactive, and the Leu mutant produced cycloartenol and parkeol. The Ala and Gly mutants formed lanosterol, cycloartenol, parkeol, achilleol A, and camelliol C. Monocycles comprise most of the Gly mutant product, showing that an alternate cyclization route can be made the major pathway by a single nonpolar mutation.

Amino Acid Substitution↗

PubMed2000

Kinetics and plasma concentrations of 26-hydroxycholesterol in baboons.

26-Hydroxycholesterol (26OHC), a major oxysterol in human blood, is believed to play an important role in reverse cholesterol transport, bile acid formation, and regulation of various cellular processes. Using isotope dilution mass spectrometry, we measured plasma 26OHC concentrations in baboons fed either a high cholesterol/saturated fat (HC-SF) or normal chow diet. Plasma 26OHC levels in baboons were comparable to those reported for humans and were positively correlated with plasma cholesterol concentrations. Animals on the HC-SF diet had significantly higher 26OHC levels (0.274+/-0.058 microM, mean+/-S.D.) than those on the chow diet (0.156+/-0.046 microM). In separate experiments, [(3)H]26OHC was injected into four tethered baboons, and multiple blood samples drawn over a 1-h period were analyzed for [(3)H]26OHC and 26OHC. Fitting the specific radioactivity data to a two-pool compartmental model indicated a rapidly turning over plasma compartment (t(1/2) 2.9-6.0 min) and a second compartment with slow turnover (t(1/2) 76-333 min). The calculated 26OHC production rate was 2.5 micromol/kg body weight/day. Assuming all 26OHC is converted to bile acids, the 26OHC production rate corresponds to about 10% of total bile acid production in adult baboons. These results indicate that rapid turnover of plasma 26OHC at submicromolar concentrations could significantly contribute to bile acid synthesis.

Animals↗

PubMed2000

Determination of in vitro permeability of drug candidates through a caco-2 cell monolayer by liquid chromatography/tandem mass spectrometry.

Studying the permeability of compounds across a Caco-2 cell monolayer is an established in vitro model to screen for oral absorption and to evaluate the mechanism of transport. This assay can also be used to evaluate compounds as potential P-glycoprotein substrates and/or inhibitors. The traditional methods of sample analysis (high-performance liquid chromatography (HPLC) with a UV or fluorescence detector) limit the throughput and sensitivity of this assay. Data are presented here describing the use of liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the analysis of samples derived from the Caco-2 cell studies. During the analysis an automatic switching valve was used to divert the flow from the HPLC column to waste for the first minute, preventing the early eluting salts from entering and contaminating the LC/MS interface. This approach allows the rapid and accurate determination of drug transport across the Caco-2 cell monolayer. The high sensitivity and specificity of LC/MS/MS make this technique an ideal candidate for the low concentration and high throughput routine analysis of Caco-2 cell solutions, especially if multiple compounds are administered and analyzed simultaneously. Thus, the use of LC/MS/MS will increase the value of the Caco-2 cell assay as an in vitro screening tool.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Expression of functional soluble human alpha-globin chains of hemoglobin in bacteria.

Individual, soluble human alpha-globin chains were expressed in bacteria with exogenous heme and methionine aminopeptidase. The yields of soluble alpha chains in bacteria were comparable to those of recombinant non-alpha chains expressed under the same conditions. Molecular mass and gel-filtration properties of purified recombinant alpha chains were the same as those of authentic human alpha chains. Biochemical and biophysical properties of isolated alpha chains were identical to those of native human alpha chains as assessed by UV/vis, circular dichroism (CD), and nuclear magnetic resonance (NMR) spectroscopy which contrasts with previous results of refolded precipitated alpha chains made in the presence of heme in vitro (M. T. Sanna et al., J. Biol. Chem. 272, 3478-3486, 1997). Mixtures of purified, soluble recombinant alpha-globin and native beta-globin chains formed heterotetramers in vitro, and oxygen- and CO-binding properties as well as the heme environment of the assembled tetramers were experimentally indistinguishable from those of native human Hb A. UV/vis, CD, and NMR spectra of assembled Hb A were also the same as those of human Hb A. These results indicate that individual expressed alpha chains are stable in bacteria and fold properly in vivo and that they then can assemble with free beta chains to form hemoglobin heterotetramers in vivo as well as in vitro.

Globins↗

PubMed2000

Synthesis of [3alpha-3H]cholesta-5,8-dien-3beta-ol and tritium-labeled forms of other sterols of potential importance in the Smith-Lemli-Optiz syndrome.

Five unsaturated sterols relevant to the Smith-Lemli-Opitz syndrome have been prepared in high radiochemical purity with a tritium label at the 3alpha position. Swern oxidation of cholesta-5,8-dien-3beta-ol and other unlabeled C27 sterols afforded the corresponding 3-ketosteroids, and reduction with tritiated NaBH4 gave the desired 3alpha-3H sterols, with double bonds at the delta(5,8), delta(5,8(14)), delta(6,8), delta(6,8(14)), and delta8 positions. High radiochemical purity of the tritiated sterols was demonstrated by normal phase, reversed phase, and silver-ion (Ag+) high-performance liquid chromatography (HPLC). In the course of this work, we developed a medium-pressure variant of Ag+-HPLC for purifying radiolabeled samples, documented significant isotopic fractionation of the 3alpha-tritiated sterols and their acetates on Ag+-HPLC, and discovered unexpected effects of a delta(8(14)) bond on the conformation of 3-keto-delta5-steroids. The synthetic and analytical methodologies described herein should provide a sound basis for investigating the origin and metabolism of sterols involved in the Smith-Lemli-Opitz syndrome and in late stages of cholesterol biosynthesis.

Cholestadienols↗

PubMed2000

Degradation of a fluoropyridinyl drug in capsule formulation: degradant identification, proposed degradation mechanism, and formulation optimization.

The purpose of this paper was to investigate the degradation chemistry of a fluoropyridinyl drug candidate in capsule formulation and to optimize the formulation based on a proposed degradation mechanism. Small developmental batches of capsules were made by tituration of drug substance and excipients using a mortar and pestle, followed by manual encapsulation. Degradants were identified by LC-MS/MS and LC-photodiode array detector (PDA) and were monitored by LC-ultraviolet detector (UVD) during stability studies. It was found that the drug could undergo a nucleophilic substitution reaction in which hydroxyl groups replace the fluorine substituents on the pyridine rings. The initial degradation rate is independent of the drug concentration but dependent on the temperature, the pH of the microenvironment, and the excipient type. On the basis of these experimental results, a nucleophilic substitution reaction mechanism for the degradation was proposed and a successful capsule formulation was developed.

Anthracenes↗