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Biomedical subjects

Y Lou

Publications and source records attributed to Y Lou.

At least 19 recordsLinked to original sources
PubMed2007

Effect of hCG stimulation on plasma androstenone concentrations and cytochrome b5 levels in testicular tissue.

The effect of Human chorionic gonadotropin (hCG) stimulation on the concentrations of free and conjugated androstenone in plasma was studied in 34 crossbred entire male pigs (Landrace x Swedish Yorkshire). Seventeen pigs were treated with hCG 4 days prior to slaughter and the remaining pigs were treated with sterile saline and served as controls. Blood samples were taken prior to hCG or saline injection and on the day before slaughter and analysed for concentrations of free and conjugated androstenone. Testicular tissue samples were taken at slaughter and analysed for the levels of cytochrome b5 (cyb5) protein. Here we have demonstrated for the first time that hCG stimulation causes an increase in the plasma levels of both free and conjugated androstenone. Not all animals responded in the same way to hCG treatment regarding levels of free and conjugated androstenone demonstrating that individual animals can have differences in their capacity to produce free and conjugated androstenone. We suggest that hCG treatment is a good way to determine the potential for androstenone conjugation when androstenone synthesis in the testis is high. The levels of cyb5 protein in the testis were slightly related (r=0.41, p < 0.10) to free androstenone levels in the pigs after hCG administration, although levels of cyb5 protein were not affected by hCG treatment.

Androsterone↗
PubMed2006

Comparative genomics of the lactic acid bacteria.

Lactic acid-producing bacteria are associated with various plant and animal niches and play a key role in the production of fermented foods and beverages. We report nine genome sequences representing the phylogenetic and functional diversity of these bacteria. The small genomes of lactic acid bacteria encode a broad repertoire of transporters for efficient carbon and nitrogen acquisition from the nutritionally rich environments they inhabit and reflect a limited range of biosynthetic capabilities that indicate both prototrophic and auxotrophic strains. Phylogenetic analyses, comparison of gene content across the group, and reconstruction of ancestral gene sets indicate a combination of extensive gene loss and key gene acquisitions via horizontal gene transfer during the coevolution of lactic acid bacteria with their habitats.

Animals↗
PubMed2006

The genome of black cottonwood, Populus trichocarpa (Torr. & Gray).

We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.

Arabidopsis↗
PubMed2006

Inhibition of growth and increase of alkaline phosphatase activity in cultured human oral cancer cells by all-trans retinoic acid.

In this study, the effects of all-trans retinoic acid (ATRA) on human oral cancer cells with regard to cell growth, the cell cycle, and alkaline phosphatase (ALP) activity were evaluated. Human oral cancer KB cells were treated with various concentrations of ATRA, and cell growth was then determined using the MTT viability assay. The cell-cycle distribution and ALP activity were analysed using a flow cytometer and chemical analyser, respectively. The KB cells were inhibited by ATRA at concentrations of 1-16 microM (1 microM, P<0.05; 2 microM, P<0.01; 4, 8 and 16 microM, P<0.001) in a dose-dependent manner. ATRA arrested KB cells in the G0/G1 phase. The ALP activity in KB cells was increased by ATRA. This is one of the first studies to focus on the expression of ALP in human head-and-neck carcinoma cells treated with retinoids. These findings suggest that the anti-tumour effects of ATRA on human oral cancer are associated with G0/G1 phase arrest and an increase in ALP activity.

Alkaline Phosphatase↗
PubMed2006

Molecular cloning and regulation of porcine SULT2A1: relationship between SULT2A1 expression and sulfoconjugation of androstenone.

Hydroxysteroid sulfotransferase (SULT2A1) is a key enzyme in the testicular and hepatic metabolism of 5alpha-androstenone, which is a major component of the off-odor and off-flavor in pork known as boar taint. The goals of this study were to determine the role of testicular and hepatic SULT2A1 activity on plasma 5alpha-androstenone sulfate levels, the accumulation of 5alpha-androstenone in adipose tissue, and to gain insight into the regulatory control of SULT2A1. Testicular SULT2A1 activity was negatively correlated (r = -0.57; P < 0.01) with 5alpha-androstenone concentrations in fat. The differences observed in SULT2A1 activity warranted investigation into potential genetic variation within porcine SULT2A1. The cDNA sequence of porcine Sult2A1 was determined to be > 82% homologous to the human, mouse, and rat Sult2A1 genes. A single nucleotide polymorphism was detected within the coding region of the Sult2A1 from individual testes and liver samples; however, this did not affect the amino acid sequence of the enzyme. Western blot analysis determined that animals with high concentrations of 5alpha-androstenone in fat and low SULT2A1 activity had corresponding low levels of SULT2A1 protein compared with animals with low levels of 5alpha-androstenone in fat. Real-time PCR analysis indicated that Sult2A1 mRNA was increased 2.8-fold in animals with high levels of the protein relative to animals with low levels of the protein. Furthermore, we demonstrated the positive role of the nuclear receptors constitutive androstane receptor and pregnane X receptor, as well as the possible role of farnesoid X receptor in the regulation of testicular SULT2A1 activity. Together, the results of this study suggest that differences in SULT2A1 expression can influence 5alpha-androstenone accumulation in fat.

Adipose Tissue↗
PubMed2006

Characterizing developmental changes in plasma and tissue skatole concentrations in the prepubescent intact male pig.

The accumulation of skatole in boars to concentrations resulting in carcass taint has been associated with elevated concentrations of steroid hormones in plasma. Studying boar taint in vivo has been challenging because steroid hormones are highly variable between individual boars. However, a peak in steroid hormones occurs between 2 and 4 wk postpartum; therefore, skatole production was investigated in the prepubescent pig. Plasma concentrations of estrone sulphate, dehydroepiandrosterone sulphate, and testosterone peaked between 2 and 4 wk postpartum in intact male pigs, whereas plasma concentrations of these steroid hormones remained low or undetectable in gilts and barrows. However, plasma skatole concentration peaked in all 3 groups of animals between 2 and 3 wk postweaning. The effects of weaning time, intestinal cell turnover, and diet on tissue skatole concentrations were then investigated. Intact male piglets were weaned at 14, 21, 28, or 35 d of age. Plasma skatole concentrations were measured weekly for a period of 63 d and peaked at 17 +/- 1, 14 +/- 1, 13 +/- 1, and 10 +/- 2 d postweaning, respectively. Intestinal cell turnover, as evaluated by villous height:crypt depth ratio, was not correlated with skatole concentrations in cecal contents, suggesting that cellular debris did not constitute a gross source of tryptophan for hindgut fermentation. The inclusion of 10% chicory inulin to piglet diets suppressed the postweaning increase in plasma skatole. Cecal skatole concentrations were also 3.3-fold lower in inulin-supplemented piglets compared with controls. The rise in plasma skatole in the prepubescent intact male pig was not associated with increased steroidogenesis but is likely due to the postweaning adaptation of the intestinal flora to an abrupt dietary change.

Aging↗
PubMed2004

Effect of the erbium dopant architecture on the femtosecond relaxation dynamics of silicon nanocrystals.

Femtosecond pump-probe absorption spectroscopy is used to investigate the role of Er(3+) dopants in the early relaxation pathways of photoexcited Si nanocrystals. The fate of photoexcited electrons in three different Si nanostructures was studied and correlated with the effect of Er-doping and the nature of the dopant architecture. In Si nanocrystals without Er(3+) dopant, a trapping component was identified to be a major electron relaxation mechanism. Addition of Er(3+) ions into the core or surface shell of the nanocrystals was found to open up additional nonradiative relaxation pathways, which is attributed to Er-induced trap states in the Si host. Analysis of the photodynamics of the Si nanocrystal samples reveals an electron trapping mechanism involving trap-to-trap hopping in the doped nanocrystals, whereby the density of deep traps seem to increase with the presence of erbium. To gain additional insights on the relative depths of the trapping sites on the investigated nanostructures, benzoquinone was used as a surface adsorbed electron acceptor to facilitate photoinduced electron transfer across the nanocrystal surface and subsequently assist in back electron transfer. The established reduction potential (-0.45 V versus SCE) of the electron acceptor helped reveal that the erbium-doped nanocrystal samples have deeper trapping sites than the undoped Si. Furthermore, the measurements indicate that internally Er-doped Si have relatively deeper trapping sites than the erbium surface-enriched nanocrystals. The electron-shuttling experiment also reveals that the back electron transfer seems not to recover completely to the ground state in the doped Si nanocrystals, which is explained by a mechanism whereby the electrons are captured by deep trapping sites induced by erbium addition in the Si lattice.

Journal Article↗
PubMed2004

Molecular cloning, expression and functional characterization of the cytochrome P450 2A6 gene in pig liver.

Raising intact male pigs would have a significant economic impact on the pork industry because intact males have improved feed efficiency and a greater lean yield of the carcass compared with barrows. However, the presence of skatole, a major cause of boar taint, in meat from intact male pigs could be highly objectionable to consumers. It has been shown that CYP2A6 is a key enzyme in the hepatic metabolism of skatole and that the activity of CYP2A6 is negatively correlated with skatole accumulation in fat. The aim of this study was to isolate and characterize CYP2A6 from pig liver, as well as identify genetic polymorphisms in the CYP2A6 gene, and examine the association between these polymorphisms and skatole level. We identified a single base deletion in CYP2A6, resulting in a frame shift in the coding region that produces a non-functional enzyme, which was associated with high levels of skatole in fat tissue.

Adipose Tissue↗
PubMed2002

Critical processing factors affecting rheological behavior of a wax based formulation.

The use of a wax-based vehicle is one approach to stabilize a drug which is susceptible to hydrolysis and/or oxidation. The drug used in the study, as a microfine powder, is dispersed in the wax mixture and encapsulated in a soft gelatin capsule. To ensure reproducibility of drug content uniformity and encapsulability of the soft gelatin capsule dosage form, optimal viscosity and lot to lot uniformity of the viscosity of the suspension are required. The objective of the study was to identify the critical processing factors which could affect the rheological behavior of the wax based vehicle. Rheological behavior of the vehicle at temperatures ranging from 15 to 90 degrees C was evaluated using a CSL Rheometer equipped with parallel plates and a shear rate sweep mode, unless otherwise specified. Viscosity vs. temperature profiles of the vehicle were determined using the same conditions at different cooling rates ranging from 1.3 to 20 degrees C per min. Three distinct regions of phase transition of the wax mixture can be seen in the Arrhenius plot: (i) a sol region at temperatures above 50 degrees C, (ii) a transition of gel to sol at temperatures ranging from 30 to 45 degrees C, and (iii) a gel region at temperatures below 30 degrees C. The vehicle in a sol region behaved as a Newtonian fluid, indicating minimal interactions between the hydrocarbon chains of the vehicle. The vehicle in a gel region behaved thixotropic in nature, as indicated by a hysteresis loop. The shear rate had a more pronounced effect on the area of thixotropy than the shear time. The cooling rate had a pronounced effect on the resultant viscosity. At the same applied shear rate, the vehicle which was cooled at a faster rate, may cause a recrystallization of the wax mixture in different crystalline forms, resulting in a higher viscosity than the vehicle cooled at a slower rate. This effect was more pronounced when the shear was applied at a lower rate. The results of this study indicate that shear rate and cooling rate are the critical processing factors in controlling the viscosity of the final product and must be well controlled in the manufacturing procedure.

Calorimetry, Differential Scanning↗
PubMed2002

A gene therapy for cancer based on the angiogenesis inhibitor, vasostatin.

The growth and persistence of solid tumors and their metastasis are angiogenesis-dependent. Vasostatin, the N-terminal domain of calreticulin inclusive of amino acids 1-180, is a potent angiogenesis inhibitor. To investigate whether intramuscular administration of vasostatin gene has the antitumor activity in mouse tumor models, we constructed a plasmid DNA encoding vasostatin and a control vector. Production and secretion of vasostatin protein by COS cells transfected with the plasmid DNA encoding vasostatin (pSecTag2B-vaso) were confirmed by Western blot analysis and ELISA. Conditioned medium from vasostatin-transfected COS cells apparently inhibited human umbilical vein endothelial cell (HUVEC) and mouse endothelial cell (SVEC4-10) proliferation, compared with conditioned medium from the COS cells transfected with control vector or non-transfected cells. Treatment with pSecTag2B-vaso twice weekly for 4 weeks resulted in the inhibition of tumor growth and the prolongation of the survival of tumor-bearing mice. The sustained high level of vasostatin protein in serum could be identified in ELISA. Angiogenesis was apparently inhibited in tumor by immunohistochemical analysis. Angiogenesis was also inhibited in the chicken embryo CAM assay and mouse corneal micropocket assay. The increased apoptotic cells were found within the tumor tissues from the mice treated with plasmid DNA encoding vasostatin. Taken together, the data in the present study indicate that the cancer gene therapy by the intramuscular delivery of plasmid DNA encoding vasostatin, is effective in the inhibition of the systemic angiogenesis and tumor growth in murine models. The present findings also provide further evidence of the anti-tumor effects of the vasostatin, and may be of importance for the further exploration of the application of this molecule in the treatment of cancer.

Angiogenesis Inhibitors↗
PubMed2001

Molecular cloning and characterization of chemokine-like factor 1 (CKLF1), a novel human cytokine with unique structure and potential chemotactic activity.

Cytokines are small proteins that have an essential role in the immune and inflammatory responses. The repertoire of cytokines is becoming diverse and expanding. Here we report the identification and characterization of a novel cytokine designated as chemokine-like factor 1 (CKLF1). The full-length cDNA of CKLF1 is 530 bp long and a single open reading frame encoding 99 amino acid residues. CKLF1 bears no significant similarity to any other known cytokine in its amino acid sequence. Expression of CKLF1 can be partly inhibited by interleukin 10 in PHA-stimulated U937 cells. Recombinant CKLF1 is a potent chemoattractant for neutrophils, monocytes and lymphocytes; moreover, it can stimulate the proliferation of murine skeletal muscle cells. These results suggest that CKLF1 might have important roles in inflammation and in the regeneration of skeletal muscle.

Amino Acid Sequence↗
PubMed2001

Pharmacokinetics and safety of amprenavir and ritonavir following multiple-dose, co-administration to healthy volunteers.

OBJECTIVE: To evaluate the safety and pharmacokinetic interaction between amprenavir (APV) and ritonavir (RTV). METHODS: Three open-label, randomized, two-sequence, multiple-dose studies having the same design (7 days of APV or RTV alone followed by 7 days of both drugs together) used 450 or 900 mg APV with 100 or 300 mg RTV every 12 h with pharmacokinetic assessments on days 7 and 14. Safety was monitored as clinical adverse events (AEs) and laboratory abnormalities. RESULTS: Relative to APV alone, RTV co-administration resulted in a 3.3- to 4-fold and 10.84 to 14.25-fold increase in the geometric least-square (GLS) mean area under the plasma concentration--time curve (AUC(tau,ss)) and minimum concentration (C(min,ss)), respectively. APV 900 mg with RTV 100 mg resulted in a 2.09-fold and 6.85-fold increase in the GLS mean AUC(tau,ss) and C(min,ss), respectively. On day 14, the geometric mean (95% confidence interval) for 450 mg APV AUC(tau,ss) (micro x h/mL) was 23.49 (19.32--28.57) with 300 mg RTV and 35.42 (30.46--44.42) with 100 microg RTV, and for the 900 mg APV with 100 mg RTV 47.11 (39.47--61.24). The 450 mg APV C(min,ss) (microg/ml) were 1.32 (1.05--1.67) and 2.01 (1.70--2.61), and 2.47 (2.08--3.32) for 900 mg APV. The most common AEs were mild and included diarrhea, nausea/vomiting, oral parasthesias, and rash. The triglyceride and cholesterol increased significantly from RTV exposure. CONCLUSION: Adding RTV to APV resulted in clinically and statistically significant increases in APV AUC and C(min) with variable effects on maximum concentration. The two RTV doses had similar effects on APV but AEs were more frequent with 300 mg RTV.

Administration, Oral↗
PubMed2001

Patterns of multiallelic polymorphism maintained by migration and selection.

Evolution at a multiallelic locus under the joint action of migration and viability selection is investigated. Generations are discrete and nonoverlapping. The monoecious, diploid population is subdivided into finitely many panmictic colonies that exchange adult migrants independently of genotype. The forward migration matrix is arbitrary, but time independent and ergodic (i.e., irreducible and aperiodic). Several examples of globally attracting multiallelic equilibria are presented. Migration can cause global fixation even if, without migration, there is a globally attracting multiallelic equilibrium in every colony. Migration can also cause the global fixation of an allele that, without migration, is eliminated in every colony. Without dominance, generically, the number of alleles present at equilibrium cannot exceed the number of colonies. Some general properties and examples of the Levene model are studied in detail. If in each colony there is either no dominance or, without migration, a globally attracting internal equilibrium, then there exists a globally attracting equilibrium with migration. Therefore, if an internal equilibrium exists, it is the global attractor.

Alleles↗
PubMed2001

Pharmacokinetic and pharmacodynamic study of the human immunodeficiency virus protease inhibitor amprenavir after multiple oral dosing.

In a dose-ranging study of amprenavir (formerly 141W94), an inhibitor of the protease enzyme of human immunodeficiency virus (HIV) type 1, single-dose and steady-state pharmacokinetic parameters were estimated from plasma samples collected on day 1 and during week 3, respectively. Amprenavir was administered on either a twice-daily (b.i.d.) or three-times-daily dosage schedule to 62 HIV-infected adults, 59 of whom had pharmacokinetic data. Log-log regression analysis (the power model) revealed that the steady-state area under the curve (AUC(ss)) and the maximum, minimum, and average concentrations at steady state (C(max,ss), C(min,ss), and C(avg,ss), respectively) increased in a dose-proportional manner over the 300- to 1,200-mg dose range. Steady-state clearance was dose independent. AUC(ss)/AUC(0-->infinity) decreased linearly with dose and correlated significantly with treatment-associated decreases in alpha(1)-acid glycoprotein. After 3 weeks, the dose of 1,200 mg b.i. d. provided a median amprenavir C(min,ss) (0.280 microg/ml) that was higher than the median in vitro 50% inhibitory concentration for clinical HIV isolates (0.023 microg/ml), even after adjustment for protein binding. The median amprenavir C(min,ss) was also greater than the estimated in vivo trough concentration calculated to yield 90% of the maximum antiviral effect (0.228 microg/ml) over 4 weeks. A pharmacodynamic analysis of the relationship between steady-state pharmacokinetic parameters and safety revealed headache and oral numbness to be the only side effects significantly associated with C(max). The pharmacodynamic relationship defined in this study supports the use of 1,200 mg b.i.d. as the approved dose of amprenavir.

Adolescent↗
PubMed2001

Pharmacokinetic study of human immunodeficiency virus protease inhibitors used in combination with amprenavir.

In an open-label, randomized, multicenter, multiple-dose pharmacokinetic study, we determined the steady-state pharmacokinetics of amprenavir with and without coadministration of indinavir, nelfinavir, or saquinavir soft gel formulation in 31 human immunodeficiency virus type 1-infected subjects. The results indicated that amprenavir plasma concentrations were decreased by saquinavir soft gel capsule (by 32% for area under the concentration-time curve at steady state [AUC(ss)] and 37% for peak plasma concentration at steady state [C(max,ss)]) and increased by indinavir (33% for AUC(ss)). Nelfinavir significantly increased amprenavir minimum drug concentration at steady state (by 189%) but did not affect amprenavir AUC(ss) or C(max,ss). Nelfinavir and saquinavir steady-state pharmacokinetics were unchanged by coadministration with amprenavir compared with the historical monotherapy data. Concentrations of indinavir, coadministered with amprenavir, in plasma decreased in both single-dose and steady-state evaluations. The changes in amprenavir steady-state pharmacokinetic parameters, relative to those for amprenavir alone, were not consistent among protease inhibitors, nor were the changes consistent with potential interactions in CYP3A4 metabolism or P-glycoprotein transport. No dose adjustment of either protease inhibitor in any of the combinations studied is needed.

Adult↗
PubMed2001

Pharmacokinetic Interaction between amprenavir and rifabutin or rifampin in healthy males.

The objective of this study was to determine if there is a pharmacokinetic interaction when amprenavir is given with rifabutin or rifampin and to determine the effects of these drugs on the erythromycin breath test (ERMBT). Twenty-four healthy male subjects were randomized to one of two cohorts. All subjects received amprenavir (1,200 mg twice a day) for 4 days, followed by a 7-day washout period, followed by either rifabutin (300 mg once a day [QD]) (cohort 1) or rifampin (600 mg QD) (cohort 2) for 14 days. Cohort 1 then received amprenavir plus rifabutin for 10 days, and cohort 2 received amprenavir plus rifampin for 4 days. Serial plasma and urine samples for measurement of amprenavir, rifabutin, and rifampin and their 25-O-desacetyl metabolites, were measured by high-performance liquid chromatography. Rifabutin did not significantly affect amprenavir's pharmacokinetics. Amprenavir significantly increased the area under the curve at steady state (AUC(ss)) of rifabutin by 2.93-fold and the AUC(ss) of 25-O-desacetylrifabutin by 13.3-fold. Rifampin significantly decreased the AUC(ss) of amprenavir by 82%, but amprenavir had no effect on rifampin pharmacokinetics. Amprenavir decreased the results of the ERMBT by 83%. The results of the ERMBT after 2 weeks of rifabutin and rifampin therapy were increased 187 and 156%, respectively. Amprenavir plus rifampin was well tolerated. Amprenavir plus rifabutin was poorly tolerated, and 5 of 11 subjects discontinued therapy. Rifampin markedly increases the metabolic clearance of amprenavir, and coadministration is contraindicated. Amprenavir significantly decreases clearance of rifabutin and 25-O-desacetylrifabutin, and the combination is poorly tolerated. Amprenavir inhibits the ERMBT, and rifampin and rifabutin are equipotent inducers of the ERMBT.

Adolescent↗
PubMed2001

In vivo effect of alpha(1)-acid glycoprotein on pharmacokinetics of amprenavir, a human immunodeficiency virus protease inhibitor.

Observations from early clinical pharmacology studies of amprenavir, an inhibitor of human immunodeficiency virus type 1 (HIV-1) protease that is highly bound to human plasma proteins (approximately 90%), showed the single-dose pharmacokinetics of amprenavir to be variable between and within individuals. A cross-study analysis of various demographic, laboratory, and clinical covariates was therefore performed. Differences in amprenavir pharmacokinetics could be due to variable concentrations in alpha(1)-acid glycoprotein (AAG), the predominant plasma protein to which amprenavir binds. Therefore, AAG was considered an important factor to study since the literature suggested that AAG levels vary by race, age, and weight and following trauma or infection, including HIV disease. Pooled data from three single-dose studies analyzed by stepwise linear regression indicated that AAG concentrations significantly correlated with age and race and that only AAG concentrations were a significant predictor of amprenavir apparent total clearance (CL/F). A significant inverse linear relationship was found between AAG and amprenavir CL/F. Compared to white subjects, black subjects had significantly lower AAG concentrations and therefore significantly higher amprenavir CL/F. Although AAG has a significant influence on the variability of total drug pharmacokinetics, unbound, or free, drug concentrations are not affected by AAG concentrations. Incorrect conclusions could be drawn on the pharmacokinetics of highly protein-bound drugs if AAG concentration is not included in the analysis.

Adolescent↗