Biomedical subjects

Yi Gu

Publications and source records attributed to Yi Gu.

At least 19 recordsLinked to original sources

PubMed2007

Determination of secnidazole in human plasma by high-performance liquid chromatography with UV detection and its application to the bioequivalence studies.

A simple, accurate, precise and sensitive HPLC-UV method was developed for the determination of secnidazole in human plasma. Secnidazole and tinidazole (IS) were extracted from 0.2 mL of human plasma by ethyl acetate. Secnidazole was then separated by HPLC on a Diamond C(18) column and quantified by ultraviolet detection at 319 nm. The mobile phase consisted of acetonitrile-aqueous 5 mm sodium acetate (30:70, v/v) containing of 0.1% acetic acid adjusted to pH 4.0, and the flow rate was 1.0 mL/min. The low limit of quantification was 0.1 microg/mL. The method was linear over the concentration range 0.1-25.0 microg/mL (R(2) = 1.000). The recovery of secnidazole from human plasma ranged from 76.5 to 89.1%. Inter- and intra-assay precision ranged from 3.3 to 10.7%. Secnidazole in plasma was stable when stored at ambient temperature for 8 h, at -20 degrees C for 2 weeks and at -20 degrees C for three freeze-thaw cycles. The developed method was successfully applied to the pharmacokinetic and bioequivalence studies between test and reference secnidazole tablets following a single 500 mg oral dosage to 20 healthy volunteers of both genders. Pharmacokinetics parameters T(max), C(max), AUC(0-)t, AUC(0-infinity), T(1/2) were determined of both preparations. The analysis of variance (ANOVA) did not show any significant difference between the two preparations and 90% confidence intervals fell within the acceptable range for bioequivalence. It was concluded that the two secnidazole preparations are bioequivalence and may be used interchangeably.

Administration, Oral↗

PubMed2006

Quantitative determination of ginsenoside Rh2 in rat biosamples by liquid chromatography electrospray ionization mass spectrometry.

Ginsenoside Rh2 is a "hot" natural compound with great potential as a new anti-cancer drug based on abundant pharmacological experiments. However, no systemic pharmacokinetic study of Rh2 was reported because current analysis methods could not fully meet the requirements. Thus, we developed a simple LC/MS method with highly improved sensitivities for the determination of Rh2 in rat plasma, bile, urine, feces and most tissues. The tissues and feces were firstly homogenized mechanically using buffer and methanol as the media, respectively. Plasma, bile, urine and tissue homogenates were extracted with diethyl ether for sample preparation. Feces homogenates were directly deproteinized with acetonitrile. The subsequent analysis procedures were performed on a Shimadzu LCMS2010A system (electrospray ionization single quadrupole mass analyzer), with an ODS column (150 mm x 2.0-mm i.d., 5 microm) plus a C18 guard column for separation and ammonium chloride (500 micromol) as mobile phase additive. The proportions of mobile phase were changed timely according to gradient programs. Chlorinated adducts of molecular ions [M + Cl]- of Rh2 at m/z 657.35 and internal standard digitoxin at m/z 799.55 were monitored in selective ion monitoring mode of negative ions. The method was validated to be accurate, precise and rugged with good linearity in all matrices, according to the FDA guidelines. The lower limits of quantitation in rat plasma, urine and feces were 0.2, 0.2 and 20 ng/mL respectively. Stability studies were also performed, indicating that there were no stability-related problems in the analytical procedure of Rh2. The proposed method was successfully applied to the preclinical pharmacokinetic research of Rh2 in rats, including plasma kinetics, tissue distribution and excretion studies.

Animals↗

PubMed2006

RhoH GTPase recruits and activates Zap70 required for T cell receptor signaling and thymocyte development.

RhoH is a hematopoietic-specific, GTPase-deficient member of the Rho GTPase family with unknown physiological function. Here we demonstrate that Rhoh-/- mice have impaired T cell receptor (TCR)-mediated thymocyte selection and maturation, resulting in T cell deficiency. RhoH deficiency resulted in defective CD3zeta phosphorylation, impaired translocation of the signaling molecule Zap70 to the immunological synapse and reduced activation of Zap70-mediated signaling in thymic and peripheral T cells. Proteomic analyses demonstrated that RhoH is a component of TCR signaling and is required for recruitment of Zap70 to the TCR through interaction with RhoH noncanonical immunoreceptor tyrosine-based activation motifs (ITAMs). In vivo reconstitution studies also demonstrated that RhoH function depends on phosphorylation of the RhoH ITAMs. These findings suggest that RhoH is a critical regulator of thymocyte development and TCR signaling by mediating recruitment and activation of Zap70.

Animals↗

PubMed2006

Activation and roles of ALK4/ALK7-mediated maternal TGFbeta signals in zebrafish embryo.

Activin, Nodal, and Vg1, members of the transforming growth factor beta (TGFbeta) superfamily, transduce signal through type I receptors ALK4 or ALK7 and play important roles in mesoderm induction and patterning during vertebrate embryogenesis. However, the timing and magnitude of the ALK4/ALK7-mediated maternal TGFbeta signals are not clear. SB-431542 is identified as an inhibitor of the ALK4/ALK5/ALK7-mediated TGFbeta signals and its specificity in vertebrate embryos has not been reported. We demonstrate that SB-431542 is able to specifically and reproducibly block the Smad2/3-mediated TGFbeta signals in zebrafish embryo. Embryos exposed to SB-431542 exhibit various defects phenocopying Nodal-deficient mutants. SB-431542 treatments starting at different cell cycles before the midblastula transition lead to different degrees of developmental defects in mesoderm induction and patterning, suggesting that maternal TGFbeta signals are activated right after fertilization and required for mesoderm formation and patterning.

Activin Receptors↗

PubMed2006

Simultaneous determination of erythromycin ethylsuccinate and its metabolite erythromycin in human plasma using liquid chromatography-electrospray ionization mass spectrometry for clinical study.

A sensitive and selective liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for simultaneous identification and quantification of erythromycin ethylsuccinate and erythromycin in human plasma, which can be well applied to clinical study. The method was based on liquid-liquid extraction, followed by a LC procedure with an ODS C18 column, and mixture of acetonitrile and 1.67 mmol/l acetic acid as mobile phase. MS detection was performed using a single quadrupole mass spectrometer in positive selected ion monitoring (SIM) mode. The method was validated to be linear, precise and accurate. The lower limit of quantification of erythromycin ethylsuccinate and erythromycin were both 0.5 ng/ml. The proposed method enables the unambiguous identification and quantification of erythromycin ethylsuccinate and erythromycin for clinical drug monitoring.

Adult↗

PubMed2006

In vitro assessment of plasma protein binding of 20(R)-ginsenoside Rh2 by equilibrium dialysis and LC-MS analysis: a case of species differences.

20(R)-Ginsenoside Rh2 is isolated from Chinese traditional ginsengs with main antitumor effects. To support its pharmacokinetic study which was essential for the pre-clinical research for new drug development, in this paper, 20(R)-Rh2 plasma protein binding was assessed in vitro at four concentration levels (50, 100, 200, 400 ng/ml) both in rat and human plasma using equilibrium dialysis and followed by LC-MS analysis. The method was optimized against some influencing factors during both experimental procedures. And it was validated to be specific, sensitive, accurate, precise and of satisfactory recovery. The results showed the binding fractions were about 70% for rats and 27% for human within four concentration levels. It exhibited a significant species difference between human and rats for the plasma protein binding of 20(R)-Rh2.

Animals↗

PubMed2005

Functional analysis of mutations in the kinase domain of the TGF-beta receptor ALK1 reveals different mechanisms for induction of hereditary hemorrhagic telangiectasia.

Genetic studies in mouse and zebrafish have established the importance of activin receptor-like kinase 1 (ALK1) in formation and remodeling of blood vessels. Single-allele mutations in the ALK1 gene have been linked to the human type 2 hereditary hemorrhagic telangiectasia (HHT2). However, how these ALK1 mutations contribute to this disorder remains unclear. To explore the mechanism underlying effect of the HHT-related ALK1 mutations on receptor activity, we generated 11 such mutants and investigated their signaling activities using reporter assay in mammalian cells and examined their effect on zebrafish embryogenesis. Here we show that some of the HHT2-related mutations generate a dominant-negative effect whereas the others give rise to a null phenotype via loss of protein expression or receptor activity. These data indicate that loss-of-function mutations in a single allele of the ALK1 locus are sufficient to contribute to defects in maintaining endothelial integrity.

Activin Receptors, Type I↗

PubMed2005

Simultaneous determination of loratadine and pseudoephedrine sulfate in human plasma by liquid chromatography-electrospray mass spectrometry for pharmacokinetic studies.

To support the pharmacokinetic and bioavailability study of an extended-release loratadine (LOR)/pseudoephedrine sulfate (PES) tablet, a high performance liquid chromatographic-electrospray ionisation-mass spectrometric method (LC-MS) was developed for the simultaneous determination of LOR and PES in human plasma. Diazepam (DP) and phenylpropanolamine (PPA) were used as internal standards for LOR and PES, respectively. Analytes were extracted from alkalized human plasma by liquid/liquid extraction using ethyl ether. Chromatographic separation was performed on an ODS column at flow rate of 0.2 ml/min. The total chromatographic run time was 10.5 min with the retention time of 7.1 min and 6.2 min for LOR and DP, respectively, and 2.2 min for both of PES and PPA. The LOQ was 10 pg/ml and 50 pg/ml for LOR and PES, respectively. The method is accurate and precise enough for its intended purpose.

Calibration↗

PubMed2005

Study on the characteristics of pectin-ketoprofen for colon targeting in rats.

Pectin-ketoprofen (PT-KP) prodrug with the potential for colon targeted delivery has been evaluated. A sensitive HPLC method was established for the determination of concentration of ketoprofen (KP) in rats. This method was also used to evaluate the colon targeting property of PT-KP. KP or PT-KP was given to rats by oral administration at a dosage of 10mg/kg. Plasma and the different parts of gastrointestinal (GI) tract were taken after 2, 4, 6, 8, 10 and 12h of oral administration of KP or PT-KP to rats and the concentration of KP was measured by HPLC. Preliminary experiments show KP distributes mainly in stomach, proximal small intestine and distal small intestine. However, KP released from PT-KP mainly distributes in cecum and colon. Therefore, this approach suggests that PT-KP prodrug has a good colon targeting property.

Animals↗

PubMed2005

RhoH GTPase: a key regulator of hematopoietic cell proliferation and apoptosis?

Rho GTPases are well characterized as critical regulators of cell growth and actin cytoskeleton in eukaryotic cells. The RhoE/Rnd3 subfamily member RhoH is hematopoietic- specific and GTPase deficient and thus is expected to be in the constitutively active, GTP-bound conformation. The activity of RhoH is likely regulated by the level of expression rather than GTP-binding/GTP-hydrolysis cycle in the cell. By RNAi based knock-down and overexpression approaches we recently have shown in hematopoietic progenitor cells that RhoH negatively impacts on growth factor-induced proliferation and survival and modulates chemokine-induced actin reorganization and cell migration. In addition, RhoH appears to counteract Rac GTPase activities, suggesting a possible mechanism by which RhoH functions as an antagonist of Rac signaling in the regulation of cell growth and actin-based functions in blood lineages.

Actins↗

PubMed2004

RhoH, a hematopoietic-specific Rho GTPase, regulates proliferation, survival, migration, and engraftment of hematopoietic progenitor cells.

Rho guanosine triphosphatases (GT-Pases) are recognized as critical mediators of signaling pathways regulating actin assembly, migration, proliferation, and survival in hematopoietic cells. Here, we have studied a recently identified hematopoietic-specific Rho GTPase, RhoH. Unlike most members of the Rho GTPase family, RhoH is GTPase deficient and does not cycle between GTP- and guanosine diphosphate (GDP)-bound forms, suggesting that regulation of RhoH expression may be critical in its activity. We found that RhoH is expressed in murine hematopoietic progenitor cells (HPCs) and fully differentiated myeloid and lymphoid lineages. In cytokine-stimulated HPCs, knockdown of RhoH expression via RNA interference stimulates proliferation, survival, and stromal cell-derived factor-1 alpha (SDF-1 alpha)-induced migration in vitro. Conversely, RhoH overexpression in these cells via retrovirus-mediated gene transfer is associated with impaired activation of Rac GTPases, reduced proliferation, increased apoptosis, and defective actin polymerization and chemotaxis. In vivo, HPCs with RhoH overexpression demonstrate defective hematopoietic reconstitution capability compared with control vector-transduced cells. Our results suggest that RhoH serves as a negative regulator of both growth and actin-based function of HPCs possibly via suppression of Rac-mediated signaling.

Actins↗

PubMed2004

Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and chemotaxis in neutrophils.

Despite having a high degree of sequence similarity, the Rho guanosine triphosphatases Rac1 and Rac2 regulate distinct functions in neutrophils. Here we demonstrate that the unique Rac2 localization and functions in neutrophils are regulated by two separate C-terminal motifs, the hypervariable domain and aspartic acid 150, one of which has not previously been linked to the function of Rho GTPases. In addition, we show an unexpected dependence of Rac1 localization on Rac2 activity in these same cells, demonstrating a degree of crosstalk between two closely related Rho GTPases. Thus, we have defined specific sequences in Rac that specify subcellular localization and determine the specificity of Rac2 in neutrophil chemotaxis and superoxide generation.

Actins↗

PubMed2004

Zinc oxide quantum rods.

Nanoscale zinc oxide (ZnO) rods of diameters close to the Bohr-exciton radius ( approximately 2 nm) can be prepared from a simple acetate precursor, resulting in ligand-capped rods of ZnO, highly dispersible in nonpolar solvents. Zinc oxide, ZnO, is a wide band-gap semiconductor with applications in blue/ultraviolet (UV) optoelectronic devices and piezoelectric devices. We observe self-assembly into uniform stacks of nanorods aligned parallel to each other with respect to the long axis, and photoluminescence measurements provide evidence for one-dimensional quantum confinement.

DNA Probes↗

PubMed2004

The Ser(+r83k) mutation is a second site mutation of SerD affecting the N-terminus of serrate.

The Serrate gene encodes an essential ligand for Notch signaling used during development of the adult wing and other systems in Drosophila melanogaster. Animals heterozygous or homozygous for the Ser(D) allele of this gene display characteristic defects in wing margin formation. We have characterized a spontaneously arising intragenic suppressor of Ser(D) named Ser(+r83k). Homozygous double mutant Ser(+r83k), Ser(D) animals are viable, with normal wing margin formation, but display an aberrant outspread wing posture. The two mutations can be separated by meiotic recombination which restores the Ser(D) mutant phenotype and demonstrates that in the absence of Ser(D) the Ser(+r83k) mutation is homozygous lethal. These two mutations therefore display allelic compensation. Molecular analysis reveals a single C-T transition mutation within the 5' (protein encoding region) of the Ser(+r83k) transcript. This mutation is predicted to change Arginine(176) to Cysteine, possibly leading to altered interactions with the Notch receptor.

Amino Acid Sequence↗

PubMed2004

Multiple signaling pathways and a selector protein sequentially regulate Drosophila wing development.

Drosophila wing development is a useful model to study organogenesis, which requires the input of selector genes that specify the identity of various morphogenetic fields (Weatherbee, S. D. and Carroll, S. B. (1999) Cell 97, 283-286) and cell signaling molecules. In order to understand how the integration of multiple signaling pathways and selector proteins can be achieved during wing development, we studied the regulatory network that controls the expression of Serrate (Ser), a ligand for the Notch (N) signaling pathway, which is essential for the development of the Drosophila wing, as well as vertebrate limbs. Here, we show that a 794 bp cis-regulatory element located in the 3' region of the Ser gene can recapitulate the dynamic patterns of endogenous Ser expression during wing development. Using this enhancer element, we demonstrate that Apterous (Ap, a selector protein), and the Notch and Wingless (Wg) signaling pathways, can sequentially control wing development through direct regulation of Ser expression in early, mid and late third instar stages, respectively. In addition, we show that later Ser expression in the presumptive vein cells is controlled by the Egfr pathway. Thus, a cis-regulatory element is sequentially regulated by multiple signaling pathways and a selector protein during Drosophila wing development. Such a mechanism is possibly conserved in the appendage outgrowth of other arthropods and vertebrates.

Animals↗

PubMed2004

[Substitute valve at popliteal vein in treating deep venous valve insufficiency of lower extremities].

OBJECTIVE: To study the effectiveness of substitute valve at the popliteal vein in treatment of deep venous valve insufficiency of lower extremities. METHODS: From January 1996 to August 2002, 27 patients were diagnosed having deep venous valve insufficiency of lower extremities by color Doppler and radiography with an average disease course of 17.4 years. All 27 patients had varicose vein, 25 pain, 22 swelling, 25 pigmentation in ankle area and 19 chronic ulcerations. Two cases had been treated with great saphenous vein ligation and striping. Average vein pressure in resting position was (11.00 +/- 0.73) kPa, and the ambulatory venous pressure was (9.14 +/- 0.68) kPa. All patients were treated with substitute valve at the popliteal vein, and great saphenous vein ligation and stripping, some were treated with subfascial endoscopic perforating veins ablation. RESULTS: The average ambulatory venous pressure after operation was (5.94 +/- 0.82) kPa, were significantly different from that before operation(P < 0.01). The curative results were satisfactory, and all symptom and physical sign disappeared. After a mean follow-up period of 2-6 years, 21 cases had satisfactory results. CONCLUSION: Substitute valve at the popliteal vein have the value of widespread application.

Adult↗

PubMed2004

[Behavioral features of men who have sex with men].

OBJECTIVE: This behavioral surveillance survey in Sichuan province was aimed to gain an insight into the behavioral features related to HIV prevalence among men who have sex with men (MSM). METHODS: The pilot survey was initiated in the year from September to December, 2003. Two cities, Chengdu and Nanchong, were selected as the surveillance sites. All behavioral data were collected by a special questionnaire. Convenience sampling and snowball sampling techniques were applied to recruit participants in 5 types of places where MSM appeared more often. RESULTS: Most of the participants sexed only with male partners, and the most common ways of intercourse for MSM were anal sex, mouth sex and masturbation. The cases of multiple sex partners existed generally in MSM. The median partner numbers for anal sex and mouth sex were 4.4 and 4.2 respectively. There were 491 MSM (84.7%) who had sexed with male partners 6 months before, in which 68.6% of them sexed with non-commercial regular male partners, 66.2% with non-commercial non-regular male partners, and 20.4% with commercial male partners. Condom use with different male partners varied significantly. The proportions of consistent condom use with non-commercial regular, non-commercial non-regular, and commercial male partners were 15.8%, 16.3% and 32.3% respectively. 1.9% of participants reported they had had the experience of injecting drug and 18.3% of participants reported they had been tested for HIV antibody 12 months before. CONCLUSION: High risk behaviors such as multiple sex partners, unprotected anal sex, commercial sex, and injecting drug use among the MSM population in the two cities were unveiled broadly.

Adult↗

PubMed2004

[Study on AIDS related risk behaviors and the correlated factors among three groups of population in Sichuan province].

OBJECTIVE: To provide the basis for AIDS intervention, the study on the relationship between AIDS related risk behaviors and the related factors was carried out among prostitutes, injection drug users and long-distance truck drivers. METHODS: Questionnaire investigation and statistical analysis as chi(2) test, F test, logistic regression were adopted to analysis the relationship between AIDS related risk behaviors and the correlated factors. RESULTS: Knowledge about AIDS seemed to be related to their level of understanding the problem (in commercial sex workers r = 0.307, P = 0.000, in injection drug users F = 93.07, P = 0.000, in truck man F = 30.06, P = 0.000). Condom use when entertaining their clients last time was related to the knowledge of HIV transmission in commercial sex workers and truck drivers (OR = 1.171, 1.145) and knowledge of HIV prevention (OR = 1.081, 1.397), in drug users regarding gender difference (OR = 2.121). CONCLUSION: This study addressed that the effective means to reduce the rate of AIDS risk behaviors and to lessen the harm of AIDS are to improve the knowledge of AIDS and the effective methods to prevent AIDS in the high risk population.

Acquired Immunodeficiency Syndrome↗