Pharmacodynamic comparison of pantoprazole enantiomers: inhibition of acid-related lesions and acid secretion in rats and guinea-pigs.

Pantoprazole is an irreversible proton pump inhibitor that is administered as a racemic mixture clinically. The effects of pantoprazole sodium (PAN.Na) enantiomers on acid-related lesions were compared using models of pylorus ligation induced ulcer, histamine induced ulcer and reflux oesophagitis in rats and guinea-pigs.

Development and application of rodent models for type 2 diabetes.

The increasing worldwide incidence of diabetes in adults constitutes a global public health burden. It is predicted that by 2025, India, China and the United States will have the largest number of people with diabetes. According to the 2003 estimates of the International Diabetes Federation, the diabetes mellitus prevalence in the USA is 8.

The leucyl aminopeptidase from Helicobacter pylori is an allosteric enzyme.

This study describes the cloning, genetic analysis and biochemical characterization of a leucyl aminopeptidase (LAP) from Helicobacter pylori. A gene encoding LAP was cloned from H. pylori and the expressed 55 kDa protein displayed homology to aminopeptidases from Gram-negative bacteria, plants and mammals.

Evodiamine induced human melanoma A375-S2 cell death partially through interleukin 1 mediated pathway.

We have reported that caspase cascade accompanied by the regulation of Bax/Bcl-2 and MAPK signaling were involved in evodiamine-induced A375-S2 cell death. In this study, pretreatment with interleukin 1 (IL-1) receptor antagonist (IL-1Ra) rescued the cell viability loss and reversed the ratio of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells induced by evodiamine. IL-1Ra was capable of attenuating the expression of Fas-ligand (Fas-L) and the cleavage of procaspas-8 and -3 caused by evodiamine.

Benzothieno[3,2-b]indole derivatives as potent selective estrogen receptor modulators.

A series of estrogen receptor ligands based on benzothieno[3,2-b]indole were synthesized and their binding affinity for estrogen receptor subtypes (ERalpha and ERbeta) and effects on mouse uterus and bone were evaluated. Some of these compounds showed strong binding affinity to ER and significantly increased the bone mineral density of ovariectomized mice.

Antiangiogenic activity of beta-eudesmol in vitro and in vivo.

Abnormal angiogenesis is implicated in various diseases including cancer and diabetic retinopathy. In this study, we examined the effect of beta-eudesmol, a sesquiterpenoid alcohol isolated from Atractylodes lancea rhizome, on angiogenesis in vitro and in vivo. Proliferation of porcine brain microvascular endothelial cells and human umbilical vein endothelial cells (HUVEC) was inhibited by beta-eudesmol (50-100 microM).

Roles of SIRT1 and phosphoinositide 3-OH kinase/protein kinase C pathways in evodiamine-induced human melanoma A375-S2 cell death.

We previously demonstrated that evodimine isolated from Evodia rutaecarpa (Goshuyu in Japan) induced apoptosis in human malignant melanoma A375-S2 cells within 24 h. In this study, TUNEL assay also indicated that one cause of A375-S2 cell death induced by evodiamine was apoptosis. After treatment with evodiamine for the indicated time periods, anti-apoptotic protein SIRT1 expression was decreased; p53 expression and its phosphorylation were both enhanced, whereas transient induction of downstream p21 was not enough to promote cell cycle arrest.

[Mechanism of dracorhodin perchlorate-induced Hela cell apoptosis].

Aim: To study the mechanism of dracorhodin perchlorate-induced Hela cell apoptosis.

Methods: Cell viability was measured by MTT method. Morphological changes were observed by phase contrast microscopy and Hoechst 33258 staining.

[Relationship between idiopathic epilepsy and sleep macrostructure in children].

Objective: To evaluate the relationship between epilepsy and sleep macrostructure in children.

Methods: Totally 31 children with idiopathic epilepsy aged 6-13 (mean 9.5) years were enrolled in this study, including 18 with idiopathic focal epilepsy and 13 with idiopathic generalized epilepsy.

Pharmacokinetics of chitobiose and chitotriose administered intravenously or orally to rats.

Chitooligosaccharides have attracted much attention as new biomedical materials. The biologic availability of each of these chitooligosaccharides, however, has not yet been studied. In the present study, we found that chitobiose and chitotriose appeared in the blood of rats with maximum plasma concentrations at around 1 h after administration when given orally at a dose of 30 mg/kg.

Pseudolaric acid B induces apoptosis through p53 and Bax/Bcl-2 pathways in human melanoma A375-S2 cells.

Pseudolaric acid B is a major compound found in the bark of Pseudolarix kaempferi Gordon. In our study, pseudolaric acid B inhibited growth of human melanoma cells, A375-S2 in a time- and dose-dependent manner. A375-S2 cells treated with pseudolaric acid B showed typical characteristics of apoptosis including morphologic changes, DNA fragmentation, sub-diploid peak in flow cytometry, cleavage of poly-ADP ribose polymerase (PARP) and degradation of inhibitor of caspase-activated DNase (ICAD).

Mitogen-activated protein kinase-dependent apoptosis in norcan-tharidin-treated A375-S2 cells is proceeded by the activation of protein kinase C.

Background: We have reported that norcantharidin (NCTD) induces human melanoma A375-S2 cell apoptosis and that the activation of caspase and the mitochondrial pathway are involved in the apoptotic process. This study aimed at investigating the roles of mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) in A375-S2 cell apoptosis induced by NCTD.

Methods: We assessed the effects of NCTD on cell growth inhibition using the 3-(4,5-dimethylthiazol-2-yl)-2,5-dipheyltetrazolium bromide (MTT) assay, DNA fragmentation (DNA agarose gel electrophoresis), and MAPK protein levels (Western blot analysis) in A375-S2 cells.

Development of a complex scintillation proximity assay for high-throughput screening of PPARgamma modulators.

Aim: To develop a complex high-throughput screening (HTS) assay based on scintillation proximity assay (SPA) technology for identification of novel peroxisome proliferator-activated receptor gamma (PPARgamma) modulators.

Methods: Full-length PPARgamma and retinoid X receptor alpha (RXRalpha), biotinylated PPAR response element (PPRE), [3H]BRL49653 and streptavidin-coated FlashPlate or microbead were used to develop an HTS assay based on SPA technology. This 'ABCDE' method was validated against conventional hydroxyapatite (HA) assay and applied to large-scale screening of 16,000 synthetic compounds and natural product extracts.

[Pseudolaric acid B induces human melanoma A375-S2 cell apoptosis in vitro].

Objective: To study the mechanisms of pseudolaric acid B-induced apoptosis on A375-S2 cells.

Method: MTT, fluorescence microscope observation, DNA agarose gel electrophoresis and Western blot analysis wereused.

Result: Pseudolaric acid Binduces A375-S2 cell apoptosis in a time and dose-dependent manner.

Vasodilatation produced by orientin and its mechanism study.

In this paper we investigated the vascular activity and possible mechanism of Orientin, from bamboo leaves (Phyllostachys nigra), in isolated thoracic aortic rings from New Zealand rabbit. Among the four compounds, studied, only Orientin relaxed phenylephrine-induced contractions with an IC50 value of 2.28 microM in the endothelium intact and with an IC50 value around 7.

Norcantharidin induces apoptosis in HeLa cells through caspase, MAPK, and mitochondrial pathways.

Aim: To investigate the mechanism of norcantharidin (NCTD)-induced HeLa cell apoptosis.

Methods: HeLa cell growth inhibition was measured by MTT method. Apoptosis was detected by Hoechst 33258 staining and agarose gel electrophoresis.

[Clinical analysis of 38 elderly patients with early double primary cancers].

Objective: To study the clinical features and proper treatment of 38 elderly patients with early double primary cancers.

Methods: Thirty-eight elderly patients with early double primary cancers treated from January 1980 to March 2003 were retrospectively reviewed for involved organs, treatment and prognosis.

Results: Digestive tract was the most frequently involved, followed by urogenital system and lung.

Norcantharidin induces human melanoma A375-S2 cell apoptosis through mitochondrial and caspase pathways.

Norcantharidin (NCTD) is the demethylated form of cantharidin, which is the active substance of mylabris. To examine the pathway of NCTD-induced A375-S2 cell death, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dipheyltetrazolium bromide (MTT) assay, photomicroscopical observation, DNA agarose gel electrophoresis, caspase activity assay and Western blot analysis were carried out. A375-S2 cells treated with NCTD exhibited several typical characteristics of apoptosis.

A novel nonpeptide ligand for formyl peptide receptor-like 1.

Formyl peptide receptor-like 1 (FPRL1) is a G protein-coupled receptor that binds natural and synthetic peptides as well as lipoxin A(4) and mediates important biological functions. To facilitate its pharmacological characterization, we screened a compound library and identified a substituted quinazolinone (Quin-C1, 4-butoxy-N-[2-(4-methoxy-phenyl)-4-oxo-1,4-dihydro-2H-quinazolin-3-yl]-benzamide) as a ligand for FPRL1. Quin-C1 induces chemotaxis and secretion of beta-glucuronidase in peripheral blood neutrophils with a potency of approximately 1/1000 of that of the peptide agonist WKYMVm.

The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by impairing RANKL-induced signaling.

Highly active antiretroviral therapy (HAART), which includes HIV protease inhibitors (PIs), has been associated with bone demineralization. To determine if this complication reflects accelerated resorptive activity, we studied the impact of two common HIV PIs, ritonavir and indinavir, on osteoclast formation and function. Surprisingly, we find that ritonavir, but not indinavir, inhibits osteoclast differentiation in a reversible manner and also abrogates bone resorption by disrupting the osteoclast cytoskeleton, without affecting cell number.

[Preparation and characterization of rabbit antibody against gastric cancer-related protein GCRG213].

Aim: To prepare the rabbit antibody against gastric cancer-related protein GCRG213.

Methods: The thioredoxin/GCRG213 fusion protein was expressed in E. coli.

Restoration of baroreflex function by ketanserin is not blood pressure dependent in conscious freely moving rats.

Objective: Since the end of the 1980s, the pathological importance of baroreflex function has attracted the attention of many investigators. In our previous studies, it was found that ketanserin lowered blood pressure (BP), decreased BP variability and enhanced baroreflex sensitivity (BRS). The present work was designed to test the hypothesis that the restoration of BRS by ketanserin is not dependent on BP level in conscious rats.

[Gene expression profile of human adenocarcinoma by cDNA microarray and clustering].

Objective: To investigate the gene expression profile of human gastric adenocarcinoma by means of cDNA microarray and to analyze its biological significance.

Methods: Paired tumor and non-tumor specimens from 18 cases of advanced gastric adenocarcinoma were studied. Total RNA was isolated and labeled by reverse transcription reaction with cy5 and cy3 for cDNA probe.

Pyridoxal-aminoguanidine adduct is more effective than aminoguanidine in preventing neuropathy and cataract in diabetic rats.

We examined the ability of a pyridoxal-aminoguanidine adduct with both antiglycation and antioxidant activities in vitro to protect against neuropathy and cataract in streptozotocin-diabetic rats and compared the result with that of aminoguanidine. In vivo antiglycation and antioxidant activities were also compared between the adduct and aminoguanidine. Diabetic rats were given either of the compounds in their drinking water (9 mM) for 7 weeks.