OBJECTIVETo investigate the absolute bioavailability of caffeic acid in rats and its intestinal absorption properties.

METHODThe absolute bioavailability (Fabs) of caffeic acid was obtained after iv (2 mg x kg(-1)) or ig (10 mg x kg(-1)) administration to rats. The intestinal absorption of caffeic acid was explored by the recirculating vascularly perfused rat intestinal preparation. Caco-2 cell model was applied to measure the permeability of caffeic acid from apical to basolateral said (A-B) and from basolateral to apical said (B-A).

RESULTA two-compartment pharmacokinetic model was best to describe the pharmacokinetics of caffeic acid following iv or ig administration. The Fabs of caffeic acid was 14. 7% , and its intestinal absorption was 12.4%. The values of Papp A-->B and Papp B-->A of caffeic acid were retained stable while its concentration was changed. The efflux ratio values in this study surveyed were above 2.0, and suggesting caffeic acid was active transport.

CONCLUSIONCaffeic acid was shown to have poor permeability across the Caco-2 cells, low intestinal absorption and low oral bioavailability in rats.

Animals ; Biological Availability ; Caco-2 Cells ; Caffeic Acids ; metabolism ; pharmacokinetics ; Humans ; Intestinal Absorption ; Male ; Rats ; Rats, Sprague-Dawley

A case of hereditary benign telangiectasia without family history was reported. A 39-year-old woman presented with small and tiny telangiectases on the face, neck, upper trunk and forearms at birth. The numbers and sizes of the lesions increased gradually and she had no hemorrhagic diathesis and systemic diseases. No similar patients were found in her family. Upon physical examination, telangiectases were found on the face, neck, upper trunk and forearms; and a telangiectatic erythema was found on the right forearm 25 mm × 40 mm in size. Histopathology examination showed a normal epidermis and dilation of the capillaries at upper dermis. Hereditary benign telangiectasia without family history was diagnosed.
Adult ; China ; Female ; Genetic Diseases, Inborn ; diagnosis ; Humans ; Telangiectasis ; diagnosis

Animals ; Cardiomegaly ; Constriction ; Heart ; Mice

AIMTo synthesize the selenophosphocholine analogues containing tegafur and test their antitumor activities.

METHODSThe cyclic glyceroselenophospholopid conjugate of tegafur was synthesized by the reaction of hexaethylphosphorous triamide with N1-(2-furanidyl)-N3-(hydroxyalkyl)-5-fluyorouracil and 1-O-hexadecyl glycerol as well as selenium in one-pot. Cyclic glyceroselenophospholopid conjugate of tegafur reacted with triethylamine to give title compounds.

RESULTSSix new compounds have been synthesized. Their structures were confirmed by 1H NMR, 13P NMR and elemental analysis. Antitumor activity of the title compounds against PGA1 was tested.

CONCLUSIONThe reaction of triethylamine with cyclic glyceroselenophospholopid conjugate of tegafur very readily occurred, which was finished within 2 h at room temperature. The opening-ring products of trans isomers showed antimutor activity against human uriaryl bladder cancer cell more effective than that of the tegafur.

Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Humans ; Magnetic Resonance Spectroscopy ; Organoselenium Compounds ; chemical synthesis ; pharmacology ; Phosphorylcholine ; analogs & derivatives ; Tegafur ; chemical synthesis ; pharmacology ; Urinary Bladder Neoplasms ; drug therapy ; pathology

Aim To explore the anti-psoriatic effects of honokiol on the mouse model induced by imiquimod and the underlying mechanism. Methods The mice were randomly divided into control group, model group, liposome solvent control group, dexamethasone positive group and honokiol high, medium, low dose groups. The progress of the disease was observed by the psoriasis area and severity index (PASI). The morphological changes of the skin cells were observed by HE staining, and epidermis thickness was meas-ured. The expression of IL-17, IL-23, JAK, STAT3, TNF-α and NF-κB was semi-quantitively analyzed by immunohistochemistry. Results Compared to model group, the scaling and thickness of honokiol treated groups were alleviated. Inflammatory infiltration and micro abscess were reduced. The expressions of IL-17, IL-23, JAK, STAT3, TNF-α and NF-κB in model group were higher than those in honokiol-high and honokiol-medium group in a dose-dependent manner. Conclusion Honokiol can inhibit imiquimod-induced psoriasis-like lesions in mice by inhibiting the IL-17/IL-23 inflammatory axis.

OBJECTIVETo summarize the clinical efficacy of pediatric liver transplantation, and investigate the characters of pediatric liver transplantation in their indications, surgical procedures and postoperative management.

METHODSFrom August 2000 to March 2007, 23 liver transplantations were performed on 20 children, aging from 6 months to 13 years old. The most common indications were biliary atresia, Wilson's disease, glycogen storage disease and urea cycle defects. Surgical procedures included 4 living donor liver transplantations, 1 Domino liver transplantation, 5 split grafts, 10 reduced liver grafts and 3 whole cadaveric grafts. The triple-drug (FK506, steroid and MMF) immunosuppressive regimen was used in 19 children, except one children using cyclosporine.

RESULTSThree children died of primary non-function, heart failure and abdominal infections respectively during peri-operative period, and the mortality was 15.0%. Nine children showed different post-operative complications including 2 hepatic artery thrombosis, 1 portal vein thrombosis, 1 acute rejection, 3 biliary leakage, 2 biliary stricture, 2 intestinal fistula, 3 abdominal infection, 1 pulmonary infection and 1 heart failure. Cumulative patient survival rates at 6-month, 1-and 2-year were 80.0%, 73.9% and 73.9%, respectively.

CONCLUSIONSLiver transplantation is an effective option to cure the liver disease of children with end-stage. Different surgical procedure could be chosen according to the children's age and body weight.

Adolescent ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Immunosuppressive Agents ; administration & dosage ; Infant ; Liver Transplantation ; methods ; Male ; Postoperative Complications ; therapy ; Retrospective Studies ; Survival Rate ; Treatment Outcome

BACKGROUNDAlthough liver transplantation has become a standard therapy for end-stage liver diseases, the experience of pediatric liver transplantation is limited in China. In this article we report our experience in pediatric liver transplantation, and summarize its characters in their indications, surgical techniques, and postoperative managements.

METHODSThirty-one children (< or = 18 years old) underwent liver transplantation in our centers. The mean age at transplantation was 12.4 years old (ranged from 5 months to 18 years) with 7 children being less than 4 years of age at transplantation. The most common diagnosis of patients who underwent liver transplantation were biliary atresia, Wilson's disease, primary biliary cirrhosis, glycogen storage disease, hepatoblastoma, urea cycle defects, fulminant hepatic failure, etc. The surgical procedures included 12 standard (without venovenous bypass), 6 pigyback, 6 reduced-size, 3 split, 3 living donor liver transplantation, and 1 Domino liver transplantation. The triple-drug (FK506, steroid, and mycophenolate mofetil) immunosuppressive regimen was used in most of patients. Patients were followed up for a mean of 21.8 months.

RESULTSFive of the 31 patients died during perioperative time; mortality rate was 16.1%. The reasons of death were infections, primary non-function, heart failure, and hypovolemic shock. Postoperative complications in 10 patients included biliary leakage, acute rejection, abdominal infection, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and pulmonary infection. Overall patient cumulative survival rate at 1-, 3-, and 5-year was 78.1%, 62.6%, 62.6%, respectively.

CONCLUSIONSThe most common indications of pediatric liver transplantation were congenital end-stage liver diseases. According to patients' age and body weight, standard, piggyback, reduced-size, split, or living donor liver transplantation should be performed. Pediatric liver transplantation especially requires higher surgical skills. The early postoperative management is the key to success. Postoperative bile leak was common, but most patients underwent liver transplantation had a better prognosis.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Liver Transplantation ; adverse effects ; mortality ; Male ; Postoperative Complications ; etiology ; Retrospective Studies ; Survival Rate

OBJECTIVETo explore novel pathogenic mutation in the mitochondrial DNA gene in diabetic pedigree.

METHODSTwenty-eight suspected mitochondrial DNA diabetic families were recruited. The gene fragment was produced by PCR, and mutation was detected by direct sequencing.

RESULTSIn one pedigree, the proband and her mother were found carrying the most common nt3243 A --> G mutation and another 16S rRNA 3205C --> T mutation. But only 3205C --> T was found in her affected brother. All the two patients were deaf and developed diabetes in early age, characterized by impaired beta cell function and low body mass index (BMI). The proband had relatively higher lactic acid concentration than normal individuals. A novel ND1 gene 3434 A --> G(TAT --> TGT) mutation was explored in another proband with deafness and her affected family members.

CONCLUSION16SrRNA 3205C --> T mutation was found in a mitochondrial diabetes mellitus pedigree, implying its potential pathogenic role in diabetes. Another novel ND1 3434 A --> G mutation was found in another diabetic pedigree. Because this mutation causes amino acid change (Tyr --> Cys) and is co-segregated with diabetes, it may be diabetogenic.

Adult ; Asian Continental Ancestry Group ; genetics ; DNA Mutational Analysis ; DNA, Mitochondrial ; genetics ; Diabetes Mellitus ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; RNA, Ribosomal, 16S ; analysis ; genetics

OBJECTIVETo investigate gene mutations of epidermal growth factor receptor (EGFR) and K-ras in Chinese patients with non-small cell lung cancer (NSCLC) and its clinicopathological significance, and to analyze the correlation between these mutations and tumor response to erlotinib treatment.

METHODSMutations of exons 18, 19, 20 and 21 of the EGFR and codons 12, 13 of the K-ras in 301 cases of NSCLC were detected by PCR-amplification and gene sequencing. The relationship between the mutations and clinicopathological characteristics of the 301 patients was analyzed.

RESULTSEGFR mutations were present in 32.9% (99/301) of the samples: 3 mutation in exon 18, 59 in exon 19, 2 in exon 20, and 35 in exon 21. Mutations of K-ras were present in 4.7% (14/301) of the samples: 13 in codon 12 and 1 in codon 13. EGFR mutations were never found in tumors with K-ras mutations, suggesting a mutually exclusive relationship. EGFR mutations were more common in adenocarcinomas, non-smokers and females. Seven out of 10 erlotinib-treated patients with disease control carried EGFR mutation.

CONCLUSIONThe frequency of EGFR mutation in Chinese NSCLC patients is higher than that in Westerners, but the frequency of K-ras mutation is quite opposite. Combined detection of EGFR gene and K-ras gene mutation may help clinicians to choose patients who may gain benefit from EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment, and to predict their response to erlotinib treatment and prognosis.

Adenocarcinoma ; drug therapy ; genetics ; pathology ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; pathology ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; pathology ; Codon ; Erlotinib Hydrochloride ; Exons ; Female ; Genes, erbB-1 ; Genes, ras ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; Protein Kinase Inhibitors ; therapeutic use ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins p21(ras) ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; genetics ; Sex Factors ; Smoking ; Young Adult ; ras Proteins ; genetics

AIM:To investigate the changes of short-chain acyl-CoA dehydrogenase(SCAD)in hypertensive vascular remodeling and to explore the relationship between SCAD and vascular remodeling in hypertension.METHODS:The spontaneously hypertensive rats(SHR;24 weeks old)and Wistar rats(24 weeks old)were used as experimental con-trol groups.The SHR and Wistar rats of 16 weeks old were trained by swimming as experimental groups.The systolic pres-sure was measured periodically.The thickness of vascular wall and the diameter of the vascular lumen were measured.The contents of ROS and ATP,the enzyme activity of SCAD, and the expression of SCAD at mRNA and protein levels in the aorta were determined.The free fatty acid in the serum and aorta was also measured.RESULTS:Compared with Wistar group,the diameter of vascular lumen decreased in SHR group.The thickness of vascular wall,the ratio of vascular wall and the diameter of vascular lumen,and the blood pressure in SHR group were increased significantly(P<0.05).Com-pared with SHR group,the diameter of vascular lumen increased in SHR +swim group.The thickness of vascular wall,the ratio of vascular wall and the diameter of vascular lumen,and the blood pressure in SHR +swim group were decreased sig-nificantly.Compared with control group, the expression of SCAD at mRNA and protein levels, the enzyme activity of SCAD,and the content of ATP were decreased in SHR group.However,the free fatty acid in the serum and aorta,and the content of ROS in the aorta were increased in SHR group.The expression of SCAD at mRNA and protein levels,the en-zyme activity of SCAD,the content of ATP were increased in Wistar +swim group and SHR +swim group.However, the free fatty acid in serum and aorta,and the content of ROS in the aorta were decreased in Wistar +swim group and SHR+swim group.CONCLUSION: Decrease in SCAD expression may be associated with hypertensive vascular remodeling. Swimming training can reverse hypertensive vascular remodeling by increasing the expression of SCAD in the aorta.