Inhibin B, activin A, and follistatin and the pathogenesis of polycystic ovary syndrome.
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Activins↗
Biomedical subjects
X P Chen
Publications and source records attributed to X P Chen.
A fatal chronic ketamine poisoning.
A few papers in the literature reported incident deaths by acute ketamine poisoning. In this paper, we report an unusual homicide caused by chronic ketamine poisoning. The victim was a 34-year old married woman with no previous medical history (except as reported herein) who died in her own home. The court investigation revealed that she was chronically poisoned by her husband over a period of about one year in an act of homicide. Determination of ketamine concentrations in autopsy specimens was carried out with gas-chromatography/mass spectrometry (GC-MS). The results showed that ketamine concentration was 21 microg/mL in gastric contents, 3.8 microg/mL in blood and 1.2 microg/mL in urine. The most striking forensic findings were cardiac muscle fibrosis and hyaline degeneration of small arteries in victim's heart, the pathological features of ketamine poisoning previous reported only in animal studies.
Adult↗
Involvement of hypoxia-inducible factor-1-alpha in multidrug resistance induced by hypoxia in HepG2 cells.
Aim of the study was to explore the influence of hypoxia on multidrug resistance related genes and the potential role of hypoxia-inducible factor-1-alpha (HIF-1alpha) in formation of multidrug resistance in HepG2 human hepatocellular carcinoma cell line. HepG2 cells were subjected to hypoxia in a cohort of exposed time. A cell model stably expressing HIF-1alpha was established by liposome-mediated transfection of plasmid pcDNA3/HIF-1alpha into HepG2 cells. Apoptosis of HepG2 cells exposed to hypoxia or transfected by plasmid pcDNA3/HIF-1alpha was detected by Flow Cytometry after administration of chemotherapeutic drug (5-Fu). Real-time fluorescent quantitative PCR and Western-blot technique were used to analyze the expressions of multidrug resistance related genes mdr1, MRP1 and LRP at mRNA and protein level, respectively. Apoptosis Index of HepG2 cells exposed to hypoxia stepped down as exposed time extended after administration of 5-Fu. The expression of mdr1, MRP1 and LRP gene and protein revealed a hypoxic time-dependent induction and was synchronous with the alterations of HIF-1alpha in HepG2 cells exposed to hypoxia. The expressions of these multidrug resistance related genes were remarkably increased in HIF-1alpha transfected HepG2 cells as compared to empty vector transfected cells. Apoptosis index of HIF-1alpha transfected cells was obviously less than that of control cells when they were simultaneously exposed to 5-Fu for 24hrs. In conclusion, ambient hypoxia might be one of the causes for the formation of multidrug resistance in HepG2 human hepatocellular carcinoma cell line. Hypoxia-elicited multidrug resistance related protein expression might be a pathway for resistance of HepG2 cells to chemotherapeutics and HIF-1alpha might be involved in this process.
Apoptosis↗
Chinese experience with hepatectomy for huge hepatocellular carcinoma.
BACKGROUND: The risks and outcome of hepatic resection for huge hepatocellular carcinoma (HCC) are controversial. METHODS: The clinical records of 525 patients who underwent resection of HCC greater than 10 cm in diameter were studied retrospectively. Prognostic factors for long-term survival were evaluated by univariate and multivariate analyses. RESULTS: Postoperative complications were common (26.8 per cent) and five patients (0.9 per cent) required relaparotomy. The 30-day mortality rate was 2.7 per cent. The main causes of postoperative death were liver failure (nine patients) and bleeding (four). The 3-, 5- and 10-year crude survival rates after liver resection were 34.3, 16.8 and 2.9 per cent respectively. CONCLUSION: Prognostic factors for long-term survival mainly reflected the biological behaviour of the tumour. They can be used only as a guide in balancing the risks of operation against the potential benefits of resection in a patient in poor general condition or with poor liver function. They cannot be used alone to exclude patients from liver resection with curative intent. Liver resection for huge HCC was safe and efficacious. It should be used to treat patients with acceptable surgical risks and resectable tumours.
Aged↗
Effect of the CYP2C19 oxidation polymorphism on fluoxetine metabolism in Chinese healthy subjects.
AIMS: The study was designed to investigate whether genetically determined CYP2C19 activity affects the metabolism of fluoxetine in healthy subjects. METHODS: A single oral dose of fluoxetine (40 mg) was administrated successively to 14 healthy young men with high (extensive metabolizers, n=8) and low (poor metabolizers, n = 6) CYP2C19 activity. Blood samples were collected for 5-7 half-lives and fluoxetine, and norfluoxetine were determined by reversed-phase high performance liquid chromatography. RESULTS: Poor metabolizers (PMs) showed a mean 46% increase in fluoxetine peak plasma concentrations (Cmax, P < 0.001), 128% increase in area under the concentration vs time curve (AUC(0, infinity), P < 0.001), 113% increase in terminal elimination half-life (t(1/2)) (P < 0.001), and 55% decrease in CLo (P < 0.001) compared with extensive metabolizers (EMs). Mean +/- (s.d) norfluoxetine AUC(0, 192 h) was significantly lower in PMs than that in EMs (1343 +/- 277 vs 2935 +/- 311, P < 0.001). Mean fluoxetine Cmax and AUC(0, infinity) in wild-type homozygotes (CYP2C19*1/CYP2C19*1) were significantly lower than that in PMs (22.4 +/- 3.9 vs 36.7 +/- 8.9, P < 0.001; 732 +/- 42 vs 2152 +/- 492, P < 0.001, respectively). Mean oral clearance in individuals with the wild type homozygous genotype was significantly higher than that in heterozygotes and that in PMs (54.7 +/- 3.4 vs 36.0 +/- 8.7, P < 0.01; 54.7 +/- 3.4 vs 20.6 +/- 6.2, P < 0.001, respectively). Mean norfluoxetine AUC(0, 192 h) in PMs was significantly lower than that in wild type homozygotes (1343 +/- 277 vs 3163 +/- 121, P < 0.05) and that in heterozygotes (1343 +/- 277 vs 2706 +/- 273, P < 0.001), respectively. CONCLUSIONS: The results indicated that CYP2C19 appears to play a major role in the metabolism of fluoxetine, and in particular its N-demethylation among Chinese healthy subjects.
Adolescent↗
Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19.
OBJECTIVE: Our objective was to evaluate the relationship between the disposition of sertraline and the presence of the CYP2C19 gene and to define the contribution of cytochrome P450 2C19 (CYP2C19) to sertraline N-demethylation. METHODS: A single oral 100-mg dose of sertraline was administered to 6 subjects who were extensive metabolizers and 6 subjects who were poor metabolizers recruited from 77 healthy Chinese volunteers whose genotypes were predetermined by polymerase chain reaction-based amplification, followed by restriction fragment length polymorphism analysis. Phenotypes were determined by use of the omeprazole metabolic rate. The plasma concentrations of sertraline and desmethylsertraline were determined by gas chromatography with electron-capture detection. RESULTS: Six poor metabolizers with m1 mutation had area under the plasma concentration versus time curve (AUC(0-infinity)) values (983.6 +/- 199.3 microg x h/L versus 697.6 +/- 133.0 microg x h/L; P <.05) and terminal elimination half-life values of sertraline (35.5 +/- 5.6 hours versus 23.5 +/- 4.4 hours; P <.01) that were significantly higher than the values in 6 extensive metabolizers who were either homozygous or heterozygous for CYP2C19*1. The oral clearance of sertraline in poor metabolizers (105.3 +/- 19.4 L/h) was significantly lower than that of extensive metabolizers (148.4 +/- 28.6 L/h). The area under the concentration-time curve from 0 to 144 hours and the maximum plasma concentration of desmethylsertraline in poor metabolizers were significantly lower than the values of extensive metabolizers (627.6 +/- 203.8 microg x h/L versus 972.1 +/- 270.3 microg x h/L; P <.05; and 23.6 +/- 6.5 nmol/L versus 32.4 +/- 8.2 nmol/L; P <.01; respectively). CONCLUSIONS: The polymorphic CYP2C19 appears to be a major enzyme involved in the N-demethylation of sertraline, and both extensive and poor metabolizers had marked differences in the disposition of sertraline.
Administration, Oral↗
Assessment of cytochrome P450 activity by a five-drug cocktail approach.
OBJECTIVES: Our goal was to establish and validate a modified cocktail approach including probe drugs caffeine, chlorzoxazone, mephenytoin, metoprolol, and midazolam for simultaneous phenotyping of CYP1A2, CYP2E1, CYP2C19, CYP2D6, and CYP3A. METHODS: The study was conducted in 14 healthy, nonsmoking male volunteers with a cocktail of 5 drugs consisting of 100 mg caffeine, 200 mg chlorzoxazone, 100 mg mephenytoin, 100 mg metoprolol, and 7.5 mg midazolam in a randomized manner with a 7 x 7 Latin square design. Plasma was obtained at 1, 4, and 6 hours, and urine was collected from 0 to 8 hours after oral drug administration. RESULTS: The phenotypic indexes determined for caffeine, chlorzoxazone, mephenytoin, metoprolol, and midazolam were not significantly different when the drugs were given in different combinations. There were no metabolic interactions or analytic interference of these probe drugs. CONCLUSIONS: This cocktail approach can simultaneously provide independent in vivo phenotypic measures for the cytochrome P450 (CYP) enzymes CYP1A2, CYP2E1, CYP2C19, CYP2D6, and CYP3A.
Adult↗
Plasma caffeine metabolite ratio (17X/137X) in vivo associated with G-2964A and C734A polymorphisms of human CYP1A2.
Either G-2964 or A734 in the human CYP1A2 gene was confirmed to be associated with high inducible enzyme activity in smokers, but not in nonsmokers. In this study, for the first time, we observed an association between phenotypes and genotypes of CYP1A2 with respect to the two genetic polymorphisms in 163 healthy Chinese volunteers living in Qidong. The ratio of plasma 17X/137X at 6 h after oral administration of 300 mg caffeine was employed in CYP1A2 phenotyping analysis, while genotyping analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism. The allele frequencies of A at -2964 and A at 734 in 139 non-smoking subjects were 0.25 and 0.67, respectively. The A/A-2964C/C734, G/A-2964C/C734 or A/A-2964C/A734 genotype that was thought to have lower inducibility/activity of CYP1A2 than the other genotypes did not exist in the tested Chinese subjects. The ratio of 17X/137X was 0.46 +/- 0.26 in G/G-2964A/A734 genotypes (n = 22) and 0.36 +/- 0.19 in non-G/G-2964A/A734 (n = 117). In addition, there was significant difference between them (P = 0.036). A similar result was also achieved in 24 smokers. Since Qidong is a special region with particularly high incidence of hepatocellular carcinoma in China, the association of phenotypes with genotypes of CYP1A2 in the Qidong population might result from some inducible environmental factors such as those of cigarettes in smokers.
Adult↗
Experimental research on TECA-I bioartificial liver support system to treat canines with acute liver failure.
AIM: To evaluate the efficacy and safety of the TECA-I bioartificial liver support system (BALSS) in treating canines with acute liver failure (ALF). METHODS: Ten canines with ALF induced by 80% liver resection received BALSS treatment (BALSS group). Blood was perfused through a hollow fiber tube containing 1X10(10) porcine hepatocytes. Four canines with ALF were treated with BALSS without porcine hepatocytes (control group), and five canines with ALF received drug treatment (drug group). Each treatment lasted 6 hours. RESULTS: BALSS treatment yielded beneficial effects for partial liver resection induced ALF canines with survival and decreased plasma ammonia, ALT, AST and BIL. There was an obvious decrease in PT level and increase in PA level, and there were no changes in the count of lymphocytes, immunoglobulins (IgA, IgG and IgM) and complement (C3 and C4) levels after BALSS treatment. In contrast, for the canines with ALF in non-hepatocyte BALSS group (control group) and drug group, there were no significant changes in ammonia, ALT, AST, BIL, PT and PA levels. ALF canines in BALSS group, control group and drug group lived respectively an average time of 108.0h +/- 12.0h, 24.0h +/- 6.0h and 20.4h +/- 6.4h,and three canines with ALF survived in BALSS group. CONCLUSION: TECA-I BALSS is efficacious and safe for ALF canines induced by partial liver resection.
Animals↗
Diagnosis and treatment of congenital choledochal cyst: 20 years' experience in China.
AIM: To summarize the experience of diagnosis and treatment of congenital choledochal cyst in the past 20 years (1980-2000). METHODS: The clinical data of 108 patients admitted from 1980 to 2000 were analyzed retrospectively. RESULTS: Abdominal pain,jaundice and abdominal mass were presented in most child cases. Clinical symptoms in adult cases were non-specific, resulting in delayed diagnosis frequently. Fifty-seven patients (52.7%) had coexistent pancreatiobiliary disease. Carcinoma of the biliary duct occurred in 18 patients (16.6%). Ultrasonic examination was undertaken in 94 cases, ERCP performed in 46 cases and CT in 71 cases. All of the cases were correctly diagnosed before operation. Abnormal pancreatobiliary duct junction was found in 39 patients. Before 1985 the diagnosis and classification of congenital choledochal cyst were established by ultrasonography preoperatively and confirmed during operation, the main procedures were internal drainage by cyst enterostomy. After 1985, the diagnosis was established by ERCP and CT, and cystectomy with Roux-en-Y hepaticojejunostomy was the conventional procedures.In 1994, we reported a new and simplified operative procedure in order to reduce the risk of choledochal cyst malignancy. Postoperative complication was mainly retrograde infection of biliary tract, which could be controlled by the administration of antibiotics, there was no perioperative mortality. CONCLUSION: The concept in diagnosis and treatment of congenital choledochal cyst has obviously been changed greatly.CT and ERCP were of great help in the classification of the disease.Currently, cystectomy with Roux-en-Y hepaticojejunostomy is strongly recommended as the choice for patients with type I and type IV cysts. Piggyback orthotopic liver transplantation is indicated in type V cysts (Caroli's disease) with frequently recurrent cholangitis.
Adolescent↗
TECA hybrid artificial liver support system in treatment of acute liver failure.
AIM: To assess the efficacy and safety of TECA type hybrid artificial liver support system (TECA-HALSS) in providing liver function of detoxification, metabolism and physiology by treating the patients with acute liver failure (ALF). METHODS: The porcine liver cells (1-2) x 10(10) were separated from the Chinese small swine and cultured in the bioreactor of TECA-BALSS at 37.0 degrees C and circulated through the outer space of the hollow fiber tubes in BALSS. The six liver failure patients with various degree of hepatic coma were treated by TECA-HALSS and with conventional medicines. The venous plasma of the patients was separated by a plasma separator and treated by charcoal adsorbent or plasma exchange. The plasma circulated through the inner space of the hollow fiber tubes of BALSS and mixed with the patients' blood cells and flew back to their blood circulation. Some small molecular weight substances were exchanged between the plasma and porcine liver cells. Each treatment lasted 6.0-7.0 h. Physiological and biochemical parameters were measured before,during and after the treatment. RESULTS: The average of porcine liver cells was (1.0-3.0) x 10(10) obtained from each swine liver using our modified enzymatic digestion method. The survival rate of the cells was 85%-93% by trypan blue stain and AO/PI fluorescent stain. After cultured in TECA-BALSS bioreactor for 6 h, the survival rate of cells still remained 70%-85%. At the end of TECA-HALSS treatment, the levels of plasma NH(3), ALT, TB and DB were significantly decreased. The patients who were in the state of drowsiness or coma before the treatment improved their appetite significantly and regained consciousness, some patients resumed light physical work on a short period after the treatment. One to two days after the treatment, the ratio of PTA increased warkedly. During the treatment, the heart rates, blood pressure, respiration condition and serum electrolytes (K(+), Na(+) and Cl(-)) were stable without thrombosis and bleeding in all the six patients. CONCLUSION: TECA-HALSS treatment could be a rapid, safe and efficacious method to provide temporary liver support for patients with ALF.
Acute Disease↗
Effect of long-term fertilization on soil nitrate distribution.
A thirteen years long-term field fertilizer experiment was conducted to monitor the effect of different fertilization on soil nitrate distribution. The results showed: (1) Applying relative excessive N fertilizer could result large quantities of NO3- residue and NO3- movement downward in soil profiles; amending phosphate fertilizer or organic manure with nitrogen fertilizer together could significantly improve the status of NO3- leaching downward due to the balanced uptake of nutrients by crops. (2) Appropriate amounts of nitrogen fertilizer which was equal or smaller than the optimal fertilization rate could not result in more NO3- leaching in Northern China. (3) Precipitation influenced the amounts and depth of soil NO3- leaching: NO3- could move to 80 cm depth or below at autumn or at the next spring when rainfall was higher during the rainy season through July to September in North China.
Agriculture↗
[Analysis of main chemical composition in hydrogenated rosin from Zhuzhou].
The acid fraction, the main part of the hydrogenated rosin produced by Zhuzhou Forest Chemicals Plant of China, was separated from neutral fraction by modified DEAE-Sephadex ion exchange chromatography and analyzed with GC-MS-DS technique by using DB-5 capillary column. Six dihydroabietic-type resin acids, four dihydropimaric/isopimaric-type resin acids and four tetrahydroabietic-type resin acids were identified. The hydrogenated rosin is composed mainly of 8-abietenoic acid, 18-abietanoic acid, 13-abietenoic acid, 8 alpha, 13 beta-abietanoic acid, 13 beta-8-abietenoic acid and 8-isopimarenoic acid etc.
Carboxylic Acids↗
Ganglioside control over IL-4 priming and cytokine production in activated T cells.
Our previous studies have shown that the enzymatic activities of Neu-1, an endogenous sialidase encoded in the murine MHC, are involved in promoting IL-4 synthesis by naive CD4(+)T cells. Our present studies have characterized responsible sialoconjugate targets of Neu-1 and questioned possible biochemical mechanisms responsible for their regulatory influences on IL-4 gene expression. These studies determined that treatment of T cells with the naturally occurring ganglioside GM3 inhibited the production of IL-4 without affecting the production of IL-2. An analysis of IL-4-primed CD4(+)T cells further demonstrated that GM3 treatment specifically inhibited the restimulated production of IL-4, IL-5 and IL-13, without inhibiting the production of IL-2 and IFN-gamma. The inhibitory effects of GM3 could be overcome by treatment with thapsigargin or ionomycin, suggesting ganglioside regulation occurs upstream of activation-induced calcium mobilization. GM3 treatment attenuated the level of calcium influx following CD3epsilon crosslinking, and CD4(+)T cells from Neu-1-deficient B10.SM strain mice (neu-1(a)and IL-4-deficient) expressed reduced levels of intracellular calcium following activation. Our results indicate that activities by membrane gangliosides can influence the cytokine programs in CD4(+)T cells, possibly through the modulation of calcium responses induced by T cell activation.
Animals↗
SOCS proteins, regulators of intracellular signaling.
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Animals↗
G-2964A and C734A genetic polymorphisms of CYP1A2 in Chinese population.
AIM: To observe the G-2964A and C734A genetic polymorphisms of human CYP1A2 in Chinese population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed in genotyping analysis. RESULTS: The allele frequencies of A-2964 were 0.25 and 0.22 in Qidong and Changsha populations, respectively. The incidences of A734 were 0.68 in Qidong population and 0.66 in Changsha population. No more than two low-inducibility/activity alleles were presented in one person. CONCLUSION: The distribution of the G-2964A and C734A genetic polymorphisms did not show significant difference between Chinese and Japanese populations. The incidence of C734A in Chinese was also similar to that in Caucasian population.
Adult↗
[The experience on correcting the impacted maxillary anterior teeth with fixed orthodontic technique].
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Journal Article↗
Cutting edge: SOCS-1 is a potent inhibitor of IL-4 signal transduction.
IL-4 is an important regulator of the activation, proliferation, and differentiation of many hematopoetic cells. Many of these biological effects result from the activation of Janus kinases (JAK)1 and JAK3 and the transcription factor Stat6. Recent data suggest that members of the SOCS (suppressor of cytokine signaling) family of proteins can inhibit JAK-STAT signaling. We have examined the ability of SOCS family members to suppress IL-4 signaling, and we have found that SOCS-1 potently inhibits the activation of JAK1 kinase and Stat6 in response to IL-4. Furthermore, SOCS-1 can inhibit the induction of CD23 expression by IL-4. SOCS-2 does not inhibit induction of signaling by IL-4, while inhibition of IL-4 signaling by SOCS-3 can be detected in transient transfection systems, but not in stable cell lines. These studies implicate SOCS-1 in modulation of IL-4 signaling and suggest that SOCS-1 may play a role in regulating the immune response.
Carrier Proteins↗