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Biomedical subjects

W Wang

Publications and source records attributed to W Wang.

At least 541 records · Page 30Linked to original sources

Free radical scavenging and inhibition of lipid peroxidation by magnesium lithospermate B.

AIM: To study the effect of magnesium lithospermate B (MLB) on the lipid peroxidation and on its free radical scavenging activity. METHODS: MLB was incubated in rat tissue homogenate or in a free radical generating system. MLB induced inhibition of lipid peroxidation and its scavenging activity on superoxide anions and hydroxyl radicals was studied using colorimetric estimation. RESULTS: MLB inhibited the lipid peroxidation induced by either an auto-oxidant or Fe2+/VitC in vitro, in the liver homogenate, the inhibitory rate of MLB (10 mg/L) being 69.2% and 57.7%, respectively. MLB (25 and 50 mg/kg) decreased the amount of thiobarbituric acid reactive substances (TBARS) in rat serum, liver, kidney, and heart. However, it did not inhibit the lipid peroxidation of brain homogenate ex vivo. MLB scavenged superoxide anions generated from xanthine/xanthine oxidase system and iron-dependent hydroxyl radicals. CONCLUSION: MLB is an inhibitor of lipid peroxidation and scavenge superoxide anions and hydroxyl radicals both in vitro and ex vivo.

Animals↗

Effects of magnesium lithospermate B on aggregation and 5-HT release in rabbit washed platelets.

AIM: To study the effects and mechanism of magnesium lithospermate B(MLB) on rabbit platelet aggregation and 5-HT release. METHODS: The platelet aggregation was determined by Born's method. Release of serotonin (5-HT) and formation of thromboxane A2 (TXA2) were measured by fluorophotometry and radioimmunoassay (RIA) respectively. Cytoplasmic free Ca2+ concentration ([Ca2+]i) in platelets was measured by Fura 2-AM fluorescence technique. RESULTS: In washed platelets, thrombin (200 U/L) or arachidonic acid (AA) (30 mumol/L)-induced aggregation was inhibited by MLB 50-800 mg/L in a concentration-dependent manner. In addition, MLB had more inhibitory effects on platelet aggregation in the absence of extracellular calcium with IC50 of 102 mg/L than in the presence of CaCl2 1 mmol/L with IC50 of 194 mg/L. MLB concentration-dependently decreased the thrombin-activated release of 5-HT, whereas it did not affect the formation of TXA2 in platelets. Furthermore, MLB not only inhibited the rise of [Ca2+]i in thrombin stimulated platelets, but decreased the [Ca2+]i in resting platelets. CONCLUSION: MLB inhibited the aggregation and 5-HT release in rabbit platelets and it is probably by attenuating intracellular calcium concentration.

Animals↗

In vitro proguanil activation to cycloguanil is mediated by CYP2C19 and CYP3A4 in adult Chinese liver microsomes.

AIM: To identify the cytochrome P450 isoforms involved in proguanil (PG) activation to cycloguanil (CG) in Chinese liver microsomes. METHODS: The kinetics of the CG formation from PG was determined in the liver microsomes of 6 Chinese subjects. Selective chemical inhibitors to various cytochrome P450 isoforms were employed to conduct inhibition experiments. The relationship between the CG formation and S-mephenytoin 4'-hydroxylation was analyzed. RESULTS: The kinetic behaviors of CG formation were described well by a single-enzyme Michaelis-Menten equation in five livers. The apparent Km and Vmax were (82 +/- 47) mumol.L-1 and (8 +/- 6) pmol.min-1.mg-1 protein, respectively. However, the remaining one displayed a two-enzyme kinetic behavior. Inhibition experiments showed that troleandomycin (100 mumol.L-1) and diethyldithiocarbamate (100 mumol.L-1), as potent CYP3A4 and CYP2E1 inhibitors, respectively, reduced the formation rate of CG by 81.1% and 47.23%, while quinidine (10 mumol.L-1), furafylline (20 mumol.L-1), and sulfaphenazole (10 mumol.L-1), which were inhibitors towards CYP2D6, 1A2 and 2C9/10, respectively, did not display significant inhibition. At a low PG concentration of 5 mumol.L-1, the CG formation correlated well with S-mephenytoin 4'-hydroxylation (r = 0.805, P < 0.05). Nevertheless, when a high substrate concentration (500 mumol.L-1) was used, the correlation coefficient decreased (r = 0.581, P < 0.05). CONCLUSION: The present study indicates that CYP3A4 and CYP2C19 are involved in PG activation to CG in adult Chinese liver microsomes. CYP2C19 played an important role in the clearance of PG at a substrate concentration close to in vivo therapeutic concentrations, while CYP3A4 gradually made a dominant contribution with the increase of PG concentration.

Adult↗

Probing CYP2C19 and CYP3A4 activities in Chinese liver microsomes by quantification of 5-hydroxyomeprazole and omeprazole sulphone.

AIM: To develop an analytical method for simultaneous quantification of 5-hydroxyomeprazole (5-OH-OP) and omeprazole sulfone (OPS), and explore whether omeprazole (OP) is an appropriate phenotypic probe for CYP2C19 and CYP3A4 in Chinese liver microsomes. METHODS: OP metabolism in vitro was conducted in Chinese liver microsomes, and the major metabolites 5-OH-OP and OPS were determined using high pressure liquid chromatography (HPLC). Monoclonal antibodies anti-CYP2C8/9/19 and anti-CYP3A4 were employed to conduct inhibition experiments. The protein contents of CYP2C19 and CYP3A4 were quantified using Western blot analysis and densitometric scanning. RESULTS: 5-OH-OP and OPS gave a baseline resolution in the HPLC analysis. The detection limits for both compounds were 0.01 nmol and the recovery (98%-102%) had good precision with relative standard deviation of < 9.5%. Both anti-CYP2C8/9/19 and anti-CYP3A4 had a significant inhibitory effect (P < 0.05) on the 5-OH-OP formation in a substrate concentration-dependent manner, and anti-CYP3A4 alone could almost abolish the formation of OPS (> 87%). At a substrate concentration of 2 mumol/L OP, good correlations were found between OP 5-hydroxylation and S-mephenytoin 4'-hydroxylation activities (r = 0.72, P < 0.01), OP 5-hydroxylation activities and CYP2C19 contents (r = 0.82, P < 0.01), and OP sulfoxidation activities and CYP3A4 contents (r = 0.78, P < 0.01) in Chinese liver microsomes. CONCLUSION: OP metabolism is mediated mainly by CYP2C19 and CYP3A4, and OP can be used to probe CYP2C19 and CYP3A4 activities in Chinese liver microsomes at appropriate substrate concentrations with the HPLC method presently developed.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[Detection of hepatitis C virus RNA in the tissue of hepatocellular carcinoma by multiple detection system].

OBJECTIVE: Detection of hepatic HCV RNA in hepatocellular carcinoma (HCC) is difficult, since its expression is very low. Several techniques have been established. However, false positive and negative rates still exist. In this study, we applied several conventional and recently developed detection systems to determine the exact effect of HCV RNA on the development of RCC. METHODS: Immunohistochemistry for HCV core antigen and in situ hybridization for HCV RNA had been performed in 39 cases of HCC. IS-RT-PCR was applied for detection and localization of HCV RNA. We extracted microdissected liver tissues to detect HCV RNA separately in cancerous and pericancerous tissues so that the microscopic origin of the amplicons could be controlled. The serological tests including ELISA and RT-PCR for HCV also were performed in all cases. RESULTS: The positive rate by ELISA (30.8%) was not always consistent with that by RT-PCR(43.6%)from serum samples. The latter was much more sensitive and accurate to reflect existence of HCV RNA. Immunohistochemistry showed expression of RCV core antigen in 15 of 39 HCC cases. In pericancerous tissues, the signals were mainly localized in the cytoplasm of hepatocytes. However, translocated expression of HCV core protein was observed in the nuclei of tumor cells, the translocated rate was 73.3%. According to IS-RT-PCR, the positive signals were located mainly in the cytoplasm of cancer cells, the positive rate in HCC was 53.8%, expression of HCV RNA, serum HCV RNA level was detected to be low or negative. This suggested that serum HCV RNA was not always a good reflection of hepatic HCV RNA in HCC tissues. The microdissection RT-PCR described here gave an equal positive rate (59.0%) of HCV RNA in cancerous and pericancerous tissues. CONCLUSIONS: The high detection rate of HCV RNA in HCC specimens even from seronegative patients confirms the important role of HCV RNA during malignant transformation. IS-RT-PCR is a good detection and localization method to visualize HCV RNA in HCC tissues. The microdissection RT-PCR method has a distinct advantage and we anticipate this method will provide an important evidence to determine whether HCV play a direct or indirect role in hepatocarcinogenesis.

Adult↗

[Effect of Nerium indicum on killing Oncomelania hupensis].

A laboratory experiment at 20 +/- 5 degrees C shows that the water extract of fresh Nerium indicum had an obvious effect on killing Oncomelania hupensis. Treated with 0.1% water extract for four days, the mortality of O. hupensis was up to 100%. The effect of different tissues of N. indicum on O. hupensis was in order of stem phloem > leaf > root phloem > flower. The effect of N. indicum on O. hupensis was about ten times higher than that of Pterocarya stenoptera and Rumex japonicus, and was equal to that of 1 x 10(-3) mg.L-1 niclosamidum.

Animals↗

Stimulatory activity of anti-peptide antibodies against the second extracellular loop of human M2 muscarinic receptors.

OBJECTIVE: To study the activity of anti-peptide antibodies against the second extracellular loop of human M2 muscarinic receptors on cAMP production and inward calcium currents (Ica) in guinea pig ventricular myocytes. A comparison was also made with those of a muscarinic receptor agonist. METHODS: cAMP content was determined by radioimmunoassay and the Ica in guinea pig single ventricular cells were recorded by the whole-cell patch clamp technique. RESULTS: Both the muscarinic receptor agonist, carbachol (Carb 10 mumol/L), and anti-peptide antibodies (Abs 100 nmol/L) could decrease basal cAMP levels (by 46.9% +/- 4.2% and 60.2% +/- 4.6%, respectively) and basal Ica. Both Carb (10 mumol/L) and Abs (100 nmol/L) could also inhibit the isoprenaline-induced (Iso 0.8 mumol/L) increases in cAMP production (from 108.2 +/- 7.0 to 88.4 +/- 7.2 pmol/mg.protein/min for Carb and 88.6 +/- 5.1 pmol/mg.protein/min for Abs, respectively) and the increases in Ica. The muscarinic receptor antagonist atropine (Atr) was able to prevent these effects of Carb and Abs. CONCLUSIONS: Anti-peptide antibodies against an epitope located in the second extracellular loop of human M2 muscarinic receptors, similar to muscarinic receptor agonist, could decrease the basal Ica and beta-receptor agonist stimulated increase of Ica by decreasing the basal and beta-receptor agonist stimulated increase of cAMP production, and therefore could have an effect on their target receptor. These results further suggest that autoimmunity may participate in the pathogenesis of human cardiomyopathy and the second extracellular loop of human M2 muscarinic receptor could be the main immunodominant region.

Amino Acid Sequence↗

Detecting residual ischemia and identifying coronary artery disease after myocardial infarction using dobutamine technetium-99m-MIBI SPECT.

OBJECTIVE: To evaluate dobutamine technetium-99m methoxy isobutyl nitrile (sestamibi) single-photon emission computed tomography (Dobu-ECT) in detecting residual ischemia and identifying coronary vessel disease after myocardial infarction. METHODS: Sixty-two patients with confirmed myocardial infarction were studied with Dobu-ECT at the time of coronary artery angiography. Dobutamine was administered intravenously in incremental rates from 5 to 40 micrograms.kg-1.min-1 at 3-minute intervals. At the highest infusion rate, 7.4 x 10(8) Bq 99mTc-MIBI was injected intravenously, and tomographic imaging was performed after one hour. Resting images were taken after 24 hours, with a second dose of 99mTc-MIBI. RESULTS: The sensitivity of Dobu-ECT in detecting residual ischemia of myocardial infarction was 76%, which was higher than dobutamine electrocardiography (Dobu-ECG). Regardless of the single-, double- or triple-vessel diseases, Dobu-ECT was superior to Dobu-ECG in identifying residual ischemia (56% vs 4%, 86% vs 27%, 100% vs 47%, P < 0.01, respectively). The incidence of residual ischemia in patients receiving thrombolytic therapy was 67%, lower than patients without thrombolysis (72%) or those with an old myocardial infarction (94%). But the differences were not statistically significant. Dobu-ECT detected only 56% of ischemias in non-infarct related myocardium. Eighty-two percent of all significantly stenosed vessels were detected with Dobu-ECT, and 84% of patients with multivessel disease could be accurately identified. The sensitivity of Dobu-ECT was significantly greater for detecting severe stenosis over moderate stenosis. The sensitivity for detecting stenosis in the right coronary artery was greater than left anterior descending or left circumflex, but its specificity was lower. CONCLUSION: Dobu-ECT can identify residual ischemia, as well as its location and extent after myocardial infarction. Dobu-ECT can also accurately detect significantly stenosed vessels.

Adult↗

Sequence variations of the hypervariable region of hepatitis C virus and their clinical significance.

OBJECTIVE: To understand the clinical significance of sequence variations in the hypervariable region (HVR) of hepatitis C virus during infection. METHODS: Eight patients with acute hepatitis C and 20 patients with chronic hepatitis C were followed up for two years. Blood samples were taken at intervals of six months for analysis of HCV-HVR sequences by reverse transcription-polymerase chain reaction (RT-PCR) and direct sequencing methods. RESULTS: HCV-HVR sequences of the 28 patients changed in various degrees. 92% of these nucleotide substitutions led to changes of corresponding aminoacid sequences. Only 8% of changed nucleotide were synonymous substitutions. Of 27 amino acids variation of amino acid ranged from 1 to 20 (mean 8, 30%). The most common nucleotide substitution (62%) occurred in the first position of codon, 31% in the second and the rest in the third. HVR variation rate was 0.89 x 10(-1) per genome site per year in acute hepatitis C, compared with 2.31 x 10(-1) per genome site per year in chronic hepatitis C (P < 0.05), but had no relation to HCV subtype. Variation of HVR in the flare up type (ALT > 150 mu/L) was much more than that in the quiescent type (ALT < 100 mu/L). CONCLUSION: Our results suggested that sequence variation of HVR during HCV chronic infection seems to be an adaptive response to HCV to evade the host immune pressure and might play a major role in the establishment of persistent infection as well as in the flare-up of hepatitis.

Acute Disease↗

[Study on the anti-müllerian hormone served as a marker for granulosa cell tumor of ovary].

OBJECTIVE: To probe the experimental basis for anti-mullerian hormone(AMH) served as a specific tumor label in diagnosis of granulosa cell tumor(GCT) of ovary. METHODS: The expression of AMH and its receptor mRNA in early and late GCT of ovary in transgenic mice was studied by using immunohistochemistry, in stiu hybridization and Northern hybridization. Furthermore, the expression of AMH and its receptor mRNA in cultured GCT cells was also determined by using radioiodine labeling method and Northern hybridization. RESULTS: In the early ovary GCT of transgenic mice, immunohistochemistry showed that AMH was positively stained as brownish yellow granulars, which were located in the cell membrane of the tumor, in situ hybridization showed its receptor mRNA was positive as blue granulars, which were also located in the cell membrane. The positive rate of both AMH and its receptor mRNA was 100%. Results by northern hybridization also showed that the positive rate of AMH and its receptor mRNA in the early ovary GCT and GCT cells was 100%. Radioautography indicated that there was a radioactive bright point, the binding rate of 125I labeled AMH with tumor cells reached 100%. CONCLUSIONS: AMH can be served as a specific tumor marker in the diagnosis of difficult and complicated tumors of ovary, and in the diagnosis, treatment and follow-up survey of the early GCT.

Animals↗

[Serum leptin levels in normal pregnant women and their babies].

OBJECTIVE: To investigate serum leptin levels in normal pregnant women and their babies. METHODS: Immunoradioassay was used to measure the serum levels of leptin in 10 non-pregnant women, 63 pregnant women (31 in the firs, 10 in the second, and 22 in the third trimester), 27 women at delivery, 18 women in the first week after delivery and in 18 newborns' cord serum. Serum leptin levels were correlated with body weight, body mass index (BMI), fasting insulin levels and lipids. RESULTS: Serum insulin, cholesterol, triglyceride were increased since the second trimester during pregnancy. One week after delivery serum insulin but not cholesterol and triglicetride level was decreased to the levels of non-pregnancy. Serum leptin levels were (7.98 +/- 4.42) micrograms/L in non-pregnant women and (7.03 +/- 3.42) micrograms/L in the first trimester. Then the levels were increased to (13.97 +/- 8.03) micrograms/L in second trimester and (14.86 +/- 6.25) micrograms/L in the third trimester, (19.89 +/- 9.66) micrograms/L at the delivery time and returned to (10.86 +/- 9.18) micrograms/L in the first week after delivery, respectively. Cord serum leptin levels of newborns were (8.93 +/- 6.95) micrograms/L. Serum leptin levels in pregnant women were positively correlated with their body weight, BMI, fasting serum insulin and glycerol levels. Cord serum leptin levels was positively correlated with newborn birth weights as well as their insulin levels. CONCLUSIONS: (1) Serum leptin levels increase in the second and third trimester, and may contribute to the inhibition of increased food intake, body weight and body fat. (2) Newborn serum leptin may come from themselves, and the levels were lower than those in their mothers. (3) Birth weight, possibly adiposity, as well as serum insulin positively regulates serum leptin levels in neonates as in adults.

Adult↗

[Clinical and pathological analysis of 114 patients with postoperative wound infections by M. abscessus].

OBJECTIVE: To evaluate the pathological findings of postoperative wound infections by M. abscessus. METHODS: Proven sources of infections in 114 patients with postoperative wound infections were contaminated instrument disinfection liquid. According to the wound exudates cultivation and bacteriologic identification, the pathogen of postoperative infections was proved M. abscessus. Pathological features of postoperative wound infections were analyzed retrospectively. RESULTS: The postoperative wound infections in 114 cases involved cutaneous and subcutaneous tissue 95(83.3%), deep muscular tissue 21(18.4%), local lymph nodes 13(11.4%) and visceral organ, peritoneum and mesentery 3(2.6%). The main pathological appearances were granulomatous lesions and nonspecific chronic pyogenic inflammations. The granulomatous lesions include pyogenic tuberculosis-like granuloma, atypical tuberculosis-like granuloma and tuberculosis-like granuloma. The three types of granuloma could be seen in the same case and the percentage of three types was 75.4%, 28.1%, 59.6% respectively. 38 cases (33.3%) were showed red mycobacterium at acid-fast stain. CONCLUSIONS: The pathological appearances of most postoperative wound infections by M. abscessus were more or less different from those of tuberculosis. Awareness of the pathologic features of the postoperative wound M. abscessus infections will facilitate the diagnosis so that appropriate therapy may be initiated before the disease is far advanced and prevent infection dissemination.

Adolescent↗

[Comparison between therapeutic effect of Risperidone in treating different traditional Chinese medicine syndrome types of first-episode schizophrenia].

OBJECTIVE: To study the therapeutic effect, side effects and cognize improvement of Risperidone in treating different TCM Syndrome-types of first-episode schizophrenia. METHODS: Applying Risperidone to treat first-episode schizophrenics who were divided into Phlegm-Dampness type, Phlegm-Fire type and other types in TCM, and observing them with PANSS, TESS and Wisconsin Card Sorting Test (WCST). RESULTS: It is important to assess the therapeutic effect of patient with Fire Syndrome or without. Insomnia is the most prevalent side effect, while akathisia in Phlegm-Fire type is the most serious side effect, cognition deficiency in Phlegm-Dampness type is the most serious before treatment, and reduction of total card number of WCST in Phlegm-Fire type is significant after treatment (P < 0.05). CONCLUSION: It is the best way to use Risperidone combined with TCM Syndrome Differentiation so as to elevate the efficacy.

Adolescent↗

[Carcinogenesis effects of gastric and duodenal refluxate on esophageal mucosa].

OBJECTIVE: To investigate the effects of different refluxant on esophageal carcinogenesis in rats. METHODS: The animal models of gastroesophageal reflux (G), duodenoesophageal reflux (D) and duodenogastroesophageal reflux (DG) and no reflux as control (C) were made by operations. The rats in all of the groups were given carcinogen (methyl-n-amyl nitrosamine, MANA). They were killed at 4, 20, 26, 40-week, then their esophagi were taken to the morphologic study and the expression of p53, cyclinD(1), CDK(4) studied with immunohistochemical studies. RESULTS: At 4-week without carcinogen, most of rats in reflux groups displayed evidence of esophageal mucosal injury. The degree of mucosal injury in D group was greater than that in DG which was greater than that in G; and became severity with the time. At 40 weeks, the incidences of papillomas in group D, DG, G were 94.7%, 95.2%, 70.5%, respectively. All of them compared to the group C (38.5%) were significant difference. Only in both D and DG group, there were 24 with esophageal columnar metaplasia, 20 with dysplasia and 11 with cancer. The overexpression of p53, CDK(4), cyclin D(1) was seen in D and DG groups, while in G group, the overexpression of p53 and cyclin D(1) were seen only. CONCLUSION: Both of gastric juice and duodenal contents reflux can promote tumourgenesis of MANA on esophagi by changing the expression of cell cycle-related protein. The effect of duodenal contents is stronger. It may play an important role in tumourgenesis of gastroesophageal reflux disease.

Animals↗

[Neural electrophysiological observations on the external anal sphincter in patients with anorectal malformation].

OBJECTIVE: To explore the functional damage of the nerves controlling external anal sphincter in patients with congenital anorectal malformation and to design a new method for measuring the conductive time of sacral spinal center in the pudendo-anal reflex arc. METHODS: 45 patients with anorectal malformation and 20 normal subjects were subjected to detect the latency for pudendo-anal reflex, spinal-anal response and evoked potential of caude equine simultaneously. The conduction time of afferent motor nerve, efferent sense nerve and sacral spinal center in the pudendo-anal reflex arc were quantitatively analyzed. RESULTS: The normal latency for pudendo-anal reflex was 23.3 +/- 6.9 ms, for spinal-anal response was 4.6 +/- 1.9 ms, and for evoked potential of caude equine was 3.8 +/- 0.9 ms. The conduction time of sacral spinal center was 14.8 +/- 6.6 ms. In patients with anorectal malformation, the latencies were prolonged obviously, especially the conduction time of sacral spinal center. There was a significant negative correlation between the latency and clinical scores. The correlation coefficient for pudendo-anal reflex was -0.68, for spinal-anal response was -0.64, and for conduction time of sacral spinal center was -0.60. CONCLUSIONS: The abnormality of nerves serving anal sphincters was one of the important causes for postoperative fecal incontinence. The neural lesions are specially serious in the sacral spinal center.

Adolescent↗