Cutaneous Fistula ; Digestive System Abnormalities ; therapy ; Endoscopy, Gastrointestinal ; methods ; Female ; Humans ; Infant ; Treatment Outcome

Objective:To investigate the expression of chemokine receptor CXCR4 in hepatocellular carcinoma tissues,hepatocellular carcinoma cell line-MHCC97,human umbilical vein endothelial cells(HUVECs)and the ascites level of CXCL12,ligand of CXCR4,so as to lay a foundation for studying the role of CXCR4 in the metastasis of hepatocellular carcinoma.Methods:The expression of CXCR4 mRNA and protein was examined by RT-PCR and Western blotting in 21 specimens of hepatocellular carcinoma tissues,MHCC97 cells,HUVECs,and 17 specimens of normal hepatic tissues.Meanwhile,the levels of CXCL12 in ascitic fluids were assayed by ELISA in 18 hepatic cancer patients.Results:The relative expression values of CXCR4 mRNA in hepatocellular carcinoma tissues,MHCC97 cells,and HVECs were 2.21?1.09,2.14?1.15 and 1.72?1.20,respectively;and those of CXCR4 protein were 1.51?0.12,1.76?0.25,and 1.89?0.24,respectively;and those of CXCR4 protein were 1.51?0.12,1.76?0.25,and 1.89?0.24,respectively.CXCR4 mRNA and protein were not detected in normal hepatic tissues.ELISA results showed that the 18 hepatocellular carcinoma samples had a CXCL12 concentration range of 783-8 364 pg/ml(median value 6 871 pg/ml)in ascitic fluids.Conclusion:CXCR4 is highly expressed in the hepatocellular carcinoma tissues and cells,which is not associated with the clinical staging of the cancer.The elevated CXCL12 level in the ascitic fluid of cancer patients indicate that CXCR4 may play an important role in the metastasis of hepatocellular carcinoma.

Objective To compare the effects of hepatic vein occlusion with tourniquet and Satinsky clamp in reseeting liver tumor involving the second hepatic portal.Methods From Jan 2003 to Jun 2006,180 patients underwent major liver resection with the selective hepatic vascular exclusion (SHVE).According to methods of hepatic vein occlusion,they were divided into two groups:Occlusion with tourniquet(tourniquet group,n=95)and occlusion with Satinsky clamp(Satinsky clamp group,n= 85).In tourniquet group,the hepatic veins were encircled and occluded with tourniquet,and in Satinsky clamp group,the hepatic veins were not encircled and clamped directly with Satinsky clamp.Data regarding the intraoperative and postoperative courses of the patients were analyzed.Results There was no difference between the two groups regarding the operating time,ischemia time,intraoperative blood loss and postoperative complications rate.The dissecting time of hepatic veins was significantly shorter in Satinsky group(6.2?2.4 min vs 18.3?6.2 min).lu the tourniquet group,five hepatic veins(one fight hepatic vein and four common trunk of left-middle hepatic veins)could not be dissected and encircled because of the tumors involving the cava hepatic junction.Another patient's common trunk of left-middle hepatic vein was inadvertently lacerated during the dissection.Hepatic veins in these 6 patients were occluded with Satinsky clamp successfully.Conclusion Occlusion with Satinsky clamping is safer and easier procedure than tourniquets in the resection of liver tumor involving the second porta hepatis.

AIMTo study the pharmacokinetics of genistein at different doses in Beagle dogs.

METHODSSuspended in 0.5% CMC-Na solution, genistein was orally administered to Beagle dogs at doses of 2.67, 5.34 and 10.68 mg.kg(-1). At various time intervals, 1.5 mL of blood was drawn from the femoral vein of dogs in their front legs. The plasma was treated with beta-glucuronidase. The genistein in plasma was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (v/v = 8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. 20 microL solution was drawn and detected by high-performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software.

RESULTSThe plasma drug concentration-time data were fitted to the two-compartment model. When the dose was 2.67 mg.kg(-1), the MRT and AUC of parent compound were 52.9 min and 6.7 mg.min. L(-1), respectively. When the dose rose to 5.34 mg.kg(-1), the MRT and AUC of parent compound became 224.8 min and 26.1 mg.min.L(-1), respectively. However, when the dose increased to 10.68 mg .kg(-1), the MRT and AUC of parent compound increased to 267.7 min and 33.2 mg.min L(-1), respectively. The AUC of glucuronidated genistein was 33.9, 70.1 and 140.5 mg.min.L(-1) at the dose of 2.67, 5.34 and 10.68 mg.kg(-1), respectively.

CONCLUSIONDue to significant first pass metabolism, the drug was mainly existed in the form of glucuronidated genistein in the plasma. With the increase of dose, the absorption of genistein became saturated and the half life prolonged.

Animals ; Anticarcinogenic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Dogs ; Dose-Response Relationship, Drug ; Female ; Genistein ; administration & dosage ; blood ; pharmacokinetics ; Glucuronides ; blood ; pharmacokinetics ; Male

Objective To observe the protein and mRNA expression of thyroid-stimulating hormone receptor (TSHR) in mammary gland tissue of lactating rats,and to explore iodine uptake mechanism.Methods Eighty adult Wistar rats (60 female and 20 male),weighting 210-250 g were selected.All female Wistar rats were randomly divided into 6 groups according to their body mass:normal non-pregnant group,lactating for 5-,10-,15-and 20-day groups and weaning for 5 days group,10 rats in each group.All rats were fed with conventional fodder and tap water freely.In addition to the normal non-pregnant group,other five groups of female and male rats were mated at 3 ∶ 1,respectively.Then the rats in all groups were killed on the 5th,10th,15th and 20th day after lactation and on the 5th day after weaning to get the mammary gland tissue.The protein and mRNA expression of TSHR were determined by immunohistochemical staining and real-time quantitative PCR.Results TSHR protein was expressed in mammary acinar and ductal epithelial cytoplasm.The expression of TSHR in mammary gland showed significant differences between groups (x2 =14.612,P ＜ 0.05),the staining intensity of mammary gland tissue in normal non-pregnant rats(weak,n =4; moderate,n =6) was weaker than that of lactating for 5 days(weak,n =2; moderate,n =3; strong,n =5) and 10 days groups(barely detectable,n =1;moderate,n =4; strong,n =5; x2 =4.113,5.250,all P＜ 0.05).The expression of TSHR mRNA in mammary gland showed significant differences between groups(F=20.488,P ＜ 0.05); the expression of TSHR mRNA in lactating for 10 days group(0.31 ± 0.06) was higher than that of lactating for 5 days group(0.22 ± 0.04,P ＜ 0.01),and the expression of lactating for 15 days group (0.16 ± 0.08) was significantly lower than that of lactating for 5 days group (P ＜ 0.05).Conclusions TSHR is widely expressed in mammary gland of lactating rats.The iodine uptake of mammary gland is enhanced in early lactation period when the body may be more susceptible to iodine deficiency,therefore iodine should be supplemented reasonably.

Objective To observe the travel,divisions,and the lengths,diameters,branches,artery supplies of the main segments of maxillary nerve.Methods Fifty formalin-preserved adult half-head specimens with intravascular injection of red color emulsion were used for the gross and microanatomical studies of maxillary nerve.The lengths,diameters,branches and artery supplies of four main segments of maxillary nerve were observed.SPSS 11.5 software was used to analyze the data.Results The length and diameter of cranial middle fossa segment of maxillary nerve were ( 10.70 ± 1.31 ) mm and (4.01 ± 0.52 )mm respectively,which was supplied by inferior-lateral cavernous sinus artery.The length and diameter of pterygopalatine fossa segment were (16.21 ± 1.80) mm and (3.27 ±0.62) mm respectively,in which one zygomatic branch, one to three posterior superior alveolar nerves, two ganglion branches and tuberal descending branches; were given off,and the segment was supplied by foramen rotundum artery.The length and diameter of infraorbital segment were ( 25.73 ± 2.03 ) mm and ( 3.30 ± 0.52 ) mm and it gave off middle superior alveolar nerve (64％) and anterior superior alveolar nerve and was supplied by infraorbital artery.Facial segment gave off superior labial branches,internal and external nasal branches,inferior palpebral branches,buccal branch and zygomatic branch and these branches were supplied by infraorbital artery and superior labial and angular artery originating from facial artery.Conclusions Understanding of travel and artery supply of maxillary nerve is helpful to regional anaesthesia and surgery for maxillary nerve.Foramen rotundum,sphenopalatine foramen and infraorbital nerve are important marks for endoscopic surgery in pterygopalatine fossa.

AIMTo study the metabolic kinetics of MN9202 in Beagle dog liver microsome.

METHODSBeagle dog liver microsomes were prepared by using ultracentrifuge method. After incubating 0.4 micromol x L(-1) MN9202 with 1 g x L(-1) microsomes for 30 min at 37 degrees C, the reaction was terminated by adding 0.5 mL alkalization. The RP-HPLC was used to determine the drug in the incubation mixture. The Michaelis-Menten parameters Km, and Vmax in Beagle dog liver microsomes were initially estimated by analyzing Lineweave-Brurk plot. Various selective CYP inhibitors were used to investigate their inhibitory effect on the metabolism of MN9202.

RESULTSThe Km, Vmax and CLint of MN9202 were (22.6 +/- 8.0) micromol x L(-1), (0.54 +/- 0.17) micromol x g(-1) x min(-1) and (0.0242 +/- 0.0009) L x g(-1) x min(-1), respectively. The metabolism of MN9202 was significantly inhibited by ketoconazole (Ket) and troleandomycin (Tro) in Beagle dog liver microsomes. Tranylcypromine (Tra) could inhibit the metabolism of drug as well. While other inhibitors showed little inhibitory effect on the metabolism of MN9202.

CONCLUSIONIt was shown that CYP3A and CYP2C19 were involved in MN9202 metabolism. The inhibitors of human CYP3A and CYP2C19 may have potential interaction with MN9202, and this can reduce the metabolism rate and increase the toxicity of MN9202.

Animals ; Aryl Hydrocarbon Hydroxylases ; antagonists & inhibitors ; Calcium Channel Blockers ; metabolism ; pharmacokinetics ; Cytochrome P-450 CYP2C19 ; Cytochrome P-450 CYP3A Inhibitors ; Dihydropyridines ; metabolism ; pharmacokinetics ; Dogs ; Ketoconazole ; pharmacology ; Microsomes, Liver ; metabolism ; Mixed Function Oxygenases ; antagonists & inhibitors ; Nitrobenzenes ; metabolism ; pharmacokinetics ; Tranylcypromine ; pharmacology ; Troleandomycin ; pharmacology

OBJECTIVETo investigate the effect of chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 on liver metastasis of human colon cancer.

METHODSExpression of CXCR4 in different colon cancer cell lines and SDF-1 in different tissues were detected by using Western-blot technique. Effect of SDF-1 and anti-CXCR4 monoclonal antibody (McAb) on proliferation and migration of HT-29 cells were measured using MTT methods. Model mimicking liver metastasis of human colon cancer was established by injecting HT-29 cells intrasplenically into BALB/C nude mice. Mice were randomly divided into AMD3100 treated group and control group. Liver metastatic rate and tumor foci were measured 7 weeks after.

RESULTSHT-29 cells expressed higher level of CXCR4 protein, and liver tissue expressed higher level of SDF-1 protein. Compared with the control, SDF-1 could significantly induced the proliferation and migration of the HT-29 cells, and anti-CXCR4 McAb could inhibited both functions of SDF-1. The liver metastasis rate in the control group was 100%, and it was 40% in the AMD3100 treating group (P < 0.05). The mean liver metastasis number also significantly decreased by AMD3100 (7.8 +/- 2.6 vs 22.4 +/- 8.6, P < 0.05).

CONCLUSIONSSDF-1/CXCR4 biological axis play an important role in liver metastasis of human colon cancer. Arrest of CXCR4 can inhibit liver metastasis of colon cancer through blocking cell proliferation and migration induced by SDF-1.

Animals ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Chemokine CXCL12 ; metabolism ; physiology ; Colonic Neoplasms ; metabolism ; pathology ; HT29 Cells ; Humans ; Liver Neoplasms, Experimental ; secondary ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Receptors, CXCR4 ; metabolism ; physiology ; Xenograft Model Antitumor Assays

OBJECTIVEThis study was aimed at evaluating and comparing the quality of life in patients who underwent laparoscopic and open cholecystectomy for chronic cholecystolithiasis.

METHODSThe study included 25 patients with laparoscopic cholecystectomy (LC group) and 26 with open cholecystectomy (OC group). The quality of life was measured with the Gastrointestinal Quality of Life Index (GLQI) preoperatively, thereafter regularly at 2, 5, 10 and 16 weeks after the operation.

RESULTSThe mean preoperative overall GLQI scores were 112.5 and 110.3 in LC and OC group respectively (P>0.05). In the LC group, the mean overall GLQI score reduced slightly to 110.0 two weeks after the operation (P>0.05). The LC group showed significant improvement in overall score and in the aspects of symptomatology, emotional and physiological status from 5 to 16 weeks postoperatively. In the OC group, the GLQI score reduced to 102.0 two weeks after surgery (P<0.05). Significant reductions were shown in the aspects of symptomatology, physiological and social status. The GLQI scores returned to the preoperative level of 115.6 ten weeks after the operation (P>0.05). The patients experienced significant improvements of GLQI sixteen weeks after OC operation (P<0.01~0.05). Within the 10 postoperative weeks, the LC group had significantly higher GLQI scores than the OC group (P<0.05).

CONCLUSIONSLC can improve the quality of life postoperatively better and more rapidly than OC. The assessment of quality of life assessment is a valid method for measuring the effects of surgical treatment.

Adult ; China ; epidemiology ; Cholecystectomy ; statistics & numerical data ; Cholecystolithiasis ; epidemiology ; surgery ; Comorbidity ; Female ; Health Status ; Humans ; Laparoscopy ; statistics & numerical data ; Male ; Middle Aged ; Pain, Postoperative ; epidemiology ; Patient Satisfaction ; Postcholecystectomy Syndrome ; epidemiology ; Quality Assurance, Health Care ; methods ; Quality of Life ; Treatment Outcome

AIMTo study the pharmacokinetics of m-nifedipine (m-Nif) in Beagle dogs.

METHODSThe Beagle dogs were divided into two groups. m-Nif was intravenously administered to the Beagle dogs in group 1 at the dose of 0. 288 mg x kg(-1), and it was orally administered to the Beagle dogs in group 2, 3 and 4 at the dose of 1.152, 3.456 and 10.370 mg x kg(-1), respectively. m-Nif in plasma was detected by reversed phase high performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software.

RESULTSWhen m-Nif was intravenously administered, the plasma concentration-time curve was fit to a two-compartment model and T1/2beta was 117 min. When m-Nif was orally administered, the plasma concentration-time curve was fit to a one-compartment model. T1/2 (Ke) and Cmax were 147 min and 20 microg x L(-1); at the low dose of 1.152 mg x kg(-1). T1/2 (Ke) was 122 min and Cmax was 36 microg x L(-1) at the middle dose of 3.456 mg x kg(-1). T1/2 (Ke) was 144 min and Cmax was 69 microg x L(-1) at the high dose of 10.37 mg x kg(-1), respectively.

CONCLUSIONIt was showed that the speed of elimination of m-Nif was high in Beagle dogs. The absolute bioavailability of m-Nif given orally was very low.

Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Calcium Channel Blockers ; administration & dosage ; pharmacokinetics ; Dogs ; Injections, Intravenous ; Isomerism ; Nifedipine ; administration & dosage ; pharmacokinetics