Chronic hepatitis B (CHB) has a wide range of outcomes depending on host immune responses mainly Toll-like receptors (TLRs) signaling and released cytokines. Toll-like receptor 2 (TLR2) single nucleotide polymorphisms (SNPs) and interleukin 6 (IL-6) may influence the course of CHB. We aimed to elucidate the relation between TLR-2 polymorphism, IL-6 profile, and CHB progression. We analyzed TLR-2 polymorphism (SNP; rs3804099) in 185 CHB patients and 60 controls using TaqMan allelic discrimination assay. Serum IL-6 levels were assessed by ELISA. IL-6 levels were considerably higher in active CHB and cirrhotic patients compared with inactive carriers and controls (P < 0.001). IL-6 showed positive correlation with ALT and advanced fibrosis in active CHB patients (r = 0.31, P = 0.02). A significant positive correlation was noticed between IL-6 and HBV DNA PCR in all CHB groups. TT genotype of rs3804099/TLR-2 was significantly more prevalent in inactive carriers compared to active hepatitis patients (P = 0.04, OR = 0.39 and 95% CI: 0.16–0.95). Both heterozygous CT and mutant TT genotypes were significantly more frequent among inactive carriers compared to cirrhotic patients (P = 0.01, OR = 0.33, 95% CI: 0.13–0.81 and P = 0.009, OR = 0.32, 95% CI: 0.13–0.77). TT genotype was significantly related to lower IL-6 levels in active hepatitis and cirrhotic groups (P = 0.005 and P = 0.001, respectively) showing that TLR mutations would be associated with milder hepatitis activity and lower possibility for disease progression. There may be a positive association between TLR2 rs3804099 polymorphism and hepatitis B activity. IL-6 is a good indicator of CHB disease progression.
Cyclosporine is a powerful immunosuppressant with a narrow therapeutic window and considerable inter- and intrapatient variability.
The pre-dose trough concentration (Cmin) is commonly used for therapeutic drug monitoring. With the new microemulsion (Neoral), intrapatient variability was reduced.
However, the usefulness of Neoral Cmin was questioned. Firstly, because of the improved and more-rapid absorption, accidental intake before blood sampling has a
greater impact on Cmin than with classic cyclosporine. Secondly, Cmin may be low despite high drug exposure, due to rapid clearance in children. A full pharmacokinetic (PK) profile with determination
of the area under the curve (AUC) is expensive and cumbersome, and therefore a search for an abbreviated AUC began. Here,
we present a retrospective analysis of 84 PK profiles from 78 pediatric renal transplant recipients. By analysis of rejection
episodes and toxicity, we estimated a target AUC above 5,000 ng×h/ml in the early post-transplant period and 3,900 ng×h/ml
beyond 100 days. The abbreviated AUC using the 2- and 6-h concentrations (C2 and C6) and a simple estimate derived from the
3-h concentration (C3) were equally well correlated with the AUC. From our data, we recommend a target C3 at approximately
800 ng/ml early after transplantation and 450–550 ng/ml beyond 100 days.
Received: 28 January 1998 / Revised: 10 June 1998 / Accepted: 15 June 1998 相似文献
BACKGROUND/AIMS: Obstructive jaundice due to intraductal tumour growth is a rare symptom in association with hepatocellular carcinoma (HCC). METHODS: We report a 65-year-old white male who was admitted to our department with a 2-week history of progressive jaundice. At laparotomy, the liver showed advanced cirrhosis due to long-standing biliary obstruction. Cholangiography confirmed total obstruction of the main bifurcation of the hepatic duct by intraductal tumour growth. Combination treatment with surgical segment III drainage, transcatheter arterial embolization and radioembolization with yttrium-90 resin particles and endoscopic stenting was performed. This form of treatment has never been reported before. RESULTS: With these combined procedures, relief of jaundice and a survival time of 32 months could be achieved. CONCLUSION: The combination of palliative methods may relieve jaundice, ensure a good quality of life and possibly prolong survival in patients with mechanical tumour obstruction of the biliary tree by HCC. 相似文献
2-(1-Aryl-1-hydroxymethyl)- and 2-aroyl-DHAQ derivatives (DHAQ, 1,4-dihydroxy-9,10-anthraquinone), and 2-(1-aryl-1-hydroxymethyl)-ATO derivatives (ATO, anthracene-1,4,9,10-tetraone) were synthesized and their antitumor activities were determined. 2-(1-Aryl-1-hydroxymethyl)-DHAQ derivatives showed a stronger cytotoxicity compared to the series of 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinone derivatives. It was suggested that the presence of aryl group at the side chain accelerated the bioreductive activation leading to cell death. 2-Aroyl-DHAQ derivatives, despite their higher electrophilicity, revealed smaller cytotoxicity and antitumor activity (expressed by T/C value) than 2-(1-aryl-1-hydroxymethyl)-DHAQ derivatives. Thus, no consistent relationship between the electronic effect on aromatic side chain and the cytotoxicity was observed. ATO series exhibited a higher antitumor activity (T/C, 125 to approximately 218%), though their cytotoxicity was not further improved compared to that of 2-(1-aryl-1-hydroxymethyl)-1,4-dihydroxy-9,10-anthraquinones. They manifested no correlation between the cytotoxicity and the antitumor activity. In case of 2-[1-hydroxy-1-(4-propylphenyl)-methyl]-ATO, the most bioactive one in vivo among the same series, it showed an ED50 value of 10.2 mg/mL and a T/C value of 218%. It is assumed that the anthracene-1,4,9,10-tetraones after uptake into cellular tissues might be transformed to a cytotoxic metabolite(s). 相似文献
To determine the role of site of tumor implantation on tumor angiogenesis, we implanted gastric cancer cells in the orthotopic (stomach) and ectopic (subcutaneous) locations in nude mice. Tumors in the stomach demonstrated greater vascularization, higher levels of vascular endothelial growth factor (VEGF) expression, and greater proliferation compared with tumors in the subcutaneous tissues. These data suggest that the relationships among the expression of VEGF, vascularization, and proliferation of human gastric cancer cells are regulated by the organ microenvironment. In addition, VEGF may provide a target for anti-angiogenic therapy for gastric cancers. 相似文献
The BUT of 51 strabismus patients were measured before and after operation. The average pre-op BUT was 28.75 seconds(10.96"-91.80"). The post-op BUT in all operated eyes were reduced significantly, no matter what procedures had been performed and whether dellen appeared or not(P<0.01). The BUT in the group complicated dellen reduced from 23.22"(pre-op) to 8.61"(post-op). The incidence of dellen was 22.54% in this study. The incidence of dellen after rectus resection procedure(47.75%) was much higher than that after rectus recession(5.13%)(P<0.01). This study showed that dellen was closelyre related to the BUT and occurred more often in the eyes on which resection procedure was performed. It is considered that excessive lacrimation and elevation of the bulbar conjunctiva near the limbus may disturb the stability of the precornea tearfilm and cause the tearfilm break up earlier. Local corneal dehydration and dellen formation may be caused by reduced BUT. The incidence of dellen after operation may be higher if the cornea was carefully observed. 相似文献