Induction of rat liver drug-metabolizing enzymes by tetrachloroethylene

The effect of tetrachloroethylene on Phase I and II drug-metabolizing enzymes in rat liver was examined. Rats were treated orally with tetrachloroethylene daily for five days, at doses of 125, 250, 500, 1,000 and 2,000 mg/kg. The higher doses (>500 mg/kg) of tetrachloroethylene induced the hepatic microsomal 7-pentoxyresorufin O-depentylase and 7-benzyloxyresorufin O-debenzylase activities associated with the CYP2B subfamily. 7-ethoxyresorufin O-deethylase activity was also induced about 2-fold compared with that of control rats at 500, 1,000, and 2,000 mg/kg dose levels of tetrachloroethylene. However, 7-ethoxycoumarin O-deethylase and 7-methoxyresorufin O-demethylase activities were increased significantly at only the 1,000 mg/kg dose level of tetrachloroethylene (1.4- and 1.5-fold). Although other cytochrome P450-mediated monooxygenase activities such as nitrosodimethylamine N-demethylase, aminopyrine N-demethylase and erythromycin N-demethylase were also induced by tetrachloroethylene, the relative induction to control activity was lower than those of 7-pentoxyresorufin O-depentylase and 7-benzyloxyresorufin O-debenzylase. Western immunoblotting showed that the levels of CYP2B1 and CYP2B2 proteins in liver microsomes were increased at doses of 1,000 and 2,000 mg/kg of tetrachloroethylene. In addition to cytochrome P450-mediated monooxygenases, there was significant induction of the Phase II drug-metabolizing enzymes, DT-diaphorase, glutathione S-transferase activities towards 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene, and UDP-glucuronyltransferase activities towards 4-nitrophenol and 7-hydroxycoumarin. The results indicate that tetrachloroethylene induces both Phase I (CYP2B-mediated monooxygenase) and Phase II drug-metabolizing enzymes (DT-diaphorase, glutathione S-transferase and UDP-glucuronyltransferase) in the rat liver.     

Dedifferentiated liposarcoma with chondroblastic osteosarcomatous dedifferentiation

We describe a rare case of dedifferentiated liposarcoma with features resembling chondroblastic osteosarcoma in the dedifferentiated component. The tumor was removed from the left thigh in a 78-year-old male. It consisted of a well-differentiated liposarcoma and an anaplastic component that contained numerous osteoid and cartilaginous tissues surrounded by high-grade spindle cell sarcoma. To our knowledge, only two cases similar to the divergent chondroblastic osteosarcomatous dedifferentiation of this disease have been reported in the literature.     

Expression of EGF, EGF-receptor, p53, v-erb B and ras p21 in colorectal neoplasms by immunostaining paraffin-embedded tissues

Immunohistochemical studies were performed to clarify the significance of the expression or overexpression of epidermal growth factor (EGF), EGF-receptor (EGFR), p53, v- erb B, ras p21 in 23 cases each of tubular adenoma and adenocarcinoma. The expression of EGF, EGFR, p53, v- erb B, and ras p21 in paraffin-embedded tissues, from 46 patients with colorectal tumors (adenoma: 23 cases; 14 mild dysplasia, six moderate dysplasia, three severe dysplasia, adenocarcinoma: 23 cases; 17 well differentiated, two moderately differentiated, three poorly differentiated, one mucinous carcinoma was analyzed immunohistochemically using anti-EGF, EGFR, p53, v- erb B and ras p21 antibodies. The EGF and ras p21 tended to express more strongly in carcinoma cases than in the adenoma cases, and in severe and moderate dysplasia than in mild dysplasia (EGF: stained positive in five adenomas [21.74%] and 17 adenocarcinomas [73.91%]; ras p21: stained positive in six adenomas [26.09%] and 14 adenocarcinomas [60.87%]. The EGFR stained positive in two adenomas (8.70%) and two adenocarcinomas (8.70%). The p53 and v- erb B showed positive staining only in the carcinoma cases (p53: stained positive in four cases [17.39%]; v- erb B: stained positive in eight cases [34.78%]). This study suggests that these factors seem to have some role in the progression of colon neoplasms. It suggests that genetic alteration is not always equal to the overexpression of protein products, but that it reflects them well, and that the staining makes some contribution to differential diagnosis in colorectal neoplasms.     

Inhibition of rat hepatic cytochrome P450 activities by biodegradation products of 4-tert-octylphenol ethoxylate.

1. The effects of some biodegradation products of 4-tert-octylphenol ethoxylate (OPEO), namely 4-tert-octylphenol (OP), 4-tert-octylphenol diethoxylate (OP2EO) and 4-tert-octylphenol monocarboxylate (OPIEC) on the kinetics of cytochrome P450 (P450) -dependent monooxygenases in rat liver microsomes have been studied. 2. Testosterone 16beta-hydroxylase (TS16BH), testosterone 2alpha-hydroxylase (TS2AH) and testosterone 6beta-hydroxylase (TS6BH) activities were extensively inhibited by OP at 100 microM (56.0-90.3%). Inhibition was competitive for all P450-dependent monooxygenases. Ki(s) of TS16BH, TS2AH and TS6BH from Lineweaver-Burk plots were 6.37, 3.38 and 34.8 microM respectively. 3. The activities of acetanilide 4-hydroxylase (AA4H), 7-ethoxycoumarin O-deethylase (ECOD) and bufuralol 1'-hydroxylase (BF1'H) were also effectively inhibited by OP at 100 microM (48.6-56.0%). The inhibition of these P450-dependent monooxygenases was non-competitive, and Ki(s) (50.1-63.90 microM) were higher than those of TS16BH, TS2AH and TS6BH. 4. OP2EO also inhibited AA4H, ECOD, TS16BH, TS2AH, BF1'H and TS6BH activities by 38.7-69.3% at 100 microM, although the inhibition rates were slightly lower than those for OP. K(i)s were 14.4-106 microM, and the inhibition was of mixed type (AA4H and ECOD), competitive (TS16BH, TS2AH and TS6BH) and non-competitive (BF1'H). 5. Testosterone 7alpha-hydroxylase (TS7AH), 4-nitrophenol 2-hydroxylase (4NP2H) and lauric acid omega-hydroxylase (LAOH) activities were only slightly affected by OP and OP2EO. 6. The ability of OP1EC to inhibit P450-dependent monooxygenase activities was generally weaker than that of OP and of OP2EO: Ki >200 microM. 7. These results suggest that OPEO biodegradation products interact with constitutive P450 isoforms, CYP1A2, CYP2A2, CYP2B2, CYP2C11 and CYP3A2 in rat liver in vitro (OP > OP2EO > OP1EC), and that the mechanism of this interaction differs depending on the compound and P450 isoform.     

A case of recurrent cholangitis after bile duct injury during laparoscopic cholecystectomy: Value of scintigraphy with Tc-99m GSA and hepatobiliary scintigraphy for indication of lobectomy

A 39-year-old woman with acute cholecystitis and gallstones underwent laparoscopic cholecystectomy. She suffered from recurrent episodes of cholangitis due to injury of the major bile ducts during laparoscopic cholecystectomy. Hepatobiliary scintigraphy with Tc-99m Sn-N-pyridoxyl-5-methyltryptophan was performed. Although normal bile excretion was found from the left hepatic duct to the percutaneous transhepatic biliary drainage (PTBD) tube, excretion from the right hepatic lobe was prolonged. Scintigraphy with Tc-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin demonstrated atrophy of the right hepatic lobe and enlargement of the left hepatic lobe. Cholangiography via the PTBD tube revealed complete obstruction of the left hepatico-jejunal anastomosis and could not enhance the right intrahepatic bile duct. A right hepatic lobectomy was performed because of the atrophy, glissonitis and the absence of an appropriate bile duct for reconstruction. Postoperatively she was active and exhibited no evidence of recurrent cholangitis.     

Exacerbation of Ulcerative Colitis with Tocilizumab: A Report of Two Cases,One with Takayasu Arteritis and the Other with Relapsing Polychondritis

Tocilizumab (TCZ), a biologic that blocks the signal transduction of interleukin-6, has been used for the treatment of various autoimmune diseases. Many of these cases are sometimes complicated by ulcerative colitis (UC). However, the effect of TCZ on UC is unclear. We experienced two cases with concomitant UC that were treated with TCZ, one for Takayasu arteritis (TAK) and the other for relapsing polychondritis (RP). TCZ did not improve UC in either of these cases. TCZ might have adverse effects on the intestinal tract, since interleukin-6 signaling plays an important role in intestinal epithelium maintenance. Treatment with TCZ should therefore be carefully provided in patients complicated with UC.     

VDR Gene Polymorphisms,Interaction with Smoking and Risk of Periodontal Disease in Japanese Women: the Kyushu Okinawa Maternal and Child Health Study

Epidemiological evidence on the relationship between vitamin D receptor (VDR) polymorphisms and periodontal disease is inconsistent. We investigated associations between four VDR single‐nucleotide polymorphisms (SNPs) including rs731236 (TaqI), rs7975232 (ApaI), rs1544410 (BsmI) and rs2228570 (FokI), and the risk of periodontal disease among young Japanese women. Cases included 131 women who had at least one tooth with a probing depth of 3.5 mm or deeper. Controls included 1019 women without periodontal disease. Adjustment was made for age, region of residence, education, toothbrushing frequency and use of an interdental brush. Compared with the AA genotype of SNP rs731236, the GG genotype had a significantly increased risk of periodontal disease: the adjusted OR was 3.68 (95% confidence interval: 1.06–12.78). There were no significant relationships between SNPs rs7975232, rs1544410 or rs2228570 and periodontal disease. None of the haplotypes were significantly related to periodontal disease. Compared with subjects with the AA or AG genotype of SNP rs731236 who had never smoked, those with the GG genotype who had ever smoked had a significantly increased risk of periodontal disease; nevertheless, neither multiplicative nor additive interaction was significant. The additive interaction between SNP rs7975232 and smoking was significant, although the multiplicative interaction was not statistically significant. No multiplicative or additive interactions were observed between the other SNPs and smoking. Our results indicated that VDR SNP rs731236 might be associated with periodontal disease. In addition, we present new evidence for a biological interaction between VDR SNP rs7975232 and smoking that affects periodontal disease.     

Clinical evaluation of peginterferon α plus ribavirin for patients co-infected with HIV and HCV at Nagoya Medical Center

At Nagoya Medical Center, 10 patients co-infected with HIV and HCV received peginterferon α (PEG-IFNα) plus ribavirin therapy. Three of the cases were HCV genotype 1b, 2 cases were HCV 3b, and 1 case each were 2b, 2c, 3a, 4a and 6n. Nine patients received anti HIV therapy from the beginning. In 5 of these patients, anti HIV therapy was modified when PEG-IFNα plus ribavirin treatment was started. Of the above, 7 patients completed the protocol. No patients had severe adverse effects. Sustained virological response was achieved in 1 of 4 (25%) of the patients with genotypes 1 or 4, and in 5 of 6 (83%) of the patients with other genotypes. PEG-IFNα plus ribavirin therapy is considered a safe and efficacious treatment for patients co-infected with HIV and HCV.     

Salivary Cotinine Concentrations and Prevalence of Periodontal Disease in Young Japanese Women: The Kyushu Okinawa Maternal and Child Health Study

Background: The authors investigated the relationship between objectively assessed tobacco smoke exposure and periodontal disease. Methods: This cross‐sectional study included 1,103 women with a mean age of 31.5 years. Information on potential confounding factors was obtained through a self‐administered questionnaire. Periodontal disease was defined as positive if a woman had at least one tooth with a probing depth of ≥3.5 mm. Exposure to tobacco smoke was determined based on salivary cotinine concentration. Adjustment was made for age, region of residence, household income, education, toothbrushing frequency, and use of an interdental brush. Results: The prevalence of periodontal disease was 11.3%. Salivary cotinine concentration was independently positively associated with the prevalence of periodontal disease: the adjusted odds ratio for every 1‐unit (ng/mL) increase in salivary cotinine was 1.004 (95% confidence interval: 1.000 to 1.007). Conclusion: Salivary cotinine concentrations were positively associated with the prevalence of periodontal disease among young women.