Divergent effects of different enzyme-inducing agents on endogenous and exogenous testosterone

Summary The effects of three different enzyme-inducing drugs (antipyrine 1200 mg, phenobarbital 100 mg, rifampicin 600 mg per day for 7 days) on plasma and urinary testosterone concentrations, plasma gonadotropin levels, antipyrine kinetics, and urinary 6-hydroxycortisol excretion were studied in 18 healthy volunteers. Changes in plasma and urinary testosterone concentrations following exogenous testosterone undecanoate (TU) were also investigated.Although both antipyrine and rifampicin increased antipyrine clearance by about 60%, they produced contrary effects on testosterone: antipyrine lowered the total morning plasma testosterone and plasma testosterone AUC following TU, while rifampicin led to increases of about 20% and 78%, respectively. By contrast, phenobarbital did not significantly alter the endogenous and exogenous plasma testosterone concentrations, but it increased the urinary excretion of testosterone by more than 60%. The other two enzyme inducers did not alter this parameter. Gonadotropin levels remained unchanged.The results indicate that different enzyme-inducing agents exert divergent effects on endogenous and exogenous testosterone concentrations and suggest that the effect of enzyme induction on endogenous testosterone depends on the type of microsomal enzyme-inducing drug used rather than on the extent of the induction achieved.     

Regulation and inactivation of brain phosphocholine-phosphatase activity

Regulation of phosphocholine-hydrolyzing phosphatase (phosphocholine-phosphatase) activity, purified from bovine brain, was examined under physiological conditions. Various endogenous phosphomonoesters, which were utilized as substrate, inhibited the phosphocholine-phosphatase activity competitively (Ki, 5.5-82.0 microM); among phosphomonoesters tested, there was a similar order of capability between the binding affinity of substrate and the inhibitory potency. In addition, phosphate ions also inhibited the phosphatase activity competitively with a Ki value of approximately 167 microM. Although leucine or theophylline inhibited the phosphatase activity at pH 9.0, their inhibitory action decreased greatly at pH 7.4. The pH-Km and pH-Vm profiles indicate that ionizable amino acids are involved in substrate binding as well as catalysis, alluding that the phosphatase activity may be highly dependent on the intracellular pH. Amino acid modification study supports the existence of tyrosine, arginine or lysine residue in the active site, and the participation of tyrosine residue in the catalytic action may be suggested positively from the susceptibiliy to the action of tetranitromethane or HOI-generator. Separately, the oxidative inactivation of phosphocholine-phosphatase activity was investigated. Of oxidants tested, HOONO, HOCl, HOI and ascorbate/Cu2+ system were effective to inactivate the phosphatase activity. Noteworthy, a remarkable inactivation was accomplished by 30 microM HOCl in combination with 1 mM KI. In addition, Cu2+ (3 microM) in combination with ascorbate at concentrations as low as 0.1-0.3 mM reduced the phosphatase activity to a great extent. From these results, it is proposed that the phosphocholine-phosphatase activity may be regulated endogenously and susceptible to the various oxidant systems in vivo.     

The clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography–computed tomography (PET–CT) in follow-up of curatively resected pancreatic cancer patients

Background

Computed tomography and serum tumor markers have limited value in detecting recurrence after curative surgery of pancreatic cancer. This study evaluated the clinical utility of 18F-fluorodeoxyglucose positron emission tomography–computed tomography (PET–CT) in diagnosing recurrence.

Methods

One hundred ten patients underwent curative resection of pancreatic cancer were enrolled. The diagnostic value of abdominal computed tomography (CT), PET–CT and serum carbohydrate antigen (CA) 19-9 concentration were compared. The prognostic value of SUVmax on PET–CT was evaluated.

Results

PET–CT showed relatively higher sensitivity (84.5% vs. 75.0%) and accuracy (84.5% vs. 74.5%) than CT, whereas PET–CT plus CT showed greater sensitivity (97.6%) and accuracy (90.0%) than either alone. In detecting distant recurrences, PET–CT showed higher sensitivity (83.1% vs. 67.7%) than CT. Nineteen patients showed recurrences only on PET–CT, with eleven having invisible or suspected benign lesions on CT, and eight had recurrences in areas not covered by CT. SUVmax over 3.3 was predictive of poor survival after recurrence.

Conclusions

PET–CT in combination with CT improves the detection of recurrence. PET–CT was especially advantageous in detecting recurrences in areas not covered by CT. If active post-operative surveillance after curative resection of pancreatic cancer is deemed beneficial, then it should include PET–CT combined with CT.     

Broad dispersion and lung localization of virus-specific memory B cells induced by influenza pneumonia

Although memory B cells (B(Mem)) contribute significantly to resistance to infection, B(Mem) population characteristics that may relate to protective efficacy have received little attention. Here, we report a comprehensive quantitative analysis of virus-specific IgG and IgA B(Mem) dispersion after transient influenza pneumonia in mice. From early in the response, B(Mem) circulated continuously and dispersed widely to secondary lymphoid tissues. However, a complicated picture emerged with B(Mem) frequency differences between secondary lymphoid tissues indicating an influence of local tissue factors on trafficking. B(Mem) numbers increased and stabilized at tissue-specific frequencies without contraction of the B(Mem) pool during the period of analysis. The lung was notable as a nonsecondary lymphoid tissue where a rapid influx of IgG and IgA B(Mem) established relatively high frequencies that were maintained long term. Our findings provide insights into the pattern of B(Mem) dispersion, and emphasize the lung as a complex repository of immune memory after local infection.     

Clinicopathologic findings of colorectal traditional and sessile serrated adenomas in Korea: a multicenter study

Background/Aims: Serrated polyps have emerged as important evidence supporting the serrated polyp-neoplasia pathway in colorectal carcinogenesis, an alternate to the classical adenoma-carcinoma sequence. However, there is confusion over the diagnostic criteria for serrated polyps including traditional serrated adenoma (TSA) and sessile serrated adenoma (SSA). In addition, clinical and pathologic characteristics of each are largely unknown and need further exploration. Methods: The 753 polyps that were previously diagnosed as serrated adenoma (SA) from 14 tertiary care university hospitals in Korea between 2003 and 2005 were evaluated for the clinicopathologic findings of TSA and SSA. Results: Among 753 cases, 420 (55.8%) were reclassified as TSA and 56 (7.4%) as SSA. Among the pathologic parameters, crypt branching, crypt dilatation, and horizontal crypts were more frequent in SSA than in TSA (p < 0.001). SSA was larger than TSA (12.6 +/- 7.3 vs. 9.8 +/- 6.9 mm, p = 0.005), was more likely to be flat type (p = 0.006), and was more frequently located in the proximal colorectum (p = 0.012). There were no significant differences in age, sex, and body mass index between TSA and SSA. Conclusions: Locationand endoscopic features of the polyps with abnormal crypt morphology in histologic findings could be helpful for the diagnosis and classification of SAs.     

Apolipoprotein B is a better marker than non-HDL-cholesterol for the metabolic syndrome in Koreans

Apolipoprotein B (apoB) concentration reflects the number of atherogenic particles and is closely associated with atherosclerosis. Non-HDL-cholesterol (non-HDL-C) has been considered a therapeutic target for patients with hypertriglyceridemia. We compared the predictive values of apoB and non-HDL-C for the metabolic syndrome (MetS) in 3335 Korean adults (mean age, 45.2 years) who participated consecutively in a health examination in a university hospital. Anthropometry, blood pressure, fasting glucose, lipid profiles and apoB were measured. MetS, as defined by a modification of the NCEP-ATP III criteria, was present in 22.1% of men and 16.1% of women. Among the components of the MetS, triglycerides showed the strongest correlation with apoB (r=0.393, P<0.001 in men, and r=0.326, P<0.001 in women) and non-HDL-C (r=0.376, P<0.001 in men, and r=0.349, P<0.001 in women). When apoB and non-HDL-C were mutually adjusted, the ORs for the MetS of non-HDL-C were not significant. As a function of the quartile of apoB levels, the ORs for the MetS were 2.04 (1.26-3.30), 3.54 (2.11-5.93), and 5.38 (3.16-9.17) in men (P for trend <0.001) and 3.75 (1.42-9.87), 5.55 (2.09-14.69), and 13.41 (5.02-35.79) in women (P for trend <0.001), respectively. These findings indicate that apoB is a better marker than non-HDL-C for identifying the MetS among Koreans.     

Antioxidant, antimutagenic, and antitumor effects of pine needles (Pinus densiflora)

Pine needles (Pinus densiflora Siebold et Zuccarini) have long been used as a traditional health-promoting medicinal food in Korea. To investigate their potential anticancer effects, antioxidant, antimutagenic, and antitumor activities were assessed in vitro and/or in vivo. Pine needle ethanol extract (PNE) significantly inhibited Fe(2+)-induced lipid peroxidation and scavenged 1,1-diphenyl- 2-picrylhydrazyl radical in vitro. PNE markedly inhibited mutagenicity of 2-anthramine, 2-nitrofluorene, or sodium azide in Salmonella typhimurium TA98 or TA100 in Ames tests. PNE exposure effectively inhibited the growth of cancer cells (MCF-7, SNU-638, and HL-60) compared with normal cell (HDF) in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In in vivo antitumor studies, freeze-dried pine needle powder supplemented (5%, wt/wt) diet was fed to mice inoculated with Sarcoma-180 cells or rats treated with mammary carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA, 50 mg/kg body weight). Tumorigenesis was suppressed by pine needle supplementation in the two model systems. Moreover, blood urea nitrogen and aspartate aminotransferase levels were significantly lower in pine needle-supplemented rats in the DMBA-induced mammary tumor model. These results demonstrate that pine needles exhibit strong antioxidant, antimutagenic, and antiproliferative effects on cancer cells and also antitumor effects in vivo and point to their potential usefulness in cancer prevention.