Effect of octreotide acetate on the plasma concentration and urinary excretion of uridine and purine bases

To determine the effect of octreotide acetate on urinary excretion of uric acid and plasma concentration of uridine, we subcutaneously administered octreotide acetate (1 microg/kg of body weight) to 5 healthy subjects. Ninety minutes after administration, octreotide acetate increased the plasma concentration of uridine by 15% and decreased the plasma concentration of glucagon by 24% and that of insulin to below the detection limits. In addition, octreotide acetate decreased the urinary excretion of uric acid, sodium, and chloride by 60%, 40%, and 38%, respectively, at 1 hour after administration. However, octreotide acetate did not affect the concentrations of hypoxanthine, xanthine, uric acid, cyclic AMP in plasma, lactic acid and pyruvic acid in blood, urinary excretion of hypoxanthine and xanthine, or creatinine clearance. From these results, we speculated that octreotide acetate decreases the urinary excretion of uric acid by decreasing the concentration of glucagon and/or urinary excretion of sodium, and increases the plasma concentration of uridine via decreased concentrations of glucagon and insulin.     

Normative data and psychometric properties of the strengths and difficulties questionnaire among Japanese school-aged children

Background

Although child mental health problems are among the most important worldwide issues, development of culturally acceptable mental health services to serve the clinical needs of children and their families is especially lacking in regions outside Europe and North America. The Strengths and Difficulties Questionnaire (SDQ), which was developed in the United Kingdom and is now one of the most widely used measurement tools for screening child psychiatric symptoms, has been translated into Japanese, but culturally calibrated norms for Japanese schoolchildren have yet to be established. To this end, we examined the applicability of the Japanese versions of the parent and teacher SDQs by establishing norms and extending validation of its psychometric properties to a large nationwide sample, as well as to a smaller clinical sample.

Methods

The Japanese versions of the SDQ were completed by parents and teachers of schoolchildren aged 7 to 15 years attending mainstream classes in primary or secondary schools in Japan. Data were analyzed to describe the population distribution and gender/age effects by informant, cut-off scores according to banding, factor structure, cross-scale correlations, and internal consistency for 24,519 parent ratings and 7,977 teacher ratings from a large nationwide sample. Inter-rater and test-retest reliabilities and convergent and divergent validities were confirmed for a smaller validation sample (total n?=?128) consisting of a clinical sample with any mental disorder and community children without any diagnoses.

Results

Means, standard deviations, and banding of normative data for this Japanese child population were obtained. Gender/age effects were significant for both parent and teacher ratings. The original five-factor structure was replicated, and strong cross-scale correlations and internal reliability were shown across all SDQ subscales for this population. Inter-rater agreement was satisfactory, test-retest reliability was excellent, and convergent and divergent validities were satisfactory for the validation sample, with some differences between informants.

Conclusions

This study provides evidence that the Japanese version of the SDQ is a useful instrument for parents and teachers as well as for research purposes. Our findings also emphasize the importance of establishing culturally calibrated norms and boundaries for the instrument’s use.     

Apolipoprotein E phenotypes in patients with gout: relation with hypertriglyceridaemia.

OBJECTIVE--To elucidate the relationship, if any, between lipid abnormalities and apolipoprotein E (apo E) polymorphism, by investigating apo E phenotype and allele frequency. METHODS--Fasting blood samples were taken for determination of apo E phenotype and serum lipids in 221 male patients with gout and 141 control male subjects. Apo E phenotype was determined by one dimensional flat gel isoelectric focusing. RESULTS--Frequencies of apo E phenotypes in gout were apo E3/3 67.9%, E4/3 18.1%, E4/4 2.3%, E4/2 1.8%, E3/2 9.5%, and E2/2 0.5%; those in control male subjects were 74.5%, 15.6%, 0%, 1.4%, 7.1%, and 1.4%, respectively. Frequencies of the e2, e3, and e4 alleles in gout were 0.061, 0.817 and 0.122, compared with the corresponding control frequencies of 0.057, 0.858 and 0.085. These differences in apo E phenotype and allele frequencies between gout and control subjects were not significant. The frequency of apo e4 allele in hyperlipidaemic gout subjects was significantly greater than that in normolipidaemic gout subjects; in contrast, its frequency was not different between hyperlipidaemic and normolipidaemic control subjects. Serum triglyceride, total cholesterol, apo B and E concentrations were significantly greater in gouty patients with the apo E4/3 phenotype than in those with gout having the apo E3/3 phenotype. CONCLUSIONS--These data suggest that gout subjects with hyperlipidaemia (hypertriglyceridaemia, hypercholesterolaemia or both) possess the apo e4 allele with higher frequency than those with normolipidaemia. They also suggest that apo e4 may induce some susceptibility to the development of hyperlipidaemia in gout in addition to that induced by obesity or excessive alcohol consumption, and may contribute to the high prevalence of atherosclerotic diseases in gout patients.     

Intrahepatic cholangiocarcinoma arising 10 years after the excision of congenital extrahepatic biliary dilation

Received: October 6, 2000 / Accepted: January 26, 2001     

Caspase activation during hepatocyte apoptosis induced by tumor necrosis factor‐α in galactosamine‐sensitized mice

Abstract: Background/Aims: To clarify the mechanism of hepatocyte apoptosis induced by tumor necrosis factor‐α (TNF‐α), caspase cascade and ceramide formation were investigated in the liver of D‐galactosamine (GalN)‐sensitized mice treated with TNF‐α. Methods: Seven‐week‐old male BALB/c mice were intraperitoneally injected with 20 mg GalN 30 min prior to the intravenous injection of recombinant mouse TNF‐α (0.5 μg/mouse). Cytochrome c release and processing of procaspases in the liver were analyzed by Western blotting. Activities of caspases were measured using chromogenic peptides as substrates. Ceramide content was determined using Escherichia coli diacylglycerol kinase. Results: Apoptosis of hepatocytes was observed in mice treated with both GalN and TNF‐α (GalN/TNF‐α), but not GalN or TNF‐α alone. Activation of caspases‐9 and ‐3, and cytochrome c release were observed only in liver from mice treated with GalN/TNF‐α. In a cell‐free system, processing of procaspases‐9 and ‐3, and cytochrome c release were observed in the postnuclear fraction of liver obtained from GalN/TNF‐α‐treated mice, but not in that from control mice. Processing of procaspase‐3 was inhibited by a caspase‐9 inhibitor, but not by inhibitor for caspase‐8 or ‐2. In a reconstitution assay system, procaspase‐9 processing occurred, when both cytosol and membrane fractions were obtained from the liver of mice treated with GalN/TNF‐α. Ceramide accumulation was observed only in apoptotic liver and preceded cytochrome c release and caspase activation. Conclusion: Cytochrome c release and caspase‐9 activation are required for the activation of executor caspase‐3 in TNF‐α‐induced hepatocyte apoptosis, but caspases‐8 and ‐2 play, if any, a minimal role. Ceramide may be implicated in this apoptotic process.     

Serum concentration of L‐kynurenine predicts the clinical outcome of patients with diffuse large B‐cell lymphoma treated with R‐CHOP

Purpose: Introduction of rituximab has largely improved the prognosis of patients with diffuse large B‐cell lymphoma(DLBCL). Such change in therapeutic outcome necessitates the identification of additional prognostic factors to conventional indexes that have been validated for CHOP without rituximab. Indoleamine 2,3‐dioxygenase (IDO) exerts intense immunomodulatory effects because of enzymatic activities that catalyze the breakdown of the essential amino acid L‐tryptophan. The activity of IDO can be estimated by measuring the serum concentration of L ‐kynurenine. Here, we investigated the role of L ‐kynurenine as a prognostic marker in R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy. Experimental design: Data from 73 consecutive patients treated with eight cycles of R‐CHOP or R‐THP (tetrahydropyranyl adriamycin)‐COP between December 2002 and March 2007 were analyzed. L ‐kynurenine concentrations in serum samples obtained at admission were measured by high‐performance liquid chromatography. Results: The median serum L ‐kynurenine level was 1.575 μm (range 0.537–9.588). The complete response (CR) rates of patients with L ‐kynurenine <1.5 and ≥1.5 μm were 83% and 61%, respectively (P < 0.05). The three‐yr overall survival (OS) rates for patients with L ‐kynurenine <1.5 and ≥1.5 μm were 89% and 58%, respectively (P < 0.005). In addition, higher age, poor performance status, elevated serum lactate dehydrogenase, and unfavorable as well as revised International Prognosis Index were significantly worse factors for CR rate and OS. Multivariate analyses revealed only L ‐kynurenine as an independent prognostic factor for OS. Conclusions: Serum L ‐kynurenine might be a novel prognostic factor to determine the treatment outcome of DLBCL with the R‐CHOP regimen.