The usefulness of combined brain perfusion single-photon emission computed tomography, Dopamine-transporter single-photon emission computed tomography, and 123 I-metaiodobenzylguanidine myocardial scintigraphy for the diagnosis of dementia with Lewy bodies.

BACKGROUND: Current diagnostic criteria recommend neuroimaging as a diagnostic support tool for the clinical diagnosis of dementia with Lewy bodies (DLB). Because DLB causes characteristic impairments and disabilities, such as neuroleptic hypersensitivity, which may significantly increase morbidity and mortality, its prompt and correct diagnosis is very important. The aim of this study was to evaluate the extent to which diagnostic accuracy can be increased by using different combinations of brain perfusion single-photon emission computed tomography (bp-SPECT), 123 I-metaiodobenzylguanidine myocardial scintigraphy (MIBG scintigraphy), and DAT-SPECT. Taking finances and patient burden into consideration, we compared the tests to determine priority. METHODS: Thirty-four patients with probable DLB (75.0 ± 8.3 years old; 14 men, 20 women) underwent bp-SPECT, MIBG scintigraphy, and DAT-SPECT. RESULTS: Our comparison of three functional imaging techniques indicated that MIBG scintigraphy (79%) and Dopamine-transporter (DAT) SPECT (79%) had better sensitivity for characteristic abnormalities in DLB than bp-SPECT (53%). The combination of the three modalities could increase sensitivity for diagnosis of DLB to 100%. Additionally, the ratio of patients with rapid eye movement sleep behaviour disorder was significantly higher in the positive finding group on MIBG scintigraphy than in the negative finding group. CONCLUSIONS: In terms of stand-alone diagnostic means, priority should be placed on MIBG scintigraphy or DAT-SPECT for the diagnosis of DLB. However, our results suggest that the combination of bp-SPECT, MIBG scintigraphy, and DAT-SPECT increased the accuracy of the clinical diagnosis of DLB.

Comparative oral toxicity of coenzyme Q10 and its (2Z)-isomer in rats: single and four-week repeated dose toxicity studies.

It has been reported that coenzyme Q10 (CoQ10) functions as an electron transfer carrier in mitochondria, and can produce an improvement in heart diseases such as congestive heart failure. Its (2Z)-isomer contains a cis-double bond at the 2-position of the decaprenyl side chain. As the original organic industrial synthesis of CoQ10 resulted in a product that contained a small amount of this isomer, the efficacy and safety of CoQ10 was determined using CoQ10 containing this isomer; however, no toxicity data have been reported for the (2Z)-isomer itself. Thus, we conducted single (2,000 mg/kg) and 4-wk repeated (1,000 mg/kg) oral dose toxicity studies in rats to compare the toxicological profiles of CoQ10 and its (2Z)-isomer. The two compounds displayed similar toxicological profiles, and it was concluded that neither CoQ10 nor its (2Z)-isomer produce toxic effects in rats in single or repeated doses.

Evaluation of liver and peripheral blood micronucleus assays with 9 chemicals using young rats. A study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Japanese Environmental Mutagen Society (JEMS)-Mammalian Mutagenicity Study Group (MMS).

We conducted simultaneous liver and peripheral blood micronucleus assays in young rats with seven rodent hepatocarcinogens-4,4'-methylenedianiline (MDA), quinoline, o-toluidine, 4-chloro-o-phenylenediamine (CPDA), dimethylnitrosamine (DMN), p-dimethylaminoazobenzene (DAB), and di(2-ethylhexyl)phthalate (DEHP)-and two mutagenic chemicals-kojic acid and methylmethanesulfonate (MMS). Quinoline, DMN, and DAB were positive in the liver assay, while o-toluidine, kojic acid, DAB, and MMS were positive in the peripheral blood assay. o-Toluidine, kojic acid, and DAB are reportedly negative in mouse bone marrow micronucleus assays, indicating a species difference. Our results revealed a correlation between micronucleus induction in hepatocytes and hepatocarcinogenicity. This technique can be useful for the detection of micronucleus-inducing chemicals that require metabolic activation, and it enables simultaneous comparison of the micronucleus-inducing potential of chemicals in the liver and peripheral blood in the same individual.

Oxazolone-induced colitis in BALB/C mice: a new method to evaluate the efficacy of therapeutic agents for ulcerative colitis.

A number of experimental models of colitis have been proposed. However, few studies have presented T helper-2 (Th-2) type colitis models that substitute for human ulcerative colitis (UC). In recent years, the murine oxazolone (OXA)-induced colitis model came to be accepted as a Th-2 type model, but it has yet to be used in any pharmacological study. In the present study, we modified the OXA-induced colitis model in BALB/C mice to evaluate the efficacy of treatments for UC. Colitis was induced by intrarectal administration of OXA solution (7.5 mg/mL in 40% ethanol) in a BALB/C strain that is known to favor Th-2 immune responses. A lower mortality rate was obtained in the BALB/C strain than was found in the original method. Histological examination showed that there were morphological similarities to human UC. Increased mRNA expression of interleukin-13, a Th-2 cytokine, was observed in mesenteric lymph nodes. Intrarectal administration of 5-aminosalicylic acid or sodium prednisolone phosphate resulted in a significant improvement in the colitis. These results suggest that the OXA-induced colitis model in the BALB/C strain provides a new way to evaluate the efficacy of therapeutic agents for UC.