Clinical improvement in two dogs with hydrocephalus and syringohydromyelia after ventriculoperitoneal shunting.

Two young Miniature Dachshunds were presented with abnormal gait. Magnetic resonance imaging showed, hydrocephalus with expanding fourth ventricle, and syringohydromyelia in the cervical spinal cord. These dogs underwent ventricle-peritoneal shunting, after which hydrocephalus, syringohydromyelia, and their clinical signs, improved.

Reversible splenial lesion with restricted diffusion in a wide spectrum of diseases and conditions.

OBJECTIVE: Reversible lesion in the central area of the splenium of the corpus callosum (SCC) is a unique phenomenon occurring particularly in patients with encephalitis or encephalopathy and in patients receiving antiepileptic drugs (AED). We report MR imaging findings, clinical courses, and outcomes in eight patients with various diseases and conditions. MATERIALS AND METHODS: Eight patients with a reversible SCC lesion with transiently restricted diffusion were reviewed retrospectively. Diseases and conditions that were associated with a reversible lesion included epilepsy receiving AED (n=1), seizure from eclampsia receiving AED (n=1), mild infectious encephalitis (n=2), hypernatremia resulting in osmotic myelinolysis (n=1), and neoplasm (n=3) such as acute lymphocytic leukemia, spinal meningeal melanocytoma, and esophageal cancer. We evaluated MR imaging findings and clinical findings. RESULTS: Seven patients had isolated SCC lesions; one patient with osmotic myelinolysis showed additional parenchymal lesions. The reversible SCC lesion shape was oval (n=6) or extended (n=2). The mean apparent diffusion coefficient value of the splenial lesion was 0.40+/-0.16 x 10-3 mm2/s, ranging from 0.22 to 0.64 x 10-3 mm2/s. In a patient with osmotic myelinolysis, additional white matter lesions, shown as restricted diffusion, were revealed as not reversible on follow-up MR imaging. Neurological courses and outcomes were good in seven patients with isolated SCC lesions, but poor in one with osmotic myelinolysis. CONCLUSION: Reversible SCC lesion with restricted diffusion is apparent in a wide spectrum of diseases and conditions. Neurological courses and outcomes are good, particularly in patients with isolated SCC lesions. Knowledge of MR imaging findings and the associated spectrum of diseases and conditions might prevent unnecessary invasive examinations and treatments.

Simultaneous determination of alpha-, gamma-tocopherol and their quinones in rats plasma and tissues using reversed-phase high-performance liquid chromatography.

We established a method to determine simultaneously alpha- and gamma-tocopherol (-Toc) and their quinones (alpha-TQ and p-gamma-TQ) in biological samples by reverse-phase high-performance liquid chromatography (HPLC). Tocs had a shorter retention time than TQs, and alpha-forms had a shorter retention times than gamma-forms. Four peaks of Tocs and TQs were completely separated by this method. Subsequently, we investigated the distribution of alpha-, gamma-Toc and TQ in rat tissues and the excretion of Tocs and TQs in rat bile by the above HPLC method. Rats deficient in vitamin E were divided into two groups, gamma-Toc group and alpha+ gamma-Toc group, and tissues were collected at 6 and 24 h after intravenous administration of Tocs. Also, bile collection was started immediately and performed at 3 h intervals during 24 h after intravenous administration. The concentration of alpha- and gamma-Toc and their quinones in plasma, tissues and bile were determined by this method. Gamma-Toc concentration in the liver of alpha+gamma-Toc group was higher than that of gamma-Toc group. However, p-gamma-TQ in the liver was not significantly different between alpha+gamma-Toc group and gamma-Toc group. Also, both alpha-TQ and p-gamma-TQ were present in very low concentrations in all tissues. Therefore, we suggested that the distribution of gamma-Toc is affected by alpha-Toc present in vivo, but the oxidative production of p-gamma-TQ from gamma-Toc is not affected.

Impairment in the expression and activity of Fyn during differentiation of naive CD4+ T cells into the Th2 subset.

We previously showed that the amounts of Fyn protein in Th2 clones were approximately one-third to one-fifth of those in Th1 clones. In this study we examined the role of Fyn in the polarization of naive CD4+ T cells toward the Th2 subset using fyn(-/-) mice. The fyn(-/-) naive CD4+ T cells efficiently produced Th2 cytokines and polarized toward the Th2 subset even in the absence of IL-4 and IL-13. The expression of Fyn in wild-type CD4+ T cells decreased at a transcription level concomitant with polarization toward the Th2 subset. These results suggest that Fyn plays a role in the down-regulation of the differentiation of naive CD4+ T cells into the Th2 subset.

Alpha-tocopherol affects the urinary and biliary excretion of 2,7,8-trimethyl-2 (2'-carboxyethyl)-6-hydroxychroman, gamma-tocopherol metabolite, in rats.

In this study, we investigated a change in the excretory content of 2,7,8-trimethyl-2(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC), a gamma-tocopherol (gamma-Toc) metabolite, in rat urine and bile by using a new high-performance liquid chromatography-electrochemical detection (HPLC-ECD) method. In this determination, CEHC [alpha- and gamma-CEHC, where alpha-CEHC = 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman] in the biological specimens were treated with 3 N methanolic HCl to hydrolyze conjugates and to promote esterification. The methylated samples were extracted by n-hexane/water (1:2). The analyses of the methyl esters of alpha-CEHC and gamma-CEHC were performed by an HPLC-ECD using an ODS-3 column at 35 degrees C. The mobile phase was acetonitrile/water (45:55, vol/vol) containing 50 mM sodium perchlorate. After rat urine and bile samples, respectively, were methylated as described above, methylated biliary metabolites were identified by liquid chromatography-mass spectrometry as methyl esters of gamma-CEHC. Furthermore, we examined the differences in the excretion of gamma-CEHC between rat urine and bile after an oral administration of gamma-Toc or alpha- + gamma-Toc by the above HPLC method. In the gamma-Toc group, each vitamin E-deficient rat was given 0.5 mL of a stripped corn oil preparation containing 10 mg of gamma-Toc. In the alpha- + gamma-Toc group, the rat was given 10 mg of alpha-Toc and 10 mg of gamma-Toc. The content of gamma-CEHC in rat urine from the alpha- + gamma-Toc group was increased more in comparison to the gamma-Toc group at 18-36 h after oral administration. Moreover, the content of gamma-CEHC in rat bile in the alpha- + gamma-Toc group was increased more in comparison to the gamma-Toc group at 6-18 h after oral administration. Therefore, we have suggested that gamma-CEHC was shifted mainly to urinary excretion after gamma-CEHC had been excreted into the bile. Furthermore, we assume that alpha-Toc may affect the metabolism of gamma-Toc to gamma-CEHC in the body.

Effect of sesamin on mitochondrial and peroxisomal beta-oxidation of arachidonic and eicosapentaenoic acids in rat liver.

The effects of dietary sesamin on the hepatic metabolism of arachidonic (AA) and eicosapentaenoic (EPA) acids, were investigated with respect to their beta-oxidation and secretion as triacylglycerol (TG). For 2 wk, rats were fed three types of dietary oils: (i) corn oil (control) group; (ii) EPA group: EPA ethyl esters/rapeseed oil = 2:3; (iii) AA group: AA ethyl esters/palm oil/perilla oil = 2:2:1, with or without 0.5% (w/w) of sesamin. Dietary sesamin significantly increased the activities of hepatic mitochondrial and peroxisomal fatty acid oxidation enzymes (mitochondrial carnitine acyltransferase I, acyl-CoA dehydrogenase, and peroxisomal acyl-CoA oxidase). Dietary EPA increased mitochondrial carnitine acyltransferase I and peroxisomal acyl-CoA oxidase. Dietary AA, however, had an effect on peroxisomal acyl-CoA oxidase only. In whole liver and the TG fraction, EPA and AA concentrations were significantly increased by dietary EPA and AA, respectively, and were decreased by dietary sesamin. In hepatic mitochondria and peroxisomes, EPA concentration was increased by dietary EPA, but AA was not changed by dietary AA. The addition of dietary sesamin to the EPA-supplemented diet significantly decreased the EPA concentration compared to concentrations found with consumption of dietary EPA alone. These results suggest that sesamin increased beta-oxidation enzyme activities and reduced hepatic EPA and AA concentrations by degradation. The stimulating effect of sesamin on beta-oxidation, however, was more significant in the EPA group than in the AA group. Hepatic AA concentration was altered by the joint effect of sesamin through esterification into TG and the stimulation of beta-oxidation.

Regulation by long-chain fatty acids of the expression of cholesteryl ester transfer protein in HepG2 cells.

Cholesteryl ester transfer protein (CETP) is an important determinant of lipoprotein function, especially high density lipoprotein (HDL) metabolism, and contributes to the regulation of plasma HDL levels. Since saturated and polyunsaturated fatty acids (FA) appear to influence the CETP activity differently, we decided to investigate the effects of FA on the expression of CETP mRNA in HepG2 cells using an RNA blot hybridization analysis. Long-chain FA (>18 carbons) at a 0.5 mM concentration were added to the medium and incubated with cells for 48 h at 37 degrees C under 5% CO2. After treatment with 0.5 mM arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acid (DHA), the levels of CETP mRNA were less than 50% of the control levels (AA, P = 0.0005; EPA, P < 0.01; DHA, P < 0.0001), with a corresponding significant decrease in the CETP mass. These results suggest that FA regulate the gene expression of CETP in HepG2 and this effect is dependent upon the degree of unsaturation of the acyl carbon chain in FA.

The effect of dietary carotenoids on lung tumorigenesis induced by intratracheally instillated diesel exhaust particles.

The purpose of this study is to examine the carotenoid effects on lung tumorigenesis induced by intratracheal instillation of diesel exhaust particles (DEP) into mice weekly for 20 wk. It was suggested that active oxygen radicals might play an important role in DEP-induced lung tumorigenesis. Mice were divided to 4 groups of diet containing 0.02% of palm oil carotene, 0.02% of beta-carotene, or no carotenoid with or without DEP. The BF group (4% fat) and the HF group (16% fat) were prepared for each diet group. The experimental period was 12 mo. By the administration of palm oil carotene, neither adenocarcinoma nor adenoma was found in the BF group. In the HF group with palm oil carotene, no adenocarcinoma was observed, and adenoma was reduced. Adenoma in the HF group was not greatly reduced by beta-carotene, but rather increased in the BF group. No adenocarcinoma was found in either the BF or the HF groups with beta-carotene. The 8-hydroxydeoxyguanosine/deoxyguanosine ratio in palm carotene groups was lower than in the other groups, while that in beta-carotene groups was not. From these results, palm oil carotene was suggested to prevent lung tumorigenesis by its protective effect on DNA from active oxygen. Beta-carotene was supposed to have different effects from palm oil carotene on lung tumorigenesis. Besides the chemopreventive effect, the growth of mice was inhibited by the administration of palm oil carotene. Further studies are necessary to elucidate the mechanisms of carotenoid effects.

Antioxidant ability of various flavonoids against DPPH radicals and LDL oxidation.

Flavonoids, a group of polyphenolic compounds, exist naturally and serve as antioxidants in vegetables, fruits, and so on. The inhibition of low density lipoprotein (LDL) oxidation may be an effective way to prevent or delay the progression of atherosclerosis. In the present study, we analyzed the radical scavenging capacity of 10 flavonoids (catechin, epicatechin [EC], epigallocatechin [EGC], epicatechin gallate [ECg], epigallocatechin gallate [EGCg], myricetin, quercetin, apigenin, kaempferol, and luteolin) toward 1,1-diphenyl-2-picryl-hydrazyl [DPPH]. After 20 min of incubation, EGCg was the most effective DPPH radical scavenger, luteolin being the least active of this flavonoid group. The mutual antioxidant effect of flavonoids with alpha-tocopherol (alpha-toc) on LDL oxidizability was investigated by using the lipophilic azo radical initiator 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) [AMVN-CH3O]. An inhibitory effect of flavonoids on LDL oxidation was observed in the order of luteolin>ECg>EC>quercetin>catechin>EGCg>EGC>myricetin>kaempferol> apigenin. The shortened lag time induced by higher doses of alpha-toc (6 mg/100 mL) was restored by flavonoids. These results suggest that 1) radical trapping effects of flavonoids differ according to their structure, and 2) flavonoids act as hydrogen donors to alpha-toc radical; furthermore, by interaction with alpha-toc, they have a greater potential to delay the oxidation of LDL.

Vasoactive intestinal peptide influences neurite outgrowth in cultured rat spinal cord neurons.

Vasoactive intestinal peptide (VIP) is a neuropeptide which has been shown to exhibit a wide range of neurotrophic effects both in vivo and in vitro. For the purpose of clarifying the effect of VIP on spinal cord neurons, we studied the effect of VIP on neurite outgrowth of fetal rat ventral and dorsal portions of spinal cord in cultures. VIP-treated ventral spinal cord cultures (VSCC), compared with control VSCC, had a significant neurite outgrowth at 10(-8), 10(-6), and 10(-4) M. The effect was considered to be concentration dependent. Morphological changes of the dorsal spinal cord cultures (DSCC) remained unchanged by VIP treatment. Because of their close sequence homology with VIP, PHI-27 (peptide, histidylisoleucine amide) and secretin were also examined with the same experimental conditions as was VIP. Both PHI-27 and secretin had neurite promoting effects in VSCC at 10(-8) and 10(-6) M, respectively. However, there were no neurite promoting effects in DSCC in both of them at any concentrations. VIP had the most potent effect on neurite outgrowth in VSCC, followed by PHI-27, and secretin in their effectiveness concentrations. Our data showing VIP, PHI-27 and secretin have neurotrophic action on VSCC and suggest that a potential therapeutic use of VIP and its related peptides in treating diseases that involve degeneration and death of spinal motor neurons, such as motor neuropathy and amyotrophic lateral sclerosis.

Positive and negative regulation of IL-12 receptor expression of naive CD4(+) T cells by CD28/CD152 co-stimulation.

IL-12 is a critical cytokine for polarizing naive CD4(+) T cells toward Th1 subset. Therefore, it is important to elucidate the mechanism of IL-12R expression of naive CD4(+) T cells. In this report, we present evidence to show that expression of both IL-12Rbeta1 and beta2 mRNA is regulated by signals mediated through CD28 and CD152. Naive CD4(+) T cells stimulated with anti-CD3 alone neither expressed IL-12Rbeta2 mRNA nor bound detectable level of rIL-12, although they expressed a very low level of IL-12Rbeta1 mRNA when stimulated with a high dose of anti-CD3. Expression of IL-12Rbeta1 and beta2 mRNA was induced by the co-ligation of CD3 and CD28, and it was down-regulated by the ligation of CD152. CD28 ligation induced not only IL-12Rbeta1 and beta2 mRNA expression, but also enhanced IFN-gammaR to mediate up-regulation of IL-12R by IFN-gamma.