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  • 1
    ISSN: 1573-2568
    Keywords: arteriovenous malformation ; pancreas ; duodenal ulcer ; color Doppler ultrasonography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We report the color Doppler ultrasonography features of arteriovenous malformation (AVM) of the pancreas, a very rare disease. The patient was a 52-year-old man with congenital AVM of the pancreas and a duodenal ulcer that had been resistant to medication. Endoscopic color Doppler ultrasonography (color Doppler EUS) revealed many abnormal color signals showing pulsatile wave form at the portion of the duodenal wall involving the duodenal ulcer. Extracorporeal color Doppler ultrasonography revealed a mosaic-like color signal, caused by turbulent flow, in the portal trunk. Angiography demonstrated a vascular network with extensive proliferation at the pancreatic head and early portal filling. It is possible that the pancreatic AVM had caused the duodenal ulcer. Color Doppler EUS can be a useful modality for detection of vessel abnormalities of the gastrointestinal tract.
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  • 2
    ISSN: 1432-0738
    Keywords: Key words Butyltin compounds ; Cytochrome P450 ; Hepatotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The role of cytochrome P450 in the induction of hepatotoxicity by butyltin compounds such as tributyltin chloride (TBTC) and dibutyltin dichloride (DBTC) was investigated in vivo. The pretreatment of mice with SKF-525A, which decreased hepatic levels of cytochrome P450, suppressed TBTC-induced hepatotoxicity, as estimated by serum ornithine carbamyl transferase activity, whereas pretreatment with phenobarbital (PB), which increased the levels of cytochrome P450, enhanced the hepatotoxicity of TBTC. In the case of DBTC, PB pretreatment enhanced hepatotoxicity, while SKF-525A had no effect. Under these experimental conditions only PB pretreatment was found to increase hepatic levels of tin in mice treated with TBTC. These results suggest that hepatic metabolism of butyltin compounds by cytochrome P450 is more closely related to the induction of hepatotoxicity by TBTC than by DBTC. The active tin compounds formed during hepatic metabolism, which are responsible for induction of hepatotoxicity, will be discussed
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  • 3
    ISSN: 1432-0738
    Keywords: Key words Chromium (VI)  ;  Vitamin E  ;  Cytotoxicity  ; Lipid peroxidation  ;  Hepatocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pretreatment of primary cultures of rat hepatocytes with α-tocopherol succinate (vitamin E) for 20 h prior to exposure to K2Cr2O7 resulted in a marked decrease of chromium (VI)-induced cytotoxicity, as evaluated by the leakage of lactate dehydrogenase, without affecting cellular uptake and subcellular distribution of chromium. The levels of chromium (VI)-induced lipid peroxidation, as monitored by malondialdehyde formation, were also inhibited by pretreatment with the vitamin. Pretreatment with vitamin E normalized the levels of nonenzymatic antioxidants such as glutathione and vitamin C suppressed by dichromate, and caused a distinct accumulation of vitamin E in hepatocytes. However, vitamin E pretreatment did not affect the activities of enzymatic antioxidants including glutathione reductase, superoxide dismutase, and catalase suppressed by dichromate. These results indicate that the protective effect of vitamin E against chromium (VI)-induced cytotoxicity as well as lipid peroxidation, may be associated more with the level of nonenzymatic antioxidants than the activity of enzymatic antioxidants.
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  • 4
    ISSN: 1432-0738
    Keywords: Key words Butyltin compounds ; Hepatotoxicity ; Cytochrome P450
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of pretreatment with SKF-525A, which inhibits hepatic cytochrome P450 enzymes, on metabolism and hepatotoxicity was examined in mice orally administered tributyltin chloride (TBTC) or dibutyltin dichloride (DBTC) at a dose of 180 μmol/kg. Analysis of butyltin compounds showed that the main metabolites in liver of mice treated with TBTC alone were DBTC (40%) and dibutyl(3-carboxylpropyl)tin chloride (TCOOH; 12–26%), with the levels of other butyltin compounds including TBTC comprising 〈12% of total butyltin compounds at 3–24 h following treatment. The pretreatment with SKF-525A resulted in four- to tenfold increased TBTC levels and a significant decrease of debutylated metabolites, particularly DBTC (60 and 37% decrease) at both 3 and 6 h in liver of mice treated with TBTC, leading to complete inhibition of hepatotoxicity at 24 h. At 24 h after TBTC treatment, hepatic levels of TBTC and most of the debutylated metabolites in mice pretreated with SKF-525A did not differ significantly when compared to those in unpretreated mice, resulting in the induction of hepatotoxicity at 48 h, although levels of TCOOH decreased even at 24 h. In the case of DBTC treatment, 〉95% of the butyltin compounds were detected as DBTC in liver, and the levels of DBTC inside cells as well as the induction of DBTC hepatotoxicity were unaffected by pretreatment with SKF-525A. These results suggest that debutylated metabolites, in particular DBTC, are the main metabolites of butyltin compounds responsible for the induction of hepatotoxicity following in vivo administration of TBTC. The results also indicate that cytochrome P450 enzymes may play a greater role in the metabolism of TBTC to form DBTC or butyltin trichloride (MBTC) than that of DBTC to form MBTC in liver of mice.
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  • 5
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The blood-brain barrier (BBB) to endogenous albumin was studied in the olfactory bulb and pons of the senescence-accelerated prone (SAMP8) mouse and senescence-accelerated resistant (SAMR1) mouse strains by using a quantitative immunocytochemical procedure. Ultrathin sections of Lowicryl K4M-embedded samples were exposed to anti-mouse albumin antiserum followed by protein A-gold. Morphometric analysis of the electron micrographs revealed that in the olfactory bulb of both groups of animals, especially in the internal granular layer, some percentage of capillaries and slightly larger microvessels showed leakage of albumin. However, this percentage was larger in SAMP8 than in SAMR1 mice. In the pons, no significant differences in the permeability of blood microvessels were observed in both groups of mice, although a small fraction of capillaries in SAMP8 mice showed limited extravasation of blood plasma albumin. These observations indicate that the BBB in the olfactory bulb of control and SAMP8 mice is not as tight as it is in the pons or in the previously examined cerebral cortex. The labelling density of the neuropil was slightly higher than in the cerebral cortex, suggesting that albumin may have extravasated locally, in addition to having acces to the parenchyma of the olfactory bulb and pons from neighbouring areas supplied with the non-BBB-type of microvasculature. Furthermore, the data obtained suggest that there is limited (segmental), premature agerelated impairment of the BBB function in SAMP8 mice.
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  • 6
    ISSN: 1432-1041
    Keywords: Key words Fluconazole ; Mexiletine; CYP1A2 ; drug interaction ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objective. To investigate the effect of fluconazole on the kinetics of mexiletine. Methods. Six healthy male volunteers participated in a crossover study. On the 1st day, the subjects received 200 mg mexiletine alone. On days 2–7 they received 200 mg fluconazole orally, and on day 8 they received 200 mg mexiletine and 200 mg fluconazole concomitantly. In a third phase two subjects received 400 mg fluconazole daily. Results. No differences in concentrations were observed between the three phases. The area under the concentration curves (AUC) after administration of mexiletine alone and in combination with fluconazole 200 mg/day were 6.63 and 7.31 μg ⋅ h ⋅ ml−1, respectively. Conclusion. These findings suggest that fluconazole does not inhibit mexiletine metabolism.
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  • 7
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The passage of blood-borne horseradish peroxidase (HRP) into the amygdaloid area of the mouse brain was examined with light and electron microscopy. Staining reaction for HRP appeared in medial portions of the amygdaloid area, especially adjacent to the optic tract. Ultrastructural examination of some vessels in that area revealed that the staining reaction for HRP appeared in the perivascular space, the basal lamina, the cytoplasm or vesicular structures of the perivascular cells, vesicular profiles of the endothelial cell cytoplasm including abluminal pits and the adjacent extracellular space. These findings suggest that intravascular macromolecules can invade medial portions of the amygdaloid area of the mouse brain.
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  • 8
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Previously, we have reported that the inactivation of putative tumor-suppressor gene(s) on chromosome 5q21–22 may play an important role in the progression of lung cancer. Here, we describe the establishment of a yeast artificial chromosome (YAC) contig that spans 8–10 Mb at the 5q21–22 region. Six cosmid contigs have also been established in this YAC contig. About 35 exon-like fragments have been detected by exon-amplification, direct screening, cross-species hybridization, and searches of a database. Thus far, 14 cDNAs have been isolated, and two of them coincide with known genes, viz., cysteine dioxygenase I and geranylgeranyltransferase I. The other 12 cDNAs are considered to be novel genes. Two of these novel cDNA show partial homology to known genes, viz., semaphorin CD100 and the 28S rRNA gene. In addition, four known genes, including APC (adenomatous polyposis coli), MCC (mutated in colorectal cancer), proto-oncogene tyrosine kinase FER, and genomic imprinted gene U2AF1-RS1, have also been mapped in this contig. This large contig and expression map should prove crucial in the identification of susceptibility gene(s) related to the progression of lung cancer.
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  • 9
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The mutation responsible for Machado-Joseph disease (MJD) has been identified as an expansion of a CAG trinucleotide repeat in a novel gene on chromosome 14q32.1. The CAG repeat tract is followed by C or G, and alleles are thereby divided into two types on the basis of molecular configuration, (CAG)nC and (CAG)nG. We have studied the relationship between the repeat length and the configuration in 38 patients from 28 Japanese families with MJD, and 31 unrelated normal Japanese subjects. The CAG repeat length in 100 normal alleles ranged from 13 to 37 repeats, while 38 MJD patients had one expanded allele with 64 to 84 repeats. Surprisingly, the expanded alleles had exclusively the (CAG)nC configuration, while both (CAG)nC and (CAG)nG were seen in normal alleles from MJD and control subjects. Furthermore, in normal alleles, the CAG repeat tract was significantly longer in (CAG)nC than in (CAG)nG. These findings suggest that the (CAG)nC configuration is related to repeat instability of the MJD gene.
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  • 10
    ISSN: 1432-1041
    Keywords: Key words Pirmenol ; Arrhythmia ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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