Case of cutaneous Scedosporium apiospermum infection successfully treated with voriconazole

We report a case of cutaneous infection due to Scedosporium apiospermum in a 75-year-old immunocompromised male patient who had received long-term corticosteroid and immunosuppressant therapy for the treatment of nephrotic syndrome. The patient came to our department complaining of erythema with a number of pustules on the dorsal surface of the right hand. S. apiospermum was identified from a culture taken from the pus. After unsuccessful treatment with topical ketoconazole, oral itraconazole and oral terbinafine, the lesion quickly resolved with the daily administration of 400 mg voriconazole. No recurrence was observed despite discontinuation of voriconazole due to drug-induced hepatitis. Voriconazole holds out the promise of an effective treatment for invasive Scedosporium infection.     

Tissue- and subcellular-distribution of the binding site of [3H]9-methyl-7-bromoeudistomin D,a potent caffeine-like Ca2+ releaser,in rabbits

Abstract— Tissue and subcellular distribution of the binding site of ³H-labelled 9-methyl-7-bromoeudistomin D ([³H]MBED), a powerful caffeine-like Ca²⁺ releaser, were investigated in rabbits. The order of specific activities of total homogenates was liver > brain > other tissues. All binding was completely suppressed by 10 Mm caffeine, indicating that all [³H]MBED binding sites are modulated by caffeine. [³H]MBED binding sites distributed mainly in membrane fractions rather than soluble fractions in most tissues. In lung and liver, [³H]MBED binding was enriched in microsomes. [³H]MBED may be useful as a probe to investigate the actions of caffeine at the molecular level not only in muscles but also in a variety of tissues including liver, kidney and lung.     

Potentiation of carbon tetrachloride-induced liver damage by dibutylyl-3',5'-cyclic AMP in unstarved rats

It has been reported that carbon tetrachloride-induced liver damage is potentiated by starvation partly due to fat accumulation in the liver and a decrease in hepatic reduced glutathione concentration and that dibutylyl-3′,5′-cyclic AMP (DBcAMP) affects fuel metabolism and decreases hepatic reduced glutathione. We investigated the effects of DBcAMP on carbon tetrachloride-induced liver damage both in unstarved and starved rats. In unstarved rats, intraperitoneal administration of DBcAMP potentiated an increase in serum alanine aminotransferase activity and fatty vacuolization in the liver, both of which were induced by carbon tetrachloride. Hepatic reduced glutathione concentration was also reduced by DBcAMP, although the change was not significant. In contrast, the administration of DBcAMP in starved rats did not affect carbon tetrachloride-induced changes in serum alanine aminotransferase activity, histological alterations and hepatic reduced glutathione concentration. Administration of DBcAMP to control rats induced different responses in unstarved control rats compared with starved control rats: in unstarved rats, blood glucose concentration decreased but serum free fatty acid concentration increased, whereas in starved rats, blood glucose concentration increased and serum free fatty acid concentration decreased. It was suggested that DBcAMP potentiated carbon tetrachloride-induced liver damage in unstarved rats, probably due to hepatic fat accumulation and a decreased hepatic reduced glutathione concentration. The former could increase the affinity of the liver for carbon tetrachloride and the latter could accelerate carbon tetrachloride-induced lipid peroxidation. It was also suggested that DBcAMP failed to affect carbon tetrachloride-induced liver damage in starved rats, probably because starvation had already decreased hepatic glutathione concentration and DBcAMP had different effects on fuel metabolism compared with effects observed in unstarved rats.     

Hepatotoxicity of Agents That Enhance Formation of Focal Hepatocellular Proliferative Lesions (Putative Preneoplastic Foci) in a Rapid Rat Liver Bioassay

Hepatotoxicity of Agents That Enhance Formation of Focal HepatocellularProliferative Lesions (Putative Preneoplastic Foci) in a RapidRat Liver Bioassay. WARD, J. M., TSUDA, H., TATEMATSU, M., HAGIWARA,A., AND ITO, N. (1989). Fundam Appl Toxicol. 12., 163–171.The histopathology of hepatic toxicity for 58 chemicals previouslytested in a rapid rat liver bioassay for demonstrating potentialhepatocellular carcinogens and/or tumor promoters was reviewed.Rats received the test diet for 1 week prior to partial hepatectomyand for an additional 5 weeks thereafter at doses near the estimatedmaximally tolerated dose. These rats served as controls forothers receiving initiation by N-nitrosodiethylamine (DEN) andthe test diets. Twenty-two of these chemicals were previouslyfound to enhance the formation of glutathione S-transferase,placental form (GST-P)-positive putative preneoplastic hepatocellularfoci (promoters) following DEN initiation in this rapid bioassay,whereas 36 chemicals did not. Of the agents that promoted GST-P-positivefoci, 14/22 (63.6%) produced toxic hepatocyte lesions whileonly 4/36(11.1%) of the nonpromoters did so at the doses used.Biliary toxicity was found for 7/22 (31.8%) of the promotersand 6/36 (16.7%) of the nonpromoters. Only 2/13 (15%) chemicalsthat inhibited GST-P-positive foci produced hepatic toxicity.Thus, agents that were presumed hepatic tumor promoters characteristicallywere hepatotoxins while nonpromoters of carcinogenesis werenot hepatotoxins in this rapid rat liver bioassay.     

Mechanism of action and therapeutic indication of prosthetic mandibular advancement in obstructive sleep apnea syndrome

Abstract Prosthetic mandibular advancement (PMA) was applied to nine patients with obstructive sleep apnea syndrome (OSAS) and its therapeutic usefulness, mechanism of action, and clinical indication were discussed based on polysomnographic findings and serial examination of upper airway before and during PMA treatment. Apnea hypopnea index significantly decreased during PMA treatment compared with the value before treatment ( P < 0.01) and the rate of the treatment responder counted 78.1%. Cephalometric variables indicated forward and inferior advancement of mandible in our subjects. Magnetic resonance imaging of the upper airway during sleep revealed a marked improvement of velopharyngeal obstruction in most subjects. In addition, intraesophageal negative pressure during sleep decreased significantly. Our results confirmed the high therapeutic efficacy of PMA for OSAS and indicated forward advancement of the mandible and decrease of negative pressure loading on upper airway with PMA might suppress velopharyngeal collapse. Thus, PMA was regarded as one of the treatments of choice for OSAS occurring based on with velopharyngeal narrowing.     

Multiple ileal ulcers and an ileal Dieulafoy's lesion induced by loxoprofen sodium

Loxoprofen sodium is one of the non‐steroidal anti‐inflammatory drugs (NSAIDs) that is a prodrug. Several adverse effects of the drug have been described, but ileal ulcer has not been reported so far. We experienced an 87‐year‐old male patient with disk herniation complicated with loxoprofen sodium‐induced multiple ileal ulcers and an ileal Dieulafoy's lesion that caused massive intestinal bleeding. The patient was saved by wedge resection of the Dieulafoy's lesion and discontinuance of the NSAID. ^99mTc‐red blood cell scintigraphy and intraoperative enteroscopy of the small bowel were useful in the diagnosis. This is the first case of multiple ileal ulcers with an ileal Dieulafoy's lesion induced by loxoprofen sodium.     

The effects of dichloroacetate on liver damage and circulating fuels in rats exposed to carbon tetrachloride

Abstract It has been known that carbon tetrachloride-induced liver damage in starved rats is ameliorated simply by restoration of feeding. An analogue of dichloroacetate has been reported to ameliorate carbon tetrachloride-induced liver damage, and dichloroacetate has been shown to have a variety of effects on fuel metabolism. We investigated simultaneously the effects of dichloroacetate on liver damage and on circulating fuels in rats exposed to carbon tetrachloride. The effects of carbon tetrachloride varied with the rat's condition. In starved rats, the liver damage was more severe, and serum ketone body concentration decreased. In non-starved rats, the liver damage was not as severe and the serum ketone body concentration increased. The administration of dichloroacetate ameliorated liver damage both in starved and in non-starved rats given carbon tetrachloride: the administration of dichloroacetate protected from the liver damage particularly in starved rats. There were associated changes in the concentractions of circulating fuels. When the pyruvate-lowering effect of dichloroacetate was diminished in carbon tetrachloride-injected, starved rats, the alanine aminotransferase-lowering effect of dichloroacetate was also diminished. We propose that dichloroacetate's effect on fuel metabolism may produce a hepato-protective effect.     

Developmental change in activity of red cell porphobilinogen deaminase and its electrophoretic variant in the Japanese population

The activity of porphobilinogen deaminase (PBGD), an enzyme whose partial deficiency is associated with acute intermittent porphyria (AIP), changes during development. Little is known about the postnatal change of PBGD activity and the prevalence of its electrophoretic variant in the Japanese population. The activity of PBGD was measured fluorometrically in 194 infants aged 0–12 months, while isoelectric focusing of PBGD was performed in 400 healthy Japanese adults aged 20–45 years and 30 children with various hematological disorders aged 1–15 years. The PBGD level was 1.9 times higher in the neonates than in the adults, decreased abruptly during the first month of life, and reached the adult level at the age of 9 months. None of the 400 healthy Japanese adults and the 30 children with hematological disorders showed any electrophoretic variant. These results suggest that there is no need to consider any polymorphism in the gene dose study of PBGD and that the biochemical screening of AIP is applicable to since the late infancy.