Obturator pyomyositis and labium majus cellulitis: A case report and literature review.

Pyomyositis is a rare, subacute, deep bacterial infection of the skeletal muscle. When treatment is delayed, pyomyositis causes abscess formation and progresses to sepsis; therefore, its early diagnosis is important. However, the clinical presentation and laboratory findings of pyomyositis are not specific; hence, diagnosis often takes time. We encountered the case of a girl with obturator pyomyositis and redness and swelling of the labium majus, which we considered as potentially important symptoms for distinguishing obturator pyomyositis from septic hip arthritis. An 8-year-old Japanese girl presented to our hospital with fever and right hip pain. On physical examination, she had redness and swelling of the right labium majus and a right limp. She was diagnosed with obturator pyomyositis and labium majus cellulitis with magnetic resonance imaging. Her clinical presentation markedly improved after starting antibiotic therapy with intravenous cefazolin for 2 weeks and oral cefaclor for 1 week. Improvement in the inflammation of the obturator muscle and labium majus was confirmed with follow-up magnetic resonance imaging. She recovered fully with no long-term sequelae. In conclusion, obturator pyomyositis rather than septic hip arthritis should be considered in children with a limp and hip and perineal pain, particularly girls with redness and swelling of the labium majus. In addition, imaging studies, including magnetic resonance imaging, should be performed for early diagnosis.

Contribution of Human Liver and Intestinal Carboxylesterases to the Hydrolysis of Selexipag In Vitro.

In liver microsomes, selexipag (NS-304; ACT-293987) mainly undergoes hydrolytic removal of the sulfonamide moiety by carboxylesterase 1 (CES1) to yield the pharmacologically active metabolite MRE-269 (ACT-333679). However, it is not known how much CES in the liver and intestine contributes to the hydrolysis of selexipag or how selexipag is metabolized in the intestine, including by hydrolysis. To obtain a better understanding of selexipag metabolism in humans, we determined the percentage contribution of CES1 and carboxylesterase 2 (CES2) to the hydrolysis of selexipag and 7 of its analogs with different sulfonamide moieties and evaluated its nonhydrolytic metabolism in human liver microsomes and human intestinal microsomes (HIMS). For selexipag, the percentage contributions of CES1 and CES2 in human liver microsomes were 77.0% and 9.99%, respectively, while the percentage contribution of CES2 in HIMS was 100%. In HIMS, the rate of hydrolysis of selexipag was the lowest among the compounds tested, and no difference between the presence and absence of nicotinamide adenine dinucleotide phosphate was noted. We infer from these results that selexipag is likely to be hydrolyzed by CES2 as well as CES1, and only selexipag itself and the MRE-269 produced by hydrolysis in the intestine would be absorbed after oral administration.

Development of a simple measurement method for GluR2 protein expression as an index of neuronal vulnerability.

In vitro estimating strategies for potential neurotoxicity are required to screen multiple substances. In a previous study, we showed that exposure to low-concentrations of some chemicals, such as organotin, decreased the expression of GluR2 protein, which is a subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors, and led to neuronal vulnerability. This result suggested that GluR2 decreases as an index of neuronal cell sensitivity and vulnerability to various toxic insults. Accordingly, we developed a versatile method that is a large scale determination of GluR2 protein expression in the presence of environmental chemicals by means of AlphaLISA technology. Various analytical conditions were optimized, and then GluR2 protein amount was measured by the method using AlphaLISA. The GluR2 amounts were strongly correlated with that of measured by western blotting, which is currently used to determine GluR2 expression. An ideal standard curve could be written with the authentic GluR2 protein from 0 ng to 100 ng. Subsequently, twenty environmental chemicals were screened and nitenpyram was identified as a chemical which lead to decrease in GluR2 protein expression. This assay may provide a tool for detecting neurotoxic chemicals according to decreases in GluR2 protein expression.