Neurothekeoma of the eyelid: a case report

The purpose of this article is to describe a rare benign tumor of nerve sheath origin arising from the eyelid in an elderly male. Local excision was done and histopathological examination revealed a neurothekeoma. Six months later the patient was doing well with no recurrence. The case was unique in that the patient was an elderly male while neurothekeoma is commonly seen on the face of young adults, especially females.     

Stereoselective inhibition of cytochrome P450 forms by lansoprazole and omeprazole in vitro

The stereoselectivity of the inhibitory interaction potential of lansoprazole and omeprazole isomers on six human cytochrome P450 forms was evaluated using human liver microsomes. Lansoprazole enantiomers showed stereoselective inhibition of CYP2C9-catalysed tolbutamide 4-methylhydroxylation, CYP2C19-catalysed S-mephenytoin 4'-hydroxylation, CYP2D6-catalysed dextromethorphan O-demethylation, CYP2E1-catalysed chlorzoxazone 6-hydroxylation and CYP3A4-catalysed midazolam 1-hydroxylation, whereas omeprazole only inhibited CYP2C19 stereoselectively. Of the P450 forms tested, CYP2C19-catalysed S-mephenytoin 4'-hydroxylation was extensively inhibited by both the lansoprazole and omeprazole enantiomers in a competitive and stereoselective manner; the S-enantiomers of both drugs inhibited the hydroxylation more than the R-enantiomers. The estimated K(i) values determined for CYP2C19-catalysed S-mephenytoin 4'-hydroxylation were 0.6, 6.1, 3.4 and 5.7 microM for S-lansoprazole, R-lansoprazole, S-omeprazole and R-omeprazole, respectively. The results indicate that although both lansoprazole and omeprazole are strong inhibitors of CYP2C19, the inhibition of CYP2C19 by lansoprazole is highly stereoselective, whereas the inhibition by omeprazole is less stereoselective. In addition, S-lansoprazole, the most potent CYP2C19 inhibitor, is not a good CYP2C19-selective inhibitor owing to its inhibition of other P450 forms.     

Effect of CYP2C19 genetic polymorphism on pharmacokinetics and pharmacodynamics of a new proton pump inhibitor, ilaprazole

It is well known that the CYP2C19 genetic polymorphism influences the pharmacokinetics and pharmacodynamics of proton pump inhibitors (PPIs), but no report has addressed the effects on ilaprazole, a newly developed PPI. To investigate the effects of the CYP2C19 genetic polymorphism on the disposition and pharmacodynamics of ilaprazole, multiple doses of once-daily 10 mg ilaprazole were repeatedly administered for 7 days to 27 healthy Korean participants, comprising 9 homozygous CYP2C19 extensive metabolizers (homo EMs), 10 heterozygous EMs (hetero EMs), and 8 homozygous poor metabolizers (PMs). The plasma concentration and pharmacodynamic response were measured in the last dose interval. Each genotype group was matched for gender and thus was composed of 4 male and 4 female participants when the analysis was conducted. The pharmacokinetic parameters estimated from the plasma concentrations of ilaprazole and its metabolite ilaprazole sulfone, the serum gastrin level, and the 24-hour intragastric pH were compared among the CYP2C19 genotype groups. No statistically significant differences in the maximum plasma concentration at steady state(C(ss,max)) and the area under the concentration-time curve from zero to 24 hours (AUC(τ)) of ilaprazole and ilaprazole sulfone were observed among the homo EM, hetero EM, and PM CYP2C19 genotypes. In addition, the mean 24-hour intragastric pH, the percentage of time at pH >4, and the AUC(τ) of serum gastrin showed no significant differences among the CYP2C19 genotype groups. The data suggests that the pharmacokinetics and pharmacodynamics of ilaprazole are not significantly influenced by the CYP2C19 genetic polymorphism in healthy participants.     

Regulation of tumor necrosis factor secretion in leukocytes from alpha-1-antitrypsin deficient humans.

Alpha-1-antitrypsin (AT) is one of several alpha-globulins which have been shown to be inhibitors of human peripheral blood monocyte TNF secretion in vitro. AT deficiency states exist, within which individuals of either the PiSS or PiZZ phenotype have reduced hepatocyte and mononuclear phagocyte AT secretion when compared to normal PiMM subjects. Here we have compared the capacity of peripheral blood monocytes of all three phenotypes to respond to both enhancers and inhibitors of TNF secretion. All monocytes exposed to lipopolysaccharide (LPS), interferon-gamma (IFN-gamma) and endotoxin, PGE2, transforming growth factor-beta 1, whole plasma alpha-globulins, purified AT and IL-6 responded equally with respect to the secretion of TNF. Our findings show that the regulation of TNF secretion in leukocytes from AT deficient humans is normal and suggest that defective AT secretion alone does not result in the aberrant regulation of TNF secretion.     

Atypical Presentation of Postpartum Cerebral Angiopathy Shown as a Small Penetrating Arterial Territory Infarct with Severe Peri‐Infarct Edema

Postpartum cerebral angiopathy mostly occurs in the large or medium‐sized cerebral arteries. In this case, we aimed to report a case of postpartum cerebral angiopathy presented as an asymmetrical penetrating arterial territory infarct with severe surrounding vasogenic edema. A 26‐year‐old woman admitted because of sudden headache after an attack of seizure. On initial computerized tomography (CT), hypodense lesion in the right basal ganglia was observed. The diffusion‐weighted image on 5th day revealed focal acute ischemic infarction with surrounding extensive vasogenic edema in right basal ganglia. The CT angiography showed multifocal arterial narrowing of intracranial cerebral arteries that completely resolved on the follow‐up study. This case suggested that asymmetrical small penetrating arterial territory infarct can occur as an atypical presentation of postpartum cerebral angiopathy.