Antifungal Mechanism of Action of Lauryl Betaine Against Skin-Associated Fungus Malassezia restricta

Betaine derivatives are considered major ingredients of shampoos and are commonly used as antistatic and viscosity-increasing agents. Several studies have also suggested that betaine derivatives can be used as antimicrobial agents. However, the antifungal activity and mechanism of action of betaine derivatives have not yet been fully understood. In this study, we investigated the antifungal activity of six betaine derivatives against Malassezia restricta, which is the most frequently isolated fungus from the human skin and is implicated in the development of dandruff. We found that, among the six betaine derivatives, lauryl betaine showed the most potent antifungal activity. The mechanism of action of lauryl betaine was studied mainly using another phylogenetically close model fungal organism, Cryptococcus neoformans, because of a lack of available genetic manipulation and functional genomics tools for M. restricta. Our genome-wide reverse genetic screening method using the C. neoformans gene deletion mutant library showed that the mutants with mutations in genes for cell membrane synthesis and integrity, particularly ergosterol synthesis, are highly sensitive to lauryl betaine. Furthermore, transcriptome changes in both C. neoformans and M. restricta cells grown in the presence of lauryl betaine were analyzed and the results indicated that the compound mainly affected cell membrane synthesis, particularly ergosterol synthesis. Overall, our data demonstrated that lauryl betaine influences ergosterol synthesis in C. neoformans and that the compound exerts a similar mechanism of action on M. restricta.

Schizencephaly:Correlation of Clinical Outcome with Imaging Findings

Schizencephaly is an infrequent congenital disorder of neuronal migration characterized by gray matter-lined clefts that extent through the entire cerebral hemisphere, from the ependymal lining of the lateral ventricle to the pial covering of the cortex. We have studied seven patients with schizencephaly retrospectively to correlate clinical outcome with the type, Size, and location of the clefts and to find associated brain anomalies. Three patients had bilateral clefts(one with two open lip clefts and the other two with a left open lip cleft and a right closed lip cleft), another two patients had left unilateral open lip clefts, and the rest two patients had right closed lip clefts. Clinically, these patients presented motor dysfunction such as hemiparesis, seizures, and variable developmental delay. Patients with bilateral clefts, particularly open lip type, had worse motor and developmental impairment than those with unilateral clefts. Patient with unilateral medium open lip cleft had worse motor and inte llectual impairment than those with unilateral closed lip clefts or small open lip cleft. All patients with frontal lobe involvement had motor dysfunction. Absence of septum pellucidum, gray matter heterotopia, polymicrogyria, and hypoplasia of optic nerves were also frequently found to be associated with schizencephaly. Three patients with skull canges such as enlargement of the hemicranium or erosion of the inner table of the skull were shunted but only one patient improved in the imaging study. We conclude that the severity of patient's symptoms is related to the amount, type, and location of the involved brain.