2,3-Butanedione monoxime protects mice against the convulsant effect of picrotoxin by facilitating GABA-activated currents

While adult mice receiving picrotoxin (PTX) alone responded with clonic and tonic-clonic seizures, this response was greatly suppressed for mice simultaneously injected with 2,3-butanedione monoxime (BDM). For example, 60% and 10% of the mice convulsed when injected (i.p.) with 3.0 mg/kg PTX alone or PTX plus 205 mg/kg of BDM, respectively. In contrast, a non-oxime analogue of BDM, 2,3-butanedione (BTD), did not have this anticonvulsant effect. In order to explore the basis for the anticonvulsant effect of BDM, we recorded GABA-activated currents (I_GABA) of frontal cortical as well as ventromedial hypothalamic neurons before, during and after exposure to this oxime. BDM had a biphasic effect on concentrations (100 μM-40 mM) decreased and lower concentrations (0.01 μM–0.001 μM) potentiatedI_GABA; these effects of BDM reversed upon washout of the oxime. In contrast, BTD had no effect onI_GABA. Finally, when 0.001 μM BDM, 10–30 μM PTX and GABA were co-applied the inhibitory effect of the toxin onI_GABA was markedly suppressed. These data suggest that the anticonvulsant effect of oximes involves facilitation of the inhibitory action of GABA.     

Assessment of sodium and potassium intakes

The sodium, potassium and creatinine contents of three non-consecutive 24-h urine samples collected by 34 selected adult individuals (10 m; 24 f) living in Cork City were determined. The pooled mean 24-h excretion of sodium and potassium in collections adjudged to be complete were 152 mmol and 78 mmol, respectively. There was no significant difference between group average weekday and weekend-day excretion of Na or K, for either males or females. This suggests that weekend 24-h urinary collections, which most subjects find more convenient, are suitable for studies of sodium and potassium intakes of groups. The ratios of intra- to inter-individual variation for 24-h urinary sodium were 1.4 and 2.1 for males and females, respectively. The corresponding ratios for 24-h urinary potassium were 6.6 for males and 4.9 for females. These ratios indicated that there were large individual day-to-day variations in urinary sodium and potassium excretion in this group. It was estimated that a sample size of 35-60 individuals would be required to estimate group mean sodium and potassium intakes by means of single 24-h urine collections.     

Validation of a Flow-Through Diffusion Cell for Use in Transdermal Research

A flow-through finite-dose diffusion cell has been designed for use in transdermal drug delivery research. The diffusion cell consists of an upper donor chamber and a lower receiver compartment through which a continuous supply of fresh solvent flows. The flow is directed to an automatic fraction collector. To validate the flow-through cell, its performance was compared directly against that of a conventional single-reservoir Franz cell. Homologous alkyl p-aminobenzoates were diffused through dimethylpolysiloxane membranes, and permeability coefficients increased with increasing chain length, reaching a plateau at the butyrate ester for both types of cells. This behavior suggests a shift from membrane-controlled diffusion to boundary layer control. Permeation of the butyrate and valerate compounds was significantly faster when the flow-through cell was used, suggesting that better mixing is obtained through the flow-through cell design. Considering the advantages offered in terms of time and labor saved through its use, the flow-through cell with automatic fraction collector appears to be a viable alternative to the conventional Franz cell.     

Elevated choline levels in brain. A non-cholinergic component of organophosphate toxicity

The role of cholinergic and non-cholinergic mechanisms in mediating organophosphate cholinesterase (ChE) inhibitor-induced elevations in choline levels in brain was investigated. The nerve agents soman and sarin, when administered to rats at doses greater than the IC50 for acetylChE inhibition, significantly increased the levels of choline and acetylcholine in both the striatum and hippocampus. The elevation in choline levels was evident 1 hr after injection with a maximal increase at 2 hr. Levels of choline returned to control by 4 hr. In contrast, the administration of diisopropyl phosphorofluoridate at doses greater than the IC50 for acetylChE inhibition increased the levels of acetylcholine, but did not alter the concentration of choline during the first 3 hr. Between 4 and 24 hr after injection, however, a significant decrease in choline levels was apparent. This effect persisted for 48 hr. When rats were pretreated with the anticonvulsant diazepam, the sarin- and soman-induced increases in choline levels were attenuated significantly. Results indicate that the organophosphates differentially alter the levels of choline in brain and suggest that the effect of soman and sarin to elevate choline levels is not a reflection of excessive cholinergic activity, but rather may be a consequence of the excitotoxic actions of these compounds.     

Infantile Digital Fibroma Treated With Mohs Micrographic Surgery

BACKGROUND: Infantile digital fibroma (IDF) is a rare benign fibrous tumor of childhood that frequently recurs despite local excision. Conservative, nonsurgical management may result in regression and/or joint deformity. OBJECTIVE: To describe the histologic features of IDF and discuss a case excised using Mohs micrographic surgery (MMS). METHODS: Case report and review of the clinical, histologic, and ultrastructural features. RESULTS: Characteristic inclusion bodies of actin were identified with hematoxylin and eosin, Masson's trichrome, and rapid actin immunostain. The tumor was debulked and the majority was removed after one stage of MMS, except where the deep margin approached the joint space. The defect healed by secondary intention. At 2 years the patient had no recurrence or functional joint deformity. CONCLUSION: MMS is a surgical treatment option for IDF.