Intravenous antiepileptic drugs are required in patients needing urgent treatment or unable to take oral medication. The safety of intravenous levetiracetam has been established in prospective studies of adult epilepsy and healthy participants. The authors performed a prospective, single-center study to evaluate the safety of a rapid loading dose of intravenous levetiracetam. Patients were divided into 3 equal dosing groups (N = 15 each): 20, 40, and 60 mg/kg (corresponding to maximum doses of 1, 2, and 3 g). Electrocardiogram and safety assessment were performed during the infusion. Ages were 4 to 32 years. Postinfusion serum levetiracetam concentrations were 14 to 189 microg/mL. There were no significant changes in blood pressure, no local infusion site reactions, and no electrocardiogram abnormalities. The authors concluded that high serum levels of parenteral levetiracetam can be achieved rapidly and safely, in a small infusion volume. This finding has important implications for the treatment of status epilepticus.

Cell culture, a powerful tool for the study of cell biology, offers advantages for the study of renal cell function. Epithelial cells derived from a variety of organs, including the kidney, form oriented epithelial sheets in culture that have many structural characteristics (microvilli, tight junctions) of epithelia in situ. There is evidence of transepithelial transport of salt and water by cells of two lines (MDCK and LLC-PK1) derived from mammalian kidney. LLC-PK1 cells may also manifest the glucose transport system of the proximal tubule. Cells of both lines have adenylate cyclase activity sensitive to hormones. Two lines of cells derived from toad urinary bladder form epithelia with a high transepithelial resistance and transport sodium actively from apical to basolateral surface. The rate of sodium transport in both lines is stimulated by cyclic AMP and by aldosterone. There are important differences in the characteristics of the response of the two lines to aldosterone as well as in their sensitivity to inhibition of sodium transport by amiloride. These differences may lead to new insights regarding the molecular events in the response to aldosterone and in the inhibitory action of amiloride. Cultures of kidney cells have also been used effectively to study the biosynthesis of the hormonal derivative of vitamin D and to study prostaglandin production. In addition, cell culture is ideally suited for study of the developmental biology of the kidney.

The characteristics of a continuous line of toad kidney epithelial cells (A6) are described. These cells form a monolayer epithelium of high transepithelial electrical resistance (about 5,000 omega . cm2). The cells generate a transepithelial potential difference (apical surface negative) of about 9 mV. The short-circuit current is equivalent to net sodium flux. Net sodium flux is stimulated by aldosterone and by analogues of cAMP. The stimulation is readily reversible. Neither urea permeability nor osmotic water flow is altered by analogues of cAMP. Amiloride eliminates 90% of the short-circuit current. Thus A6 cells form an epithelium with several differentiated properties including hormonal regulation of transport.

A continuous line of cells (A6) derived from toad kidney has been shown to form epithelia in culture that manifest aldosterone-stimulatable transepithelial sodium transport. In this study an efficient filtration assay for nuclear binding of [3H]aldosterone was validated. Specific high-affinity aldosterone and corticosterone binding sites in the particulate (nuclear-enriched) fraction were characterized in intact epithelia. Despite metabolism of both steroids, two high-affinity binding sites for each were demonstrable: aldosterone, K'd1 = 0.85 (+/- 0.19) X 10(-10) and K'd2 = 1.6 (+/- 0.42) X 10(-8) M; corticosterone, K'd1 = 0.5 (+/- 0.31) X 10(-10) and K'd2 = 0.32 (+/- 0.19) X 10(-8) M. Analogue competition-binding studies indicated a qualitative difference in the two sites and co-occupancy of both sites by the two steroids. The sodium transport response to aldosterone and corticosterone approximated a linear function of occupancy of the lower affinity sites. Although the lower affinity sites resemble mammalian glucocorticoid receptors in terms of relative binding affinities for analogues, we conclude that they are the receptors which mediate the aldosterone and corticosterone stimulation of Na+ transport in these epithelia.