Freeze-dried, ultrathin cryosections of directly frozen mouse liver and brain have been prepared and characterized by low-dose dark-field scanning transmission electron microscopy (STEM). These improved cryosections gave images comparable to those from conventional plastic sections. They were thin enough (< < 1.0 elastic mean free path) to use established dark-field techniques, modified for thickness-dependent nonlinearities, to measure the dry mass fraction of individual organelles, and hence to deduce their water content. Digital STEM imaging in combination with electron and X-ray spectroscopy has important biological applications, as illustrated by studies on calcium regulation in Purkinje neurons. Calcium concentrations per unit dry weight of dendritic compartments were determined by the peak/continuum method of energy-dispersive X-ray spectroscopy (EDXS), which necessarily overstates elemental concentrations because of beam-induced mass loss. The dry mass content of organelles at low dose and the percentage of dry mass retained after analysis at high dose were as follows: mitochondria (46.0 g dry mass/100 g hydrated mass, 67% mass retained); endoplasmic reticulum (27.9 g/100 g, 57%); and cytoplasm (16.3 g/100 g, 41%). These values were used to correct elemental concentrations for mass loss. Results indicated that the major calcium storage organelle in Purkinje cell dendrites is the endoplasmic reticulum, of which there are two types distinguished by their levels of calcium. Parallel electron energy loss spectroscopy of dendritic organelles corroborated EDXS measurements, with an improved sensitivity that indicates the feasibility of quantitative calcium mapping.

Animals↗

PubMedDate not supplied

Pharmacokinetic profile of a 300-mg extended phenytoin sodium capsule (Dilantin) formulation.

The pharmacokinetic profile of a newly developed Dilantin 300-mg Kapseal formulation was compared with that of currently marketed Dilantin 100-mg Kapseals in both a 300-mg single-dose bioequivalence study in nine healthy volunteers and a once-daily 300-mg multiple-dose study in 18 patients with seizures. Results of these studies indicate the rate and extent of absorption of the 300-mg extended phenytoin (PHT) sodium capsule formulation are similar to that of 100-mg extended PHT sodium capsules based on PHT plasma maximum concentrations and time to achieve them (Cmax, tmax), and area under the curve (AUC) values and the urinary excretion of total hydroxy phenylhydantoin (HPPH) in the single-dose study and steady-state PHT plasma Cmax, tmax, minimum plasma concentrations (Cmin), and AUC values and urinary excretion of total HPPH in the multiple-dose study. Control of seizures in patients was equally maintained on a once-daily 300-mg multiple-dosing regimen administered as either one 300-mg extended PHT sodium capsule daily or three 100-mg extended PHT sodium capsules daily. Therefore, 300-mg extended PHT sodium capsules can be safely and effectively interchanged with three 100-mg extended PHT sodium capsules in patients requiring a once-daily 300-mg PHT sodium dosing regimen.

Adult↗

PubMedDate not supplied

A clinical study of the effect of phenobarbital on diphenylhydantoin plasma levels.

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Adolescent↗

PubMedDate not supplied

Morphometric changes in pericyte-capillary endothelial cell associations correlated with vasoactive stimulus.

The arterially-derived capillaries of the eel rete mirabile are heavily invested with highly arborized pericytes. By perfusing vasoactive agents through these capillaries, measuring changes in outflow volume and analyzing alterations in capillary and pericyte morphology a set of vasoactive agent-correlated changes were quantified. Morphometric analysis of the capillary ultrastructure revealed that alterations in flow and appearance were associated with changes in the extension of pericyte processes. These responses of the arterial pericytes to the vasoactive agents used in this study suggest that pericyte contraction alters the architecture of the arterially-derived capillaries of the rete in a manner which affects their permeability.

Anguilla↗

PubMedDate not supplied