One area that has been overlooked in the evolution of magnetic nanoparticle technology is the possibility of introducing informational atoms into the iron oxide core of the coated colloid. Introduction of suitable atoms into the iron oxide core offers an opportunity to produce a quantifiable probe, thereby adding one or more dimensions to the magnetic colloid's informational status. Lanthanide-doped iron oxide nanoparticles have been synthesized to introduce informational atoms through the formation of colloidal mixed ferrites. These colloids are designated ultrasmall mixed ferrite iron oxides (USMIOs). USMIOs containing 5 mol % europium exhibit superparamagnetic behavior with an induced magnetization of 56 emu/g Fe at 1.5 T, a powder X-ray diffraction pattern congruent with magnetite, and R1 and R2 relaxivity values of 15.4 (mM s) (-1) and 33.9 (mM s) (-1), respectively, in aqueous solution at 37 degrees C and 0.47 T. USMIO can be detected by five physical methods, combining the magnetic resonance imaging (MRI) qualities of iron with the sensitive and quantitative detection of lanthanide metals by neutron activation analysis (NA), time-resolved fluorescence (TRF), X-ray fluorescence, along with detection by electron microscopy (EM). In addition to quantitative detection using neutron activation analysis, the presence of lanthanides in the iron oxide matrix confers attractive optical properties for long-term multilabeling studies with europium and terbium. These USMIOs offer high photostability, a narrow emission band, and a broad absorption band combining the high sensitivity of time-resolved fluorescence with the high spatial resolution of MRI. USMIO nanoparticles are prepared through modifications of traditional magnetite-based iron oxide colloid synthetic methods. A 5 mol % substitution of ferric iron with trivalent europium yielded a colloid with nearly identical magnetic, physical, and chemical characteristics to its magnetite colloid parent.

Primary cultures of dispersed hypothalamic cells were prepared from embryonic rats to study the release of immunoreactive somatostatin. The immunoreactive somatostatin content of these cultures increased during the first 2 weeks after plating and was readily measurable for several weeks thereafter; this material was characterized by gel permeation and reverse-phase chromatography. Depolarization of the cells with 60 mM K+ or with veratridine resulted in a calcium-dependent release of immunoreactive somatostatin which cochromatographed with synthetic somatostatin on reverse-phase chromatography. Tetrodotoxin blocked the veratridine-evoked release. However, even in the absence of exogenous stimuli, immunoreactive somatostatin was released by the cells into the medium. More than 70% of this tonic release was found to be calcium dependent and to be inhibited by tetrodotoxin, indicating that spontaneous electrical activity in the cultures leads to a release of immunoreactive somatostatin. gamma-Aminobutyric acid inhibited the tonic release of immunoreactive somatostatin and this was reversed by bicuculline. These findings support the hypothesis that gamma-aminobutyric acid inhibits somatostatin release in vivo.

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OBJECTIVE-To evaluate use of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) to estimate glomerular filtration rate (GFR) by plasma clearance and use of an ELISA as the method of Gd-DTPA quantification. ANIMALS-16 dogs of various sexes and breeds (12 dogs were clinically normal, and 4 dogs were polyuric and polydipsic with no other clinical or biochemical abnormalities). PROCEDURES-GFR was estimated by measuring the plasma clearance of Gd-DTPA and iohexol by use of an ELISA and high-performance liquid chromatography (HPLC), respectively. The GFR was determined by use of a 1-compartment model for both methods. The GFRs obtained by Gd-DTPA plasma clearance were compared with those obtained by iohexol plasma clearance by use of correlation analysis, paired t tests, and limits of agreement analysis. A paired t test was used to evaluate differences between the 2 plasma clearance methods. RESULTS-A strong linear correlation (r(2) = 0.90) was found between GFRs derived from the plasma clearance of Gd-DTPA and those derived from the plasma clearance of iohexol. By use of limits of agreement analysis, almost all (13/14) dogs had Gd-DTPA GFRs that were within 12% of iohexol GFRs. The remaining dog had a Gd-DTPA GFR that was 45% higher than the iohexol GFR. There was no significant difference between Gd-DTPA GFRs and those obtained with iohexol. CONCLUSIONS AND CLINICAL RELEVANCE-This study revealed that plasma clearance of Gd-DTPA measured by use of an ELISA is an effective method to estimate GFR in dogs because it compared favorably with results for the iohexol-HPLC method.