Effects of absorption enhancers on the transport of model compounds in Caco-2 cell monolayers: assessment by confocal laser scanning microscopy.

Three typical absorption enhancers, i.e., sodium caprate (Cap-Na), sodium deoxycholate (Deo-Na), and dipotassium glycyrrhizinate (Grz-K), were compared in terms of their permeability-enhancing effects on hydrophilic and hydrophobic model compounds in Caco-2 cell monolayers. The transepithelial electrical resistance (TEER) of the monolayers was reduced concentration-dependently by treatment with Cap-Na and Deo-Na, while treatment with Grz-K increased the TEER. Two patterns of TEER reduction were observed: one pattern indicated that Cap-Na had a rapid reducing effect, and another indicated that Deo-Na had a delayed reducing effect. These reductions in the TEER were accompanied by the increased transepithelial transport of two hydrophilic model compounds, sodium fluorescein (Flu-Na; MW = 376, log P = -1.52) and fluorescein isothiocyanate-dextran 4000 (FD-4; MW = 4400, log P = -2.0), and one hydrophobic model compound, rhodamine 123 hydrate (Rh123; MW = 381, log P = 1.13). The transport-enhancing effects of Cap-Na and Deo-Na on these model compounds decreased in the following order: FD-4 > Rh123 > Flu-Na, while Grz-K was found to have no effect on the transport of any of these model compounds. Confocal laser scanning microscopy (CLSM) of Caco-2 cell monolayers revealed that Cap-Na and Deo-Na enhanced the transepithelial transport of the hydrophilic model compounds via the paracellular route and that of the hydrophobic model compound via both paracellular and transcellular routes. Semiquantitative visual information obtained from CLSM images reflected the results of the transport experiment.

Assessment of myometrial invasion by endometrial carcinoma: transvaginal sonography vs contrast-enhanced MR imaging.

OBJECTIVE: A prospective study was designed to compare transvaginal sonography with contrast-enhanced MR imaging to determine preoperatively the depth of myometrial invasion in patients with early-stage endometrial carcinoma. SUBJECTS AND METHODS: In 40 patients, findings on transvaginal sonograms, unenhanced T2-weighted MR images, and contrast-enhanced T1-weighted Mr images were compared with histologic findings. The depth of myometrial invasion was classified as stage E (tumor limited to endometrium, n = 12), stage S (superficial invasion: tumor invades up to 50% of the myometrium, n = 15), or stage D (deep invasion: tumor invades more than 50% of the myometrium, n = 13). RESULTS: Findings on transvaginal sonograms were accurate in 27 of 40 patients (accuracy, 68%); the depth of invasion was overestimated in five patients and underestimated in eight patients. The results of unenhanced T2-weighted MR images were accurate in 27 patients (accuracy, 68%), with four overestimations and nine underestimations. The results of contrast-enhanced T1-weighted MR images were accurate in 34 patients (accuracy, 85%), with five underestimations and one overestimation. In the assessment of each stage of myometrial invasion, the sensitivity and specificity of contrast-enhanced T1-weighted imaging were higher than those of T2-weighted MR imaging and transvaginal sonography. The false-positive diagnoses based on transvaginal sonograms and T2-weighted images, respectively, involved polypoid tumors (n = 4 and 2), distension of the endometrial cavity by pyometra (n = 2 and 1), the presence of myoma (n = 2 and 1), atrophy of the myometrium (n = 1 and 0), and poor tumor/myometrium contrast (n = 0 and 2). On contrast-enhanced MR images, accuracy was influenced only in a case of polypoid tumor, because tumor, endometrial cavity, and myometrium were clearly distinguished and residual myometrium was clearly visualized. With all imaging techniques, false-negative diagnoses were caused mainly by tumors with superficially spreading growth or microscopic invasion. With transvaginal sonography, infiltrative tumor also tended to be understaged (n = 3). CONCLUSION: Contrast-enhanced MR imaging is significantly superior to transvaginal sonography and unenhanced T2-weighted MR imaging for detecting myometrial invasion.