Dihydropyridine calcium channel blockers inhibit ascorbic acid accumulation in human intestinal Caco-2 cells.

We investigated the effect of commonly used medications on the accumulation of ascorbic acid in human intestinal Caco-2 cells. Although ascorbic acid is negatively charged at physiological pH, anionic compounds including drugs and metabolites had little effect on its accumulation. On the other hand, hydrophobic 1,4-dihydropyridine compounds (nifedipine and nicardipine), but not other structurally unrelated calcium channel blockers, were found to be potent inhibitors. They inhibited both Na+-dependent and Na+-independent (K+ substituting Na+) accumulation of ascorbic acid. The inhibition was non-competitive with a Ki of 108 microM and 9 microM for nifedipine and nicardipine, respectively. The efflux of ascorbic acid from cells was not affected. Previously, we reported a similar inhibition of ascorbic acid accumulation by estrogens. When nifedipine and estrogens were included in the buffer together, the combined inhibitory effect was less than additive implying that they may act through the same mechanism. The potential clinical significance of dihydropyridine usage on ascorbic acid status in human needs to be considered.

The importin/karyopherin Kap114 mediates the nuclear import of TATA-binding protein.

Two high copy suppressors of temperature-sensitive TATA-binding protein (TBP) mutants were isolated. One suppressor was TIF51A, which encodes eukaryotic translation initiation factor 5A. The other high copy suppressor, YGL241W, also known as KAP114, is one of 14 importin/karyopherin proteins in yeast. These proteins mediate the transport of specific macromolecules into and out of the nucleus. Cells lacking Kap114 partially mislocalize TBP to the cytoplasm. Kap114 binds TBP in vitro, and binding is disrupted in the presence of GTPgammaS. Therefore, Kap114 is an importer of TBP into the nucleus, but alternative import pathways must also exist.

Effect of antiproliferative flavonoids on ascorbic acid accumulation in human colon adenocarcinoma cells.

Dietary flavonoids were found to be antiproliferative for human colon cancer cells, Caco-2 and HT-29, and rat nontransformed intestinal crypt cells, IEC-6. The antiproliferative potency was found to be structure-dependent. We report here a correlation between the antiproliferative potency of these flavonoids and their ability to inhibit cellular accumulation of ascorbic acid (vitamin C). Caco-2, HT-29 and IEC-6 cells were found to accumulate ascorbic acid in a sodium-dependent fashion although some ascorbic acid may also enter the cells through sodium-independent mechanisms. Flavonoids that have been found to be antiproliferative, quercetin and genistein, inhibited the accumulation of ascorbic acid. The inhibition was dose-dependent and could be observed after as short as 10-min of incubation. The degree of inhibition of accumulation was more during rapid cell division as compared to post-confluency Caco-2 cells. Flavonoids that were found to show little antiproliferative effect, naringenin and catechin, also had little effect on ascorbic acid accumulation. The antiproliferative property of flavonoids could be linked to their ascorbic acid deprivation property.

CT of pancreatitis with renal and juxtarenal manifestations.

Involvement of the juxtarenal spaces and kidneys in pancreatitis has been well known. Although delineation of the regions of accumulation of exudate has been elegantly confirmed with the advent and advance of refined computerized tomography (CT) there has been relatively little description in the earlier literature of these phenomena. This essay serves to illustrate the wide range of findings that have been encountered and recorded more recently.

Cystic adrenal lesions: CT features.

PURPOSE: To define computed tomographic (CT) features of cystic adrenal lesions that differentiate them from similar-appearing adenoma. MATERIALS AND METHODS: CT scans of 13 cystic adrenal lesions (four endothelial cysts, three benign pseudocysts, one nonspecific benign cyst, one carcinoma, one pheochromocytoma, and three stable lesions with no histologic diagnosis) were analyzed retrospectively. Reports in the literature of 26 benign adrenal cysts were also reviewed. RESULTS: Mean lesion diameter was 6.2 cm, and six lesions were less than 5.0 cm. Mean attenuation values was 21 HU, and in eight cases it was less than 15 HU. Partial adrenal involvement was noted in six cases. Ten lesions contained wall or septal calcification. Wall thickness was 3 mm or less in nine and exceeded 6 mm in three lesions; one of the latter was cystic carcinoma. Wall enhancement (but no intralesional enhancement) was found in two of six lesions. Of 37 reviewed benign cysts, 19 had mural and seven had central calcification, 28 were unilocular, and seven had high attenuation value. Wall thickness was 3 mm or less in 31 lesions. CONCLUSION: CT findings of a nonenhancing mass with or without wall calcification allow differentiation of adrenal cyst from adenoma. A small adrenal cyst with near-water attenuation and a thin (< or = 3-mm) wall is likely to be benign.

MR imaging artifacts that simulate disease: how to recognize and eliminate them.

Occasionally, artifacts may simulate pathologic conditions on magnetic resonance (MR) images. Motion artifacts especially affect images of the chest and abdomen. There are a number of techniques for reducing motion artifacts, including respiratory and cardiac gating, k-space phase reordering, gradient moment nulling, even echo rephasing, and physical restraints. Aliasing occurs when the field of view does not include all of the anatomic structures present in the imaged section. Aliasing artifacts can be eliminated by increasing the field of view, oversampling, and use of saturation pulses or surface coils. Truncation artifacts represent the difference between the original and the reconstructed image and can be reduced with data extrapolation algorithms or image filtering. Chemical shift artifacts and magnetic susceptibility artifacts are due to a local deformity of the magnetic field, resulting in spatial misregistration. Chemical shift artifacts are more severe in images acquired with a narrow-bandwidth technique; magnetic susceptibility artifacts are more severe in images acquired with a long echo time. Pitfalls in the interpretation of MR images can be avoided by becoming familiar with the appearances and causes of common MR imaging artifacts.

The association between tuberous sclerosis and insulinoma.

We describe a patient with tuberous sclerosis and an insulinoma. The neurologic abnormalities typically present in patients with tuberous sclerosis may, in rare cases, be manifestations of hypoglycemia. We discussed a possible association between tuberous sclerosis and multiple endocrine neoplasia type I.

MRI anatomy of the rat kidney at 1.5 T in different states of hydration.

The objective of this study was to determine correlation between structural anatomy and surface coil spin-echo MR imaging of the rat kidney and the effect of hydration state on MR signal intensities of the cortex and medulla. Twelve rats were studied in a pilot study with a 3-inch surface coil in a 1.5 T magnet under five different states of hydration. Serum and urine osmolality measurements were obtained immediately prior to each scan. Signal intensity measurements were made from both T1- and T2-weighted images of the cortex and medulla of both kidneys in each state of hydration. Gross and histological anatomy of the rat kidneys was correlated with the MR images. Four distinct layers were detected in vivo on MRI images of the rat kidney; these correlated with the histological layers. T1-weighted cortico-medullary differentiation was most pronounced at 48 h dehydration; T2 cortico-medullary differentiation was greatest at 72 h of dehydration. We concluded that different parts of the mammalian nephron can be identified by MR imaging and that cortico-medullary differentiation is affected by the hydration state of the animal.

Magnetic resonance imaging of dissection in pseudocoarctation of the aorta.

Two patients with pseudocoarctation complicated by dissection are presented. They are the first cases in which pseudocoarctation with dissection have been imaged by magnetic resonance (MR). MR imaging is an excellent noninvasive modality in the evaluation of dissection in pseudocoarctation of the aorta.