PubMed · 8169815
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M A Battey. 1994. Absorbable fixation.. https://doi.org/10.7547/87507315-84-2-98
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A detailed microscopic analyses of the mode of lead uptake and localization in root, stem and leaf initials of corn seedlings grown in cultural solution is reported. Lead, as other minerals, was passively absorbed into the root tip region and transported by the active apical growth force. The entrance of lead was mainly from the thin epidermal cell walls at the meristematic region. Only limited amounts of lead entered into protoplasts, primarily during the early stage of cell development. However, accumulation of lead within cell walls increased as cells matured. Both local and long distance transport of lead were apoplastic. Once the vascular stele differentiated from the ground meristem, lead entered into the central conducting systems. Lead was also absorbed from the water absorbing zone but this lead mainly remained in the cortex. The Casparin strip was an effective barrier limiting the movement of lead. However, transport through passage cells was observed. The direction of lead movement was also mainly towards high growth rate areas as seen at meristematic root initials, the leaf primordia and the transaction zone at the stem apical meristem. Damaged plasmalemmae allowed lead to enter cells from cell walls. Lead deposition in the cytoplast was observed.
The synthesis, structure-activity relationship (SAR) studies, and antidiabetic characterization of 1,2-dihydro-4-[[4-(methylthio)phenyl]methyl]-5-(trifluoromethyl)-3H- pyrazol-3-one (as the hydroxy tautomer; WAY-123783, 4) are described. Substitution of 4-methylthio, methylsulfinyl, or ethyl to a benzyl group at C4, in combination with trifluoromethyl at C5 of pyrazol-3-one, generated potent antihyperglycemic agents in obese, diabetic db/db mice (16-30% reduction in plasma glucose at 2 mg/kg). The antihyperglycemic effect was associated with a robust glucosuria (> 8 g/dL) observed in nondiabetic mice. Chemical trapping of four of the seven possible tautomeric forms of the heterocycle by mono- and dialkylation at the acidic hydrogens provided several additional potent analogs (39-43% reduction at 5 mg/kg) of the lead 4 as well as a dialkylated pair of regioisomers that showed separation of the associated glucosuric effect produced by all of the active analogs in normal mice. Further pharmacological characterization of the lead WAY-123783 (ED50 = 9.85 mg/kg, po in db/db mice), in oral and subcutaneous glucose tolerance tests, indicated that unlike the renal and intestinal glucose absorption inhibitor phlorizin, pyrazolone 4 does not effectively block intestinal glucose absorption. SAR and additional pharmacological data reported herein suggest that WAY-123783 represents a new class of potent antihyperglycemic agents which correct hyperglycemia by selective inhibition of renal tubular glucose reabsorption.
BACKGROUND: Carcinoembryonic antigen (CEA) is used as a serum marker to detect and monitor the status of various kinds of malignant tumors. To determine whether CEA might be detected in secretions collected topically from around the nipple area, and whether its secretion might differ in a cancerous versus a noncancerous breast, we developed a simple method for collecting and measuring CEA, using a small cellulose membrane disk and an enzyme immunoassay. METHODS: We measured the amount of CEA excreted from the nipple area of 22 healthy control women and 32 women with unilateral breast carcinoma confirmed histologically. Secretions were collected from the nipple area by affixing a small (20 mm diameter) absorbent disk made of nitrocellulose membrane backed with filter paper to that area for 24 hours. Substances absorbed by the membrane were then subjected to an immunoassay for CEA using anti-CEA antibodies. RESULTS: In the 22 healthy subjects, a small amount of CEA (0.6 +/- 0.9 units) was secreted from each nipple, which was equally low regardless of the phase of the menstrual cycle. In contrast, 30 of the 32 women with breast carcinoma secreted significantly greater amounts of CEA from the cancerous (16.1 +/- 8.2) than the noncancerous (2.0 +/- 2.2) breast. Such a difference (14.1 +/- 8.0) in CEA excretion was not observed in the healthy controls (0 +/- 0). CONCLUSIONS: These findings suggest that such disks may provide a simple and noninvasive method of collecting trace molecules, including CEA, in skin secretions around the nipple to evaluate functional disorders of the mammary glands, particularly breast carcinoma. Additional studies are indicated in larger groups of women with various stages of breast carcinoma as well as with benign breast diseases.