This study investigated the sex- and age-related alterations in calcium homeostasis in 39- to 82-week-old rats raised from weaning on a vitamin D deficient (-D) diet. It was found that vitamin D deprivation decreased the life span of male, but not female, rats. Female -D animals exhibited a steady increase in serum calcium with age from 39 to 82 weeks, although circulating calcium of -D animals never reached normocalcemic levels. There was no attenuation of the secondary hyperparathyroidism. Serum calcium of -D males was significantly lower than that of age-matched females at all ages when sufficient males were alive to make the comparison. Serum parathyroid hormone levels were decreased in -D females when serum calcium was elevated to hypercalcemic levels by calcium injection. Similarly, administration of vitamin D3 or 1,25-dihydroxyvitamin D3 elevated serum calcium and depressed parathyroid hormone in 14- and 22-month-old -D females. These animals also exhibited increased intestinal calcium binding protein content. Administration of vitamin D3 or dihydroxyvitamin D3 repaired renal adenylate cyclase refractoriness to parathyroid hormone. The sex- and diet-related alterations in serum phosphorus that were found at earlier ages disappeared by 67 weeks of age. Serum calcitonin was elevated in mature and aging +D males and females and -D females relative to younger animals. In -D males, calcitonin levels were less markedly elevated. The results of this study indicate that there are several important sex differences related to the regulation of calcium homeostasis in mature and aging rats. In addition, it was found that mature (14 month) and old (22 month) chronically -D female rats were able to respond to repletion with dihydroxyvitamin D3 or vitamin D within 10 days.

Aging↗

PubMedDate not supplied

Synthesis and in vitro evaluation of an 111In-labeled ST-peptide enterotoxin (ST) analogue for specific targeting of guanylin receptors on human colonic cancers.

BACKGROUND: Human colonic cancer cells are known to express guanylate cyclase C (GC-C) receptors for guanylin and uroguanylin. E. coli ST is a peptide with high metabolic stability that specifically binds to GC-C receptors. An in vitro evaluation of a new synthetic indium-111 labeled ST conjugate for specific targeting of human colonic cancers that express GC-C receptors was performed. MATERIALS AND METHODS: A DOTA conjugated ST analogue DOTA-NCS-6-Ahx-Phe19-ST[1-19] (DOTA-NCS-ST) was synthesized and labeled with indium-111. The non-radioactive indium analogue (In-DOTA-NCS-ST) was also prepared in macroscopic quantities. 111In-DOTA-NCS-ST was produced as a single species (>80% RCP) and purified by HPLC. Human colon cancer CaCO-2 and T-84 cells were used to evaluate the in vitro IC50 values for GC-C receptor binding and determine the cell uptake and retention of radioactivity. RESULTS: The DOTA-NCS-ST and In-DOTA-NCS-ST conjugates exhibit high in vitro binding affinity for GC-C receptors with IC50 values <10 nM. The in vitro cell binding studies with the 111In-DOTA-NCS-ST conjugate demonstrated that 111In-label ST internalizes in human colon cancer cells and exhibits long-term retention. CONCLUSION: The combination of radiolabeling efficacy and specific in vitro cell uptake and retention suggests that the DOTA-NCS-ST construct holds potential for the development of diagnostic or therapeutic radiopharmaceuticals labeled with trivalent radiometals for specific targeting of human colonic cancers.

Amino Acid Sequence↗