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Regenerative and degenerative neurites are components of classical senile plaques found in brain tissue of patients with Alzheimer's disease (AD). Amyloid beta/A4-protein derived from its precursor, amyloid beta/A4-protein precursor (APP/ABPP), constitutes the major portion of the amyloid core of senile plaques. A large N-terminal portion of APP (approximately Mr 100,000) is released from cells, leaving a minor C-terminal portion (approximately Mr 15,000) behind. A series of antisera against various sequences of APP were prepared and used to study the localization of each sequence in brain tissue. Plaque neurites stained as intensely as neuronal cell bodies with three antisera against the N-terminal portion of APP (N-terminal to a.a. 225), whereas five other antisera directed against the other C-terminal portions of APP (a.a. 284 to C-terminal) and antisera against the Kunitz-type protease inhibitor portion of APP stained plaque neurites less intensely than neuronal cell bodies in the hippocampus. These results suggest that a major part of the APP present in the neuritic component of senile plaques is a fragment representing the N-terminal one-third of the molecule.

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Determination of mycophenolate area under the curve by limited sampling strategy.

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Intraperitoneal pulse calcitriol in the treatment of secondary hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis.

OBJECTIVE: To determine whether it is practicable to use intraperitoneal calcitriol to treat continuous ambulatory peritoneal dialysis (CAPD) patients with secondary hyperparathyroidism and whether this form of therapy is effective and safe. DESIGN: A prospective, nonrandomized study. SETTING: Division of Nephrology, Tertiary Hospital. METHOD: Eight patients from our CAPD population were recruited (5 F, 3 M), aged 24 to 63 years (mean 38.9 +/- 7.6 yr). They had been on CAPD for 8 to 84 months (mean 47.6 +/- 24.6 months). All the patients had bone biopsy-proven secondary hyperparathyroidism with 2 patients showing mixed lesions. The CAPD system was changed to the twin-bag system (Ultrabag, Baxter Healthcare, McGaw Park, IL, U.S.A.) in all 8 patients, who were taught to inject the calcitriol directly through the short transfer set and the Tenckhoff catheter into the peritoneal cavity, twice per week before bedtime. Calcium carbonate or calcium acetate was used as the main phosphate binder. Intact parathyroid hormone level (iPTH), serum ionized calcium (iCa), serum phosphate, and serum total alkaline phosphatase (alk. phos.) levels were measured at baseline and then every 4 weeks. The mean duration of follow-up was 10.5 months +/- 1.9 months. RESULTS: There was a significant drop of iPTH level from the pretreatment level of 100.6 +/- 35.8 pmol/L to a level of 63.8 +/- 48.7 pmol/L at 24 weeks (p = 0.036). The lowest level of iPTH attained was 43.4 +/- 27.0 pmol/L at 48 weeks. Serum total alk. phos. also dropped from 232.4 +/- 83.3 IU/L pretreatment to 147.9 +/- 52.0 IU/L at 24 weeks (p = 0.017). The decrease in alk. phos. level paralleled the decrease in iPTH level. The mean serum iCa level did not show any significant rise throughout the study period. The maximum dose of calcitriol used was 6.6 +/- 1.5 microg/week and the average dose of calcitriol was 5.4 +/- 1.2 microg/week. One patient did not respond satisfactorily and she subsequently had a parathyroidectomy. Two episodes of peritonitis occurred during the study period, giving a peritonitis rate of one episode per 42 patient-months. There was no significant change in the urea clearance tests or the peritoneal equilibration tests before and after the study. CONCLUSION: Intraperitoneal calcitriol is practicable, effective, and safe in the treatment of secondary hyperparathyroidism in CAPD patients.

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