Biomedical subjects
Publications and source records attributed to M Manoharan.
Novel oligonucleotide analogs that bear phosphodiester and bioreversible S-pivaloyl 2-mercaptoethyl (SPME) phosphate triester internucleosidic linkages are described. Their synthesis employs a novel methodology of oligonucleotide deprotection under mild, non-aqueous conditions.
OBJECTIVE: To reassess the effects of jejunoileal bypass on the gastrointestinal absorption and bone metabolism of certain minerals in rats, and to see if jejunoileal bypass in rats was a suitable model in which to study formation of calcium oxalate renal stones. DESIGN: Controlled study. SETTING: Division of Experimental Surgery, University of Erlangen, Germany. MATERIAL: 43 male Sprague-Dawley rats. INTERVENTION: 23 rate underwent jejunoileal bypass, and 20 laparotomy, with transsection and anastomosis of the jejunum and ileotomy and suture (sham operation). RESULTS: Rats that had undergone jejunoileal bypass ate less and gained less weight than those that had had sham operations. Absorption of calcium and phosphorus from the intestine was impaired, but that of magnesium was unchanged. Absorption of oxalate from the small intestine was unchanged, but that from the colon was increased. There were no signs of hyperoxaluria or urolithiasis. Serum mineral homeostasis was not affected by jejunoileal bypass nor were bone volume, density, or mineral concentrations. Serum concentrations of parathyroid hormone and 1,25-dihydroxycholecalciferol remained low, suggesting that jejunoileal bypass might have induced some calcium flux towards the vascular space. CONCLUSIONS: Jejunoileal bypass halts weight increase in rats; the model may be helpful in elucidating associations between enteric factors and calciotropic hormones, and several metabolic features that are altered by jejunoileal bypass in man are not altered in rats.
The currently preferred calcium preparations for supplementation of food vary widely with respect to calcium availability, effects on systemic mineral metabolism, acid-base status, and the calciuria-induced risk of urinary tract stone formation. In eight healthy males we studied the response to an acute load with alkali(sodium)-containing soluble calcium citrate (CSC) (molar ratio calcium/sodium/citrate approx. = 1/1/1), when taken in three different doses (10, 20, 30 mmol calcium) together with a continental breakfast. Intestinal calcium absorption, serum calcium, calcitonin, parathyroid hormone (PTH) other markers of bone metabolism, net acid excretion and calcium oxalate crystallization in urine were evaluated. CSC evoked a dose-dependent increase in calcium absorption, calcium in serum and urine, but no overt hypercalcemia, and calciuria was low relative to the excess calcium ingested; PTH fell and calcitonin rose (p < 0.05 vs. breakfast alone), but the diet-independent markers of bone resorption declined only insignificantly, while the markers of bone formation and turnover remained unchanged. There was a significant "once-daily" effect (= cumulative 24 h postload response) of CSC: a decrease in urinary cyclic AMP, phosphorus, and ammonium, and an increase in urinary bicarbonate. Soon after CSC intake, urinary calcium oxalate and hydroxyapatite supersaturation increased dose-dependently, the calcium oxalate crystal diameter was increased, but crystal aggregation time, which is crucial for stone formation, remained statistically unchanged. Thus, CSC provides calcium in a bioavailable form, creates mild systemic alkalinisation and inhibition of bone resorption, but leaves the risk of developing urinary stones unchanged. Comparative long-term studies on bone growth and the maintenance of bone health, using alkali-containing versus alkali-free calcium citrate, appear worthwhile.