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Biomedical subjects

M D Sitrin

Publications and source records attributed to M D Sitrin.

69 records · Page 4Linked to original sources
PubMed1983

Amino acid-induced hypercalciuria in patients on total parenteral nutrition.

Ingestion of protein is known to increase urinary calcium excretion. By studying the effect of intravenous amino acid infusion on calcium excretion, the variables of diets and intestinal absorption are avoided. Five patients on total parenteral nutrition with otherwise constant nutrient infusions containing 240 mg of calcium were randomized to two different levels of amino acid infusion. On 1 g/kg ideal body weight amino acid infusion, two patients excreted more than 240 mg of calcium in the urine, while on 2 g/kg ideal body weight amino acid infusion all five patients lost more calcium in urine than was infused. Mean urinary calcium excretion was increased from 287 to 455 mg/day. On the higher amino acid dose, mean glomerular filtration rate increased from 102 to 143 ml/min. There was no effect of amino acid dose on serum calcium, ionized calcium, parathyroid hormone, and 25 (OH) vitamin D. Calcium excretion corrected for the glomerular filtration rate was increased at the higher amino acid dose, indicating a decrease in renal calcium reabsorption. Daily urinary excretion of sulfate, ammonia, and titratable acidity were increased during the high amino acid infusion. Hypercalciuria induced by high levels of amino acid infusion during total parenteral nutrition may contribute to the development of metabolic bone disease.

Adult↗
PubMed1982

Comparison of vitamin D and 25-hydroxyvitamin D absorption in the rat.

We have studied the intestinal absorption of physiological amounts of vitamin D and 25-hydroxyvitamin D [25(OH)D3] in vivo from jejunal sacs in rats with thoracic and bile duct cannulas. Under all test conditions, absorption of 25(OH)D was greater than absorption of vitamin D. The majority of absorbed vitamin D and 25(OH)D was transported from the intestine in portal blood rather than lymph. When the luminal fluid contained 2.5 mM oleic acid and monoolein, the presence of taurocholate did not affect total intestinal absorption of vitamin D or 25(OH)D but increased recovery of vitamin in lymph. When luminal fat content was increased to 10 mM oleic acid and monoolein, total absorption of both vitamin D and 25(OH)D was enhanced by taurocholate. No significant metabolism of vitamin D or 25(OH)D occurred during absorption and transport in lymph. Fifty-three percent of lymph vitamin D was found in the chylomicron fraction, compared with only 13% of 25(OH)D. Inhibition of chylomicron synthesis by cycloheximide decreased vitamin D absorption by 46% but diminished 25(OH)D absorption by only 30%. These differences in behavior of vitamin D and 25(OH)D during absorption may explain the superior absorption of 25(OH)D in patients with malabsorption.

25-Hydroxyvitamin D 2↗
PubMed1982

Treatment of hyperlipidemic pancreatitis in pregnancy with total parenteral nutrition.

A 29-yr-old pregnant woman presented in her third trimester with severe pancreatitis, hyperlipidemia, and small-for-dates fetus. Studies suggested that her pancreatitis was caused by profound hypertriglyceridemia, which was the result of an underlying lipoprotein disorder exacerbated by pregnancy. Throughout the first 7 wk of hospitalization, attempts to refeed the patient with solid food and various elemental diets resulted in the induction of hypertriglyceridemia and relapses of pancreatitis. Concern for the nutritional status of the mother and the possibility of further growth retardation of the fetus prompted the use of total parenteral nutrition for the last 2 wk of gestation. This treatment was well tolerated by the mother, promptly reversed maternal weight loss, caused a rapid resolution of her pancreatitis, and did not induce further hypertriglyceridemia. This report documents that total parenteral nutrition may be safely and effectively used in the management of hyperlipidemic pancreatitis in pregnancy.

Adult↗
PubMedDate not supplied

Hepatic vitamin D 25-hydroxylase: inhibition by bile duct ligation or bile salts.

Bone disease and low serum levels of 25-hydroxyvitamin D are prevalent in cholestatic syndromes such as primary biliary cirrhosis and biliary atresia. Defective hydroxylation, along with malabsorption of vitamin D, could be a factor in 25-hydroxyvitamin D depletion. To assess hepatic hydroxylation during experimental cholestasis, we studied vitamin D 25-hydroxylase activity in liver homogenates of rats after 7, 14, and 21 days of bile duct ligation. We have also studied the effects of bile acids on this enzyme in vitro. Hepatic 25-hydroxylation was depressed after 7 days ligation in only 1 of 4 animals, but by 14 days, all animals showed a marked reduction with a mean decrease of 64% in specific activity. Total liver enzyme activity was reduced by 43% at 14 days. In the ligated animals, liver histology showed progressive bile stasis, focal necrosis, bile ductular proliferation, periductular and periportal inflammation, and fibrosis. Addition of bile acids to the in vitro assay in concentrations approximating those found in cholestasis produced marked inhibition of vitamin D 25-hydroxylase activity.

25-Hydroxyvitamin D 2↗
PubMedDate not supplied

Intestinal calcium absorption and vitamin D status in chronic cholestatic liver disease.

Metabolic bone disease is common in patients with cholestatic liver disease. The importance of vitamin D status and calcium malabsorption in the pathogenesis of bone disease in these patients remains undefined. We have measured intestinal calcium absorption in relation to vitamin D status in 14 patients with chronic cholestatic liver disease including 11 with primary biliary cirrhosis. Fractional calcium absorption was determined from radioactive counts in the right forearm after separate oral and intravenous doses of 47CaCl2 in the fasting state. Eight of 14 patients (57%) had a decreased calcium absorption compared to controls. A significant correlation was observed between serum 25-hydroxyvitamin D levels and fractional calcium absorption (r = 0.623, p less than 0.02). Treatment with oral 25-hydroxyvitamin D3 in three patients with low serum 25-hydroxyvitamin D levels resulted in correction of serum 25-hydroxyvitamin D levels and improvement in fractional calcium absorption. No correlation was found between serum 1,25-dihydroxyvitamin D levels and fractional calcium absorption (r = 0.221). Calcium malabsorption was common in this series of patients, and serum 25-hydroxyvitamin D levels were useful in predicting fractional calcium absorption. Treatment with oral 25-hydroxyvitamin D3 was accompanied by improved calcium absorption.

Adult↗
PubMedDate not supplied

Pattern and prognosis of liver function test abnormalities during parenteral nutrition in inflammatory bowel disease.

The pattern of liver function test abnormalities was examined during total parenteral nutrition (TPN), using both dextrose and fat emulsions as caloric sources, in 92 patients with inflammatory bowel disease. Seventy-two patients had completely normal tests before TPN while 20 had one or more abnormal liver function tests before TPN was started. Serum bilirubin levels were normal in all patients before TPN; within 2 weeks on TPN, 25% of patients had elevated bilirubin levels. Serum alkaline phosphatase rose to values above normal in 25% of patients with normal starting values but did not change in those with abnormal baseline liver function tests. Elevations of SGPT were characteristically more pronounced than were elevation of SGOT. After 2 weeks of TPN, mean serum SGOT rose from 15 to 26 IU per liter (p less than 0.01) in patients with normal baseline values and from 28 to 50 IU per liter in those with abnormal baseline values. Elevations of serum SGPT were most common, affecting 25% of patients with normal baseline. The mean SGPT value rose from 13 to 38 IU per liter (p less than 0.01) at 1 week of TPN. In patients with abnormal tests before TPN, the mean SGPT value rose from 45 to 102 IU per liter (p less than 0.05). Liver biopsies performed in four patients with substantial elevations of aminotransferases revealed only minor nonspecific changes and no fatty infiltration. Elevated liver function tests promptly returned to baseline after TPN was discontinued, and progressive liver disease was not observed in any patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMedDate not supplied

Rapid effects of 1,25(OH)2 vitamin D3 on signal transduction systems in colonic cells.

Previous work from our laboratory demonstrated that 1,25(OH)2D3 rapidly stimulated hydrolysis of membrane polyphosphoinositides (PI) in rat colonocytes and in Caco-2 cells, generating the second messengers DAG and IP3. [Ca2+]i subsequently increased due to IP3-mediated release of intracellular Ca2+ stores, and to Ca2+ influx through a receptor-mediated Ca channel. Studies examining purified antipodal plasma membranes and experiments using Caco-2 cell monolayers found that 1,25(OH)2D3 influenced PI turnover only in the basolateral (BLM) and not brush border (BBM) membranes. Vitamin D analogues with poor affinity for the vitamin D receptor were found to effectively stimulate PI turnover, suggesting the presence of a unique vitamin D receptor in the BLM. Studies from our laboratory have demonstrated saturable, reversible binding of 1,25(OH)2 D3 to colonocyte BLM. Recently, we found that 1,25(OH)2D3 activated the tyrosine kinase c-src in colonocyte BLM by a heterotrimeric guanine nucleotide binding protein (G-protein)-dependent mechanism, with subsequent phosphorylation, translocation to the BLM, and activation of PI-specific phospholipase C gamma. Due to the rise in [Ca2+]i and DAG, two isoforms of protein kinase C (PKCalpha and PKCbeta2), but not other isoforms were activated by 1,25(OH)2D3 in rat colonocytes. Recent studies demonstrated that the seco-steroid translocated the beta2 isoform to the BLM, but not the BBM. In contrast, the alpha isoform did not translocate to either antipodal plasma membrane, but modulated IP3-mediated Ca2+ release from the endoplasmic reticulum. Preliminary studies have shown that 1,25(OH)2D3 also activated phosphatidylcholine phospholipase D (PLD) in Caco-2 cells, generating phosphatidic acid and contributing to the sustained rise in DAG. PLD stimulation occurred by both PKC-dependent and -independent mechanisms. Inhibitors of G-proteins, c-src, and PKC blunted the seco-steroid-mediated activation of PLD. Cells stably transfected with sense PKCalpha showed increased 1,25(OH)2D3-stimulated PLD activation, whereas transfectants with antisense PKCalpha had an attenuated response. In addition, 1,25(OH)2D3 also regulated PLD by activating the monomeric G-protein rho A by a mechanism independent of the G-protein/ c-src/PKC pathway.

Animals↗
PubMedDate not supplied

Reduction of total parenteral nutrition-induced urinary calcium loss by increasing the phosphorus in the total parenteral nutrition prescription.

Hypercalciuria and negative calcium balance are potential complications of total parenteral nutrition (TPN). Dietary phosphorus has been observed to have an hypocalciuretic effect. The present study evaluates the effects of administration of increasing intravenous phosphorus (P) loads on urinary calcium excretion in TPN patients. Urinary calcium exceeded daily calcium intake by 50 mg/d when 700 mg/d P was administered, was equal to intake at 1000 mg/d P, and was 30 mg/d less than calcium intake when 1300 mg/d P was given. These findings suggest that TPN-induced hypercalciuria can be attenuated in the short-term by intravenous phosphate. Reevaluation of the phosphorus requirement in patients receiving long-term TPN should be considered.

Adult↗
PubMedDate not supplied

Endoscopic, radiographic, and clinical response to prolonged bowel rest and home parenteral nutrition in Crohn's disease.

Total parenteral nutrition is widely used as a therapeutic measure in patients with severe, active Crohn's disease unresponsive to conventional medical management. We have reviewed our experience with 10 patients with nonfistulous Crohn's disease treated by home parenteral nutrition (HPN) and bowel rest (nothing-by-mouth) assessing the nutritional, radiologic, endoscopic, and clinical responses. After a mean of 4.1 months of treatment, all patients had a marked improvement in nutritional status and resolution of gastrointestinal symptoms; 90% reduced their corticosteroid dose. Eight of nine patients had endoscopic and/or radiographic evidence of mucosal healing. Although 60% of patients were able to avoid surgery and tolerate refeeding, all six patients continue to require steroids to control symptoms. Our study suggests that HPN and bowel rest is a useful therapeutic approach to selected patients with active Crohn's disease, which permits a reduction in corticosteroid dosage and partial healing of mucosal lesions in most. Further studies are required to determine which patients should receive HPN and its optimal duration.

Adolescent↗
PubMedDate not supplied

Pulmonary deposition of calcium phosphate crystals as a complication of home total parenteral nutrition.

A patient on home total parenteral nutrition (TPN) developed a diffuse granulomatous interstitial pneumonitis secondary to calcium phosphate deposition. Calcium and phosphorus concentrations in the TPN formula were not unusually high, indicating that other factors contributed to calcium phosphate crystallization. The effects of duration of storage of the TPN formulation, solution temperature, pH, and magnesium concentration on calcium phosphate precipitation are discussed.

Adult↗
PubMedDate not supplied

Inorganic phosphorus reduces hypercalciuria during total parenteral nutrition by enhancing renal tubular calcium absorption.

BACKGROUND: Increasing the inorganic phosphorus content of total parenteral nutrition (TPN) formulas has been shown to decrease TPN-induced hypercalciuria in experimental animals and humans. The mechanism of this effect, however, has been uncertain. METHODS: By using a randomized cross-over design, seven patients on cyclic TPN were given otherwise identical formulas providing either 15 or 45 mmol/d of inorganic phosphorus. Urinary calcium excretion, serum ultrafilterable calcium, filtered calcium load, fractional calcium excretion, urinary cyclic adenosine 5'-monophosphate (cAMP), and serum levels of ionized calcium, parathyroid hormone (PTH), and vitamin D metabolites were determined at the end of each study period. RESULTS: Urinary calcium excretion was significantly lower when the patients received the higher inorganic phosphorus formula. Increasing the inorganic phosphorus in the TPN formula did not change ultrafilterable calcium or filtered calcium load, but significantly reduced fractional calcium excretion. No differences in serum levels of ionized calcium, PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, or urinary cAMP were observed between treatments. CONCLUSIONS: These results demonstrate that increasing the inorganic phosphorus content of the TPN formula decreases urinary calcium excretion by increasing renal tubular calcium resorption. This effect is not due to alterations in the PTH-1,25-dihydroxyvitamin D axis, but likely reflects a direct action of inorganic phosphorus on the renal tubules.

Absorption↗