Cord leptin level and fetal macrosomia.

OBJECTIVE: To determine the relationships among serum leptin, insulin-like growth factor-I, and insulin levels in large for gestational age (LGA) infants. METHODS: Serum samples were collected from maternal veins and umbilical arteries of 52 consecutive, term, LGA neonates of nondiabetic mothers. Maternal and neonatal serum samples were analyzed for levels of leptin, insulin-like growth factor-I, and insulin by specific radioimmunoassays. Multiple regression analysis was used to determine independent risk factors for fetal macrosomia. RESULTS: The independent risk factor significantly associated with fetal macrosomia was umbilical cord leptin concentration (P <.01, beta = 0.59). There was a statistically significant correlation between umbilical cord leptin and insulin-like growth factor-I levels and birth weight (r = 0.51, P <.01; r = 0.37, P <.01; respectively). The correlation between umbilical cord insulin levels and birth weight was not statistically significant (r = 0.06, P =.63), nor was that between maternal body mass index and birth weight (r = 0.09, P =.50). CONCLUSION: Our data showed that umbilical cord leptin concentration was an independent risk factor for fetal macrosomia.

Gorging and plasma HDL-cholesterol--the Ramadan model.

OBJECTIVES: To evaluate the effect of a single evening meal (gorging) on plasma lipids and lipoproteins in normal individuals observing the Ramadan Fast. During the Ramadan month, Muslims refrain from food and liquids during the day and eat a large meal after sundown. DESIGN: Sequential measurement of plasma lipids and lipoproteins in Muslims observing the Ramadan Fast and non-fasting individuals. SETTING: The study was conducted in the Bedouin town of Rahat, in the northern Negev area of Israel. SUBJECTS: Twenty-two healthy subjects who fasted during Ramadan and 16 non-fasting laboratory workers, were studied before Ramadan, at week 1, 2 and 4 of the Ramadan month, and again four weeks after the end of Ramadan. RESULTS: Plasma high-density lipoprotein cholesterol (HDL) rose significantly (P < 0.001) at the week 4 measurement, returning to basal levels 4 weeks after the end of Ramadan. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), very-low density lipoprotein cholesterol (VLDL), and lipoprotein (a) [Lp(a)] did not change significantly. CONCLUSIONS: Plasma HDL increased by 23% after four weeks of gorging. The dietary change did not affect the composition of other lipoproteins, such as LDL, VLDL or Lp(a), other plasma biochemical parameters, or BMI. Prolonged gorging, well tolerated by all individuals, is a very effective non-pharmacological method to increase plasma HDL-cholesterol.

The relationship between plasma and dialysate lipoproteins and apoproteins in patients treated by continuous ambulatory peritoneal dialysis.

End-stage renal disease is frequently associated with lipoprotein abnormalities, manifested primarily by elevated very low-density lipoprotein levels combined with a decrease in high-density lipoprotein levels. These lipoprotein disturbances are further exacerbated in continuous ambulatory peritoneal dialysis. We examined the lipoprotein and apolipoprotein profiles in the blood and dialysate effluents of eight normolipidemic and five hypertriglyceridemic patients with end-stage renal failure treated with continuous ambulatory peritoneal dialysis. The normolipidemic patients were found to have significantly greater losses, as expressed by the fractional catabolic rates through the dialysate, for protein, total cholesterol, and very low-density lipoprotein cholesterol. These results suggest that the hypertriglyceridemia associated with continuous ambulatory peritoneal dialysis may be mitigated in some patients by the excessive loss of very low-density lipoprotein, or some other plasma constituent, into the dialysate effluent.

Lipoprotein profile of children with asthma receiving long-term theophylline therapy: a preliminary study.

Lipid profiles were determined in three groups of children: children with asthma receiving long-term therapy with slow-releasing theophylline, children with asthma not treated with theophylline, and a control group of children without asthma. Total cholesterol, high-density lipoprotein cholesterol, and apolipoprotein A levels and the high-density lipoprotein/low-density lipoprotein ratio were significantly higher among theophylline-treated children. The observed changes do not seem to increase the risks of atherosclerotic coronary artery disease.

The hypocholesterolemic effect of an antacid containing aluminum hydroxide.

STUDY OBJECTIVE: To evaluate the efficacy, safety, and hypocholesterolemic effect of an aluminum hydroxide-containing antacid in hypercholesterolemic individuals. DESIGN: A prospective, randomized, double-masked, placebo-controlled phase of 2 months' duration, followed by an open-design treatment phase of 2 months' duration and a washout phase of 2 months' duration. SETTING: Family practice clinics of two rural communities (kibbutzim) in Israel. PATIENTS: Fifty-six men and women with hypercholesterolemia (type IIa or IIb). Fifty individuals completed the study. INTERVENTION: After 2 months of dietary modification (low-fat, low-cholesterol diet), the participants were randomized into two matched groups. Group 1 (28 participants) was treated for 2 months with a chewable antacid tablet containing simethicone, magnesium hydroxide, and 113 mg of aluminum hydroxide per tablet, at a dose of two tablets four times daily. Group 2 (22 participants) was given a similar number of placebo tablets for 2 months. During the following 2 months, both groups received the antacid at the above dose. MEASUREMENTS AND MAIN RESULTS: Lipoprotein levels were evaluated at baseline and every 2 months thereafter for 6 months. Compared with pretreatment levels, Group 1 experienced a decrease in low-density lipoprotein cholesterol (LDL-C) of 9.8% after 2 months (p less than 0.001) and 18.5% after 4 months (p less than 0.001). Compared with Group 2, the decrease in LDL-C in Group 1 was 6.2% at the end of the 2-month double-masked, placebo phase. Although the high-density lipoprotein cholesterol (HDL-C) was also reduced in Group 1 at the end of 4 months of therapy (10.2%), the HDL-C/LDL-C ratio increased by 13% during the same interval (p less than 0.05). The treatment was well tolerated, with minimal side effects. CONCLUSIONS: An aluminum hydroxide-containing antacid reduces LDL-C in hypercholesterolemic individuals. Although HDL-C was also reduced to a lesser extent, the overall atherogenic index was improved. Further studies should be conducted to evaluate the long-term safety and efficacy of antacids containing aluminum hydroxide in hypercholesterolemic patients.

Metabolism of 25-OH-vitamin D3 by peritoneal macrophages from CAPD patients.

The active metabolite of vitamin D, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), is produced mainly by the kidney, but there is evidence for extrarenal production in certain circumstances. We studied whether peritoneal macrophages (PM) from CAPD patients were capable of metabolizing 25-OH-D3 to 1,25(OH)2D3. We found that PM were able to metabolize 25-OH-D3 in vitro; the main product following 16 hours of incubation was 19-nor, 10-oxo, 25-OH-D3 with smaller amounts of 1,25(OH)2D3. However, after shorter incubations of three and five hours a larger portion of 1,25(OH)2D3 was produced. The metabolism of 25-OH-D3 was greatly enhanced in PM harvested during episodes of peritonitis. This property was specific for PM of CAPD patients, and was not found in PM from normal subjects. However, incubation of control PM with peritoneal effluent from CAPD patients resulted in induction of the ability of these cells to metabolize 25-OH-D3. This induction was enhanced by preincubation with peritoneal effluent from CAPD patients suffering from peritonitis. Prostaglandin E2 was found to be involved in this synthesis: addition of PGE2 to normal PM induced metabolism of 25-OH-D3, and incubation of PM from CAPD patients with indomethacin decreased the metabolism of 25-OH-D3. The vitamin D metabolites produced by PM from CAPD patients could have a role in immunological resistance to peritoneal infections.

Enhancement of 24,25-dihydroxyvitamin D levels in patients treated with continuous ambulatory peritoneal dialysis.

We measured 24,25-dihydroxyvitamin D [24,25(OH)2D] levels in patients treated with chronic ambulatory peritoneal dialysis (CAPD), before and after receiving vitamin D2 or 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3). Vitamin D2 administration led to an increase in 25-hydroxyvitamin D (25-OH-D) and a concomitant rise in 24,25(OH)2D. No change was observed in 1,25-dihydroxyvitamin D [1,25(OH)2D]. Administration of 1 alpha-OH-D3 resulted in an increase in 1,25(OH)2D3, and a concomitant rise in 24,25(OH)2D, but no change in 25-OH-D3. Thus, 24,25(OH)2D levels may be increased in CAPD patients by raising 25-OH-D levels, or by raising 1,25(OH)2D3 levels. Since the latter enhances specifically the renal 24-hydroxylase enzyme, we conclude that this enzyme is present in CAPD patients with kidneys in situ, and may be stimulated by adequate 1,25(OH)2D3 levels. Thus, administration of 1 alpha-OH-D3 to CAPD patients with kidneys in situ seems to be sufficient to obtain normal levels of 1,25(OH)2D3 and 24,25(OH)2D3. However, anephric patients require vitamin D2 in addition as a source of 25-OH-D, the substrate for extrarenal production of 24,25(OH)2D.

Parathormone, calcitonin, and vitamin D metabolites during normal fracture healing in geriatric patients.

In order to study the role of calcium-regulating hormones during callus formation in elderly patients, serum levels of parathormone (PTH), calcitonin (CT), 25-hydroxyvitamin D [25-OH-D], 1,25-dihydroxyvitamin D [1,25(OH)2D], 24,25-dihydroxyvitamin D [24,25(OH)2D], and calcium (Ca) were determined in 41 patients with fractures of long bones, primarily hip fractures. The parameters were measured on admission and after eight weeks. There were almost no changes in hormone serum levels during bone repair, except for a decrease in serum levels of 1,25(OH)2D from 25.3 +/- 2.3 pg/ml on admission to 21.0 +/- 2.0 pg/ml eight weeks later (p less than .001). Patients with fractures compared to normal elderly humans have lower serum levels of PTH (0.99 +/- 0.06 ng/ml versus 1.88 +/- 0.34 ng/ml; p less than .001), 25-OH-D (10.7 +/- 1.0 ng/ml versus 17.1 +/- 1.8 ng/ml; p less than .001), and Ca (9.1 +/- 0.1 mg% versus 9.7 +/- 0.1 mg%; p less than .001) and higher serum levels of 1,25(OH)2D (25.3 +/- 2.3 pg/ml versus 17.1 +/- 2.3 pg/ml; p less than .001). Female patients have lower serum levels of 24,25(OH)2D compared to males (1.65 +/- 0.15 ng/ml versus 2.06 +/- 0.29 ng/ml; p less than .05). A similar trend was noted in serum CT levels during callus formation (0.12 +/- 0.02 ng/ml versus 0.16 +/- 0.02 ng/ml; p less than .05). Patients with subcapital fractures of the femur have significantly lower serum levels of all vitamin D metabolites on admission, compared with patients suffering from extracapsular fractures.(ABSTRACT TRUNCATED AT 250 WORDS)

Feto-maternal relationships between vitamin D metabolites in Israeli Bedouins and Jews.

The major metabolites of vitamin D, 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D were assayed in the blood of mothers at delivery and in the cord blood of their infants. Twelve Bedouin women and nine Jewish women were investigated; all lived in the Negev desert in Israel. All three vitamin D metabolites were significantly lower in cord than in maternal blood in both groups. Bedouin mothers and infants had significantly lower levels of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D than did Jewish mothers and infants. Concentrations of 1,25-dihydroxyvitamin D did not differ significantly between the ethnic groups and in both maternal groups were well above the normal range (Bedouins 83.6 pg/ml +/- 11.3; Jews 98.6 pg/ml +/- 12.3). Cord and maternal values for this metabolite were significantly correlated (r = 0.71, p less than 0.001).

Induction of cytosolic receptors for 1 alpha, 25-dihydroxyvitamin D3 in the immature rat uterus by oestradiol.

The role of oestradiol-17 beta in the induction of specific cytosolic receptors for 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) was examined in the immature rat uterus. An acrylamide gel electrophoretic analysis was developed to separate the specific receptor for 1,25(OH)2D3 from the plasma binding protein for vitamin D3 metabolites. Employing this sensitive method the presence of receptors for 1,25(OH)2D3 in the mature rat uterus was evident. Such receptors were not found in the uterus of saline-treated immature rats. However, oestradiol administration caused an induction of these receptors in the immature rat uterus, together with a significant increase in the uterine weight, progesterone receptor level and peroxidase activity. These results suggest a mechanism for oestradiol regulation of calcium metabolism in the uterus at times of high demand for this cation during the gestation period.

Losses of 1,25- and 24,25-dihydroxycholecalciferol in the peritoneal fluid of patients treated with continuous ambulatory peritoneal dialysis.

We measured peritoneal losses of the active vitamin D metabolites 1,25(OH)2D3 and 24,25(OH)2D3 in patients receiving continuous ambulatory peritoneal dialysis (CAPD). The serum concentration of 24,25(OH)2D3 was considerably lower than in hemodialysis patients. The serum concentration of 1,25(OH)2D3 was undetectable and rose to levels similar to those in hemodialysis patients only after loading with much higher oral doses of 1-alpha-vitamin D3 than those received by hemodialysis patients. Losses of both metabolites in peritoneal fluid were considerable, averaging approximately 6-8% of the plasma pool per day. These losses lead to low serum levels of these active vitamin D metabolites in CAPD patients, which may be an important factor in exacerbating renal osteodystrophy. Our results indicate the need for increased replacement doses of vitamin D metabolites in CAPD patients.