Safety and tolerability of esterified phytosterols administered in reduced-fat spread and salad dressing to healthy adult men and women.

OBJECTIVE/DESIGN: The safety and tolerability of three levels of plant sterol-esters administered in reduced-fat spread and salad dressing vs. control products were evaluated in this randomized, double-blind, four-arm parallel study. METHODS: Eighty-four free-living men and women consumed reduced-fat spread and salad dressing providing 0.0 g/day (n = 21), 3.0 g/day (n = 21), 6.0 g/day (n = 19) or 9.0 g/day (n = 23) of phytosterols as esters for an eight-week treatment period. RESULTS: Side effects did not differ among the groups during the study, and there were no study product-related serious adverse events. There were no changes in clinical laboratory values in response to phytosterol intake. Blood concentrations of all fat-soluble vitamins remained within normal reference ranges, and there were no differences in serum vitamin responses among the four groups. Alpha- and trans-beta-carotene levels were reduced in the 9.0 g/day group vs. control (p < 0.05), but all carotenoid values remained within normal ranges throughout the study. All groups receiving phytosterols had significant increases in serum campesterol vs. control (p < 0.001), but beta-sitosterol responses did not differ from control. Total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol responses did not differ significantly among the groups. The total:HDL cholesterol response in the 9.0 g/day group was significantly different from the control group response (-9.6% vs. 2.6%, p < 0.05). A median increase of 7.8% in serum triglycerides was observed in the control group, which differed significantly from the response in the 3.0 g/day arm (-13.3%, p < 0.05). DISCUSSION: The results of this study indicate that phytosterol esters are well tolerated and show no evidence of adverse effects at a daily intake of up to 9.0 g of phytosterols for eight weeks.

Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step I diet.

BACKGROUND: Plant sterol esters reduce cholesterol absorption and lower circulating blood cholesterol concentrations when incorporated into the habitual diet. OBJECTIVE: This randomized, double-blind, 3-group parallel, controlled study evaluated the influence of esterified plant sterols on serum lipid concentrations in adults with mild-to-moderate primary hypercholesterolemia. DESIGN: Subjects incorporated a conventional 50%-fat spread into a National Cholesterol Education Program Step I diet for a 4-wk lead-in period, followed by a 5-wk intervention period of the diet plus either a control reduced-fat spread (40% fat; n = 92) or a reduced-fat spread enriched with plant sterol esters to achieve intakes of 1.1 g/d (n = 92; low-sterol group) or 2.2 g/d (n = 40; high-sterol group). RESULTS: Subjects in the low- and high-sterol groups who consumed > or = 80% of the scheduled servings (per-protocol analyses) had total cholesterol values that were 5.2% and 6.6% lower, LDL-cholesterol values that were 7.6% and 8.1% lower, apolipoprotein B values that were 6.2% and 8.4% lower, and ratios of total to HDL cholesterol that were 5.9% and 8.1% lower, respectively, than values for the control group (P < 0.001 for all). Additionally, triacylglycerol concentrations decreased by 10.4% in the high-sterol group. Serum concentrations of fat-soluble vitamins and carotenoids were generally within reference ranges at baseline and postintervention. Serum plant sterol concentrations increased from baseline (0.48% of total sterol by wt) to 0.64% and 0.71% by wt for the low- and high-sterol groups, respectively (P < 0.05 compared with control). CONCLUSION: A reduced-fat spread containing plant sterol esters incorporated into a low-fat diet is a beneficial adjunct in the dietary management of hypercholesterolemia.

Role of somatostatin in glucose regulation during endotoxicosis in the rat.

This study assessed the role of somatostatin in regulating glucose homeostasis during endotoxicosis in the rat. Plasma levels of somatostatin, glucose, lactate, insulin, and glucagon were measured in control and endotoxin-treated rats. Cysteamine was used to block endogenous somatostatin release before endotoxin treatment. Early during the course of endotoxicosis, plasma levels of somatostatin-like immunoreactivity (SLI) were significantly elevated along with glucose, lactate, insulin, and glucagon. Pretreatment of endotoxic rats with cysteamine virtually blocked the elevated SLI levels and prevented the early appearance of hyperglycemia. Endotoxin-induced increases in lactic acid and glucagon levels were attenuated by cysteamine pretreatment, but elevated insulin levels were not appreciably altered. Elevated somatostatin levels appeared to support the occurrence of the early hyperglycemia and prevent the development of late hypoglycemia during endotoxicosis by sustaining elevated glucagon levels and thus facilitating the maintenance of glucose levels. The results suggest that somatostatin plays a significant role in the glucoregulatory response to endotoxicosis. Endotoxicosis may alter the relative "physiological" ability of somatostatin to inhibit the secretion of insulin and glucagon.

Polymyxin-B suppresses endotoxin-induced insulin hypersecretion in pancreatic islets.

Endotoxin induces insulin hypersecretion in vivo, which results in hyperinsulinemia and glucose dyshomeostasis. Polymyxin-B (PMX-B), an inhibitor of protein kinase C (PKC), has been shown to ameliorate the consequences of endotoxin-induced hyperinsulinemia in vivo. To explore the mechanism for this effect in vitro, this study determined whether PMX-B could alter endotoxin-induced insulin hypersecretion in isolated pancreatic islets of Langerhans. Pancreases were obtained from fasted, male, Sprague-Dawley rats treated with either saline (control) or endotoxin (S. enteritidis B, 16.7 mg/kg, i.v.). Three hours after the experimental treatment, islets were isolated by collagenase digestion and then incubated for 1 hr in Krebs Ringer bicarbonate buffer containing 0.5% bovine albumin, 10 mM HEPES, 300 mg/dl D-glucose, phorbol 12-myristate 13-acetate (PMA, 1 microM when present), and PMX-B (1 or 10 mM when present). In the absence of PMA and PMX-B, "endotoxic" islets hypersecreted immunoreactive insulin (IRI) relative to control islets. PMA, the prototypical PKC activator, significantly increased IRI secretion from both control and "endotoxic" islets. The additional inclusion of PMX-B (1 mM or 10 mM) in the incubation media significantly reduced insulin secretion from both control and "endotoxic" islets and suppressed the insulin hypersecretion observed in "endotoxic" islets. Since insulin secretion occurs at least partially through mechanisms dependent on PKC activation, the ability of PMX-B to suppress insulin hypersecretion in "endotoxic" islets suggests that activation of PKC within pancreatic beta-cells may play a role in the excess insulin secretion and hyperinsulinemia associated with endotoxicosis.

Insulin-inhibiting effects of epinephrine are blunted during endotoxicosis in the rat.

This study was conducted to examine the conditions under which epinephrine (EPI) blocks glucose-induced hyperinsulinemia in normal and endotoxic rats. Nutritional state (fasting vs. feeding) and anesthetic state (conscious vs. sodium pentobarbital anesthesia) were explored as factors that could influence the effects of epinephrine on immunoreactive insulin (IRI) levels. Exogenous epinephrine infusion into control rats significantly blunted hyperinsulinemia in response to an exogenous glucose challenge in fed rats, but not fasted rats. Endotoxin-treated rats (3.3 mg/kg) showed endogenously elevated levels of both EPI and IRI during the hyperglycemic period that is characteristic of early endotoxicosis. All endotoxic rats showed hyperinsulinemia in response to an exogenous glucose challenge, despite the simultaneous presence of elevated catecholamine levels. However, hyperinsulinemia (induced by glucose challenge) was two-fold higher in pentobarbital-anesthetized, endotoxic rats (both fed and fasted) than in respective control rats under the same conditions. These results show that fasted rats are resistant to the insulin-inhibiting effects of epinephrine. In addition, since hyperinsulinemia occurs during endotoxicosis (in both fed and fasted states) despite the presence of elevated catecholamine levels, the results indicate that endotoxin treatment decreases the inhibitory effects of epinephrine on insulin levels. This effect is potentiated by pentobarbital anesthesia and is more pronounced in the fed rat than in the fasted rat.

Ontogenesis of immunocytochemically demonstrable somatotrophs in the adenohypophyseal pars distalis of the developing chick embryo.

Growth hormone (GH)-containing cells in the hypophyseal pars distalis of the chick embryo were identified immunohistochemically using anti-chicken GH sera. GH cells are first demonstrable in Rathke's Pouch as early as Day 4.5 of incubation. By Day 9.5, when the two lobes (rostral and caudal) of the pars distalis are easily recognized, GH cells are confined exclusively to the caudal lobe. Although the number of GH cells increases gradually during embryonic development, there is a statistically significant difference between Days 10.5 and 12.5 in both the cellular density and the percentage of somatotrophs. GH cells, which contain coarse granules evenly distributed throughout the cytoplasm, varied in diameter from 9.3 micron on Day 4.5 to 11.8 micron on Day 20.5, while the nuclear diameter of these cells increased from 2.8 micron on Day 4.5 to 4.9 micron on Day 20.5. There was a statistically significant difference in the nuclear/cytoplasmic ratio between Days 4.5 and 13.5 and between Days 13.5 and 20.5 of incubation. Aspects of the regulation of growth hormone synthesis and secretion in the chick embryo are discussed.