Influence of formula versus breast milk on cholesterol synthesis rates in four-month-old infants.

We investigated whether supplementation of regular formula (RF) with cholesterol (Ch) (RF+Ch) influenced circulating Ch levels and de novo synthesis compared with their breast-fed (BF) counterparts in 4-mo-old infants. The incorporation rate of deuterium in body water into erythrocyte membrane-free Ch over 48 h was used as an index of cholesterogenesis. Plasma total-Ch and LDL-Ch concentrations were highest (p < 0.02) in BF infants, compared with infants in the RF-fed groups. Infants in the RF+Ch groups showed an intermediate response; their plasma total-Ch and LDL-Ch concentrations were not significantly different from the BF or the RF-fed groups. Plasma total/HDL-Ch and LDL/HDL-Ch ratios were higher (p < 0.05) in BF, and higher in RF+Ch-fed infants, compared with those fed RF, whereas not different between BF and RF+Ch-fed infants. At 4 mo of age, Ch FSR was 4-fold lower (p < 0.0001) in BF versus other groups, but not significantly different between RF- and RF+Ch-fed infants. Thus, despite addition of Ch to the concentration found in breast milk, FSR remained elevated compared with that of the group fed breast milk, with an intermediate response in circulating Ch levels. It is speculated that factors other than Ch intake account for the differential Ch metabolism between formula-fed and BF infants.

Effect of tactile stimulation on serum lactate in the newborn rat.

Maturation of the CNS in neonatal animals is dependent upon both sensory input and the constant availability of metabolic fuel. Previous reports indicate that the preferred metabolic substrate for the developing rat brain is lactate. In this study, we used the neonatal Sprague-Dawley rat to investigate a possible interactive role between touch and the regulation of serum lactate. Two hundred and fifty rats (postnatal d 0-7) were exposed to a standard tactile stimulation (TS) regimen to mimic nonspecific maternal stimulation. This regimen consisted of stroking the dorsum with a soft camel hair brush for 30 s every minute for 10 min. Serum lactate and glucose levels were measured after TS. In newborn (d 0) rats, lactate levels were increased by 207% in stroked pups versus controls. This elevation of serum lactate persisted for 30 min after cessation of TS. On d 7, TS increased lactate only 11%. Glucose levels were unaffected at all ages. In neonatal pups, pretreatment with pentobarbital blocked the effect of TS, whereas epidermal growth factor evoked a synergistic response. Capsaicin pretreatment had no effect. Mixed arteriovenous blood gases revealed a mild increase in pH and a decrease in Pco2 after TS. We conclude that TS in newborn rats is a regulator of circulating lactate. This response is maximal in the immediate postnatal period and wanes over the 1st wk of life. We speculate that the transduction of sensory signals by the skin is a mechanism regulating the availability of cerebral energy substrates in the newborn mammal.

Myocardial infarction in a 35-year-old man with homocysteinemia, high plasminogen activator inhibitor activity, and resistance to activated protein C.

Our specific aim was to examine the interface between risk factors for atherosclerosis, thrombosis, and hypofibrinolysis in a previously healthy 35-year-old male who had sustained a recent myocardial infarction. By angiography, the right, left main, and left anterior descending coronary arteries were smooth-walled, widely patent, and free of significant obstruction; the circumflex exhibited total, probably thrombotic occlusion of the distal large second marginal branch. The patient was found to have prothrombotic high homocysteine (46.4 mumol/L), prothrombotic resistance to activated protein C (ratio, 1.47), and hypofibrinolytic high plasminogen activator inhibitor (PAI-Fx) activity (54 U/mL). He was homozygous for the 677C-->T; A-->V mutation in the methylenetetrahydrofolate reductase (MTHFR) gene causing homocysteinemia, heterozygous for the mutant factor V Leiden gene causing resistance to activated protein C, and heterozygous for the 4G/5G polymorphism in the PAI-1 promoter gene causing high PAI-Fx. Other major risk factors for coronary artery disease included previously undiagnosed adult-onset diabetes, high triglycerides (291 mg/dL), and low high-density lipoprotein (HDL) cholesterol (26 mg/dL). The patient's prothrombotic status (homocysteinemia and resistance to activated protein C) and hypofibrinolysis (high PAI-Fx) apparently facilitated occlusive coronary artery thrombus formation and retention. Prothrombotic factors and hypofibrinolysis appear to play important pathogenetic roles in premature myocardial infarction. In patients with severe premature coronary artery disease, we suggest that interactions between prothrombotic factors, hypofibrinolysis, and hyperlipidemia-atherosclerosis be regularly evaluated, since such interactions may have ramifications for the outcome of short- and long-term secondary prevention. Moreover, in patients with heritable prothrombotic factors or hypofibrinolysis, it should be important to optimize lipid and lipoprotein cholesterol levels with the goal of stabilizing coronary plaques to reduce the likelihood of plaque rupture and thrombosis.