Increased LDL cholesterol and atherosclerosis in LDL receptor-deficient mice with attenuated expression of scavenger receptor B1.

Scavenger receptor BI (SR-BI) is a multiligand cell-surface receptor that plays a central role in high density lipoprotein homeostasis in rodents. To investigate a role for SR-BI in atherosclerosis, mice with attenuated SR-BI expression were crossed with low density lipoprotein (LDL) receptor-deficient mice. Compound-homozygous mutants showed increased plasma cholesterol, surprisingly due primarily to increased LDL cholesterol and apolipoprotein B levels. LDL turnover studies showed that this resulted from increased LDL cholesterol production rather than decreased LDL catabolism. Atherosclerotic lesion size was significantly increased in male compound-mutant mice relative to LDL receptor-deficient controls (93 427+/-16 079 versus 34 448+/-5 331 microm(2), respectively; P=0.003). The proatherogenic effect of attenuated SR-BI expression may in part be due to increased LDL cholesterol levels. These findings suggest that upregulation of the receptor could have therapeutic potential for the treatment of atherosclerosis.

Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium.

Vascular endothelium is an important transducer and integrator of both humoral and biomechanical stimuli within the cardiovascular system. Utilizing a differential display approach, we have identified two genes, Smad6 and Smad7, encoding members of the MAD-related family of molecules, selectively induced in cultured human vascular endothelial cells by steady laminar shear stress, a physiologic fluid mechanical stimulus. MAD-related proteins are a recently identified family of intracellular proteins that are thought to be essential components in the signaling pathways of the serine/threonine kinase receptors of the transforming growth factor beta superfamily. Smad6 and Smad7 possess unique structural features (compared with previously described MADs), and they can physically interact with each other, and, in the case of Smad6, with other known human MAD species, in endothelial cells. Transient expression of Smad6 or Smad7 in vascular endothelial cells inhibits the activation of a transfected reporter gene in response to both TGF-beta and fluid mechanical stimulation. Both Smad6 and Smad7 exhibit a selective pattern of expression in human vascular endothelium in vivo as detected by immunohistochemistry and in situ hybridization. Thus, Smad6 and Smad7 constitute a novel class of MAD-related proteins, termed vascular MADs, that are induced by fluid mechanical forces and can modulate gene expression in response to both humoral and biomechanical stimulation in vascular endothelium.

Cosmetics and the esthetic patient and laboratory communication.

With increasing consumer awareness of the innovative procedures available for cosmetic dentistry, this area of practice is growing rapidly and has become an excellent source for patient referrals. Unfortunately, it can also be a large source of stress for the practitioner. Esthetics has been described by The Pocket Oxford Dictionary as "the philosophy of beautiful"; its perception varies from individual to individual. In the field of dentistry, there are criteria which define one tooth as being more esthetic than another and one individual's smile as more pleasing than another. However, that which is esthetically pleasing to the clinician may not be esthetically pleasing to the patient.

Use of exogenous glutathione for metabolism of peroxidized methyl linoleate in rat small intestine.

The potential effects of dietary glutathione on the metabolism of peroxidized lipid ingested in the diet were studied using everted sacs of rat small intestine and peroxidized methyl linoleate. Peroxidized methyl linoleate was added to the luminal side, and the appearance of thiobarbituric acid-reactive (TBA-reactive) material on the contraluminal side was measured. Incubation with N,N,bis(2-chloroethyl)-N-nitrosourea (BCNU) under conditions in which it inhibits the glutathione disulfide reductase/glutathione peroxidase system increased the appearance of TBA-reactive material, indicating that at least a portion of the TBA-reactive material passing through the epithelium is peroxide in nature. Adding glutathione (GSH) to the luminal side substantially decreased the appearance of TBA-reactive material on the contraluminal side, either without or with BCNU treatment. Inhibition of GSH transport and control experiments with GSH, peroxidized methyl linoleate and purified brush border membranes showed that this decrease was due primarily to uptake of luminal GSH and its use to support intracellular GSH-dependent reactions. Thus, the results indicate that exogenous GSH, which can exist in certain diets, can be taken up by the small intestine and used to protect against absorption of lipid peroxidation products.

Hypercysteinemia and delayed sulfur excretion in cirrhotics after oral cysteine loads.

Biosynthesis of cysteine from methionine via the hepatic transsulfuration pathway is impaired in some cirrhotic patients, who therefore might require cysteine in the diet. However, because further metabolism of cysteine also occurs primarily in the liver, the metabolic clearance of this amino acid could be impaired in cirrhosis. We administered oral loads of L-cysteine to cirrhotic patients and healthy volunteers. Plasma cyst(e)ine (free and protein-bound cysteine, and 1/2 cystine) and urinary sulfur-containing constituents were measured at various times postload. Cirrhotic subjects exhibited a greater maximal plasma cyst(e)ine concentration and plasma elimination half-life (t1/2) and a delayed excretion of metabolic end products after an oral L-cysteine load. The postload increase in total plasma cyst(e)ine was accounted for primarily by an increase in the disulfide form (cystine). These studies show that cirrhotics have an impaired ability to clear cyst(e)ine from the plasma.

Calcium, phosphorus, and magnesium contents of human milk during early lactation.

Early milk samples from 102 American mothers were examined for Ca, P, and Mg contents in relation to stage of lactation, intake of prenatal mineral supplements, maternal age, parity, and previous history of lactation. A total of 415 samples were collected at three stages of lactation: early transitional (4-7 days postpartum); transitional (10-14 days postpartum); and mature (30-45 days postpartum). No diurnal variations in element concentrations were observed in representative samples of late evening (PM) and early morning (AM) feedings collected during the transitional and mature stages. The mean concentrations for the major elements were highest in early transitional milk and in some cases decreased significantly (p less than 0.05) as lactation progressed. Ca, P, and Mg contents (means +/- SEM) were 26.3 +/- 0.6, 14.6 +/- 0.4, 5.3 +/- 0.1 mg/100 g in early transitional milk and 26.2 +/- 0.5, 13.3 +/- 0.3, and 5.0 +/- 0.1 in mature milk, respectively. Increasing uniformity in the elemental content of milk was noted among the mothers as lactation became established. No significant relationship was found between intake of dietary supplements containing Ca and Mg and levels of these elements in milk. Also, no significant correlations were found between maternal age, parity, or previous history of lactation and the elemental content of milk. From these data, it was estimated that fully breast-fed infants would receive approximately 33, 18, and 6.5 mg/kg/day of Ca, P, and Mg, respectively, during the neonatal period.

Copper, iron, and zinc contents of human milk at early stages of lactation.

The Cu, Fe, and Zn contents of early milk from 102 American mothers were examined in relation to stage of lactation, intake of prenatal mineral supplements, maternal age, parity, and previous history of lactation. A total of 412 samples was collected at three stages of lactation: early transitional (4 to 7 days postpartum); transitional (10 to 14 days postpartum); and mature (30 to 45 days postpartum). For the transitional and mature stages, representative samples of late evening (PM) and early morning (AM) feedings were collected. Diurnal variation in concentration was observed only for Fe. Concentrations of all elements decreased significantly at successive stages of lactation with Zn showing the greatest decline. Cu, Fe, and Zn contents (means +/- SEM) were 104.1 +/- 5.4, 96.5 +/- 6.5, and 520 +/- 20 micrograms/100 g in early transitional milk; 93.9 +/- 3.6, 85.4 +/- 4.5, and 410 +/- 10 micrograms/100 g in transitional milk, and 84.7 +/- 3.8, 76.1 +/- 3.8, and 290 +/- 10 micrograms/100 g in mature milk, respectively. No significant relationship was found between levels of Cu and Zn in milk and whether mothers had taken dietary supplements containing these elements. In addition, no significant correlations were found between maternal age, parity, or previous history of lactation and the elemental content of milk. Based on these data, it was estimated that fully breast-fed infants would receive approximately 0.11, 0.10, and 0.50 mg/kg per day of Cu, Fe, and Zn, respectively, during the neonatal period.

PIP: The copper, iron and zinc contents of early milk from 102 American mothers is examined in relation to stage of lactation, intake of prenatal mineral supplements, maternal age, parity, and previous history of lactation. A total of 412 samples were collected at 3 stages of lactation: early transitional (4-7 days postpartum); transitional (10-14 days postpartum); and mature (30-45 days postpartum). For the transitional and mature stages, representative samples of late evening (PM) and early morning (AM) feedings were collected. Diurnal variation in concentration is observed only for iron. Concentrations of all elements decreased significantly at successive stages of lactation with zinc showing the greatest decline. Copper, iron and zinc contents (means plus or minus SEM) were 104.1 +or- 5.4, 96.5 +or- 6.5 and 520 +or- 20 ug/100 gm in early transitional milk; 93.9 +or- 3.6, 85.4 +or- 4.5, and 410 +or- 10 ug/100 gm in transitional milk, and 84.7 +or- 3.8, 76.1 +or- 3.8, and 290 +or- 10 ug/100 gm in mature milk, respectively. No significant relationship is found between levels of copper and zinc in milk and whether mothers had taken dietary supplements containing these elements. In addition, no significant correlations are found between maternal age, parity, or previous history of lactation and the elemental content of milk. Based on these data, it is estimated that fully breast fed infants would receive approximately 0.11, 0.10, and 0.50 mg/kg per day of copper, iron and zinc, respectively, during the neonatal period.

Structural codes and patient safety: does strict compliance make sense?

The authors of this Comment note recent trends rigidifying the enforcement of building and safety codes for health care facilities and compare the estimated costs (in terms of dollars spent) of those trends with their anticipated benefits (in terms of potential years of human life saved). They estimate that for each potential year of life saved, strict enforcement of the Life Safety Code of the National Fire Protection Association would cost $12.7 to $63.5 million for hospitals and $1.1 to $2.6 million for nursing homes, the latter figure based on Massachusett's experience. These figures are contrasted to the cost of routine kidney dialysis, which is generally acknowledged to be an extremely expensive technology, costing approximately $20,000 per potential year of life saved. The authors suggest that even if strict enforcement of the Code were fully effective (which, given the current structure of the Code, seems doubtful), a portion of the substantial financial resources expended from our limited national health care budget in hewing to the letter of the Code might be better spent on other activities with greater potential yield in improving the quality of life for patients in hospitals and nursing homes.

Major fatty acids and proximate composition of dairy products.

Data are reported on the major fatty acids and moisture, protein, fat, lactose, and ash content of several important dairy products, including major cheeses, presently available to the consumer. Samples of milk products, cheeses, wheys produced in processing, and the original milks from which the products were made were obtained from dairy processing plants. Samples of cheeses were also obtained from retail markets in six geographic areas of the United States. Nonfat fluid whole milk contained amounts of protein, lactose, and ash similar to those found in fluid whole milk. The fatty acid distribution of milk fat was not appreciably altered by the processing employed for this study. Protein and fat values were quite constant among samples of each cheese. No lactose was detected in the ripened cheeses. Mean fatty acid patterns for the different cheeses were not appreciably different from each other. The butyric acid (4:0) in the cheeses showed the greatest sample variation. The cheeses did not contain appreciably different proportions of polyunsaturated fatty acids. Procedures for converting data on fatty acid methyl ester to fatty acids (free acids or triglycerides) as weight percentages of the food are presented.