Supplemental Conjugated Linoleic Acid Consumption Does Not Influence Milk Macronutrient Contents in all Healthy Lactating Women

The term “conjugated linoleic acid” (CLA) refers to a group of positional and geometric isomers that are derived from linoleic acid and are found primarily in meat and milk products from ruminant animals. Due to the array of putative benefits associated with various forms of CLA, there has been recent interest in supplementing human diets with these fatty acids especially when weight loss is desired. However, in many animal models, CLA has been shown to decrease milk fat production. There is some concern, therefore, that maternal CLA supplementation during lactation might inadvertently decrease nutrient supply to the nursing infant. However, there is only limited research on the effect of CLA consumption on milk fat content in women. Based on previously published work from our laboratory, we hypothesized that CLA supplementation would reduce the milk fat percentage in lactating women in a dose-dependent manner. Breastfeeding women (n = 12) were assigned randomly to treatments of 4 g/day safflower oil (SFO), 2 g/day CLA plus 2 g/day SFO, or 4 g/day CLA in a double blind, 3 × 3 Latin square design. Conjugated linoleic acid supplements contained approximately equal amounts of cis9,trans11–18:2 and trans10,cis12–18:2; the two most common isoforms of CLA. Milk was collected by complete breast expression on the last day (day 5) of each intervention period and analyzed for macronutrient and fatty acid composition. On day 4 of each intervention period, infant milk consumption was estimated by 24 h weighing of the infant. Washout periods were 9 days in length. We observed a dose-dependent increase in the concentrations of cis9,trans11–18:2 and trans10,cis12–18:2 in the milk fat. However, we detected neither a change in overall macronutrient composition nor infant milk consumption. These data do not support those obtained from animal models or our previous human work suggesting that consumption of CLA mixtures necessarily reduces milk fat. It is possible that either (1) the interpretation of our previously published data should be reevaluated, and/or (2) there are important intra- and inter-species differences in this regard.     

Consumption of c9,t11-18:2 or t10,c12-18:2 enriched dietary supplements does not influence milk macronutrients in healthy, lactating women

Substantial research suggests that the t10,c12–18:2, but not the c9,t11–18:2, isomer of conjugated linoleic acid (CLA) reduces milk fat synthesis in lactating bovine and rodent species. Because fat is the major energy-yielding component in human milk, we were interested in whether this is true for women as well. Thus, the effects of c9,t11–18:2 and t10,c12–18:2 on milk fat were examined in breast-feeding women (n = 12) in a double-blind, placebo-controlled, crossover study with latin-square design. The study was divided into six periods: baseline (3 days), three intervention periods (5 days each), and two washout periods (9 days each). During each intervention period, women consumed 750 mg/day of a supplement containing predominantly c9,t11–18:2, t10,c12–18:2, or 18:1 (olive oil placebo). Milk was collected by complete breast expression on the final day of each period. Infant milk consumption was estimated by 24 h weighing on the penultimate day of each intervention and washout period, and maternal adiposity (% body fat) was determined at baseline using dual energy X-ray absorptiometry. Milk c9,t11–18:2 and t10,c12–18:2 concentrations were greater (P < 0.05) during the corresponding CLA treatment periods as compared to the placebo period, providing strong evidence of subject compliance. Both CLA isomers were transferred into milk fat at relatively high efficiency; average transfer efficiency was estimated to be 23.3%. Compared to the placebo treatment, milk fat content was not reduced during either CLA treatment. Data indicate that body fatness did not modify any putative effect of isomeric CLA consumption on milk fat concentration. The evidence from this study suggests that the sensitivity of lactating women’s mammary tissue to an anti-lipogenic effect of the t10,c12–18:2 isoform of CLA may be less than previously hypothesized.     

Identifying the dominant failure mode in the hot extrusion tooling used to forge nickel based superalloy

The dies used in the extrusion of nickel based super alloys are subject to severe mechanical and thermal stresses, resulting in shortened life and high manufacturing costs. It is necessary to understand the dominant damage mode in order to guide improvements for increased tool life. The operation under examination consists of the hot extrusion of a nickel based superalloy using nitrided hot work tool steel, glassed workpieces and graphite lubrication. The investigation was conducted through a combination of metallurgical analysis, metrology and finite element analysis. Out of the damage modes observed under these conditions, the plastic deformation of the substrate was found to be the cause for tool failure. This paper discusses the relationship between plastic deformation of the substrate and the formation of scoring marks, which fail the die.     

A nurse practitioner intervention model to maximize efficient use of telemetry resources

BACKGROUND: Telemetry monitoring is widely used in hospitals; the importance of being able to monitor and examine dysrhythmias has been universally accepted. Yet it is often used for patients who do not actually require this technology. A model to improve the efficiency of telemetry use entailed the use of an advanced practice nurse (APN; identical to a nurse practitioner) to provide concurrent review and intervention of floating telemetry, which is available for patients independently of the floor location and who do not need an intensive care unit bed. ADDRESSING OVERUSE: The demand for floating telemetry at Hackensack University Medical Center had equaled or exceeded the telemetry availability virtually 100% of the time, even after local guidelines had been disseminated in 1998. The APN carried out concurrent monitoring and intervened with the attending physician when patients were on telemetry for longer than 48 hours and did not meet the local telemetry guidelines. RESULTS: The mean number (standard error [SE]) of hours per patient declined from 65.2 +/- 0.7 hours (95% confidence interval, 63.8 to 66.6 hours) for the 11 months before the intervention to a mean of 49.6 +/- 0.4 hours (95% confidence interval, 48.7 to 50.2 hours) for the 29 months after intervention--representing a decrease of 34% (p < 0.0001). This decrease led to an increase in the number of patients per month put on telemetry. DISCUSSION: The APN model, an aggressive approach that induced change almost immediately, was then applied to other quality improvement projects.     

Correcting temperature-sensitive protein folding defects

Recently, we found that different low molecular weight compounds, all known to stabilize proteins in their native conformation, are effective in correcting the temperature-sensitive protein folding defect associated with the deltaF508 cystic fibrosis transmembrane regulator (CFTR) protein. Here we examined whether the folding of other proteins which exhibit temperature-sensitive folding defects also could be corrected via a similar strategy. Cell lines expressing temperature-sensitive mutants of the tumor suppressor protein p53, the viral oncogene protein pp60src, or a ubiquitin activating enzyme E1, were incubated at the nonpermissive temperature (39.5 degrees C) in the presence of glycerol, trimethylamine N-oxide or deuterated water. In each case, the cells exhibited phenotypes similar to those observed when the cells were incubated at the permissive temperature (32.5 degrees C), indicative that the particular protein folding defect had been corrected. These observations, coupled with our earlier work and much older studies in yeast and bacteria, indicate that protein stabilizing agents are effective in vivo for correcting protein folding abnormalities. We suggest that this type of approach may prove to be useful for correcting certain protein folding abnormalities associated with human diseases.     

Solution structure of the heparin-binding domain of vascular endothelial growth factor

Tricorn protease was previously described as the core enzyme of a modular proteolytic system displaying multicatalytic activity. Here we elucidate the mode of cooperation between Tricorn and its interacting factors, and we identify two additional factors, F2 and F3, closely related aminopeptidases of 89 kDa. In conjunction with these three factors, Tricorn degrades oligopeptides in a sequential manner, yielding free amino acids. We have been able to reconstitute a proteolytic pathway comprising the proteasome, Tricorn, and its interacting factors, F1, F2, and F3, which converts proteins efficiently into amino acids. Therefore, it is quite likely that Tricorn also acts in vivo downstream of the proteasome and, in cooperation with its interacting factors, completes protein catabolic pathways.     

XR-C1, a new CHO cell mutant which is defective in DNA-PKcs, is impaired in both V(D)J coding and signal joint formation

DNA-dependent protein kinase (DNA-PK) plays an important role in DNA double-strand break (DSB) repair and V(D)J recombination. We have isolated a new X-ray-sensitive CHO cell line, XR-C1, which is impaired in DSB repair and which was assigned to complementation group 7, the group that is defective in the XRCC7 / SCID ( Prkdc ) gene encoding the catalytic subunit of DNA-PK (DNA-PKcs). Consistent with this complementation analysis, XR-C1 cells lackeddetectable DNA-PKcs protein, did not display DNA-PK catalytic activity and were complemented by the introduction of a single human chromosome 8 (providing the Prkdc gene). The impact of the XR-C1 mutation on V(D)J recombination was quite different from that found in most rodent cells defective in DNA-PKcs, which are preferentially blocked in coding joint formation, whereas XR-C1 cells were defective in forming both coding and signal joints. These results suggest that DNA-PKcs is required for both coding and signal joint formation during V(D)J recombination and that the XR-C1 mutant cell line may prove to be a useful tool in understanding this pathway.