Effects of insulin-like growth factor I combined with growth hormone on glucocorticoid-induced whole-body protein catabolism in man

Treatment with insulin-like growth factor I (IGF-I) alone failed to affect glucocorticoid-induced protein catabolism in a previous study from our laboratory. To assess the effects of the combination of IGF-I and GH in a similar protocol, 24 normal subjects received (in a double-blind, randomized, placebo-controlled manner) s.c. injections of either GH alone (0.3 IU/kg.day), the combination of IGF-I (80 micrograms/kg.day) and GH (0.3 IU/kg.day), or placebo for a period of 6 days during which they were treated with methylprednisolone (0.5 mg/kg.day). Whole-body protein kinetics measured, using the [1-13C]-leucine infusion technique, demonstrated that leucine flux (a parameter of protein breakdown) increased during administration of glucocorticoids alone (placebo group) and during GH-treatment, whereas the glucocorticoid-induced increase was abolished during IGF-I plus GH (P < 0.03 vs. GH). Leucine oxidation (a parameter of irreversible protein catabolism) increased in the placebo group (+60 +/- 14.5%, P < 0.005, day 7 vs. day 1), remained unchanged in the GH group (+2.5 +/- 10%), and decreased in the combination group (-17.7 +/- 3.3%, P < 0.002, day 7 vs. day 1). Glucose MCR decreased in the group receiving placebo (P < 0.05) and remained unchanged during combined treatment with IGF-I plus GH. It is concluded that glucocorticoid-induced protein, catabolism (leucine oxidation) is abolished during coadministration of GH (anticatabolic effect), whereas treatment with IGF-I and GH results in a net anabolic effect without adverse effects on peripheral glucose clearance.     

Differential divalent cation requirements uncouple the assembly and catalytic reactions of human immunodeficiency virus type 1 integrase

Previous in vitro analyses have shown that the human immunodeficiency virus type 1 (HIV-1) integrase uses either manganese or magnesium to assemble as a stable complex on the donor substrate and to catalyze strand transfer. We now demonstrate that subsequent to assembly, catalysis of both 3' end processing and strand transfer requires a divalent cation cofactor and that the divalent cation requirements for assembly and catalysis can be functionally distinguished based on the ability to utilize calcium and cobalt, respectively. The different divalent cation requirements manifest by these processes are exploited to uncouple assembly and catalysis, thus staging the reaction. Staged 3' end processing and strand transfer assays are then used in conjunction with exonuclease III protection analysis to investigate the effects of integrase inhibitors on each step in the reaction. Analysis of a series of related inhibitors demonstrates that these types of compounds affect assembly and not either catalytic process, therefore reconciling the apparent disparate results obtained for such inhibitors in assays using isolated preintegration complexes. These studies provide evidence for a distinct role of the divalent cation cofactor in assembly and catalysis and have implications for both the identification and characterization of integrase inhibitors.     

Enhanced calcium–magnesium–aluminosilicate (CMAS) resistance of GdAlO3 (GAP) for composite thermal barrier coatings

The impact of calcium–magnesium–alumino-silicate (CMAS) degradation is a critical factor for development of new thermal and environmental barrier coatings. Several methods of preventing damage have been explored in the literature, with formation of an infiltration inhibiting reaction layer generally given the most attention. Gd₂Zr₂O₇ (GZO) exemplifies this reaction with the rapid precipitation of apatite when in contact with CMAS. The present study compares the CMAS behavior of GZO to an alternative thermal barrier coating (TBC) material, GdAlO₃ (GAP), which possesses high temperature phase stability through its melting point as well as a significantly higher toughness compared with GZO. The UCSB laboratory CMAS (35CaO–10MgO–7Al₂O₃–48SiO₂) was utilized to explore equilibrium behavior with 50:50 mol% TBC:CMAS ratios at 1200, 1300, and 1400°C for various times. In addition, 8 and 35 mg/cm² CMAS surface exposures were performed at 1425°C on dense pellets of each material to evaluate the infiltration and reaction in a more dynamic test. In the equilibrium tests, it was found that GAP appears to dissolve slower than GZO while producing an equivalent or higher amount of pore blocking apatite. In addition, GAP induces the intrinsic crystallization of the CMAS into a gehlenite phase, due in part to the participation of the Al₂O₃ from GAP. In surface exposures, GAP experienced a substantially thinner reaction zone compared with GZO after 10 h (87 ± 10 vs. 138 ± 4 μm) and a lack of strong sensitivity to CMAS loading when tested at 35 mg/cm² after 10 h (85 ± 13 versus 246 ± 10 μm). The smaller reaction zone, loading agnostic behavior, and intrinsic crystallization of the glass suggest this material warrants further evaluation as a potential CMAS barrier and inclusion into composite TBCs.     

Nanostructured component fabrication by electron beam-physical vapor deposition

Fabrication of cost-effective, nano-grained net-shaped components has brought considerable interest to Department of Defense, National Aeronautics and Space Administration, and Department of Energy. The objective of this paper is to demonstrate the versatility of electron beam-physical vapor deposition (EB-PVD) technology in engineering new nanostructured materials with controlled microstructure and microchemistry in the form of coatings and net-shaped components for many applications including the space, turbine, optical, biomedical, and auto industries. Coatings are often applied on components to extent their performance and life under severe environmental conditions including thermal, corrosion, wear, and oxidation. Performance and properties of the coatings depend upon their composition, microstructure, and deposition condition. Simultaneous co-evaporation of multiple ingots of different compositions in the high energy EB-PVD chamber has brought considerable interest in the architecture of functional graded coatings, nano-laminated coatings, and design of new structural materials that could not be produced economically by conventional methods. In addition, high evaporation and condensate rates allowed fabricating precision net-shaped components with nanograined microstructure for various applications. Using EB-PVD, nano-grained rhenium (Re) coatings and net-shaped components with tailored microstructure and properties were fabricated in the form of tubes, plates, and Re-coated spherical graphite cores. This paper will also present the results of various metallic and ceramic coatings including chromium, titanium carbide (TiC), titanium diboride (TiB₂), hafnium nitride (HfN), titanium-boron-carbonitride (TiBCN), and partially yttria stabilized zirconia (YSZ) TBC coatings deposited by EB-PVD for various applications. This paper was presented at the International Symposium on Manufacturing, Properties, and Applications of Nanocrystalline Materials sponsored by the ASM International Nanotechnology Task Force and TMS Powder Materials Committee, October 18–20, 2004, Columbus, OH.     

Variations in IC50 Values with Purity of Mushroom Tyrosinase

The effects of various inhibitors on crude, commercial and partially purified commercial mushroom tyrosinase were examined by comparing IC₅₀ values. Kojic acid, salicylhydroxamic acid, tropolone, methimazole, and ammonium tetrathiomolybdate had relatively similar IC₅₀ values for the crude, commercial and partially purified enzyme. 4-Hexylresorcinol seemed to have a somewhat higher IC₅₀ value using crude extracts, compared to commercial or purified tyrosinase. Some inhibitors (NaCl, esculetin, biphenol, phloridzin) showed variations in IC₅₀ values between the enzyme samples. In contrast, hydroquinone, lysozyme, Zn²⁺, and anisaldehyde showed little or no inhibition in concentration ranges reported to be effective inhibitors. Organic solvents (DMSO and ethanol) had IC₅₀ values that were similar for some of the tyrosinase samples. Depending of the source of tyrosinase and choice of inhibitor, variations in IC₅₀ values were observed.     

提高注射用头孢噻肟钠的成品率

在1.0g注射用头孢噻肟钠粉针制剂生产过程中,从影响成品率提高的各个环节入手,通过采取各个工序严格把关、对现有分装机缺陷进行改进等措施,1.0g注射用头孢噻肟钠成品率从97.15%提高到了98.51%.     

Effects of inbreeding on production and survival in Jerseys

Responses of registered Jersey cows to various levels of inbreeding were examined with pedigree data supplied by the American Jersey Cattle Association and test-day production data from 1970 through 1998 obtained from the Animal Breeding Center at Cornell University. Rate of increase in level of inbreeding is accelerating with time, making it more difficult for producers to make matings that avoid the potentially deleterious effects of inbreeding. Production losses caused by inbreeding were significant and curvilinear for all traits studied except somatic cell linear score, with the greatest losses at higher levels of inbreeding. Inbreeding was found to have the greatest effect on production at early ages and early in lactation. Early onset of the deleterious effects of inbreeding resulted in larger net present value losses than if effects of inbreeding occurred later in the life of an animal. Losses were probably enhanced because of the need to freshen animals as early as possible to maximize net present value returns. Survival decreased as level of inbreeding increased and was likely to have a greater negative impact on the financial health of the dairy enterprise than production losses.     

Targeted disruption of gene function in Drosophila by RNA interference (RNA-i): a role for nautilus in embryonic somatic muscle formation

The expression of the MyoD gene homolog, nautilus (nau), in the Drosophila embryo defines a subset of mesodermal cells known as the muscle "pioneer" or "founder" cells. These cells are thought to establish the future muscle pattern in each hemisegment. Founders appear to recruit fusion-competent mesodermal cells to establish a particular muscle fiber type. In support of this concept every somatic muscle in the embryo is associated with one or more nautilus-positive cells. However, because of the lack of known (isolated) nautilus mutations, no direct test of the founder cell hypothesis has been possible. We now have utilized toxin ablation and genetic interference by double-stranded RNA (RNA interference or RNA-i) to determine both the role of the nautilus-expressing cells and the nautilus gene, respectively, in embryonic muscle formation. In the absence of nautilus-expressing cells muscle formation is severely disrupted or absent. A similar phenotype is observed with the elimination of the nautilus gene product by genetic interference upon injection of nautilus double-stranded RNA. These results define a crucial role for nautilus in embryonic muscle formation. The application of RNA interference to a variety of known Drosophila mutations as controls gave phenotypes essentially indistinguishable from the original mutation. RNA-i provides a powerful approach for the targeted disruption of a given genetic function in Drosophila.     

Hypomethylation in cervical tissue: is there a correlation with folate status?

5-Aminolevulinic acid (ALA) is the first intermediate substrate in the heme synthetic pathway and is the substrate of aminolevulinic acid dehydratase (ALAD, porphobilinogen synthase). Because lead effectively inhibits ALAD activity, resulting in accumulation of ALA in urine and blood, urinary ALA (ALAU) has been used as a biomarker for lead exposure or early biologic effect of lead. Intraindividual variation in urinary excretion of ALA requires the use of 24-hour urine samples or adjustment of single urine samples by other normalizing variables, such as urinary creatinine concentration. Previous studies of ALAU concentration have used various adjustment methods; however, few have compared creatinine-adjusted ALAU concentration with ALA concentration in plasma (ALAP) from subjects with low (< 30 micrograms/dL) to moderate (< 60 micrograms/dL) levels of blood lead. To determine if creatinine-adjusted ALAU is associated with ALAP, we measured ALAU, ALAP, and urinary creatinine in 65 Korean lead workers with blood lead concentrations in the range of 14-60 micrograms/dL. ALAU, ALAU/creatinine, or ALAU/log creatinine all correlated with ALAP. However, ALAU/creatinine correlated more closely with ALAP based on Spearman's r (rs = 0.40, P, = 0.0009), supporting the use of ALA/creatinine in single urine samples as a surrogate for ALAP.