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Growth hormone (GH) stimulates osteoblasts in vitro and increases bone turnover and stimulates osteoblast activity when given to elderly subjects. Probably a major effect of GH on bone is mediated through stimulation of either circulating or locally produced insulin‐like growth factor I (IGF‐I). We determined the effect of chronic administration of the GH secretagogue, MK‐677, on serum IGF‐I and markers of bone turnover in 187 elderly adults (65 years or older) enrolled in three randomized, double‐blind, placebo‐controlled clinical studies lasting 2–9 weeks. Urine was collected for determination of N‐telopeptide cross‐links (NTXs), a marker of bone resorption, and blood was collected for determination of serum osteocalcin and bone‐specific alkaline phosphatase (BSAP), as bone formation markers, and serum IGF‐I levels pre‐ and post‐treatment. Dose response data were initially obtained in healthy elderly subjects who received oral doses of 10 mg or 25 mg of MK‐677 or placebo for 2 weeks (n= 10–12/group). Treatment with 10 mg and 25 mg of MK‐677 for 2 weeks increased mean urine NTXs 10% and 17%, respectively (p< 0.05 vs. placebo). Additionally, 50 healthy elderly subjects received either placebo (n= 20) for 4 weeks or 25 mg of MK‐677 (n= 30) daily for 2 weeks followed by 50 mg daily for 2 weeks. MK‐677 increased mean serum osteocalcin by 8% (p< 0.05 vs. placebo). In both studies, MK‐677 increased serum IGF‐I levels significantly (55–94%). Subsequently, the biological effects of MK‐677 were studied in 105 elderly subjects who met objective criteria for functional impairment. Subjects were randomized to receive oral doses of placebo for 9 weeks or either 5, 10, or 25 mg of MK‐677 daily for an initial 2 weeks followed by 25 mg of MK‐677 daily for the next 7 weeks(n= 63 on MK‐677 and n= 28 on placebo completed 9 weeks of therapy). Treatment with MK‐677 (all MK‐677 groups combined) for 9 weeks increased mean serum osteocalcin by 29.4% and BSAP by 10.4% (p< 0.001 vs. placebo) and mean urinary NTX excretion by 22.6% (p< 0.05 vs. placebo). The change from baseline serum osteocalcin correlated with the change from baseline serum IGF‐I in the MK‐677 group (r= 0.37; p< 0.01). In conclusion, once daily dosing with MK‐677, an orally active GH secretagogue, stimulates bone turnover in elderly subjects based on elevations in biochemical markers of bone resorption and formation.

Growth hormone (GH) stimulates osteoblasts in vitro and increases bone turnover and stimulates osteoblast activity when given to elderly subjects. Probably a major effect of GH on bone is mediated through stimulation of either circulating or locally produced insulin‐like growth factor I (IGF‐I). We determined the effect of chronic administration of the GH secretagogue, MK‐677, on serum IGF‐I and markers of bone turnover in 187 elderly adults (65 years or older) enrolled in three randomized, double‐blind, placebo‐controlled clinical studies lasting 2–9 weeks. Urine was collected for determination of N‐telopeptide cross‐links (NTXs), a marker of bone resorption, and blood was collected for determination of serum osteocalcin and bone‐specific alkaline phosphatase (BSAP), as bone formation markers, and serum IGF‐I levels pre‐ and post‐treatment. Dose response data were initially obtained in healthy elderly subjects who received oral doses of 10 mg or 25 mg of MK‐677 or placebo for 2 weeks (n= 10–12/group). Treatment with 10 mg and 25 mg of MK‐677 for 2 weeks increased mean urine NTXs 10% and 17%, respectively (p< 0.05 vs. placebo). Additionally, 50 healthy elderly subjects received either placebo (n= 20) for 4 weeks or 25 mg of MK‐677 (n= 30) daily for 2 weeks followed by 50 mg daily for 2 weeks. MK‐677 increased mean serum osteocalcin by 8% (p< 0.05 vs. placebo). In both studies, MK‐677 increased serum IGF‐I levels significantly (55–94%). Subsequently, the biological effects of MK‐677 were studied in 105 elderly subjects who met objective criteria for functional impairment. Subjects were randomized to receive oral doses of placebo for 9 weeks or either 5, 10, or 25 mg of MK‐677 daily for an initial 2 weeks followed by 25 mg of MK‐677 daily for the next 7 weeks(n= 63 on MK‐677 and n= 28 on placebo completed 9 weeks of therapy). Treatment with MK‐677 (all MK‐677 groups combined) for 9 weeks increased mean serum osteocalcin by 29.4% and BSAP by 10.4% (p< 0.001 vs. placebo) and mean urinary NTX excretion by 22.6% (p< 0.05 vs. placebo). The change from baseline serum osteocalcin correlated with the change from baseline serum IGF‐I in the MK‐677 group (r= 0.37; p< 0.01). In conclusion, once daily dosing with MK‐677, an orally active GH secretagogue, stimulates bone turnover in elderly subjects based on elevations in biochemical markers of bone resorption and formation.

A recombinant plasmid composed of segments of herpes simplex virus and simian virus 40 viral DNA inserted into the bacterial plasmid pBR322 was microinjected into pronuclei of fertilized mouse oocytes. The embryos were implanted in the oviducts of pseudopregnant females and allowed to develop to term. DNA from newborn mice was evaluated by the Southern blotting technique for the presence of DNA homologous to the injected plasmid. Two of 78 mice in one series of injections showed clear homology, though the injected sequences had been rearranged. Band intensities from the two positive mice were consistent with the presence of donor DNA in most or all of the cells of the newborns. These results demonstrate that genes can be introduced into the mouse genome by direct insertion into the nuclei of early embryos. This technique affords the opportunity to study problems of gene regulation and cell differentiation in a mammalian system by application of recombinant DNA technology.

Abstract: The growth of ultrathin (1.7–7.3 nm) YBa2Cu3O7−x films on the SrTiO3(100) substrate is investigated by the mean-energy ion scattering technique. It is found that the growth of islands proceeds according to the two-dimensional and three-dimensional models and depends on the growth conditions.