Post-prandial alterations in LDL size and subclasses in patients with growth hormone deficiency

Several studies have suggested that lipoproteins generated during the post-prandial phase are highly atherogenic, with modifications in low-density lipoproteins (LDL) size and density. In the present study we assessed post-prandial variations in LDL size and subclasses in patients with growth hormone deficiency (GHD).

Insulin-like growth factor-I treatment in primary growth hormone insensitivity: effect of recombinant human IGF-I (rhIGF-I) and rhIGF-I/rhIGF-binding protein-3 complex

Growth hormone insensitivity syndrome (GHIS) is a rare cause of growth retardation characterized by high serum GH levels, and low serum insulin-like growth factor I (IGF-I) levels associated with a genetic defect of the GH receptor (GHR) as well post-GHR signaling pathway. Based on clinical, as well as biochemical characteristics, GHIS can be genetically classified as classical/Laron's syndrome and nonclassical/atypical GHIS. Recombinant human IGF-I (rhIGF-I) treatment is effective in promoting growth in subjects who have GHIS. Further, pharmacological studies of a IGF-I compound containing a 1:1 molar complex of rhIGF-I and rhIGF-binding protein-3 (BP-3) demonstrated that the complex was effective in increasing levels of circulating total and free IGF-I and that the administration in patients with GHIS should be safe, well-tolerated and more effective than rhIGF-I on its own.

Prolonged amelioration of acute lung allograft rejection by sequential overexpression of human interleukin-10 and hepatocyte growth factor in rats

The effect of prolonged electroporation-mediated human interleukin-10 (hIL-10) overexpression 24 hours before transplantation, combined with sequential human hepatocyte growth factor (HGF) overexpression into skeletal muscle on day 5, on rat lung allograft rejection was evaluated. Left lung allotransplantation was performed from Brown-Norway to Fischer-F344 rats. Gene transfer into skeletal muscle was enhanced by electroporation. Three groups were studied: group I animals (n = 5) received 2.5 μg pCIK-hIL-10 (hIL-10/CMV [cytomegalovirus] early promoter enhancer) on day -1 and 80 μg pCIK-HGF (HGF/CMV early promoter enhancer) on day 5. Group II animals (n = 4) received 2.5 μg pCIK-hIL-10 and pUbC-hIL-10 (hIL-10/pUbC promoter) on day -1. Control group III animals (n = 4) were treated by sham electroporation on days -1 and 5. All animals received daily nontherapeutic intraperitoneal dose of cyclosporin A (2.5 mg/kg) and were sacrificed on day 15. Graft oxygenation and allograft rejection were evaluated. Significant differences were found between study groups in graft oxygenation (Pao(2)) (P = .0028; group I vs. groups II and III, P < .01 each). Pao(2) was low in group II (31 ± 1 mm Hg) and in group III controls (34 ± 10 mm Hg), without statistically significant difference between these 2 groups (P = .54). In contrast, in group I, Pao(2) of recipients sequentially transduced with IL-10 and HGF plasmids was much improved, with 112 ± 39 mm Hg (vs. groups II and III; P < .01 each), paralleled by reduced vascular and bronchial rejection (group I vs. groups II and III, P < .021 each). Sequential overexpression of anti-inflammatory cytokine IL-10, followed by sequential and overlapping HGF overexpression on day 5, preserves lung function and reduces acute lung allograft rejection up to day 15 post transplant as compared to prolonged IL-10 overexpression alone.

A review of the cost effectiveness of bisphosphonates in the treatment of post-menopausal osteoporosis in Switzerland

The economic burden associated with osteoporosis is considerable. As such, cost-effectiveness analyses are important contributors to the diagnostic and therapeutic decision-making process. The aim of this study was to review the cost effectiveness of treating post-menopausal osteoporosis with bisphosphonates and identify the key factors that influence the cost effectiveness of such treatment in the Swiss setting. A systematic search of databases (MEDLINE, EMBASE and the Cochrane Library) was conducted to identify published literature on the cost effectiveness of bisphosphonates in post-menopausal osteoporosis in the Swiss setting. Outcomes were compared with similar studies in Western European countries. Three cost-effectiveness studies of bisphosphonates in this patient population were identified; all were from a healthcare payer perspective. Outcomes showed that, relative to no treatment, treatment with oral bisphosphonates was predicted to be cost saving for most women aged ≥70 years with osteoporosis or at least one risk factor for fracture, and cost effective for women aged ≥75 years without prior fracture when used as a component of a population-based screen-and-treat programme. Results were most sensitive to changes in fracture risk, cost of fractures, cost of treatment, nursing home admissions and adherence with treatment. Swiss results were generally comparable to those in other European settings. Assuming similar clinical efficacy, lowering treatment cost (through the use of price-reduced brand-name or generic drugs) and/or improving adherence should both contribute to further improving the cost effectiveness of bisphosphonates in women with post-menopausal osteoporosis. Published evidence indicates that bisphosphonates are estimated to be similarly cost effective or cost saving in most treatment scenarios of post-menopausal osteoporosis in Switzerland and in neighbouring European countries.

Bilateral post-traumatic acetabular dysplasia

Traumatic disruption of the acetabular triradiate cartilage is an infrequent injury. When it occurs in early childhood, it may lead to growth changes in acetabular morphology. The morphology of this kind of acetabular dysplasia is uniform and differs significantly from that seen in classic developmental dysplasia of the hip. We present a case of bilateral post-traumatic acetabular dysplasia, which to our knowledge has not been reported. The morphology and the symptoms of impingement and periacetabular osteotomy of the hip joint are discussed.

Differential expression and activity of 11beta-hydroxysteroid dehydrogenase in human placenta and fetal membranes from pregnancies with intrauterine growth restriction

OBJECTIVES: To study the expression and the function of the 11beta-hydroxysteroid dehydrogenase enzyme 1 (11beta-HSD1) and 2 (11beta-HSD2) in placenta and the fetal membranes from pregnancies with intrauterine growth restriction (IUGR) and from controls. METHODS: Amnion, chorion, decidua and cotyledon were separated from placenta; mRNA was analyzed by TaqMan real-time technology and proteins by Western blot; enzyme activities were measured by the conversion of 3H-cortisol to 3H-cortisone and vice versa. RESULTS: Predominant mRNA expression (p < 0.001) was found for 11beta-HSD1 in chorion and for 11beta-HSD2 in decidua and cotyledon. In pregnancies with IUGR, 11beta-HSD1 was upregulated in chorion (mean DeltaCt 11beta-HSD:18S mRNA 193.5 vs. 103.0 in controls respectively, p < 0.05) and 11beta-HSD2 was downregulated in decidua (mean DeltaCt 11beta-HSD2:18S mRNA 0.18 vs. 15.88 in controls respectively, p < 0.05). 11beta-HSD1 protein levels were reduced in amnion and 11beta-HSD1 and 11beta-HSD2 oxidase activity in decidua and cotyledon were reduced from pregnancies with IUGR. CONCLUSION: Reduced synthesis or activity of 11beta-HSD1 or 2 in cases of IUGR is shown in some but not in all tissues. The local mRNA expression of 11beta-HSD1 in chorion may reflect a mechanism on the post-transcriptional gene regulation to stimulate the formation of cortisone in IUGR. To provoke increasing activity with oxidase stimulators could be a future therapy in cases of IUGR.

Hsp90 transcriptionally and post-translationally regulates the expression of NDRG1 and maintains the stability of its modifying kinase GSK3beta

N-myc downstream-regulated gene 1 (NRDG1) is a stress-induced protein whose putative function is suppression of tumor metastasis. A recent proteonomic study showed NDRG1 interacts with the molecular chaperone heat shock protein 90 (Hsp90). From their reported association, we investigated if NDRG1 is dependent on Hsp90 for its stability and is therefore a yet unidentified Hsp90 client protein. Here, we demonstrate that endogenous NDRG1 and Hsp90 physically associate in hepatocellular cancer cell lines. However, geldanamycin (GA)-mediated inhibition of Hsp90 did not disrupt their interaction or result in NDRG1 protein destabilization. On the contrary, inhibition of Hsp90 led to a transcriptional increase of NDRG1 protein which was associated with cell growth arrest. We also observed that GA inhibited the phosphorylation of NDRG1 by targeting its regulating kinases, serum- and glucocorticoid-induced kinase 1 (SGK1) and glycogen synthase kinase 3 beta (GSK3beta). We demonstrate that in the presence of GA, GSK3beta protein and activity were decreased thus indicating that Hsp90 is necessary for GSK3beta stability. Taken together, our data demonstrate that NDRG1 is not a classic client protein but interacts with Hsp90 and is still dually regulated by Hsp90 at a transcriptional and post-translational level. Finally, we suggest for the first time GSK3beta as a new client protein of Hsp90.

Political process and government growth: a theoretical and empirical investigation

A striking feature of virtually al western industrialized countries sice the middle of the past century has been the persistent growth of their government sector. From the beginning of the century to the late 1970's, the government expenditures' share of gross national product has increased from 7% to 36% in the U.S., 11% to 40% in the U.K., and 3% to 25% in Japan. In Germany, it went from 7% to 42% (1872-1978), while in France it soared from 11% to 59% (1872-1979). The evolution of the number of government employees followed a similar pattern. In the U.S., for instance, the average annual rate of growth of the government labor force over the period 1899-1974 has been 3.17%, compared to a 1.62% average annual growth rate of the working population. Less quantifiable aspects like the number and scope of regulations also refelct a growing public sector.

Posttraumatic Growth in Parents of Childhood Cancer Survivors

BACKGROUND: When a child is diagnosed with cancer, parents are confronted with the potential fatality of the disease. This traumatic stressor is often followed by additional stressful events during treatment. However, once their child is cured many parents also reported experiencing psychological growth. We aimed to describe post-traumatic growth (PTG) in parents of adolescent childhood cancer survivors, compare it with PTG in existing samples experiencing stressful events, and describe characteristics of parents who report PTG.