Problems of LNG spill hazard assessment

It is apparent from the literature on LNG spills that there is a considerable lack of knowledge in many areas of technical importance to the safety assessment of LNG receiving terminals. For this reason, a thorough critical review of the state-of-the-art regarding the technical aspects of LNG spill evaluation is in preparation. The purpose of this review is to focus attention on these aspects of the problem that are least understood and which are crucial to a proper assessment of the hazards. It is realized that ERDA has already conducted an LNG Safety and Control Workship, the outcome of which was a set of conclusions and recommendations regarding the safety and control issues of LNG operations

Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice

Ghrelin stimulates both GH secretion and food intake. The orexigenic action of ghrelin is mainly mediated by neurons that coexpress agouti-related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). GH also stimulates food intake and, importantly, ARHAgRP/NPY neurons express GH receptor (GHR). Thus, ghrelin-induced GH secretion may contribute to the orexigenic effect of ghrelin. Here, we investigated the response to ghrelin in male mice carrying GHR ablation specifically in neurons (brain GHR knockout [KO] mice) or exclusively in ARHAgRP/NPY neurons (AgRP GHR KO mice). Although brain GHR KO mice showed normal ghrelin-induced increase in plasma GH levels, these mutants lacked the expected orexigenic response to ghrelin. Additionally, brain GHR KO mice displayed reduced hypothalamic levels of Npy and Ghsr mRNA and did not elicit ghrelin-induced c-Fos expression in the ARH. Furthermore, brain GHR KO mice exhibited a prominent reduction in AgRP fiber density in the ARH and paraventricular nucleus of the hypothalamus (PVH). In contrast, AgRP GHR KO mice showed no changes in the hypothalamic Npy and Ghsr mRNAs and conserved ghrelin-induced food intake and c-Fos expression in the ARH. AgRP GHR KO mice displayed a reduced AgRP fiber density (∼16%) in the PVH, but this reduction was less than that observed in brain GHR KO mice (∼61%). Our findings indicate that GHR signaling in the brain is required for the orexigenic effect of ghrelin, independently of GH action on ARHAgRP/NPY neurons.Fil: Wasinski, Frederick. Universidade de Sao Paulo; BrasilFil: Barrile, Franco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Pedroso, João A. B.. Universidade de Sao Paulo; BrasilFil: Quaresma, Paula G. F.. Universidade de Sao Paulo; BrasilFil: Dos Santos, Willian O.. Universidade de Sao Paulo; BrasilFil: List, Edward O.. Ohio University; Estados UnidosFil: Kopchick, John J.. Ohio University; Estados UnidosFil: Perelló, Mario. Multidisciplinary Institute Of Cell Biology; ArgentinaFil: Donato, Jose. Universidade de Sao Paulo; Brasi

Gene expression of key regulators of mitochondrial biogenesis is sex dependent in mice with growth hormone receptor deletion in liver

Mitochondrial biogenesis is an essential process for cell viability. Mice with disruption of the growth hormone receptor (GHR) gene (Ghr gene) in the liver (LiGHRKO), in contrast to long-lived mice with global deletion of the Ghr gene (GHRKO), are characterized by lack of improved insulin sensitivity and severe hepatic steatosis. Tissue-specific disruption of the GHR in liver results in a mouse model with dramatically altered GH/IGF1 axis. We have previously shown increased levels of key regulators of mitochondrial biogenesis in insulin-sensitive GHRKO mice. The aim of the present study is to assess, using real-time PCR, the gene expression of key regulators of mitochondrial biogenesis (Pgc1 alpha, Ampk, Sirt1, Nrf2 and Mfn2) and a marker of mitochondrial activity (CoxIV) in brains, kidneys and livers of male and female LiGHRKO and wild-type (WT) mice. There were significant differences between males and females. In the brain, expression of Pgc1 alpha, Ampk, Sirt1, Nrf2 and Mfn2 was lower in pooled females compared to pooled males. In the kidneys, expression of Ampk and Sirt1 was also lower in female mice. In the liver, no differences between males and females were observed. Sexual dimorphism may play an important role in regulating the biogenesis of mitochondria

Growth hormone inhibits hepatic de novo lipogenesis in adult mice

Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have low growth hormone (GH) production and/or hepatic GH resistance. GH replacement can resolve the fatty liver condition in diet-induced obese rodents and in GH-deficient patients. However, it remains to be determined whether this inhibitory action of GH is due to direct regulation of hepatic lipid metabolism. Therefore, an adult-onset, hepatocyte-specific, GH receptor (GHR) knockdown (aLivGHRkd) mouse was developed to model hepatic GH resistance in humans that may occur after sexual maturation. Just 7 days after aLivGHRkd, hepatic de novo lipogenesis (DNL) was increased in male and female chow-fed mice, compared with GHR-intact littermate controls. However, hepatosteatosis developed only in male and ovariectomized female aLivGHRkd mice. The increase in DNL observed in aLivGHRkd mice was not associated with hyperactivation of the pathway by which insulin is classically considered to regulate DNL. However, glucokinase mRNA and protein levels as well as fructose-2,6-bisphosphate levels were increased in aLivGHRkd mice, suggesting that enhanced glycolysis drives DNL in the GH-resistant liver. These results demonstrate that hepatic GH actions normally serve to inhibit DNL, where loss of this inhibitory signal may explain, in part, the inappropriate increase in hepatic DNL observed in NAFLD patients

Interaction of a viral insulin-like peptide with the IGF-1 receptor produces a natural antagonist

Lymphocystis disease virus-1 (LCDV-1) and several other Iridoviridae encode viral insulin/IGF-1 like peptides (VILPs) with high homology to human insulin and IGFs. Here we show that while single-chain (sc) and double-chain (dc) LCDV1-VILPs have very low affinity for the insulin receptor, scLCDV1-VILP has high affinity for IGF1R where it can antagonize human IGF-1 signaling, without altering insulin signaling. Consequently, scLCDV1-VILP inhibits IGF-1 induced cell proliferation and growth hormone/IGF-1 induced growth of mice in vivo. Cryo-electron microscopy reveals that scLCDV1-VILP engages IGF1R in a unique manner, inducing changes in IGF1R conformation that led to separation, rather than juxtaposition, of the transmembrane segments and hence inactivation of the receptor. Thus, scLCDV1-VILP is a natural peptide with specific antagonist properties on IGF1R signaling and may provide a new tool to guide development of hormonal analogues to treat cancers or metabolic disorders sensitive to IGF-1 without affecting glucose metabolism. The authors previously identified a family of viral insulin-like peptides (VILPs) with high homology to human insulin/IGF−1. Here, they report that one of these VILPs exhibits antagonist properties associated with a unique conformation of the IGF1R

Growth Hormone Influence on the Morphology and Size of the Mouse Meibomian Gland

Purpose. We hypothesize that growth hormone (GH) plays a significant role in the regulation of the meibomian gland. To test our hypothesis, we examined the influence of GH on mouse meibomian gland structure. Methods. We studied four groups of mice, including (1) bovine (b) GH transgenic mice with excess GH; (2) GH receptor (R) antagonist (A) transgenic mice with decreased GH; (3) GHR knockout (−/−) mice with no GH activity; and (4) wild type (WT) control mice. After mouse sacrifice, eyelids were processed for morphological and image analyses. Results. Our results show striking structural changes in the GH-deficient animals. Many of the GHR−/− and GHA meibomian glands featured hyperkeratinized and thickened ducts, acini inserting into duct walls, and poorly differentiated acini. In contrast, the morphology of WT and bGH meibomian glands appeared similar. The sizes of meibomian glands of bGH mice were significantly larger and those of GHA and GHR−/− mice were significantly smaller than glands of WT mice. Conclusions. Our findings support our hypothesis that the GH/IGF-1 axis plays a significant role in the control of the meibomian gland. In addition, our data show that GH modulates the morphology and size of this tissue

Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice

The aging process is associated with the development of several chronic diseases. White adipose tissue (WAT) may play a central role in age-related disease onset and progression due to declines in adipogenesis with advancing age. Recent reports indicate that the accumulation of senescent progenitor cells may be involved in age-related WAT dysfunction. Growth hormone (GH) action has profound effects on adiposity and metabolism and is known to influence lifespan. In the present study we tested the hypothesis that GH activity would predict age-related WAT dysfunction and accumulation of senescent cells. We found that long-lived GH-deficient and -resistant mice have reduced age-related lipid redistribution. Primary preadipocytes from GH-resistant mice also were found to have greater differentiation capacity at 20 months of age when compared to controls. GH activity was also found to be positively associated with senescent cell accumulation in WAT. Our results demonstrate an association between GH activity, age-related WAT dysfunction, and WAT senescent cell accumulation in mice. Further studies are needed to determine if GH is directly inducing cellular senescence in WAT or if GH actions on other target organs or alternative downstream alterations in insulin-like growth factor-1, insulin or glucose levels are responsible