Lack of Effect of Metyrapone and Exogenous Cortisol on Early Porcine Conceptus Development

In many species, including swine, fetal plasma glucocorticoids such as cortisol increase as term approaches and are responsible for final maturational changes in numerous tissues (e.g. Silver, 1990; Sangild et al. 1993, 1994; Fowden et al. 1995). On the contrary, excessive exposure to glucocorticoids during gestationmay cause intra-uterine growth retardation, developmental abnormalities or death, or lead to increased incidence of certain diseases during adult life (Blackburn et al. 1965; Reinisch et al. 1978; Seckl et al. 2000). Hence, one might speculate that a closely regulated glucocorticoid exposure is necessary throughout gestation to ensure appropriate development and survival (Klemcke et al. 1999). We have previously demonstrated in pregnant and cyclic pigs that intra-uterine cortisol increases 4- to 6.7-fold between days 10 and 19 of pregnancy (Klemcke et al. 1998). At this time (days 10–19) in conceptus (embryo plus associated extra-embryonic membranes) development, the blastocyst is undergoing quite dramatic changes (Marrable, 1971; Anderson, 1978; Anderson et al. 1993). Part of this development involves the allantois, which rapidly expands between days 18 and 30 owing to water accumulation (Bazer et al. 1981) that might in part result from Na+,K+-ATPase-generated water movement (Macknight & Leaf, 1977). Corticosteroids are known to regulate Na+,K+-ATPase in various tissues (e.g. Verrey et al. 1996)

Lack of Effect of Metyrapone and Exogenous Cortisol on Early Porcine Conceptus Development

In many species, including swine, fetal plasma glucocorticoids such as cortisol increase as term approaches and are responsible for final maturational changes in numerous tissues (e.g. Silver, 1990; Sangild et al. 1993, 1994; Fowden et al. 1995). On the contrary, excessive exposure to glucocorticoids during gestationmay cause intra-uterine growth retardation, developmental abnormalities or death, or lead to increased incidence of certain diseases during adult life (Blackburn et al. 1965; Reinisch et al. 1978; Seckl et al. 2000). Hence, one might speculate that a closely regulated glucocorticoid exposure is necessary throughout gestation to ensure appropriate development and survival (Klemcke et al. 1999). We have previously demonstrated in pregnant and cyclic pigs that intra-uterine cortisol increases 4- to 6.7-fold between days 10 and 19 of pregnancy (Klemcke et al. 1998). At this time (days 10–19) in conceptus (embryo plus associated extra-embryonic membranes) development, the blastocyst is undergoing quite dramatic changes (Marrable, 1971; Anderson, 1978; Anderson et al. 1993). Part of this development involves the allantois, which rapidly expands between days 18 and 30 owing to water accumulation (Bazer et al. 1981) that might in part result from Na+,K+-ATPase-generated water movement (Macknight & Leaf, 1977). Corticosteroids are known to regulate Na+,K+-ATPase in various tissues (e.g. Verrey et al. 1996)

Life or Death? A Physiogenomic Approach to Understand Individual Variation in Responses to Hemorrhagic Shock

Severe hemorrhage due to trauma is a major cause of death throughout the world. It has often been observed that some victims are able to withstand hemorrhage better than others. For decades investigators have attempted to identify physiological mechanisms that distinguish survivors from nonsurvivors for the purpose of providing more informed therapies. As an alternative approach to address this issue, we have initiated a research program to identify genes and genetic mechanisms that contribute to this phenotype of survival time after controlled hemorrhage. From physiogenomic studies using inbred rat strains, we have demonstrated that this phenotype is a heritable quantitative trait, and is therefore a complex trait regulated by multiple genes. Our work continues to identify quantitative trait loci as well as potential epigenetic mechanisms that might influence survival time after severe hemorrhage. Our ultimate goal is to improve survival to traumatic hemorrhage and attendant shock via regulation of genetic mechanisms and to provide knowledge that will lead to genetically-informed personalized treatments

Robot-era project: Preliminary results on the system usability

The European project Robot-Era is an ambitious integrated project (FP7-ICT-2011.5.4), which objective is the development of advanced robotic services, integrated in intelligent environments, to provide independent living to older people. In order to guarantee the matching of the users� need and the demands, two loops of experimentation were conceived, in realistic and real setting. The aim of the paper is to described the methods applied and the main results coming from the first experimental loop, concerning the degree of usability of the interfaces and provide guidelines for testing socially assistive robots with older people. � Springer International Publishing Switzerland 2015

Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven®)

Background. A range of plasma volume expanders is used clinically, often in settings where haemostasis may already be impaired. The haemostatic agent, recombinant activated factor VII (rFVIIa, NovoSevenw), may be used to improve haemostasis but potential interactions with different volume expanders are poorly understood. Methods. Clot formation was measured by thromboelastography (TEG) using blood from healthy volunteers. In vitro effects of rFVIIa with haemodilution, acidosis, and hypothermia were examined. Conditions were induced by dilution with NaCl (0.9%), lactated Ringer’s solution, albumin 5%, or hydroxyethyl starch (HES) solutions [MW (molecular weight) 130–670 kDa]; by adjusting pH to 6.8 with 1 M HEPES (N-2-hydroxyethylpiperazine-N0-2-ethanesulphonic acid) buffer; or by reducing temperature to 328C. We also studied the effect of low vs high MW HES (MW 200 vs 600 kDa) and rFVIIa on in vivo bleeding time (BT) in rabbits. Results. Haemodilution progressively altered TEG parameters. rFVIIa improved TEG par-ameters in the presence of acidosis, hypothermia or 20 % haemodilution (P,0.05). At 40 % hae-modilution, the rFVIIa effect was diminished particularly with high MW HES. In vivo, rFVIIa shortened the BT (P,0.05) with low but not high MW HES. Conclusions. Efficacy of rFVIIa was affected by the degree of haemodilution and type of volume expander, but not by acidosis or hypothermia

Effects of intrauterine exposure to synthetic glucocorticoids on fetal, newborn, and infant hypothalamic-pituitary-adrenal axis function in humans : a systematic review

BACKGROUND: Synthetic glucocorticoids are commonly used in reproductive medicine. Fetal organ systems are highly sensitive to changes in the intrauterine environment, including overexposure to glucocorticoids. Structural and functional alterations resulting from such changes may persist throughout life and have been associated with diverse diseases. One system that could be particularly sensitive to fetal glucocorticoid overexposure is the hypothalamic-pituitary-adrenal (hpa) axis. Many human studies have investigated this possibility, but a systematic review to identify consistent, emergent findings is lacking. METHODS: We systematically review 49 human studies, assessing the effects of intrauterine exposure to synthetic glucocorticoids on fetal, neonate, and infant hpa function. RESULTS: Study quality varied considerably, but the main findings held true after restricting the analyses to higher-quality studies: intrauterine exposure to synthetic glucocorticoids reduces offspring hpa activity under unstimulated conditions after pain but not pharmacological challenge. Although reduced unstimulated hpa function appears to recover within the first 2 wk postpartum, blunted hpa reactivity to pain is likely to persist throughout the first 4 months of life. There is some evidence that the magnitude of the effects is correlated with the total amount of glucocorticoids administered and varies with the time interval between glucocorticoid exposure and hpa assessment. CONCLUSIONS: This systematic review has allowed the demonstration of the way in which intrauterine exposure to various regimens of synthetic glucocorticoids affects various forms of hpa function. As such, it guides future studies in terms of which variables need to be focused on in order to further strengthen the understanding of such therapy, whilst continuing to profit from its clinical benefits

Haemostatics in surgery and our experience in the enucleoresection of renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>30 patients, with T1 renal cell carcinomas (RCC) who underwent open enucleoresection of the tumour, were randomized to the use of a topical haemostatic agent (Floseal) or to an infrared-sapphire coagulator (ISC), to compare their efficacy in achieving haemostasis. Methods: Successful intra-operative haemostasis, intra- and post-operative bleeding, operative time, hospital discharge were evaluated.</p> <p>Results</p> <p>Statistically higher rates of successful haemostasis and shorter time-to-haemostasis (8,1 vs 12,9 min) were observed in the FloSeal group (p < 0.001 both). Patients operative time was not different between Group 1 vs 2 (58.7 ± 12 vs 62.4 ± 15; p > 0.05). The average blood loss during surgery was less (60 +/- 25.5 mL) for the FloSeal group than for the ISC group (85 +/- 40.5 mL) (p < 0.05). Postoperative blood loss was 25 +/- 5 mL and 40 +/- 45 mL for Floseal and ISC respectively, (p < 0.05). Length of the postoperative hospital discharge was 2.5 +/- 1.2 days for FloSeal group and 3.5 +/- 1.3 for the Group 2 (p < 0.05). No major immediate or delayed complications were observed in either Groups.</p> <p>Conclusions</p> <p>The use of Floseal and ISC offer a safe and efficacy haemostasis in the enucleoresection of RCC. Moreover, our results show a less intra-operative and post-operative blood loss as well as a shorter time to haemostasis of Floseal in respect to ISC.</p

Dehydrogenase and Oxoreductase Activities of Porcine Placental 11β-Hydroxysteroid Dehydrogenase

Dehydrogenase (cortisol to cortisone) and oxoreductase (cortisone to cortisol) activities of porcine placental 11β-hydroxysteroid dehydrogenase ( 11β-HSD) were measured in tissue fragment cultures on day 75 of gestation. Dehydrogenase activity was over fivefold greater than oxoreductase activity (p \u3c .001). There were positive linear associations (p \u3c .01) between net dehydrogenase activity (dehydrogenase minus oxoreductase) and fetal weight, fetal length, and placental weight. These data indicate a predominance of placental 11β-HSD dehydrogenase activity at this gestational stage that would insure a net conversion of cortisol to cortisone as it traverses the placenta. The data further suggest that 11β-HSD activities may provide an optimal glucocorticoid environment that is supportive of enhanced fetal and placental growth