Seasonal and spatial variations in the RNA:DNA ratio and its relation to growth in sub-Arctic scallops

We examined the RNA and DNA concentration of field-caught scallops Chlamys islandica, maintained in suspended cultures at 15 and 30 m depth, and scallops from a wild population at 50 to 60 m in Kobbefjord, southwest Greenland. General relations between RNA and DNA concentrations and individual shell height were established, and we found that the RNA:DNA ratio (RD) worked well as a standardisation of the RNA concentration independent of size and sex. During an experimental period of 14 mo, we observed a pronounced seasonal pattern in RD and mass growth, and differences between depths. Even though the period with high levels of RD reflected the growth season relatively well, RD was a poor predictor of individual mass growth rates of C. islandica. However, we found a non-linear response in RD to increased food concentrations resulting in RD being up- and down-regulated at the beginning and end of the productive summer season, respectively. These results indicate that short-term dynamics in the actual mass growth rate might be controlled through regulation of ribosome activity rather than ribosome number (RNA concentration). This adaption would allow scallops to up-regulate protein synthesis more rapidly, thereby ensuring efficient utilisation of the intense peaks in food availability in coastal areas in the Arctic. Therefore, we suggest that RD in C. islandica reflects the growth potential rather than the actual growth rate. Still, the amount of unexplained variance in RD is considerable and not independent over time, suggesting the existence of unresolved mechanisms or relationships

Characteristics of survivors: growth and nutritional condition of early stages of the hake species Merluccius paradoxus and M. capensis in the southern Benguela ecosystem

Larval mortality in marine fish is strongly linked to characteristic traits such as growth and condition, but the variability in these traits is poorly understood. We tried to identify the variability in growth in relation to conditions leading to greater survival chances for early stages of Cape hake, Merluccius paradoxus and M. capensis, in the Benguela upwelling ecosystem. During two cruises in 2007 and one cruise in 2008, hake larvae and juveniles were caught. Otolith microstructures revealed a larval age ranging from 2 to 29 days post-hatching (dph), whereas juvenile age was 67–152 dph. RNA:DNA ratios, used to evaluate nutritional condition, were above the relevant threshold level for growth. No strong coupling between growth and condition was detected, indicating a complex relationship between these factors in the southern Benguela ecosystem. Merluccius paradoxus juveniles caught in 2007 (the surviving larvae of 2006) had significantly higher larval growth rates than larvae hatched in 2007 and 2008, possibly indicating selection for fast growth in 2006. High selection pressure on growth could be linked to predation avoidance, including cannibalism

Divergent responses of Atlantic cod to ocean acidification and food limitation

In order to understand the effect of global change on marine fishes, it is imperative to quantify the effects on fundamental parameters such as survival and growth. Larval survival and recruitment of the Atlantic cod (Gadus morhua) were found to be heavily impaired by end-of-century levels of ocean acidification. Here, we analysed larval growth among 35–36 days old surviving larvae, along with organ development and ossification of the skeleton. We combined CO2treatments (ambient: 503 µatm, elevated: 1,179 µatm) with food availability in order to evaluate the effect of energy limitation in addition to the ocean acidification stressor. As expected, larval size (as a proxy for growth) and skeletogenesis were positively affected by high food availability. We found significant interactions between acidification and food availability. Larvae fed ad libitum showed little difference in growth and skeletogenesis due to the CO2 treatment. Larvae under energy limitation were significantly larger and had further developed skeletal structures in the elevated CO2 treatment compared to the ambient CO2 treatment. However, the elevated CO2 group revealed impairments in critically important organs, such as the liver, and had comparatively smaller functional gills indicating a mismatch between size and function. It is therefore likely that individual larvae that had survived acidification treatments will suffer from impairments later during ontogeny. Our study highlights important allocation trade-off between growth and organ development, which is critically important to interpret acidification effects on early life stages of fish

Angiopoietin-like protein 4 is an exercise-induced hepatokine in humans, regulated by glucagon and cAMP

Objective: Angiopoietin-like protein-4 (ANGPTL4) is a circulating protein that is highly expressed in liver and implicated in regulation of plasma triglyceride levels. Systemic ANGPTL4 increases during prolonged fasting and is suggested to be secreted from skeletal muscle following exercise. Methods: We investigated the origin of exercise-induced ANGPTL4 in humans by measuring the arterial-to-venous difference over the leg and the hepato-splanchnic bed during an acute bout of exercise. Furthermore, the impact of the glucagon-to-insulin ratio on plasma ANGPTL4 was studied in healthy individuals. The regulation of ANGPTL4 was investigated in both hepatic and muscle cells. Results: The hepato-splanchnic bed, but not the leg, contributed to exercise-induced plasma ANGPTL4. Further studies using hormone infusions revealed that the glucagon-to-insulin ratio is an important regulator of plasma ANGPTL4 as elevated glucagon in the absence of elevated insulin increased plasma ANGPTL4 in resting subjects, whereas infusion of somatostatin during exercise blunted the increase of both glucagon and ANGPTL4. Moreover, activation of the cAMP/PKA signaling cascade let to an increase in ANGPTL4 mRNA levels in hepatic cells, which was prevented by inhibition of PKA. In humans, muscle ANGPTL4 mRNA increased during fasting, with only a marginal further induction by exercise. In human muscle cells, no inhibitory effect of AMPK activation could be demonstrated on ANGPTL4 expression. Conclusions: The data suggest that exercise-induced ANGPTL4 is secreted from the liver and driven by a glucagon-cAMP-PKA pathway in humans. These findings link the liver, insulin/glucagon, and lipid metabolism together, which could implicate a role of ANGPTL4 in metabolic diseases

The effect of food availability, age or size on the RNA/DNA ratio of individually measured herring larvae: laboratory calibration

RNA/DNA ratios in individual herring (Clupea harengus) larvae (collected from Kiel Bay, Baltic Sea, in 1989) were measured and proved suitable for determining nutritional status. Significant differences between fed and starving larvae appeared after 3 to 4 d of food deprivation in larvae older than 10 d after hatching. The RNA/DNA ratio showed an increase with age or length of the larvae and was less pronounced in starving larvae compared to fed larvae. The individual variability of RNA/DNA ratios in relation to larval length of fed larvae and of larvae deprived of food for intervals of 6 to 9 d is presented. Based on the length dependency and the individual variability found within the RNA/DNA ratios, a laboratory calibration is given to determine whether a larva caught in the field has been starving or not. An example for a field application is shown

Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh-HGF) in patients with fulminant hepatitis: a phase I/II clinical trial, following preclinical studies to ensure safety

<p>Abstract</p> <p>Background</p> <p>Hepatocyte growth factor (HGF) stimulates hepatocyte proliferation, and also acts as an anti-apoptotic factor. Therefore, HGF is a potential therapeutic agent for treatment of fatal liver diseases. We performed a translational medicine protocol with recombinant human HGF (rh-HGF), including a phase I/II study of patients with fulminant hepatitis (FH) or late-onset hepatic failure (LOHF), in order to examine the safety, pharmacokinetics, and clinical efficacy of this molecule.</p> <p>Methods</p> <p>Potential adverse effects identified through preclinical safety tests with rh-HGF include a decrease in blood pressure (BP) and an increase in urinary excretion of albumin. Therefore, we further investigated the effect of rh-HGF on circulatory status and renal toxicity in preclinical animal studies. In a clinical trial, 20 patients with FH or LOHF were evaluated for participation in this clinical trial, and four patients were enrolled. Subjects received rh-HGF (0.6 mg/m²/day) intravenously for 12 to 14 days.</p> <p>Results</p> <p>We established an infusion method to avoid rapid BP reduction in miniature swine, and confirmed reversibility of renal toxicity in rats. Although administration of rh-HGF moderately decreased BP in the participating subjects, this BP reduction did not require cessation of rh-HGF or any vasopressor therapy; BP returned to resting levels after the completion of rh-HGF infusion. Repeated doses of rh-HGF did not induce renal toxicity, and severe adverse events were not observed. Two patients survived, however, there was no evidence that rh-HGF was effective for the treatment of FH or LOHF.</p> <p>Conclusions</p> <p>Intravenous rh-HGF at a dose of 0.6 mg/m²was well tolerated in patients with FH or LOHF; therefore, it is desirable to conduct further investigations to determine the efficacy of rh-HGF at an increased dose.</p

GDF15 is an exercise-induced hepatokine regulated by glucagon and insulin in humans

ObjectiveGrowth differentiation factor (GDF)-15 is implicated in regulation of metabolism and circulating GDF15 increases in response to exercise. The source and regulation of the exercise-induced increase in GDF15 is, however not known.MethodPlasma GDF15 was measured by ELISA under the following conditions: 1) Arterial-to-hepatic venous differences sampled before, during, and after exercise in healthy male subjects (n=10); 2) exogenous glucagon infusion compared to saline infusion in resting healthy subjects (n=10); 3) an acute exercise bout with and without a pancreatic clamp (n=6); 4) healthy subjects for 36 hours (n=17), and 5) patients with anorexia nervosa (n=25) were compared to healthy age-matched subjects (n=25). Tissue GDF15 mRNA content was determined in mice in response to exhaustive exercise (n=16).ResultsThe splanchnic bed released GDF15 to the circulation during exercise and increasing the glucagon-to-insulin ratio in resting humans led to a 2.7-fold (P&lt;0.05) increase in circulating GDF15. Conversely, inhibiting the exercise-induced increase in the glucagon-to-insulin ratio blunted the exercise-induced increase in circulating GDF15. Fasting for 36 hours did not affect circulating GDF15, whereas resting patients with anorexia nervosa displayed elevated plasma concentrations (1.4-fold, P&lt;0.05) compared to controls. In mice, exercise increased GDF15 mRNA contents in liver, muscle, and adipose tissue.ConclusionIn humans, GDF15 is a “hepatokine” which increases during exercise and is at least in part regulated by the glucagon-to-insulin ratio. Moreover, chronic energy deprivation is associated with elevated plasma GDF15, which supports that GDF15 is implicated in metabolic signalling in humans

Treatment of hepatic encephalopathy by on-line hemodiafiltration: a case series study

<p>Abstract</p> <p>Background</p> <p>It is thought that a good survival rate of patients with acute liver failure can be achieved by establishing an artificial liver support system that reliably compensates liver function until the liver regenerates or a patient undergoes transplantation. We introduced a new artificial liver support system, on-line hemodiafiltration, in patients with acute liver failure.</p> <p>Methods</p> <p>This case series study was conducted from May 2001 to October 2008 at the medical intensive care unit of a tertiary care academic medical center. Seventeen consecutive patients who admitted to our hospital presenting with acute liver failure were treated with artificial liver support including daily on-line hemodiafiltration and plasma exchange.</p> <p>Results</p> <p>After 4.9 ± 0.7 (mean ± SD) on-line hemodiafiltration sessions, 16 of 17 (94.1%) patients completely recovered from hepatic encephalopathy and maintained consciousness for 16.4 ± 3.4 (7-55) days until discontinuation of artificial liver support (a total of 14.4 ± 2.6 [6-47] on-line hemodiafiltration sessions). Significant correlation was observed between the degree of encephalopathy and number of sessions of on-line HDF required for recovery of consciousness. Of the 16 patients who recovered consciousness, 7 fully recovered and returned to society with no cognitive sequelae, 3 died of complications of acute liver failure except brain edema, and the remaining 6 were candidates for liver transplantation; 2 of them received living-related liver transplantation but 4 died without transplantation after discontinuation of therapy.</p> <p>Conclusions</p> <p>On-line hemodiafiltration was effective in patients with acute liver failure, and consciousness was maintained for the duration of artificial liver support, even in those in whom it was considered that hepatic function was completely abolished.</p