Ethyl pyruvate reduces liver injury at early phase but impairs regeneration at late phase in acetaminophen overdose

Introduction: Inflammation may critically affect mechanisms of liver injury in acetaminophen (APAP) hepatotoxicity. Kupffer cells (KC) play important roles in inflammation, and KC depletion confers protection at early time points after APAP treatment but can lead to more severe injury at a later time point. It is possible that some inflammatory factors might contribute to liver damage at an early injurious phase but facilitate liver regeneration at a late time point. Therefore, we tested this hypothesis by using ethyl pyruvate (EP), an anti-inflammatory agent, to treat APAP overdose for 24-48 hours.Methods: C57BL/6 male mice were intraperitoneally injected with a single dose of APAP (350 mg/kg dissolved in 1 mL sterile saline). Following 2 hours of APAP challenge, the mice were given 0.5 mL EP (40 mg/kg) or saline treatment every 8 hours for a total of 24 or 48 hours.Results: Twenty-four hours after APAP challenge, compared to the saline-treated group, EP treatment significantly lowered serum transaminases (ALT/AST) and reduced liver injury seen in histopathology; however, at the 48-hour time point, compared to the saline therapy, EP therapy impaired hepatocyte regeneration and increased serum AST; this late detrimental effect was associated with reduced serum TNF-α concentration and decreased expression of cell cycle protein cyclin D1, two important factors in liver regeneration.Conclusions: Inflammation likely contributes to liver damage at an early injurious phase but improves hepatocyte regeneration at a late time point, and prolonged anti-inflammation therapy at a late phase is not beneficial. © 2012 Yang et al.; licensee BioMed Central Ltd

The diurnal time course of net photosynthesis of soybean leaves: Analysis with a physiologically based steady-state photosynthesis model

A physiologically based steady-state model of whole leaf photosynthesis (WHOLEPHOT) is used to analyze observed net photosynthesis daily time courses of soybean, Glycine max (L.) Merr., leaves. Observations during two time periods of the 1978 growing season are analyzed and compared. After adjustment of the model for soybean, net photosynthesis rates are calculated with the model in response to measured incident light intensity, leaf temperature, air carbon dioxide concentration, and leaf diffusion resistance. The steady-state calculations closely approximate observed net photosynthesis. Results of the comparison reveal a decrease in photosynthetic capacity in leaves sampled during the second time period, which is associated with decreasing ability of leaves to respond to light intensity and internal air space carbon dioxide concentration, increasing mesophyll resistance, and increasing stomatal resistance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47732/1/442_2004_Article_BF00346258.pd

Using the SWAT model to improve process descriptions and define hydrologic partitioning in South Korea

Watershed-scale modeling can be a valuable tool to aid in quantification of water quality and yield; however, several challenges remain. In many watersheds, it is difficult to adequately quantify hydrologic partitioning. Data scarcity is prevalent, accuracy of spatially distributed meteorology is difficult to quantify, forest encroachment and land use issues are common, and surface water and groundwater abstractions substantially modify watershed-based processes. Our objective is to assess the capability of the Soil and Water Assessment Tool (SWAT) model to capture event-based and long-term monsoonal rainfall–runoff processes in complex mountainous terrain. To accomplish this, we developed a unique quality-control, gap-filling algorithm for interpolation of high-frequency meteorological data. We used a novel multi-location, multi-optimization calibration technique to improve estimations of catchment-wide hydrologic partitioning. The interdisciplinary model was calibrated to a unique combination of statistical, hydrologic, and plant growth metrics. Our results indicate scale-dependent sensitivity of hydrologic partitioning and substantial influence of engineered features. The addition of hydrologic and plant growth objective functions identified the importance of culverts in catchment-wide flow distribution. While this study shows the challenges of applying the SWAT model to complex terrain and extreme environments; by incorporating anthropogenic features into modeling scenarios, we can enhance our understanding of the hydroecological impact

Analyzing the causes and spatial pattern of the European 2003 carbon flux anomaly using seven models

Globally, the year 2003 is associated with one of the largest atmospheric CO<sub>2</sub> rises on record. In the same year, Europe experienced an anomalously strong flux of CO<sub>2</sub> from the land to the atmosphere associated with an exceptionally dry and hot summer in Western and Central Europe. In this study we analyze the magnitude of this carbon flux anomaly and key driving ecosystem processes using simulations of seven terrestrial ecosystem models of different complexity and types (process-oriented and diagnostic). We address the following questions: (1) how large were deviations in the net European carbon flux in 2003 relative to a short-term baseline (1998–2002) and to longer-term variations in annual fluxes (1980 to 2005), (2) which European regions exhibited the largest changes in carbon fluxes during the growing season 2003, and (3) which ecosystem processes controlled the carbon balance anomaly . <br><br> In most models the prominence of 2003 anomaly in carbon fluxes declined with lengthening of the reference period from one year to 16 years. The 2003 anomaly for annual net carbon fluxes ranged between 0.35 and –0.63 Pg C for a reference period of one year and between 0.17 and –0.37 Pg C for a reference period of 16 years for the whole Europe. <br><br> In Western and Central Europe, the anomaly in simulated net ecosystem productivity (NEP) over the growing season in 2003 was outside the 1σ variance bound of the carbon flux anomalies for 1980–2005 in all models. The estimated anomaly in net carbon flux ranged between –42 and –158 Tg C for Western Europe and between 24 and –129 Tg C for Central Europe depending on the model used. All models responded to a dipole pattern of the climate anomaly in 2003. In Western and Central Europe NEP was reduced due to heat and drought. In contrast, lower than normal temperatures and higher air humidity decreased NEP over Northeastern Europe. While models agree on the sign of changes in simulated NEP and gross primary productivity in 2003 over Western and Central Europe, models diverge in the estimates of anomalies in ecosystem respiration. Except for two process models which simulate respiration increase, most models simulated a decrease in ecosystem respiration in 2003. The diagnostic models showed a weaker decrease in ecosystem respiration than the process-oriented models. Based on the multi-model simulations we estimated the total carbon flux anomaly over the 2003 growing season in Europe to range between –0.02 and –0.27 Pg C relative to the net carbon flux in 1998–2002

Analyzing the causes and spatial pattern of the European 2003 carbon flux anomaly in Europe using seven models

International audienceGlobally, the year 2003 is associated with one of the largest atmospheric CO2 rises on record. In the same year, Europe experienced an anomalously strong flux of CO2 from the land to the atmosphere associated with an exceptionally dry and hot summer in Western and Central Europe. In this study we analyze the magnitude of this carbon flux anomaly and key driving ecosystem processes using simulations of seven terrestrial ecosystem models of different complexity and types (process-oriented and diagnostic). We address the following questions: (1) how large were deviations in the net European carbon flux in 2003 relative to a short-term baseline (1998–2002) and to longer-term variations in annual fluxes (1980 to 2005), (2) which regions exhibited the largest shift in carbon fluxes during the growing season 2003, and (3) which processes controlled the carbon balance anomaly . In Western and Central Europe, the anomaly in net ecosystem productivity (NEP) over growing season 2003 was outside the 1s bound of the carbon flux anomalies for 1980–2005. The estimated growing season anomaly ranged between –29 and –196 Tg C for Western Europe and between 13 and –94 Tg C for Central Europe depending on the model used. All models responded to a dipole pattern of the climate anomaly in 2003. In Western and Central Europe NEP was reduced due to heat and drought. Over Western Russia NEP was decreased in response to lower than normal temperatures and high precipitation. While models agree on changes in simulated NEP and gross primary productivity anomalies in 2003 over Western and Central Europe, models diverge in the estimates of anomalies in ecosystem respiration. Except for two process models which simulate respiration increase, most models simulated a decrease in ecosystem respiration in 2003. The diagnostic models showed a weaker decrease in ecosystem respiration than the process-oriented models. Based on the multi-model simulations we estimated the total carbon flux anomaly over the 2003 growing season in Europe to range between –0.02 and –0.27 Pg C relative to the net flux in 1998–2002

Socially optimal contribution rate and cap in a proportional (DC) pension system

In our model, the government operates a mandatory proportional (DC) pension system to substitute for the low life-cycle savings of the lower-paid myopic workers, while maintaining the incentives of the higher-paid far-sighted ones in contributing to the system. The introduction of an appropriate cap on pension contribution (or its base)—excluding the earnings above the cap from the contribution base—raises the optimal contribution rate, helping more the lower-paid myopic workers and reserving enough room for the saving of higher-paid far-sighted ones. The social welfare is almost independent of the cap in a relatively wide interval but the maximal welfare is higher than the capless welfare by 0.3–4.5 %.info:eu-repo/semantics/publishedVersio

Analyzing the causes and spatial pattern of the European 2003 carbon flux anomaly using seven models

Globally, the year 2003 is associated with one of the largest atmospheric CO2 rises on record. In the same year, Europe experienced an anomalously strong flux of CO2 from the land to the atmosphere associated with an exceptionally dry and hot summer in Western and Central Europe. In this study we analyze the magnitude of this carbon flux anomaly and key driving ecosystem processes using simulations of seven terrestrial ecosystem models of different complexity and types (process-oriented and diagnostic). We address the following questions: (1) how large were deviations in the net European carbon flux in 2003 relative to a short-term baseline (1998–2002) and to longer-term variations in annual fluxes (1980 to 2005), (2) which European regions exhibited the largest changes in carbon fluxes during the growing season 2003, and (3) which ecosystem processes controlled the carbon balance anomaly . In most models the prominence of 2003 anomaly in carbon fluxes declined with lengthening of the reference period from one year to 16 years. The 2003 anomaly for annual net carbon fluxes ranged between 0.35 and –0.63 Pg C for a reference period of one year and between 0.17 and –0.37 Pg C for a reference period of 16 years for the whole Europe. In Western and Central Europe, the anomaly in simulated net ecosystem productivity (NEP) over the growing season in 2003 was outside the 1σ variance bound of the carbon flux anomalies for 1980–2005 in all models. The estimated anomaly in net carbon flux ranged between –42 and –158 Tg C for Western Europe and between 24 and –129 Tg C for Central Europe depending on the model used. All models responded to a dipole pattern of the climate anomaly in 2003. In Western and Central Europe NEP was reduced due to heat and drought. In contrast, lower than normal temperatures and higher air humidity decreased NEP over Northeastern Europe. While models agree on the sign of changes in simulated NEP and gross primary productivity in 2003 over Western and Central Europe, models diverge in the estimates of anomalies in ecosystem respiration. Except for two process models which simulate respiration increase, most models simulated a decrease in ecosystem respiration in 2003. The diagnostic models showed a weaker decrease in ecosystem respiration than the process-oriented models. Based on the multi-model simulations we estimated the total carbon flux anomaly over the 2003 growing season in Europe to range between –0.02 and –0.27 Pg C relative to the net carbon flux in 1998–2002

Inhibition of platelet aggregation by carbon monoxide-releasing molecules (CO-RMs): comparison with NO donors

Carbon monoxide (CO) and CO-releasing molecules (CO-RMs) inhibit platelet aggregation in vitro. Herein, we compare the anti-platelet action of CORM-3, which releases CO rapidly (t½ 1 min), and CORM-A1, which slowly releases CO (t½ = 21 min). The anti-platelet effects of NO donors with various kinetics of NO release were studied for comparison. The effects of CO-RMs and NO donors were analyzed in washed human platelets (WP), platelets rich plasma (PRP), or whole blood (WB) using aggregometry technique. CORM-3 and CORM-A1 inhibited platelet aggregation in human PRP, WP, or WB, in a concentration-dependent manner. In all three preparations, CORM-A1 was more potent than CORM-3. Inhibition of platelets aggregation by CORM-A1 was not significantly affected by a guanylate cyclase inhibitor (ODQ) and a phosphodiesterase-5 inhibitor, sildenafil. In contrast, inhibition of platelet aggregation by NO donors was more potent with a fast NO releaser (DEA-NO, t½ = 2 min) than slow NO releasers such as PAPA-NO (t½ = 15 min) or other slow NO donors. Predictably, the anti-platelet effect of DEA-NO and other NO donors was reversed by ODQ while potentiated by sildenafil. In contrast to NO donors which inhibit platelets proportionally to the kinetics of NO released via activation of soluble guanylate cyclase (sGC), the slow CO-releaser CORM-A1 is a superior anti-platelet agent as compared to CORM-3 which releases CO instantly. The anti-platelet action of CO-RMs does not involve sGC activation. Importantly, CORM-A1 or its derivatives representing the class of slow CO releasers display promising pharmacological profile as anti-platelet agents

Liver Transplantation because of Acute Liver Failure due to Heme Arginate Overdose in a Patient with Acute Intermittent Porphyria

In acute attacks of acute intermittent porphyria, the mainstay of treatment is glucose and heme arginate administration. We present the case of a 58-year-old patient with acute liver failure requiring urgent liver transplantation after erroneous 6-fold overdose of heme arginate during an acute attack. As recommended in the product information, albumin and charcoal were administered and hemodiafiltration was started, which could not prevent acute liver failure, requiring super-urgent liver transplantation after 6 days. The explanted liver showed no preexisting liver cirrhosis, but signs of subacute liver injury and starting regeneration. The patient recovered within a short time. A literature review revealed four poorly documented cases of potential hepatic and/or renal toxicity of hematin or heme arginate. This is the first published case report of acute liver failure requiring super-urgent liver transplantation after accidental heme arginate overdose. The literature and recommendations in case of heme arginate overdose are summarized. Knowledge of a potentially fatal course is important for the management of future cases. If acute liver failure in case of heme arginate overdose is progressive, super-urgent liver transplantation has to be evaluated