The journal of trauma and acute care surgery, Dec 1, 2018
BACKGROUND: It has been established that glucagon-like peptide 1 (GLP 1) inhibits pancreatic β-ce... more BACKGROUND: It has been established that glucagon-like peptide 1 (GLP 1) inhibits pancreatic β-cell apoptosis, increases insulin secretion, and improves glucose tolerance in scald injury. However, the effects of Exendin-4, a long-acting incretin similar to GLP 1, remained unclear in severe scald injury. Hence, this study attempted to investigate whether Exendin-4 had similar effects by protecting the histology of pancreas in severely scalded rats. METHODS: One hundred sixty-two adult Wistar rats were equally randomized to sham burn group, burn group and burn with Exendin-4 treatment group. Rats were subjected to full skin thickness scald injuries (total body surface area: 50%) and were injected subcutaneously with Exendin-4 (4 μg/kg) twice daily. The histological changes of islets, the apoptosis of β cells, the amount of glucagon and insulin, and the concentration of plasma glucagon and insulin were observed; and the intraperitoneal glucose tolerance test was performed as well. RESULTS: The islets and β cells were injured and the number of secretory granules decreased in the scalded rats, but less histopathological changes were seen in the rats treated with Exendin-4. The apoptosis index of treated rats was significantly lower than that of the scalded rats (p < 0.05). There was significant difference in β-cell density postinjury between the two groups (p < 0.05). More insulin and less glucagon in islets and plasma were found in the treated rats (p < 0.05), suggesting improved intraperitoneal glucose tolerance (p < 0.05) and fasting blood glucose (p < 0.05) in this group. CONCLUSION: Based on our previous finding that GLP-1 could control hyperglycemia by increasing insulin secretion and inhibiting β-cell apoptosis in severe scald injuries, this study further confirmed that Exendin-4 could increase glycemic control following severe scald by preserving the histology of β cells in pancreatic islets and inhibiting their apoptosis.
Centre for Nutritional and Physical Exercise Metabolism Department of Public Health UNESP-Sao Pau... more Centre for Nutritional and Physical Exercise Metabolism Department of Public Health UNESP-Sao Paulo State University
American Journal of Physiology-endocrinology and Metabolism, Sep 1, 1989
Estimates of substrate oxidation obtained from appearance of 13C or 14C from tracers in breath mu... more Estimates of substrate oxidation obtained from appearance of 13C or 14C from tracers in breath must be corrected for retention of labeled carbon in the body. We aimed to determine the effect of a defined experimental diet and metabolic status on recovery of infused Na [13C]bicarbonate in breath. Six healthy male subjects consumed an experimental diet for 7 days before receiving a continuous infusion of formula without tracer on day 8 and received either an intragastric (ig) or intravenous (iv) infusion of Na [13C]bicarbonate on day 9 or 11 during a 4-h postabsorptive (PA), 4-h continuously fed period. A trend toward increasing PA breath enrichment during the first 7 diet days approached statistical significance (P = 0.051), whereas breath enrichments measured 3 h postbreakfast were consistently higher than PA values throughout and did not change over the 7-day period. Breath enrichments during a 4-h continuous ig infusion of formula without tracer on day 8 rose 2.0 +/- 0.5 atom percent excess (APE).10(-3) above base line (P less than 0.001, ANOVA). In the tracer studies, breath enrichments were similar for the ig and iv routes of tracer infusion. For the ig infusion the fraction of infused Na [13C]bicarbonate recovered in breath as 13CO2 was 0.74 +/- 0.02 for the PA period and 0.79 +/- 0.02 for the fed period. For the iv infusion the fraction recovered was 0.70 +/- 0.04 for the PA period and 0.82 +/- 0.03 for the fed period. Fractional recoveries were not significantly different for ig and iv routes of administration but were different for PA and fed periods (P less than 0.0001, 2-way ANOVA). The fractional recoveries for the fed period obtained here were similar to the value 0.81 reported in a number of other studies. Recovery of tracer in breath increased linearly with O2 uptake and CO2 production, suggesting that factors affecting respiratory gas exchange may alter recovery. We conclude that the primary factor determining label recovery is the immediate and recent nutritional status of the host.
Available tools in liver surgery planning rely on the future remnant liver (FRL) volume. Inapprop... more Available tools in liver surgery planning rely on the future remnant liver (FRL) volume. Inappropriate decision might be made since the same FRL volume might represent different liver functions depending on the severity of underlying liver damage. This study developed an alternative system to estimate FRL function and to predict the risk of postoperative liver failure. Current study recruited 71 prehepatectomy patients and 71 healthy volunteers. A technetium-99-labelled asialoglycoproteins was given to participants and SPECT was used to capture the intensity of the signal, represented by uptake index (UI). The agreement between preoperative UI values, liver function tests, and Child scores were evaluated. Linear regression was used to evaluate the agreement between predicted UI for FRL and postoperative UI values. Area under the receiver operating characteristic (AUC) curve was used to evaluate the discriminative performance of UI in differentiating patient with high risk of liver failure. Preoperative UIs are highly correlated with Child score (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), especially to identify patients with ascites and elevated bilirubin. The predicted UIs were in close agreement with the actual postoperative UI values (r = 0.95 P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The AUC analysis indicated that UI values had a high accuracy in predicting the risk of liver failure (AUC = 0.95,…
American Journal of Physiology-endocrinology and Metabolism, Dec 1, 1996
The quantitative roles of the splanchnic region and the kidneys in whole body (WB) arginine and c... more The quantitative roles of the splanchnic region and the kidneys in whole body (WB) arginine and citrulline metabolism were assessed in postabsorptive mongrel dogs with primed constant intravenous infusions of [15N2-guanidino, 5,5-2H2]arginine and [13C-ureido]citrulline or [13C-guanidino]arginine and [15N]urea tracers. Isotope and metabolite concentration balances of arginine and citrulline were measured across the gut, liver, splanchnic region, and kidneys, together with WB arginine and citrulline fluxes and urea production rate. The WB citrulline flux and rate of citrulline to arginine (C-A) conversion were 16 and 9.4 mumol.kg-1.h-1, respectively. Concentration balance of citrulline across kidneys was +8.2 mumol.kg-1.h-1, and metabolism of citrulline by kidneys was 8.7 mumol.kg-1.h-1, which was derived about equally from intestine and liver. The appearance rate of citrulline-derived arginine in renal vein was 6.8 mumol.kg-1.h-1. These three separate estimates of C-A conversion within the kidneys were in good agreement, indicating 40% of blood C-A conversion occurring outside kidneys. These findings of interorgan metabolism are discussed in reference to the current knowledge derived largely from studies in laboratory rodents.
SUMMARY This chapter briefly introduces basic biochemistry of protein and amino acids (AAs) and t... more SUMMARY This chapter briefly introduces basic biochemistry of protein and amino acids (AAs) and their chemical structures, followed by the discussion on the dynamic process of protein and amino digestion, absorption, and their turnover in whole body and specific tissues in vivo as the biochemical and physiological basis in assessing protein requirements. The latter part of the chapter provided an in-depth discussion of the latest knowledge of the indicators used to assess protein requirements and AA requirements. The chapter finishes with a discussion of the current recommended intakes for protein and AAs, along with aspects of their use in nutritional assessment and issues in developing recommendations of protein/AAs for health maintenance throughout the life cycle.
Organismal evolution led to innovations in metabolic pathways, many of which certainly modified t... more Organismal evolution led to innovations in metabolic pathways, many of which certainly modified the surface chemistry of the Earth. Volcanic activity introduced inorganic compounds (H 2 , CO 2 , CH 4 , SO 2 , and H 2 S) driving the metabolism of early organisms of the domains archaea and bacteria. In the absence of light, H 2 S and Fe 2+ would have been the major electron donors and the electron acceptors could be either oxidized species such as the sulfurs, sulfate, and elemental sulfur, or carbon dioxide by the fermentation of acetate (forming methane). Elemental sulfur was produced by the reaction between H 2 S and SO 2 , while anoxygenic photosynthesis may have provided the sulfate which removed oceanic ferrous iron by its precipitation as sulfide into sediments. Hence, the sulfur cycle participation in life evolution comes from ancient anoxygenic elemental sulfur reduction generating environmental sulfide incorporated as mitochondrial Fe-S for the electrontransport chains. Anoxygenic photosynthesis may have provided the necessary sulfate to promote the evolution of sulfate-reducing bacteria. The evolution of oxygenic photosynthesis provided for diverse metabolic possibilities including non-photosynthetic sulfide oxidation, nitrification, and methanotrophy. An increase in oxygen levels would account for oxidative sulfur cycle, evolution of colorless sulfur bacteria, and emergence of large multicellular animals. Oxygen, initially a waste product of photosynthesis, first reacted with sulfur, iron or methane and latter accumulated in atmosphere resulting in more carbon production. Oxygenic photosynthesis becomes a positive feedback on the oxidation of the Earth-surface environment causing the growth and stabilization of continental platforms and carbon burial with more atmosphere oxidation. An increase in oxygen levels would account for oxidative sulfur cycle, evolution of colorless sulfur bacteria, and emergence of large multicellular animals. Oxygen enabled more efficient energy transformation from dietary food to ATP. However, evolution for mammals living on dry land has been closely linked to the adaptation of changes in O 2 concentration in the environment, which means mitochondrial aerobic respiration. By using ancestral geochemistry of iron-sulfur clusters at the protein complexes I and II, the respiratory chains become
Burn-induced insulin resistance is associated with increased morbidity and mortality; however, th... more Burn-induced insulin resistance is associated with increased morbidity and mortality; however, the impact of burn injury on tissue-specific insulin sensitivity and its molecular mechanisms with consideration of insulin state remains unknown in rodent models. This study was designed to characterize a burn mouse model with tissue-specific insulin resistance under insulin clamp conditions. C57BL6/J mice were subjected to 30% full-thickness burn injury and underwent the combination of hyperinsulinemic isoglycemicclamp (HIC) and positron emission tomography (PET). Hepatic glucose production (HGP) and peripheral glucose disappearance rate (Rd) were measured at different time points up to 7 days post injury. Burned mice showed a significant fasting hypoglycemia and hypoinsulinemia (P < 0.01) on post-burn day (PBD) 3 and 7 along with significantly higher energy expenditure (P < 0.01). HICon PBD 3 demonstrated that burn injury induced systemic insulin resistance, resulting from a significant decrease in insulin-stimulated Rd (33.0 ± 10.2 vs 68.3 ± 5.9 mg/kg/min; P < 0.05). In contrast, HGP of burned and sham mice was comparable both in the basal and clamp period. PET on PBD 3 showed a lower insulin-stimulated 18F-labeled 2-fluoro-2-deoxy-D-glucose uptake in the quadriceps of burned mice compared with sham-burned mice. Gastrocnemius muscle harvested from burned mice on PBD 3
Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) qS=1, 81% qS=2, 92% qS=3, p<0.001) or deve... more Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) qS=1, 81% qS=2, 92% qS=3, p<0.001) or developed a complication (11% of admissions with a complication had qS=0, 26% qS=1, 52% qS=2, 62% qS=3, p<0.001). Patients with higher qS were more severely injured as measured by median Injury Severity Scores (qS=0 had median ISS 9 [IQR 5–13]; qS=1, ISS 13 [9–24]; qS=2, ISS 27 [16–41]; qS=3, ISS 35 [22–45]). On multivariate analysis, qS was an independent predictor of mortality (qS=1 OR 5.2 [IQR 3.8–7.1], qS=2 OR 15.1 [IQR 9.7–23.7], qS=3 OR 16.2 [IQR 4.0–65.4], each p<0.001). Conclusions: Calculation of the qS following blunt trauma could be used a quick and simple method, without imaging or surgery, to predict risk of death and other adverse outcomes and thereby prioritize resource allocation.
Burn injury mediated hypermetabolic syndrome leads to increased mortality among severe burn victi... more Burn injury mediated hypermetabolic syndrome leads to increased mortality among severe burn victims, due to liver failure and muscle wasting. Metabolic changes may persist up to 2 years following the injury. Thus, understanding the underlying mechanisms of the pathology is crucially important to develop appropriate therapeutic approaches. We present detailed metabolomic and lipidomic analyses of the liver and muscle tissues in a rat model with a 30% body surface area burn injury located at the dorsal skin. Three hundred and thirty-eight of 1587 detected metabolites and lipids in the liver and 119 of 1504 in the muscle tissue exhibited statistically significant alterations. We observed excessive accumulation of triacylglycerols, decreased levels of S-adenosylmethionine, increased levels of glutamine and xenobiotics in the liver tissue. Additionally, the levels of gluconeogenesis, glycolysis, and tricarboxylic acid cycle metabolites are generally decreased in the liver. On the other h...
The journal of trauma and acute care surgery, Dec 1, 2018
BACKGROUND: It has been established that glucagon-like peptide 1 (GLP 1) inhibits pancreatic β-ce... more BACKGROUND: It has been established that glucagon-like peptide 1 (GLP 1) inhibits pancreatic β-cell apoptosis, increases insulin secretion, and improves glucose tolerance in scald injury. However, the effects of Exendin-4, a long-acting incretin similar to GLP 1, remained unclear in severe scald injury. Hence, this study attempted to investigate whether Exendin-4 had similar effects by protecting the histology of pancreas in severely scalded rats. METHODS: One hundred sixty-two adult Wistar rats were equally randomized to sham burn group, burn group and burn with Exendin-4 treatment group. Rats were subjected to full skin thickness scald injuries (total body surface area: 50%) and were injected subcutaneously with Exendin-4 (4 μg/kg) twice daily. The histological changes of islets, the apoptosis of β cells, the amount of glucagon and insulin, and the concentration of plasma glucagon and insulin were observed; and the intraperitoneal glucose tolerance test was performed as well. RESULTS: The islets and β cells were injured and the number of secretory granules decreased in the scalded rats, but less histopathological changes were seen in the rats treated with Exendin-4. The apoptosis index of treated rats was significantly lower than that of the scalded rats (p < 0.05). There was significant difference in β-cell density postinjury between the two groups (p < 0.05). More insulin and less glucagon in islets and plasma were found in the treated rats (p < 0.05), suggesting improved intraperitoneal glucose tolerance (p < 0.05) and fasting blood glucose (p < 0.05) in this group. CONCLUSION: Based on our previous finding that GLP-1 could control hyperglycemia by increasing insulin secretion and inhibiting β-cell apoptosis in severe scald injuries, this study further confirmed that Exendin-4 could increase glycemic control following severe scald by preserving the histology of β cells in pancreatic islets and inhibiting their apoptosis.
Centre for Nutritional and Physical Exercise Metabolism Department of Public Health UNESP-Sao Pau... more Centre for Nutritional and Physical Exercise Metabolism Department of Public Health UNESP-Sao Paulo State University
American Journal of Physiology-endocrinology and Metabolism, Sep 1, 1989
Estimates of substrate oxidation obtained from appearance of 13C or 14C from tracers in breath mu... more Estimates of substrate oxidation obtained from appearance of 13C or 14C from tracers in breath must be corrected for retention of labeled carbon in the body. We aimed to determine the effect of a defined experimental diet and metabolic status on recovery of infused Na [13C]bicarbonate in breath. Six healthy male subjects consumed an experimental diet for 7 days before receiving a continuous infusion of formula without tracer on day 8 and received either an intragastric (ig) or intravenous (iv) infusion of Na [13C]bicarbonate on day 9 or 11 during a 4-h postabsorptive (PA), 4-h continuously fed period. A trend toward increasing PA breath enrichment during the first 7 diet days approached statistical significance (P = 0.051), whereas breath enrichments measured 3 h postbreakfast were consistently higher than PA values throughout and did not change over the 7-day period. Breath enrichments during a 4-h continuous ig infusion of formula without tracer on day 8 rose 2.0 +/- 0.5 atom percent excess (APE).10(-3) above base line (P less than 0.001, ANOVA). In the tracer studies, breath enrichments were similar for the ig and iv routes of tracer infusion. For the ig infusion the fraction of infused Na [13C]bicarbonate recovered in breath as 13CO2 was 0.74 +/- 0.02 for the PA period and 0.79 +/- 0.02 for the fed period. For the iv infusion the fraction recovered was 0.70 +/- 0.04 for the PA period and 0.82 +/- 0.03 for the fed period. Fractional recoveries were not significantly different for ig and iv routes of administration but were different for PA and fed periods (P less than 0.0001, 2-way ANOVA). The fractional recoveries for the fed period obtained here were similar to the value 0.81 reported in a number of other studies. Recovery of tracer in breath increased linearly with O2 uptake and CO2 production, suggesting that factors affecting respiratory gas exchange may alter recovery. We conclude that the primary factor determining label recovery is the immediate and recent nutritional status of the host.
Available tools in liver surgery planning rely on the future remnant liver (FRL) volume. Inapprop... more Available tools in liver surgery planning rely on the future remnant liver (FRL) volume. Inappropriate decision might be made since the same FRL volume might represent different liver functions depending on the severity of underlying liver damage. This study developed an alternative system to estimate FRL function and to predict the risk of postoperative liver failure. Current study recruited 71 prehepatectomy patients and 71 healthy volunteers. A technetium-99-labelled asialoglycoproteins was given to participants and SPECT was used to capture the intensity of the signal, represented by uptake index (UI). The agreement between preoperative UI values, liver function tests, and Child scores were evaluated. Linear regression was used to evaluate the agreement between predicted UI for FRL and postoperative UI values. Area under the receiver operating characteristic (AUC) curve was used to evaluate the discriminative performance of UI in differentiating patient with high risk of liver failure. Preoperative UIs are highly correlated with Child score (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), especially to identify patients with ascites and elevated bilirubin. The predicted UIs were in close agreement with the actual postoperative UI values (r = 0.95 P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The AUC analysis indicated that UI values had a high accuracy in predicting the risk of liver failure (AUC = 0.95,…
American Journal of Physiology-endocrinology and Metabolism, Dec 1, 1996
The quantitative roles of the splanchnic region and the kidneys in whole body (WB) arginine and c... more The quantitative roles of the splanchnic region and the kidneys in whole body (WB) arginine and citrulline metabolism were assessed in postabsorptive mongrel dogs with primed constant intravenous infusions of [15N2-guanidino, 5,5-2H2]arginine and [13C-ureido]citrulline or [13C-guanidino]arginine and [15N]urea tracers. Isotope and metabolite concentration balances of arginine and citrulline were measured across the gut, liver, splanchnic region, and kidneys, together with WB arginine and citrulline fluxes and urea production rate. The WB citrulline flux and rate of citrulline to arginine (C-A) conversion were 16 and 9.4 mumol.kg-1.h-1, respectively. Concentration balance of citrulline across kidneys was +8.2 mumol.kg-1.h-1, and metabolism of citrulline by kidneys was 8.7 mumol.kg-1.h-1, which was derived about equally from intestine and liver. The appearance rate of citrulline-derived arginine in renal vein was 6.8 mumol.kg-1.h-1. These three separate estimates of C-A conversion within the kidneys were in good agreement, indicating 40% of blood C-A conversion occurring outside kidneys. These findings of interorgan metabolism are discussed in reference to the current knowledge derived largely from studies in laboratory rodents.
SUMMARY This chapter briefly introduces basic biochemistry of protein and amino acids (AAs) and t... more SUMMARY This chapter briefly introduces basic biochemistry of protein and amino acids (AAs) and their chemical structures, followed by the discussion on the dynamic process of protein and amino digestion, absorption, and their turnover in whole body and specific tissues in vivo as the biochemical and physiological basis in assessing protein requirements. The latter part of the chapter provided an in-depth discussion of the latest knowledge of the indicators used to assess protein requirements and AA requirements. The chapter finishes with a discussion of the current recommended intakes for protein and AAs, along with aspects of their use in nutritional assessment and issues in developing recommendations of protein/AAs for health maintenance throughout the life cycle.
Organismal evolution led to innovations in metabolic pathways, many of which certainly modified t... more Organismal evolution led to innovations in metabolic pathways, many of which certainly modified the surface chemistry of the Earth. Volcanic activity introduced inorganic compounds (H 2 , CO 2 , CH 4 , SO 2 , and H 2 S) driving the metabolism of early organisms of the domains archaea and bacteria. In the absence of light, H 2 S and Fe 2+ would have been the major electron donors and the electron acceptors could be either oxidized species such as the sulfurs, sulfate, and elemental sulfur, or carbon dioxide by the fermentation of acetate (forming methane). Elemental sulfur was produced by the reaction between H 2 S and SO 2 , while anoxygenic photosynthesis may have provided the sulfate which removed oceanic ferrous iron by its precipitation as sulfide into sediments. Hence, the sulfur cycle participation in life evolution comes from ancient anoxygenic elemental sulfur reduction generating environmental sulfide incorporated as mitochondrial Fe-S for the electrontransport chains. Anoxygenic photosynthesis may have provided the necessary sulfate to promote the evolution of sulfate-reducing bacteria. The evolution of oxygenic photosynthesis provided for diverse metabolic possibilities including non-photosynthetic sulfide oxidation, nitrification, and methanotrophy. An increase in oxygen levels would account for oxidative sulfur cycle, evolution of colorless sulfur bacteria, and emergence of large multicellular animals. Oxygen, initially a waste product of photosynthesis, first reacted with sulfur, iron or methane and latter accumulated in atmosphere resulting in more carbon production. Oxygenic photosynthesis becomes a positive feedback on the oxidation of the Earth-surface environment causing the growth and stabilization of continental platforms and carbon burial with more atmosphere oxidation. An increase in oxygen levels would account for oxidative sulfur cycle, evolution of colorless sulfur bacteria, and emergence of large multicellular animals. Oxygen enabled more efficient energy transformation from dietary food to ATP. However, evolution for mammals living on dry land has been closely linked to the adaptation of changes in O 2 concentration in the environment, which means mitochondrial aerobic respiration. By using ancestral geochemistry of iron-sulfur clusters at the protein complexes I and II, the respiratory chains become
Burn-induced insulin resistance is associated with increased morbidity and mortality; however, th... more Burn-induced insulin resistance is associated with increased morbidity and mortality; however, the impact of burn injury on tissue-specific insulin sensitivity and its molecular mechanisms with consideration of insulin state remains unknown in rodent models. This study was designed to characterize a burn mouse model with tissue-specific insulin resistance under insulin clamp conditions. C57BL6/J mice were subjected to 30% full-thickness burn injury and underwent the combination of hyperinsulinemic isoglycemicclamp (HIC) and positron emission tomography (PET). Hepatic glucose production (HGP) and peripheral glucose disappearance rate (Rd) were measured at different time points up to 7 days post injury. Burned mice showed a significant fasting hypoglycemia and hypoinsulinemia (P < 0.01) on post-burn day (PBD) 3 and 7 along with significantly higher energy expenditure (P < 0.01). HICon PBD 3 demonstrated that burn injury induced systemic insulin resistance, resulting from a significant decrease in insulin-stimulated Rd (33.0 ± 10.2 vs 68.3 ± 5.9 mg/kg/min; P < 0.05). In contrast, HGP of burned and sham mice was comparable both in the basal and clamp period. PET on PBD 3 showed a lower insulin-stimulated 18F-labeled 2-fluoro-2-deoxy-D-glucose uptake in the quadriceps of burned mice compared with sham-burned mice. Gastrocnemius muscle harvested from burned mice on PBD 3
Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) qS=1, 81% qS=2, 92% qS=3, p<0.001) or deve... more Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) qS=1, 81% qS=2, 92% qS=3, p<0.001) or developed a complication (11% of admissions with a complication had qS=0, 26% qS=1, 52% qS=2, 62% qS=3, p<0.001). Patients with higher qS were more severely injured as measured by median Injury Severity Scores (qS=0 had median ISS 9 [IQR 5–13]; qS=1, ISS 13 [9–24]; qS=2, ISS 27 [16–41]; qS=3, ISS 35 [22–45]). On multivariate analysis, qS was an independent predictor of mortality (qS=1 OR 5.2 [IQR 3.8–7.1], qS=2 OR 15.1 [IQR 9.7–23.7], qS=3 OR 16.2 [IQR 4.0–65.4], each p<0.001). Conclusions: Calculation of the qS following blunt trauma could be used a quick and simple method, without imaging or surgery, to predict risk of death and other adverse outcomes and thereby prioritize resource allocation.
Burn injury mediated hypermetabolic syndrome leads to increased mortality among severe burn victi... more Burn injury mediated hypermetabolic syndrome leads to increased mortality among severe burn victims, due to liver failure and muscle wasting. Metabolic changes may persist up to 2 years following the injury. Thus, understanding the underlying mechanisms of the pathology is crucially important to develop appropriate therapeutic approaches. We present detailed metabolomic and lipidomic analyses of the liver and muscle tissues in a rat model with a 30% body surface area burn injury located at the dorsal skin. Three hundred and thirty-eight of 1587 detected metabolites and lipids in the liver and 119 of 1504 in the muscle tissue exhibited statistically significant alterations. We observed excessive accumulation of triacylglycerols, decreased levels of S-adenosylmethionine, increased levels of glutamine and xenobiotics in the liver tissue. Additionally, the levels of gluconeogenesis, glycolysis, and tricarboxylic acid cycle metabolites are generally decreased in the liver. On the other h...
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