Adult respiratory distress syndrome during pregnancy and immediately postpartum.

From 1976 to 1983, the adult respiratory distress syndrome occurred in 14 patients during pregnancy or within a month postpartum. There were 8 survivors, giving a 43% mortality. All but 2 patients had obstetric-related precipitating events--labor problems, infections, eclampsia-toxemia, and obstetric hemorrhages. During emergency cesarean sections, 3 patients had respiratory problems that may have caused their respiratory distress syndrome. The average duration of mechanical ventilatory support was 16 days. Six patients had barotrauma with 1 patient sustaining an irreversible anoxic central nervous system injury. Infections were documented in 8 patients, 6 of whom had obstetric foci. There is a lack of information regarding the adult respiratory distress syndrome in this patient group. Though uncommon, it can cause substantial mortality and morbidity.     

The evolution of endothermy in terrestrial vertebrates: Who? When? Why?

Avian and mammalian endothermy results from elevated rates of resting, or routine, metabolism and enables these animals to maintain high and stable body temperatures in the face of variable ambient temperatures. Endothermy is also associated with enhanced stamina and elevated capacity for aerobic metabolism during periods of prolonged activity. These attributes of birds and mammals have greatly contributed to their widespread distribution and ecological success. Unfortunately, since few anatomical/physiological attributes linked to endothermy are preserved in fossils, the origin of endothermy among the ancestors of mammals and birds has long remained obscure. Two recent approaches provide new insight into the metabolic physiology of extinct forms. One addresses chronic (resting) metabolic rates and emphasizes the presence of nasal respiratory turbinates in virtually all extant endotherms. These structures are associated with recovery of respiratory heat and moisture in animals with high resting metabolic rates. The fossil record of nonmammalian synapsids suggests that at least two Late Permian lineages possessed incipient respiratory turbinates. In contrast, these structures appear to have been absent in dinosaurs and nonornithurine birds. Instead, nasal morphology suggests that in the avian lineage, respiratory turbinates first appeared in Cretaceous ornithurines. The other approach addresses the capacity for maximal aerobic activity and examines lung structure and ventilatory mechanisms. There is no positive evidence to support the reconstruction of a derived, avian-like parabronchial lung/air sac system in dinosaurs or nonornithurine birds. Dinosaur lungs were likely heterogenous, multicameral septate lungs with conventional, tidal ventilation, although evidence from some theropods suggests that at least this group may have had a hepatic piston mechanism of supplementary lung ventilation. This suggests that dinosaurs and nonornithurine birds generally lacked the capacity for high, avian-like levels of sustained activity, although the aerobic capacity of theropods may have exceeded that of extant ectotherms. The avian parabronchial lung/air sac system appears to be an attribute limited to ornithurine birds.     

Dinitrophenol-induced mitochondrial uncoupling in vivo triggers respiratory adaptation in HepG2 cells

Here, we show that 3 days of mitochondrial uncoupling, induced by low concentrations of dinitrophenol (10 and 50 microM) in cultured human HepG2 cells, triggers cellular metabolic adaptation towards oxidative metabolism. Chronic respiratory uncoupling of HepG2 cells induced an increase in cellular oxygen consumption, oxidative capacity and cytochrome c oxidase activity. This was associated with an upregulation of COXIV and ANT3 gene expression, two nuclear genes that encode mitochondrial proteins involved in oxidative phosphorylation. Glucose consumption, lactate and pyruvate production and growth rate were unaffected, indicating that metabolic adaptation of HepG2 cells undergoing chronic respiratory uncoupling allows continuous and efficient mitochondrial ATP production without the need to increase glycolytic activity. In contrast, 3 days of dinitrophenol treatment did not change the oxidative capacity of human 143B.TK(-) cells, but it increased glucose consumption, lactate and pyruvate production. Despite a large increase in glycolytic metabolism, the growth rate of 143B.TK(-) cells was significantly reduced by dinitrophenol-induced mitochondrial uncoupling. We propose that chronic respiratory uncoupling may constitute an internal bioenergetic signal, which would initiate a coordinated increase in nuclear respiratory gene expression, which ultimately drives mitochondrial metabolic adaptation within cells.     

Thiazolidinedione response in familial lipodystrophy patients with LMNA mutations: a case series

Type 2 familial partial lipodystrophy (FPLD2) patients show impaired glucose and lipid metabolism resulting from lipodystrophic 'lipid pressure' and an intrinsic defect in skeletal muscle metabolism. Since mutated lamin A may interfere with peroxisome proliferator activator gamma (PPARγ) expression, we hypothesized that PPARγ stimulation improves fat distribution and metabolic abnormalities in these patients. 5 nondiabetic FPLD2 patients were treated with rosiglitazone over 12 months. We assessed body composition, body fat distribution, and skinfold thickness/subcutaneous tissue thickness. We also determined venous glucose, insulin, and free fatty acid (FFA) concentrations, and respiratory quotient (RQ) before and during oral glucose tolerance testing. Adipose tissue and muscle fasting and postprandial metabolism were studied by microdialysis. Within 12 months treatment, hip circumference increased from 93.6±2.78 cm to 96.2±2.3 cm (p<0.05). Rosiglitazone reduced fasting glucose levels and liver transaminases. Baseline and postprandial FFA concentrations were significantly lower after 12 months treatment. RQ and muscle interstitial pyruvate and lactate did not respond to treatment. We conclude that PPARγ stimulation with rosiglitazone modestly improves glucose metabolism in FPLD2 patients presumably through proximal adipose tissue expansion. The intrinsic muscular metabolic defect does not respond to rosiglitazone.     

Bimodal Respiration in Aquatic and Terrestrial Apodan Amphibians

SYNOPSIS. New data on resting metabolism, aerobic capacity,respiratory morphology and bimodal breathing capacities offourcaecilian species were combined with previously known data oncaecilian and amphibian biology to discern differing or unifyingthemes of gas exchange within the Gymnophiona and among theAmphibia. Discoveries include 1) a uniform resting metabolismamong caecilians that is distinctly lower than that of anuransand urodeles, 2) an aerobic capacity following activity thatrivals or exceeds that of other amphibians, and 3) despite previoussuggestions to the contrary, a substantial contribution of theskin to respiratory gas exchange, apparently sufficient to sustainthe low resting metabolism. In contrast, pulmonary gas transportappears to dominate during metabolic recovery from exercise,which is comparatively fast. The contributing roles of the skinand lungs to this extreme scope of respiratory needs in caeciliansare further discussed in light of the structural nature of andcirculatory supply to each respiratory bed, and the respiratoryproperties of caecilian blood.     

高果糖高脂饮食对小鼠体内能量代谢的影响

目的:高热量物质的过度摄入是导致机体代谢紊乱,诱发2型糖尿病等代谢性疾病的主要原因,本文通过比较高果糖、高脂及高果糖高脂混合喂饲对小鼠体内能量代谢的影响,探索饮食诱发代谢紊乱性疾病的可能发病机制。方法:采用20%高果糖水,60%高脂饲料,及二者混合方式饲养C57BL/6小鼠3个月后,观察各组小鼠24小时内氧气消耗量,二氧化碳生成量,呼吸商及能量消耗的改变。结果:不同饮食喂饲3个月,与对照组小鼠相比,高果糖组、高脂组、及高果糖高脂组小鼠均表现出明显的肝内脂质蓄积,氧气消耗量增加,呼吸商下降,能量消耗增加。结论:过剩的高热量物质摄入导致机体内物质代谢、能量代谢发生改变,糖代谢受损,脂代谢增强,能量代谢方式从糖氧化为主转变为脂氧化供能。     

Metabolic Reprogramming towards Aerobic Glycolysis Correlates with Greater Proliferative Ability and Resistance to Metabolic Inhibition in CD8 versus CD4 T Cells

T lymphocytes (T cells) undergo metabolic reprogramming after activation to provide energy and biosynthetic materials for growth, proliferation and differentiation. Distinct T cell subsets, however, adopt metabolic programs specific to support their needs. As CD4 T cells coordinate adaptive immune responses while CD8 T cells become cytotoxic effectors, we compared activation-induced proliferation and metabolic reprogramming of these subsets. Resting CD4 and CD8 T cells were metabolically similar and used a predominantly oxidative metabolism. Following activation CD8 T cells proliferated more rapidly. Stimulation led both CD4 and CD8 T cells to sharply increase glucose metabolism and adopt aerobic glycolysis as a primary metabolic program. Activated CD4 T cells, however, remained more oxidative and had greater maximal respiratory capacity than activated CD8 T cells. CD4 T cells were also associated with greater levels of ROS and increased mitochondrial content, irrespective of the activation context. CD8 cells were better able, however, to oxidize glutamine as an alternative fuel source. The more glycolytic metabolism of activated CD8 T cells correlated with increased capacity for growth and proliferation, along with reduced sensitivity of cell growth to metabolic inhibition. These specific metabolic programs may promote greater growth and proliferation of CD8 T cells and enhance survival in diverse nutrient conditions.     

ANGPTL8 in metabolic homeostasis: more friend than foe?

ANGPTL8 is an important cytokine, which is significantly increased in type 2 diabetes mellitus (T2DM), obesity and metabolic syndrome. Many studies have shown that ANGPTL8 can be used as a bio-marker of these metabolic disorders related diseases, and the baseline ANGPTL8 level has also been found to be positively correlated with retinopathy and all-cause mortality in patients with T2DM. This may be related to the inhibition of lipoprotein lipase activity and the reduction of circulating triglyceride (TG) clearance by ANGPTL8. Consistently, inhibition of ANGPTL8 seems to prevent or improve atherosclerosis. However, it is puzzling that ANGPTL8 seems to have a directing function for TG uptake in peripheral tissues; that is, ANGPTL8 specifically enhances the reserve and buffering function of white adipose tissue, which may alleviate the ectopic lipid accumulation to a certain extent. Furthermore, ANGPTL8 can improve insulin sensitivity and inhibit hepatic glucose production. These contradictory results lead to different opinions on the role of ANGPTL8 in metabolic disorders. In this paper, the correlation between ANGPTL8 and metabolic diseases, the regulation of ANGPTL8 and the physiological role of ANGPTL8 in the process of glucose and lipid metabolism were summarized, and the physiological/pathological significance of ANGPTL8 in the process of metabolic disorder was discussed.     

Dinitrophenol-induced mitochondrial uncoupling in vivo triggers respiratory adaptation in HepG2 cells

Here, we show that 3 days of mitochondrial uncoupling, induced by low concentrations of dinitrophenol (10 and 50 μM) in cultured human HepG2 cells, triggers cellular metabolic adaptation towards oxidative metabolism. Chronic respiratory uncoupling of HepG2 cells induced an increase in cellular oxygen consumption, oxidative capacity and cytochrome c oxidase activity. This was associated with an upregulation of COXIV and ANT3 gene expression, two nuclear genes that encode mitochondrial proteins involved in oxidative phosphorylation. Glucose consumption, lactate and pyruvate production and growth rate were unaffected, indicating that metabolic adaptation of HepG2 cells undergoing chronic respiratory uncoupling allows continuous and efficient mitochondrial ATP production without the need to increase glycolytic activity. In contrast, 3 days of dinitrophenol treatment did not change the oxidative capacity of human 143B.TK⁻ cells, but it increased glucose consumption, lactate and pyruvate production. Despite a large increase in glycolytic metabolism, the growth rate of 143B.TK⁻ cells was significantly reduced by dinitrophenol-induced mitochondrial uncoupling. We propose that chronic respiratory uncoupling may constitute an internal bioenergetic signal, which would initiate a coordinated increase in nuclear respiratory gene expression, which ultimately drives mitochondrial metabolic adaptation within cells.     

Inactivation of protein kinase C in rat liver during late hypoglycemic phase of sepsis

Changes in protein kinase C (PKC) (calcium- and phospholipid-dependent protein kinase) activity in rat liver during different metabolic phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into three groups: control, early sepsis, and late sepsis. Early and late sepsis refers to those animals sacrificed at 9 and 18 h, respectively, after CLP. Hepatic PKC was extracted and partially purified by ammonium sulfate fractionation and DEAE-cellulose chromatography. PKC activity was assayed based on the rate of incorporation of ³²p from [-³²P]ATP into histone. The results show that during early sepsis, both membrane-associated and cytosolic PKC activities remained relatively unaltered. During late sepsis, membrane-associated PKC was unaffected while cytosolic PKC activity was decreased by 19.5-34.4%. Kinetic analysis of the data on cytosolic PKC during late phase of sepsis reveals that the V_max values for ATP, histone, Ca²⁺, phosphatidylserine, and diacylglycerol were decreased by 23.4, 22.1, 19.5, 25, and 34.4%, respectively, with no changes in their K_m values. These data indicate that cytosolic PKC activity was inactivated in rat liver during late hypoglycemic phase of sepsis. Since PKC-mediated phosphorylation plays an important role in regulating hepatic glucose metabolism, an inactivation of cytosolic PKC may contribute to the development of hypoglycemia during late phase of sepsis.     

Evidence that NADPH is the actual substrate of the oxidase responsible for the "respiratory burst" of phagocytosing polymorphonuclear leukocytes

The relationship between glucose metabolism and the "respiratory burst" of phagocytosing polymorphonuclear leukocytes (PMN) was studied in a Renex 30-treated cell system of guinea pig PMN by a polarometric technique. Phagocytosing PMN were treated with a detergent (Renex 30) and recovery of respiratory activity was examined by addition of various concentrations of NADP and glucose-6-phosphate (G6P) to determine the availability of endogenously formed NADPH via the hexose monophosphate (HMP) pathway. The oxygen uptake by phagocytosing PMN ceased after the treatment with Renex 30 and was restored by the addition of NADP and G6P. Furthermore, the restoration of oxygen uptake was linearly proportional to the rate of NADPH formation on increase in either NADP or G6P concentration. Resting PMN showed no respiratory activity even in the presence of excess NADP and G6P, in which NADPH was formed at the same rate as in phagocytosing PMN. In a parallel experiment, recovery of respiratory activity was examined in the same system by addition of NAD and glyceraldehyde-3-phosphate (G3P) in that order to clarify whether the respiratory enzyme can utilize NADH formed via the glycolytic pathway. In contrast to the results in the NADPH-forming system, the addition of NAD and G3P induced slight oxygen uptake of Renex 30-treated PMN, but there was no difference in the oxygen uptake between resting and phagocytosis-activated PMN. The results indicated that the primary oxidase responsible for the "respiratory burst" is NADPH oxidase, and that its activity is coupled with glucose oxidation via the HMP pathway without the participation of other metabolic pathways such as glycolysis.     

Studies on the respiratory metabolism of isolated human adipose cells

1. Some metabolic characteristics of fat cells isolated from 50 patients were examined. 2. The respiratory activity of human fat cells was of the same order of magnitude as cells obtained from the rat, whether the comparison was based on the molar triglyceride content of cells or the nitrogen content of tissue. 3. There was no difference in the respiratory metabolism of fat cells isolated from three separate age groups: 20-40, 40-60 and 60-80 years. 4. The respiratory activity of human adipose cells was partially inhibited by malonate (0.1m), arsenite (1mm) and iodoacetate (1mm). 5. Oxygen consumption by human adipose cells could not be stimulated by adding glucose or glucose plus palmitic acid to the medium. However, stimulation of oxygen uptake with these substrates was observed after the tissue had been preincubated for 5hr. in a bicarbonate buffer. 6. After the tissue had been preincubated for 5hr., there was a linear relationship between the oxygen uptake by isolated cells and the amount of oleic acid added to the incubation medium. Stimulation of oxygen uptake by oleic acid (0.95mumole/ml.) was dependent on the presence of glucose (5.6mm) in the incubation medium. 7. Of the total [1-(14)C]palmitic acid metabolized by human adipose cells, over 99.8% of the radioactivity was recovered in the neutral-lipid fraction and less than 0.2% in carbon dioxide. Under conditions where oxygen uptake is stimulated by [(14)C]-palmitic acid, the radioactivity of the 1,2-diglyceride pool increased 20-fold.     

Environmental reprogramming of the expression of protein kinase CK2β subunit in fish

Interleukin-8 (IL-8) is considered as the major polymorphonuclear neutrophils (PMNs) chemoattractant cytokine in lung diseases such as asthma and adult respiratory distress syndrome (ARDS). However, controversial results were obtained regarding the involvement of IL-8 in the pathogenesis of pneumonia. This study examines the role of IL-8 in the recruitment and activation of PMNs in the lung of pneumonia patients. The interesting aspect of this study is that it is a site- specific analysis of the infected and uninfected lungs of the same patient. The level of IL-8 mRNA, protein and myeloperoxidase present in the cells of the bronchioalveolar lavages (BALs) taken from the areas of known pneumonic consolidations on chest X-ray (infected lung) are compared with the BALs obtained from areas of no obvious infiltrate (non-infected lung). The results obtained from the infected and non-infected lungs of pneumonic patients were further compared with that of a control group of non-smoking patients. The level of IL-8 mRNA and protein were determined by RT-PCR and ELISA respectively. There was a significant increase in the level of IL-8 mRNA in the infected lung as compared to its level in the non-infected lung (p < 0.001). In correlation with the increase in mRNA, IL-8 protein concentrations in BAL fluids from the infected lung were 6 fold higher than those taken from the non-infected lung (p < 0.0001). This pattern was also consistent with MPO activity in the BALs (4.5 fold more MPO activity in the infected lung as compared to that of the non-infected lung), indicating that IL-8 is directly implicated in neutrophil accumulation that follows acute respiratory infection. The results of the present study, therefore, indicate the involvement of IL-8 in the pathogenesis of pneumonia.     

A small metabolic flux model to identify transient metabolic regulations in Saccharomyces cerevisiae

The understanding of dynamic metabolic regulations is important for physiological studies and strain characterization tasks. The present study combined transient experiments with online metabolic flux analysis (MFA) in order to quantify metabolic regulations, namely carbon catabolite repression of respiration and transient acetic-acid production, in Saccharomyces cerevisiae during aerobic growth on glucose. The aim was to investigate which additional information can be gained from using a small metabolic flux model to study transient growth provoked by shift-up and shift-down experiments, compared to online monitoring alone. The MFA model allowed us to propose new correlations between pathways of the central metabolism. A linear correlation between glycolytic flux and respiratory capacity holds for shift-down and shift-up experiments. This confirmed that respiratory functions were subjected to carbon catabolite repression and suggested that respiratory capacity is controlled by the glycolytic flux rather than the glucose influx. Furthermore, the model showed that control of repression of respiration by the glycolytic flux was a dynamic phenomenon. Co-factor balancing within the MFA model showed that transient acetic-acid production indicated a transient limitation in another part of the central metabolism but not in oxidative phosphorylation. However, at super-critical growth rates and when coupling of anabolism and catabolism is resumed, the limitation shifts to oxidative phosphorylation, with the consequence that ethanol is formed. The online application of small metabolic flux models to transient experiments enhanced the physiological insight into transient growth and opens up the use of transient experiments as an efficient tool to understand dynamic metabolic regulations.     

Effect of Methionine and Sulfate on the Metabolism of Cephalosporium acremonium

The metabolism of Cephalosporium acremonium grown in a complex medium supplemented with DL-methionine or inorganic sulfate was studied. More growth occurred in a sulfate medium than in a methionine medium. Methionine-grown cells had an increased rate of respiration, a higher rate of catabolism with acetate and glucose as substrate, and higher specific activities of certain respiratory enzymes than sulfate-grown cells. Labeled acetate and glucose were assimilated at a faster rate by methionine-grown cells than sulfate-grown cells. Taurine, cystathionine, and small quantities of four acidic compounds were present in the amino acid pool of methionine-grown cells, but they were not detected in the pool of sulfate-grown cells. The differences in metabolic activity of sulfate and methionine-grown cells are discussed in regard to cephalosporin C synthesis.     

Alterations of glucose metabolism in Escherichia coli mutants defective in respiratory-chain enzymes

The effects of reduced efficiency of proton-motive force (pmf) generation on glucose metabolism were investigated in Escherichia coli respiratory-chain mutants. The respiratory chain of E. coli consists of two NADH dehydrogenases and three terminal oxidases, all with different abilities to generate a pmf. The genes for isozymes with the highest pmf-generating capacity (NADH dehydrogenase-1 and cytochrome bo? oxidase) were knocked out singly or in combination, using a wild-type strain as the parent. Analyses of glucose metabolism by jar-fermentation revealed that the glucose consumption rate per cell increased with decreasing efficiency of pmf generation, as determined from the growth parameters of the mutants. The highest rate of glucose metabolism was observed in the double mutant, and the lowest was observed in the wild-type strain. The respiration rates of the single-knockout mutants were comparable to that of the wild-type strain, and that of the double mutant was higher, apparently as a result of the upregulation of the remaining respiratory chain enzymes. All of the strains excreted 2-oxoglutaric acid as a product of glucose metabolism. Additionally, all of the mutants excreted pyruvic acid and/or acetic acid. Interestingly, the double mutant excreted L-glutamic acid. Alterations of the fermentation profiles provide clues regarding the metabolic regulation in each mutant.     

Metabolic characteristics of brain structures during conscious and unconscious anxiety

Metabolic processes accompanying conscious and unconscious anxiety states in patients with multiple sclerosis were studied. The correspondence between glucose metabolism rates (evaluated using positron emission tomography images) and indices of conscious and unconscious anxiety (according to the Taylor and Luscher test scores) was estimated. Data on the specific features of brain activity at various levels of conscious and unconscious anxiety were obtained. The elevation of conscious anxiety was accompanied by an increase in the metabolic activity of the left-hemisphere cortical and subcortical structures, as well as by a decrease in the glucose metabolism rate in the majority of right-hemisphere structures (except limbic and thalamic structures). The elevation of unconscious anxiety was accompanied by a decrease in the rate of glucose metabolism in the left frontal structures, whereas in the amygdala, as well as in the other limbic structures (gyrus temporalis inferior), its rate increased.     

Aerobic glucose metabolism of Saccharomyces kluyveri: growth, metabolite production, and quantification of metabolic fluxes.

The growth and product formation of Saccharomyces kluyveri was characterized in aerobic batch cultivation on glucose. At these conditions it was found that ethyl acetate was a major overflow metabolite in S. kluyveri. During the exponential-growth phase on glucose ethyl acetate was produced at a constant specific rate of 0.12 g ethyl acetate per g dry weight per hour. The aerobic glucose metabolism in S. kluyveri was found to be less fermentative than in S. cerevisiae, as illustrated by the comparably low yield of ethanol on glucose (0.08 +/- 0.02 g/g), and high yield of biomass on glucose (0.29 +/- 0.01 g/g). The glucose metabolism of S. kluyveri was further characterized by the new and powerful techniques of metabolic network analysis. Flux distributions in the central carbon metabolism were estimated for respiro-fermentative growth in aerobic batch cultivation on glucose and respiratory growth in aerobic glucose-limited continuous cultivation. It was found that in S. kluyveri the flux into the pentose phosphate pathway was 18.8 mmole per 100 mmole glucose consumed during respiratory growth in aerobic glucose-limited continuous cultivation. Such a low flux into the pentose phosphate pathway cannot provide the cell with enough NADPH for biomass formation which is why the remaining NADPH will have to be provided by another pathway. During batch cultivation of S. kluyveri the tricarboxylic acid cycle was working as a cycle with a considerable flux, that is in sharp contrast to what has previously been observed in S. cerevisiae at the same growth conditions, where the tricarboxylic acid cycle operates as two branches. This indicates that the respiratory system was not significantly repressed in S. kluyveri during batch cultivation on glucose.