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Treatment of carbapenemase‐producing Enterobacteralesbloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase‐producing Enterobacteralesbloodstream infections. A multinational, retrospective (2004‐2016) cohort study (INCREMENT‐SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30‐day all‐cause mortality. The INCREMENT‐SOT‐CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT‐CPE mortality score ≥8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT‐CPE score ≥8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76‐0.88) and classified patients into 3 strata: 0‐7 (low mortality), 8‐11 (high mortality), and 12‐17 (very‐high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very‐high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13‐7.06, P= .03) and high (HR 9.93, 95% CI 2.08‐47.40, P= .004) mortality risk strata. A score‐based algorithm is provided for therapy guidance. The authors develop a predictive risk score for a solid organ transplant recipient's for mortality in patients with bloodstream infections due to carbapenemase‐producing Enterobacterales, which is useful to differentiate patients who can be treated with antimicrobial monotherapy from those who should receive combination therapy.

This paper presents a methodology for the optimal management of water and energy in irrigation systems. A two-layer management scheme is proposed. In the upper layer, an optimal control strategy is used to plan how to serve the demanded water within a prediction horizon of five days ahead in order to minimize electricity costs associated to pumping satisfying the physical limitations of the pipes. At the lower layer, a scheduling algorithm decides how to schedule the different pumps of the pumping stations in order to supply the desired flow with the maximum efficiency and minimum cost. A part of the Bardenas irrigation system in Spain is used as the case study to illustrate the proposed approach.

The aim of this study was to investigate the effect of the anti-inflammatory and anti-fibrotic actions of ANX1 on erectile function (EF). Forty-eight male Wistar rats were randomly distributed into four equal groups: one group (sham operation—control) and three groups (bilateral cavernous nerve (CN) crush injury). Crush injury groups were treated prior to injury with an intravascular injection of either ANX1 (50 or 100 µg?kg-1) or vehicle. EF was assessed by CN electrical stimulation at 2 and 7 days after CN injury with histomorphometric and immunohistochemical analysis. ANX1 demonstrated functional preservation as the increase in intracavernous pressure (ICP). A dose–response relationship regarding the effect on penile tissue was confirmed, and preservation of the penile dorsal nerves and anti-apoptotic effects in the corpus cavernosum (real P-value vs injured control). ANX1 treatment prevented collagen deposition and smooth muscle loss in the penis. ANX1 normalized the expression of vascular endothelial growth factor and decreased tumor necrosis factor-a in the lumen of the blood vessels of the organ. ANX1 proved effective in preserving EF in a rat model of neurogenic erectile dysfunction. ANX1 treatment before CN injury in rats improved erectile recovery, enhanced vascular regeneration and preserved the micro-architecture of the corpus cavernosum. The clinical availability of this compound merits application in penile rehabilitation studies following radical prostatectomy.

Both classical mechanics and thermodynamics live in the core of physics. They are two different aspects of the same thing, one can say. The thermodynamic equivalent of a mechanical system is one of the main achievements of the 19th century. Regarding only thermodynamics, the introduction of entropy, roughly defined in many textbooks as the unuseful energy present in a physical system, is a victory of Rudolf Clausius. Unlike energy, entropy can be produced in a physical system under certain conditions. We can act to increase the degree of disorder (statistical mechanics) in a physical system. Here, we propose to apply the entropy generation (Ṡgen) concept to the simple pendulum by using a very unknown result: the Gouy–Stodola theorem. When considering the ideal case, where only conservative forces act on the system, one has Ṡgen=0, and the entropy variation is null. However, as shall be seen, the entropy variation is not null all the time. Considering a nonconservative force proportional to the pendulum velocity, the amplitude of oscillations decreases to zero as tgrows. Then, Ṡgen>0may be related with the energy dissipation, as stated by the Gouy–Stodola theorem. Hence, as shall be seen, the greater the strength of the nonconservative force, the greater are both the energy dissipation and the time rate of entropy variation.

Las infecciones en humanos por Raoultellaspp. son raras, y se desconocen actualmente las repercusiones que Raoultellaspp. pudiese tener como patógeno humano. Se describe un caso clínico de bacteriemia relacionada con catéter causada por Raoultella ornithinolytica, que fue tratada con éxito con terapia antibiótica aplicada (cefepima intravenosa y sellado del catéter con amikacina).

This work analysed the environmental and economic impacts of extracts enriched in ergosterol and vitamin D2production from bio-residues of Agaricus Bisporusmushrooms. The main hotspots of the extractive processes in environmental terms were identified through the standardized methodology Life Cycle Assessment. In respect to the economic analysis, the Material Flow Cost Accounting approach was applied to identify production costs, distinguishing between valued and wasted costs. The LCA results showed that electricity consumption is a key factor in environmental aspects, having the highest contribution to the process's environmental impact. In general, the most electricity-consuming unit processes analysed were lyophilization, extraction and evaporation. Despite evaporation being a process with great energy consumption, it also mitigates environmental impacts, since it allows solvent recovery through the extraction and reutilization phases in new iterations. The production costs for the identified extracts were determined: extract enriched in ergosterol (2.43€/1 g of extract) and extract enriched in vitamin D2(8.28€/1 g of extract). Recovered solvent incorporation in posterior iterations resulted in a total cost decrease of about 47% for ergosterol-extract and about 39% for vitamin D2extract. Solvent's recovery and reutilization allowed to not only reduce the environmental impacts but also the production costs.

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of abnormal liver function and correlates with central adiposity, obesity, insulin resistance, the metabolic syndrome and type 2 diabetes mellitus. The pathological spectrum of NAFLD ranges from fatty liver to non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and even hepatocellular carcinoma. Though NAFLD and NASH are becoming a major public health problem, ethical constraints on obtaining human liver tissue limit the interpretability of the data and the ability to delineate cause and effect from complex, interactive disease pathogenic pathways. Animal models of NASH can provide critical information leading to identify potential drug targets and to understand their molecular mechanisms, and are platforms for compound screening in drug development and for the assessment of novel therapeutic strategies. This review is aimed to offer an updated overview of the nutritional, genetic and pharmacologic animal models of NASH. Though the information derived from these models has clear relevance for the comprehension of the molecular basis of human disease, most of them fail to reproduce the full spectrum of liver pathology and the metabolic context that characterizes human NASH. Consequently, it is necessary to establish animal models that can best mimic the actual etiology, progression, and pathogenesis of the disease, and prove effectiveness for examining and selecting compounds with potential therapeutic benefit in NASH.

In this study, the chemical vapour deposition (CVD) technique is used to modify the surface of Li2O–ZrO2–BaO–SiO2glass fibre with Nb2O5, using NbCl5as the precursor. Glass fibres were coated as follows: without thermal pretreatment but followed by air exposure after the reaction with NbCl5; without thermal treatment followed by water hydrolysis, with thermal treatment at 300°C for 2 h and air exposure; and finally, with thermal treatment and hydrolysis in water. The best result was obtained with the fibre chemically modified with Nb2O5after heat treatment followed by water hydrolysis. This procedure resulted in fibres coated with a homogeneous layer of Nb2O5without cracks. The fibres were characterised by scanning electron microscopy and energy dispersive X-ray spectroscopy. The fibres were evaluated in the qualitative determination of a mixture of methanol, ethanol and 1-butanol by solid phase microextraction and gas chromatography, yielding better results than those of the fibre coated with Nb2O5prepared by metallo-organic decomposition.

Reactive oxygen and nitrogen species (ROS/RNS), whether produced endogenously as a consequence of normal cell functions or derived from external sources, pose a constant threat to cells living in an aerobic environment. When the production of ROS/RNS overrides the antioxidant capability of the target cells, oxidative damage may occur as a consequence of the interaction with DNA, protein, and lipids. Hepatitis C virus (HCV) is a major cause of viral hepatitis. Although the molecular mechanisms of HCV pathogenesis remain unclear, oxidative stress is emerging as a key step and a major initiator in the development and the progression of liver damage, and the evaluation of oxidative stress may be useful for a better understanding of the pathogenesis of hepatitis C. Liver steatosis is one of the most important histopathological features in patients with chronic hepatitis C. Both viral and host factors contribute to the development of steatosis, and putative defects caused by ROS/RNS may be involved through abnormalities in lipid metabolism. This review is aimed to offer an updated overview of the relationship between oxidative stress and HCV infection, focusing on the significance of ROS/RNS in the pathogenesis of liver disease. The potential role played by oxidative stress in the pathogenic mechanisms of HCV-related steatosis is also discussed.

There is a lack of universally accepted clinical parameters to guide the utilization of donation after cardiac death (DCD) donor livers and it is unclear as to which patients would benefit most from these organs. We reviewed our experience in 141 patients who underwent liver transplantation using DCD allografts from 1993 to 2007. Patient outcomes were analyzed in comparison to a matched cohort of 282 patients who received livers from donation after brain death (DBD) donors. Patient survival was similar, but 1-, 5- and 10-year graft survival was significantly lower in DCD (69, 56, 44) versus DBD (82, 73, 63) subjects (p < 0.0001). Primary nonfunction and biliary complications were more common in DCD patients, accounting for 67 of early graft failures. A donor warm ischemia time >20 min, cold ischemia time >8 h and donor age >60 were associated with poorer DCD outcomes. There was a lack of survival benefit in DCD livers utilized in patients with model for end-stage liver disease (MELD) ?30 or those not on organ-perfusion support, as graft survival was significantly lower compared to DBD patients. However, DCD and DBD subjects transplanted with MELD >30 or on organ-perfusion support had similar graft survival, suggesting a potentially greater benefit of DCD livers in critically ill patients.

There is a lack of universally accepted clinical parameters to guide the utilization of donation after cardiac death (DCD) donor livers and it is unclear as to which patients would benefit most from these organs. We reviewed our experience in 141 patients who underwent liver transplantation using DCD allografts from 1993 to 2007. Patient outcomes were analyzed in comparison to a matched cohort of 282 patients who received livers from donation after brain death (DBD) donors. Patient survival was similar, but 1-, 5- and 10-year graft survival was significantly lower in DCD (69%, 56%, 44%) versus DBD (82%, 73%, 63%) subjects (p < 0.0001). Primary nonfunction and biliary complications were more common in DCD patients, accounting for 67% of early graft failures. A donor warm ischemia time >20 min, cold ischemia time >8 h and donor age >60 were associated with poorer DCD outcomes. There was a lack of survival benefit in DCD livers utilized in patients with model for end-stage liver disease (MELD) ≤30 or those not on organ-perfusion support, as graft survival was significantly lower compared to DBD patients. However, DCD and DBD subjects transplanted with MELD >30 or on organ-perfusion support had similar graft survival, suggesting a potentially greater benefit of DCD livers in critically ill patients.

Flavonoids are a large class of naturally occurring compounds widely present in fruits, vegetables, and beverages derived from plants. Reports have suggested that these compounds might be useful for the prevention of a number of diseases, partly due to their antiinflammatory properties. It has been demonstrated that flavonoids are able to inhibit expression of isoforms of inducible nitric oxide synthase, ciclooxygenase and lipooxygenase, which are responsible for the production of a great amount of nitric oxide, prostanoids and leukotrienes, as well as other mediators of the inflammatory process such as cytokines, chemokines or adhesion molecules. Modulation of the cascade of molecular events leading to the over-expression of those mediators include inhibition of transcription factors such as nuclear factor kappa B, activator protein 1, signal transducers and activators of transcription, CCAAT/enhancer binding protein and others. Effects on the binding capacity of transcription factors may be regulated through the inhibition of protein kinases involved in signal transduction, such as mitogen activated protein kinases. Although the numerous studies published with in vitro approaches allow identifying molecular mechanisms of flavonoid effects, the limited bioavailability of these molecules makes necessary validation in humans. Whatever the case, the data available make clear the potential utility of dietary flavonoids or new flavonoid-based agents for the possible treatment of inflammatory diseases. The present review summarizes recent research data focusing on the modulation of the expression of different inflammatory mediators by flavonoids and the effects on cell signaling pathways responsible for their anti-inflammatory activity.

Many remote sensing‐based evapotranspiration (RSBET) algorithms have been proposed in the past decades and evaluated using flux tower data, mainly over North America and Europe. Model evaluation across South America has been done locally or using only a single algorithm at a time. Here, we provide the first evaluation of multiple RSBET models, at a daily scale, across a wide variety of biomes, climate zones, and land uses in South America. We used meteorological data from 25 flux towers to force four RSBET models: Priestley–Taylor Jet Propulsion Laboratory (PT‐JPL), Global Land Evaporation Amsterdam Model (GLEAM), Penman–Monteith Mu model (PM‐MOD), and Penman–Monteith Nagler model (PM‐VI). ETwas predicted satisfactorily by all four models, with correlations consistently higher (R2>0.6) for GLEAM and PT‐JPL, and PM‐MOD and PM‐VI presenting overall better responses in terms of percent bias (−10

Radiological features and biochemical changes were investigated during the parenchymal and ductal phases of chronic Fasciola hepatica infection in sheep. The activities of plasma aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT), plasma levels of IgG anti- F. hepatica and serial ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) findings were studied in eight sheep infected with 150 F. hepatica metacercariae. Experimental fluke infection provoked an increase in plasma level of IgG directed against F. hepatica and in plasma LDH and AST activities from 4 weeks after infection. Enzyme activities did not significantly differ from the baseline after 15 and 12 weeks for LDH and AST, respectively. GGT activity increased from 9 weeks postinfection and still remained significantly elevated at 18 weeks. In the parenchymal phase, both CT and MRI showed nodular lesions in five animals and MRI could also detect early tracks in the subcapsular area in three sheep. Ultrasound findings were nonspecific in this phase. Ductal dilatation was shown by ultrasound, CT and MRI in almost all animals, although MRI was inferior to CT in depicting a mild ductal dilatation. Moving echogenic forms in the dilated bile ducts were observed by ultrasound from 9 weeks postinfection in seven of the eight sheep. Moving worms were only demonstrated in four sheep at CT and in a single sheep at MRI. This study shows that radiological findings may be useful in studies of fluke-induced liver damage.

We have previously reported that melatonin modifies carbohydrate and lipid utilization in exercised rats, maintaining glycemia and reducing plasma and liver lactate and plasma β‐hydroxybutyrate. This study was undertaken to determine whether effects on fuel metabolism were related to changes in nitric oxide (NO) production or growth hormone (GH) secretion. Male Wistar rats received melatonin i.p. at a dose of 0.5 mg/kg body weight 30 min before being exercised to exhaustion on a treadmill at a speed of 24 m/min and a 12% slope. Melatonin ameliorated the decrease in plasma glucose and the increase in plasma urea, free fatty acid, β‐hydroxybutyrate, and nitrite induced by exercise. Melatonin‐treated exercised rats had significantly elevated liver glycogen content and hepatic tissue showed a lowered expression of both inducible and constitutive NO synthase (iNOS and cNOS). Administration of the NO inhibitor NG‐nitro‐l‐arginine (l‐NAME) to exercised rats caused a significant reduction in plasma nitrite, but liver glycogen and biochemical parameters in blood did not significantly differ from untreated exercised animals, indicating the absence of a direct association between melatonin effects on fuel metabolism and NO levels. Although results of treatment with pyridostigmine, a cholinergic agonist drug that stimulates GH release, partially differed from that of melatonin, modulation of GH secretion could play a role in the metabolic actions of the hormone because effects of melatonin on exercised rats were almost completely blocked by simultaneous administration of l‐NAME.

The yellow leaf curl disease of tomato is caused by a complex of virus species, two of which, tomato yellow leaf curl virus (TYLCV)-Sar and TYLCV-Is, are involved in epidemics of southern Spain. Plants of Mercurialis ambiguaand Solanum luteumshowing abnormal upward leaf curling and leaf distortion collected in the vicinity of tomato crops were found to be naturally infected with TYLCV-Is and TYLCV-Sar, respectively. These weed species, as well as Datura stramoniumand S. nigrum, which had also been found to be naturally infected by TYLCVs in the same region in previous studies, were tested for susceptibility to TYLCV-Sar or TYLCV-Is by Agrobacterium tumefaciens-mediated and by Bemisia tabaciinoculation. Results indicated that both TYLCV-Sar and TYLCV-Is were able to infect D. stramoniumand M. ambigua, whereas only TYLCV-Sar infected S. nigrumand S. luteum. Implications for the epidemiology of TYLCV are discussed. This is the first report of M.ambiguaand S. luteumas hosts of TYLCV.

Background. This study aimed to evaluate purified protein derivative (PPD) reactivity and its interrelationship with anergy panel and CD4+ lymphocytes in HIV-infected subjects as compared to PPD reactivity in HIV-uninfected individuals in a tuberculosis endemic and high Bacillus Calmette-Guérin (BCG) coverage environment.
Method. Clients of four Mexico City HIV detection centres were screened for HIV-1 antibodies (ELISA or haemagglutination, Western Blot); reactivity to PPD (Mantoux PPD, 5TU RT-23), Candida (1:1000, 0.1 ml), and tetanus toxoid (10Lf, 0.1 ml); and CD4+ T cells. Active tuberculosis was excluded. Informed consent was obtained.
Results. From 5130 clients 1168 subjects were enrolled; of these 801 (68.6%) were HIV positive. Reactivity to PPD among HIV-positive subjects was found in 174 (22%), 261 (32.6%), and 296 (37%), at PPD cutoff levels of 10 mm, 5 mm, and 2 mm as compared to 224 (61%) of 367 HIV-negative individuals' reactors to PPD (10 mm) (P&lt;0.001). After exclusion of anergic individuals using two cutoff levels for cutaneous allergens (2 mm and 5 mm), PPD reactivity between HIV-infected and uninfected individuals continued to be significantly different. Only HIV-infected individuals with CD4+ T cells 500 cells/mm³ had similar reactivity to PPD as HIV-uninfected individuals. Variables associated with PPD reactivity were CD4+ T cell counts, BDG scar, HIV infection and age.
Conclusion. PPD reactivity was useful to diagnose tuberculosis infection only among HIV-infected individuals with CD4+ counts 500 cells/mm³. Among individuals with lower counts, lowering cutoff levels or using anergy panel did not permit comparable reactivity as that observed among HIV-uninfected individuals.

This study aimed to evaluate purified protein derivative (PPD) reactivity and its interrelationship with anergy panel and CD4+ lymphocytes in HIV-infected subjects as compared to PPD reactivity in HIV-uninfected individuals in a tuberculosis endemic and high Bacillus Calmette-Guérin (BCG) coverage environment.

Abstract: The purpose of our study was to assess the effects of experimental dicroceliosis on the antioxidant defense capability of the liver in hamsters. Studies were carried out at 80 and 120 days after infection with an oral dose of 40 metacercariae of Dicrocoelium dendriticum. The parasitic pathology was ascertained by the presence of fluke eggs in feces, increased serum ALT and AST activities, and histological findings. The concentration of thiobarbituric acid-reactive substances (TBARS) and the ratio of oxidized to reduced glutathione (GSSG/GSH), measured as markers of oxidative stress, were significantly increased [TBARS: +40% and +84% at 80 and 120 days postinfection (p.i.), respectively; GSSG/GSH: +200% and +117%]. Dicroceliosis increased Se-dependent glutathione peroxidase (GPx) activity in both cytosol (+24% and +46%) and mitochondria (+73% and +41%). Superoxide dismutase activity was significantly reduced in cytosol (−19% and −38%) and mitochondria (−20% and −39%). No significant change was found in the activity of Se-independent GPx or catalase. The ratio of glutathione peroxidase/glutathione reductase at 80 and 120 days p.i. was increased by 25% and 63%, respectively. Gamma-glutamyl cysteinyl synthetase activity was increased by 27% and 20%, respectively. Our data indicate that although dicroceliosis courses with activation of antioxidant enzymes and glutathione synthesis, inefficient scavenging of reactive oxygen species takes place, resulting in oxidative liver damage.

The role of nitric oxide (NO) in acute renal failure (ARF) is not yet completely understood. L-Arginine (L-arg) is protective against different ARF models, while L-arg addition in isolated proximal tubules enhances hypoxia/reoxygenation (H/R) injury. The aim of this study was to evaluate the effects of L-arg on renal ischaemia.

This paper deals with aspects of the production and use of soybeans in Brazil, and the contribution by the Instituto de Tecnologia de Alimentos, ITAL, to the research and development of popular institutionalized products, based on soybeans. Two programs for food supplementation, one on a national level, and the other on a regional level, are described. All the products utilized contain soybeans as a protein source, and are directed at 6-to-14-yr-olds. The paper also describes products that the food industry has commercialized for the official institutional programs, industrial and hospital restaurants. The report also shows the results of a campaign to increase the use of soybeans by the population.

Abstract: This paper deals with aspects of the production and use of soybeans in Brazil, and the contribution by the Instituto de Tecnologia de Alimentos, ITAL, to the research and development of popular institutionalized products, based on soybeans. Two programs for food supplementation, one on a national level, and the other on a regional level, are described. All the products utilized contain soybeans as a protein source, and are directed at 6-to-14-yr-olds. The paper also describes products that the food industry has commercialized for the official institutional programs, industrial and hospital restaurants. The report also shows the results of a campaign to increase the use of soybeans by the population.

Acid phosphatase from bee venom was purified by a combination of saturated ammonium sulphate precipitation, gel filtration and ion exchange chromatography. The final product which is a glycoprotein contained less than 0.1% phospholipase A2or hyaluronidase activity and existed in two molecular weight (96,000 and 45,000) forms. Acid phosphatase is a potent allergen, in bee venom allergic patients, which is capable of releasing histamine from sensitized human basophils and of inducing a wheal and flare reactions in sensitized human skin.

Transient transfection of expression vectors for various members of the hematopoietin receptor family and STAT proteins into COS-1 cells indicated that each receptor was capable of stimulating the DNA binding activity of STAT1, STAT3, and STAT5B. However, gp130 preferentially activated STAT1 and STAT3. Activation of STAT5B differed from that of the other two in that the box 3 sequence motif in the cytoplasmic domain of gp130 was not required. Moreover, STAT5B and STAT3 enhanced gene transcription via separate regulatory elements. This study has identified two potential signal transduction pathways by which hematopoietin receptors, including the interleukin-6 receptor, control transcription of acute phase plasma protein genes in hepatic cells.

Treatment of rat hepatoma cells with insulin attenuated the interleukin 6 (IL-6) stimulation of acute phase plasma protein genes. To identify the potential mechanism of this action, the influence of insulin on IL-6 signal transduction was determined. An insulin dose-dependent reduction in signal transducer and activator of transcription 3 (STAT3) gene transcription, mRNA accumulation, protein concentration, and IL-6-inducible DNA binding activity was detected. A reduction in the IL-6-activated sis-inducible element binding of STAT3 was observed within 4 h of insulin treatment, whereas a maximal 3-4-fold lower STAT protein concentration was measured after 8-24 h of insulin treatment. Insulin mediated a similar magnitude reduction in the amount of mRNA encoding the IL-6 receptor alpha subunit and IL-6 binding activity. These effects of insulin appear to contribute to the strongly suppressed transcriptional induction of the IL-6-responsive acute phase plasma protein genes.

Several endocrine hormones which influence liver metabolism are known to increase in activity during the acute phase of injury or inflammation. We determined whether these hormones have the potential to influence acute-phase protein production in human and rat hepatoma cells. Catecholamines, glucagon, growth hormone, triiodothyronine, and cyclic nucleotides individually or in combination did not modulate the basal or the interleukin-1 (IL-1)-, IL-6-, and dexamethasone-stimulated levels of acute-phase plasma proteins. Insulin, however, was found to be a rapid, nonspecific, and dose-dependent inhibitor of the cytokine and glucocorticoid stimulation of acute-phase protein gene expression and to exert its effect at the transcriptional level. The insulin inhibition applied to all cytokines tested but to various degrees, depending upon the particular acute-phase gene. Insulin resulted in an early and prominent increase in the transcription of genes encoding the AP-1 components of JunA, JunB, and c-Fos, as has been observed for other growth factors. However, the effect of insulin on C/EBP beta was unexpected and paradoxical: while insulin completely inhibited the transcriptional activation of the C/EBP beta gene in cytokine- and dexamethasone-treated cells, the level of cytoplasmic C/EBP beta RNA was elevated. Quantitation of C/EBP beta mRNA by Northern (RNA) blot analysis and of C/EBP beta DNA binding activity by Southwestern (DNA-protein) blot analysis showed that insulin, when combined with cytokines and dexamethasone, stimulated both the mRNA and DNA binding activity by a factor of 1.6 compared with that of cells treated with cytokines and dexamethasone alone. Transient transfection of H-35 and HepG2 cells with a chloramphenicol acetyltransferase (CAT) gene expression vector containing the C/EBP beta response element also resulted in a 1.5-fold increase of C/EBP beta-mediated transcription in insulin-treated cells. Transfection of CAT gene constructs containing increasing lengths of heptaglobin gene 5' flanking sequences indicated that insulin inhibition of IL-6 stimulation required the presence of the region from -4100 to -1030. These results suggest that insulin has the potential to control the transcription of acute-phase genes by at least two separate mechanisms.