Infusion of tumor necrosis factor/cachectin promotes muscle catabolism in the rat. A synergistic effect with interleukin 1.

To improve our understanding of the metabolic role of cytokines in protein wasting, we estimated the rates of protein synthesis and degradation in muscle and liver tissues in intact rats treated with several doses of recombinant IL 1 and/or tumor necrosis factor (TNF)/cachectin. Protein breakdown in muscle and liver were derived in vivo from the relationship between [14C]leucine distribution and tissue dilution in reference to circulating leucine. Synthesis was derived from the relationship between [14C]leucine appearance in the protein-bound and free-tissue leucine pools. To specifically relate changes in leucine tracer metabolism to protein dynamics, we separately measured the effect of these cytokines on blood flow to different tissues. The increase in dilution of the tissue-free [14C]leucine by TNF and TNF/IL 1 mixture, but not by IL 1 alone, could not be explained by a hemodynamic effect of these cytokines. Rather, this finding indicated that muscle proteolysis is enhanced by TNF and synergistically augmented by the addition of IL 1. Compatible with these data was the finding that more prolonged infusions of recombinant TNF/cachectin and the combination with IL 1 increased urinary nitrogen excretion. Changes in [14C]leucine dilution in the liver were less pronounced than those in skeletal muscle and consistent with net anabolic effect of TNF on liver protein. We conclude that rats exposed systemically to sublethal doses of TNF respond with increasing muscle and decreasing liver proteolysis, similar to that observed in inflammation and in cancer.

Surface-enhanced vibrational spectra of 2-nitrofluorene.

The infrared and Raman spectra of the isolated adsorbate 2-nitrofluorene (2NF) have been registered and the spectral assignment was performed on the basis of both previous data concerning related molecules and density functional theory DFT calculations. The theoretical calculations were compared to the experimental results, obtaining a good agreement with the IR and Raman data. The surface-enhanced infrared and Raman spectra, SEIRA and SERS, of 2NF on different metal surfaces were registered; the best spectra were obtained by using the 633nm laser line. The most probable orientation and organization of the adsorbate on the surface were inferred from the reflection-absorption infrared spectrum RAIRS and SERS and SEIRA data.

Vibrational and surface-enhanced vibrational spectra of 6-nitrochrysene.

The infrared and Raman spectra of solids and thin solid films of 6-nitrochrysene, its electronic spectra, and resonance Raman scattering (RRS) obtained with UV-laser excitation at 325 nm are reported. The vibrational assignment is supported by ab initio computations at the B3LYP/6-311G(d, p) level of theory. The molecular organization in nanometric films evaporated onto smooth metal surfaces of silver and copper was probed using reflection-absorption infrared spectroscopy (RAIRS). The results of the surface-enhanced Raman scattering (SERS) and surface-enhanced infrared absorption (SEIRA) obtained from nanometric films evaporated onto silver island films are also discussed. It was found that the molecule efficiently interacts with silver island film surfaces, and that the interaction leads to extensive photochemical reaction at the metal surface under laser illumination.

Effect of interleukin-1 and tumor necrosis factor/cachectin on glucose turnover in the rat.

We studied the effect of recombinant human interleukin-1 beta (IL-1) and recombinant human tumor necrosis factor alpha/cachectin (TNF) on glucose kinetics in healthy rats by means of a primed constant infusion of D-(6-3H)glucose and D-[U-14C]glucose. During the isotope (6-hour) and monokine (4-hour) infusion, plasma levels of glucagon and insulin were determined and correlated with changes in glucose metabolism. The rates of glucose appearance (Ra) and disappearance (Rd) were elevated only with IL-1 and were associated with an increase in glucagon and a concomitant decrease in the ratio of insulin to glucagon. Plasma glucose concentration was increased early after IL-1 administration and coincided with the peak in the Ra. The augmentation of the metabolic clearance rate (MCR) and percent of flux oxidized by IL-1 suggest that this monokine induces the utilization of glucose as a substrate. TNF administration failed to modify the Ra or Rd, percent of flux oxidized, or MCR. TNF-treated rats increased the percent of glucose recycling, but not the total rate of glucose production. The results of this experiment suggest that endogenous macrophage products participate in the diverse alterations of carbohydrate metabolism seen during injury and/or infection.

Ciprofibrate versus gemfibrozil in the treatment of mixed hyperlipidemias: an open-label, multicenter study.

Mixed hyperlipidemia is a common risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of ciprofibrate versus gemfibrozil for the treatment of patients with mixed hyperlipidemia carefully selected for similar lipid profiles. A total of 68 patients who had mixed hyperlipidemia after following an isocaloric American Heart Association (AHA) phase I diet for 4 weeks were included. The plasma lipid levels at the inclusion were low-density lipoprotein-cholesterol (LDL-C) > or = 130 mg/dL, cholesterol > or = 240 mg/dL, and triglycerides > or = 200 mg/dL. Patients were randomly assigned to receive ciprofibrate 100 mg/d or gemfibrozil 1,200 mg/d. At the end of the 8-week treatment period, efficacy and safety parameters were compared with baseline values. The primary efficacy parameters of the study were percentage changes in triglycerides and LDL-C from baseline. After 8 weeks, plasma triglyceride concentrations were decreased by 43.5% and 54% compared with baseline during ciprofibrate and gemfibrozil therapy, respectively (P <.001). High-density lipoprotein-cholesterol (HDL-C) concentrations were increased 20.8% and 19.3% during ciprofibrate and gemfibrozil, respectively (P <.001). Apoprotein B, cholesterol, and very-low-density lipoprotein-cholesterol (VLDL-C) concentrations were also improved by the study drugs (18.6%, 13.2%, and 30.9%, respectively, during ciprofibrate and 44%, 13.8%, and 14.4%, respectively, during gemfibrozil). Meanwhile, the effect of the drug was minimal on LDL-C. A significant decrease in non-HDL-C resulted from both treatments (19% and 19.5%, respectively, P <.05). The only statistically significant difference observed between treatments was the effects on fibrinogen concentration, a coronary risk factor. Ciprofibrate significantly decreased its concentration by 18.8%, fibrinogen was slightly increased during gemfibrozil treatment. No patient had a significant modification on any of the safety tests. In summary, ciprofibrate and gemfibrozil are well-tolerated and efficacious treatments for mixed hyperlipidemia. Significant reductions in triglycerides, non-HDL-C, and apolipoprotein B were achieved with both drugs. A significant fibrinogen reduction was obtained with ciprofibrate.

Role of biochemical mediators in clinical nutrition and surgical metabolism.

Over the past several decades, research on the role of mediators in inflammation, immunity, repair processes, cell growth, and substrate metabolism have centered around the use of purified products of stimulated macrophages. With the current availability of recombinant mediators, the participation of individual monokines in cellular metabolism has been more clearly defined. Interactions among various mediators have been demonstrated, but their exact role in metabolism is currently under intense study. With the use of recombinant monokines, formal evidence for their participation in the acute phase response has been developed. Their use has also assisted in the reinterpretation of data gathered in older studies using purified preparations, which were almost certainly contaminated with several monokines. In this review we will try to give the reader insight into recent advances in the understanding of the role of cellular mediators in relation to nutrition and intermediary metabolism. With a clearer knowledge of the role of cellular mediators in the pathophysiology of disease, it may be possible to develop rationales for their therapeutic use as modulators of substrate metabolism during critical illness.

Vibrational spectra and surface-enhanced vibrational spectra of 1-nitropyrene.

The present report on the vibrational spectra of 1-nitropyrene (1NP) describes the infrared and Raman spectra; their interpretation is aided by local density functional theory (DFT) calculations at the B3LYP/6-311G(d, p) level of theory and by the surface-enhanced vibrational spectra (SEVS) with the final objective of trace organic analytical applications. The surface-enhanced Raman scattering (SERS) on silver island films and mixed silver/gold island films was investigated with several laser lines in the visible region. Surface-enhanced infrared absorption (SEIRA) was attempted on silver and gold island films. The interface of the organic 1-NP with smooth metal surfaces of silver and copper was also probed using reflection-absorption infrared (RAIRS) spectra that, in conjunction with the transmission spectra, allow one to extract the molecular orientation in vacuum evaporated thin solid films. Chemical adsorption of 1-NP on silver and further photochemical decomposition of the 1-NP-metal adsorbates was detected with all visible laser lines. Resonance Raman scattering (RRS) using UV-laser excitation at 325 nm was also recorded.

Diets enriched with N-3 fatty acids ameliorate lactic acidosis by improving endotoxin-induced tissue hypoperfusion in guinea pigs.

The effect of 6 weeks dietary lipid manipulation on the acute physiologic response to 7-hour continuous endotoxin infusion in guinea pigs was examined. One diet was enriched with N-3 fatty acids, whereas the other contained N-6 fatty acids, primarily linoleic acid. Animals fed N-6 fatty acids developed significant lactic acidemia, microvascular muscle hypoperfusion, and pulmonary infiltrates in response to endotoxin infusion. N-3 fatty acid-fed animals demonstrated improved lactate levels, microvascular muscle perfusion, and lung morphology compared to N-6 fatty acid-fed animals after endotoxin infusion. There was no significant change in cardiac output, PaO2, or mean arterial blood pressure at the end of the endotoxin infusion in either group. Pretreatment with indomethacin, or BM 13505, a specific thromboxane A2 receptor blocker, ameliorated the development of metabolic acidosis in N-6 fatty acid-fed animals, demonstrating a role for prostanoids in the sequelae of endotoxemia. The ability of dietary pretreatment with N-3 fatty acids to influence favorably the physiologic response to endotoxin represents a novel nutrient-metabolic interaction with potential therapeutic implications.

Leukocyte endogenous mediator fails to alter protein dynamics in a model of liver dysfunction.

This study examines the effect of a purified leukocyte-derived endogenous mediator (LEM) on protein metabolism during liver dysfunction and after sham surgery and the role of a nonsteroidal, antiinflammatory drug (indomethacin sodium trihydrate) in modifying this response. Febrile response, protein kinetics, urinary end products of protein metabolism, and plasma acute phase protein levels were studied in rats given a pyrogenic dose of LEM or saline solution, and these same indicators were studied after the administration of the same dose of LEM plus 2 mg/kg indomethacin 3 weeks after a portacaval shunt (PCS) or sham operation. In both surgical groups given LEM, a maximum of 1.1 degrees C fever was observed. LEM increased protein turnover and urinary excretion of nitrogen and urea in sham-operated rats but not in the PCS animals. Administration of indomethacin decreased the plasma oxidation of L[1-14C]leucine and prevented the increased excretion of total nitrogen and urea in sham-operated animals treated with LEM. PCS animals showed a constant excretion of nitrogen and urea independent of treatment. alpha 1-Acid glycoprotein levels increased significantly in sham-operated animals treated with LEM but not in the PCS group until indomethacin was added. The coadministration of LEM and indomethacin in shams also enhanced the levels of alpha 2-macroglobulin and alpha 1-acid glycoprotein over values found with LEM alone. These findings confirm the catabolic effect of LEM in normal animals and identify the essential role of the liver in the acute phase response. The data also suggest that indomethacin may modify the acute phase response by reducing plasma amino acid oxidation as well as enhancing the levels of some specific acute phase proteins.