[The influence of alanyl-glutamine on immunologic functions and morbidity in postoperative total parenteral nutrition. Preliminary results of a prospective randomized trial]. / Einfluss von Alanyl-Glutamin bei der postoperativen totalen parenteralen Ernährung auf die Morbidität unter besonderer Berücksichtigung der Immunfunktion. Erste Ergebnisse einer prospektiv randomisierten Studie.

Glutamine seems to play an important role in metabolism and function of immunologic cells and therefore could also influence postoperative immunosuppression in surgical patients. Nevertheless, the influence of glutamine substitution in postoperative total parenteral nutrition on immunologic function and postoperative morbidity of patients is still unknown. Therefore, the impact of glutamine substitution on postoperative immunosuppression and incidence of complications was investigated in patients with surgical interventions on esophagus or stomach and total parenteral nutrition in a prospective randomized trial. To analyse the immunologic competence of the patients, the expression of CD-3, CD-4, and CD-8 on lymphocytes as well as the expression of HLA-DR and CD-14 on monocytes were evaluated before, 1, 2, 4, 7 days after surgery. Furthermore, plasma levels of IL-6 and IL-10 were analysed during the perioperative course. Actually, 34 patients have been included (with glutamine: n = 18 vs. without glutamine: n = 16) in the study. Patients with glutamine substitution showed non significantly decreased systemic inflammation (IL-6-plasma levels, leucocytosis) and significantly faster compensation of postoperative immunosuppression (HLA-DR-monocytes). Incidence of postoperative complications was decreased after glutamine substitution compared with the control group. Patients without postoperative complications showed no significant difference in postoperative immunosuppression. Although additional substitution of the amino acid glutamine might possibly decrease incidence of postoperative complications in patients with total parenteral nutrition a general advantage in postoperative immune function could not be demonstrated.

Multicomponent trace-gas analysis by three intracavity photoacoustic cells in a CO laser: observation of anaerobic and postanaerobic emission of acetaldehyde and ethanol in cherry tomatoes.

Three serial photoacoustic cells are employed within the cavity of a liquid-nitrogen-cooled CO laser to monitor on-line trace-gas concentrations. Multicomponent gas analysis is performed on sequential repetitive measurements of ethylene, acetaldehyde, CO2, ethanol, and H2O. To demonstrate the high sensitivity of the laser photoacoustic detector for the biologically interesting gases, acetaldehyde (0.1-parts per billion in volume detection limit) and ethanol (10 parts per billion in volume), we follow the time-dependent release by cherry tomatoes during changing aerobic-anaerobic conditions.

[Effect of alanyl-glutamine in postoperative total parenteral nutrition on postoperative immunosuppression and morbidity. Preliminary results of a prospective randomized study]. / Einfluss von Alanyl-Glutamin bei der postoperativen totalen parenteralen Ernährung auf die postoperative Immunsuppression und die Morbidität. Vorläufige Ergebnisse einer prospektiv randomisierten Studie.

The impact of glutamine substitution on postoperative immunosuppression and morbidity was investigated in patients with surgical interventions and total parenteral nutrition in a prospective randomized trial. To analyze immune competence, the expression of CD3, CD4, and CD8 on lymphocytes and of HLA-DR and CD14 on monocytes as well as the plasma levels of IL-6 and IL-10 was evaluated before, 1, 2, 4, and 7 days after surgery. A total of 34 patients have been included (with glutamine: n = 18; without glutamine: n = 16). Patients with glutamine substitution showed decreased systemic inflammation, significant faster compensation for postoperative immunosuppression and a lower incidence of postoperative complications. Patients without postoperative complications showed no significant differences in postoperative immunosuppression.

[Immune stimulation with G-CSF (Neupogen) in septic patients with immune paralysis]. / Immunstimulation durch G-CSF (Neupogen) bei septischen Patienten mit Immunparalyse.

Ten patients with sepsis (HLA-DR+ monocytes < 30%) were treated with G-CSF (300 mg Filgrastin, Neupogen 30, Amgen). All patients showed a rise in HLA-DR+ monocytes during therapy. In six patients the high level of HLA-DR+ monocytes persisted after therapy; these patients survived. In the other four patients the number of HLA-DR+ monocytes declined after application of G-CSF, and the patients died of multiorgan failure. Some patients with sepsis might profit from immunestimulating therapy with G-CSF, but further studies are needed to prove whether or not this is true.

Dynamics of Acetaldehyde Production during Anoxia and Post-Anoxia in Red Bell Pepper Studied by Photoacoustic Techniques.

Acetaldehyde (AA), ethanol, and CO2 production in red bell pepper (Capsicum annum L.) fruit has been measured in a continuous flow system as the fruit was switched between 20% O2 and anaerobic conditions. Minimum gas phase concentrations of 0.5 nL L-1, 10 nL L-1, and 1 mL L-1, respectively, can be detected employing a laser-based photoacoustic technique. This technique allows monitoring of low production rates and transient features in real time. At the start of anaerobic treatment respiration decreases by 60% within 0.5 h, whereas AA and ethanol production is delayed by 1 to 3 h. This suggests a direct slow-down of the tricarboxylic acid cycle and a delayed onset of alcoholic fermentation. Reexposure of the fruit to oxygen results in a 2- to 10-fold upsurge in AA production. A short anoxic period leads to a sharp transient peak lasting about 40 min, whereas after numerous and longer anoxic periods, post-anoxic AA production stays high for several hours. High sensitivity of the fruit tissue to oxygen is further evidenced by a sharp decrease in post-anoxic AA production upon an early return to anaerobic conditions. Ethanol oxidation by the "peroxidatic" action of catalase is proposed to account for the immediate post-anoxic AA upsurge.

On-line monitoring of nitrogenase activity in cyanobacteria by sensitive laser photoacoustic detection of ethylene.

A new and extremely sensitive method for measuring nitrogenase activity through acetylene reduction is presented. Ethylene produced by nitrogenase-mediated reduction of acetylene is detected by using laser photoacoustics (LPA). This method possesses a detection limit making it 3 orders of magnitude more sensitive than traditional gas chromatographic analysis. Photoacoustic detection is based on the strong and unique absorption pattern of ethylene in the CO(inf2) laser wavelength region (9 to 11 (mu)m). The high sensitivity allowed on-line monitoring of nitrogenase activity in a culture of the heterocystous cyanobacterium Nodularia spumigena, which was isolated from a water bloom in the Baltic Sea. This setup makes it unnecessary to take subsamples from the culture and avoids long incubations in sealed vials. The fast response of the LPA technique allows measurement of real-time dynamic changes of nitrogenase activity. The method was used to analyze in vivo saturation of nitrogenase by acetylene in N. spumigena. It is demonstrated that 20% acetylene does not saturate nitrogenase and that the degree of saturation depends on light intensity. With concentrations of acetylene as low as 2.5% it is possible to assess the degree of saturation and to extrapolate to total nitrogenase activity. In N. spumigena nitrogenase activity becomes independent of light intensity above 20 to 80 (mu)mol of photons m(sup-2) s(sup-1) at 20% O(inf2).

Monocyte deactivation--rationale for a new therapeutic strategy in sepsis.

Inflammatory cells, in particular monocytes/macrophages, release pro-inflammatory mediators in response to several infectious and non-infectious stimuli. The excessive release of these mediators, resulting in the development of whole body inflammation, may play an important role in the pathogenesis of sepsis and septic shock. TNF-alpha, acting synergistically with cytokines such as IL-1, GM-CSF and IFN-gamma, is the key mediator in the induction process of septic shock, as shown in several experimental models. Based on this concept and on the encouraging results obtained in several experimental models, a number of clinical sepsis trials targeting the production or action of TNF-alpha or IL-1 have been performed in recent years. Unfortunately, these trials have failed to demonstrate a therapeutic benefit. One reason for this may be the lack of exact immunologic analyses during the course of septic disease. Recently, we demonstrated that there is a biphasic immunologic response in sepsis: an initial hyperinflammatory phase is followed by a hypo-inflammatory one. The latter is associated with immunodeficiency which is characterized by monocytic deactivation, which we have called "immunoparalysis". While anti-inflammatory therapy (e.g. anti-TNF antibodies, IL-1 receptor antagonist, IL-10) makes sense during the initial hyperinflammatory phase, immune stimulation by removing inhibitory factors (plasmapheresis) or the administration of monocyte activating cytokines (IFN-gamma, GM-CSF) may be more useful during "immunoparalysis".

Mechanism of endotoxin desensitization: involvement of interleukin 10 and transforming growth factor beta.

Tolerance of monocytes/macrophages to endotoxin (lipopolysaccharide [LPS]) can be induced both in vivo and in vitro by LPS itself. Exposure to LPS, even at a very low dose, induces a downregulation of cytokine response to a second high dose LPS challenge. To learn more about the unknown mechanisms of this phenomenon, we studied the role of antiinflammatory cytokines in this process. Preculture of human peripheral blood monocytes for 24 hours with low concentrations of LPS induced hyporesponsiveness to high-dose LPS rechallenge with respect to tumor necrosis factor (TNF) alpha and interleukin (IL) 10 but not IL-1RA production. These results suggest that LPS tolerance reflects a functional switch of monocytes rather than a general LPS hyporesponsiveness. IL-10 and transforming growth factor (TGF) beta 1 showed additive effects in replacing LPS for induction of LPS hyporesponsiveness in vitro. Additionally, neutralizing anti-IL-10 and anti-TGF-beta monoclonal antibodies prevented induction of LPS tolerance. In vitro induced LPS tolerance looks like the ex vivo LPS hyporesponsiveness of monocytes from septic patients with fatal outcome: downregulation of LPS-induced TNF-alpha and IL-10 production but not of IL-1RA secretion. LPS hyporesponsiveness in septic patients was preceded by expression of IL-10 at both the mRNA and protein level. In summary, our data suggests that IL-10 and TGF-beta mediate the phenomenon of LPS tolerance in vitro and perhaps in vivo (septic patients), too.

Cytomegalovirus reactivation and tumour necrosis factor.

Tumour necrosis factor-alpha (TNF) stimulates cytomegalovirus (CMV) activity in a transfected human monocytic cell line. We assessed whether this finding is relevant in vivo by evaluating the frequency of active CMV infection in patients with diseases that enhance plasma TNF. In septic disease, peripheral blood mononuclear cells of almost all patients studied were positive for CMV. Furthermore, CMV antigenaemia and enhanced plasma TNF occurred in many patients with liver cirrhosis, common variable immunodeficiency, and B-cell chronic lymphocytic leukaemia. Thus, TNF may have a central role in CMV reactivation.

The strategies and autonomy of university hospitals in competitive environments.

University-owned hospitals face increasingly threatening and unstable environments. This article examines the strategies that university-owned hospitals are using, and can use, to respond to their changing environments. Further, it examines factors that can hinder or promote the effective development of university-owned hospital strategies.

Arachidonic acid metabolism in human granulosa cells: evidence for cyclooxygenase and lipoxygenase activity in vitro.

In view of the studies demonstrating the involvement of eicosanoids (prostaglandins and hydroxyperoxides, including leukotrienes) in ovulation in several mammalian species, we have examined the activity of the two enzyme systems, lipoxygenase and cyclooxygenase in human granulosa cells obtained from women undergoing in-vitro fertilization--embryo transfer. The activity of cyclooxygenase was assessed by radioimmunoassay of prostaglandin E and of 6-keto-prostaglandin F1 alpha, the conversion product of prostacyclin, accumulated in the culture medium of granulosa cells. Lipoxygenase activity was detected by the conversion of [14C]arachidonic acid into its products (hydroxyperoxides and leukotrienes) separated by reversed phase high-performance liquid chromatography. The results confirmed the activity of cyclooxygenase in human granulosa cells, production in vitro of prostaglandin E and prostacyclin and demonstrated the presence of active lipoxygenase enzymes. These results support the possible involvement of eicosanoids in ovulation of the human.