Regulatory potential of n-3 fatty acids in immunological and inflammatory processes.

Over the last few years immunonutrition has gained increasing importance. Among other compounds lipids, especially n-3 polyunsaturated fatty acids, were shown to influence the immune response. The anti-inflammatory effects they exert can be induced by free fatty acids, triglyceride fatty acids, after incorporation into the membrane phopspholipid bilayer or following metabolism to eicosanoids. n-3 Fatty acids influence inflammatory cell activation processes from signal transduction to protein expression even involving effects at the genomic level. n-3 Fatty acid-mediated mechanisms decreased cytokine-induced adhesion molecule expression, thereby reducing inflammatory leucocyte-endothelium interactions and modified lipid mediator synthesis, thus influencing the transendothelial migration of leucocytes and leucocyte trafficking in general. Even the metabolic repertoire of specific immunocompetent cells such as cytokine release or proliferation is modified by n-3 fatty acids. Beyond this they regulate lipid homeostasis shifting the metabolic pathways towards energy supply thus optimizing the function of immune cells. Due to the regulatory impact on different processes of inflammatory and immune cell activation n-3 fatty acids provide positive effects on various states of immune deficiencies and diseases with a hyperinflammatory character, among which selected examples are presented.

Parenteral nutrition with n-3 lipids in sepsis.

Dietary supplements of n-3 fatty acids have long been used to influence chronic inflammatory disorders. Recent studies with an immune-enhancing diet partly based on n-3 fatty acids report beneficial effects in patients with acute hyper-inflammatory diseases, such as the sepsis syndrome or adult respiratory distress syndrome (ARDS). The possible suppression of exaggerated leucocyte activity, the improvement of microcirculatory events, as well as the opportunity to administer intravenous lipids enriched in n-3 fatty acids signal the possibility of a combination of parenteral caloric support and pharmacological intervention. Using parenteral administration of fish oil-based lipids, a new rapid and highly effective anti-inflammatory agent may allow the option to alter the immune status in hyper-inflammatory diseases such as sepsis and ARDS.

n-3 fatty acids in psoriasis.

Increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Replacement of arachidonic acid by alternative precursor polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA), which can be metabolized via the same enzymatic pathways as AA, might be a therapeutic option in psoriasis. However the results of studies evaluating the therapeutic benefit of dietary fish oil have been conflicting and not clearly dose-dependent. To overcome the slow kinetics and limited availability of oral supplementation, we have performed three studies to assess the efficacy and safety of an intravenously administered fish oil derived lipid emulsion on different forms of psoriasis. Patients received daily infusions of either an n-3 fatty acid-based lipid emulsion (Omegaven) or a conventional n-6 lipid emulsion (Lipoven) in different time and dose regimens. In addition to an overall assessment of the clinical course of psoriasis, EPA- and AA-derived neutrophil 5-lipoxygenase (LO)--products, thromboxane (TX) B2/B3, PAF and plasma free fatty acids were investigated. Treatment with n-3 fatty acids resulted in a considerably higher response rate than infusion of n-6 lipids. A more than 10-fold increase in neutrophil EPA-derived 5-LO product formation was noted in the n-3 group, accompanied by a rapid increase in plasma-free EPA within the first days. In conclusion, intravenous n-3-fatty acid administration causes reduction of psoriasis, which may be related to changes in inflammatory eicosanoid generation. The rapidity of the response to intravenous n-3 lipids exceeds by orders of magnitude the hitherto reported kinetics of improvement of psoriatic lesions upon use of oral supplementation.

Immunonutrition--supplementary amino acids and fatty acids ameliorate immune deficiency in critically ill patients.

BACKGROUND: Immunonutrition with omega-3 fatty acids and the "conditionally essential" amino acids arginine, glutamine, cysteine, and taurine can enhance the immune response in critically ill patients. This is due to the immunomodulating properties of these nutrients. Immunonutrition is especially important when a patient's immune response is compromised, as is the case post-operatively or after trauma. Immune deficiency is severely aggravated in sepsis and the systemic inflammatory response syndrome (SIRS). The resulting metabolic stress is characterized by glycolysis, lipolysis, and proteolysis, which may escalate to an hypercatabolic response or "autocannabilism." Catabolic metabolism results in insufficiency of both specific and unspecific immunocompetent cells. CONCLUSIONS: Immunonutrition should be started early in such patients for an optimal beneficial effect, preferably via the enteral route. It should include medium chain and long chain triglycerides, polyunsaturated omega-3 and omega-6 fatty acids (in the ratio 1:2), olive oil, and conventional amino acid preparations supplemented with the conditionally essential amino acids arginine, glutamine, cysteine, and taurine.

Omega-3 lipid infusion in a heart allotransplant model. Shift in fatty acid and lipid mediator profiles and prolongation of transplant survival.

BACKGROUND: omega-3 Fatty acids may have a major impact on immune responses involved in heart transplant rejection. We compared the effects of posttransplant intravenous supplementation with omega-3-rich versus omega-6-rich lipid emulsions on graft survival, plasma fatty acid profiles, and levels of arachidonic acid versus eicosapentaenoic acid-derived lipid mediators. METHODS AND RESULTS: Inbred PVG and Wistar-Kyoto rats were used as donors and recipients, respectively, in a model of heterotopic heart transplantation. Animals received 9 g/kg body wt per day of either fish oil-derived (n = 8) or soybean oil-derived fat (n = 7) in the form of a continuously infused lipid emulsion; controls were sham-infused with saline (n = 8). Graft rejection was assessed by loss of activity of the transplant. The fish oil-derived preparation but not that originating from soybean oil caused an increase in total and free plasma fatty acids. Substantial quantities of eicosapentaenoic acid and docosahexaenoic acid appeared in the free fatty acid fraction, surpassing those of arachidonic acid. Ex vivo stimulation of neutrophils with the Ca2+ ionophore A23187 demonstrated an increase in 5-series leukotriene (LT) generation in animals undergoing omega-3 lipid infusion (LTB5, omega-oxidation products of LTB5, LTA5 secretion), with 5-series/4-series LT ratios ranging between 0.08 and 0.36. Ratios of TX B3/B2 liberated from ex vivo stimulated platelets even approached 1:1 in omega-3 supplemented rats. Graft survival was 7.6 +/- 0.3 (mean +/- SEM) days in saline-infused, 10.4 +/- 0.7 in omega-6 lipid-infused, and 12.9 +/- 0.4 in omega-3 lipid-infused animals. CONCLUSIONS: Posttransplant intravenous alimentation with fish oil-derived lipid emulsions prolongs heart transplant survival in excess to omega-6 lipids. Profound changes in fatty acid profiles and lipid mediator generation may underlie this finding.

[Kinetics of bacterial wash-out in the Haemonetics Cell Saver III]. / Kinetik der Bakterienauswaschung im Cell-Saver III Haemonetics.

Autologous, outdated blood units were inoculated with four types of bacteria--Pseudomonas aeruginosa, Escherichia coli, Streptococcus faecalis, Staphylococcus aureus--in two concentrations (10e4, 10e6) to test the effect of the washing procedure (Cell Saver III Haemonetics) on the elimination of bacteria. The elimination rate ranged from 17% (Streptococcus faec. 10e4) to 96% (Pseudomonas aer. 10e6). These results confirm the routine use of wash centrifuge systems (type Cell Saver) to process shed wound blood as well as drainage blood for autologous transfusions.

Effect of selective ultraviolet phototherapy on DNA and antinuclear antibody titers in psoriatic patients.

The sera of 21 psoriatics treated by selective ultraviolet phototherapy (SUP) for 1-7 months were screened for IgG- and IgM-anti-DNA antibodies and antinuclear antibodies (ANAs) by standardized ELISA and the indirect immunofluorescence technique. No patients developed IgG-antibodies against native DNA under SUP, but two patients increased their IgM-antibody titers five- and tenfold, respectively. The IgG- and IgM-anti-single-stranded-(ss)DNA antibody titers remained unaltered in 38% and 57% of the patients. In 43% and 24%, respectively, they rose to a maximum of three times their original; and in 20% they decreased to a minimum of 40% of their pretherapeutic titers. After 1 month therapy no patient had produced ANAs, but all three patients showing ANAs before therapy had increased titers (one titer step). These remained on the elevated level or were even further increased by one-titer step during progressive therapy. Two patients out of 14 developed low titers of IgM-(1:20) or IgA-(1:40)ANAs against deoxyribonucleoprotein (DNP), initially after 3 months of irradiation; in one of them IgG-ANAs (titer 1:10) against DNP were additionally formed after 6 months of therapy. Our results suggest that lesions in DNA and DNP generated by SUP trigger an immune response to nuclear antigens.

Criteria for interpretation of agar diffusion susceptibility tests of norfloxacin performed by the ICS method.

Using regression analysis to correlate MIC values and inhibition zone diameters, an attempt was made to establish criteria for interpreting the results of the agar diffusion test with norfloxacin discs (10 mcg). The test was performed on DST agar in accordance with ICS recommendations. The correlation was moderate (r = -0.8547); the regression equation was x = -0.30y + 15.80, where x was log2 MIC + 9 and y the inhibition zone diameter. The position of the MIC breakpoints of norfloxacin and the distribution of the MIC values of the bacterial population did not permit precise inhibition zone breakpoints to be established. To allow a safety margin it is recommended that for the meantime norfloxacin inhibition zones be interpreted as sensitive from 15 mm onwards.

[What do we know of nutrition of children and juveniles in prehistoric and early historic time?]. / Was wissen wir über ur- und frühgeschichtliche Kindernahrung?

News are added to Peiper's "chronicle of pediatrics" concerning nutrition of children and juveniles in prehistoric and early historic periods. This may make possible some conclusions about "paleonutrition". Items come from 15 exactly localised sites and 4 more vague defined regions from the neolithic period to 1000 A. D.

[Home remedies and prescriptions for children and juveniles, based on individual data from the 17th through the 19th century]. / Hausmittel und ärztliche Verordnungen im Kindes- und Jugendalter nach individuellen Angaben aus dem 17. bis 19. Jahrhundert.

In personal recollections, letters a.s.o. written by 23 authors in the sixteenth to the nineteenth century are to be found 52 remarks on home remedies or prescriptions for children or juveniles. It seems that they belong more to dietetics than to pharmacotherapy.

[Beverages of children and youth in the 16th to 19th century, documented by contemporary recollections (author's transl)]. / Getränke für Kinder und Jugendliche im 16. bis 19. Jahrhundert, nach zeitgenössischen Selbstzeugnissen.

227 remarks on beverages, found in biographies, personal recollections, letters a. s. o. from the 16th to the 19th century are reviewed. As early as in the children's age alcoholic drinks are represented in 27%. There is a slight trend to a reduction of alcoholic drinks in the 19th century compared with three centures before. Remarks on tea and coffee and chocolate resp. cocoa are increasing in 19th century, especially in children.