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Metabolic and immune effects of dietary arginine, glutamine and omega-3 fatty acids supplementation in immunocompromised patients.
Chuntrasakul C; Siltharm S; Sarasombath S; Sittapairochana C; Leowattana W; Chockvivatanavanit S; Bunnak A
Research Center for Nutritional Support, Siriraj Hospital.
J Med Assoc Thai (Thailand) May 1998, 81 (5) p334-43

To evaluate the nutritional, metabolic and immune effects of dietary arginine, glutamine and omega-3 fatty acids (fish oil) supplementation in immunocompromised patients, we performed a prospective study on the effect of immune formula administered to 11 severe trauma patients (average ISS = 24), 10 burn patients (average % TBSA = 48) and 5 cancer patients. Daily calorie and protein administration were based on the patient's severity (Stress factor with the range of 35-50 kcal/kg/day and 1.5-2.5 g/kg/day, respectively) Starting with half concentration liquid immune formula through nasogastric tube by continuous drip at 30 ml/h and increasing to maximum level within 4 days. The additional energy and protein requirement will be given either by parenteral or oral nutritional support. Various nutritional, metabolic, immunologic and clinical parameters were observed on day 0 (baseline), day 3, 7, and 14. Analysis was performed by paired student-t test. Initial mean serum albumin and transferrin showed mild (trauma ) to moderate (burn and cancer) degree of malnutrition. Significant improvement of nutritional parameters was seen at day 7 and 14 in trauma and burn patients. Significant increase of total lymphocyte count (day 7, P < 0.01), CD4 + count (day 7, p < 0.01), CD8 + count (day 7, p < 0.0005 & day 14, p < 0.05), complement C3 (day 7, p < 0.005 day 14, p < 0.01), IgG (day 7, and 14, p < 0.0005), IgA (day 7, p < 0.0005 & day 14, p < 0.05), in all patients. C-reactive protein decreased significantly on day 7 (p < 0.0005) and day 14 (p < 0.005). 3 cases of burn wound infection, one case of UTI and one case of sepsis were observed. Two cases of hyperglycemia in burn, 3 cases of hyperbilirubinemia in trauma, 10 cases of elevated LFT (5 trauma /5 burn), and one case of hyponatremia in cancer patients were observed. Two cases of nausea, 4 cases of vomiting, 5 cases of diarrhea (< 3 times/day), 2 cases of abdominal cramp, 1 case of distension were observed. The feeding of IMMUNE FORMULA was well tolerated and significant improvement was observed in nutritional and immunologic parameters as in other immunoenhancing diets. Further clinical trials of prospective double-blind randomized design are necessary to address the so that the necessity of using immunonutrition in critically ill patients will be clarified.

Changes in the plasma concentrations of retinol, alpha-tocopherole and beta-carotene in polytraumatized patients and in patients with osteitis in dependence on the outcome of injury
Weiss E.; Buchholz I.; Schweigert F.J.
Dr. E. Weiss, Leiter Abteilung fur Unfallchirurgie, Parkkrankenhaus Leipzig-Dosen, Akad. Lehrkrankenhaus Univ. Leipzig, Chemnitzer Str. 50, D-04289 Leipzig Germany
Zentralblatt fur Chirurgie (Germany), 1998, 123/11 (1277-1283)

In 17 patients with osteitis and 16 polytraumatized patients changes in the plasma levels of vitamin A, vitamin E and beta-carotene were investigated. Plasma samples taken preoperatively, daily during the first three days and then twice a week postoperatively were analysed for fat-soluble vitamins by high performance liquid chromatography (HPLC). Significant changes in plasma levels of all three components depending on the outcome of injury were found in all patients. Increased levels were observed in patients that survived the injury, while in those who died a significant decrease was observed. Recommendations regarding the supplementation with these vitamins in clinical practice can not be made based on these results, but substitute might prove beneficial for vitamin E in certain types of injury.

Aphthous ulcers and vitamin B12 deficiency
Weusten B.L.A.M.; van de Wiel A.
B.L.A.M. Weusten, University Hospital Utrecht, Department of Internal Medicine, PO Box 85500, 3800 ED Amersfoort Netherlands
Netherlands Journal of Medicine (Netherlands), 1998, 53/4 (172-175)

Aphthous ulcers of the oral cavity are frequently encountered in general practice. Although the exact pathophysiology remains obscure, many factors can contribute to the pathogenesis of these lesions, such as immunological factors, local trauma, smoking, stress, hormonal state, family history, food hypersensitivity, and infection. We describe three patients in whom a clear relationship appeared to exist between recurrent aphthous ulcers and a deficiency of vitamin B12. It is concluded that in all patients with recurrent aphthous ulceration, deficiency of vitamin B12 should be considered.

Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics
Hibbeln J.R.; Linnoila M.; Umhau J.C.; Rawlings R.; George D.T.; Salem N. Jr.
Dr. J.R. Hibbeln, Outpatient Clinic, Natl. Inst. Alcohol Abuse/Alcoholism, 12420 Parklawn Drive, Rockville, MD 20852 United States
Biological Psychiatry (United States), 1998, 44/4 (235-242)

Background: Impulsive violence, suicide, and depression are strongly associated with low concentrations of cerebrospinal fluid 5- hydroxyindoleacetic acid (CSF 5-HIAA). Increased suicide and trauma reported in some cholesterol-lowering trials may be related to altered concentrations of polyunsaturated fatty acids rather than cholesterol, a possible surrogate marker.

Methods: CSF 5-HIAA and homovanillic acid (HVA), total cholesterol, and plasma fatty acid concentrations were examined in 176 subjects, including 49 healthy volunteers, and 88 early- and 39 late-onset alcoholics.

Results: Among each group, polyunsaturated fatty acids predicted both CSF 5-HIAA and CSF HVA concentrations, but total cholesterol was unrelated to either neurotransmitter metabolite. The relationships between plasma 22: 6n3 and CSF 5-HIAA were significantly different when healthy volunteers (r = .35) were compared to early-onset alcoholics (r = -.38) (p <02).

Conclusions: Dietary studies are indicated to determine if essential fatty acid supplementation can influence central nervous system serotonin and dopamine metabolism and modify impulsive behaviors related to these neurotransmitters.

Treatment of hyperpathia/allodinia in CRPS, earlier called RSDS, a metabolic approach
Moesker A.
Dr. A. Moesker, Pain Treatment Department, Refaja Hospital, Boerhaavestroat 1, 9501 HE Stadskanaal Netherlands
Pain Clinic (Netherlands), 1998, 10/4 (261-274)

Why some people, often after a mild trauma, are developing a Chronic Regional Pain Syndrome is at present still not understood. For decades, sympathetic nervous involvement was the main goal of understanding. The most effective therapy was blocking the sympathetic innervation by phenol ore themolaesion, or by the farmacon guanethidine. Restoring the circulation by a serotonine- antagonist, ketanserin, was a development in a way that most of the complaints could be treated, but not the symptoms of hyperpathia and allodinia. In recent years an interesting new field of treatment was explored. Because of the fact that oxigen free radicals are found in cases of CRPS, an oxigen free radical scavenger, dimethylsulfoxide was applied on the affected area. On the basis of these experiences a new hypothesis was build. Because of the symptoms there must be an area of ischemia. In this area the metabolism has to use the anaerobiosis. In the anaerobiosis there will be a production of ATP, free radicals and lactate. Restoring the circulation will not always be sufficient to facilitate the metabolism in the direction of aerobiosis. Carnitine is a pivotal factor in stimulating the aerobiosis by enhancing the fatty acid oxidation. These processes take place in the mitochondrion. Carnitine is a metabolic modulator by way of stimulation of the beta-oxidation. It will modulate the ATP production, reduce the lactate production, inhibite the formation of superoxide, and reduce the formation of hydrogen peroxide. ATP seems to be a co-transmitter for the sympathetic nerve endings. In this way the circle is complete and the involvement of the sympathetic nerves is explained. In cases of CRPS in the Pain Clinic of the Refaja Hospital a trial investigated the possibility of treating CRPS patients with restoring circulation by ketanserin and to restore the metabolism by carnitine. The results of the first 12 patients were very promising and are presented. Not only the circulation disorders did react better, but also the hyperpathia and allodinia diminished in a way we never had seen.

Influence of arginine, omega-3 fatty acids and nucleotide-supplemented enteral support on systemic inflammatory resp. syndrome and multiple organ failure in patients after severe trauma
Weimann A.; Bastian L.; Bischoff W.E.; Grotz M.; Hansel M.; Lotz J.; Trautwein C.; Tusch G.; Schlitt H.J.; Regel G.
Dr. A. Weimann, Klin. Abdom.-/Transplantationschir., Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover Germany
Nutrition (United States), 1998, 14/2 (165-172)

This study investigated the influence of an enteral diet supplemented with arginine, omega-3 fatty acids, and nucleotides (Impact, Sandoz Nutrition, Berne, Switzerland) on the incidence of systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF) in patients after severe trauma . Thirty-two patients with an injury-severity score >20 were included in this prospective, randomized, double-blind, controlled study. Primary endpoints were the incidence of SIRS and MOF. Secondary endpoints were parameters of acute phase and immune response as well as infection rate, mortality, and hospital stay. For statistical analysis 29 patients (test group n = 16, control n = 13) were eligible. In the test group, significantly fewer SIRS days per patient were found during 28 d. The difference was highly significant between d 8-14 (P < 0.001). MOF score was significantly lower in the test group on d 3 and d 8-11 (P < 0.05). Acute phase parameters showed lower C-reactive protein serum levels (significant on D day 4) and fibrinogen plasma levels (significant on d 12 and 14; P < 0.05). HLA-DR expression on monocytes showed significantly higher fluorescence activity on d 7. No significant difference was found for T-lymphocyte CD4/CD8 ratio, interleukin- 2 receptor expression, infection rate, mortality (2/16 vs. 4/13), and hospital stay. The results of the study provide further support for beneficial effects of arginine, omega-3-fatty acids and nucleotide- supplemented enteral diet in critically ill patients.

Impact of supplemented enteral nutrition in patients with multiple trauma
Bastian L.; Weimann A.; Bischoff W.; Meier P.N.; Grotz M.; Stan C.; Regel G.
Dr. L.Bastian, Unfallchirurgische Klinik, Medizinische Hochschule Hannover, D-30623 Hannover Germany
Unfallchirurg (Germany), 1998, 101/2 (105-114)

Previous studies in critically ill patients have shown the beneficial effects of early enteral nutrition supplemented with arginine, omega-3 fatty acids and nucleotides (Impact) on immunological response, infection rate and length of stay in hospital. No specific data exist for patients with severe multiple injury, who represent a high risk group for systemic inflammatory response syndrome (SIRS), septic complications and multiple organ failure (MOF). In this prospective, randomized, double-blind controlled clinical study on patients after severe trauma (ISS ca. 40) the primary study endpoints were incidence of SIRS and MOF (definitions according to Am Soc Crit Care Med (5) and Goris (23), Sauaia (43)). Thirty-two patients enrolled in the study, and 29 were eligible for analysis: test (Impact) (n = 16), control (n = 13). Both groups were comparable according to age, body mass index and severity of trauma (PTS-test: 38.8 plus or minus 12.5, PTS-control: 40.8 plus or minus 15.5, ISS-test: 39.6 plus or minus 11.4, ISS-control: 40.5 plus or minus 9.2). Patients were randomized to receive either Impact (test) or an isonitrogenous isocaloric diet (control). Feeding was started on the 2nd day after trauma via endoscopically placed nasoduodenal or-jejunal feeding tubes. The experimental diet was safe and well tolerated. During the 1st week the enteral feeding amount was about 2000 ml without significant difference. Test-fed patients developed SIRS significantly less frequently between day 1 and day 28 (8 vs 13.3; P < 0.05) and especially between day 8 and day 14 (3 vs 6.2; P < 0.001). In the control group the Goris score was significantly worse (P < 0.05) on days 3, 4, 6, 7, 10, 11, 16 and 17 and the Sauaia score on days 8, 9, 10 and 11 (P < 0.05; P < 0.01). Mortality rate did not significantly differ (test 2/16, control 4/13), nor did length of ICU or hospital stay. With regard to the acute-phase response, C-reactive protein was significantly lower on day 4 in the test group (test: 131 plus or minus 67 mg/1, control: 221 plus or minus 110 mg/l) as was fibrinogen on day 12 (6.6 plus or minus 1.4 vs 7.5 plus or minus 1,4 g/l) and day 14 (7.1 plus or minus 1.3 vs 7.8 plus or minus 0,8 g/l). No significant difference could be observed for CD4/CD8 ratio, CD45 isotope on activated T-cells and lymphocytic interleukin (II)-2- receptor- and 11-6 level. However, HLA-DR antigen presentation on peripheral monocytes was significantly elevated on day 7 in the test group (P < 0.05). According to the results, arginine, omega-3 fatty acids and nucleotides-enriched diet during early enteral feeding leads to reduction of SIRS after severe multiple injury. There is evidence for improvement of post-traumatic immunological response which helps to overcome the immunological depression after trauma .

Diets and infection: Composition and consequences
Alexander J.W.; Ogle C.K.; Nelson J.L.
Dr. J.W. Alexander, Department of Surgery, Transplantation Division, Univ. of Cincinnati Medical Center, 231 Bethesda Avenue, Cincinnati, OH 45267-0558 United States
World Journal of Surgery (United States), 1998, 22/2 (209-212)

This brief review focuses on the effects of nutrient composition of enteral diets on the outcome of surgical patients and experimental models of infection. Complete enteral diets containing combinations of immunonutrients (arginine, glutamine, RNA, omega-3 fatty acids), when given postoperatively or after trauma to surgical patients, can reduce hospital stay, overall costs, and the incidence of wound complications and acquired infections. Immunonutrient diets can also reduce the length of hospital stay when given to patients admired to the surgical intensive care unit. A high protein diet is usually required for optimal benefit, although administration of high protein immunoenhancing diets may have adverse effects in animals with severe untreated peritonitis because of a sustained overproduction of cytokines.

[Nutritional support for the large burn patient]
Pelaez J; Garcia de Lorenzo A; Denia R; Martinez Ratero S; Lopez Martinez J; Caparros T
Servicio de Medicina Intensiva de la Fundacion Jimenez Diaz, Hospital La Paz, Madrid, Espana.
Nutr Hosp (Spain) May-Jun 1997, 12 (3) p121-33

Large burn patients make up a subgroup of critical patients in whom the nutro-metabolic support reaches its maximum importance, due to the fact thermal aggression induces a hypermetabolic response which is prolonged until the wounds heal. In fact, there are few deubt with regard to the importance of nutritional support tin the management of these patients for reducing the complications and facilitating the closing of the wounds and the recovery of the patients. Thermal trauma induces the release of counter-regulatory hormones and of other mediators which favor proteineic catabolism, mainly muscular, lipolysis, and gluconeogenesis; as well, there is an alteration of thermoregulation, raising the equilibrium point. The estimate of the energetic requirements may be done by means of predictive equations, although these tend to over-estimate it; indirect calorimetry is the most exact method and this permits monitorization of the evolution, which is very variable in time, it gives the metabolic response to the thermal aggression, at the same time as permitting the analysis of the use of the administrated substrates. Its use has meant a dramatic decrease in the supply of calories administered to burn patients, with the present recommendation being 35-40 kcal/kg/d. The supply of non-proteineic calories has also been modified: It is recommended that at least 60-70% of the calories administered, be in the form of carbohydrates, without surpassing 1600 kcal/kg/d. The optimal relation of non-proteineic kcal:nitrogen, is 150:1. The administration route of the artificial nutrition support should be individualized in each patient, with the enteral route being the route of choice, as this is the most physiologic, the cheapest, and the safest; its use prevents the appearance of certain complications (Curling ulcer, cholecystitis, bacterial translocation); however, if his does not cover nutritional requirements of the burn patient, parenteral nutrition should be associated to this. (108 Refs.)

Effects of intravenously infused fish oil on platelet fatty acid phospholipid composition and on platelet function in postoperative trauma
Roulet M; Frascarolo P; Pilet M; Chapuis G
Nutrition Unit, University of Lausanne, Switzerland.
JPEN J Parenter Enteral Nutr (United States) Sep-Oct 1997, 21 (5) p296-301

BACKGROUND: The aim of this study was to assess the short-term effect of IV infusion of fish oil emulsion on the fatty acid profiles of platelet phosphatidylcholine and phosphatidylethanolamine and on platelet function in postoperative patients.

METHODS: Over a 7-day period, 10 patients received a 20% soybean fat emulsion with an added 10% marine fish oil emulsion, whereas 9 controls received only 20% soybean fat emulsion.

RESULTS: By comparison with controls, in patients receiving fish oil, (1) a large increase in eicosapentaenoic acid (20:5n-3) was observed in both platelet phosphatidylcholine (1.55% +/- 0.17% vs 0.38% +/- 0.06% by weight, p < .01) and phosphatidylethanolamine 2.21% +/- 0.18% vs 0.66% +/- 0.08% by weight, p < .01); (2) eicosapentaenoic acid (20:5n-3)/arachidonic acid (20:4n-6) ratios doubled in both platelet phosphatidylcholine (p < .01) and phosphatidylethanolamine (p < .05); (3) with collagen as aggregating factor, maximal reaction speed decreased (p < .02) and latency increased (p < .002); and (4) no toxic effect, in particular no increase of postoperative bleeding and no perturbation of hepatic and renal function, was observed during the fish oil infusion.

CONCLUSIONS: A short-term IV infusion of fish oil clearly modifies the platelet composition and changes some parameters of platelet function.

The effect of nutritional support on the perioperative course in patients after extensive surgical procedures
Kalacinski J; Kalacinska B; Kurczych K; WojdyLo A
OddziaLu Chirurgii Ogolnej, Apteki Szpitalnej Szpitala Miejskiego w Oswiecimiu.
Wiad Lek (Poland) 1997, 50 Su 1 Pt 2 p447-51

Nutritional treatment in patient undergoing extensive surgical procedures is a condition of shortening of catabolic phase of postoperative period. Giving a basal quantity of nutritional components, authors tried to do a clinical evaluation of treated patients and possibilities of the nutritional treatment in a provincial hospital. 51 patients was fed parenterally or/and enterally, all-in-one admixtures or with multi- bottles system, with using of peristaltic/infusion pump or gravity. Patients were divided into 4 groups: 1. treated with laparostomy because of pancreatic necrosis or complications of acute pancreatitis, 2. with complications after total or subtotal gastrectomy, 3. with complications after extensive resections of jejunum or colon Clinical status, weight loss, accessible laboratory investigations were studied. Authors gave on the average: energy 32 kcal/kg b.m./day, protein 0.15 gN/kg b.m./day, potassium 1.15 mEq/kg b.m./day. In 37 patients appeared weight loss av. 4.8 kg. In 20 patients with decreased serum protein level or blood cell count-plasma and erythrocytes were applied. In examined groups 9 persons died because of myocardial infarction, pulmonary embolism, intestinal necrosis with peritonitis, lesions of CNS following trauma, sepsis. Conclusions: 1. Effective treatment of postoperative complications is possible with application of nutritional treatment. 2. Adequate (not excessive) nutritional components administration should be applied intravenously, enterally or by both of them.

Vitamins Q and E, extracorporal circulation and hemolysis.
Karlsson J; Ronneberg R; Semb B
Mol Cell Biochem (Netherlands) Aug 1997, 173 (1-2) p33-41

Whole blood vitamin Q (ubiquinone), plasma vitamins Q and E (alpha-(alpha-)tocopherol) and free cholesterol (FC) were studied before (control or base-line value, sample I) and during open chest surgery and extracorporal circulation (samples II-IV) in 10 male IHD patients. Identity existed between control whole blood and plasma ubiquinone. During surgery an increased discrepancy with lower plasma vitamin Q levels were seen. Control plasma vitamins Q, E and FC averaged 0.88 +/- 0.16 (SE), 12.1 +/- 2.2 mg x l(-1) and 0.75 +/- 0.15 g x l(-1). Corresponding molar values were 1.02 +/- 0.17, 28.1 +/- 5.1 micromol x l(-1) and 1.94 +/- 0.74 mmol x l(-1). Vitamin Q and E decreased continuously and averaged 0.64 mg x l(-1) in sample IV (0.74 micromol x l(-1), p < 0.001) and 9.4 mg x l(-1) in sample III (21.8 micromol x l(-1), p < 0.001). Hemolysis in all sample IV vials, ruined all vitamin E determinations. When normalized for FC (NQ and NE), decreases were found to be 17 (IV) and 12% (III), respectively. Large interindividual variations existed. High control NQ and NE values allowed a larger antioxidant vitamin depletion. High NQ seemed also to be a prerequisite for NE depletion. In addition, signs indicated an active liver vitamin Q release for patients rich in control antioxidant values. It was suggested that the antioxidant vitamin depletion did not prevent from radical trauma to membrane structural lipids (especially omega-3 fatty acids or vitamin F1), less membrane fluidity, erythrocyte fragility and hemolysis.

Metabolic response to injury and sepsis: changes in protein metabolism.
Biolo G; Toigo G; Ciocchi B; Situlin R; Iscra F; Gullo A; Guarnieri G
Institute of Clinical Medicine, University of Trieste, Italy.
Nutrition (United States) Sep 1997, 13 (9 Suppl) p52S-57S

The metabolic response to trauma and sepsis involves an increased loss of body proteins. Specific sites of changes of protein and amino acid metabolism have been identified. In skeletal muscle, the rate of proteolysis is accelerated greatly. The rate of protein synthesis also may be increased but not enough to match the increase in degradation. Intramuscular glutamine concentration is decreased because of increased efflux and possibly decreased de novo synthesis. In the liver, the rate of synthesis of selected proteins (i.e., albumin, transferrin, prealbumin, retinol-binding protein, and fibronectin) is decreased, whereas acute phase protein synthesis is accelerated. Tissues characterized by rapidly replicating cells, such as enterocytes, immune cells, granulation tissue, and keratinocytes, exhibit early alterations in the case of decreased protein synthesis capacity. In these tissues, glutamine use is accelerated. Increased stress hormone (cortisol and glucagon) and cytokine secretion, as well as intracellular glutamine depletion, are potential mediators of altered protein metabolism in trauma and sepsis. However, the relative importance of these factors has not been clarified. Therapy of acute protein catabolism may include the use of biosynthetic human growth hormone, possibly in combination with insulin-like growth factor-1, and the administration of metabolites at pharmacologic doses. We recently studied the effects of carnitine and alanyl-glutamine administration in severely traumatized patients. We found that both carnitine and the glutamine dipeptide restrained whole-body nitrogen loss without affecting selected indices of protein metabolism in the skeletal muscle. (52 Refs.)

Carotenoids and antioxidant vitamins in patients after burn injury.
Rock CL; Dechert RE; Khilnani R; Parker RS; Rodriguez JL
Department of Surgery, the University of Michigan, Ann Arbor, USA.
J Burn Care Rehabil (United States) May-Jun 1997, 18 (3) p269-78; discussion 268

Oxidative stress may contribute to secondary tissue damage and impaired immune function in patients after burn injury. The purpose of our study was to describe plasma antioxidant micronutrient concentrations in 26 adult patients admitted with extensive burn injuries (> 20 % total burn surface area) to a level-1 trauma burn center during a 21-day period after admission. The effect of administering beta-carotene was also examined with use of a prospective randomized subjects design: patients received either placebo or 30 mg/day in an enteral feeding. Plasma concentrations of alpha- and gamma-tocopherol, carotenoids (alpha and beta-carotene, lycopene, beta-cryptoxanthin, lutein), and retinol were measured with high- performance liquid chromatography, and vitamin C was quantified with spectrophotometry, at baseline and twice per week. Vitamin C, tocopherol, and retinol concentrations were low at baseline, but levels increased significantly over the study period in both groups (p < 0.05). Plasma beta-carotene concentration increased when this carotenoid was provided in the oral feeding. Otherwise, plasma carotenoid concentrations were low at baseline and remained low throughout the study period despite normalization of associated lipids.

The role of IGFs in catabolism
Botfield C.; Ross R.J.M.; Hinds C.J.
C. Botfield, Dept. of Intensive Care, St Bartholomew's Hospital, London EC1A 7BE U.K.
Bailliere's Clinical Endocrinology and Metabolism (United Kingdom), 1997, 11/4 (679-697)

The hypercatabolic response to trauma, extensive surgery and sepsis is characterized by an increased metabolic rate, severe muscle wasting and a negative nitrogen balance. This process of 'autocannibalism' may be in part a consequence of a disordered growth hormone (GH)/insulin-like growth factor (IGF) axis. In this chapter the normal physiology of the GH/IGF axis is first briefly reviewed. This is followed by a discussion of the changes that accompany fasting and catabolic illness, the effects of IGF-1 administration in health and disease and a comparison of the effects of IGF-1, GH and insulin on catabolism. Although initial investigations of IGF-1 administration in animals and human volunteers have often been encouraging, studies in catabolic patients have so far proved disappointing. Combined treatment with GH, IGF-1 (and insulin) or with IGF-1 and its major binding protein, may prove more effective, especially when used in conjunction with nutritional supplements such as glutamine.

Antioxidant defense of the brain: A role for astrocytes
Wilson J.X.
J.X. Wilson, Dept. of Physiology, University of Western Ontario, London, Ont. N6A 5C1 Canada
Canadian Journal of Physiology and Pharmacology (Canada), 1997, 75/10-11 (1149-1163)

Partially reduced forms of oxygen are produced in the brain during cellular respiration and, at accelerated rates, during brain insults. The most reactive forms, such as the hydroxyl radical, are capable of oxidizing proteins, lipids, and nucleic acids. Oxidative injury has been implicated in degenerative diseases, epilepsy, trauma, and stroke. It is a threshold phenomenon that occurs after antioxidant mechanisms are overwhelmed. Oxidative stress is a disparity between the rates of free radical production and elimination. This imbalance is initiated by numerous factors: acidosis; transition metals; amyloid beta-peptide; the neurotransmitters dopamine, glutamate, and nitric oxide; and uncouplers of mitochondrial electron transport. Antioxidant defenses include the enzymes superoxide dismutase, glutathione peroxidase, and catalase, as well as the low molecular weight reductants alpha-tocopherol (vitamin E), glutathione, and ascorbate (reduced vitamin C). Astrocytes maintain high intracellular concentrations of certain antioxidants, making these cells resistant to oxidative stress relative to oligodendrocytcs and neurons. Following reactive gliosis, the neuroprotective role of astrocytes may be accentuated because of increases in a number of activities: expression of antioxidant enzymes; transport and metabolism of glucose that yields reducing equivalents for antioxidant regeneration and lactate for neuronal metabolism; synthesis of glutathione; and recycling of vitamin C. In the latter process, astrocytes take up oxidized vitamin C (dehydroascorbic acid, DHAA) through plasma membrane transporters, reduce it to ascorbate, and then release ascorbate to the extracellular fluid, where it may contribute to antioxidant defense of neurons.

Parenteral nutritional treatment
Schricker T.; Geisser W.; Georgieff M.
Prof. Dr. M. Georgieff, Universitatsklinik Anasthesiologie, Klinikum, Universitat Ulm, Steinhovelstrasse 9, D-89075 Ulm Germany
Anaesthesist (Germany), 1997, 46/5 (371-384)

The object of this review is to demonstrate the non-nutritional importance of carbohydrates and fat as they represent the classic energy carriers in parenteral nutrition. Concerning the pathophysiological changes of organ metabolism and intermediary metabolism as well as the pharmacological function of this nutritive substrates it is necessary to adjust parenteral nutrition strategy to various clinical pictures. The major goals of parenteral applicated carbohydrates are to avoid hyperglycemia, to return the increased hepatic glucose production during trauma and sepsis back to normal, and to reduce protein catabolism. Realizing this goals the dosage of glucose infusion underlies close metabolic borders depending on the present disease. Because of favourable effects of hepatic glucose and protein metabolism, xylitol, a non-glucose polyol, represents an useful alternative energy source to glucose. The non-energetic nutrition therapy with fat consists of application of the essential fatty acids linoleic and alpha-linolenic acid and considers the immunmodulatory effects of various fatty acids as precursors in the eicosanoid metabolism. As demonstrated at the organ systems of liver and lung this pharmacological effect of any lipid infusion might influence specific organ functions.

Influence of large intakes of trace elements on recovery after major burns
Berger M.M.; Cavadini C.; Chiolero R.; Guinchard S.; Krupp S.; Dirren H.; Shenkin A.
CHUV,CH-1011 Lausanne Switzerland
Nutrition (United States) 1994, 10/4 (327-334+352)

Because Cu, Se, and Zn are involved in immune and antioxidative defense mechanisms and tissue repair, deficiencies might aggravate complications classically observed with burns. After measuring massive cutaneous trace element losses in 10 burn patients, our aim in this study was to determine whether large intravenous intakes of Cu, Zn, and Sc can modify serum trace element levels and recovery after major burns. Ten patients, aged 34 +/- 6 yr (mean +/- SD), admitted to the burns center of a Swiss university hospital with thermal burns on 41 +/- 9% of their body surface were studied prospectively, with trace element balance studies from day 1 (D1) to D7 postinjury. Urine and blood samples were also collected on D10, D15, D20, and D25. The patients were divided into two groups of five and received either standard (group 1, control) or greatly increased (group 2, treatment: 4.5 mg Cu, 190 mug Se, and 40 mg Zn/day) trace element intakes. Energy and protein intake and wound treatment were similar in both groups. The treatment group was characterized by improved Cu, Se, and Zn status (increase in serum levels and various protein indicators), a much larger leukocyte increase between D4 and D14 (mainly neutrophils), and shorter hospital stay (45 days) compared with the untreated group (57 days). Grafting requirements were more extensive in group 1. Although severity of injury and wound treatment were similar in the groups, the duration of hospitalization was lower in the treated group. Further studies are required to determine whether this is related to trace element supplementation.

Proline metabolism in adult male burned patients and healthy control subjects
Jaksic T.; Wagner D.A.; Burke J.F.; Young V.R.
Shriners Burns Institute, 51 Blossom Street,Boston, MA 02114 United States
American Journal of Clinical Nutrition (United States) 1991, 54/2 (408-413)

Postabsorptive proline flux, oxidation, and endogenous biosynthesis were determined in five severely burned intensive-care-unit patients (x- age 27 y) and in six healthy, young-adult control subjects. Continuous primed, intravenous, 160-min, dual stable-isotope-tracer infusions of L-(1-sup 1sup 3C)proline and L-(methyl-sup 2Hinf 3)leucine were used in conjunction with measurement of plasma proline concentration and 24-h urinary hydroxyproline output. Burn patients, compared with normal individuals, demonstrated a doubling in proline and leucine flux (P < 0.01 for both findings), a threefold enhancement of proline oxidation (P < 0.05), a trend toward decreased proline synthesis, and a 37% reduction in plasma proline concentrations (P < 0.05). Further, the injured group, unlike the control group, was in a distinct negative body proline balance, as proline oxidation greatly exceeded endogenous proline biosynthesis (P < 0.01). These studies indicate that significant proline deficits may evolve during the postabsorptive period in severely burned patients and that an exogenous supply of proline might benefit the nitrogen economy of the traumatized patient.

Magnesium- deficiency syndrome in burns.
Broughton A; Anderson IR; Bowden CH
Lancet (England) Nov 30 1968, 2 (7579) p1156-8

No abstract.

Reversal of postburn immunosuppression by the administration of vitamin A
Fusi S.; Kupper T.S.; Green D.R.; Ariyan S.
Department of Surgery, Yale University School of Medicine, New Haven, CT United States
Surgery (United States) 1984, 96/2 (330-335)

The effect of high doses of vitamin A was evaluated on the suppression of cellular immunity after a 30% body surface area experimental scald burn in a mouse model. Male CBA/J mice were treated postburn with daily intraperitoneal injections of either 3000 IU of vitamin A or an equal volume of 0.9N saline. Similar groups of unburned mice were also studies as controls. At the seventh postburn day, one-way mixed lymphocyte reactions were tested for each group with whole spleen cells of CBA/J mice used as responders and mitomycin C-treated whole spleen cells of C57 BL/6 mice used as stimulators. When results were expressed as mean percentage of the values of control animals, no significant difference was observed between the saline-injected unburned control group (taken as 100%) and the vitamin A -treated unburned control groups (89%). The burned animals treated with saline showed suppression to 21% of the control values. However, the burned animals treated postburn with vitamin A improved the response rate dramatically to 52% of control values. This improvement over the untreated burned animals was significant in all experiments performed (p < 0.02). This study suggests that vitamin A may be an effective agent in the reversal of cellular immunosuppression after burns.

Serum carotene, vitamin A, retinol-binding protein and lipoproteins before and after jejunoileal bypass surgery.
Vahlquist A; Carlson K; Hallberg D; Rossner S
Int J Obes (England) 1982, 6 (5) p491-7

The plasma vitamin A and carotene transport in 45 obese patients was examined before and at various times after bypass surgery. The serum levels of lipoproteins, carotene, vitamin A and retinol-binding protein (RBP) were monitored and compared to those of healthy controls. LDL-cholesterol levels were decreased by 40 per cent (P less than 0.001) within the first year after surgery and remained low thereafter. The reduction of serum carotene (from a mean of 64 to 17 micrograms/dl) was rapid and constant. This change was observed already within 1-2 weeks post-surgery. The serum concentrations of carotene and LDL-cholesterol were highly correlated (r = 0.74). The concentrations of vitamin A and RBP were normal before the operation and remained so until 30 months after surgery, when slight reductions were observed compared to the control values [46 +/- 28 vs 66 +/- 11 micrograms/dl for vitamin A (P less than 0.01) and 32 +/- 8 vs 41 +/- 6 mg/l for RBP (P less than 0.01)]. No overt signs of vitamin A deficiency were observed. The mechanisms by which carotene (but not vitamin A) decreases so rapidly after bypass surgery cannot be explained by the decreased LDL levels.

Bypass phrynoderma. Vitamin A deficiency associated with bowel-bypass surgery.
Barr DJ; Riley RJ; Greco DJ
Arch Dermatol (United States) Jul 1984, 120 (7) p919-21

A 41-year-old woman had multiple keratotic papules and nodules on the trunk and extremities four years after a bowel-bypass procedure for morbid obesity. The microscopic features were those of a perforating folliculitis. Serum vitamin A levels were extremely low. Oral vitamin A therapy resulted in dramatic improvement of the cutaneous lesions.


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