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The role of oxidative stress in HIV disease.
Pace GW; Leaf CD
Research Triangle Pharmaceuticals, Durham, NC, USA.
Free Radic Biol Med Oct 1995, 19 (4) p523-8
Evidence has accumulated suggesting that HIV-infected
patients are under chronic oxidative stress. Perturbations to
the antioxidant defense system, including changes in levels of
ascorbic acid, tocopherols, carotenoids, selenium, superoxide
dismutase, and glutathione, have been observed in various
tissues of these patients. Elevated serum levels of
hydroperoxides and malondialdehyde also have been noted and
are indicative of oxidative stress during HIV infection.
Indications of oxidative stress are observed in asymptomatic
HIV-infected patients early in the course of the disease.
Oxidative stress may contribute to several aspects of HIV
disease pathogenesis, including viral replication,
inflammatory response, decreased immune cell proliferation,
loss of immune function, apoptosis, chronic weight loss, and
increased sensitivity to drug toxicities. Glutathione may play
a role in these processes, and thus, agents that replete
glutathione may offer a promising treatment for HIV-infected
patients. Clinical studies are underway to evaluate the
efficacy of the glutathione-repleting agents,
L-2-oxothiazolidine-4-carboxy lic acid (OTC) and
N-acetylcysteine (NAC), in HIV-infected patients. (93
Refs.)
Micronutrients in critical illness
Demling RH; DeBiasse MA
Department of Surgery, Brigham and Women's Hospital, Boston,
Massachusetts, USA.
Crit Care Clin Jul 1995, 11 (3) p651-73
[published erratum appears in Crit Care Clin 1996
Oct;12(4):xi]
Micronutrients play a key role in many of the metabolic
processes that promote survival from critical illness. For
vitamins, these processes include oxidative phosphorylation,
which is altered in the patient with systemic inflammation,
and protection against mediators, in particular oxidants.
Trace elements are essential for direct antioxidant activity
as well as functioning as cofactors for a variety of
antioxidant enzymes. Wound healing and immune function also
depend on adequate levels of vitamins and trace elements
(Table 6). Of extreme importance is the ease with which a
deficiency state can develop in the critically ill because of
decreased nutrient intakes and increased requirements. Daily
intakes up to or exceeding many times the RDA usually are
required. The enteral route is preferred, although, if not
available, most of these agents can be given by the parenteral
route. In that case, however, dose recommendations are less
clear. Attention to micronutrients is paramount both in
optimizing the nutritional management of the critically ill
and in the overall management of these patients. It also is
essential in promoting positive outcomes and decreasing
complications. (40 Refs.)
Melatonin in edible plants identified by
radioimmunoassay and by high performance liquid
chromatography-mass spectrometry.
Dubbels R; Reiter RJ; Klenke E; Goebel A; Schnakenberg E;
Ehlers C; Schiwara HW; Schloot W
Center of Human Genetics and Genetic Counselling, University
of Bremen, Germany.
J Pineal Res (Denmark) Jan 1995, 18 (1) p28-31
Melatonin, the chief hormone of the pineal gland in
vertebrates, is widely distributed in the animal kingdom.
Among many functions, melatonin synchronizes circadian and
circannual rhythms, stimulates immune function, may increase
life span, inhibits growth of cancer cells in vitro and cancer
progression and promotion in vivo, and was recently shown to
be a potent hydroxyl radical scavenger and antioxidant .
Hydroxyl radicals are highly toxic by-products of oxygen
metabolism that damage cellular DNA and other macromolecules.
Herein we report that melatonin, in varying concentrations, is
also found in a variety of plants. Melatonin concentrations,
measured in nine different plants by radioimmunoassay, ranged
from 0 to 862 pg melatonin/mg protein. The presence of
melatonin was verified by gas chromatography/mass
spectrometry. Our findings suggest that the consumption of
plant materials that contain high levels of melatonin could
alter blood melatonin levels of the indole as well as provide
protection of macromolecules against oxidative damage.
Exercise-induced changes in immune function :
effects of zinc supplementation.
Singh A; Failla ML; Deuster PA
Department of Military and Emergency Medicine, Uniformed
Services University of the Health Sciences, Bethesda, Maryland
20814.
J Appl Physiol Jun 1994, 76 (6) p2298-303
To examine the effect of zinc (Zn) supplementation on
exercise-induced changes in immune function, five male runners
were randomly assigned in a double-blind crossover design to
take a supplement (S; 25 mg of Zn and 1.5 mg of copper) or
placebo (P) twice daily for 6 days. On morning 4 of each
phase, 1 h after taking S or P, subjects ran on a treadmill at
70-75% of maximal oxygen uptake until exhaustion
(approximately 2 h). Blood samples were obtained before (Pre),
immediately after (Post), and 1 (Rec1) and 2 (Rec2) days after
the run. [3H]thymidine incorporation by mitogen-treated
mononuclear cell cultures was significantly lower (P <
0.05) Post than Pre, Rec1, or Rec2 for both S and P.
Respiratory burst activity of isolated neutrophils was
enhanced after exercise with P but not with S (P: Pre 12.0 +/-
1.1 vs. Post 17.6 +/- 2.3 nmol O2-/10(6) cells; S: Pre 11.7
+/- 0.3 vs. Post 12.1 +/- 1.2 nmol O2-/10(6) cells). Thus
supplemental Zn blocked the exercise-induced increase in
reactive oxygen species. Whether this antioxidant effect of Zn
will benefit individuals exposed to chronic physical stress
remains to be determined.
Dietary lipids and risk of autoimmune
disease.
Fernandes G
Department of Medicine, University of Texas Health Science
Center, San Antonio 78284-7874.
Clin Immunol Immunopathol Aug 1994, 72 (2)
p193-7
In summary, it is well established that moderate calorie
restriction or reduction in overall high calorie food intake
prevents or forestalls the development of age-associated
disease incidence such as breast cancer and renal disease in
rodents. A similar approach could also readily be applied in
humans for preventing the risk and rise of life-shortening
diseases. Many age-associated diseases, particularly
autoimmune diseases with viral etiology, appear to be
exacerbated in the presence of adverse lipid intake such as an
increased level of vegetable oils or trans-fatty acids from
the usage of hydrogenated dietary oils. At present, nearly
35-40% of the total calories are from dietary fats and/or of
lipid origin. Although usage of saturated fat, which increases
cardiovascular disease, has been reduced to a large extent in
the United States, consumption of both monounsaturated and
polyunsaturated fats of omega-6 origin has either increased or
simply been substituted in place of saturated fats. Further,
for the past 50 years, a significant reduction in highly
polyunsaturated fat consumption such as marine oil has also
occurred specifically in the United States. The reduction in
omega-3 lipids of marine or vegetable source occurs primarily
because of short shelf life due to rancidity. However, the
increased consumption of omega-6 or a vegetable source of oils
and decreased omega-3 intake may increase in vivo the
production of free radicals and higher proinflammatory
cytokines. Our ongoing studies reveal that proinflammatory
vegetable oil could increase autoimmune disease by increasing
the free radical formation by decreasing the antioxidant
enzyme mRNA levels, thereby further decreasing immune
function, particularly the production of anti-inflammatory
cytokines such as IL-2 and TGF beta mRNA levels. In contrast,
omega-3 lipid intake in the presence of an antioxidant
supplement appears to exert protection against autoimmunity by
enhancing antioxidant enzymes and TGF beta mRNA levels and by
preventing the rise in oncogene expression. However, detailed
studies are required to establish the protective and
deleterious role of different commonly consumed lipids or
dietary oils by the general population, particularly during
middle and aging years. Further, we also propose that
combining nonsteroidal drug therapy along with moderate
calorie reduction in the presence of more protective omega-3
dietary lipids of either marine or vegetable source and
decreasing the levels of mono- and polyunsaturated lipids may
provide additional protection against the age-associated rise
in malignancy and autoimmune disorders. (43 Refs.)
Longitudinal exposure of human T lymphocytes to
weak oxidative stress suppresses transmembrane and nuclear
signal transduction.
Flescher E; Ledbetter JA; Schieven GL; Vela-Roch N; Fossum D;
Dang H; Ogawa N; Talal N
Clinical Immunology Section, Audie L. Murphy Memorial
Veterans Hospital, San Antonio, TX.
J Immunol Dec 1 1994, 153 (11) p4880-9
Products of polyamine oxidase activity, at micromolar
levels and during a period of 2 to 3 days, down-regulate IL-2
mRNA levels and activity in human lymphocytes. We studied
whether this suppression was associated with signal
transduction abnormalities. We found that polyamine oxidase
activity suppresses both anti-CD3-induced IL-2 production and
protein tyrosine phosphorylation. Polyamine oxidase activity
also caused a reduction in intracellular calcium mobilization
after mitogenic stimulation. The most distal step of
CD3-mediated signal transduction is dependent upon
transcription factors that regulate a set of genes, including
IL-2. We found that polyamine oxidase-treated cells exhibited
very low DNA binding activity of two such factors: NFAT and
NF-kappa B. On the other hand, AP-1 DNA binding activity was
enhanced in polyamine oxidase-treated cells, suggesting a
possible role for AP-1 in the human lymphocyte stress
response. In accordance with the oxidation dependence of this
suppressive mechanism, N-acetylcysteine (NAC; an antioxidant )
significantly reversed the polyamine oxidase effects on
lymphokine production and signal transduction. These results
suggest that NAC contributes, under oxidizing conditions, to
the preservation of immune function . In summary, our data
suggest that chronic low-level oxidative stress, via
suppression of mitogen-induced transmembrane signaling
(protein-tyrosine phosphorylation and calcium mobilization),
causes a decrease in the DNA binding activity of transcription
factors that regulate the IL-2 gene. This results in decreased
IL-2 production.
Critical reappraisal of vitamins and trace minerals
in nutritional support of cancer patients.
Stahelin HB
Geriatric University Clinic, Kantonsspital, Basel,
Switzerland.
Support Care Cancer (Germany) Nov 1993, 1 (6)
p295-7
The potential of a high intake of fresh fruits and
vegetables in cancer prevention is well established.
Epidemiological studies support carotene, vitamins A, C, E and
selenium as the active compounds. Antioxidant properties and
direct effects (e.g. inhibition of N-nitrosamine formation or
cell-to-cell interactions) are invoked. The role of other
trace elements is less clear. The modulation of immune
function by vitamins and trace elements remains important and
affects survival. In established cancers, the site-specific
differences in the diet/cancer relation require appropriate
dietary changes, e.g. low fat (20% by energy) in breast
cancer, or high vegetable or fruit intake in lung cancer.
Single high-dose supplements (e.g. vitamin C) have proved to
have no curative or life-prolonging effect. Chemotherapy and
radiation increase the requirements for antioxidant compounds.
Supplementation can diminish the damage induced by
peroxidation. Carefully planned and monitored trials that
establish the optimal intake of micronutrients as adjuvants in
cancer patients are required. (18 Refs.)
Preventive nutrition: disease-specific dietary
interventions for older adults.
Johnson K; Kligman EW
Dept. of Family and Community Medicine, University of Arizona
College of Medicine, Tucson.
Geriatrics Nov 1992, 47 (11) p39-40, 45-9
Disease prevention through dietary management is a
cost-effective approach to promoting healthy aging. Fats,
cholesterol, soluble fiber, and the trace elements copper and
chromium affect the morbidity and mortality of CHD. Decreasing
sodium and increasing potassium intake improves control of
hypertension. Calcium and magnesium may also have a role in
controlling hypertension. The antioxidant vitamins A and
beta-carotene, vitamin C, vitamin E, and the trace mineral
selenium may protect against types of cancer. A decrease in
simple carbohydrates and an increase in soluble dietary fiber
may normalize moderately elevated blood glucose levels.
Deficiencies of zinc or iron diminish immune function .
Adequate levels of calcium and vitamin D can help prevent
senile osteoporosis in both older men and women. (27
Refs.)
Immunocompetence and oxidant defense during
ascorbate depletion of healthy men.
Jacob RA; Kelley DS; Pianalto FS; Swendseid ME; Henning SM;
Zhang JZ; Ames BN; Fraga CG; Peters JH
Western Human Nutrition Research Center, USDA Agricultural
Research Service, Presidio of San Francisco, CA 94129.
Am J Clin Nutr Dec 1991, 54 (6 Suppl)
p1302S-1309S
To determine nonscorbutic effects of moderate vitamin C
deficiency we measured immune function and oxidative damage in
eight healthy men (25-43 y) who consumed 5-250 mg/d of
ascorbic acid over 92 d on a metabolic unit. During ascorbic
acid intakes of 5, 10, or 20 mg/d, subjects attained a state
of moderate ascorbic acid deficiency as ascorbic acid
concentrations in plasma, leucocytes, semen, and buccal cells
dropped to less than 50% of baseline with no scorbutic
symptoms observed. No changes in cell proliferation,
erythrocyte antioxidant enzymes, and DNA strand breaks were
observed; however, blood levels of glutathione and NAD(P)
decreased during ascorbic acid deficiency, as did delayed
hypersensitivity responsiveness. Concentrations of the
oxidatively modified DNA base, 8-hydroxydeoxyguanosine in
sperm DNA and fecapentaenes, ubiquitous fecal mutagens, were
increased during ascorbic acid depletion. Moderate vitamin C
deficiency, in the absence of scurvy, results in alteration of
antioxidant chemistries and may permit increased oxidative
damage.
Vitamin E and immune functions.
Bendich A
Clinical Nutrition, Hoffmann La Roche Inc., Nutley, NJ
07110.
Basic Life Sci 1988, 49 p615-20
Vitamin E, the major lipid-soluble antioxidant present in
all cellular membranes, is an important nutrient for optimal
immune function . When animals are fed nutritionally complete
diets lacking vitamin E, immune responses are adversely
affected. Supplementation of these diets with higher than
nutritionally adequate levels of vitamin E enhances immune
responses. High levels of PUFA are immunosuppressive, and
vitamin E can partially overcome this immunosuppression. High
levels of vitamin C can protect tissue levels of vitamin E and
may indirectly contribute to the immunoenhancement by vitamin
E. Severe selenium deficiency is immunosuppressive. Vitamin E
can protect some aspects of immune responses from the adverse
effects of selenium deficiency. These data clearly indicate
that nutrients that affect the overall antioxidant status have
important effects on immune functions. In addition,
antioxidant nutrient interactions can synergize to overcome
the adverse effects of polyunsaturated fatty acids on immune
functions (Fig 2). (26 Refs.)
Functional food science and the cardiovascular
system
Hornstra G.; Barth C.A.; Galli C.; Mensink R.P.; Mutanen M.;
Riemersma R.A.; Roberfroid M.; Salminen K.; Vansant G.;
Verschuren P.M.
Dr. G. Hornstra, Department of Human Biology, Maastricht
University, PO Box 616, NL-6200 MD, Maastricht
Netherlands
British Journal of Nutrition (United Kingdom), 1998,
80/Suppl. 1 (S113-S146)
Cardiovascular disease has a multifactorial aetiology, as
is illustrated by the existence of numerous risk indicators,
many of which can be influenced by dietary means. It should be
recalled, however, that only after a cause-and-effect
relationship has been established between the disease and a
given risk indicator (called a risk factor in that case), can
modifying this factor be expected to affect disease morbidity
and mortality. In this paper, effects of diet on
cardiovascular risk are reviewed, with special emphasis on
modification of the plasma lipoprotein profile and of
hypertension. In addition, dietary influences on arterial
thrombotic processes, immunological interactions, insulin
resistance and hyperhomocysteinaemia are discussed. Dietary
lipids are able to affect lipoprotein metabolism in a
significant way, thereby modifying the risk of cardiovascular
disease. However, more research is required concerning the
possible interactions between the various dietary fatty acids,
and between fatty acids and dietary cholesterol. In addition,
more studies are needed with respect to the possible
importance of the postprandial state. Although in the
aetiology of hypertension the genetic component is definitely
stronger than environmental factors, some benefit in terms of
the development and coronary complications of atherosclerosis
in hypertensive patients can be expected from fatty acids such
as alpha-linolenic acid, eicosapentaenoic acid and
docosahexaenoic acid. This particularly holds for those
subjects where the hypertensive mechanism involves the
formation of thromboxane A2 and/or alpha1-adrenergic
activities. However, large-scale trials are required to test
this contention. Certain aspects of blood platelet function,
blood coagulability, and fibrinolytic activity are associated
with cardiovascular risk, but causality has been
insufficiently proven. Nonetheless, well-designed intervention
studies should be initiated to further evaluate such promising
dietary components as the various n-3 and n-6 fatty acids and
their combination, antioxidants, fibre, etc. for their effect
on processes participating in arterial thrombus formation.
Long-chain polyenes of the n-3 family and antioxidants can
modify the activity of immunocompetent cells, but we are at an
early stage of examining the role of immune function on the
development of atherosclerotic plaques. Actually, there is
little, if any, evidence that dietary modulation of immune
system responses of cells participating in atherogenesis
exerts beneficial effects. Although it seems feasible to
modulate insulin sensitivity and subsequent cardiovascular
risk factors by decreasing the total amount of dietary fat and
increasing the proportion of polyunsaturated fatty acids,
additional studies on the efficacy of specific fatty acids,
dietary fibre, and low-energy diets, as well as on the
mechanisms involved are required to understand the real
function of these dietary components. Finally, dietary
supplements containing folate and vitamins B6 and/or B12
should be tested for their potential to reduce cardiovascular
risk by lowering the plasma level of homocysteine.
Monounsaturated fats and immune function
Yaqoob P.
P. Yaqoob, Division of Human Nutrition, School of Biological
Sciences, Biomedical Sciences Building, Bassett Crescent East,
Southampton SO16 7PX United Kingdom
Brazilian Journal of Medical and Biological Research
(Brazil), 1998, 31/4 (453-465)
Animal studies suggest that olive oil is capable of
modulating functions of cells of the immune system in a manner
similar to, albeit weaker than, fish oils. There is some
evidence that the effects of olive oil on immune function in
animal studies are due to oleic acid rather than to trace
elements or antioxidants. Importantly, several studies have
demonstrated effects of oleic acid-containing diets on in vivo
immune responses. In contrast, consumption of a
monounsaturated fatty acid (MUFA)-rich diet by humans does not
appear to bring about a general suppression of immune cell
functions. The effects of this diet in humans are limited to
decreasing aspects of adhesion of peripheral blood mononuclear
cells, although there are trends towards decreases in natural
killer cell activity and proliferation. The lack of a clear
effect of MUFA in humans may be attributable to the higher
level of monounsaturated fat used in the animal studies,
although it is ultimately of importance to examine the effects
of intakes which are in no way extreme. The effects of MUFA on
adhesion molecules are potentially important, since these
molecules appear to have a role in the pathology of a number
of diseases involving the immune system. This area clearly
deserves further exploration.
Cancer chemopreventive and therapeutic activities
of red ginseng
Xiaoguang C.; Hongyan L.; Xiaohong L.; Zhaodi F.; Yan L.;
Lihua T.; Rui H.
C. Xiaoguang, Department of Pharmacology, Chinese Academy of
Medical Sciences, Peking Union Medical College, Beijing 100050
China
Journal of Ethnopharmacology (Ireland), 1998, 60/1
(71-78)
Red ginseng extract A and B are the active components of
Panax ginseng. Red ginseng is a classical traditional Chinese
medicine. Among Chinese herbs, red ginseng has been considered
as one of the tonics. Many studies indicated that red ginseng
could enhance immune function of the human body. The effects
of red ginseng extracts on transplantable tumors,
proliferation of lymphocyte, two-stage model and rat liver
lipid peroxidation were studied. In a two-stage model, red
ginseng extracts had a significant cancer chemoprevention. At
50-400 mg/kg, they could inhibit DMBA/Croton oil-induced skin
papilloma in mice, decrease the incidence of papilloma,
prolong the latent period of tumor occurrence and reduce tumor
number per mouse in a dose-dependent manner. Red ginseng
extract B could effectively inhibit the Fe2+/cysteine-induced
lipid peroxidation of rat liver microsome, suggesting that red
ginseng extract B has a stronger antioxidative effect than
that of extract A. The results indicated that red ginseng
extracts (50 similar 400 mg/kg) could significantly inhibit
the growth of transplantable mouse sarcoma S180 and melanoma
B16. Red ginseng extracts A (0.5 mg/ml) and B (0.1 and 0.25
mg/ml) might effectively promote the transformation of T
lymphocyte, but there was no influence on lymphocyte
proliferation stimulated by concanavalin A. This suggests that
red ginseng extracts have potent tumor therapeutic activity
and improve the cell immune system.
Nutrition and immune function: Overview
Beisel W.R.
NAIDS, 8210 Ridgelea Court, Frederick, MD 21702-2938
USA
Journal of Nutrition (USA), 1996, 126/10 Suppl.
(2611S-2615S)
Malnutrition can have adverse, even devastating effects on
the antigen- specific arms of the immune system and on
generalized host defensive mechanisms. Protein/energy
malnutrition and/or deficiencies of single nutrients that
assist in nucleic acid metabolism generally lead to atrophy of
lymphoid tissues and dysfunctions of cell-mediated immunity.
Deficiencies of single nutrients can impair production of key
proteins. Trace element deficiencies are often multifactorial.
Essential fatty acid deficiencies can reduce or perturb the
synthesis of cytokine-induced eicosanoids. Arginine deficiency
can diminish the production of nitric oxide, and deficiencies
of antioxidant nutrients can allow increases in the damaging
effects of free oxygen radicals. Humoral immunity continues to
be maintained, although new primary responses to
T-cell-dependent antigens are generally subnormal in both
magnitude and quality. Immunological dysfunctions associated
with malnutrition have been termed Nutritionally Acquired
Immune Deficiency Syndromes (NAIDS). Infants and small
children are at great risk because they possess only immature,
inexperienced immune systems and very small protein reserves.
The combination of NAIDS and common childhood infections is
the leading cause of human mortality. NAIDS can generally be
corrected by appropriate nutritional rehabilitation, but from
a viewpoint highly important to this Workshop, AIDS and NAIDS
are intensely synergistic. AIDS-induced malnutrition can lead
to the secondary development of NAIDS, with its much broader
array of additional immunological dysfunctions. The complex
and far reaching insults to the immune system caused by NAIDS,
and the synergistic combination of NAIDS and AIDS, thereby
hasten the demise of many victims of AIDS. Aggressive
nutritional support for children with HIV infections could
delay, or lessen, the development of NAIDS and avoidance of
NAIDS would improve both quality and length of life.
Vitamin E and immunomodulation for cancer and AIDS
resistance
Liang B.; Watson R.R.
Prevention Center, University of Arizona, 1501 N. Campbell
Avenue, Tucson, AZ 85724 USA
Expert Opinion on Investigational Drugs (United Kingdom),
1996, 5/9 (1221-1225)
Nutrition has a profound effect on immunity and health.
Nutritional deficiencies impair immune responsiveness,
thereby, increase morbidity and mortality. On the other hand,
nutritional supplementation often enhances certain aspects of
immune function . Vitamin E, as a potent antioxidant and
immunostimulant, has recently received a great deal of
attention because of its action on immunity and disease
aetiology. We recently reviewed the interaction of vitamin E
with the immune system, AIDS, circulatory system, and
pulmonary system. This paper is a summary of several recent
studies on the mechanisms by which vitamin E affects cancer
resistance by immunomodulation via nuclear factor-kappaB
(NF-kappaB) inhibition.
Vitamin E in humans: Demand and delivery
Traber M.G.; Sies H.
Department of Molecular/Cell Biology, University of
California, Berkeley, CA 94720 USA
Annual Review of Nutrition (USA), 1996, 16/-
(321-347)
How much vitamin E is enough? An established use of
supplemental vitamin E in humans is in the prevention and
therapy of deficiency symptoms. The cause of vitamin E
deficiency, characterized by peripheral neuropathy and ataxia,
is usually malabsorption-a result of fat malabsorption or
genetic abnormalities in lipoprotein metabolism. Genetic
abnormalities in the hepatic alpha-tocopherol transfer protein
also cause vitamin E deficiency- defects in this protein cause
an impairment in plasma vitamin E transport. Impaired delivery
of vitamin E to tissues, thereby, results in deficiency
symptoms. Also discussed is the use of supplemental vitamin E
in chronic diseases such as ischemic heart disease,
atherosclerosis, diabetes, cataracts, Parkinson's disease,
Alzheimer's disease, and impared immune function, as well as
in subjects receiving total parenterol nutrition. In healthy
individuals, a daily intake of about 15-30 mg of
alpha-tocopherol is recommended to obtain 'optimal plasma
alpha-tocopherol concentrations' (30 microM or greater).
Vitamin E stimulation of disease resistance and
immune function
Liang B.; Lane L.; Watson R.R.
Department of Family Medicine, University of Arizona, Tucson,
AZ 85724 USA
Expert Opinion on Investigational Drugs (United Kingdom),
1995, 4/3 (201-211)
As the most powerful and versatile biological defence
mechanism of animals and man, the immune system identifies
foreign substances and defends the body against their attack.
The immune response is concerned not only with providing
protection against disease-causing infectious agents, such as
bacteria and viruses, that invade the body, but also in
recognising and destroying pre-cancerous, tumour-forming cells
that develop within the body. Recent evidence indicates that
vitamin E is a vital link in optimal immune system functioning
and can enhance resistance to disease. The interaction of
vitamin E and immune systems, AIDS, oxidative stress, and
circulatory and pulmonary system are reviewed in this
paper.
Nutritional support in critically ill
patients
Grant J.P.
Duke University Medical Center, Durham, NC 27710 USA
Ann. Surg. (USA), 1994, 220/5 (610-616)
Objective. The author reviews the newer nutritional
substrates in use or under investigation for enteral and
parenteral nutrition. Management of the critically ill patient
remains a significant challenge to clinicians, and it is hoped
that dietary manipulations, such as those outlined, may
augment host barriers and immune function and improve
survival.
Summary Background Data. The role of nutrition in patient
well-being has long been recognized, but until the past 25
years, the technology to artificially provide nutrients when
patients could not eat was not developed. With current, new
methods for enteral and vascular access, patients can be fed
nonvolitionally with little difficulty. Continued efforts have
been directed toward identifying optimal feeding formulations,
which have resulted in a multitude of commercially available
products. In the past several years, attention has been turned
to evaluation of four specialized nutrients and the use of
other substrates as pharmacologic agents.
Methods. Pertinent laboratory and clinical data were
reviewed to present the pros and cons for each nutritive
substrate.
Conclusions. Medium-chain fatty acids, branched-chain amino
acids, and glutamine have been shown to be of clinical benefit
and should be in common use in the near future. Short-chain
fatty acids still are under investigation. Albumin, vitamins E
and C, arginine, glutamine, and omega-3 fatty acids show great
promise as pharmacologic agents to manipulate the stress
response. Nucleotides remain investigational. Contents
Summary. The application of some new nutritional substrates
for use in critically ill patients, both as caloric sources
and as pharmacologic agents, are reviewed.
Nutritional status and immune function in cocaine
and heroin abusers and in methadone treated subjects
Huggins N.D.; Khaled M.A.; Cornwell P.E.; Alvarez J.O.
USA
Res. Common. Subst. Abuse (USA), 1991, 12/4
(209-215)
The plasma levels of some essential nutrients and the
lymphocyte CD4 to CD8 ratio were measured in four groups of
individuals that included: (a) cocaine and (b) heroin abusers,
(c) methadone treated and (d) healthy subjects. Folate and
B-carotene levels were lower in the three drug groups while
vitamin C was lower in the methadone and heroin subjects.
Vitamin E levels were borderline low in the methadone and
cocaine groups. The methadone group also showed a
significantly higher level of lipid peroxidation which
correlated well with the low values observed for the
antioxidant nutrients. Interestingly, the methadone group was
the only one with a significantly reduced lymphocyte CD4/CD8
ratio.
Regulation of copper/ zinc and manganese superoxide
dismutase by UVB iradiation, oxidative stress and
cytokines.
Isoherranen K; Peltola V; Laurikainen L; Punnonen J; Laihia
J; Ahotupa M; Punnonen K
Department of Clinical Chemistry, University of Turku,
Finland.
kirsi.isoherranen@utu.fi
J Photochem Photobiol B (Switzerland) Oct 1997, 40 (3)
p288-93
We have examined the effects of UVB irradiation, oxidative
stress and cytokines on the antioxidant enzymes copper/zinc
and manganese superoxide dismutase (CuZnSOD and MnSOD) in HeLa
cells. A single dose of UVB irradiation regulated
dose-dependently the expression of the 4 kb transcript of
MnSOD although it did not have any significant effect on MnSOD
enzymatic activity. In contrast, UVB irradiation reduced both
the enzymatic activity and the expression of the 0.7 and 0.9
kb mRNA transcripts of CuZnSOD. The cytokines TNF-alpha (1 ng
ml-1 and 10 ng ml-1) and IL-6 (100 U ml-1) induced MnSOD
activity, and TNF-alpha also upregulated MnSOD mRNA
expression. Interestingly, genistein, a soy isoflavone and a
tyrosine kinase inhibitor, was able to inhibit the induction
of Mn-SOD activity and mRNA expression by TNF-alpha. Enzymatic
CuZnSOD activity was depressed by a high dose of H2O2 while
IL-6 or TNF-alpha had no effect on CuZnSOD activity. Our
results demonstrate that, in addition to enzyme activity
level, UVB irradiation can regulate the superoxide dismutases
at the mRNA level. We also suggest that UVB irradiation,
oxidative stress and cytokines regulate differentially CuZnSOD
and MnSOD, and that the activities and expression of these
antioxidant enzymes are controlled by distinct mechanisms.
Changes in cytokine production and T cell
subpopulations in experimentally induced zinc-deficient
humans.
Beck FW; Prasad AS; Kaplan J; Fitzgerald JT; Brewer GJ
Department of Internal Medicine, Wayne State University
School of Medicine, Detroit,
Am J Physiol Jun 1997, 272 (6 Pt 1) pE1002-7
We have utilized an experimental model of human zinc
deficiency for study of cytokines production by TH1 and TH2
cells. Additionally, we determined ratios of CD4+ to CD8+ and
CD4+ CD45RA+ to CD4+CD45RO+ cells and percentages of CD73+ T
cytolytic cells in the CD8+ subset. The data were collected
during baseline, at the end of the zinc -restricted period,
and following zinc repletion. Our results showed that
functions of TH1 cells, as evidenced by production of
interferon-gamma, interleukin-2 (IL-2), and tumor necrosis
factor-alpha, were decreased, whereas functions of TH2 cells
(production of IL-4, IL-6, and IL-10) were unaffected by zinc
deficiency. Thus an imbalance between TH1 and TH2 cells
resulted because of zinc deficiency in humans. Our studies
also showed that zinc may be required for regeneration of new
CD4+ T lymphocytes and maintenance of T cytolytic cells. We
conclude that an imbalance between TH1 and TH2 cells,
decreased recruitment of T naive cells, and decreased
percentage of T cytolytic cells may account for decreased
cell-mediated immune functions in zinc -deficient
subjects.
Zinc deficiency: changes in cytokine production and
T-cell subpopulations in patients with head and neck cancer
and in noncancer subjects.
Prasad AS; Beck FW; Grabowski SM; Kaplan J; Mathog RH
Department of Internal Medicine, Wayne State University
School of Medicine, Detroit, MI
Proc Assoc Am Physicians Jan 1997, 109 (1)
p68-77
Cell-mediated immune dysfunctions and susceptibility to
infections have been observed in zinc -deficient human
subjects. In this study, we investigated the production of
cytokines and characterized the T-cell subpopulations in three
groups of mildly zinc -deficient subjects. These included head
and neck cancer patients, healthy volunteers who were found to
have a dietary deficiency of zinc, and healthy volunteers in
whom we induced zinc deficiency experimentally by dietary
means. We used cellular zinc criteria for the diagnosis of
zinc deficiency. We assayed enzyme-linked immunosorbent assay
the production of cytokines from phytohemagglutinin-stimulated
peripheral blood mononuclear cells and assessed by flow
cytometry the differences in T-cell subpopulations. Our
studies showed that the cytokines produced by TH1 cells were
particularly sensitive to zinc status, inasmuch as the
production of interleukin-2 (IL-2) and interferon-gamma were
decreased even though the deficiency of zinc was mild in our
subjects. TH2 cytokines (IL-4, IL-5, and IL-6) were not
affected by zinc deficiency. Natural killer cell lytic
activity also was decreased in zinc -deficient subjects.
Recruitment of naive T cells (CD4+CD45 RA+) and CD8+ CD73+
CD11b-, precursors of cytolytic T cells, were decreased in
mildly zinc -deficient subjects. An imbalance between the
functions of TH1 and TH2 cells and changes in T-cell
subpopulations are most probably responsible for cell-mediated
immune dysfunctions in zinc deficiency.
Zinc regulates DNA synthesis and IL-2, IL-6, and
IL-10 production of PWM-stimulated PBMC and normalizes the
periphere cytokine concentration in chronic liver
disease
Reinhold D.; Ansorge S.; Grungreiff K.
Dr. K. Grungreiff, Heydeckstr. 9, D-39104 Magdeburg
Germany
Journal of Trace Elements in Experimental Medicine (USA),
1997, 10/1 (19-27)
Zinc (zinc ions and/or chelated zinc ) plays an important
role in the maintenance of immune function. Patients with
chronic liver disease, particularly liver cirrhosis,
frequently have endotoxemia, increased serum concentrations of
cytokines, e.g., interleukin-6 (IL-6), and reduced serum zinc
levels. The aim of the present study was to investigate the
effects of zinc (ZnCl2, ZnO, ZnSO4) on DNA synthesis and
cytokine production (IL-2, IL-6, IL-10) in pokeweed mitogen
(PWM)-stimulated peripheral blood mononuclear cells (PBMC). In
addition, we examined the effect of long-term zinc
supplementation ( zinc -hydrogen-aspartate; UNIZINK 50; 3 x 1
= 29.76 mg/day) on IL-6 and IL-10 serum levels in patients
with chronic liver disease (n = 16), all with reduced serum
zinc levels. It could be shown that zinc concentrations up to
0.1 mM stimulate DNA synthesis and cytokine production by
PWM-stimulated PBMC, whereas higher concentrations (0.2-0.4
mM) have a strongly inhibitory effect. Zinc concentrations
exceeding 0.5 mM were found to have a toxic effect on these
immune cells. Interestingly, in most patients with chronic
liver disease (n = 10), zinc supplementation decreased IL-6,
and to a lesser extent, IL-10 serum levels, and normalized the
serum zinc concentrations. We conclude that zinc plays a
regulatory role in DNA synthesis and cytokine production by
PBMC. The critical zinc concentration for immune cells lies in
the range of 0.5 mM, which is equivalent to a daily dose of
similar45 mg zinc salt. Furthermore, zinc supplementation in
chronic liver disease with reduced serum zinc levels appears
to normalize IL-6 and IL-10 production.
The effect of zinc and vitamin A supplementation on
immune response in an older population.
Fortes C; Forastiere F; Agabiti N; Fano V; Pacifici R;
Virgili F; Piras G Guidi L; Bartoloni C; Tricerri A; Zuccaro
P; Ebrahim S; Perucci CA
National Institute of Health, Rome, Italy.
J Am Geriatr Soc Jan 1998, 46 (1) p19-26
OBJECTIVE: To determine if either supplemental vitamin A,
zinc, or both increases cell - mediated immune response in an
older population.
DESIGN: A double-blind, randomized, controlled trial of
supplementation with vitamin A and zinc.
SETTING: Casa Di Riposo Roma III, a public home for older
people in Rome, Italy.
SUBJECTS: The health and nutritional status of 178
residents were evaluated. One hundred thirty-six residents
agreed to participate in the trial and were randomized into
four treatment groups, and 118 of these residents completed
the trial.
INTERVENTION: The four treatments consisted of: (1) Vitamin
A (800 micrograms retinol palmitate); (2) Zinc (25 mg as zinc
sulfate); (3) Vitamin A and Zinc (800 micrograms retinol
palmitate and 25 mg as zinc sulfate); (4) Placebo capsules
containing starch.
MAIN OUTCOME MEASUREMENTS: Immune tests-counts of
leucocytes, lymphocytes, T-cell subsets, and lymphocyte
proliferative response to mitogens-were measured before and
after supplementation.
RESULTS: Zinc increased the number of CD4 + DR + T-cells (P
= .016) and cytotoxic T-lymphocytes (P = .005). Subjects
treated with vitamin A experienced a reduction in the number
of CD3 + T-cells (P = .012) and CD4 + T-cells (P = .012).
CONCLUSIONS: These data indicate that zinc supplementation
improved cell - mediated immune response, whereas vitamin A
had a deleterious effect in this older population. Further
research is needed to clarify the clinical significance of
these findings.
Nutritional modulation of cytokine biology.
Grimble RF
Institute of Human Nutrition, University of Southampton,
United Kingdom.
Nutrition Jul-Aug 1998, 14 (7-8) p634-40
The pro-inflammatory cytokines and oxidant molecules
produced during the inflammatory response, which follows
infection and injury, may be beneficial, or detrimental to the
patient, depending on the amounts and contexts in which they
are produced. Aberrant or excessive production has been
implicated in inflammatory disease, and sepsis. The
upregulation of cytokine production by NF kappa B and NFIL-6
activation by oxidants increases the likelihood of
cytokine-induced mortality and morbidity. Complex systems
exist for the control of cytokine production and oxidant
actions. The former include the hormones of the
hypothalamo-pituitary-adrenal axis, acute phase proteins, and
endogenous inhibitors of interleukin (IL)-1 and tumor necrosis
factor (TNF). The latter include endogenously synthesized
antioxidants, such as glutathione and dietary antioxidants,
such as tocopherols, ascorbates and cachectins. Nutrients
change cytokine production and potency by influencing tissue
concentrations of many of the molecules involved in cytokine
biology. Monounsaturated fatty acids and omega-3
polyunsaturated fatty acids (PUFAs) suppress TNF and IL-1
production and actions, while n-6 PUFAs exert the opposite
effect. Changes in eicosanoid production are more likely to
underlie this effect than alterations in membrane fluidity.
Low antioxidant intake results in enhanced cytokine production
and effects. The anorexia that follows infection and injury,
may be purposeful to permit release of substrate from
endogenous sources to support and control the inflammatory
process. Therefore, prior as well as concurrent nutrient
intake are of importance in determining the outcome of the
inflammatory response. (88 Refs.)
Beta-carotene-induced enhancement of natural killer
cell activity in elderly men: an investigation of the role of
cytokines.
Santos MS; Gaziano JM; Leka LS; Beharka AA; Hennekens CH;
Meydani SN
Jean Mayer US Department of Agriculture Human Nutrition
Research Center on Aging at Tufts University, Boston, MA
02111, USA.
Am J Clin Nutr Jul 1998, 68 (1) p164-70
We showed previously that natural killer (NK) cell activity
is significantly greater in elderly men supplemented with beta
-carotene than in those taking placebo. In an attempt to
determine the mechanism of beta -carotene 's effect, we
analyzed the production of NK cell-enhancing cytokines
(interferon alpha, interferon gamma, and interleukin 12).
Boston-area participants in the Physicians' Health Study (men
aged 65-88 y; mean age, 73 y) who had been supplemented with
beta -carotene (50 mg on alternate days) for an average of 12
y were enrolled in a randomized, placebo-controlled,
double-blind study. Elderly subjects taking beta -carotene
supplements had significantly greater plasma beta -carotene
concentrations than those taking placebo. Beta -carotene
-supplemented elderly men had significantly greater NK cell
activity than did elderly men receiving placebo. Percentages
of NK cells (CD16+CD56+) were not significantly different
between the beta -carotene and placebo groups. Production of
interleukin 12, interferon alpha, or concanavalin A-stimulated
interferon gamma by cultured peripheral blood mononuclear
cells was not significantly different between
beta-carotene-supplemented elderly and those taking placebo.
Our results indicate that beta -carotene -induced enhancement
of NK cell activity is not mediated by changes in percentages
of CD16+CD56+ NK cells nor through up-regulation of
interleukin 12 or interferon alpha.
Does N-acetyl-L- cysteine influence cytokine
response during early human septic shock?
Spapen H; Zhang H; Demanet C; Vleminckx W; Vincent JL;
Huyghens L
Department of Intensive Care, Academic Hospital, Vrije
Universiteit, Brussels, Belgium.
Chest Jun 1998, 113 (6) p1616-24
STUDY OBJECTIVE: To assess the effects of adjunctive
treatment with N-acetyl-L-cysteine (NAC) on hemodynamics,
oxygen transport variables, and plasma levels of cytokines in
patients with septic shock.
DESIGN: Prospective, randomized, double-blind,
placebo-controlled study.
SETTING: A 24-bed medicosurgical ICU in a university
hospital.
PATIENTS: Twenty-two patients included within 4 h of
diagnosis of septic shock.
INTERVENTIONS: Patients were randomly allocated to receive
either NAC (150 mg/kg bolus, followed by a continuous infusion
of 50 mg/kg over 4 h; n= 12) or placebo (n=10) in addition to
standard therapy.
MEASUREMENTS: Plasma concentrations of tumor necrosis
factor-alpha (TNF), interleukin (IL)-6, IL-8, IL-10, and
soluble tumor necrosis factor-alpha receptor-p55 (sTNFR-p55)
were measured by sensitive immunoassays at 0, 2, 4, 6 and 24
h. Pulmonary artery catheter-derived hemodynamics, blood
gases, hemoglobin, and arterial lactate were measured at
baseline, after infusion (4 h), and at 24 h.
RESULTS: NAC improved oxygenation (PaO2/FIO2 ratio,
214+/-97 vs 123+/-86; p<0.05) and static lung compliance
(44+/-11 vs 31+/-6 L/cm H2O; p<0.05) at 24 h. NAC had no
significant effects on plasma TNF, IL-6, or IL-10 levels, but
acutely decreased IL-8 and sTNFR-p55 levels. The
administration of NAC had no significant effect on systemic
and pulmonary hemodynamics, oxygen delivery, and oxygen
consumption. Mortality was similar in both groups (control,
40%; NAC, 42%) but survivors who received NAC had shorter
ventilator requirement (7+/-2 days vs 20+/-7 days; p<0.05)
and were discharged earlier from the ICU (13+/-2 days vs
32+/-9 days; p<0.05).
CONCLUSION: In this small cohort of patients with early
septic shock, short-term IV infusion of NAC was
well-tolerated, improved respiratory function, and shortened
ICU stay in survivors. The attenuated production of IL-8, a
potential mediator of septic lung injury, may have contributed
to the lung-protective effects of NAC.
Pro- and anti-inflammatory cytokines in healthy
volunteers fed various doses of fish oil for 1 year.
Blok WL; Deslypere JP; Demacker PN; van der Ven-Jongekrijg J;
Hectors MP; van der Meer JW; Katan MB
Department of General Internal Medicine, University Hospital
Nijmegen, The Netherlands.
Eur J Clin Invest (England) Dec 1997, 27 (12)
p1003-8
Dietary supplementation with n-3 fatty acids from fish oil
alleviates inflammation in various chronic inflammatory
disease states. Reductions in the production of
pro-inflammatory cytokines interleukin 1 beta (IL-1 beta),
tumour necrosis factor alpha (TNF-alpha), and interleukin 6
(IL-6) have been seen in humans after short-term n-3 fatty
acid supplementation. We investigated long-term effects of
dietary n-3 fatty acids on circulating cytokine concentrations
and on ex vivo stimulated whole-blood production of IL-1 beta,
TNF-alpha and interleukin 1 receptor antagonist (IL-1Ra), the
naturally occurring antagonist of IL-1. A total of 58 monks
with a mean age of 56 years were randomized into four groups
and their diets were supplemented with 0, 3, 6, or 9 g of fish
oil, providing 0, 1.06, 2.13 or 3.19 g of n-3 fatty acids per
day. Subjects received equal amounts of saturated fatty acids,
vitamin E and cholesterol. Compliance was excellent and
erythrocyte fatty acid profiles closely reflected the amounts
of n-3 fatty acids ingested. In the group receiving 9 g of
fish oil per day, no influence of n-3 fatty acids on
circulating cytokine concentrations was observed relative to
placebo. Endotoxin-stimulated whole-blood cytokine production
was measured at 26 and 52 weeks after the start and at 4, 8
and 26 weeks after cessation of supplementation. In all
groups, the production of IL-1 beta and IL-1Ra was higher
during supplementation than afterwards. However, no
differences in cytokine production were noted between the
placebo group and the various treatment groups at any point in
time. Our results suggest that long-term supplementation of
fish oil does not affect ex vivo cytokine production in
man.
Distinct mechanisms for N-acetylcysteine inhibition
of cytokine-induced E-selectin and VCAM-1 expression.
Faruqi RM; Poptic EJ; Faruqi TR; De La Motte C; DiCorleto
PE
Department of Cell Biology, Cleveland Clinic Foundation, Ohio
44195, USA.
Am J Physiol Aug 1997, 273 (2 Pt 2) pH817-26
We have examined the effects of N-acetyl-L- cysteine (NAC),
a well-characterized, thiol-containing antioxidant, on
agonist-induced monocytic cell adhesion to endothelial cells
(EC). NAC inhibited interleukin-1 (IL-1 beta)-induced, but not
basal, adhesion with 50% inhibition at approximately 20 mM.
Monocytic cell adhesion to EC in response to tumor necrosis
factor-alpha (TNF-alpha), lipopolysaccharide (LPS),
alpha-thrombin, or phorbol 12-myristate 13-acetate (PMA) was
similarly inhibited by NAC. Unlike published studies with
pyrrolidinedithiocarbamate, which specifically inhibited
vascular cell adhesion molecule 1 (VCAM-1), NAC inhibited IL-1
beta-induced mRNA and cell surface expression of both
E-selectin and VCAM-1. NAC had no effect on the half-life of
E-selectin or VCAM-1 mRNA. Although NAC reduced nuclear
factor-kappa B (NF-kappa B) activation in EC as measured by
gel-shift assays using an oligonucleotide probe corresponding
to the consensus NF-kappa B binding sites of the VCAM-1 gene
(VCAM-NF-kappa B), the antioxidant had no appreciable effect
when an oligomer corresponding to the consensus NF-kappa B
binding site of the E-selectin gene (E-selectin-NF-kappa B)
was used. Because NF-kappa B has been reported to be redox
sensitive, we studied the effects of NAC on the EC redox
environment. NAC caused an expected dramatic increase in the
reduced glutathione (GSH) levels in EC. In vitro studies
demonstrated that whereas the binding affinity of NF-kappa B
to the VCAM-NF-kappa B oligomer peaked at a GSH-to-oxidized
glutathione (GSSG) ratio of approximately 200 and decreased at
higher ratios, the binding to the E-selectin-NF-kappa B
oligomer appeared relatively unaffected even at ratios >
400, i.e., those achieved in EC treated with 40 mM NAC. These
results suggest that NF-kappa B binding to its consensus
sequences in the VCAM-1 and E-selectin gene exhibits marked
differences in redox sensitivity, allowing for differential
gene expression regulated by the same transcription factor.
Our data also demonstrate that NAC increases the GSH-to-GSSG
ratio within the EC suggesting one possible mechanism through
which this antioxidant inhibits agonist-induced monocyte
adhesion to EC.
Plasma levels of lipid and cholesterol oxidation
products and cytokines in diabetes mellitus and cigarette
smoking: effects of vitamin E treatment.
Mol MJ; de Rijke YB; Demacker PN; Stalenhoef AF
Department of Medicine, University Hospital Nijmegen,
Netherlands.
Atherosclerosis (Ireland) Mar 21 1997, 129 (2)
p169-76
To evaluate the role of both oxidation and inflammation in
atherosclerosis, we compared LDL oxidizability, in vivo lipid
and cholesterol oxidation, and basal and lipopolysaccharide
(LPS)-stimulated production of various cytokines in
normolipidemic patients with diabetes mellitus (DM: n = 11),
cigarettes smokers (n = 14). In addition, the effects of
vitamin E (600 I.U./day for 4 weeks) on these parameters were
evaluated. Initial LDL oxidation characteristics before and
after vitamin E were identical in the 3 groups. Plasma
thiobarbituric acid reactive substances were higher in DM and
smokers versus controls (0.77 +/- 0.22, 0.74 +/- 0.14 versus
0.62 +/- 0.10 mumol malondialdehyde equivalents/l,
respectively; P versus controls < 0.05) and normalized
after vitamin E supplementation. Total plasma oxysterols were
higher in smokers versus controls (354 +/- 104 versus 265 +/-
66 nmol/l, P < 0.05) and unaffected by vitamin E. The basal
and LPS-stimulated levels of interleukin-1 beta and tumour
necrosis factor alpha (TNF alpha) and the basal level of
interleukin-1-receptor antagonist (IL-1RA) were identical for
the 3 groups. LPS-stimulated IL-1RA was higher in DM versus
controls (10.7 +/- 2.0 versus 8.1 +/- 1.7 pmol/l, P <
0.05). After vitamin E, TNF alpha dropped in controls and
smokers, and IL-1RA in smokers only. Results suggest increased
in vivo oxidative stress and inflammation in DM and smoking,
which is partly overcome by vitamin E.
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 1998 May;81(5):334-43
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.
Reversal of doxorubicin-induced cardiac metabolic
damage by L-carnitine
Sayed-Ahmed MM; Shaarawy S; Shouman SA; Osman AM
Pharmacology Unit, Cancer Biology Department, National Cancer
Institute, Cairo University, Cairo, Egypt
Pharmacol Res, 39(4). 289-5 1999 Apr
Biopharmacological evaluations of the protective effects of
L-carnitine (a naturally occurring quaternary ammonium
compound) against doxorubicin-induced metabolic damage were
carried out in isolated cardiac myocytes and in isolated rat
heart mitochondria. Perfusion of the heart with DOX (0.5 mM)
caused a significant 70% inhibition of palmitate oxidation in
cardiac myocytes, while L-carnitine (5 mM) perfusion caused
stimulation which accounted for 37%. Perfusion of the heart
with L-carnitine after 10-min perfusion with DOX (0.5 mM)
caused 88% reversal of DOX-induced inhibition of palmitate
oxidation in cardiac cells. In rat heart mitochondria, DOX has
no effect on either palmitate oxidation or acyl-CoA synthetase
activity, whereas Enoximone (c-AMP-dependent phosphodiesterase
inhibitor), caused a significant inhibition of palmitate
oxidation and acyl-CoA activity (40 and 27%, respectively).
The oxidation of palmitoyl-CoA, an index of carnitine
palmitoyltransferse reaction was significantly inhibited by
DOX as a function of DOX concentration. Preincubation of
mitochondria with L-carnitine caused reversal of DOX-induced
inhibition of palmitoyl-CoA oxidation depending on the
concentration of L-carnitine. Moreover, L-carnitine treatment
did not interfere with the cytotoxic effect of doxorubicin
against the growth of solid Ehrlich carcinoma. The findings of
this study may suggest that inhibition of fatty acid oxidation
in the heart is at least a part of doxorubicin cardiotoxicity
and that L-carnitine can be used to prevent the
doxorubcin-induced cardiac metabolic damage without
interfering with its antitumour activities. Copyright 1999 The
Italian Pharmacological Society.
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