Life Extension Magazine




May 5, 2000

 

References


 

211. Serum selenium, plasma glutathione (GSH) and erythrocyte glutathione
peroxidase (GSH?Px)?levels in asymptomatic versus symptomatic human
immunodeficiency virus?1 (HIV?1)?infection.
Look MP, Rockstroh JK, Rao GS, Kreuzer KA, Barton S, Lemoch H, Sudhop T, Hoch J, Stockinger K, Spengler U, Sauerbruch T
Department of General Internal Medicine, University of Bonn, Germany.
Eur J Clin Nutr. 1997 Apr;51(4):266-72.

OBJECTIVES: Antioxidant defense status was investigated in HIV?infected patients by measuring serum selenium, erythrocyte glutathione peroxidase (GSH?Px) activity, plasma thiol (?SH) and glutathione (GSH) concentrations along with the assessment of the clinical stage and surrogate markers of HIV?disease. DESIGN, SETTING AND SUBJECTS: Serum selenium levels were determined cross?sectionally in 104 sequentially selected HIV?infected patients (83 outpatients and 21 patients with ongoing AIDS defining events). The patients were classified into three stages of the disease, I, II and III according to the 1993 Centers For Disease Control (CDC) classification system for HIV?infection. GSH?Px activities, plasma SH and plasma GSH concentrations were determined in a subset of 24 patients at stage I and 12 patients at stage III with an active AIDS?defining disease. RESULTS: Mean serum selenium levels were lower in CDC stage II (68.7 +/? 20.9 micrograms/l; P < 0.01; n = 34) and stage III (51.4 +/? 14.7 micrograms/l; P < 0.01; n = 37) HIV?infected patients than in healthy subjects (89.2 +/? 20.9 micrograms/l; n = 72) and stage I patients (82.3 +/? 20.5; microgram/l; n = 33). Serum selenium levels were positively correlated with CD4?count (r = 0.42; P < 0.001; n = 104) and inversely with levels of soluble tumor necrosis factor receptors type II (r = ?0.58; P < 0.01; n = 35), neopterin (r = ?0.5; P < 0.001; n = 80) and beta 2?microglobulin (r = ?0.4; P < 0.001; n = 94). Hepatitis C virus (HCV) and HIV?coinfected patients at CDC stages I and II showed markedly lower selenium concentrations compared to HIV?infected patients without concomitant HCV?infection. Serum selenium and GSH?Px activity in hospitalized AIDS patients was significantly lower as compared to asymptomatic patients and healthy subjects, whereas plasma SH and GSH concentrations were lower in both, asymptomatic ?and AIDS?patients, than in the controls. CONCLUSION: The results show that stages I?III of HIV?disease are characterized by significant impairments of antioxidative defenses provided by selenium, GSH?Px, SH?groups and GSH.

212. Micronutrient levels in HIV?1?infected children.
Periquet BA; Jammes NM; Lambert WE; Tricoire J; Moussa MM; Garcia J; Ghisolfi J; Thouvenot J
Purpan Hospital, Toulouse, France.
AIDS, 1995 Aug, 9:8, 887?93

OBJECTIVE: Micronutrients (zinc, copper, selenium, vitamin A, E, and carotenoids) are essential for the integrity of host defences. This study was designed to determine the prevalence of abnormalities of the micronutrient levels in HIV?1?seropositive children. DESIGN: Prospective study. SETTING: The study was performed on HIV?1?infected children at the Paediatric Haematology and Oncology Unit of Toulouse Hospital, France. PATIENTS: Twenty?one children, suffering from HIV?1 infection and 21 control subjects of similar age (2?9 years) were included in the study. In the HIV?1?infected children, two subgroups were considered according to stage (non?AIDS or AIDS), based on the Centers for Disease Control and Prevention 1987 criteria. RESULTS: The first statistically significant deficiencies occurred at non?AIDS stage and were confirmed at AIDS stage: P < 0.05 for lycopene, retinol, tocopherol and P < 0.001 for transthyretin and serum albumin. Levels of copper (40%) and long?chain polyunsaturated fatty acids (21%) were higher in the non?AIDS group than the controls. CONCLUSION: Biological impairing of the micronutrient levels was observed in the non?AIDS stage without clinical sign. This information is useful in delineating eventual and well considered nutritional intervention strategies that may improve the clinical status of HIV?1?infected children and perhaps alter the course of their disease.

213. Selenium supplementation suppresses tumor necrosis factor alpha?induced human
immunodeficiency virus type 1 replication in vitro.
Hori K; Hatfield D; Maldarelli F; Lee BJ; Clouse KA
Division of Cytokine Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20852, USA.
AIDS Res Hum Retroviruses, 1997 Oct, 13:15, 1325?32

Selenium is a nutritionally essential trace element that is important for optimal function of the immune system. It is incorporated into selenoproteins as the amino acid selenocysteine and it is known to inhibit the expression of some viruses. In this study, we show that selenium supplementation for 3 days prior to exposure to tumor necrosis factor alpha (TNF?alpha) partially suppresses the induction of human immunodeficiency virus type 1 (HIV?1) replication in both chronically infected T lymphocytic and monocytic cell lines. In acute HIV?1 infection of T lymphocytes and monocytes in the absence of exogenous TNF?alpha, the suppressive effect of selenium supplementation was not observed. However, selenium supplementation did suppress the enhancing effect of TNF?alpha on HIV?1 replication in vitro in acutely infected human monocytes, but not in T lymphocytes. Selenium supplementation also increased the activities of the selenoproteins, glutathione peroxidase (GPx) and thioredoxin reductase (TR), which serve as cellular antioxidants. Taken together, these results suggest that selenium supplementation may prove beneficial as an adjuvant therapy for AIDS through reinforcement of endogenous antioxidative systems.

214. natural antimutagenic agents may prolong efficacy of human immunodeficiency virus drug therapy.
McCarty MF
Nutrition 21, San Diego, CA 92109, USA.
Med Hypotheses, 1997 Mar, 48:3, 215?20

The long?term efficacy of new combination drug therapies for human immunodeficiency virus infection may be limited by the tendency of transfected human immunodeficiency virus to mutate to drug?resistant forms. This argues for the use of safe antimutagenic measures as adjuvants to such therapies. Certain nutrients and food factors?notably selenium, green?tea polyphenols, and cruciferous phytochemicals?can suppress cancer initiation and mutagenesis in animal and cell culture models; epidemiological studies suggest that ambient variations in consumption of these food factors can have an important impact on human cancer rates. Low?fat diets may reduce deoxyribonucleic acid base damage in human leukocytes, whereas increased body iron stores are
likely to increase mutation rates. Thus, ample but safe intakes of selenium, green?tea
polyphenols, and cruciferous vegetables, in the context of a diet low in fat and assimilable iron, can be expected to prolong the efficacy of drug therapy in subjects infected with the human immunodeficiency virus. These measures can also be recommended for cancer prevention in the general population

215. Serum selenium concentration and disease progress in patients with HIV infection.
Cirelli A; Ciardi M; de Simone C; Sorice F; Giordano R; Ciaralli L; Costantini S
Istituto Malattie Infettive, University La Sapienza, Rome, Italy.
Clin Biochem, 1991 Apr, 24:2, 211?4

The selenium concentration in the serum of 67 patients with HIV infection was measured to determine whether selenium deficiency occurred in the different stages of the disease. In the first stage of the study, patients were divided into four groups: symptom?free subjects, PGL (persistent generalized lymphadenopathy), ARC (AIDS related complex), and AIDS (acquired immunodeficiency syndrome). Selenium concentrations were normal in HIV antibody positive symptom?free subjects (1.18 +/? 0.27 mumol/L) and lower than normal in the other three groups (p less than 0.001). There was a significant correlation (p less than 0.001) between selenium levels and values of hemoglobin and erythrocyte sedimentation rate. Selenium deficiency was in no case associated with a lack of zinc in serum (also determined in all patients). In the second stage of the study, 12 patients were treated for a period of two months with low doses of selenium to assess whether such supplementation was able to restore their impaired immunological and hematological functions. The therapy increased serum selenium concentrations (from 0.77 +/? 0.23 to 1.44 +/? 0.41 mumol/L) and symptomatic improvements were noted. However, no changes were observed in the immunological and hematological parameters.

216. Serum selenium, plasma glutathione (GSH) and erythrocyte glutathione peroxidase
(GSH?Px)?levels in asymptomatic versus symptomatic human immunodeficiency virus?1
(HIV?1)?infection.
Look MP; Rockstroh JK; Rao GS; Kreuzer KA; Barton S; Lemoch H; Sudhop T; Hoch J;
Stockinger K; Spengler U; Sauerbruch T
Department of General Internal Medicine, University of Bonn, Germany.
Eur J Clin Nutr, 1997 Apr, 51:4, 266?72

OBJECTIVES: Antioxidant defense status was investigated in HIV?infected patients by measuring serum selenium, erythrocyte glutathione peroxidase (GSH?Px) activity, plasma thiol (?SH) and glutathione (GSH) concentrations along with the assessment of the clinical stage and surrogate markers of HIV?disease. DESIGN, SETTING AND SUBJECTS: Serum selenium levels were determined cross?sectionally in 104 sequentially selected HIV?infected patients (83 outpatients and 21 patients with ongoing AIDS defining events). The patients were classified into three stages of the disease, I, II and III according to the 1993 Centers For Disease Control (CDC) classification system for HIV?infection. GSH?Px activities, plasma SH and plasma GSH concentrations were determined in a subset of 24 patients at stage I and 12 patients at stage III with an active AIDS?defining disease. RESULTS: Mean serum selenium levels were lower in CDC stage II (68.7 +/? 20.9 micrograms/l; P < 0.01; n = 34) and stage III (51.4 +/? 14.7 micrograms/l; P < 0.01; n = 37) HIV?infected patients than in healthy subjects (89.2 +/? 20.9 micrograms/l; n = 72) and stage I patients (82.3 +/? 20.5; microgram/l; n = 33). Serum selenium levels were positively correlated with CD4?count (r = 0.42; P < 0.001; n = 104) and inversely with levels of soluble tumor necrosis factor receptors type II (r = ?0.58; P < 0.01; n = 35), neopterin (r = ?0.5; P < 0.001; n = 80) and beta 2?microglobulin (r = ?0.4; P < 0.001; n = 94). Hepatitis C virus (HCV) and HIV?coinfected patients at CDC stages I and II showed markedly lower selenium concentrations compared to HIV?infected patients without concomitant HCV?infection. Serum selenium and GSH?Px activity in hospitalized AIDS patients was significantly lower as compared to asymptomatic patients and healthy subjects, whereas plasma SH and GSH concentrations were lower in both, asymptomatic ?and AIDS?patients, than in the controls. CONCLUSION: The results show that stages I?III of HIV?disease are characterized by significant impairments of antioxidative defenses provided by selenium, GSH?Px, SH?groups and GSH.

217. Selenium and HIV infection [editorial]
Constans J; Conri C; Sergeant C
Nutrition, 1999 Sep, 15:9, 719?20
Abstract unavailable online.

218. Selenium supplementation of symptomatic human immunodeficiency virus infected patients.
Olmsted L; Schrauzer GN; Flores Arce M; Dowd J
Department of Family Medicine, School of Medicine, University of California, San Diego, La Jolla 92093.
Biol Trace Elem Res, 1989 Apr, 20:1?2, 59?65

The mean whole blood selenium levels in male San Diego, CA patients with acquired immune deficiency syndrome (AiDS) are 0.123 +/? 0.030 micrograms/mL (n = 24), and 0.126 +/? 0.038 micrograms/mL (n = 26) in patients with AIDS?related complex (ARC), compared to 0.195 +/?0.020 micrograms/mL (n = 28) in San Diego healthy controls (males). To establish whether intestinal absorption of dietary selenium is impaired in AIDS or ARC, a supplementation trial was conducted in which 19 symptomatic HIV?antibody positive male patients with AIDS or ARC were taking 400 micrograms of selenium/d in form of selenium yeast for up to 70 d. The mean whole blood Se levels increased to 0.28 +/? 0.08 micrograms/mL after 70 d of supplementation, the selenium supplements were well tolerated. A rationale for adjuvant selenium supplementation of symptomatic and asymptomatic HIV carriers is proposed.

219. Genomic structures of viral agents in relation to the biosynthesis of selenoproteins.
Taylor EW; Nadimpalli RG; Ramanathan CS
Computational Center for Molecular Structure and Design, University of Georgia, Athens
30601?2352, USA. wtaylor@rx.uga.edu
Biol Trace Elem Res, 1997 Jan, 56:1, 63?91

The genomes of both bacteria and eukaryotic organisms are known to encode selenoproteins, using the UGA codon for seleno?cysteine (SeC), and a complex cotranslational mechanism for SeC incorporation into polypeptide chains, involving RNA stem?loop structures. These common features and similar codon usage strongly suggest that this is an ancient evolutionary development. However, the possibility that some viruses might also encode selenoproteins remained unexplored until recently. Based on an analysis of the genomic structure of the human immunodeficiency virus HIV?1, we demonstrated that several regions overlapping known HIV genes have the potential to encode selenoproteins (Taylor et al. [31], J. Med. Chem. 37, 2637?2654 [1994]). This is provocative in the light of overwhelming evidence of a role for oxidative stress in AIDS pathogenesis, and the fact that a number of viral diseases have been linked to selenium (Se) deficiency, either in humans or by in vitro and animal studies. These include HIV?AIDS, hepatitis B linked to liver disease and cancer, Coxsackie virus B3, Keshan disease, and the mouse mammary tumor virus (MMTV), against which Se is a potent chemoprotective agent. There are also established biochemical mechanisms whereby extreme Se deficiency can induce a proclotting or hemorrhagic effect, suggesting that hemorrhagic fever viruses should also be examined for potential virally encoded selenoproteins. In addition to the RNA stem?loop structures required for SeC insertion at UGA codons, genomic structural features that may be required for selenoprotein synthesis can also include ribosomal frameshift sites and RNA pseudoknots if the potential selenoprotein module overlaps with another gene, which may prove to be the rule rather than the exception in viruses. One such pseudoknot that we predicted in HIV?1 has now been verified experimentally; a similar structure can be demonstrated in precisely the same location in the reverse transcriptase coding region of hepatitis B virus. Significant new findings reported here include the existence of highly distinctive glutathione peroxidase (GSH?Px)?related sequences in Coxsackie B viruses, new theoretical data related to a previously proposed potential selenoprotein gene overlapping the HIV protease coding region, and further evidence in support of a novel frameshift site in the HIV nef gene associated with a well?conserved UGA codon in the 1?reading frame.

220. Clin Chim Acta 1994 Oct 14;230(1):35-42
Vitamin, trace element and peroxide status in HIV seropositive patients:
asymptomatic patients present a severe beta-carotene deficiency.
Sappey C, Leclercq P, Coudray C, Faure P, Micoud M, Favier A
Groupe de Recherche et d'etude sur les Pathologies Oxydatives (GREPO), Faculte de
Medecine et de Pharmacie, La Tronche, France.

We have investigated whether nutritional status and peroxidation process are associated with the degree of development of HIV infection. This was done by measuring the status of vitamins (E, A and beta-carotene), of antioxidant trace elements (zinc, selenium) and lipid peroxide levels (lipid hydroperoxides and thiobarbituric acid reactants) in HIV-seropositive patients at CDC II and CDC IV stages and in comparison with normal subjects. There was a decrease in vitamin and trace element levels related to the severity of disease. The most dramatic decrease, however, was seen for carotenoids (0.94 +/- 0.46 mumol/l) and beta-carotene (0.24 +/- 0.14 mumol/l vs. 0.56 +/- 0.29 mumol/l) whose stage II levels were only half the normal value. Paradoxically, lipid peroxidation was higher at stage II than at stage IV. This can be attributed to an overproduction of oxygen radicals by polymorphonuclears in stage II. This deficiency in
antioxidant status, often found in patients suffering from peroxidative diseases, may have
important consequences on cellular immunity. Furthermore, the concomitant overproduction of free radicals may also affect HIV multiplication.

 




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