References
191. Selenium deficiency in
HIV infection and the acquired immunodeficiency syndrome
(AIDS).
Dworkin BM
Section of Nutrition, New York Medical College, Valhalla
10595.
Chem Biol Interact, 1994 Jun, 91:2?3, 181?6
Selenium is required for activity of the enzyme
glutathione peroxidase, and selenium deficiency may be
associated with myopathy, cardiomyopathy and immune
dysfunction including oral candidiasis, impaired phagocytic
function and decreased CD4 T?cells. We assessed selenium
status in 12 patients with AIDS compared to normals and found
significantly low plasma and red blood cell levels. Plasma
selenium in AIDS was 0.043 +/? 0.01 microgram/ml vs 0.095 +/?
0.016 in controls (P < 0.001). Selenium status correlated
with serum albumin (r = 0.77; P < 0.001) and 60% had
documented GI malabsorption as determined by abnormal
D?Xylose tests. In a subsequent study blood selenium and
glutathione peroxidase were diminished in 12 AIDS and 8 ARC
patients compared with normals (all P < 0.001). For
glutathione peroxidase the mean levels
were decreased by 45% in AIDS and 27% in ARC versus controls
(P < 0.001). Both plasma selenium and glutathione
peroxidase significantly correlated with total lymphocyte
counts (r = 0.65; P < 0.001; glutathione peroxidase and
lymphocyte counts). This occurred in both homosexuals and
drug users with AIDS and irrespective of the presence or
absence of diarrhea or GI malabsorption. To determine if
tissue levels of selenium were also depleted we studied
cardiac selenium levels in autopsy AIDS hearts compared to
age and sex matched controls. Cardiac selenium in AIDS was
0.327 +/? 0.082 micrograms/g dry weight versus 0.534 +/?
0.184 in controls (P < 0.01). Two cases had histologic
cardiomyopathy pathologically consistent with the
cardiomyopathy described in Keshan disease associated with
low selenium blood levels. To further assess mechanisms of
nutrient and selenium deficiency in AIDS we studied dietary
intake in outpatients and inpatients with various stages of
HIV infection. Inadequate selenium intake based on a computer
(Nutritionist 3) analysis of 72 h diet records was present in
only 17% of clinically stable HIV positive outpatients and
71% of inpatients with AIDS. Conclusions: Selenium deficiency
is common in HIV positive patients as documented by low
plasma and red blood cell levels of selenium, diminished
activity of glutathione peroxidase, and low cardiac selenium
levels in AIDS hearts. Patients with AIDS tend to have more
severe deficits than those with earlier stages of HIV
infection. The selenium deficit in blood does correlate with
serum albumin levels and total lymphocyte counts. Poor
dietary intake and malabsorption could lead to this condition
which has important implications for both cardiac and immune
functions in HIV positive patients.
192. Serum selenium and the
risk of coronary heart disease and stroke.
Virtamo J; Valkeila E; Alfthan G; Punsar S; Huttunen JK;
Karvonen MJ
Am J Epidemiol, 1985 Aug, 122:2, 276?82
The association between serum selenium concentration and
five?year risk of cardiovascular disease was studied in 1,110
men aged 55 to 74 years in two rural areas of Finland. In the
total cohort, all?cause and cardiovascular deaths were
associated significantly with serum selenium of less than 45
micrograms/liter, an adjusted relative risk of 1.4 (95%
confidence interval (Cl), 1.0?2.0, p less than 0.05) and 1.6
(95% Cl, 1.1?2.3, p less than 0.05), respectively. Among men
free of coronary heart disease at the outset, these
associations were of similar magnitude but did not attain
statistical significance. Among men free of stroke at the
outset, low serum selenium was associated significantly with
stroke mortality, an adjusted relative risk of 3.7 (95% Cl,
1.0?13.1). The associations of coronary deaths and myocardial
infarctions with low serum selenium were
nonsignificant.
193. Selenium status and
chronic disease mortality: Dutch epidemiological
findings.
Kok FJ; De Bruijn AM; Hofman A; Valkenburg HA
Int J Epidemiol, 1987 Jun, 16:2, 329?32
This paper summarizes Dutch epidemiological findings on the
impact of a low selenium (Se) status on mortality from
cardiovascular disease (CVD) and cancer. Se status parameters
of Dutch subjects are compared to those from Finland and the
USA, and the concept of a threshold effect for Se on disease
risk is discussed. Case?control analyses of prospective data
suggest that low serum Se (below 105 micrograms/l) is not
clearly associated with an excess risk of CVD death (relative
risk RR = 1.6, 90% confidence interval Cl = 0.9?2.9). Se
cancer findings indicate a possible gender difference in risk
(in males RR = 2.7, 90% Cl = 1.2?6.2; in females RR = 1.5,
90% Cl = 0.5?4.5). Larger studies, monitoring a combination
of Se status parameters are recommended.
194. Selenium and vitamin E in
relation to risk factors for coronary heart disease.
Ellis NI; Lloyd B; Lloyd RS; Clayton BE
J Clin Pathol, 1984 Feb, 37:2, 200?6
Fasting blood samples taken from 116 apparently healthy men
aged 30?50 years were assayed for selenium, glutathione
peroxidase activity, vitamin E, cadmium, lead, glucose,
lipids, and albumin. Blood pressure was measured in each
subject, and details of height, weight, smoking habits, and
alcohol consumption were recorded. Multivariate analysis of
the data showed that the decrease in blood and serum
concentrations of selenium and the increase in whole blood
cadmium concentrations in the cigarette smokers was
independent of alcohol consumption. There was no correlation
between blood selenium concentrations or glutathione
peroxidase activities and the risk factors for cardiovascular
disease. Neither alcohol consumption nor smoking had an
effect on the vitamin E concentrations. There was a strong
association, however, between vitamin E and serum lipid
concentrations, although the increase in triglyceride
concentrations in the smokers was not matched by a comparable
increase in vitamin E. The possible role of selenium in the
aetiology of heart disease remains unresolved.
195. Selenium and
cardiovascular diseases??an update.
Huttunen JK
National Public Health Institute, Helsinki, Finland.
Biomed Environ Sci, 1997 Sep, 10:2?3, 220?6
Dietary deficiency of selenium has been incriminated in
the etiology of cardiovascular diseases. Thus, cardiomyopathy
associated with low selenium intake has been described in
areas of exceptionally low selenium intake and in patients
receiving total parenteral nutrition. Epidemiological studies
have provided some evidence for the role of selenium
deficiency in the etiology of atherosclerotic disease. An
inverse association between the incidence of ischaemic heart
disease and selenium intake has been described in population
comparisons. The results of longitudinal studies within
populations are conflicting. While some investigations have
observed a relationship between low serum?selenium levels and
the risk of coronary disease, others have not. Final evidence
for the role of selenium in preventing atherosclerotic
disease can be obtained only from controlled prevention
trials.
196. Lipid peroxidation level
and antioxidant micronutrient status in a pre?aging
population; correlation with chronic disease prevalence in a
French epidemiological study (Nantes, France).
Coudray C; Roussel AM; Mainard F; Arnaud J; Favier A
Laboratoire de Biochimie, Hopital Albert Michallon, La
Tronche, France.
J Am Coll Nutr, 1997 Dec, 16:6, 584?91
OBJECTIVE: The general objective of the Etude du
Viellissement Arterial (EVA) program is to follow vascular
aging and the decline in cognitive functions at the
cerebrovascular level longitudinally over a 4?year period.
One of the specific objectives of this EVA study is to
examine epidemiologically the relationship between the
markers of oxidative stress (lipid peroxidation), the
antioxidant micronutrient status (particularly of selenium,
vitamin E, and the carotenoids) and the prevalence of chronic
disorders occurring during the pre?aging period. METHODS:
1389 subjects aged from 59 to 71 years were studied. RESULTS:
The concentration of plasma lipid peroxides was higher than
in young adults (2.91 +/? 0.38, men; 2.97 +/? 0.40, women
(mumol/l). On the other hand, plasma Se (1.09 +/? 0.21, men;
1.10 +/? 0.19, women (mumol/l)), erythrocyte vitamin E (5.32
+/? 1.29, men; 5.52 +/? 1.28, women (mumol/l)), and total
plasma carotenoids (2.19 +/? 0.98, men; 3.07 +/? 1.33, women
(mumol/l)) were comparable to values in young adults. In our
cohort, 40% of subjects had unremarkable medical histories.
The disorders most often encountered were lipemia (29.8% of
men, 36.1% of women), and hypertension (28.9% of men, 30.4%
of women). CONCLUSION: Se and vitamin E levels were raised in
cases of lipemia, especially in those treated with fibrates.
The mechanism of the increase is unknown. In hypertensives
and diabetics, there was a decrease in total carotenoids
associated with increased peroxidative risk.
197. Preventing heart disease
and cancer. What randomized, primary?prevention studies
show.
Lush DT
Primary Care Unit, MCP Hahnemann University, Philadelphia,
PA, USA.
Postgrad Med 1999 Oct 15;106(5):143?8
Several chemical agents appear to be useful in primary
prevention of CAD and cancer.
Randomized trials have found that in specific patient
subgroups, tamoxifen and raloxifene decreased the occurrence
of breast cancer, and lovastatin and aspirin decreased the
frequency of CAD events. Secondary analysis of randomized
primary?prevention studies has supported the use of vitamin E
and selenium in cancer prevention.
198. Protective role of selenium
against hepatitis B virus and primary liver
cancer in Qidong.
Biol Trace Elem Res 1997 Jan;56(1):117?24
Yu SY, Zhu YJ, Li WG
Cancer Institute, Chinese Academy of Medical Sciences,
Peking Union Medical College, Beijing, China.
High rates of hepatitis B virus (HBV) infection and
primary liver cancer (PLC) are present in Qidong county.
Epidemiological surveys demonstrated an inverse association
between selenium (Se) level and regional cancer incidence, as
well as HBV infection. Four?year animal studies showed that
dietary supplement of Se reduced the HBV infection by 77.2%
and liver precancerous lesion by 75.8% of ducks, caused by
exposure to natural environmental etiologic factors. An
intervention trial was undertaken among the general
population of 130,471. Individuals in five townships were
involved for observation of the preventive effect of Se. The
8?yr follow?up data showed reduced PLC incidence by 35.1% in
selenized table salt supplemented vs the nonsupplemented
population. On withdrawal of Se from the treated group, PLC
incidence rate began to increase. However, the inhibitory
response to HBV was sustained during the 3?yr cessation of
treatment. The clinical study among 226 Hepatitis B Surface
Antigen (HBsAg)?positive persons provided either 200
micrograms of Se in the form of selenized yeast tablet or an
identical placebo of yeast tablet daily for 4 yr showed that
7 of 113 subjects were diagnosed as having PLC in the placebo
group, whereas no incidence of PLC was found in 113 subjects
supplemented with Se. Again on cessation of treatment, PLC
developed at a rate comparable to that in the control group,
demonstrating that a continuous intake of Se is essential to
sustain the chemopreventive effect.
199. 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.
200. Hepatitis C virus encodes
a selenium?dependent glutathione peroxidase gene.
Implications for oxidative stress as a risk factor in
progression to hepatocellular carcinoma.
Zhang W; Cox AG; Taylor EW
Department of Pharmaceutical and Biomedical Sciences,
University of Georgia, Athens, USA.
Source Med Klin, 1999 Oct, 94 Suppl 3:, 2?6
Using structural bioinformatics methods, the aim is to
assess the hypothesis that hepatitis C virus (HCV) encodes a
glutathione peroxidase (GPx) gene in an overlapping reading
frame, linking HCV expression and pathogenesis to the Se
status and dietary oxidant/Antioxidant balance of the host.
METHODS: The putative HCV GPx gene was identified by
searching viral sequence databases, using conserved GPx
active site sequences as probes, giving particular weight to
the UGA (selenocysteine) codon. Multiple sequence alignments
were generated and analyzed to validate the sequence
similarity, and to establish the degree of conservation of
the identified genomic features in HCV. Molecular modeling
was used to assess the structural feasibility of the proposed
homology. RESULTS: The GPx homology region overlaps the NS4
gene, and is well conserved in HCV. The sequence similarity
of the conserved active site regions to a set of known GPx is
high (4 to 6 SD greater than expected for similar random
sequences). The computed strain energy of a molecular model
of the HCV GPx is energetically favorable, comparable to the
bovine GPx structure. CONCLUSIONS: By linking HCV replication
and pathogenesis to the Se status and dietary
oxidant/antioxidant balance of the host, the existence of a
viral GPx gene could help to explain why HCV disease
progression is accelerated by oxidant stresses such as
alcoholism and iron overload.