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Abstracts of Publication Cited in the Longevity Institute
Web Site :
Role of Nd3+ and Pb2+ on the RNA Cleavage Reaction by a
Small Ribozyme.
Site-Specific Cleavage Reaction Catalyzed by Leadzyme is
Enhanced by Combined Effect of Lead and Rare Earth Ions.
Is There a Prevention and Treatment Strategy for Macular
Degeneration?
Free radicals and Antioxidant Supplementation: A Review of
Their Roles in Age-Related Macular Degeneration.
Antioxidants and Eye Disease.
Are antioxidants or Supplements Protective For Age-Related
Macular Degeneration?
Preventative Ophthalmology. Age-related Macular
Degeneration.
Nutritional Supplement Use and Age-Related Macular
Degeneration.
Are Antioxidants or Other Supplements Protective for
Age-Related Macular Degeneration?
Antioxidants and Age-Related Eye Disease. Current and Future
Perspectives.
Evidence for Protection Against Age-Related Macular Degeneration
by Carotenoids and Antioxidant Vitamins.
Association of Zinc and Antioxidant Nutrients with Age-Related
Maculopathy.
Multicenter Ophthalmic and Nutritional Age-Related Macular
Degeneration Study
Dietary modification of human macular pigment density.
Moderate wine consumption is associated with decreased odds of
developing age-related macular degeneration in NHANES-1.
Aluminum exposure and metabolism.
Intestinal malabsorption, celiac disease and associated
lymphoma
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Role of Nd3+ and Pb2+ on the
RNA Cleavage Reaction by a Small Ribozyme. :
Author : Ohmichi T; Sugimoto N
Address : Department of Chemistry, Faculty of Science, Konan University, Higashinada-ku,
Kobe, Japan.
Journal : Biochemistry, 36(12):3514-21 1997 Mar 25
Abstract : Leadzyme is a ribozyme that requires Pb2+. We have previously shown that the
addition of Nd3+ in the presence of Pb2+ increased significantly the yield of the RNA cleavage reaction by a
leadzyme, although other rare earth ions or divalent ions except Pb2+ did not promote the reaction [Sugimoto,
N., & Ohmichi, T. (1996) FEBS Lett. 393, 97-100]. To investigate the combined effects of Nd3+ and Pb2+ on
the binding and cleavage steps of a leadzyme, CUGGGAGUCC, with a substrate, GGACCGAGCCAG, kinetics for the
leadzyme reaction have been measured at various concentration ratios of Nd3+ and Pb2+. At low concentration
ratios of Nd3+ under a constant total concentration of metal ions, Nd3+ increased the stability of the
complex between the leadzyme and the substrate. In contrast, at high concentration ratios of Nd3+, the
addition of Nd3+ decreased the stability of the complex. The rate constant of the cleavage step was maximized
when the ratio of Nd3+ to Pb2+ was 1:1. These results suggest that the complex between the leadzyme and the
substrate has binding sites for Nd3+ ion that influence complex stability and catalyze directly the cleavage
reaction. On the basis of the results, we propose a two-metal-ion mechanism in which Pb2+ and Nd3+ play the
roles of base and acid catalyst, respectively.
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Site-Specific Cleavage
Reaction Catalyzed by Leadzyme is Enhanced by Combined Effect of Lead and Rare Earth Ions.
Author : Sugimoto N; Ohmichi T.
Address : Department of Chemistry, Faculty of Science, Konan University, Kobe, Japan.
sugimoto@konan-u.ac.jp
Journal : FEBS Lett, 393(1):97-100 1996 Sep 9
Abstract : Lead-dependent ribozyme (leadzyme) is a ribozyme working with Pb2+. In this paper, we have
investigated the combined effect of metal ions, especially rare earth ions, on the cleavage reaction by the
leadzyme. As a result, it was observed that although only a rare earth ion or another divalent ion except
Pb2+ did not play a role as the catalyst, the addition of a rare earth ion in the presence of Pb2+ increased
significantly the yield of the cleavage reaction. The result suggests that the complex between the leadzyme
and the substrate should have two classes of metal ion binding sites.
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Is There a Prevention and
Treatment Strategy for Macular Degeneration?
Author : Richer SP.
Origin : VA Medical Center, N. Chicago, IL 60064.
Journal : Journal of the American Optometric Association, 1993 Dec, 64(12):838-50.
Abstract :
BACKGROUND : Reduced antioxidant defense of the retina secondary to poor nutrition and smoking combined with
increased life expectancy and exposure to solar radiation can provide a triple assault on the aging retina.
If left untreated, without prophylactic measures, 7.5 million American adults will suffer vision loss from
ARM by the year 2020.
METHODS : Better known pathobiologic interrelationships between ARM, nutritional/antioxidant status and
UV/blue visible solar exposure risk based on animal research and recent epidemiologic studies is presented,
along with an overview of ocular free radical biochemistry.
RESULTS : Because ARM begins parafoveally, and confounding ocular lens changes often occur, there have been
practical clinical/research difficulties in early diagnosis, and assessing improvement/loss from nutritional
intervention. Threshold Amsler grid testing, contrast sensitivity and more recently red foveal flicker
fusion frequency testing are presented as promising tests, for discerning subtle pathologic and functional
changes in vision.
CONCLUSIONS : A conservative prevention/treatment strategy is presented involving identification of at-risk
patients, solar radiation protection, nutritional counseling based on the new USDA Food Pyramid concept and
vitamin/mineral supplementation if necessary for non-compliant high risk patients. Excessive vitamin intake
of particular micronutrients has some drawbacks, and the optometrist should be aware of the implications
of self-prescribed OTC ocular formulations, the difference between UV risk vs. "blue light hazard" and
ongoing clinical trials.
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Antioxidants and Eye Disease.
Author : Christen WG Jr.
Origin : Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Journal : American Journal of Medicine, 1994 Sep 26, 97(3A):14S-17S; discussion 22S-28S.
Abstract : Oxidative mechanisms are believed to play an important role in the pathogenesis of
age-related eye disease, in particular, cataract and macular degeneration, the two most important causes of
visual impairment in older adults. For this reason, there is considerable interest in determining whether
vitamins and trace minerals with antioxidant properties can be of benefit in preventing the onset or
progression of disabling eye disease. Basic research studies have shown that antioxidants can protect
against the cumulative effects of oxidative stress in animal models of cataract and macular degeneration.
Data from observational epidemiologic studies in humans, however, are inconclusive. While results from
several studies, primarily cross-sectional and case-control, are compatible with a possible protective
role for micronutrients in cataract and macular degeneration, data for specific nutrients or specific
disease types have often been inconsistent. Further, these observational studies are limited because of
the inherent imprecision of dietary exposure data and the likely effects of uncontrolled confounding. Thus,
reliable data regarding a potentially important benefit of vitamin supplementation in eye disease will
emerge mainly from well-designed, large-scale, randomized trials. Such data are already being collected in
the National Eye Institute-sponsored Age Related Eye Disease Study, as well as in the Physicians' Health
Study and Women's Health Study.
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Are antioxidants or Supplements Protective For Age-Related Macular Degeneration?
Author : West S; Vitale S; Hallfrisch J; Munoz B; Muller D; Bressler S; Bressler NM.
Origin : Dana Center for Preventive Ophthalmology, Johns Hopkins Hospital, Baltimore, Md.
Journal : Archives of Ophthalmology, 1994 Feb, 112(2):222-7.
Abstract :
OBJECTIVES : The relationships between fasting plasma levels of retinol, ascorbic acid, alpha-tochopherol,
and beta-carotene and age-related macular degeneration (AMD) were studied in a population enrolled in the
Baltimore Longitudinal Study of Aging (BLSA), in which most of the data were collected 2 or more years before
assessment of macular status.
DESIGN : A total of 976 participants in the study were scheduled for a biennial examination from January
1988 through January 1, 1990, which included taking lens and macular photographs. A total of 827 (85%) of the
participants had fundus photographs taken, and most plasma data were available for 82% of those subjects
with fundus photographs. Age-related macular degeneration was defined as neovascular changes, geographic
and nongeographic atrophy, large or confluent drusen, or hyperpigmentation. A total of 226 cases of AMD
were available for analysis.
RESULTS : Logistic regression analyses suggested that alpha-tocopherol was associated with a protective
effect for AMD, adjusted for age, sex, and nuclear opacity. An antioxidant index, including ascorbic acid,
alpha-tocopherol, and beta-carotene, was also protective for AMD. Our conclusions must be tempered with
the knowledge that the population under study was basically well nourished, and few individuals had any
clinically deficient status. The study cannot exclude the possibility that quite low levels of
micronutrients, lower than those observed in this study, might be risk factors for AMD.
CONCLUSIONS : The data suggest a protective effect for AMD of high plasma values of alpha-tocopherol. An
antioxidant index, composed of plasma ascorbic acid, alpha-tocopherol, and beta-carotene, was also
protective. The use of vitamin supplements to prevent AMD is not supported by these data, which showed no
protective effect of vitamin use.
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Preventative Ophthalmology. Age-related Macular Degeneration.
Author : Bressler NM; Bressler SB.
Journal : Ophthalmology, 1995; Aug, 102(8):1206-11.
Abstract :
PURPOSE : This report was designed to review the current knowledge degeneration (AMD) and visual loss
associated with this entity in practical terms for the comprehensive ophthalmologist.
METHODS : Animal studies, epidemiologic studies, and clinical trials identified through the use of MEDLINE,
a reference list of articles reviewed, and personal contact with experts in this area provided information
reviewed for this report.
RESULTS : Reports concerning ultraviolet and visible light provide limited, inconsistent, and conflicting
data to support the theory that light exposure leads to AMD. Micronutrient supplementation is a provocative
but largely unproven hypothesis. Positive associations of cigarette smoking and cardiovascular disease or
certain risk factors for cardiovascular disease with AMD provide potential clues as to the underlying
pathogenesis of AMD and are yet another reason to treat these health problems. Drusen may disappear after
laser to the macula; however, this intervention will require careful, randomized, prospective trials to
determine if this therapy can reduce the risk of choroidal neovascularization and visual loss developing in
patients with AMD.
CONCLUSIONS : It is reasonable to have individuals wear sunglasses for comfort and possible protection from
ultraviolet light exposure to all ocular structures (especially the lens) at little or no risk to the
patient. Physicians probably should be reluctant to prescribe micronutrients or suggest other interventions
(such as laser to drusen) until their health claims have been substantiated and their long-term safety
soundly established.
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Are Antioxidants or Other Supplements Protective for Age-Related Macular Degeneration?
Author : Fekrat S; Bressler SB.
Origin : Retinal Vascular Center, Wilmer Ophthalmological Institute, Johns Hopkins University
School of Medicine, Baltimore, MD 21287, USA.
Journal : Curr Opin Ophthalmol, 1996 Jun, 7(3):65-7
Abstract : As the number of individuals with age-related macular degeneration increases, the economic
and social consequences of this blinding disease rise. No proven preventive measures exist to halt
development or progression of this disease. The specific insults that trigger and perpetuate age-related
macular degeneration are unknown; however, it may be the result of repetitive oxidative injuries. Several
studies suggest a possible protective role for antioxidant micronutrients and other trace minerals, but data
for specific antioxidants have been inconsistent between studies. Although promising, the preliminary
evidence is limited. Reliable data on whether antioxidant vitamins or trace minerals decrease the development
or progression of age-related macular degeneration will emerge from several ongoing large-scale randomized
clinical trials. Based on the currently available information, it is not possible to recommend antioxidant
micronutrient supplementation to protect against development or retard progression of age-related macular
degeneration.
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Antioxidants and Age-Related Eye Disease. Current and Future Perspectives.
Author : Christen WG.Christen WG; Glynn RJ; Hennekens CH.
Origin : Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Journal : Annals of Epidemiology, 1996 Jan, 6(1):60-6
Abstract : Oxidative mechanisms may play an important role in the pathogenesis of age-related eye
disease, in particular cataract and macular degeneration, the two most important causes of visual
impairment in older adults. For this reason, there is considerable interest in determining whether vitamins
and trace minerals with antioxidant properties can be of benefit in preventing the onset or progression of
disabling eye disease. Basic research studies have shown that antioxidants can protect against the cumulative
effects of oxidative stress in animal models of cataract and macular degeneration. Data from observational
epidemiological studies in humans, however, are inconclusive. While results from several studies, primarily
cross-sectional and case-control, are compatible with a possible protective role for micronutrients in
disease development, data for specific nutrients or specific disease types have often been inconsistent.
Further, these observational studies are limited because of the inherent imprecision of dietary exposure
data and the likely effects of uncontrolled confounding. Thus, reliable data regarding a potentially
important benefit of vitamin supplementation in eye disease will emerge mainly from well-designed,
large-scale, randomized trials.
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Association of Zinc and Antioxidant Nutrients with Age-Related Maculopathy.
Author : Mares-Perlman JA; Klein R; Klein BE; Greger JL; Brady WE; PaltaM; Ritter LL.
Origin : Department of Ophthalmology, University of Wisconsin, Madison, USA.
Journal : Archives of Ophthalmology, 1996 Aug, 114(8):991-7.
Abstract :
OBJECTIVE : To quantify relationships between dietary intake of zinc and antioxidant nutrients and early and
late age-related maculopathy (ARM).
DESIGN : A retrospective longitudinal cohort design using data pertaining to diets in the past (1978-1980),
which were assessed retrospectively using a food frequency questionnaire.
SETTING : Beaver Dam, Wis.
PATIENTS : A 50% random sample of free-living Beaver Dam Eye Study participants, 43 to 86 years of age
(N = 1968).
MAIN OUTCOME MEASURE : The presence of early and late ARM determined from fundus photography.
RESULTS : People in the highest vs lowest quintiles for intake of zinc from foods had lower risk for early,
ARM (odds ratio = 0.6, 95% confidence interval, 0.4-1.0, P for trend .05). This relationship appeared to be
stronger for some types of early ARM (increased retinal pigment) than for others. Zinc intake was unrelated
to late ARM. However, small numbers (n = 30) of people with this condition limit the ability to draw
conclusions about this later stage. Levels of carotenoids were unrelated to early or late ARM. Odds for early
ARM were lower in people in the highest vs lowest quintiles for the intake of vitamins C or E. However,
these associations were not statistically significant.
CONCLUSIONS : The data are weakly supportive of a protective effect of zinc on the development of some
forms of early ARM. Prospective studies are needed to further evaluate the potential influence of these and
other nutritional factors on different types and stages of age-related macular degeneration.
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Multicenter Ophthalmic and Nutritional Age-Related Macular Degeneration Study: Part 1: Design,
Subjects and Procedures.
Author : Richer S.
Origin : Eye Clinic 112e, DVA Medical Center, North Chicago, IL 60064, USA.
Journal : Journal of the American Optometric Association, 1996 Jan, 67(1):12-29.
Abstract :
BACKGROUND : A prospective 18 month, double-blind case-controlled study was designed to determine whether
a specific over-the-counter multivitamin/mineral/antioxidant nutrient capsule taken twice daily prevents
the progression of, or improves the outcome of non-exudative ARMD. Two randomly assigned experimental
ARMD groups are compared to each other, to age matched ARMD-free case controls and to 1994 NHANES III
nutritional data.
METHODS : Thirty-two dry ARMD patients assigned to group one (placebo) and 39 dry ARMD patients were
assigned to group two (Ocuguard, a broad spectrum antioxidant capsule). A third age and sex matched
ARMD-free case control group of 13 patients who met the same entrance criteria were also selected.
All participants underwent thorough visual and nutritional evaluation prior to initiation of the study.
Both ophthalmic tests and dietetic assessments were also performed at 6, 12 and 18 months following a 2-week
initiation period.
RESULTS : In comparison to NHANES-III age stratified population data and the Recommended Daily Allowance
(but not case controls), the ARMD population manifested decreased intake of nutrients vital to
cardiovascular health: vitamin E, magnesium, zinc, vitamin B6 and folic acid. The two randomly assigned
experimental groups were well matched, with little difference in baseline demographic, ocular, hematologic
and pre-intervention symptoms. There were differences in nutritional intake between the two groups, due
primarily to significantly higher percent ideal body weight in group two.
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Dietary modification of human macular pigment density.
Author : Hammond BR Jr; Johnson EJ; Russell RM; Krinsky NI; Yeum KJ; Edwards RB; Snodderly DM.
Origin : Department of Social and Behavioral Sciences, College of Arts and Sciences, Arizona State
University West, Phoenix 85069-7100, USA.
Journal : Investigative Ophthalmology and Visual Science, 1997 Aug, 38(9):1795-801.
Abstract :
PURPOSE : The retinal carotenoids lutein (L) and zeaxanthin (Z) that form the macular pigment (MP) may help
to prevent neovascular age-related macular degeneration. The purpose of this study was to determine whether
MP density in the retina could be raised by increasing dietary intake of L and Z from foods.
METHODS : Macular pigment was measured psychophysically for 13 subjects. Serum concentrations of L, Z, and
beta-carotene were measured by high-performance liquid chromatography. Eleven subjects modified their usual
daily diets by adding 60 g of spinach (10.8 mg L, 0.3 mg Z, 5 mg beta-carotene) and ten also added 150 g of
corn (0.3 mg Z, 0.4 mg L); two other subjects were given only corn. Dietary modification lasted up to
15 weeks.
RESULTS : For the subjects fed spinach or spinach and corn, three types of responses to dietary modification
were identified: Eight "retinal responders" had increases in serum L (mean, 33%; SD, 22%) and in MP density
(mean, 19%; SD, 11%); two "retinal nonresponders" showed substantial increases in serum L (mean, 31%) but not
in MP density (mean, -11%); one "serum and retinal nonresponder" showed no changes in serum L, Z, or
beta-carotene and no change in MP density. For the two subjects given only corn, serum L changed little
(+11%, -6%), but in one subject serum Z increased (70%) and MP density increased (25%).
CONCLUSIONS : Increases in MP density were obtained within 4 weeks of dietary modification for most, but not
all, subjects. When MP density increased with dietary modification, it remained elevated for at least
several months after resuming an unmodified diet. Augmentation of MP for both experimental and clinical
investigation appears to be feasible for many persons.
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Moderate wine consumption is associated with decreased odds of developing age-related macular
degeneration in NHANES-1.
Author : Obisesan TO; Hirsch R; Kosoko O; Carlson L; Parrott M.
Origin : Department of Internal Medicine, Howard University Hospital, Washington, DC 20060, USA.
Journal : Journal of the American Geriatrics Society, 1998 Jan,; 46(1):1-7.
Abstract :
OBJECTIVE : To determine the association between alcohol intake and the risk of developing age-related
macular degeneration (AMD).
DESIGN : Case control study.
PARTICIPANTS : The sample consisted of 3072 adults 45 to 74 years of age with macular changes indicative
of AMD who participated in a nationally representative sample of the first National Health Nutrition and
Examination Survey (NHANES-1) between 1971 and 1975: (a) the ophthalmology data set and (b) the medical
history questionnaire.
MAIN OUTCOME MEASURES : Alcohol intake and the risk of developing AMD were measured. AMD was determined by
staff at the National Eye Institute by fundoscopy examination using standardized protocol.
RESULTS : Overall, 184 individuals (6%) had AMD. We observed a statistically significant but negative
association between AMD and the type of alcohol consumed in a bivariate model (OR 0.86; 95% CI 0.73, 0.99).
In the same model, age maintained a consistently strong association with AMD (OR 1.08; 95% CI 1.06-1.11;
P < .001). Among the different types of alcohol consumed in NHANES-1 (beer, wine, and liquor), the effect of
wine, either alone (OR 0.66; 95% CI 0.55-0.79) or in combination with beer (OR 0.66; 95% CI 0.55-0.79) or
liquor (OR 0.74; 95% CI 0.63-0.86), dominated the negative association observed between AMD and alcohol type.
Additionally, a statistically significant and negative association between wine and AMD was noted after
adjusting for the effect of age, gender, income, history of congestive heart failure, and hypertension
(OR 0.81; 95% CI 0.67-0.99).
CONCLUSION : Moderate wine consumption is associated with decreased odds of developing AMD. Health promotion
and disease prevention activities directed at cardiovascular disease may help reduce the rate of
AMD-associated blindness among older people.
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Aluminum exposure and metabolism
Author : Greger JL. Sutherland JE.
Origin : Department of Nutritional Sciences, University of Wisconsin, Madison 53706, USA.
Journal : Critical Reviews in Clinical Laboratory Sciences, 1997 Oct, 34(5):439-74.
Abstract : Aluminum (Al) is a nonessential, toxic metal to which humans are frequently exposed.
Oral exposure to aluminum occurs through ingestion of aluminum-containing pharmaceuticals and to a lesser
extent foods and water. Parenteral exposure to aluminum can occur via contaminated total parenteral
nutrition (TPN), intravenous (i.v.) solutions, or contaminated dialysates. Inhalation exposure may be
important in some occupational settings. The gut is the most effective organ in preventing tissue aluminum
accumulation after oral exposure. Typically .i.Al:gastrointestinal absorption; of aluminum from diets is
< 1%. Although the mechanisms of aluminum absorption have not been elucidated, both passive and active
transcellular processes and paracellular transport are believed to occur. Aluminum and .i.Al:calcium; may
share some absorptive pathways. Aluminum absorption is also affected by the speciation of aluminum and a
variety of other substances, including citrate, in the gut milieu. Not all absorbed or parenterally
delivered aluminum is excreted in urine. Low .i.Al:glomerular filtration; of aluminum reflects that most
aluminum in plasma is nonfiltrable because of complexation to proteins, predominantly .i.Al:transferrin;.
The importance of .i.Al:biliary secretion; of aluminum is debatable and the mechanism(s) is poorly
understood and appears to be saturable by fairly low oral doses of aluminum.
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Intestinal malabsorption, celiac disease and associated lymphoma: from symptoms to diagnosis
Gasbarrini G
Author : Gasbarrini G; Corazza GR; Biagi F; Brusco G; Andreani ML; Malservisi S; Greco AV.
Origin : Istituto di Medicina Interna, Universitˆ Cattolica Sacro Cuore, Roma.
Journal : Riv Eur Sci Med Farmacol, 16 Suppl 1:39-68, 1994 Sep-Dec
Abstract : The clinical consequences of intestinal malabsorption are extremely variable and a
dissociation between malabsorption, malabsorption syndrome and enteropathy is often noted. Enteropathy
does not always results in malabsorption and in an alteration of the tests exploring the absorptive function.
The following have particular relevance in clinical practice: coeliac disease, malabsorption induced by
microbiologic agent (including Whipple's disease), post-surgical malabsorption and selective carbohydrate
malabsorption. In particular, coeliac disease has been analyzed in its various aspects, from studies with
organ cultures to immunological hypotheses, from the classical variety to subclinical forms and to serious
complications, such as enteropathy-associated T cell lymphoma. Malabsorption syndromes are dramatically
underdiagnosed: in the typical case of coeliac disease, enteropathy represents a clinical iceberg, and the
discovery of the submerged portion, represented by the polymorphous subclinical varieties, has just started.
As far as intestinal malabsorption is concerned, the main clinical problem regards the diagnosis.
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