Medline Articles in the treatment of Disease
Trace Elements Arguments in Alzheimer's Disease
Dietary boron, brain function, and cognitive performance.
The importance of boron nutrition
for brain and psychological function.
Penland JG.
US Department of Agriculture, Agricultural Research Service, Grand Forks Human
Nutrition Research Center, ND 58202-9034, USA.
Boron (B) nutriture has been related to bone, mineral and lipid metabolism,
energy utilization, and immune function. As evidence accumulates that B is
essential for humans, it is important to consider possible relationships between
B nutriture and brain and psychological function. Five studies conducted in our
laboratory are reviewed. Assessments of brain electrical activity in both
animals and humans found that B deprivation results in decreased brain
electrical activity similar to that observed in nonspecific malnutrition.
Assessments of cognitive and psychomotor function in humans found that B
deprivation results in poorer performance on tasks of motor speed and dexterity,
attention, and short-term memory. However, little support was found for
anecdotal reports that supplementation with physiologic amounts of B helps
alleviate the somatic and psychological symptoms of menopause. Parallels between
nutritional and toxicological effects of B on brain and psychological function
are presented, and possible biological mechanisms for dietary effects are
reviewed. Findings support the hypothesis that B nutriture is important for
brain and psychological function in humans.
Publication Types:
Where do Alzheimer's plaques and
tangles come from? Aging-induced protein degradation inefficiency.
Chen M, Fernandez HL.
Department of Pharmacology and Therapeutics, University of South Florida
College of Medicine, Tampa, Florida, USA. michen@com1.med.usf.edu
Amyloid plaques and neurofibrillary tangles are prominent lesions in the
aging brain and they may be responsible for cell death in Alzheimer's
disease. But a basic question has not been answered: why and how are plaques
and tangles formed during aging? In this study, we approach this question by
first examining what happens in the aging body. Plaques and tangles do not
come alone, but together with many other aging markers in the body
(cholesterol deposition, gallstones, hair graying, and bone loss, etc.).
Because these aging markers occur to a certain extent in all elderly and at
about the same time in life, it is reasonable to conceive that they
originate from a common cause, that is, aging-induced metabolic
inefficiency. If cholesterol and gallstone depositions are the results of
inefficient degradation/clearance of lipids and minerals, then similarly
plaque and tangle formation in most people would be the results of
inefficient normal degradation of ?-amyloid precursor protein (APP) and tau,
respectively. By this view, our studies should focus on the enzymes
responsible for APP and tau normal degradation and their natural changes in
aging, rather than on presumed pathological factors. Whatever precise
mechanisms underlying their depositions, plaques and tangles are the natural
products of aging, thus fundamentally different from pathological events
such as cancer growth in concept.
Publication Types:
[Selenium deficiency and brain
functions: the significance for methylmercury toxicity].
[Article in Japanese]
Watanabe C.
Department of Human Ecology, Graduate School of Medicine, University of
Tokyo, Tokyo.
Selenium has been long recognized as one of the essential trace elements.
Although many selenoproteins have been identified in the last decade, the
physiological roles of Se and selenoproteins remain to be elucidated. Since
iodothyronine deiodinases (DIs), which regulate the tissue levels of thyroid
hormone, are (likely to be) selenoproteins, Se might have specific roles for
developing brain. In fact, when rodents are depleted of Se perinatally, the
thyroid hormone economy of the fetus is disturbed, which may lead to the
abnormal development of the brain and to the abnormal postnatal behavior
observed in Se-deficient animals. When the animals were depleted of Se after
weaning, when the role of thyroid hormone on brain development is minimal,
neurochemical and neurophysiological alterations were found in the
dopaminergic system. These postnatally-depleted rodents also showed abnormal
open-field behavior, which was distinct from that observed with perinatally-depleted
animals. The molecular events that convert Se-deficient status to these
neurochemical, neurophysiological, and behavioral functions are largely
unknown, and need to be further examined. The interaction between Se and
mercury compounds has also been the focus of many research, but there have
been few reports on the interaction between the physiological (nutritional)
level of Se and the toxicity of prenatal methylmercury (MeHg). Experimental
findings showed that Se-deficient rodents are more susceptible to the
prenatal toxicity of MeHg. It is noteworthy that MeHg specifically altered
the metabolism of Se in fetal/neonatal brain. Significance of the alteration
of the activities of selenoenzymes such as glutathione peroxidase and DIs in
animals by prenatal MeHg exposure are discussed in relation to the
neurobehavioral toxicity of MeHg.
Publication Types:
Boron neutron capture therapy of
brain tumors: functional and neuropathologic effects of blood-brain barrier
disruption and intracarotid injection of sodium borocaptate and
boronophenylalanine.
Yang W, Barth RF, Rotaru JH, Boesel CP, Wilkie DA, Bresnahan JC,
Hadjiconstantinou M, Goettl VM, Joel DD, Nawrocky MM.
Department of Pathology, The Ohio State University, Columbus 43210, USA.
Sodium borocaptate (BSH) and boronophenylalanine (BPA) are two drugs that have
been used clinically for boron neutron capture therapy (BNCT) of brain tumors.
We previously have reported that hyperosmotic mannitol-induced disruption of the
blood-brain barrier (BBB-D), followed by intracarotid (i.c.) administration of
BPA or BSH, either individually or in combination, significantly enhanced tumor
boron delivery and the efficacy of BNCT in F98 glioma bearing rats. The purpose
of the present study was to determine the short-term neuropathologic
consequences of this treatment and the long-term effects on motor and cognitive
function, as well as the neuropathologic sequelae 1 year following neutron
capture irradiation. BBB-D was carried out in non-tumor bearing Fischer rats by
infusing a 25% solution of mannitol i.c. followed by i.c. injection of BPA or
BSH, either individually or in combination, immediately thereafter. Animals were
euthanized 2 days after compound administration, and their brains were processed
for neuropathologic examination, which revealed sporadic, mild, focal neuronal
degeneration, hemorrhage, and necrosis. To assess the long-term effects of such
treatment followed by neutron capture irradiation, non-tumor bearing rats were
subjected to BBB-D after which they were injected i.c. with BPA (25 mg B/kg body
weight (b.w)) or BSH (30 mg B/kg b.w.) either individually or in combination (BPA
12.5 mg and BSH 14 mg B/kg b.w.). Two and a half hours later they were
irradiated at the Medical Research Reactor, Brookhaven National Laboratory,
Upton, NY, with the same physical radiation doses (5.79, 8.10 or 10.06 Gy),
delivered to the brain, as those that previously had been used for our therapy
experiments. The animals tolerated this procedure well, after which they were
returned to Columbus, Ohio where their clinical status was monitored weekly.
After 1 year, motor function was assessed using a sensitive and reliable
locomotor rating scale for open field testing in rats and cognitive function was
evaluated by their performance in the Morris water maze, the results of which
were similar to those obtained with age matched controls. After functional
evaluation, the rats were euthanized, their brains were removed, and then
processed for neuropathologic examination. Subtle histopathologic changes were
seen in the choroid plexuses of irradiated animals that had received BPA, BSH or
saline. Radiation related ocular changes consisting of keratitis, blepharitis,
conjunctivitis and cataract formation were seen with similar frequency in most
rats in each treatment group. Based on these observations, and the previously
reported significant therapeutic gain associated with BBB-D and i.c. injection
of BSH and BPA, the present observations establish its safety in rats and
suggest that further studies in large animals and humans are warranted.
PMID: 11100816 [PubMed - indexed for MEDLINE]
The justification for providing
dietary guidance for the nutritional intake of boron.
Nielsen FH.
United States Department of Agriculture, Agricultural Research Service, Grand
Forks Human Nutrition Research Center, ND 58202-9034, USA.
Because a biochemical function has not been defined for boron (B), its
nutritional essentiality has not been firmly established. Nonetheless, dietary
guidance should be formulated for B, because it has demonstrated beneficial, if
not essential, effects in both animals and humans. Intakes of B commonly found
with diets abundant in fruits, vegetables, legumes, pulses, and nuts have
effects construed to be beneficial in macromineral, energy, nitrogen, and
reactive oxygen metabolism, in addition to enhancing the response to estrogen
therapy and improving psychomotor skills and cognitive processes of attention
and memory. Perhaps the best-documented beneficial effect of B is on calcium
(Ca) metabolism or utilization, and thus, bone calcification and maintenance.
The paradigm emerging for the provision of dietary guidance that includes
consideration of the total health effects of a nutrient, not just the prevention
of a deficiency disease, has resulted in dietary guidance for chromium (Cr) and
fluoride; both of these elements have beneficial effects in humans, but neither
has a defined biochemical function. Knowledge of B nutritional effects in humans
equals or is superior to that of Cr and fluoride; thus, establishing a dietary
reference intake for B is justified. An analysis of both human and animal data
suggests that an acceptable safe range of population mean intakes of B for
adults could well be 1-13 mg/d. Recent findings indicate that a significant
number of people do not consistently consume more than 1 mg B/d; this suggests
that B could be a practical nutritional or clinical concern.
Publication Types:
Determining human dietary
requirements for boron.
Sutherland B, Strong P, King JC.
Department of Nutritional Sciences, University of California, Berkeley 94720,
USA.
A dietary requirement is defined as the lowest continuing intake of a nutrient
that for a specified indicator of adequacy, will maintain a defined level of
nutriture in an individual. An essential dietary component is one that the body
cannot synthesize in sufficient quantities to maintain health. Recommended
dietary allowances (RDAs) are based on estimates of the dietary requirements,
and are designed to prevent deficiency diseases and promote health through an
adequate diet. In 1996, the Food and Nutrition Board (FNB) began a revision
process of the RDAs using as criteria specific indicators of adequacy and
functional end points for reducing the risk of chronic disease. Boron (B) is a
dietary component, and evidence from animal studies indicates that it is a
dietary essential; it cannot be synthesized in tissues, and organisms exposed to
very low levels of B show developmental defects. In humans, there is evidence of
homeostatic regulation of B and an interrelationship with bone metabolism. To
understand better the relationship between dietary B and B homeostasis, we
measured the dietary B intake and urinary B losses in seven male participants of
a controlled metabolic study of Zn homeostasis. Average dietary B intake for the
repeated menu days, days 1, 2, and 3, was 4.56, 1.87, and 4.75 mg/d,
respectively. Urinary B excretion during the 42-d collection period averaged
3.20 +/- 0.41 mg/d. When dietary B was low, urinary B loss (2.92 mg/d) was
significantly lower than when B intake was higher (3.15 and 3.54 mg/d). Our
study showed that urinary B excretion changes rapidly with changes in B intake,
indicating that the kidney is the site of homeostatic regulation. To enable
establishment of a dietary requirement for B in the future, further research of
homeostatic regulation and functional markers of B metabolism need to be
performed, followed by epidemiological studies to identify health conditions
associated with inadequate dietary B.
PMID: 10050920 [PubMed - indexed for MEDLINE]
PMID: 10721907 [PubMed - indexed for MEDLINE]
Selenoprotein W: a review.
Whanger PD.
Department of Environmental and Molecular Toxicology, Oregon State University,
Corvallis 97331, USA. phil.whanger@orst.edu
Purification of selenoprotein W (Se-W) from rat and monkey muscles was shown to
exist in multiple forms: with or without reduced glutathione and/or a 41-Da
moiety (identity still unknown). TGA is located at coding position 13 in Se-W
complementary DNA (cDNA) from all five species studied (rats, mice, sheep, human
and monkey). TGA is also the stop codon in the rodents and sheep cDNA, but TAA
is the stop codon in primates. There is an 80% homology of the nucleotide
sequence in the coding region among the five species of animals, and the
predicted amino acid sequences are 83% identical (rodents identical and primates
identical). Se-W levels are highest in muscle, heart and brain from sheep and
primates, but very low in rodent hearts. Studies with tissue cultures of muscle
and brain cells indicated that selenium influenced Se-W levels. Although the
metabolic function of Se-W is unknown, preliminary data suggest that it has an
antioxidant function.
Publication Types:
Thalamic distribution of zinc-rich
terminal fields and neurons of origin in the rat.
Mengual E, Casanovas-Aguilar C, Perez-Clausell J, Gimenez-Amaya JM.
Departamento de Anatomia, Facultad de Medicina, Universidad de Navarra, ES-31008
Pamplona, Navarra, Spain. elm2002@med.cornell.edu
Several cortico-cortical and limbic-related circuits are enriched in zinc, which
is considered as an important modulator of glutamatergic transmission. While
heavy metals have been detected in the thalamus, the specific presence of zinc
has not been examined in this region. We have used two highly sensitive
variations of the Timm method to study the zinc-rich innervation in the rat
thalamus, which was compared to the distribution of acetylcholinesterase
activity. The origin of some of these zinc-rich projections was also
investigated by means of retrograde transport after intracerebral infusions of
sodium selenium (Na2SeO3). The overall zinc staining in the thalamus was much
lower than in the neocortex, striatum or basal forebrain; however, densely
stained terminal fields were observed in the dorsal tip of the reticular
thalamic nucleus, the anterodorsal and lateral dorsal thalamic nuclei and the
zona incerta. In addition, moderately stained zinc-rich terminal fields were
found in the rostral intralaminar nuclei, nucleus reuniens and lateral habenula.
Intracerebral infusions of Na2SeO3 in the lateral dorsal nucleus resulted in
retrogradely labeled neurons that were located in the postsubiculum, and also in
the pre- and parasubiculum. These results are the first to establish the
existence of a zinc-rich subicular-thalamic projection. Similar infusions in
either the intralaminar nuclei or the zona incerta resulted in labeling of
neurons in several brainstem structures related to the reticular formation. Our
results provide morphological evidence for zinc modulation of glutamatergic
inputs to highly selective thalamic nuclei, arising differentially from either
cortical limbic areas or from brainstem ascending activation systems.
PMID: 11182249 [PubMed - indexed for MEDLINE]Calcium-mediated
proteolytic damage in white matter of hydrocephalic rats?
Del Bigio MR.
Department of Pathology, University of Manitoba, Winnipeg, Canada.
Hydrocephalus is a pathological dilatation of the cerebrospinal fluid (CSF)-containing
ventricles of the brain. Damage to periventricular white matter is
multifactorial with contributions by chronic ischemia and gradual physical
distortion. Acute ischemic and traumatic brain injuries are associated with
calcium-dependent activation of proteolytic enzymes. We hypothesized that
hydrocephalus is associated with calcium ion accumulation and proteolytic enzyme
activation in cerebral white matter. Hydrocephalus was induced in immature and
adult rats by injection of kaolin into the cisterna magna and several different
experimental approaches were used. Using the glyoxal bis (2-hydroxyanil) method,
free calcium ion was detected in periventricular white matter at sites of
histological injury. Western blot determinations showed accumulation of calpain
I (mu-calpain) and immunoreactivity for calpain I was increased in
periventricular axons of young hydrocephalic rats. Proteolytic cleavage of a
fluorogenic calpain substrate was demonstrated in white matter. Immunoreactivity
for spectrin breakdown products was detected in scattered callosal axons of
young hydrocephalic rats. The findings support the hypothesis that
periventricular white matter damage associated with experimental hydrocephalus
is due, at least in part, to calcium-activated proteolytic processes. This may
have implications for supplemental drug treatments of this disorder.
PMID: 11089572 [PubMed - indexed for MEDLINE]
[Migraine
and prevention of migraine: the value of magnesium].
[Article in German]
Schuck P, Bohmer K, Resch KL.
Forschungsinstitut fur Balneologie und Kurortwissenschaft (FBK) Bad Elster,
Deutschland. peter.schuck@mail.iz-plauen.de
Migraine (with and without aura) is characterised by a marked heterogeneity of
clinical symptoms. A variety of pathophysiological models has been proposed and
a multitude of prophylactic strategies recommended. It appears that prophylaxis
is still problematic, despite considerable progress in acute treatment. Most
substances used for the former purpose either have substantial side effects or a
wide range of contraindications. Magnesium (Mg) seems to play a significant role
in the pathogenesis of migraine. A few clinical trials have produced preliminary
evidence of therapeutic efficacy. There is a reasonable amount of empirical
evidence, and further research is warranted considering its low cost and
favourable side effects profile. An attempt at prophylaxis in mild to mid-severe
migraine with a daily dose of 600 mg (about 50 mEq) Mg seems to be justified.
Publication Types:
· Review
· Review, tutorial
Rational
dosages of nutrients have a prolonged effect on learning disabilities.
Carlton RM, Ente G, Blum L, Heyman N,
Davis W, Ambrosino S.
Stonybrook University, Medical School, NY, USA.
CONTEXT: Reports that administration of nutrients has increased the academic
performance of learning-disabled children exist in the literature. OBJECTIVE: To
document the effects of nutrients on learning-disabled children in a controlled
study. DESIGN: A randomized, double-blind, placebo-controlled crossover trial,
which followed 1 year of open-label nutrients. Children who improved in the
open-label trial were eligible to enter the controlled phase of the study.
SETTING: Subjects were enrolled from the general community through
advertisements. PATIENTS OR OTHER PARTICIPANTS: Twenty children met the criteria
for being learning disabled. INTERVENTION: Each child was tried out on some (but
not necessarily all) of the B vitamins and minerals used in this study. These
were administered semi-blinded for the first year; double-blinded in crossover
rotations during the second year; and open-label in the ensuing years. MAIN
OUTCOME MEASURES: At various time points, school-certified psychologists
administered psychoeducational tests. School report cards were evaluated at
baseline and for all subsequent periods. RESULTS: Twenty learning-disabled
children entered the study, but 1 dropped out because of nausea. The remaining
19 children showed significant academic and behavioral improvements within a few
weeks or months of open-label treatment with nutrient supplements. Some children
gained 3 to 5 years in reading comprehension within the first year of treatment;
and all children in special education classes became mainstreamed, and their
grades rose significantly. Twelve of the children completed the 1-year
double-blind phase, after which approximately half of the children chose to
remain on the nutrients for at least 2 additional years. For those who
discontinued, it took at least 1 year to begin to see the first indications of
decline in academic performance, and another year for their grades to drop
significantly. In contrast, for children who remained on nutrients, the gains
continued the upward trend; at the end of year 4, the difference in scores
between the 2 groups had reached statistical significance (P < .01).
CONCLUSION: The overall results of this study tentatively support the concept
that learning disabilities may in some cases be a nutrient-responsive disorder.
Publication Types:
· Clinical trial
· Randomized controlled trial
PMID: 10802909 [PubMed - indexed for MEDLINE]
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: J Altern Complement Med 2000 Feb;6(1):7-17
Attention
deficit/hyperactivity disorder (ADHD) in children: rationale for its
integrative management. · Review · Review, tutorial
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