Copyright
National Institutes of Health (U.S.). Nutrition Co.

Annual report : National Institutes of Health. Program in Biomedical and Behavioral Nutrition Research and Training (Volume 1989) online

. (page 6 of 19)
Online LibraryNational Institutes of Health (U.S.). Nutrition CoAnnual report : National Institutes of Health. Program in Biomedical and Behavioral Nutrition Research and Training (Volume 1989) → online text (page 6 of 19)
Font size
QR-code for this ebook


offspring will be neurologically evaluated.

RESEARCH DIRECTIONS

The following are among the many relevant
issues which, through investigation, may help
clarify the relationship of diet and neurologic
function:



37



• The nutritional needs of the brain and
nervous system to maintain its health
throughout life.

• Understanding the blood-brain barrier
nutrient transport process.

• The relationship, if any, between specific
dietary factors and certain brain functions
such as memory, alertness, and response
time.

• The effects of excessive intake of nutrients
and supplements on nervous system function.

• The role of specific dietary factors in the
etiology and prevention of neurologic
disorders such as stroke, Alzheimer's
disease, and Parkinson's disease.

• The identification and role of dietary-
derived neurotoxins.

OUTLOOK

Rapid research advances in the neurological
sciences have been realized, creating
opportunities to prevent, cure, or alleviate the
many neurological disorders now afflicting
many Americans. Studies elucidating the role
of nutrients, food additives, and general
dietary patterns in the development and
subsequent function of the brain and nervous
system will continue to be supported by NINDS
during the 1990's — the Decade of the Brain.



For more information on the NINDS nutrition
activities, contact:

Patricia Turner

Program Analyst

Legislation and Analysis Branch

National Institute of Neurological Disorders

and Stroke

Building 31, Room 8A03

National Institutes of Health

Bethesda, MD 20892

301-496-9271



38



NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES



Although the NIAID was established in 1948,
it traces its roots back to the Laboratory of
Hygiene, a bacteriological laboratory which
was founded in 1887 and was the forerunner of
the NIH and the NIAID. The NIAID supports
basic and clinical research in microbiology,
infectious diseases, immunology, and allergy.
A major component of NIAID's basic research is
concerned with fundamental life processes as
exemplified in microorganisms and in animal
cells in vitro. Techniques and basic biologic
principles, developed as a result of this
fundamental research in microbiology and
immunology, have then been applied to the
other areas of biology and medicine, including
nutrition.

The complex interrelationships among
nutrition, microbial infections, and immunology
have important health implications. In the
developing world, more than 1 billion cases of
infectious diarrheal disease occur yearly in
children under the age of 5 years. Malnutrition
both predisposes to diarrhea and occurs as a
result of diarrhea. Immunodeficiency states,
such as AIDS, cause malnutrition and set the
stage for superinfections which accelerate the
cycle of malnutrition and infection. Asthma
and allergic diseases affect over 40 million
Americans. Surgery and trauma lay the
groundwork for infection and subsequent
malnutrition. Many of these infections or their
complications can be mitigated, at least in part,
by appropriate nutrition.

PROGRAM HIGHLIGHTS

NIAID's studies on nutrition are an integral
part of the Institute's research to lessen the
adverse health consequences of immunologic
and infectious diseases. Of particular
significance are the consequences of wasting on
the underlying AIDS disease process, its
infectious and immunological complications,
and the outcome of antimicrobial drug therapy.

Continuing concerns are the prevalence of
infections among the malnourished, the effect



of infections on nutritional status, the
prevalence of food-borne microbial illness and
its control, and the effect of malnutrition on
resistance to infection, especially to infectious
diarrhea in young children.

Additional interests include the following:

• The infectious and immunological
complications of surgery and trauma, the
dissection of the underlying immunological
mechanisms involved, and better control
through immunological and nutritional
means.

• The effects of iron, zinc and related elements
on microbial virulence.

• Investigations concerning whether food
allergy plays an important role in
gastrointestinal disease.

AIDS and Nutrition

Since the recognition of AIDS in 1981, the
NIAID has mounted a coordinated and
comprehensive program of basic and clinical
research against AIDS and its microbial and
immunological complications.

Infection by the immunologically devastating
human immunodeficiency virus (HIV-1) sets
the stage for weight loss and deteriorating
nutritional status. Common features of
advanced AIDS are anorexia, vomiting,
diarrhea, malabsorption of fats,
carbohydrates, protein and other nutrients, and
a profound cachexia. One goal of NIAID's
mission of developing and testing potentially
useful drugs against AIDS is the maintenance of
AIDS patients in optimal health. Weight loss,
whose onset often precedes the diagnosis of
AIDS, can be so severe that it interferes with
anti-viral drug therapy and predisposes to
superinfections by other microbial agents.

Recent studies have indicated, for example,
that malnutrition in Americans with AIDS is so
pronounced that body cell mass near the time of
death averages just slightly over 50 percent of
normal and that total body weight is 33 percent



39



below ideal body weight. This degree of
wasting is similar to that reported for fatal
starvation, as in the siege of Leningrad during
World War II. These observations would
suggest that better supportive nutritional
therapy could significantly prolong survival in
AIDS patients.

In a study from the NIAID's Intramural
Program, low serum vitamin B12 levels were
found in some patients with AIDS but a
majority of AIDS patients had abnormally low
absorption of Bi2-intrinsic factor complex.
Each of these latter patients had mild to
moderate chronic inflammatory changes in
duodenal and colonic biopsy spjecimens. In a
subsequent study of patients who were HIV-1
positive but without AIDS, 7 percent were
found with low serum B12 levels. Since several
years are required to produce B12 deficiency,
these low serum B12 levels reflect a long-
standing abnormality of intestinal function
associated with HIV-1 infection. The
significance of B|2 deficiency on clinical
outcome in HIV-1 infection and its possible
deleterious effect on drug therapy remain to be
determined.

Immunology and Nutrition

Severe malnutrition due to any cause will
impair the body's normal cell-mediated
immunity and may diminish the immunity
effected by antibodies.

Lack of appropriate amounts of trace elements
in the diet may contribute to severe
immunologic deficits. Deficits of trace metals
such as iron and zinc are already known to
impair neutrophil function. Of particular
significance are the effects of specific
unsaturated fatty acids on immune functions in
infections, allergies, immunologically
mediated diseases, and transplantation.

Food Allergy

Food allergy may play an important role in
gastrointestinal disease, but little is known



concerning how widespread the problem is, its
mechanism of action, and its control. An
MAlD-sponsored Food Allergy Working Group
has been established to develop clinical
criteria, to furnish standardized food allergy
preparations, to develop appropriate in vitro
assay materials and methodologies, and to
conduct clinical studies of food allergens using
standardized protocols. Investigators also are
developing standard diagnostic tests to
determine who may be at risk from allergic
reactions to foods.

Other NlAlD-supported research has studied
the natural history, immunopathophysiology
and potential diagnostic, and therapeutic
aspects of IgE-mediated food hyjjersensitivity
in children with atopic dermatitis. During the
past 7 years, a NIAID-supported grantee has
studied children with severe atopic dermatitis
for food hypersensitivity. A large percentage
of patients reacted to one or more foods.
Abstinence from the offending food led to
significant improvement in eczematous signs
and symptoms and loss of symptomatic
sensitivity in one-third of children studied.

Increasing recognition of the role of food
allergies in disease should lead to better
diagnosis, improved patient care, and
eventually to the prevention of these food-
induced diseases.

RESEARCH DIRECTIONS

NIAID's interest in nutrition aims at a better
understanding of the complex inter-
relationships of nutrition, immunity, and
infection. The Institute's research directions
are correspondingly varied. They include the
following:

• AIDS and nutrition.

• The negative effect of malnutrition on
resistance to tropical infections (especially
infectious diarrheas) and the role of breast
milk as a defense against enteric infections.

• The significant morbidity and mortality of
rotavirus-induced infectious diarrhea among
infants in developing countries and a major



40



effort to develop a safe, effective, and
practical rotavirus vaccine for newborns.

• The role of minerals, especially iron, on the
metabolism and virulence of bacteria and
fungi.

• The role of nutritional factors in the immune
response to animal parasites that cause
significant human disease, e.g., schisto-
somiasis, giardiasis, and cryptosporidiosis.

• Infections in American hospitals, including
the effect of surgery on immune function,
hypercatabolism, and resistance to
infection.

• The modulating effects of specific nutrients
(e.g., vitamins, trace elements, fatty acids,
fiber, and amino adds) on basic immune
function.

• The relationship of specific foods to allergic
reactions such as anaphylaxis and eczema,
the immune response to ingested antigens
including milk, soy and egg, and the role of
foods in immunologically mediated
gastrointestinal diseases such as sprue and
inflammatory bowel disease.

OUTLOOK

Although significant advances have been made
during the past decade in acquiring new
knowledge of the interactions among nutrition,
infections, and immune disorders, much remains
to be learned of this complex interrelationship.
Intensified research on infectious diseases such
as AIDS may provide scientific advances that
help to clarify these important, unresolved
questions.



For more information on the NIAID nutrition
program, contact:

Eugene M. Zimmerman, Ph.D.

Special Assistant to the Director

Division of Allergy, Immunology, and

Transplantation

National Institute of Allergy and Infectious

Diseases

West wood Building, Room 752

National Institutes of Health

Bethesda, MD 20892

301-496-8973



41



NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES



The principal mission of the NIGMS is to
support fundamental research that undergirds
all biomedical investigations. The major focus
of the institute is on research concerned with
expanding knowledge of fundamental
biological structure and function at the cellular
and molecular level. Extramural studies
supported by the Institute include
investigations in the biophysical sciences, the
physiological sciences, in particular, the
resfX)nse of the whole body to trauma, the
structure and function of the cell, the basic
mechanisms of heredity, and the molecular
aspects of the interactions between therapeutic
drugs and agents and their target cells, tissues,
or organs.

PROGRAM HIGHLIGHTS

The great majority of the nutrition-related
research supported by NIGMS is in its trauma
and burn injury program area, which focuses on
the mechanisms involved in the body's
systemic responses to trauma. Thus, research on
the role of nutrition in decreasing morbidity
rates for patients who suffer serious trauma or
burn injury is of significant interest to the
Institute. NlGMS-supported scientists are
exploring nutritional requirements following
severe trauma and sepsis, new concepts in
parenteral therapy, branched chain amino acid
feeding during injury, and cellular function
during septic and hemorrhagic shock. In
addition, there are studies being supported
which are investigating the cellular changes
and mechanisms responsible for the protein
wasting associated with nutritional
deprivation.

Nutrition and Trauma

It has been established that changes in
metabolic patterns and nutritional status play
an important role in the development of sepsis
and multiple organ failure as well as in the
recovery from severe injury, including surgical
trauma. Recent highlights in the area of
nutritional requirements and therapy in the
traumatized patient have focused on the effects



of diet in the development of septicemia
following surgical and burn injury.

Specifically, bacterial infection is a frequent
and serious problem in patients who survive the
initial shock phase of thermal injury.
Infections in burn patients generally have been
considered to arise from exogenous organisms
coloruzing the burn wound. Until recently, very
little attention has been directed to the
indigenous microflora in the gastrointestinal
tract of the bum patient as a source of the
repeated episodes of bacteremia; yet, the gut
may serve as a reservoir for organisms causing
bacteremia in the burn patient. Bacterial
translocation has been defined as the passage
of viable bacteria from the intact
gastrointestinal tract to the mesenteric lymph
nodes and eventually into the systemic
circulation. It has been speculated that the GI
tract may cause the infections, either indirectly
by fecal organisms contaminating and
colonizing the wound, or directly by passage
through the intestinal wall. NIGMS-
supported researchers have shown that feeding
animals an elemental diet promotes
spontaneous bacterial translocation and
increases mortality in these animals after an
injection of E. coli endotoxin. Endotoxin
challenge also was associated with higher
levels of serum tumor necrosis factor (TNF), an
endo toxin-induced macrophage product which
produces cachexia. While the mechanisms
responsible for these changes are not known,
these investigators have speculated that
bacterial translocation related mortality may
in part be an amplified cytokine response to
endotoxin.

Grantees supported by the NIGMS also have
demonstrated that chronic administration of
TNF in experimental animal models reproduces
many of the physiologic findings observed in
the chronic wasting of clinical disease. During
ref)eated doses of TNF, there is a consistent
decrease in food intake in rats and mice,
decreased nitrogen balance, and weight loss.
Concomitant administration of antibody to TNF
is successful in blocking these effects. Chronic



42



starvation elicits a preferential mobilization
of fat stores with a relative sparing of skeletal
muscle. Also, in acute starvation there is a
marked wasting of liver protein accompanying
the loss in peripheral mass. By contrast,
chronic TNF administration produces an
exaggerated peripheral skeletal muscle
wasting with a preservation of liver mass
similar to that observed in injured patients.

NIGMS-suppxjrted researchers were among the
first to demonstrate that TNF markedly
suppresses the activity of lipoprotein lipase,
the enzyme which catalyzes the hydrolysis of
lipoprotein derived triacylglycerol, providing
fatty acids for storage or catabolism.

Total parental nutrition (TPN) has favorably
influenced the clinical outcome of many
malnourished and injured patients unable to
receive nutrients by the enteral route. Recent
evidence by researchers supjx^rted by NIGMS
suggests that significant differences in response
to infectious insult may exist between the
enterally and parenterally fed states. These
investigators have produced data which
suggest that bowel rest produces alterations in
host resistance to injury, independent of
malnutrition. Other investigations are
providing evidence that intravenous refeeding
blocks growth hormone provoked rises in serum
free fatty acids. In addition, hyper-
alimentation induces a metabolic background
which inhibits growth hormone secretion.

RESEARCH DIRECTIONS

The following leads are being pursued which
pertain to basic research on diseases and also
traumatic injury:

• The role of diet in organ and cellular
responses to cytokines.

• Change of metabolic patterns and
nutritional requirements following severe
injury.

• Hormonal imbalance following injury and its
effects on metabolism.

• Mechanisms involved in producing a protein
catabolic state after injury.



• Adaptive regulation of nutrient transport by
the gut. Transport appears to be governed by
nutrient-receptor proteins on specific cell
surfaces.

• Mechanism of suppression of lipoprotein
lipase activity by TNF. Pools of mRNA
which code for the lipase are perhaps
depleted in the presence of TNF.

• Which components of the host defense
system (neutrophils, immunomodulators,
etc.) are important in preventing bacterial
translocation.

• Receptors that recognize serum proteins
carrying galactosyl sugar residues, including
hormones that regulate the rate and extent
of nutrient uptake and processing in the
liver.

OUTLOOK

Research supported by the NIGMS serves to
establish the foundation of new knowledge
needed to make advances in the understanding
of many diseases. Those investigations which
are nutrition-related will help to provide the
concepts and relevant information necessary to
develop new treatments and hence, serve to
decrease morbidity and mortality.



For more information on the NIGMS nutrition
program, contact:

Yvonne T. Maddox, Ph.D.

Program Administrator

Biophysics and Physiological Sciences Program

National Institute of General Medical Sciences

Westwood Building, Room 905

Bethesda, MD 20892

301-496-7001



43



NATIONAL INSTITUTE OF CHILD HEALTH AND

HUMAN DEVELOPMENT



Since the NICHD was created in 1963, its
nutrition research program has focused on the
continuum of human development, from
conception through infancy, childhood, and
adolescence. The program emphasizes
preventive approaches to nutrition- related
conditions and stresses health promotion as
well as disease prevention. Much of the
research is multidisciplinary in nature and
involves the genetic, biochemical,
developmental, anthropometric, behavioral,
and cultural aspects of nutrition. The NICHD
supports research on maternal and fetal
nutrition; nutrition during infancy, childhood,
and adolescence; the relationship of nutrition
to reproduction; behavioral and cultural
aspects of nutrition; obesity and its nutritional
antecedents; nutritional therapy of inborn
errors of metabolism; and assessment of
nutritional status.

PROGRAM HIGHLIGHTS

The Institute has a strong interest in the
nutrient requirements of normal, premature, and
low birth weight infants, as well as in the
composition of human milk, cow milk, and
synthetic formulas, in relation to optimal
infant nutrition. In some of this work the
interest centers on metabolic processes in
neonatal adaptation and on the role played by
essential nutrients and other components of
human milk. Research on cultural and
behavioral determinants of nutritional
individuality includes studies of habits, taste,
and olfaction; food avoidances; and behavior
modification of dietary intakes. Research on
nutritional antecedents of adult disease focuses
primarily on factors in the development of
obesity in infancy, childhood, and adolescence.

Adrenoleukodystrophy

Adrenoleukodystrophy (ALD) is an X-linked
disorder characterized by the accumulation of
saturated very long chain fatty acids (VLCFA)
due to a genetic defect of a peroxisomal enzyme
that normally degrades these substances. ALD
affects mainly the nervous system white



matter, adrenal cortex, and testis. Recent
studies have demonstrated that adherence to a
diet low in fatty acids combined with daily
doses of glyceroltrierucate (the chemical name
for rapeseed oil derivative) can bring those
fatty acid levels under control. A study has
recently been initiated to test whether early
normalization of saturated VLCFA can prevent
or ameliorate the neurological impairment
associated with ALD. The study has three
components: 1) a double-blinded trial involving
adults with adrenomyeloneuropathy and
neurologically involved ALD heterozygotes; 2)
a prevention trial for neurologically
asymptomatic boys with ALD; and 3) a study of
neurologically symptomatic boys in whom the
rate of neurological progression will be
compared with that in more than 100 untreated
children with ALD.

Maternal Phenylketonuria

The success of newborn screening programs for
phenylketonuria (PKU) has created an
unexpected problem as women with PKU reach
childbearing age. Retrospective surveys have
shown a high rate of mental retardation,
microcephaly, congenital heart defects, and
intrauterine growth retardation among
offspring of women with PKU who were not
maintained on a diet with restricted amounts of
phenylalanine during pregnancy. An ongoing
collaborative study suggests that, to achieve an
optimal reproductive outcome, the diet should
be initiated prior to the 10th week of
pregnancy, and preferably before conception.
The diet should be maintained throughout
pregnancy, and the blood phenylalanine level
should be kept at 6 mg/dL or less.

Omega-3 Fatty Acids in Premature
Infants

It has been known for some time that certain
fatty acids are essential in the human diet. In
general this requirement has been considered to
be met by the provision of fatty acids of the
omega-6 class. A possible need for omega-3
fatty acids as well has been suggested by



44



observations of patients receiving parenteral
nutrition and by studies in newborn monkeys.
The issue is important because most milk
formulas for prematures, in contrast to human
milk, are very low in omega-3 fatty acids. Now
NICHD-supported research has demonstrated
that there is a delay in maturation of the rod
cells, light receptors of the retina, in very low
birth weight babies receiving formulas low in
long chain omega-3 fatty acids. Though rod
function returned to normal by the time the
infants reached 57 weeks post-conceptional age,
the results suggest that the omega-3 content of
these premature formulas is insufficient for
optimal visual development of very low birth
weight infants. The mechanism of this
developmental delay in vision needs to be
determined, along with its significance to the
long-term visual and behavioral function of
these babies.

Calciiun Transport to the Developing
Chick Embryo

Calcium is a major nutritional requirement for
vertebrate embryonic development, required for
physiological functions such as skeleton
formation, neuromuscular activity, and blood
coagulation. In avian species the
chorioallantoic membrane transports calcium
from the eggshell to the developing embryo,
and it can be used as a simple experimental
model for the study of transplacental calcium
transport.

Several components of the chick calcium
transport system have been identified by an
NICHD-supported investigator. A specific
calcium-binding protein, localized on the
surface of calcium-transporting ectodermal cells
of the chorioallantoic membrane, functions as a
calcium receptor. It is activated during
development by an enzymatic reaction which is
dependent on vitamin K. The calcium is
incorporated into a vesicle inside the cell, from
which it is eventually released by a
mechanism which involves acidification of the
vesicle. Near the receptor on the cell surface is
a calcium-activated ATPase which somehow
functions intracellularly to maintain the



vesicular calcium load. These studies
contribute to a specific understanding of calcium
transport as well as to a general understanding
of developmental functions and their
nutritional regulation.

Low Birth Weight Initiative:
Necrotizing Enterocolitis

In the United States, the most important factor
contributing to the infant mortality rate is a
birth weight of less than 2,500 g, or 5.5 lbs. At
present, 6.7 percent of all U.S. babies weigh less
than 2,500 g at birth and are termed low birth
weight infants. In FY 1985, the NICHD
inaugurated the Low Birth Weight Initiative
in order to focus more research attention on the
nationwide problem of infant mortality and
birth weight specific mortality. The nutrition
component of this initiative is divided into
several critically important facets: nutritional
management in pregnancy, nutritional
management of the very low birth weight
(VLBW) infant, and gastrointestinal
development.

As part of this initiative, NICHD has


1 2 3 4 6 8 9 10 11 12 13 14 15 16 17 18 19

Online LibraryNational Institutes of Health (U.S.). Nutrition CoAnnual report : National Institutes of Health. Program in Biomedical and Behavioral Nutrition Research and Training (Volume 1989) → online text (page 6 of 19)