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LE Magazine July 2002
Studies from throughout
the world that can help you live longer
July 2002 Table of Contents
1. GH replacement therapy
and VLDL cholesterol
Those with adult growth hormone (GH) deficiency are often dyslipidemic
and may have an increased risk of cardiovascular disease. The secretion
and clearance of very low density Lipoprotein (VLDL) are important causes
of blood lipid (fat) concentrations. This study examined the effect of
GH replacement therapy on VLDL metabolism. VLDL kinetics was determined
in 14 adult patients with GH deficiency before and after 3 months of GH
or placebo treatment. GH replacement therapy increased blood insulin-like
growth factor I (IGF-1) concentrations 2.9-fold, fasting insulin concentrations
1.8-fold, and hemoglobin A (1C) from 5.0% to 5.3%. It decreased fat mass
by 3.4 kg and increased lean body mass by 3.5 kg. The total cholesterol
concentration, the low-density lipoprotein (LDL) cholesterol concentration,
and the VLDL cholesterol/VLDL ratio decreased. GH therapy did not significantly
change the VLDL pool size, but increased the VLDL secretion rate from
9.2 to 25.9 mg/kg per day and the metabolic clearence rate (MCR) from
11.5 to 20.3 ml/min. No significant changes were observed in the placebo
group. This study suggests that GH replacement therapy improves lipid
profile by increasing the removal of VLDL. Although GH therapy actually
stimulates VLDL secretion, this increase in VLDL is ultimately reduced
by the increase in the VLDL clearance rate, which the researchers postulate
is due to its effects in increasing low-density lipoprotein (LDL) receptors
and modifying VLDL composition.
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM,
1999, Vol 84, Iss 1, pp 307-316
2. A retrospective study
of antineoplastons in brain tumors
The results of treatment of brain tumors have been disappointing. The
objective of this study was to evaluate a new treatment with antineoplastons
A10 and AS2-1. Patients received daily injections of antineoplastons A10
and AS2-1 at average dosages of 7.7 and 0.36 g/kg/day, respectively. Tumor
dimensions were documented by magnetic resonance imaging. Changes in tumor
size were categorized as defined by the National Cancer Institute. The
results showed that antineoplastons A10 and AS2-1 eliminated or substantially
reduced tumors in 44% of patients with brain tumors. Of the 36 evaluable
patients, nine had a complete response, seven a partial response, and
12 stable disease. Progressive disease occurred in eight patients. Fifteen
patients are alive today, 86.5% of them for over three years from the
beginning of treatment. Adverse drug experiences included easily treated
abnormalities in plasma electrolytes. In a small percentage of patients
additional adverse effects possibly related to antineoplastons included
skin rash (19%), somnolence (17%), weakness (14%), nausea (6%), vomiting
(3%), headaches (3%), slurred speech (6%), confusion (3%), fever (3%),
and fluid retention (3%). Adverse effects were reversed on temporary discontinuation
of the antineoplastons or dose reduction. Thus, antineoplaston therapy
produced complete or partial responses in 16 of 36 (44%) patients with
brain tumors. Compared with standard treatment, antineoplaston therapy
is associated with prolonged survival time and prolonged time to disease
progression.
CLINICAL DRUG INVESTIGATION, 1999, Vol 18, Iss
1, pp 1-10
3. Deprenyl rescues dopaminergic
neurons from toxicity
The potential neuroprotective effect of deprenyl against aspartate excitotoxicity
was investigated on rat dopaminergic neurons (nerve cells) in culture.
While 24-hour application of aspartate (100 mu M) caused a marked decrease
in the number of surviving dopaminergic neurons, simultaneous application
of deprenyl significantly weakened the toxic effect of aspartate on the
cells. However, pre-treatment of cultures with deprenyl offered no protection
against subsequent aspartate damage. This suggests that the protective
effect of deprenyl may be independent of its irreversible inhibitory action
on monoamine oxidase molecules such as serotonin, dopamine and norepinephrine
(neurotransmitters). Deprenyl was also ineffective in preventing cell
death induced by hydrogen peroxide (H2O2). The results indicate that deprenyl
protects dopaminergic neurons from aspartate excitotoxicity through a
mechanism distinct from monoamine oxidase inhibition or detoxification
of free radicals.
EUROPEAN JOURNAL OF PHARMACOLOGY, 1999, Vol 377,
Iss 1, pp 29-34
4. Effects of GH replacement
on physical performance and body composition
Adults with growth hormone (GH) deficiency complain frequently of low
energy levels resulting in a low perceived quality of life. Body composition
is altered, with increased fat mass and decreased lean body mass, and
muscle strength is reduced. The aims of this study were to determine the
effects of GH replacement on physical performance and body composition
in GH deficient (GHD) adults. This was a six-month study of the administration
of growth hormone replacement to 35 GHD adults (17F), mean age 39.8 years
(range 21.1-59.9). The dosages were 0.25 IU/Kg/week - 0.125 IU/kg/week
for the first four weeks. This period was followed by a six-month open
phase of GH therapy. Maximum aerobic capacity was measured on a motorized
treadmill. Quadriceps muscle strength was assessed by measuring maximum
voluntary contractions and body composition. The results showed no statistically
significant changes in quadriceps muscle strength between the GH and placebo
groups. In both groups, there was a significant increase in quadriceps
muscle strength at the conclusion compared to baseline (start). Compared
to baseline, muscle strength was further improved in the GH treatment
group after an additional 12 months of treatment. No further improvement
was noted in the placebo group after six months on open GH treatment.
In the placebo group, maximum aerobic capacity decreased during the placebo
period. No significant change in aerobic capacity was observed in the
GH group. During the open GH treatment phase, the previously placebo-treated
group had a significant increase of maximum aerobic capacity whereas no
significant improvement could be seen in the GH group. However, in the
GH group there was a significant increase in lean body mass and a significant
decrease in fat mass. No statistically significant changes were noted
in the placebo group regarding body mass. The changes in body composition
in the GH group during the six-month placebo-controlled period were maintained
during continued open treatment. Similar changes in body composition to
those observed in the GH group (during the six-month placebo-controlled
period) were also seen in the placebo group, once the patients received
GH treatment. The results of the data show that GH replacement in GH deficient
adults is associated with favorable changes in body composition, which
could be important in the long-term health outcome and physical activity
of those with GH deficiencies. The data support the concept that GH therapy
alone, in the absence of some form of exercise program, may increase the
amount of lean tissue but not the quality or functional capacity of this
tissue. It may be that training, in addition to GH therapy, may be necessary
to significantly increase physical performance. Future trials with GH
therapy and general approaches to the treatment of GH deficiency should
include a planned activity program as an approach to health improvement
in these patients.
CLINICAL ENDOCRINOLOGY, 1999, Vol 51, Iss 1, pp
53-60
5. Human longevity at the
cost of reproductive success
The disposable soma theory on the evolution of aging states that longevity
requires investments in somatic maintenance that reduce the resources
available for reproduction. Experiments with the fruit fly (Drosophila
melanogaster) indicate that trade-offs of this kind exist in non-human
species. This study determined the interrelationship between longevity
and reproductive success in humans using historical data from the British
aristocracy. The number of progeny was small when women died at an early
age, increased with the age of death, reaching a plateau through the sixth,
seventh and eighth decades of life, but decreased again in women who died
at an age of 80 years or over. Age at first childbirth was lowest in women
who died early and highest for women who died at the oldest ages. When
account was taken only of women who had reached menopause, who were aged
60 years and over, female longevity was oppositely associated with number
of progeny and positively associated with age at first childbirth. The
findings show that human life histories involve a trade-off between longevity
and reproduction.
NATURE, 1998, Vol 396, Iss 6713, pp 743-746
6. B-cell proliferation
from a medicinal herb
The roots of the medicinal herb, Bupleurum falcatum L., containing a pharmacologically
active pectic polysaccharide, bupleuran 2IIc, as its active component,
were administered orally to mice for seven consecutive days. Proliferative
responses of spleen cells (produces lymphocytes) were enhanced in the
presence of the purified pectic polysaccharide, bupleuran 2IIc. Spleen
cells showed that the herb also stimulated lymphocytes, depleted of adherent
cells, or T cells. The treatment increased the subpopulation of CD25 immune
cells and surface immunoglobulin lymphocytes. Immunoglobulin secretion
of spleen cells treated with bupleuran 2IIc was increased according to
the culture time. Coexistence of interleukin-6 (IL-6) (a cytokine that
stimulates the growth and differentiation of human B cells) enhanced the
secretion more than that of bupleuran 211c alone. These results suggest
that the pectin polysaccharide in the herb proliferates B immune cells
in the absence of macrophages, and find that the resulting activated B
cells are then induced into antibody-forming cells in the presence of
IL-6. (Macrophages interact with lymphocytes to facilitate antibody production.)
The results suggest that the epitopes (combine with antibody or T cell
receptors) in bupleuran 211c act as active sites of the polysaccharide
during mitosis and cell transformation.
IMMUNOLOGY, 1999, Vol 97, Iss 3, pp 540-547
7. Estrogen therapy in
preventing and slowing the progression of dementia
Evidence from animal, human cross-sectional, case-control, and prospective
studies indicate that hormone replacement therapy (HRT) is a promising
treatment to delay the onset of symptoms of dementia. The Women's Health
Initiative Memory Study (WHIMS) is the first double-masked, randomized,
placebo-controlled, long-term clinical trial designed to test the hypothesis
that HRT reduces the incidence of all-cause dementia in women aged 65
and older. WHIMS, an ancillary study to the Women's Health Initiative
(WHI) funded by the National Institutes of Health, will recruit a subgroup
of women aged 65 and older from among those enrolling in the HRT trial
of the WHI. The WHI clinical centers and 10 affiliated satellites plan
to enroll approximately 8300 women into WHIMS over a 2-year period. Participants
will be followed annually for 6 years, receiving cognitive assessments
via the Modified Mini-Mental State (3MS) Examination. Women who screen
positively for cognitive impairment on the basis of an educational and
age-adjusted 3MS cut point proceed to more extensive neuropsychological
testing and neurological evaluation. Each woman suspected to have dementia
then undergoes a series of laboratory tests that confirm the clinical
diagnosis and classify the type of dementia. WHIMS is designed to provide
more than 80% statistical power to detect a 40% reduction in the rate
of all-cause dementia, an effect that could have profound public health
implications for older women's health and functioning.
CONTROLLED CLINICAL TRIALS, 1998, Vol 19, Iss 6,
pp 604-621
8. GH deficiency: Signs,
symptoms, and diagnosis
The use of growth hormone (GH) for children with growth hormone deficiency
(GHD) is well established. However, GHD is a syndrome that affects patients
of all ages. Literature on pediatric GHD is extensive because treatment
of this condition with GH replacement was approved about 12 years ago.
Although GH-replacement therapy for adult GHD has been accepted practice
in Europe for nearly 15 years, it was approved only recently for this
indication in the United States. In adults, GHD has nonspecific symptoms,
such as fatigue and impaired psychointellectual capacities, or no symptoms.
Measurable alterations induced by GHD in adults may include altered body
composition, reduced bone mineral density, impaired physical performance,
abnormal lipid metabolism, and impaired quality of life. GHD is common
in patients with treated or untreated pituitary tumors or other disorders
of the pituitary, patients who have had cranial irradiation, and adults
with a history of childhood-onset GHD. Isolated low levels of insulin-like
growth factor-1 (IGF-1) may indicate GHD but cannot substitute for a testing
process wherein there is an inadequate response of blood GH to insulin-induced
hypoglycemia.
ENDOCRINOLOGIST, 1998, Vol 8, Iss 6, Suppl. 1,
pp 8S-14S
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