LE Magazine, July 2002 - Medical Updates

Studies from throughout the world that can help you live longer

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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