The Tenth Annual International Symposium on Man and His Environment in Health and Disease

Special Focus: Environmental Aspects of Aging and the Endocrine System

February 27 C March 1, 1992


AMolecular Basis of Aging and Health Perspectives: Spontaneity of Oxidation and Molecular Duality of Oxygen@

Majid Ali, MD

Columbia University

Bloomfield, NJ

Early proto-eukaryotes of planet Earth were sustained by a largely oxygen-free atmosphere. Their survival was threatened as blue algae acquired photosynthetic activity and began to release large quantities of oxygen into the atmosphere. Lynn Margulis proposed in 1960s that mitochondria and certain other cellular organelles evolved from certain oxygen-utilizing prokaryotes, which migrated into the bodies of proto-eukaryotes. In this symbiotic relationship, the proto-eukaryotes provided prokaryotes a safe environment. The prokaryotes, in turn, saved protokaryotes from oxygen toxicity. This theory was validated by subsequent studies.

In the mid-sixties, Bjorksten and Harmon put forth their theories of protein cross-linking and free radical injury, respectively, as the basic mechanisms of the aging process. Evidently, protein cross-linking and free radical injury result from oxidative molecular injury. Spontaneity of oxidation in human tissues, and oxidative molecular injury, which follows as its natural consequence, may be regarded as the true nature of the aging process in man. Tissue capacity for antioxidant generation, determined by certain genetic and acquired factors, provides the essential molecular counterbalance to spontaneous oxidation. The evidence for this viewpoint is drawn from a large body of clinical and experiemental data.

What are the clinical implications of this viewpoint of aging in man? Oxygen is a molecular Dr. Jeckyll and Mr. Hyde. Life-sustaining aspects of oxygen are well understood in clinical medicine. Life-terminating capability of oxygen is generally ignored. Man today faces extinction by accelerated oxidative molecular damage much like protoeukaryotes did during an earlier era. This accelerated oxidative stress is caused by the impact upon his genetic make-up of an enormous overload of aging-oxidant molecules on his internal and external environmnet. What are the best strategies for health promotion and reversal of chronic immunologic and degenerative disorders? These are the strategies that address all aspects of accelerated oxidative molecular stresses with clinical management protocols of nutritional medicine, environmental medicine, medicine of self-regulation and medicine of fitness. Integrated applications of these management protocols is the clinical practice of molecular medicine.


ANutritional Upregulation of Liver Detoxifying Enzymes@

Jeffrey Bland, PhD

HealthComm, Inc.

Gig Harbor, WA

Inactivity of the liver mixed-function oxidase enzyme system and conjugase enzyme system results in reduced capacity to detoxify endo- and exotoxins. Cytochrome P450-MFO is upregulated by exposure to xenobiotics, endogenous sterols, endotoxins, alcohol, or phenol compounds. This upregulation depends upon hepatic activation of ribosomal function by specific nutrients. Research with patients suffering from chronic fatigue-immune deficiency syndrome (CFIDS) reveals suppressed MFO and conjugase activity. Baseline MFO activity and glycine conjugation is determined by measuring salivary caffeine clearance and urinary hippuric acid excretion. A nutritional approach that supports upregulation and ribosomal synthesis of cytochrome P450 and conjugase enzymes, and provides precursors for activation of mercapturic, hippurate, and glucuronic acid pathways supports increased clearance of endo- and exotoxins in these patients.

Thirty-five CFIDS patients who demonstrated reduced salivary caffeine clearance and urinary hippuric acid output after oral benzoate challenge participated in an intervention trial to evaluate a nutritional approach for upregulating hepatic detoxification. Symptoms in the treatment group significantly declined after intervention, while those of the control group did not. The study demonstrates that nutritional upregulation of hepatic detoxication can occur in chemically distressed patients and a unique nutritional intervention program can provide significant improvement in symptoms and function of affected patients.


AMental Status, Intellectual, and Mood States Associated with Environmental Illness@

Joel R. Butler, PhD, Retired Professor, and Cynthia E. Riecken, M.S., Graduate Student

University of North Texas

Denton, TX

The purpose of the study to be presented was to begin development of a psychological profile for environmental illness patients. Test scores were drawn from a pool of 89 patients diagnosed with environmental illness by physicians who specialize in Clinical Ecology. The patients were administered a Mental Status Exam, portions of the Wechsler Adult Intelligence Scale-Revised, and the Profile of Mood States by psychologists or graduate students trained in test administration.

The results of the study indicate a primary pattern in environmental illness patients consisting of fatigue and reduced mental functioning. There was also a lack of psychotic or personality disorder indicators. The psychological tests objectively verified the subjectively reported psychological symptoms of environmental illness patients.


AAnger and Emotion: Immunological and Endocrine Correlates@

Joel R. Butler, PhD, Retired Professor

University of North Texas

Denton, TX

Susan F. Franks, MS

Medical University of South Carolina

Charleston, South Carolina

Immunological and endocrinological correlates of various anger conditions were investigated. Serum cortisol, peroxidase activity of white blood cells, percentages of total T-lymphocytes and their subtypes, suppressor-T cells and helper T-cells, as well as the ratio of helper-T to suppressor-T cells were measured. Significant differences were found between males and females in two anger scales, Anger Control and Anger Expression. Results strongly indicate that men and women differ in biopsychological responses to anger. In the female group, significant correlations were found between various anger scales and total-T cells, suppresor-T cells, and helper-T cells. In the male group, significant correlations were found between various anger scales and myeloperoxidase activity of white blood cells. Serum cortisol levels were not significantly elevated in relation to anger for males or females. The influence of ecological conditions in terms of psychoimmunological disruption will be discussed.


AMemory Patterns among Environmental Patients@

Esther O. Lockhart, MA, Doctoral Student, and Joel R. Butler, PhD, Retired Professor

University of North Texas

Denton, TX

Clinical observations indicate memory deficits among EI patients. The kind of deficits and their extent have not been sufficiently delineated. The purpose of this study is to verify objectively the memory dysfunction among these patients. Results validate the existence of such deficits and find them common in EI patients. Long-term memory remains generally intact. While there was some inconsistency in measurements between certain of the standardized tests (Wechsler Memory Scale-R, WAIS-R, and Harrell-Butler CNS), certain areas of memory dysfunction were found among EI patients and could be reliably measured. Primarily there were problems in such areas of memory as short-term, logical sequencing involving memory and performance, vision, and attention and concentration.


ANutritional Tools for the Retardation of Neurological and Endocrinological Aging@

Jean-Paul Curtay, MD

Journees de Medicine Nutritionnelle

Paris, France

Aging is associated with a functional decline of sensory systems, memory, problem-solving capacity, with increased latency to visual and somatic stimuli, with a loss of neurons, a decrease in neuronal plasticity and in some neurotransmitter levels, receptor number and affinity and with alterations of membrane fluidity and deposition of abnormal proteins in the neurons and the glial cells.

Many of these degenerative changes appear to be linked to endogenous and exogenous stressors like oxygen free radicals, xenobiotics, or environmental toxic agents. For example, a high level of noise contributes to hearing loss and an acute stress episode to loss of memory.

I will describe how nutritional tools can stimulate protective mechanisms against neurological and endocrinological degenerative processes.


AThe Male Climateric, Prime Cause of Sex Involution@

Georges Debled, MD

Clinique de la Muette

Paris, France

It is well known that the secretion of the testicles arises at the top around twent-five to thirty years and decreases progressively after this age. The secretion of male hormones falls sometimes dramatically in a few months at any age. After forty, every man will be concerned, some time or other, by the male climateric. Below a critical amount of daily hormonal production, all sexual functions are declining.

The libido becomes lukewarm and the frequency of sexual intercourse decreases. Lack of testosterone induces impotency, slerosis of the corpus cavernosum, and disturbances of ejaculation and micturition. Those conditions are the sexual expressions of the male climateric.

The diagnosis is easily made by hormonal blood tests. In the majority of the cases, hormonal treatment with male hormones is sufficient to recover all sexual functions. The treatment must be continued forever.


AThe Male Climateric, Prime Cause of Aging@

Georges Debled, MD

Clinique de la Muette

Paris, France

Testosterone is first the hormone of the proteins. It is also a leading hormone for the regulation of sugar metabolism. Through this pathway it influences the fat metabolism.

The main phenomenon of the male climacteric is a lack of male hormone, and the Asexual concept@ is too restrictive because, in fact, when testosterone is missing, all the structures of the body are involved progressively through different biochemical and physiopathological mechanisms.

Lack of testosterone induces and worsens high blood levels of sugar, cholesterol, and triglycerides; overweight; deformation of the silhouette; muscle weakness; stiffness of the movements, arthrosis and osteoporosis.

A decrease in the daily production of testosterone induces and worsens essential hypertension; arteriosclerosis and atherosclerosis; angina pectoris and myocardial infarct; and vaicosities and hemorrhoids.

Prostatic diseases such as bladder neck fibrosis and benigh hyperplasia of the prostatic glands are the consequences of hormonal disorders.

Without testosterone, the skin loses its elasticity; vision and audition can be perturbed.

The lack of male hormones is an important unsuspected etiology for nervous depression. The male climacteric is the whole of the physiopathological and psychopathological phenomenons going with the natural cessation of the male activity. Testosterone is the key treatment for all those diseases. Its use constitutes a real middle of prevention of sex involution and Aaging.@

Our experience started 18 years ago. More than 1500 patients were treated without interruption with highly impressive results and without any complication or danger.


AThe Interaction between Chemical Exposure and Classical Allergy@

Rondal Finn, MD

Royal Liverpool University Hospital

Liverpool, England

Environmental sensitivity can be due to two mechanisms (a) classical allergy, which is immunologically mediated, usually through IgE, and (b) chemical sensitivity, which is nonimmunologically mediated as in lactase deficiency causing intolerance to milk. The second group is also known as Clinical Ecology or Environmental Medicine. Although usually thought of as distinct, the two systems do interact.

The classical allergic disease, Hay Fever, is usually thought of as being due to exposure to pollen in a subject with an inherited allergic tendency. Hay Fever is, however, more common in towns than in the country and first appeared in the 19th century coincident with the start of the Industrial Revolution. This suggests that toxic damage to the nasal mucosa is necessary to initiate the allergic process. Thus, chemical sensitivity plays a major role in this classical allergic disease. Similarly, asthma is becoming more common in industrialized societies, and this is probably due to the effects of industrial pollution on the bronchial mucosa. IgE tends to be slightly higher in smokers, and this could be due to damage to the mucosal surfaces allowing more ready access to antigens. Glomerulonephritis is more common in male industrial workers, and accumulating epidemiological data suggests that this is due to heavy exposure to solvents, which damage the kidney and predispose individuals to a secondary immunolgical reaction.

Taken together, these examples suggest that many classical allergic or immunological diseases are dependent on chemically induced surface mucosal damage, which facilitates the entry of antigen and then causes an immunological reaction in genetically predisposed individuals. These observations suggest a mechanism for the increase in allergic disease in modern industrialized societies.


AImmune Deficiency in Old AgeCIntrinsic Aging or Environmental Exposure?@

Roy A. Fox, MD

Dalhousie University

Halifax, Nova Scotia, Canada

Waning immunity has long been recognized as a concomitant of normative aging. The main features include impairment of cell-mediated immunity (skin anergy, delayed graft rejection, and impaired in vitro lymphocyte transformation); impaired humoral immunity (reduced antibody response to those antigens requiring T helper cell support); a plyclonal increase in immunoglobulins and increased autoantibody production (secondary to impaired suppressor cell functions). Although impaired immunity is aggravated by nutritional deficiency and may also occur secondary to a variety of disease states that are increasingly common in old age, much of the deterioration is thought to be a primary aging effect. It has been postulated that the primary change is thymic involution. An alternative hypothesis is that the immune deficiency of aging is a secondary aging effect and occurs as a result of adverse environmental influences. It is postulated that a variety of age-related changes result in bacterial colonization and production of various mediators such as endotoxin. Endotoxin functions as a polyclonal activator inducing the various immunological change as described. Finding spontaneous lymphocyte transformation and circulating endotoxin in otherwise healthy elderly individuals supports this hypothesis. Endotoxin, postulated to be produced from abnormal bacterial colonization, is probably only one such polyclonal activator. It is well recognized that noxious environmental incitants can also result in a variety of nutritional deficiencies. It is suggested that the immune changes of aging and the devleopment of frailty be looked at more closely from an environmental perspective.


AThe Thyroid and Aging@

Eduardo Gaitan, MD

University of Mississippi School of Medicine and VA Medical Center

Jackson, MI

Histologic, anatomical, and functional changes occur in the thyroid gland with aging. Host (e.g., sex, ethnic, and immunogenetics) and environmental factors, particularly the amount of iodine intake and/or exposure, as well as possible interactions with antithyroid pollutant (e.g., PBBs, PAHs, coal-derived organics, etc.), are important determinants of these thyroid changes and associated disorders. Increases in thyroid weight and nodularity with progressive fibrosis and various degrees of lymphocytic infiltration are commonly observed. Thyroid dysfunction occurs in great frequency among populations over the age of 60. Thyroid deficiency with elevated serum thyrotropin (TSH) levels and normal free-thyroxine (FT4) estimates (subclinical hypothyroidism) is seen in 6-15%, and with low FT4 estimates (clinical hypothyroidism) in 2-4% of this elderly group. Hypothyroidism is more frequent in females than males (4:1) with autoimmune thyroiditis being the cause in two-thirds of the scases. Thyroidectomy or radioactive iodine (RAI) treatment, mainly for Graves= disease, and the use of iodine-rich or antithyroid medications account for the rest. Hyperthyroidism occurs in 0.5-2.5% of the elderly population, toxic nodular goiter being responsible in 70% of the cases. The morbidity and mortality of these conditions is high if left unattended, resulting in major public health and socioeconomic problems. On the contrary, early diagnosis using highly sensitive and specific tests available at present, followed by adequate and cautious treatment, will result in dramatic improvement in the quality of life of elderly patients.


AOn the Biology of DeathCSome Insights and Controversies@

Valerius Geist, PhD

The University of Calgary

Calgary, Alberta, Canada

Longevity within a species is closely tied to reproduction and inversely proportional to it. Early and/or heavy reproduction in mammals results in early senility and death, with few exceptions. Is senility a factor under Darwinian selection? Are there mechanisms that terminate individuals after a certain level of reproduction, even though they are physically capable of a great life span? Are there Aterminators@ within us, and how could they be subject to natural selection? This is an area of controversy within evolutionary biology. The constellation of factors favoring Aterminators@ would be a closed system of energy and nutrients, so that one individual=s loss would be another=s gain. Secondly, costs of repair and recovery from episodes of reproduction must be more costly that the original synthesis of said tissues. That is, it must be cheaper to produce new bodies than repair old ones. Offspring and parents must share resources in the zero sum game. Then it becomes adaptive for the parental genotype to terminate the parental phenotype when reproduction by offspring results in more phenotypes than reproduction by parents. Evidence is presented to support this hypothesis.


ALaboratory Evaluation of the Phagocytic Function of Environmentally Sensitive Individuals@

Bertie Griffiths, PhD

Environmental Health Center-Dallas

Dallas, TX

The phagocytic killing cascades of 70 environmentally sensitive patients with recurrent infections were investigated. These patients presented multiple manifestations to chemicals, food, inhalants, and recurrent infections. Of these, 88% were found with dysfunctions. Treatment, especially with transfer factor and autogenous vaccines, showed significant improvement in total T cells and phagocytic killing.


AContribution of Adrenal Androgen Deficiency to Aging: Adequate Treatment Is Often Gratifying@

Jacques Hertoghe, MD, and Thierry Hertoghe, MD

Antwerp Medical Center

Antwerp, Belgium


As years pass, the burden of numerous aggressors, external and internal, might disrupt several off the body=s essential organs, as the hormonal glnads, in their functional and morphologic integrity. In its turn, hormonal weakness will promote further aggravation of the cell=s overall condition. New and deleterious molecules might appear and act, contributing to the spiral of aging events, leading ultimately to death.

Could this type of degrading events happen in the adrenal cortex in the cells producing, in man and woman, the adrenal androgens?

We think this could explain the mental and physical hypotonicity of some aged patients. In these patients, blood and 24 hr urinary testing reveal definite low levels, sometimes collapsed levels of DHEA and their sulfate form.

By treating with replacement doses of this hormone, not rarely remarkable improvement has been obtainedCmore mental alertness and more physical energy and resistance.

In medical practice, DHEA screening in blood and urine should now be performed more often as it could lead to the use of another precious weapon in the battle against aging decline.


APituitary, Aging, and Environment@

Thierry Hertoghe, MD, and Thierry Hertoghe, MD

Antwerp Medical Center

Antwerp, Belgium

As any other body cells, pituitary cells might be altered by external and internal aggressors. This cold lead to far-reaching consequences as this multihormonal gland isCby excellenceCthe stimulatory endocrine gland for at least growth, thyroid, adrenal, and gonadal activity. The most recent knowledge about the influence of advancing age on the pituitary gland points to the decaying of this gland:

1. A decrease in growth hormone release, basal and stimulatory (included by GHRH). This decline would greatly contribute to overall aging.

2. A slight increase in plasma TSH as a result of age-related thyroid decline, no change in nycthemeral TSH rhythm, unaltered basal TSH release, decreased TSH release to varioius stimulations (included to TRH in elderly men).

3. Seemingly unaltered plasma ACTH levels and ACTH pulses, but a decreased response to CRF.

4. Increases in plasma FSH and LH, impressive in woman (followed in the latter stages of the post-menopause by a subsequent decline); reduced frequency of large amplitude LH pulses, a marked decreased response to various stimuli (included by LHRH).

5. A decrease in plasma prolactine (PRL) in post-menopausal women, apparently unaltered levels in men, a decrease in PRL release to surgical stress and hypothalamic TRH stimulation.

6. A decrease in plasma vasopressine (VP) and in basal and stimulatory release.

7. Apparently unaltered plasma oxytocin, unaltered or much less decreased release in basal and stimulatory conditions.

In autopsies of elderly humans, pituitaries have often been found showing diffuse fibrosis. Studies point also to decreased responsiveness of target glands and organs to pituitary hormones. All by all, with age, a certain degree of hypopituitarism develops. Attention should be paid to this clinical diagnosis. Treatment by means of adequate replacement therapy might help to put a brake on the overall aging decline. Although success will be limited by the aging accelerating effects of environmental or other aggressors as chemical toxics, infectious agents, chronic stress, and so on.


AThe Perimenopause: Successful Treatment@

Thierry Hertoghe, MD

Antwerp Medical Center

Antwerp, Belgium

The author insists on the importance of precocious treatment of the perimenopause and related hypoovarian states, years before the actual menopause occurs, as precocious gonadal aging and it corresponding troublesome symptoms start in the perimenopause. In this lecture successful treatment of perimenopausal states with natural hormonal replacement therapy is exposed. A quick overview is given on the various side effects of synthetic non-natural hormones, which can greatly be avoided with the proper use of natural hormones. Three types of treatment are discussed:

Treatment of uncomplicated menopause generally consists, following the author, of the combination of three hormones: estradiol, progesterone (even when a hysterectomy has been accomplished), and an androgen. Adjusting these treatments is more complicated and time-consuming than giving combined estroprogestative pills, but results are not only physiologically but also psychologically more satisfying. Fundamental is to obtain a correct balance between estradiol and progesterone. Diagnosing these different perimenopausal states needs investigation by blood samples taken on specific days of the cycle, but emphasis is put on the symptoms of each hormonal deficiency., which enables the physician to make the best diagnosis and obtain the most adequate hormonal balance in the treatment. Treatment of the perimenopause may well prevent unnecessarily precocious aging, with a corresponding improvement in quality of life, and, possibly, an extension of life span. This lecture is documented with multiple experimental and clinical data.


AThe Perimenopause: The Effect of Toxins on Ovarian Function@

Thierry Hertoghe, MD

Antwerp Medical Center

Antwerp, Belgium

The perimenopause is the transitional period in a woman=s genital life, when the exocrine function (ovulation) of her ovaries progressively diminishes and her endocrine function (secretion of hormones) shows a lack of balance with abnormal menstrual cycles.

This period concerns the woman of 40 to 50 years. The perimenopause is a good example of a weakened ovarian state, subjectively and objectively experienced as a precocious aging process. Acceleration of this process can arise by multiple factors.

The adverse effects of under-nutrition and malnutrition (excessive fiber intake, . . . ), chronic stress, tubal sterilization, hysterectomy and radiation therapy are here briefly investigated. Special focus is placed on the detrimental effects of toxins on ovarian function: tobacco smoking (benzopyrene, nitrous oxide, nicotine), alcohol, caffeine, the contraceptive pill, long-term testosterone administration in female athletes, PCP, lindane, DDT, methoxychlor, various medications (indomethacin, antifungal agents, phenytoin, . . . ), marihuana (THT), cocaine, food contaminants (mycotoxins, phytoestrogens, monodosium glutamate, . . .), toluene, polychlorinated biphenils, phtalates, TCDD, antineoplastic agents (cyclophosphamide, busulfan), and many others.

As several of these toxins may simultaneously be present in a woman suffering from problematic ovarian functioning and that a synergistic effect between the toxins may be present, advice about avoiding these toxins, should often be the first step in the treatment of the perimenopause and related ovarian states. Human and animal studies on the subject are being reviewed.


AInfluence of Pesticides on Visuo-Motor FunctionCPossible Acceleration of Aging@

Satoshi Ishikawa, MD, Tatsuto Namba, MD, Hiroyuki Nishimoto, MD, Akira Fujita, MD

Kanagawa, Japan

Farmers exposed to organophosphorus pesticides (OP) for over 10 years and children with environmental exposure to OP for over 3 years manifested balance disturbance and pupillary abnormality.

Body balance and pupils were quantitatively measured and compared with age-matched normal subjects.

In this presentation we will first introduce a typical patient with chronic OP intoxication. Abnormal findings obtained from above examinations will be shown, and the results of treatment by Prifinium bromide (Padrin7, Scopolamine-like drug) will be presented. When body balance and pupil involvement were quantitatively compared with the normal subjects with age-matched, impairments of visuo-motor functions were significantly advanced and suggest a possible acceleration in the aging process.


Armstrong, et al., eds. 1991. The effects of aging and environment on vision, 209-217. New York: Plenum Press.


AThe Role of Functional Brain Imaging in the Chemically Exposed Individual@

Alfred R. Johnson, DO

Environmental Health Center-Dallas

Dallas, TX

Theodore R. Simon, MD, and David C. Hickey, MD

Medical City

Dallas, TX

Cases of chemically hypersensitive individuals resulting from a specific chemical exposure will be presented. Testing procedures, including blood analysis, cognitive function, neurological function, and chemical booth challenges will be discussed. These results will be correlated with functional brai imaging (SPECT scanning).


AIndoor Air Quality Evaluation@

RCI Environmental Inc.

Dallas, TX

Modern building techniques have created homes and office buildings that are much more energy efficient than they were only a few years ago, which has created a situation called the ATight Building Syndrome.@ Buildings which are better insulated and sealed Abreathe@ less, allowing less fresh air to enter the structure. In fact, air quality evaluations show interior air is commonly 400 times more polluted than outdoor air.

These pollutants are produced from many common sources, such as carpet, paint, furniture, molds and naturally occurring gases, and they produce a variety of health effects, from allergenic reactions and weakened immune systems to lung complications and possibly even cancer. Because interior air pollutants can cause serious health effects, they are not only a health hazard but also a source of liability for an employer.

Even the best ventilation systems do not solve the problem because indoor air pollution is produced in the same area people live or work within, and some systems can actually worsen the problem by spreading the pollution. The solution is to identify harmful contaminants and confront them at their source.

An air quality evaluation can be used either to investigate and identify pollutants that are causing health problems or as a precautionary measure to discover pollutants which might lead to detrimental health effects. Either way, an air quality evaluation provides peace of mind and leads to a home or office that is free of environmental health hazards.

An RCI Indoor air quality evaluation includes identification and assessmen tof potential environmental health hazards. Because client needs and site characteristics vary, different situations require different approaches. Therefore, the scope of each RCI investigation may differ. A typical investigation would consist of the following procedures:

A. Home or Workplace Evaluation

B. Collection of Airborne Samples

Samples will be collected and analyzed for the following airborne pollutants as needed:

Biological Contamination

Airborne Pesticides (water-soluble)

Airborne Particles

Volatile Organic Chemicals (VOCs)

Naturally Occurring Gases

C. Report and Evaluation

Results obtained by RCI technicians or from independent and accredited laboratories, when such services are necessary , are consolidated into a report which contains sampling results, photographs of the site, mitigation suggestions, observations, and recommendations. Follow-up sample collection, such as an extended radon gas study or collection of solid material samples to identify sources of contamination, is also available.


AIs the Pineal Indole Melatonin an Ecological Hormone in Man?@

Georges J.M. Maestroni, PhD

Instituto Cantonale di Patologia

Locarno, Switzerland

In contrast to seasonally breeding animals, the role of melatonin in man is still obscure. However, in both animals and men, nature has devised a variety of mechanisms to safeguard its circadian synthesis and release. Apart from a series of findings that suggest but do not prove a melatonin involvement in human reproduction, other mechanisms such as activity-rest rhythm, sleep, lipid metabolism, or conditions such as eating affective disorders, immunodeficiency and tumor growth, have been related to melatonin and/or the pineal gland. In particular, conditions associated with a decreased ability to cope with environmental demands have been associated with a decreased production of nocturnal melatonin. Melatonin administered to humans can, in fact, alleviate jet lag and delayed sleep phase syndrome, decrease LDL-cholesterol, increase NK activity and secretory IgA production, and inhibit tumor growth. The general feature of these actions seems to be an improvment of the organism=s response to environmental challenges. In jet lag and delayed sleep phase syndromes, the environmental dependency is obvious. In addition, cholesterol levels are based on both genetic and dietary factors. NK cells, and IgA antibodies are the most powerful natural immune effectors against environmental threats, such as microbial pathogens, and finally, 70 to 80% of all malignancies are of environmental origin. In regard to immunological effectors, our experimental studies showed that melatonin can abolish completely the immunodepressive effect of environmental stress. In addition, it should be remembered that in animals melatonin proved to inhibit both chemical-induced carcinogenesis and tumor growth. The reproductive effects, if any, of melatonin in the human may thus be secondary to a more important role of adjusting the physiological ability of the oragnism to cope with environmental challenges. In this sense, melatonin may be considered an ecological hormone.


ACoping with Environmental Stres: A Role for Melatonin and Immuno-Derived Opioid Peptides@

George J.M. Maestroni, PhD

Instituto Cantonale di Patologia

Locarno, Switzerland

In previous studies we showed that the pineal neurohormone, melatonin, can counteract the depression of antibody response, thymus cellularity, and anti-viral resistance induced by acute stress or pharmacological treatment with corticosteroids or citostatic drugs. More recently, we have shown that these interesting anti-stress effects of melatonin are mediated by endogenous opioids. In particular, at physiological concentrations melatonin stimulates murine and human activated T-helper cells to release opioid agonists that, in turn, mediate the anti-stress effects. These melatonin-induced and lymphocyte-derived opioids were shown to compete specifically with 3H-naloxone for specific binding to opioid receptors. The anti-stress effects of these peptides were abolished either by anti-b-endorphin (a-END) or by anti-met-enkephalin (a-MET) but not by anti-dynorphin and anti-leu-enkephalin antisera. In addition, these two types of immuno-reactive opioids, i.e., those cross-reacting with a-END or with a-MET showed a target specificity because when administered in stressed or corticosteroids treated mice, a-END blocked the post-stress thymus recovery while a-MET inhibited the antibody response. Consonant with these findings, we also showed the presence of specific opioid binding sites in the thymus. Finally, the observation that these anti-opioid, anti-sera lose their activity when injected in stressed and unprimed mice or in mice in which the synthesis of endogenous melatonin was inhibited by surgical pinealectomy reinforced the evidence for the existence of a novel immuno-neuroendocrine network linking the pineal gland and the immune system via immuno-derived opioid peptides. The physiopathologic relevance of these mechanisms should be considered and studied in all stress- and immune-based diseases and in all situations associated with poor adaptation to environmental demands such as immunodeficiencies and aging.


AInfluence of Energy Intake on Aging and Related Processes@

Edward J. Masoro, PhD

University of Texas Health Science Center at San Antonio

San Antonio, TX

Restricting the food intake of rats to 60% of the intake of ad libitum fed animals retards the aging processes as well as many age-related phenomena. That the aging processes are retarded is based on the following evidence: life expectancy is increased; maximum life span is increased; the mortality rate doubling time is increased; a spectrum of physiological processes is maintained in a youthful state and age-associated diseases ranging from nephropathy and cardiomyopathy to a spectrum of neoplastic diseases are either eliminated or delayed to more advanced ages. This anti-aging action is primarily, if not solely, due to restriction of energy intake rather than a reduced intake of a particular nutrient or toxic dietary contaminant. However, it is not the result of a reduction in metabolic rate. Rather, it appears to be due to the way these altered characteristics use fuel. For example, a high rate of glucose used as fuel occurs in dietary restricted rats at lower plasma glucose and insulin levels than required for ad libitum fed rats. Also, the same rate of oxygen utilization causes less damage in dietary restricted rats than in ad libitum fed rats. The nervous and endocrine systems appear to be involved in the coupling of the reduced energy intake to thes ant-iaging actions. However, it is also possible that dietary restriction has ins anti-aging actions not be retarding one or more primary aging process(es) but by having a general protective action. In this regard, dietary restricted rats have through the life span daily periods of elevated plasma corticosterone levels compared to ad libitum fed rats. Glucocorticoids are a double-edged sword with appropriate levels being protective in regard to meeting challenges and excessive levels being damaging. Dietary restriction may act by providing a life span of appropriately protective levels. Clearly, progress has been made in understanding mechanisms underlying the action of dietary restriction.


AEffect of Electromagnetic Wave on Corneal EpitheliumCClinical and Experimental Study@

Mikio Miyata, MD, Hirohiko Higuchi, MD, and Satoshi Ishikawa, MD

Kitasato University School of Medicine

Kanagawa, Japan

We have reported that magnetic wave from cathode ray tube (CRT) aggravates experimentally induced allergic conjunctivitis.

Our next concern is the actual damage of the cells besides the above functional change. Our previous study showed that the cornea of CRT workers frequently revealed superficial erosive change. This change was found even after continuous working of VDT for four hours. In order to elucidate its mechanism, animal experiments were conducted. BALB/C mice were exposed in front of CRT (30 cm) of television. Effect of heat, light, charged particles, and noise was excluded by other experiment. Epithelial injury of the cornea was confirmed by fluorescein positive staining 24 hrs after CRT exposure. Epithelial injury was located mainly at the most superficial layer of the corneal epithelium. The corneal epithelial defect was further examined with a scanning electron microscope. The impaired area increased in a dose-dependent manner with exposure to CRT. Defect increased in two hours of CRT exposure and attained its maximum by twelve hours exposure. The corneal epithelium has good repairing ability. Therefore, the defect may not leave permanent damage on the corneal epithelium in young animals. But organic derangement may be possible to be produced on the diseased cornea such as senile degenerated cornea and so forth.


AScreening for Environmental Illness in the Elderly@

Jean Monro, MD

Breakspear Hospital

Herfordshire, Eng.

A market research survey of 100 patients who have attended the Breakspear Hospital was conducted by an independent market research company, ISIS. This shows the efficacy of environmental medicine. A proportion of these patients are in the geriatric age group, and despite their conditions being denoted as due to their age, considerable improvement was demonstrated. The details of the research will be discussed.


ALong-term Follow-up of Ecologically Treated Patients and Motion Pictures of Rowe and Rinkel@

Theron G. Randolph, MD

North Aurora, IL

Of 20,000 chronically ill private patients manifesting physical and/or mental illnesses followed during the past forty years since the chemical susceptibility problem was described, 80-90% have improved by the time of their third office visit after their case had been summarized.

The main emphasis has been finding and avoiding demonstrated environmental incitants and perpetuants of chronic ilnesses, especially specific foods, environmental chemical exposures and such inhaled materials as dust, mites, danders, pollens and molds. There has been a minimal emphasis on drug therapy of the effects of illness. Food allergy tends to be labile in that the majority tend to tolerate specific foods on a rotary diversified diet after a few months of specific avoidance. Avoidance of incriminated environmental chemicals is far less effective in reducing the degree of individual susceptibility. Results of handling inhalant allergy by means of the Lee -Miller of Rinkel techniques are approximately the same as reported by others.


AEnvironmental Aspects of Aging, Part I@

William J. Rea, MD

Environmental Health Center-Dallas

Dallas, TX

Many studies have now shown the relationship of toxic chemicals creating imbalance in the endocrine system. The studies on the thyroid presented by Gaitan at the conference will emphasize this. In adition, Hinton=s studies at the Robens using PCBs and phthalates show that there is an induction of the cytochrome P-450 in the liver, which, in turn, removes thyroid hormone. This activates the thyroid, which keeps working harder to put out more hormone until it becomes depleted. The multiple endocrine syndrome has long been known to environmental physicians, and cases of parathyroid, thymus, adrenal, and ovarian dysfunction will be discussed. Chul, in animals,and the Environmental Health Center-Dallas, in humans, have shown an accumulated reaction of the chlorinated hydrocarbons and phthalates. It is clear that prevention can be carried out using the environmental principles of the total pollutant load.

AEnvironmental Aspects of Aging, Part II@

William J. Rea, MD

Environmental Health Center-Dallas

Dallas, TX

Many similarities are found to occur between pollutant injury in the chemically sensitive and the aging process. Free radical generation occurs with chemical injury in the chemically sensitive as well as during the aging process. Damage may occur to the mitochondria, nucleus, peroxsisomes, endoplasmic reticulum, and lysomes. Evidence is that the glutathione replenishing mechanisms are damaged in both. Gut flora and absorption are altered in both conditions. In animals under feeding prolongs life where it also improves the chemical sensitivity. Transport mechanisms may be altered in both, and other problems with metabolism may be altered like renal reabsorption, conjugation, and repair. There are many similar therapies that may be beneficial that have been devised for either. Certainly, research in one field may aid in understanding the other. Studies at the Environmental Helath Center-Dallas have suggested that there are nutrient pool changes in vitamins, minerals, and amino acids and both groups of patients. Immune deregulation may occur in both.


AAging, Melatonin, and the Pineal Gland@

William Regelson, MD

Virginia Commonwealth Uiversity

Richmond, VA

Walter Pierpaoli, MD

Institute for Biomedical Research

Quartino-Magadino, Switzerland

Melatonin, produced by the pineal gland in the center of the brain, governs avian and mammalian sexuality, nesting, fat deposition, and moulting. Melatonin modulates seasonal hormonal cyclicity largely affected by day length and/or temperature. Clinically, melatonin may govern the onset of sexual maturity; it declines with age and the presence of cnacer. Melatonin levels rise during the dark (scotophase) or our circadian cycle.

Melatonin in drinking water that was given to N2B mice beginning at 6 wks of age, during the 12-hr dark phase, enhanced longevity by 20%. Based on this, similar results occurred in older 19 mo C57bl mice. In view of the pineal source of melatonin and joint pineal innervation by the superior cervical ganglion, we transplanted young 6-8 wk pineal galnds into the thymus in 16, 20, and 23-month-old syngeneic mice with significant increase in survival. Of importance to aging, the atrophying thymus regenerated in the older pineal transplanted mice with improvement in immune response and thyroid function. Thyrotrophin Releasing Hormone (TRH) is also found in the pineal and may be important to the immune response.

Currently melatonin is under clinical study for seborrhea, jet lag, and as a birth control agent in women. Melatonin=s pineal source and other pineal-related peptides may provide us with a rational approach to aging as the pineal appears to act as a neuroendocrine, clock-governing, immunologic, and reproductive response, which are the key to aging and species involved.


ARational Approaches to Aging: Dehydroepindrosterone (DHEA), Cytoprotective Agents (PX), Pyridoxine, Magnesium, PQQ, Embryonic Transplants, RU4H6, Etc.@

William Regelson, MD

Virginia Commonwealth University

Medical College of Virginia

Richmond, VA

A steroid hormone, produced in the brain, skin, and adrenals, DHEA, is a biomarker for aging, declining with progressive age. DHEA and its metabolites up regulate immune resistance to viral and bacterial infection. DHEA has anti-stress activity, prevents diabetes in inbred mice, and lowers blood insulin in man. Declining DHEA levels relate to increased coronary disease in men. DHEA lowers blood cholesterol in dogs and is under study for this action clinically. DHEA has anticarcinogenic action and may enhance energy levels in fatigue syndromes. As an adreno-cortical and neurosteroid, DHEA can be likened to a mother (pluripotential) steroid who metabolites play a wide role in human physiology related to aging.

The essence of cell survival and aging depends on maintenance of the integrity of cell membranes. This is governed by phospholipid synthesis and breakdown. Similar to cobra venom, an enzyme, phospholipase A2 (PLA2 enzymes) found in our bodies, governs membrane integrity and free radical formation. Inhibition of PLA2 by orally active PX inhibitors results in anti-inflammatory action and prolongs survival in houseflies. This PX enzyme inhibitory action, which is also antioxidative, involves the preservation of membrane integrity which relates to cell repair and survival. PX compounds are being developed as oral anti-inflammatory drugs.

As a concept of aging one has to be concerned with decreasing gastrointestinal absorption or increased need for certain vitamins or nutrilites. Among which are pyridoxine (B6), magnesium, and the new anti-oxidant vitamin PQQ. The latter quinoline derivative is involved in a host of physiologic actions, inluding those involved in Parkinson=s disease.

Finally, we must distinguish between embryonic cells and adult and cancer cells as to the differences that govern the phenomenon of aging and that can justify the use of fetal transplants or tissue culture equivalents for enhanced survival.

RU4H6 (Mifepristone) the antiprogesterone arbortifaciant is also an anti-cortico steroid effective in Cushing=s Syndrome, a disease of excess cortisone production. RU4H6 reverses the hypertension, osteoporosis, diabetes, obesity, thinning of skin immunosuppression, muscle wasting, and depression associated with this disease. All these Cushing=s-related symptoms reflect on the process of aging which reversed by RU4H6. RU4H6 should be tested as an anti-aging drug. The rationale is based on >stress@ as a key factor in aging.


APineal Gland Function in Health and Disease@

Russel J. Reiter, MD

The University of Texas Health Science Center at San Antonio

San Antonio, TX

The numerous functions of the pineal gland are only now becoming apparent. The pineal, a pea-sized outgrowth of the dorsal diencephalon in the human brain, is an endocrine organ that secretes an impotant Atime-giving@ hormone, melatonin. The regulation of melatonin synthesis and secretion are closely linked to the prevailing photoperiodic environment. The pineal gland is an end organ of the visual system, and its ability to reproduce melatonin is inhibited by light. Thus, melatonin production and secretion occurs only during the night. Because of this, circulating melatonin levels are always 5-10-fold higher at night than they are during the day. This 24-hr (or circadian) rhythm in melatonin is perturbed under conditions where the light/dark cycle is either intentionally or inadvertently altered. For example, the acute exposure of humans to light at night causes a precipitous, intensity-dependent decline in circulating melatonin levels. Also, following transmeridian travel to a new time zone, the circadian melatonin rhythm must be phase-shifted to coincide with the new light/dark environment. Likewise, individuals who are exposed to light at night (e.g., shift workers) must readjust their melatonin rhythm in line with the new photoperiodic environment. The rapidity with which the melatonin rhythm is re-entrained depends on the number of time zones traversed, the age of the individuals, intensity of light to which the individual is exposed during re-entrainment, and other factors. The melatonin rhythm provides the body with a reference standard for time of day. Besides providing time of day information to all organs, the melatonin cycle also provides time of year data since day length (and night length) change as a function of season. Melatonin has a variety of effects, including stimulatory effects on the immune system, suppression of growth of certain types of tumors,and anti-aging properties, and melatonin levels may relate to normal pubertal development. The following conditions and/or disease states may relate to either an altered amplitude or phasing of the melatonin cycle: sudden infant death syndrome, seasonal affective disorder, schizophrenia, the feeling of Ajet lag,@ chronobiological dysfunction, sleep inefficiency, reproductive and endocrine malfunctions, and lethargy and fatigue.


AImprovement in Untreatable Cases with the Macrobiotic Diet, Nutrient and Hormone Corrections@

Sherry A. Rogers, MD

Northeast Center for Environmental Medicine

Syracuse, NY

The total load has always incorporated looking at least for food, chemical, and mold sensitivities as well as nutrient and hormonal deficiencies.

Some unusual and highly resistant cases, many of which had also been to ecologists, responded dramatically to the macrobiotic diet with nutrient and/or hormonal corrections. These include reversal of sarcoidosis, acute myelogenous leukemia, chronic fatigue of 12 years, pesticide poisonings, chemical sensitivities, chronic prostatitis, amblyopia, recurrent anaphylaxis, metastatic myeloma, and more.

This presentation stresses the importance of never losing sight of the total load regardless of the improvement that the tools we are accustomed to using daily can bring about. It also stresses that, regardless of how seemingly hopeless a condition may be, the final cure seems to be limited only by our imaginations.


ATransfer FactorCResearch Results and Implications for Aging Deceleration@

Gerald H. Ross, MD

Environmental Health Center-Dallas

Dallas, TX

Transfer Factor (TF) is a biologically active component of dialysates of leukocyte extracts, which has substantial immune-stimulating properties. Evidence suggests that it appears to be primarily produced in T-helper (CD4 cells).

This paper will give a review of the experience of the Environmental Health Center-Dallas with the use of TF in the treatment of patients with immune dysfunction/deregulation and chemical sensitivity. Data will be presented on treatment results focusing on improvement in cell-mediated, delayed hypersensitivity parameters, increase in the total numbers and subsets of lymphocytes, and improvement in clinical status of the patients.

Representative case histories will be presented as an illustration of the effects of TF treatment within the context of a comprehensive environmental approach.

Implications for treatment of the immunological involution seen with aging will be explored.


APesticides in the Florida Keys@

Douglas B. Seba, PhD

Environmental Medicine Consultant

Key West, FL

The politics and science of pesticides in the Florida Keys ecosystem is reviewed, both in microcosm and macrocosm. This tropical experience can be applied to numerous other locations and has global implications.

Even though over 95% of the land in the Florida Keys (Monroe County) is in park status (the highest ratio in the country), pesticides banned in the early 1970s are found in the water, sediments, natural sea slicks and even the corals in the reef, which have in their tissues the highest levels ever reported worldwide.

These continued chemical assaults represent yet another challenge to the endocrine system of all animals (including seafood eating mammals) in this maritime environment.


AUseful Longevity@

George E. Shambaugh, Jr., MD

Shambaugh Hearing & Allergy

Hinsdale, IL

With increasing average lifespan, there is increasing interest in geriatrics and in measures which can promote useful longevity rather than dependent old age. Several excellent books on nutrition and aging, and my own personal experiences, suggest that there are about a dozen factors that can be helpful in promoting useful longevity. These will be described with special attention to the trace mineral, zinc.


AIntroduction to SPECT Scanning@

Theodore R. Simon, MD, and David C. Hickey, MD

Nuclear Medicine Consultants of Texas

Dallas, TX

Discussion will involve development of SPECT Scanning and its current uses in evaluating a variety of patients including environmentally triggered disease processes.


AElectromagnetic Fields and the Endocrine System@

Cyril W. Smith, PhD

University of Salford

Salford, Eng.

The first report that weak artificial magnetic fields of the order of the Earth=s steady magnetic field could affect the electrical activity of pineal cells appeared in 1980. The pineal appears to be a particularly sensitive organ, affected by light and other electromagnetic fields, sound, temperature, and olfactory stimuli as well as steroids and noradrenaline. It is innervated by sympathetic nerve fibers. The sympatho-adrenal system is also sensitive to magnetic stimuli. The autonomic nervous system can be strongly affected by electromagnetic fields in certain persons.

The hippocampus, which has a definite electrical activity, has a neural connection to the hypothalamus; this, in turn, has a portal connection to the pituitary, and together they control both stimulatory and inhibitory hormone systems.

Most hormone systems are controlled by feedback. The nervous system complements the endocrine distribution system, acting through the circulation with high chemical specificity. The nervous and endocrine systems are not necessarily independent. Hormonal information can be transformed into neural information and neural spikes into chemical signals; hormones may modify the excitability of neurons and may be controlled by neural inputs to endocrine organs, giving superior regulatory performance.

ACalories, Cancer, and Aging@

Richard Weindruch, PhD

University of Wisconsin

Madison, WI

Caloric restriction (CR) without malnutrition lowers the incidence of most spontaneous and induced tumors, delays their onset, and extends maximum life span in mice and rats. These outcomes were discovered over 50 years ago and appear dependent on energy restriction, per se, and not on the specific restriction of fat or other nutrients. Although the vast majority of CR studies in rodents have examined severe CR (-40-50% of the ad lib intake level) started early in life (3-6 wks of age), milder CR regimens started in mid-adulthood can also oppose the development of spontaneous cancers and extend life span in rodents. The molecular events underlying CRs actions on cancer and aging are unclear but viable nonmutually-exclusive explanations include less cellular oxidative damage, retarded immune system aging, hormonal changes, less exposure to dietary carcinogens and promoters, less energy available for cellular proliferation (and tumor growth), less carcinogen activation, and enhanced DNA repair. Now ongoing are studies that attempt to determine whether or not CR can retard the rate of aging in nonhuman primates (monkeys). Although much less is known about the relationship between caloric intake and cancer incidence in humans, recent findings are consistent with an association for certain cancers.


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