Federation proceedings最新文献

The historic studies by Robinson and Astrand as well as more recent studies present a fairly uniform rate of decline in VO2max with age at 0.40-0.50 ml X kg-1 X min-1 X year-1 in men. In women the rate of decline appears to be less--approximately 0.20-0.35 ml X kg-1 X min-1 X year-1, at least in cross-sectional studies. Further, there is no clear distinction in the rate of change in VO2max when comparing active and inactive populations. Longitudinal studies varying from 2.5 to 21 to 56 years present a confounding picture. The rate of decline in VO2max varies from 0.04 to 1.43 ml X kg-1 X min-1 X year-1. There is some indication that active individuals decline at a slower rate than inactive persons but the results are not uniform. A possible explanation is that changes in VO2max over the entire age range may be curvilinear, with active individuals declining slowly as long as they maintain a regular exercise program, and sedentary individuals declining at a rapid rate during their 20's and 30's followed by a slower rate of decline of their VO2max as they age further.

Carotenoid pigments have been found to have a protective function against photosensitization in green plants. This protective ability has been exploited in the administration of high doses of beta-carotene to patients with erythropoietic protoporphyria to ameliorate the photosensitivity associated with this disease. The carotenoids seem to exert their light-protective function by quenching excited species such as singlet oxygen and free radicals.

Mast cells are regarded as potentially critical participants in a wide variety of important biological processes. Yet it has been difficult to ascertain the precise contribution of mast cells to many of these reactions. In part, this reflects recognition that different populations of mast cells may vary in phenotype and therefore may express different functions. Another problem has been the lack of suitable model systems for identifying and quantitating the mast cell's unique roles in biological processes in intact animals. This review will outline the development of promising new approaches for analyzing mouse mast cell differentiation and phenotypic heterogeneity and for studying the roles of mast cells in vivo.

The biologically most important flavins are riboflavin and its related nucleotides, all highly sensitive to light. It is because of its photoreactivity and its presence in almost all body fluids and tissues that riboflavin assumes importance in phototherapy of neonatal jaundice. The absorption maxima of both bilirubin and riboflavin in the body are nearly identical: 445-450 (447) nm. In consequence, blue visible light will cause photoisomerization of bilirubin accompanied by photodegradation of riboflavin. This results in diminished erythrocyte glutathione reductase, which indicates generalized tissue riboflavin deficiency and red cell lysis. Single- and double-strand breaks in intracellular DNA have occurred with phototherapy. This light exposure of neonates may result also in alterations of bilirubin-albumin binding in the presence of both riboflavin and theophylline (the latter frequently given to prevent neonatal apnea). Many newborns, especially if premature, have low stores of riboflavin at birth. The absorptive capacity of premature infants for enteral riboflavin is likewise reduced. Consequently, inherently low stores and low intake of riboflavin plus phototherapy for neonatal jaundice will cause a deficiency of riboflavin at a critical period for the newborn. Supplementation to those infants most likely to develop riboflavin deficiency is useful, but dosage, time, and mode of administration to infants undergoing phototherapy must be carefully adjusted to avoid unwanted side effects.

Porphyria cutanea tarda (PCT) is the most frequently reported type of porphyria. The average patient is male more than 40 years old with a history of alcohol consumption. In women the incidence of PCT has increased with use of estrogens for birth control. The cutaneous features are those of chronic porphyrin photosensitivity on the light-exposed area of the skin: pigmentation, hirsuitism and fragility, and vesiculobullae, which has prompted the expression bullosa actinica et mechanica. One-third of the patients have glucose intolerance. PCT has been reported frequently among the Bantu people in South Africa as resulting from combinations of alcohol and cooking in ironware. The average patient has a higher than normal hematocrit, which is used as a guide to treatment by phlebotomy ranging from 8 to 14 units removed every 2-4 wk. Chemically induced PCT has been reported with chlorinated hydrocarbons, the best-known of which is hexachlorobenzene (HCB). Porphyria was noted in more than 3,000 patients in southeast Turkey between 1955 and 1961, because of consumption of seed wheat treated with HCB. In addition, more than 1,000 children under the age of 1 year died because HCB was transferred from the mother, either via the placenta or through breast milk.

Evidence for a role of estrogen metabolism in hormonal carcinogenesis was obtained with the Syrian hamster as an in vivo model system. Both natural and synthetic estrogens are capable of inducing a high incidence of renal carcinomas in this species. A high incidence of hepatocellular carcinomas can also be induced in the hamster with synthetic estrogens such as ethinyl estradiol or diethylstilbestrol, provided alpha-naphthoflavone (ANF) is present in the diet. Although steroid receptor-mediated hormonal events appear to be intimately involved in the process of in vivo cell transformation of both tissues, certain observations strongly suggest that nonhormonal events are also important. Despite their potent estrogenic activity at the doses used, ethinyl estradiol and alpha-zearalanol induce relatively low renal tumor incidences after 9.0 and 10.0 months of continuous treatment, respectively. A role for the metabolism of estrogens to reactive intermediates is also suggested by studies showing estrogen-induced renal tumorigenesis can be partially inhibited by concomitant administration of ANF or ascorbic acid. Consistent with this is the general correlation between the amount of catechol estrogen formed by a compound, as mediated by estrogen 2-/4-hydroxylase, and renal carcinogenicity data. Recently, additional supporting evidence has been obtained from studies involving the irreversible binding of reactive metabolites of steroidal or stilbene estrogens to hamster liver microsomal proteins.

Maximal O2 uptake (VO2max) and left ventricular function decrease with age. Endurance exercise training of sufficient intensity, frequency, and duration increases VO2max in the elderly. The mechanisms underlying the increased VO2max in the elderly are enhanced O2 extraction of trained muscle during maximal exercise leading to a wider arteriovenous O2 difference, and higher cardiac output in the trained state. However, increased cardiac output during true maximal exercise has not been documented in elderly subjects. Endurance exercise training results in a lower heart rate and rate pressure product during submaximal exercise at a given intensity. However, no improvement in left ventricular function has been reported in the elderly after exercise training. Highly trained master athletes exhibit proportional increases in the left ventricular end-diastolic dimension and wall thickness suggestive of volume-overload hypertrophy compared with age-matched sedentary controls. The magnitude of left ventricular enlargement is similar to that in young athletes. The failure of exercise training to alter the age-related deterioration of left ventricular function in the elderly may reflect an insufficient training stimulus rather than the inability of the heart to adapt to training in elderly subjects.

It has been postulated that life span is inversely related to energy expenditure. If this is correct, regularly performed exercise could accelerate the aging process. In two early studies, exercise shortened the life span of rats; the results of these studies have been cited as evidence for the concept that an increase in energy expenditure accelerates aging. However, subsequent studies have not confirmed this finding. Instead, the weight of evidence now indicates that rats that exercise regularly have a longer average life span than sedentary, ad libitum-fed controls. Freely eating sedentary rats become obese, indicating that their food intake is in excess of their energy requirements. Available evidence seems compatible with the interpretation that exercise results in improved survival in rats by countering deleterious effects of a sedentary life combined with overeating.

The role of metabolism in the estrogenic activity of chlorinated hydrocarbon pesticides was examined. Whether the estrogenic activity in technical grade preparations of the pesticide methoxychlor is due to methoxychlor or to contaminants was also investigated. Identified compounds in technical methoxychlor were examined by an in vitro method to determine whether they are estrogens or proestrogens. This method showed that purified methoxychlor and MDDE, an olefinic derivative of methoxychlor, are proestrogens and that monohydroxymethoxychlor and monohydroxy-MDDE are estrogens. Thus, the estrogenic activity in technical methoxychlor is due to both methoxychlor and contaminants. MDDE is an in vivo metabolite of methoxychlor, and the mono- and bishydroxy derivatives of methoxychlor and MDDE are metabolites of methoxychlor and MDDE, respectively. These metabolites exhibited in vitro estrogenic activity in the following order of potency: bis-OH-MDDE greater than bis-OH-methoxychlor greater than mono-OH-MDDE greater than mono-OH-methoxychlor. A similar order of potency was observed in vivo, demonstrating that metabolites of methoxychlor are potent estrogens. In addition to phenolic products, hepatic monooxygenases metabolize methoxychlor and MDDE to reactive intermediates that bind covalently to microsomal proteins. Further studies are needed to determine the factors controlling the two pathways of methoxychlor metabolism and determine whether covalent binding is associated with cellular and organ toxicity.

Genetically mast cell-deficient W/Wv mice are useful for the analysis of mast cell biology, especially as recipients of bone marrow cells and skin pieces. Inasmuch as suspension and clonal cultures of mast cells have been developed, we combined these in vivo and in vitro systems. Suspension-cultured mast cells had morphological and biochemical characteristics similar to those of mucosal mast cells (MMC). However, i.p. injection of such cultured mast cells gave rise to development of cells with characteristics similar to those of connective tissue mast cells (CTMC). When peritoneal cells of normal +/+ mice were cultured in methylcellulose, pure mast cell colonies appeared. Cells from individual mast cell colonies were divided and injected into the skin and stomach wall of W/Wv mice; CTMC developed in the skin and MMC in the stomach mucosa. This indicates the presence of a common precursor for CTMC and MMC. Morphology of such bipotent mast cell precursors was studied by using micromanipulation. About 4% of morphologically identifiable peritoneal mast cells may function as the bipotent precursors. Although W/Wv mice showed a defect in resistance against ixodid ticks, injection of suspension-cultured mast cells normalized the defect. The four examples mentioned above indicate that combinations of in vivo and in vitro systems increase the usefulness of W/Wv mice.