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A V Everitt

Publications and source records attributed to A V Everitt.

At least 19 recordsLinked to original sources

Morphometric analysis of gastrocnemius muscle fiber size and fiber proportions in the hypophysectomized rat after prolonged administration of growth hormone or thyroxine.

This study investigated the effects of either growth hormone or thyroxine on muscle fiber atrophy caused by hypophysectomy in male Wistar rats. Muscle fiber size is reported as equivalent circle diameter (ECD) in transverse section of fresh-frozen gastrocnemius muscle. Three months post-hypophysectomy type 1 (slow twitch) and type 2 (fast twitch) muscle fibers were smaller (p < 0.01) than those in intact controls as shown previously in this laboratory. The administration of human growth hormone (GH) (50mIU/100g body weight/day) to hypophysectomized (hypox) rats for 42 days, stimulated body growth, restored 42% of the lost gastrocnemius muscle weight (p < 0.05) and 36% of the lost type 1 fiber size, (p < 0.01), but had no effect on type 2 fiber size. Treatment of hypox rats with physiological doses of thyroxine (5 micrograms T4/100g body weight/alternate day) for 42 days did not affect body growth, gastrocnemius muscle weight or type 1 fiber size, but reduced the size of type 2 fibers (p < 0.01). Thyroxine prevented the decline in the percentage of type 2 fibers which occurs after hypophysectomy. This unique observation suggests that thyroid hormone regulates the proportion of different fiber types in the gastrocnemius muscle. Thus, in hypox rats, GH promoted growth of type 1 or slow twitch muscle fibers needed to support the increasing weight of the growing body. Physiological doses of T4 did not stimulate growth, but caused further atrophy of of type 2 fibers possibly while providing fuel for rapid movement.

Animals

The effect of neonatal pinealectomy on the inhibitory actions of food restriction on vaginal opening and collagen aging in the rat.

Long-term food restriction is known to inhibit development and aging in the rat. These actions may be mediated by the pineal hormone, melatonin, whose secretion is increased by food restriction. This mechanism was investigated by studying the effects of pinealectomy in ad libitum fed and food restricted rats of both sexes living under normal conditions of temperature (23 degrees C) and lighting 12 h light:12 h dark cycle) over a period of 400 days. Pinealectomies were performed at the age of 5 days. Pinealectomy did not affect the amount of food eaten per day. Vaginal opening occurred at age 35 days in ad libitum fed female rats and was delayed to 49 days (P < 0.001) in rats whose food intake was restricted by 35%, but only to 41 days (P < 0.001) if food restricted (FR) rats were pinealectomized (Px). The inhibitory effect of food restriction on body growth and tail tendon collagen fibre aging was the same in both intact and pinealectomized rats. At the conclusion of the study in middle age at 400 days, plasma melatonin levels 4 h into the dark cycle were higher in food restricted than in ad libitum fed rats (P = 0.015). This study provides evidence for a role of the pineal in mediating the inhibitory action of food restriction on vaginal opening, but not on body growth or collagen aging in tail tendon up to middle age.

Aging

Morphometric analysis of the muscle fibres of the soleus muscle of the ageing rat: long-term effect of hypophysectomy and food restriction.

This communication reports on the effects of ageing, hypophysectomy and food restriction on the fibre sizes of the soleus muscle which is primarily concerned with posture. The results reported here are compared with those previously shown for the gastrocnemius muscle which is involved mainly with locomotion. Muscle fibre size (measured as equivalent circle diameter) in the soleus muscle of the male Wistar rat increased from youth at 130 days (type 1 fibres, 61.2 microns; type 2, 58.3 microns) to middle age at 600 days (type 1 fibres, 70.4 microns; type 2, 68.0 microns) and then underwent atrophy in old age to 1,000 days (type 1 fibres, 54.5 microns; type 2, 38.0 microns). There was no growth or atrophy of these fibres in either hypophysectomized or food-restricted rats. There was an increased range of fibre sizes in control rats between youth and old age being 5-fold for type 1 fibres and 3-fold for type 2 fibres, but there was a loss of type 2 fibres in hypophysectomized rats. This ageing process in the range of fibre size was retarded by hypophysectomy (2-fold increase for type 1 fibres) and to a lesser extent by food restriction (3-fold increase for type 1 fibres). Muscle fibre atrophy and compensatory hypertrophy were not as prominent in the hypophysectomized and food-restricted groups as in the old control groups. In general these effects were similar to those previously shown for the gastrocnemius muscle. However, atrophy of both type 1 and type 2 fibres in old age was more pronounced in the soleus muscle. The retarded ageing of the soleus muscle in hypophysectomized and food-restricted rats was probably due to the absence or reduced circulating levels of hormones known to target muscle cells, such as growth hormone and thyroxine.

Aging

Morphometrical analysis of the short-term effects of hypophysectomy and food restriction on skeletal muscle fibers in relation to growth and aging changes in the rat.

Muscle fiber growth is impaired by lack of hormonal influence. In the case of the gastrocnemius muscle of the male Wistar rat, ablation of the pituitary at age 60 days results in cessation of the growth of type 1 muscle fibers, and a reduction in the size of type 2 muscle fibers at 120 days of age, 60 days after hypophysectomy. The effects of food restriction, which are known to reduce pituitary hormone secretion, are not as great as hypophysectomy in inhibiting muscle fiber growth. Food restriction slowed the growth of type 1 muscle fibers (hypophysectomy abolished growth) and caused cessation of growth of type 2 muscle fibers (hypophysectomy caused atrophy).

Aging

The use of hypothermia in surgical pinealectomy of the neonate rat.

A technique is described in which rat pups (5-7 days old) are induced into a state of suspended animation by placing them in the freezing compartment of a refrigerator at -20 degrees C for 8-10 minutes. This induces cessation of respiration and heart beat for 12-15 minutes. Surgical pinealectomy is undertaken during this period. Postoperation the animal is gradually warmed and restored to its dam. The effectiveness of pinealectomy was checked after some 400 days by measurement of plasma dark cycle melatonin levels using radioimmune assay. The method is reliable, robust and the results predictable, no melatonin being detectable 400 days after surgery.

Animals

Morphometrical analysis of skeletal muscle fibre ageing and the effect of hypophysectomy and food restriction in the rat.

Morphometrical analyses were carried out on muscle fibres from cross-sectional areas of the medial head of gastrocnemius muscles from 5 groups each of 4 male Wistar rats representing young (aged approximately 100 days), medium-aged (400 days), old (1,000 days), old hypophysectomized (1,000 days) and old food-restricted (1,000 days) rats. Approximately 18,000 muscle fibres were measured in each group. Rats were hypophysectomized when young at 60-70 days and food restriction began at the same age. The results show that there is a reduction in type 2 fibre size (measured as the mean equivalent circle diameter) from 59.7 micron in medium-aged controls to 50.3 micron in old controls, but there is no significant difference between the sizes of type 2 fibres in controls, hypophysectomized or food-restricted rats in old age. Analysis of type 1 fibres demonstrated no differences between young, medium-aged and old controls and the old food-restricted group, but type 1 fibres in the old hypophysectomized group (45.5 micron) were significantly smaller than in the old controls (54.6 micron) and old food-restricted rats (58.5 micron). In old controls there is a 4-fold increase in the range of fibre sizes (coefficient of variation) for type 1 fibres and a 2-fold increase for type 2 fibres, indicating fibre atrophy and hypertrophy. Long-term hypophysectomy is more effective than food restriction in preserving the smaller range of the coefficient of variation of fibre size seen in young controls.

Aging

Inhibitory effect of hypophysectomy and food restriction on glomerular basement membrane thickening, proteinuria and renal enlargement in aging male Wistar rats.

Age-related thickening of the glomerular basement membrane (GBM) was studied in three groups of male Wistar rats: (a) ad libitum fed, (b) hypophysectomized and (c) food-restricted eating the same amount of food as hypophysectomized rats, but about 45% of the ad libitum fed group. Studies were begun at 50 days (2 months) and continued throughout life. Multiple regression was used to statistically assess the effects of age and treatments. In ad libitum fed male rats GBM thickness increased from 114 nm at 50 days (2 months) to 632 nm at 1,000 days (33 months). GBM thickness at 1,000 days was 296 nm in hypophysectomized rats and 392 nm in food restricted rats. Hypophysectomy had a significantly greater inhibitory action on GBM thickening than food restriction, in rats eating the same quantity of food per day. However, a major part of the effect of hypophysectomy may be due to the permanent fall in food intake (from 16.3 to 7.9 g/day) resulting from the operation. Accompanying the age-related thickening of the GBM in ad libitum fed rats were proteinuria and renal enlargement, both of which were inhibited by hypophysectomy and food restriction.

Aging

Exophthalmos in ageing rats with Harderian gland disease.

Exophthalmos was found in aged rats in several longevity studies. Four cases were due to malignant Harderian gland neoplasia whilst others were associated with severe Harderian gland inflammation, less severe inflammation being found in rats without exophthalmos.

Aging

Skeletal muscle aging in the hind limb of the old male Wistar rat: inhibitory effect of hypophysectomy and food restriction.

By age 1 100 days (37 mth) hind leg paralysis was found in 50% of ad libitum fed (control) male Wistar rats, but only 10% of food restricted rats and no hypophysectomized rats of that age had this disease. Gastrocnemius muscle weight declined at a faster rate than whole body weight in old ad libitum fed rats but not in old hypophysectomized or food restricted rats. Light microscopic and ultrastructural changes were studied in the muscles of the hind limbs of 11 control, 5 food-restricted and 5 hypophysectomized rats aged 805 to 1 307 days. Light microscopic changes in muscles involved progressive degeneration demonstrated by the accumulation of adipocytes and degenerative inclusion bodies. The main ultrastructural changes were associated with myofibrillar breakdown. In addition there was thickening of the basal lamina around blood capillaries. However, muscle from hypophysectomized and food restricted rats of the same age range as controls possessed normal morphology with reduced thickening of the capillary basal lamina.

Aging

Effects of isolation and food restriction begun at 50 days on the development of age-associated renal disease in the male Wistar rat.

The development of proteinuria with increasing age was studied in three groups of male Wistar rats: ad libitum fed and isolated, ad libitum fed and group housed 6 to 8 rats per cage, and food restricted (one-third of the isolated ad libitum food intake) and isolated. Studies were begun at age 50 days and continued throughout life. Ad libitum fed rats when isolated ate more food, grew faster, had larger maximum body weights and developed proteinuria at a faster rate than those that were group housed. There was a small increase in the severity of glomerular pathology in old age. However, systolic blood pressure was not affected significantly by isolation, nor was life duration. Food restriction of isolated rats inhibited body growth, prevented the development of proteinuria, reduced the incidence of glomerular and tubular pathology in old age and prolonged life. Electron microscopic examination of the kidneys of old food-restricted rats revealed a much lower incidence of foot process retraction and spreading on the basement membrane of the glomerulus than in ad libitum fed rats. Cardiac enlargement was also prevented by long-term food restriction.

Aging

Comparison of extracellular space in the mature and aging rat brain using a new technique.

A new technique for measuring extracellular space in the rat brain has been developed. It involves opening the blood-brain barrier with a bolus of hyperosmotic sucrose followed by a high-pressure perfusion of the cerebral vasculature with an isotonic solution containing an impermeant radioactive tracer, [3H]sucrose. After allowing the concentration of tracer in the brain to reach a plateau, the amount of radioactivity/mg of brain tissue is expressed as a percentage of the amount of radioactivity/mg of perfusate to obtain a value for extracellular space. The addition of glutaraldehyde to the perfusate results in the brain being fixed simultaneously for electron microscopy. Reproducible estimates of extracellular space were obtained similar to those obtained by other methods (e.g. Levin et al. 1970). As it is impossible to be sure of the validity of the absolute value of extracellular space obtained by any method using perfused solutions we have used our method for comparative purposes. Extracellular space was measured in mature (control) and ageing rats to test the claim that the volume of space in the cerebral cortex is substantially reduced with ageing (Bondareff and Narotsky 1972). We found a consistent tendency for the extracellular space to increase with age in the 6 regions of brain examined. This was not statistically significant except in the group of ageing rats on a food-restricted diet. Therefore, these results do not support a generalisation that the extracellular space decreases in the ageing brain. In both control and ageing rats, extracellular space was shown to be unevenly distributed in the brain, the largest space being present in the cerebellum, olfactory bulb, inferior and superior colliculi and the least space in the white matter. These are the first measurements of extracellular space in which assessment is possible by both electron microscopy and by the measurement of a chemical tracer.

Aging

The effect of restricted food intake and refeeding on the ovarian follicle population of the pre-puberal Wistar rat.

A 50 p. 100 restriction of food intake in female Wistar rats from day 21 to day 42 of life prevented ovulation and altered the size distribution and numbers of ovarian follicles. The rate of atresia of non-growing oocytes in primordial follicles was retarded resulting in more oocytes per ovary. The number of follicles initiated to grow was reduced. Semi-starved rats allowed free access to food from day 42 of life achieved the body weight of ad libitum-fed controls at 66 days of age. A delayed puberty occurred. The numbers of non-growing oocytes in primordial follicles per ovary declined but remained significantly greater than control values at 66 days of age. Refeeding increased the numbers of follicles undergoing growth but within the size distribution found in age-matched controls. Thus semi-starvation followed by refeeding rendered the ovary developmentally younger but only in terms of total oocyte numbers. The ovarian response to starvation and refeeding is discussed in relation to pituitary function and provides new information on the potential lability of the oocyte population.

Animals

Dietary, caging and temperature factors in the ageing of collagen fibres in rat tail tendon.

The effect of dietary fat, carbohydrate and protein on tail tendon collagen ageing was studied in male Wistar rats. When rats were fed low-calorie diets there was no evidence that the content of carbohydrate, fat or protein affected the ageing of collagen. However, on high-calorie diets there was evidence that high-fat diets (21%) either saturated or unsaturated aged collagen fibres at a faster than low-fat diets (7%). Isolated housing of rats, which is necessary to control food intake, was found to slow the rate of collagen ageing. This effect was associated with reduced tail tendon temperatures.

Aging

The effects of hypophysectomy and continuous food restriction, begun at ages 70 and 400 days, on collagen aging, proteinuria, incidence of pathology and longevity in the male rat.

Hypophysectomy in young male Wistar rats aged 70 days, followed by cortisone acetate replacement therapy throughout life, retarded the rate of aging of tail tendon collagen fibres, inhibited the development of certain diseases of old age (renal disease, cardiac enlargement, hind limb paralysis, and various endocrine and non-endocrine tumors) and significantly prolonged the duration of life. Almost identical anti-aging effects were obtained by lowering the food intake of intact rats to that of hypophysectomized rats, from age 70 days until death. Hypophysectomy in middle age, at 400 days, even with cortisone acetate replacement therapy, produced a sharp increase in the mortality rate; the surviving rats exhibited significantly reduced aging of collagen fibres and of the kidney as measured by protein excretion. Food restriction begun at 400 days also inhibited renal aging, but had no demonstrable effect on collagen aging during the first 100 days. These studies suggest that procedures such as hypophysectomy and food restriction do not switch off an aging mechanism in youth but probably exert a continuing inhibitory influence on certain aging processes throughout life.

Aging

The neuroendocrine system and aging.

The course of aging in most endocrine glands is moderately well documented in man, but is somewhat less understood in the rat. With increasing age in man there is a significant decline in the secretion of hormones by the thyroid, adrenal cortex, testis and ovary; pituitary growth hormone falls but gonadotrophins rise. In man decline in the secretion of testicular and ovarian steroids appears to be due to primary age changes in the gonads, whereas in the rat age changes in the central regulatory mechanisms appear to be responsible for gonadal aging. Such findings have led to the formulation of a number of neuroendocrine theories of aging, which explain peripheral aging on the basis of an aging clock in the brain, primary age changes in neurotransmitter metabolism, age changes in the hypothalamus, pituitary and thyroid, or in the regulatory actions of these glands.

Adrenal Cortex