Homeostatic Control Mechanisms Research Articles

Effect of Dietary Cadmium on Tissue Distribution of 109Cadmium Following a Single Oral Dose in Young Goats

Cadmium metabolism was investigated following a single oral dose of 109Cd in four- to six-month-old male goats fed a practical diet with and without 100ppm of supplemental cadmium as CdCl2. Tissue distribution of 109Cd and total body retention were determined 14 days after dosing. Highest concentrations were found in the kidneys, liver, duodenum, and abomasum, respectively. Total body retention was 0.3 to 0.4% of the dose with about one-half of this in the liver, one-fourth in the kidneys, and a large part of the remainder in the gastrointestinal tissue and contents. Bone, muscle, blood, hair, skin, and connective tissues contained very small amounts. Feeding the high metabolic load of 100ppm of dietary cadmium significantly decreased 109Cd concentrations in the gastrointestinal tract tissues, but the effect was not sufficient to produce a detectable change in over-all body retention. 109Cadmium levels in other tissues were not materially influenced by cadmium feeding. Daily rate of 109Cd fecal excretion declined linearly and rapidly during the second week, with about 20% of the body burden eliminated on Day 8 and less than 5% on Day 14. After 21 days of cadmium feeding, kidney, duodenum, and liver concentrations of stable cadmium were 62, 28, and 18ppm of dry matter, compared to 2.7, 2.5, and 1.6ppm in comparable tissues of control animals. Ruminants do not have a homeostatic control mechanism for controlling cadmium absorption or excretion which is affected by level of dietary or tissue cadmium content. However, very low levels are absorbed.

Suppression of the hypothalami- c-pituitary-adrenal axis in the newborn dog.

ABSTRACT. In the newborn dog during the first 24 hr after birth, the concentration of cortisol in plasma rises after injection of ACTH. Following administration of dexamethasone, the plasma cortisol falls to low levels. The feedback mechanism of homeostatic control of adrenal secretion appears to be functional at birth in the dog. (Endocrinology85: 365, 1969)

65Zn and Stable Zinc Absorption, Excretion and Tissue Concentrations as Affected by Type of Diet and Level of Zinc in Normal Calves

The effects of dietary zinc level (2 vs. 38 ppm) in a purified diet and of a practical versus a purified diet with the same zinc level (38 ppm) on 65Zn metabolism were determined following a single oral dosing in 2.5- and 4.5-month-old male Holstein calves. The 12 animals were killed 14 days after 65Zn dosing and before those given the zinc-deficient diet developed any clinical indication of a deficiency. Calves fed the low zinc purified diet absorbed considerably more 65Zn, but there was little overall difference between groups fed the practical-type diet and the purified diet with added zinc. Those given the practical diet had a higher fecal endogenous 65Zn excretion the second week after dosing. Younger calves in the first experiment absorbed a much higher percentage of 65Zn from diets with adequate zinc than older ones in the later experiment. There was no difference in net 65Zn retention due to age among those given the zinc-deficient diet, suggesting that differences associated with age were not caused by reduced ability of animals to absorb zinc but rather to effects of other factors on the homeostatic control mechanism. Tissue samples from calves given the deficient diet retained much more of the administered 65Zn dose in all tissues than those given zinc-adequate diets. When results were calculated relative to net absorbed dose, the more active metabolic tissues including liver, heart, lung, kidney, spleen, testicles and digestive tract sections from calves fed the zinc-deficient diet still retained much more 65Zn than comparable tissues of the other calves: this effect was greater in the younger calves. As percentage of absorbed dose, diet did not have marked effects on 65Zn in tissues which metabolize 65Zn more slowly, including hair, scrotum, muscle and bone. Most tissues from calves fed the zinc-deficient diet contained somewhat less stable zinc than those from animals fed adequate zinc. Dry matter content of tissues was not affected by the diets.

The mode of action of vitamin D.

Summary1. The purpose of this review article is to re‐evaluate and integrate many of the observations related to the physiological effects of vitamin D, using as a working hypothesis the concept that the vitamin may be acting analogously to a steroid hormone in terms of its ability to interact with genetic information and ultimately elicit a physiological response. Prior to this time the problem of the mechanism of action of vitamin D has primarily been approached from the point of view that the vitamin was acting as a cofactor for some specific enzymic reaction.2. The physiological activities of vitamin D are integrated with those of parathyroid hormone to provide a homeostatic control for the regulation of primarily calcium and secondarily phosphate metabolism. It is proposed that the role of vitamin D in this homeostatic control mechanism is older and more fundamental than that of parathyroid hormone. The interaction of vitamin D on skeletal calcium metabolism may have evolved before the effects of the vitamin on intestinal calcium absorption.3. There are several physiological defects of calcium metabolism—rickets, osteo‐malacia, vitamin D‐resistant rickets and idiopathic hypercalcaemia—all of which may be a consequence of an aberration in one or another of the interlocking steps of the vitamin D‐dependent and calcium‐dependent homeostatic control mechanism.4. The most thoroughly established action of vitamin D in vivo is to promote or facilitate the intestinal absorption of calcium. Although the exact biochemical details of this process are not available, this may involve vitamin D‐mediated synthesis of the appropriate enzyme systems or the alteration of membrane structure necessary for calcium absorption. It is not yet unequivocally established whether calcium absorption is an energy‐dependent active transport process or is a passive carrier‐mediated or simple diffusion process.5. The exact action of vitamin D on bone metabolism is not as well established, but the primary effect of the vitamin is likely to mediate bone resorption. The vitamin D‐dependent activities of the cell in both the intestine and bone are to absorb calcium and transfer it to the blood.6. No direct effects of vitamin D on intestinal absorption of phosphate have been found. Furthermore the validity of a vitamin D‐mediated renal reabsorption of phosphate is questioned, for the major effects of vitamin D are cation oriented. If the renal effects of vitamin D are true, it is postulated that the mechanism of action of the vitamin here on the anion, phosphate, is fundamentally different from its cation oriented mechanism.7. There is a lag in the action of vitamin D on the vitamin mediated: (a) transport of calcium both in vivo in rats and chicks, and in vitro with everted intestinal slices;(b) the apparent increased permeability of intestinal mucosa; (c) increased levels of citric acid in serum or bone; (d) the increased incorporation of radioactive inorganic phosphorus into intestinal mucosa phospholipids. As shown by the use of radioactive vitamin D, this lag is not due to a lack of the vitamin in the target organs.8. Whereas large, unphysiological doses of radioactive vitamin D localize in all tissues and all subcellular fractions, small physiological doses of radioactive vitamin D localize predominantly in the nucleus of the intestinal mucosa. The amount of vitamin D localized in the nucleus would appear to be too low for the vitamin to function as a cofactor, and is more indicative of an interaction on or with deoxy‐ribonucleic acid.9. Actinomycin D, an inhibitor of DNA‐directed RNA synthesis, inhibits the action of vitamin D in mediating intestinal calcium absorption and bone resorption. Vitamin D also stimulates messenger‐RNA synthesis in intestinal mucosa within 1/2 hr. of vitamin treatment. Vitamin D may play a crucial role, along with parathyroid hormone and calcium, in a DNA, gene‐dependent, homeostatic control mechanism for cal, ium metabolism. In this system the vitamin D molecule has certain very specific structural requirements which are probably a reflection of the specificity of its receptor molecule, rather than structural requirements for a cofactor‐enzyme relationship.

Prevention of induced atherosclerosis by peroxidase.

Hepatocatalase peroxidase, an active peroxidase-oxidase subunit isolated from beef-liver catalase, prevents cholesterol deposition and aortic atherosclerosis in cholesterol-fed rabbits and has no apparent toxicity or undesirable de effects. No allergic or immunological reactions have been observed. The participation of this enzymatic subunit in homeostatic control mechanisms and its potential pharmacological value in the control of human atherosclerosis are suggested.

Experimental transient glaucoma in animals.

Bartels1in 1905 described a glaucoma in dogs and rabbits which followed ligating or cutting of the extraocular muscles. It was assumed that the effect was a result of occlusion of the anterior ciliary veins, although just how this venous congestion would result in a glaucoma was not adequately defined. In view of the accumulating evidence for a neurohumoral homeostatic control mechanism regulating the intraocular pressure, the present study was undertaken to further explore the various factors involved in the production of this interesting glaucoma. Method and Material Adult albino rabbits (2 to 4 kg [4.4 to 8.8 lb]) and adult mongrel dogs (8 to 10 kg [17.6 to 22 lb]) anesthetized with intravenous secobarbital were used. In all experiments following the induction of general anesthesia, the ocular tension was measured at ten-minute intervals until stable readings were obtained (usually 30 to 40 minutes). The same certified Schiotz tonometer