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Tibial dyschondroplasia is a skeletal abnormality characterized by an avascular plug of cartilage in the metaphysis of the long bones of rapidly growing birds. An avascular, thickened growth plate also occurs in vitamin D/calcium-deficient rickets. This research was conducted to evaluate tibial dyschondroplasia and rachitic tissue for factors shown to be important in normal growth plate vascularization. Immunohistochemical analysis demonstrated the presence of vascular endothelial growth factor, its receptor Flk-1, and matrix metalloproteinases MMP-9 and MMP-13 to be present in all tissues examined. In most cases, immunostaining was intracellular, except near blood vessels where the matrix was also stained. The results suggest that, for the four proteins examined, disruption of their expression is not a key factor in the development of these avascular cartilage lesions in avians. The relationship of these observations to the pathology of tibial dyschondroplasia is discussed.

To determine the effects of hypoxia on energy state and intracellular pH (pHi) in resting pulmonary and systemic arterial smooth muscles, we used31P nuclear magnetic resonance spectroscopy and colorimetric and enzymatic assays to measure pHi; intracellular concentrations of ATP, phosphocreatine, creatine, and Pi; and phosphorylation potential in superfused tissue segments from porcine proximal intrapulmonary and superficial femoral arteries. Under baseline conditions ([Formula: see text] 467 ± 12.1 mmHg), energy state and total creatine (phosphocreatine + creatine) concentration were lower and pHiwas higher in pulmonary arteries. During hypoxia ([Formula: see text] 23 ± 2.4 mmHg), energy state deteriorated more in femoral arteries than in pulmonary arteries. pHifell in both tissues but was always more alkaline in pulmonary arteries. Reoxygenation reversed the changes induced by hypoxia. These results suggest that production and/or elimination of ATP and H+was different in resting pulmonary and systemic arterial smooth muscles under baseline and hypoxic conditions. Because energy state and pHiaffect a wide variety of cellular processes, including signal transduction, contractile protein interaction, and activities of ion pumps and channels, further investigation is indicated to determine whether these differences have functional significance.

Tissues vary considerably in their sensitivity to hypoxia. Neurological cells tolerate hypoxia for only a few minutes whereas bladder smooth muscle may survive for several days without oxygen. This has important implications in the management of oxygen transport and monitoring of tissue hypoxia in critically ill patients. Regional oxygen transport and cellular use are often neglected but are important in maintaining tissue function and overall survival ### Delivery to organs and tissues The mechanisms controlling oxygen distribution are incompletely understood but involve a series of convective and diffusive processes. Convective oxygen transport refers to the bulk movement of oxygen in air or blood and depends on active, energy consuming processes generating flow in the tracheobronchial tree and circulation. Diffusive transport refers to the passive movement of oxygen down its concentration gradient across tissue barriers, including the alveolar-capillary membrane, and across the extracellular matrix between the tissue capillaries and individual cells to mitochondria. The amount of diffusive oxygen movement depends on the oxygen tension gradient and the diffusion distance. Effect of oxygen tension gradient and diffusion distance on availability of oxygen to cells In many critically ill patients tissue hypoxia is due to disordered regional distribution of blood flow both between and within organs. Regional and microcirculatory distribution of cardiac output is determined by a complex interaction of endothelial, receptor, neural, metabolic, and pharmacological factors working on small resistance arterioles and precapillary sphincters. In critical illness, particularly sepsis, hypotension and loss of normal autoregulation cause shunting and tissue hypoxia in some organs despite high global oxygen delivery and mixed venous saturation. The perfusion pressure is an important determinant of regional perfusion, but adrenaline or noradrenaline given to maintain systemic blood pressure may reduce regional distribution, particularly to the renal and splanchnic capillary beds. Severe tissue hypoxia due to capillary microthrombosis in critically ill patient with meningococcal septicaemia …

Mammalian life and the bioenergetic processes that maintain cellular integrity depend on a continuous supply of oxygen to sustain aerobic metabolism. Reduced oxygen delivery and failure of cellular use of oxygen occur in various circumstances and if not recognised result in organ dysfunction and death. Prevention, early identification, and correction of tissue hypoxia are essential skills. An understanding of the key steps in oxygen transport within the body is essential to avoid tissue hypoxia. Red blood cells entering a capillary Although oxygen is the substrate that cells use in the greatest quantity and on which aerobic metabolism and cell integrity depend, the tissues have no storage system for oxygen. They rely on a continuous supply at a rate that precisely matches changing metabolic requirements. If this supply fails, even for a few minutes, tissue hypoxaemia may develop resulting in anaerobic metabolism and production of lactate. ### Key steps in oxygen cascade Oxygen transport from atmosphere to mitochondria. Values given in parenthesis are for a healthy 70 kg adult breathing air (FiO2 0.21) at standard barometric pressure View this table: Partial pressures of oxygen at sea level (101 kPa) Oxygen transport from environmental air to the mitochondria of individual cells occurs as a series of steps. The heart, lungs, and circulation extract oxygen from the atmosphere and generate a flow of oxygenated blood to the tissues to maintain aerobic metabolism. The system must be energy efficient (avoiding unnecessary cardiorespiratory work), match oxygen distribution with metabolic demand, and allow efficient oxygen transport across the extravascular tissue matrix. At the tissue level, cells must extract oxygen from the extracellular environment and use it efficiently in cellular metabolic processes. Arterial oxygen tension (PaO2 …

Oxygen is widely available and commonly prescribed by medical and paramedical staff. When administered correctly it may be life saving, but oxygen is often given without careful evaluation of its potential benefits and side effects. Like any drug there are clear indications for treatment with oxygen and appropriate methods of delivery. Inappropriate dose and failure to monitor treatment can have serious consequences. Vigilant monitoring to detect and correct adverse effects swiftly is essential. Oxygen is often poorly prescibed. This drug chart was for a severely hypoxaemic patient with pneumonia and mild chronic obstructive pulmonary disease. The risk of carbon dioxide retention was secondary to the danger of severe hypoxaemia and inadequate oxygen was life threatening In a recent hospital survey 21% of oxygen prescriptions were inappropriate and 85% of patients were inadequately supervised. Similar studies report that oxygen is prescribed inappropriately in general practice. To ensure safe and effective treatment prescriptions should cover the flow rate, delivery system, duration, and monitoring of treatment. Tissues require oxygen for survival. Delivery depends on adequate ventilation, gas exchange, and circulatory distribution. Tissue hypoxia occurs within 4 minutes of failure of any of these systems because the oxygen reserves in tissue and lung are relatively small. The physiological and pathological mechanisms that result in tissue hypoxia will be discussed in later articles. They can be classified into two main groups: those causing arterial hypoxaemia and those causing failure of the oxygen-haemoglobin transport system without arterial hypoxaemia. More than one mechanism may contribute to tissue hypoxia, and predicting the response to supplemental oxygen requires careful evaluation of these functions. #### Checklist for safe prescribing of oxygen

The acute respiratory distress syndrome continues to be a major medical problem. Despite recent advances in treatment, such as the use of nitrogen monoxide (NO), extracorporeal membrane oxygenation (ECMO) and specialized ventilatory techniques in maintaining adequate oxygenation, mortality still remains high. The presence of activated neutrophils coupled with high inspired oxygen concentrations provide conditions that favour increased oxidative stress and this has focused attention on the possible role of free radical species in both the initiation and propagation of ARDS. Although there is evidence implicating increased free radical activity in ARDS, much of this is from animal models and the role of intervention in such processes has not been established. Although antioxidant therapy has been suggested as a possible treatment for ARDS the current literature is less than convincing. We examine the available data from human studies and suggest possible further studies and future therapeutic goals.

A series of experiments was conducted to test the hypothesis that vitamin D utilization may not be as efficient in chicks with tibial dyschondroplasia (TD). The basal diet contained 1.0% Ca and 0.45% available P with no supplemental cholecalciferol (D3). Chicks from low TD (LTD) and high TD (HTD) selected lines were fed diets supplemented with various levels of vitamin D compounds and examined for rickets and TD. When chicks were fed a D3-deficient diet containing only 1.25 micrograms/kg added D3, HTD chicks had a greater incidence of severe rickets than LTD chicks (P < 0.05). The LTD chicks did not exhibit TD when fed a diet containing adequate (20 micrograms/kg) D3. The LTD chicks fed a diet supplemented with 5 micrograms/kg D3, however, had 22% incidence of TD. When HTD chicks were fed diets supplemented with 5 micrograms/kg D3 [control diet that meets NRC (1994) requirement for D3], 20 micrograms/kg D3, 5 micrograms/kg 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] or the combination of both D3 (20 micrograms/kg) and 1,25-(OH)2D3 (5 micrograms/ kg), TD incidence was highest in HTD chicks fed the control diet. When HTD chicks were fed diets with an increased dietary level of 1,25-(OH)2D3 (10 micrograms/kg) further reduction of TD incidence (P < 0.05) occurred. A potentially toxic level (Soares et al., 1983) of 1,25-(OH)2D3 (15 micrograms/kg) fed to HTD chicks resulted in still greater suppression of incidence of TD even though growth and feed intake in HTD chicks was greater than those of LTD chicks. It is concluded that the development of TD in HTD chicks is associated with subnormal ability to metabolize vitamin D.

The effects of long-term consumption of 1 and 5 ppm of Cd on Cd, Cu, Fe, and Zn concentrations in milk and a variety of tissues of first-lactation dairy cows was investigated. Thirty-six Holstein heifers were allocated to three groups and fed similar diets differing only in the concentration of Cd (.25, 1, and 5 ppm) for a 394-d period before calving. One- and 5-ppm Cd concentrations were achieved using CdCl2. Liver, kidney cortex, and muscle were biopsied from one-half of the heifers of each group before Cd supplementation and again from the same heifers within 5 d after parturition. Colostrum and milk were sampled throughout the 150 d of lactation. Urine was sampled after an average of 450 d of Cd exposure. At slaughter (after an average of 554 d), 11 tissues were sampled from 12 cows representing all treatment groups. During the first 394 d, Cd accumulated in kidney and liver with increasing dietary concentrations of Cd but did not further increase by 554 d. However, by 554 d Cd had also accumulated in the adrenal glands, ovaries, spleen, and uteri of cows consuming 5 ppm of Cd. Dietary Cd did not influence the concentration of Cd, Cu, Fe, or Zn in colostrum or milk. However, urine pH, Zn, and K were lower in cows consuming 5 ppm of Cd. Liver Cu was reduced by 1 and 5 ppm of Cd at both 394 and 554 d.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty-six postpubertal Holstein heifers were allocated to three groups and fed the same diet, which differed only in the concentration of Cd: control group (.25 ppm of Cd), low-Cd group (1 ppm of Cd), and high-Cd group (5 ppm of Cd). Cadmium was supplemented to the low-Cd and high-Cd groups using CdCl2. Liver, kidney cortex, and abdominal muscle were biopsied for mineral analysis from one-half of the heifers of each group before Cd supplementation and again from the same animals within 5 d after parturition, 394 d later. Blood, liver, and muscle were collected from each calf within 5 h after birth. In the dam, 5 ppm of dietary Cd caused a 62-, 27-, and 4-fold increase in Cd of the kidney, liver, and muscle, respectively; kidney Zn and Fe increased (76%) and decreased (33%), respectively, whereas the serum Cu was reduced (31%). Liver Cu was reduced to 40 and 17% by dietary Cd of 1 and 5 ppm, respectively, in the dams. Calves from dams consuming 5 ppm of Cd had a 29 and 43% reduction in liver Cu and Zn, respectively. In these same calves, packed cell volume, hemoglobin concentration, and serum Cu were decreased by 17, 18, and 25%, respectively, whereas serum Zn was increased (55%). Serum sodium and potassium were reduced by 4 and 13%, respectively, and blood urea nitrogen was increased by 63% in calves from dams consuming 5 ppm of Cd. Feeding primigravid dairy cattle up to 5 ppm of Cd as CdCl2 throughout gestation did not influence the concentration of Cd in the neonate but caused reductions in liver Cu and Zn; teratogenesis was not apparent.

odel-based compartmental analysis was used to describe data on the whole body kinetics of copper metabolism in rats. Data were collected on recovery of radio-copper in plasma, liver, skin, skeletal muscle, bile, and feces for 3 days after the injection of 10 micrograms iv of copper labeled with 64Cu. Data on copper masses and on 64Cu kinetics were analyzed by the stimulation, analysis, and modeling computer programs. Observed data were fit to a 16-component “working hypothesis” model; fractional transfer coefficients were estimated, and steady-state compartment masses and copper transfer rates were calculated. The model postulates a rapid turnover of plasma nonceruloplasmin (NCp) copper (8.5 h-1), which exchanged a large amount of copper with extrahepatic tissues (16 micrograms/h) as well as liver (13 micrograms/h). In comparison, ceruloplasmin (Cp) transferred relatively little copper to tissues (less than 1 microgram/h). NCp copper is postulated to be the precursor for biliary copper. Regarding the intracellular metabolism of copper in hepatic and extrahepatic tissues, the data were compatible with a faster turning-over compartment that exchanged copper with NCp and a slower turning-over compartment with input from Cp. In the liver, the slower turning-over compartment was the copper present in peak II (mol mass 30,000–40,000 Da); this received much of its input from the faster turning-over compartment (peak III), which was hypothesized to represent, in large part, copper in metallothionein.

Enzymes play an important role in the food industry in both traditional and novel products. The ancient processes of brewing and cheese-making rely on enzyme activity at various stages of manufacture. In brewing, the malting of grain develops amylase and protease activities, which then act on the starch and protein reserves of the grain during mashing to produce fermentable sugars and other nutrients on which yeast can grow. By a process of trial and error, brewers over the millennia have optimised conditions for malting and mashing despite their lack of knowledge of enzymes. In the same way, the slaughter of animals for meat was developed so that the quality of the meat was improved. The importance of resting animals prior to slaughter, killing them without trauma and hanging the meat for several days was recognised before the role of enzymes in the process was known. It is now known that resting animals prior to slaughter ensures that sufficient glycogen is present in the muscle to act as a substrate for enzymes post mortem. The role of post mortem glycolysis and natural muscle proteases in the conversion of muscle to meat is also understood and has led to attempts to improve further the process, and therefore the quality of the meat.

The objective of this presentation is to relate the abundance and mobility of Cd in components of terrestrial ecosystems with implications for land utilization of sewage sludge. The uptake of Cd by crop plants is a function of the quantity of the element in the soil plus other soil factors affecting the Cd ion activity or electrochemical potential at the plant root surface. The natural abundance of Cd in soils has been reported as 0.5 mug/g which is higher than the background level of 0.2 mug/g found in soils studied in Pennsylvania. Experimental results indicate that the plant availability of Cd increases with each soil addition. While the plant availability of Cd is decreased by liming to increase soil pH, it has not been possible to add Cd salts or sewage sludge Cd without significantly increasing plant uptake. Field studies have shown that land application of sewage sludge can be expected to increase the Cd concentration of corn leaves from a range of 0.05-0.1 mug/g to 1-3 mug/g. Two years after the last application of sludge which added up to 10 ppm Cd to the surface soil, corn grain, sorghum grain, wheat grain, and potatoes showed a 10- to 15-fold increase in Cd over background levels. Studies were conducted with chicks, laying hens, and meadow voles (Microtus Pennsylvanias) to assess the impact of this increase in plant Cd upon the food chain. Corn and sorghum plants were grown on soils with either inorganic or sludge fertilizer for the purpose of producing herbage for use in feeding trials with meadow voles. Eight diets and a synthetic control diet were formulated to study the effect of source (plant vs. inorganic) of Cd on tissue accumulation. Significant accumulation of Cd occurred in kidney and liver, but not muscle, of voles fed diets containing sludge fertilized corn (1.09 mug/g) or sludge fertilized sorghum (2.76 mug/g). The source of Cd had little influence on tissue accumulation. In studies with broiler chicks and laying hens, natural diets containing 0.2 ppm Cd were supplemented with 3 ppm of this element. As with the meadow voles, Cd readily accumulated in liver and kidney. Although the results were not statistically significant, 3 ppm dietary Cd doubled muscle Cd content. There was no transfer of Cd to egg in a long term (12 month) experiment with laying hens. Soil management programs have been developed to maintain animal dietary levels of Cd at less than 1.0 mug/g from the use of sewage sludge on land in Pennsylvania. However, it is concluded that this level over time may cause a significant accumulation of Cd in animal tissues. Interpretation of these results in relation to those for human intake of Cd and the long range health effects of Cd is required for the proper monitoring of sewage sludge applications on land used for production of crops which enter the food chain.

A CHOLINE deficiency is readily produced in chicks by feeding a diet low in choline or certain choline precursors. The effect of choline deficiency in laying hens, however, is less clear. McCollum et al. (1912) fed a diet containing 70 parts ground polished rice previously extracted with hot alcohol and 30 parts of dried skimmed milk to laying hens and found that more lecithin was present in eggs produced by these hens than had been consumed in the diet. Therefore, these investigators concluded that large amounts of lecithin were synthesized by laying hens. Abbott and DeMasters (1940), using a diet similar to McCollum’s supplemented with other vitamins, found that addition of choline to this basal diet increased egg production, prevented weight loss, and reduced liver fat. When diets have been studied which were low in methionine and vitamin B12, good responses were obtained from the addition of choline to diets…

HIGGINS, Richert and Westerfeld (1956) observed normal development in chicks which received a purified casein diet containing approximately 0.02 mg. molybdenum per kg. of diet. An apparent molybdenum deficiency, however, was produced by feeding sodium tungstate. Tungstate feeding decreased growth rate, xanthine dehydrogenase activity and uric acid excretion, all of which were reversed by the addition of molybdenum to the diet. Reid et al. (1956) reported that chicks and turkey poults responded to additional dietary molybdenum when fed a purified diet containing isolated soybean protein. Further results by Kurnick et al. (1957) and Reid et al. (1957) indicated that tissue xanthine dehydrogenase activity as well as growth rate was increased by molybdenum supplementation of the basal diet. Using practical and purified diets, Teekel and Watts (1959) observed no beneficial effect from molybdenum supplementation when the chicks came from dams which received a regular diet. However, when the dams received a …

EARLY experiments by Titus (1932), Insko, Lyons and Martin (1938) and Lyons, Insko and Martin (1938) failed to show zinc to be a dietary essential for the chick. More recently, Mehring, Brumbaugh and Titus (1956) observed no beneficial effect upon growth of chicks from increasing the amount of zinc consumed from 42 to 820 mg. of zinc per kg. of diet. In studies on perosis, Wilgus, Norris and Heuser (1937), found that zinc as well as manganese had a beneficial effect upon the incidence of perosis, but under the conditions of their experiments manganese was shown to be the primary deficiency. Therefore, it was not until 1957, as a result of studies by O’Dell and Savage, that a true zinc deficiency was recognized in the chick. Edwards, Young and Gillis (1958), Moeller and Scott (1958), Morrison and Sarett (1958), Patrick (1958), and Roberson and Schaible (1958) have confirmed the original…

INTRODUCTION JUKES (1940) reported that choline is essential for the prevention of perosis in the chick. Further studies by Jukes and Welch (1942), Almquist and Grau (1944), Jukes, Olson and Dornbush (1945), and Jukes and Olson (1945) indicated that the intact choline molecule per se is responsible for the antiperotic properties of this substance. Betaine and other sources of labile methyl groups were ineffective in preventing perosis unless fed in combination with precursors of choline, such as monomethylethanolamine or dimethylethanolamine. However, little is known concerning the metabolic role of choline in preventing perosis. Since recent experiments in our laboratory have dealt with attempts to ascertain the role of choline in bone formation, a report by Miller et al. (1958) was of considerable interest. It was observed that the oral administration of diethylstilbestrol to choline-deficient rats protected them against death and produced certain lipotropic effects. This report is concerned with experiments …

Three types of mechanically deboned turkey meat (MDTM) were obtained from a Pennsylvania poultry processing plant and studied for nutrient composition. Samples of MDTM included meat from turkey breast cages (protein 15.4%, fat 10.2%, moisture 71.3%), turkey racks (protein 13.4%, fat 17.0%, moisture 67.9%), and turkey backs (protein 13.0%, fat 21.7%, moisture 65.9%). Protein efficiency ratios (PER) were determined on each type, and with and without an antioxidant. Material without an antioxidant resulted in gross errors. Adjusted PER values of MDTM treated with an antioxidant were significantly higher than the 2.50 value for the standard casein diet. Amino acids, fatty acids, caloric content and selected minerals were also measured.

A series of experiments were performed to examine the nature of biliary copper excretion in the chicken. Gallbladder and hepatic bile were collected from chickens fed diets that altered copper excretion. Bile was fractionated using gel filtration chromatography and SDS-PAGE. Chicks fed the control diet excreted copper that was bound primarily to a protein aggregate of greater than 600,000 daltons and secondarily, to a 7400 dalton compound. When biliary copper levels were elevated, the distribution of copper associated with the binding compounds was changed. Both the proportion and the absolute amounts of copper in the secondary pool increased dramatically when biliary copper increased. The excretion patterns observed in the control animals are believed to represent the steady-state distribution of copper in bile. A similar distribution was observed with rat bile that was obtained under steady-state conditions. These distribution patterns differ from those reported by other investigators who examined biliary copper excretion in the rat using different experimental conditions.

SummaryA somatomedin bioassay measuring sulfate incorporation into young chick epiphyseal plate cartilage was developed and used to determine somatomedin activity in two animal models. The incubation schedule consisted of 4 hr preincubation and 3 hr incubation. The average index of precision, λ, of the bioassay was 0.18 with increased precision evident in later studies. The sensitivity fell within the range of currently used somatomedin bioassays. Using radioimmunoassay techniques, serum insulin and serum growth hormone levels were measured in lean and obese Zucker rats. Serum from obese Zucker rats was found to have reduced growth hormone levels, reduced somatomedin activity, and elevated insulin levels when compared to their lean littermates. There was no difference in somatomedin activity between slow-growing Ossabaw and fast-growing Yorkshire pigs.The radioimmunoassay kit for rat growth hormone assay was supplied through the generosity of the Hormone Distribution Office, NIAMD, NIH, Bethesda, Maryland.

Three different types of mechanically deboned poultry meat (MDPM) were obtained from a Pennsylvania poultry processing plant and studied for nutrient composition. Samples of MDPM included material from broiler skinless necks (protein 15.3%, fat 7.9%, moisture 76.7%), broiler backs (protein 11.9%, fat 24%, moisture 63.1%), and a combination of skinless necks and backs (protein 13.7%, fat 17.0%, moisture 69.0%). Protein efficiency ratios (PER) were determined for each type using casein as the standard diet. MDPM from skinless necks had an adjusted PER value of 2.65 which was comparable to the standard casein diet. The combination of necks and backs MDPM also resulted in a PER value that was comparable to the standard casein diet. PER values for MDPM from backs were significantly lower possibly due to protein alternation as a result of rancidity. Amino acids, fatty acids, caloric content and selected trace minerals were measured also.

Miller and Denton (1959) and Davies et al. (1960) reported that inorganic sulfate was effective in counteracting the toxic effects of supplying chicks with excess dietary molybdenum. The former investigators fed a diet composed of practical ingredients, including 35% of soybean oil meal, while the latter fed a purified diet containing isolated soybean protein. The addition of large quantities of sulfate ion to these diets in the absence of molybdenum did not affect growth. In contrast in experiments conducted at this laboratory with chicks using a purified diet containing casein as the protein source, marked growth depression was observed by feeding high levels of sulfate ion in attempts to induce molybdenum deficiency. The basal diet used in these experiments is given in Table 1. The mineral mixture in the diet supplied 0.23 to 0.41 percent inorganic sulfate. When sulfate ion was added to the diet, the calcium, sodium and potassium …