Functional diversity and clonal frequencies of reactivity in the available antibody repertoire

Our objective was to determine the effect of level and chemical form of dietary selenium on productivity of beef cows, concentrations of triiodothyronine (T3), and thyroxine (T4) in plasma, and immunoglobulins (IgG and IgM) in plasma and colostrum of cows. Pregnant cows (n = 60) were randomly allocated among four dietary treatments of 20, 60, or 120 ppm Se as selenite and 60 ppm as selenomethionine from selenized yeast (SeY) in salts offered free-choice. Treatments began 90 d prepartum and continued through the second parturition. Treatments did not affect the final body weights of cows or birth weights or weaning weights of calves. At parturition, cows given salt with 20 ppm Se as selenite had lower (P < . 05) concentrations of Se in blood than cows with access to higher-Se salts. Treatments affected (P < .01) the concentration of T3 and the ratio of T3:T4 in plasma of cows. The concentration of T3 in plasma of cows with access to salt with 20 ppm Se was 14% lower than that in cows supplemented with 60 ppm Se as selenite or SeY. Plasma IgG in cows and calves, colostrum, and Se concentrations in colostrum, casein, and whey were lowest (P < .01) for cows given salt with only 20 ppm Se. Thus, salts with concentrations of 60 and 120 ppm Se improved measures of Se status in cows and calves. Consideration should be given to the concentrations of T3 and IgG when determining the nutritional requirements for Se in cattle.     

Selenium content of Brazil nuts from two geographic locations in Brazil

Brazil nuts (Bertholletia excelsa) natively contain very high concentrations of selenium. Since dietary selenium, including Brazil nuts, have been associated with protection against tumor development in laboratory animal studies, it was of interest to determine the selenium content of the nuts from different nut-growing regions of Brazil. In the work reported, 162 nuts from each of two regions (Acre-Rondonia and Manaus-Belem) were individually analyzed for selenium. The average +/- standard deviation and range of selenium concentrations in ppm, fresh weight for nuts from Acre-Rondonia and Manaus-Belem regions were, respectively, 3.06 +/- 4.01 (0.03-31.7) and 36.0 +/- 50.0 (1.25-512.0). The toxicology of Brazil nut consumption is discussed.     

Endogenous nitric oxide in the airways of different animal species

BACKGROUND: High amounts of endogenous nitric oxide (NO) have been demonstrated in the human upper airway, but the role of nasal NO is still unclear. The present study aims to describe nasal NO excretion in different animal species with special living conditions or anatomy. METHODS: Domestic animals (horse, cow, pig, sheep, dog, cat) and zoo-animals (Rhesus monkey, chimpanzee, gorilla, elephant, fur seal, alpaca, yak, dolphin, camel, capybara, bear, tiger, wolf, giraffe, alligator, Harris' hawk, kangaroo) were studied awake, resting or anaesthetised. NO concentrations were measured by chemiluminescence using different analysers and techniques, including measurements on mixed exhaled air, during continuous or intermittent gas sampling, and on single breaths. RESULTS: Rhesus monkeys (number of individuals N = 5) and pigs (N = 2) were compared and displayed quite different excretion patterns. Allowing NO to accumulate in the nose during timed occlusions yielded peak concentrations in monkeys of 0.46 +/- 0.07 parts per million (ppm, mean +/- SEM), 0.59 +/- 0.08 ppm, 0.70 +/- 0.08 ppm and 1.02 +/- 0.05 ppm NO after 15, 30, 60 and 120 s of occlusion. In pigs, 0.012-0.021 ppm NO were recorded, independent of occlusion time. The chimpanzee was similar to the Rhesus monkey and the highest NO value, 2.9 ppm, was recorded after 4-5 min of occlusion. In single breaths from 3 elephants 0.031-0.082 ppm, from 1 gorilla 0.029 ppm, and from 1 chimpanzee 0.069 +/- 0.003 ppm NO (8 observations) were recorded. CONCLUSIONS: We found considerable species difference in nasal NO excretion with pronounced amounts only in primates and elephants. The physiological implications of these findings remain to be defined.     

Blood selenium concentrations in cows and heifers on 253 cow-calf operations in 18 states

This study was conducted to determine the geographic distribution of selenium deficiency among beef cows and heifers in selected states. Whole blood selenium concentrations were determined for cows and heifers on 253 cow-calf operations in 18 states. Overall, 7.8% of the samples were severely deficient, and another 10.4% of the samples were considered marginally deficient for selenium. Blood selenium concentrations varied by geographic region. Cattle from the southeastern states were more commonly considered severely or marginally deficient (18.6% and 23.8%, respectively) than cattle from other regions. Herds from the southeastern states were also more commonly considered severely or marginally deficient (14.9% and 20.9%, respectively) than herds from other regions. Blood selenium concentration also varied by whether selenium had been supplemented to the herd. We conclude that blood selenium levels for cattle vary by geographic region and selenium supplementation of the herd.     

Factors affecting serum selenium and vitamin E concentrations in dairy cows

Supplementation of selenium and vitamin E to enhance disease resistance in dairy cattle has become common, particularly to prevent periparturient reproductive disorders and mastitis. To establish reference values for serum vitamin E and selenium concentrations in postparturient dairy cattle and to determine whether serum concentrations of these micronutrients varied with season and stage of lactation, cows from a stratified random sample of 50 herds were studied for 1 year. Blood samples were collected from each of the 50 study herds twice, from the 10 most recently parturient cows or from 10% of the herd, whichever was greatest. Mean concentration of vitamin E and selenium was 2.55 micrograms/ml and 78.12 ng/ml, respectively. Vitamin E concentrations were significantly (P < 0.05) higher during the summer and fall than during the winter and spring. Selenium concentrations were significantly (P < 0.05) lower during the summer and fall than during the winter and spring. Herd, season of blood sample collection, and time since parturition were significant (P < 0.02) in explaining variation in vitamin E and selenium concentrations.     

Growth and carcass characteristics of cattle and buffalo breeds reared on a dry zone pasture in Sri Lanka (Ceylon)

Growth and carcass characteristics were measured on calves from three cattle breeds-the Sinhala, Red Sindhi and Friesian-and two buffalo breeds-the local buffalo and Murrah. The growth study was carried out on Brachiaria brizantha pasture over a period of 48 weeks. The two buffalo breeds grew fastest followed by the two Bos indicus breeds. The Friesian cattle grew at the slowest rate. The Sinhala and local buffalo had normal haematocrit values while the values for all other breeds were lower. The Sinhala and local buffalo had the highest carcass dressing percentages and the highest muscle; bone ratios. Tenderness measured by Warner-Bratzler shear force values and palatability scores by a taste panel were similar for meat from cattle and buffalo.     

Comparative susceptibility of Pyrenean and Brown Swiss calves to gastrointestinal nematodes in subclinical naturally acquired infections

The susceptibility of two common breeds of cattle in the Pyrenees, Brown Swiss and Pyrenean breed, to parasitism by gastrointestinal nematodes was studied. Twenty-two female calves (13 Brown Swiss and 9 Pyrenean), 3 months old with a mean weight of 112.8 +/- 18.33 and 103.3 +/- 17.11 kg respectively at the start of the study, were used. The calves began their first grazing season grazing with 200 cattle following the traditional grazing system for mountainous areas: Stabling during winter (December-April), grazing on harvesting meadows at an elevation of 900 m in the spring (May-June) and autumn (October-November), and grazing areas between 1200-2100 m during the summer (July-September). Faeces, blood samples and calves growth rate were taken at 2-week intervals throughout the grazing season. Faecal egg counts of gastrointestinal nematodes, level of serum pepsinogen, total serum protein and blood parameters were measured. The worm egg counts and Cooperia sp. counts were significantly smaller in the calves of Pyrenean breed than in Brown Swiss throughout the experiment. Numbers of eggs of the other genera of parasites found were smaller in the calves of Pyrenean breed than in calves of Brown Swiss breed, but no statistical differences were found. Blood was compared during two periods: the prepatent and patent periods. During the first period, no differences were found between the breeds for any parameter studied. However, during the patent period, Pyrenean animals had significantly greater numbers of erythrocytes, haemoglobin values and packed cell volume (PCV) values, and smaller numbers of eosinophils than animals of the Brown Swiss breed. No differences were found in the level of serum pepsinogen, total serum protein and live weight gains between the two breeds.     

Selenium content in the blood cattle from Venezuela. I. Central and Portugueste zones

Whole blood concentrations of selenium were determined in 776 dairy cows and calves from 28 farms located in three States (Aragua, Carabobo and Guárico) of the central zone of Venezuela and in Portuguesa State. Selenium levels largely varied according to both the geographic distribution and animals breed. Cattle from Guárico State showed the lowest average concentration (0.21 ppm) and those from Portuguesa the highest one (0.67 ppm). A group of animals from Turén (a District of Portuguesa State) showed the highest average concentration (1.64 ppm, range 1.02 +/- to 3.24 ppm). Concentrations of this magnitude in animals under grazing conditions could be related to high levels of selenium either in the soil or in the pasture. It is concluded that such animals are localized inaseleniferous zone (Turén). It must be noted that Jaffé et al. (op. cit.) found high levels of selenium in sesame seeds (Sesamum indicum) from this area and in blood and urine samples of children from Villa Bruzual, a little town of Turén. The results of this wok significantly differ from those obtained in other countries (of Europe and North America), where animals are managed under conditions very different from those of the tropical areas like Venezuela. The role this factor is discussed. This is the first report on blood levels in large animals of economical importance in Venezuela.     

LD 50 and selenium concentration in the organs of rabbits following oral administration of sodium selenite and testing of the toxicity of Ursoselevit-Pr?mix

LD50/24hr was established in the first of a series of experiments on 72 rabbits for orally applied sodium selenite. The dosage was 8.62 mg/kg live weight, the confidence interval being (1 - alpha = 0.95) +/- 0.13 mg/kg. The value was four times as high following intravenous application. Complete lethality was recorded from 15 mg Na2SeO3/kg live weight within 21 hours. Thirty-six animals were involved in the second experiment of the series. They had 50 or 100 per cent Ursoselevit-Pr?mix (30 ppm Se) in their rations. Body mass development of the test animals was superior to that recorded from the controls in the first 50 days, after which limit the former declined strongly in a few days. Their general condition worsened. Postmortem findings, following slaughter, included catarrhal enteritis, toxic liver dystrophy, scattered pulpous tumours in the spleen, and interstitial nephritis. In the third experiment (50 per cent Ursoselevit-Pr?mix with 60 ppm Se in the rations), the test animals developed better than the controls during the first two months, after which point they exhibited the same clinical symptoms as those observed in the second experiment, stopped to put on weight, and eventually turned cachectic. The pathomorphological findings were identical with those obtained from the second experiment. The selenium concentrations in the organs of the test animals all were much higher than those of the controls. Their amounts in excess to base values were up to eleven times in the blood, nine times in the liver, twelve times in the kidneys, and 13 times in the muscles.     

Reversible changes of the muscle cell in experimental phosphorus deficiency

Both animal and human studies suggest that either phosphorus depletion or hypophosphatemia might have an adverse effect on muscle function and composition. Recently a possible deleterious effect was noted in patients with chronic alcoholism. In this unexplained disease, a variety of toxic and nutritional disturbances could affect the muscle cell, thus obscuring the precise role of phosphorus. Accordingly, we examined eight conditioned dogs for the possibility that phosphorus deficiency per se might induce an abnormally low resting transmembrane electrical potential difference (Em) and alter the composition of the muscle cell. Eight conditioned dogs were fed a synthetic phosphorus-deficient but otherwise nutritionally adequate diet plus aluminum carbonate gel for a 28-day period followed by the same diet with phosphorus supplementation for an additional 28 days. Sequential measurements of Em and muscle composition were made at 0 and 28 days during depletion and again after phosphorus repletion. Serum inorganic phosphorus concentration (mg/100 ml) fell from 4.2 +/- 0.6 on day 0 t0 1.7 +/- 0.1 on day 28. Total muscle phosphorus content (mmol/100 g fat-free dry wt [FFDW]) fell from 28.5 +/- 1.8 on day 0 to 22.4 +/- 2.1 on day 28. During phosphorus depletion, average Em (-mV) fell from 92.6 +/- 4.2 to 77.9 +/- 4.1 mV (P less than 0.001). Muscle Na+ and Cl- content (meq/100 g FFDW) rose respectively from 11.8 +/- 3.2 to 17.2 +/- 2.8 (P less than 0.01) and from 8.4 +/- 1.4 to 12.7 +/- 2.0 (P less than 0.001). Total muscle water content rose from 331 +/- 12 to 353 +/- 20 g/100 FFDW (P less than 0.05). A slight, but nevertheless, significant drop in muscle potassium content, 43.7 +/- 2.0-39.7 +/- 2.2 meq/100 g FFDW (P less than 0.05) was also noted. After 4 wk of phosphorus repletion, all of these measurements returned toward control values. We conclude that moderate phosphorus depletion can induce reversible changes in skeletal muscle composition and transmembrane potential in the dog, and it apparently occurs independently of profound hypophosphatemia.     

Diagnosis of paratuberculosis in dairy cattle, using enzyme-linked immunosorbent assay for detection of antibodies against Mycobacterium paratuberculosis in milk

An ELISA containing lipoarabinomannan (LAM) antigen was used to detect antibodies in milk and serum for diagnosis of Mycobacterium paratuberculosis infection in dairy cattle. In experiment 1, milk and serum samples were obtained from 25 cows, and subjected to LAM ELISA testing immediately, and after 1 year of storage at -70 C. Milk samples, with and without a commonly used chemical preservative, were tested. There was no significant difference in LAM ELISA results between fresh and frozen samples or between preserved and unpreserved milk samples. In experiment 2, milk samples were collected daily from 30 cows over a 14-day period. The day-to-day coefficient of variation was 0.19 for milk LAM ELISA and was 0.15 for serum LAM ELISA, with no statistically significant time effect detected. In experiment 3, single milk, serum, and fecal samples were obtained from 764 cows. The fecal samples were cultured for M paratuberculosis to identify infected cows, and the serum and milk samples were subjected to LAM ELISA testing. Results were compared, using the area under the receiver operating characteristic curves. The milk LAM ELISA had specificity (+/- 95% confidence limits) of 87 +/- 8.1% when the cutoff was set at 50% sensitivity, and specificity of 83 +/- 9.1% when sensitivity was set at 60%. The area under the receiver operating characteristic curve was 0.85 +/- 0.03 for the milk ELISA and 0.75 +/- 0.02 for the serum ELISA. In this population of cattle, the milk LAM ELISA had comparable accuracy to serum LAM ELISA, although the milk LAM ELISA was slightly less reproducible (higher coefficient of variation).     

Selenium and vitamin E and incidence of retained placenta in parturient dairy cows. II. Prevention in commercial herds with prepartum treatment

In a series of field experiments in Ohio involving 193 parturient cows of the Holstein and Guernsey breeds, the prophylactic efficacy of selenium and vitamin E was tested under field conditions. Herds initially were chosen because of a chronic problem with retained placenta which could not be related to a known etiological factor. Each herd was divided into three groups. Group A received an injection of 50 mg of sodium selenite 40 days prepartum and 680 units of alpha tocopherol acetate followed by the same treatment 20 days prepartum. Group B received a single injection of 50 mg of sodium selenite 20 days prepartum, and 680 IU of vitamin E. Group C served as the control. Incidence of retained placenta was reduced from a mean of 51.2% in control cows to 8.8% for animals injected with selenium and vitamin E. No differences in efficacy were between Group A and B, and it appears that the single 20 day prepartum injection of 50 mg of sodium selenite and 680 IU of alpha tocopherol acetate is an effective prophylactic for prevention of retained placenta.     

Effect of correction of acidosis on nutritional status in dialysis patients

Malnutrition is a well-recognised feature of end-stage renal failure and contributes to the continuing high morbidity and mortality in this group of patients. One of the aetiological factors is metabolic acidosis which has been shown to increase protein degradation in both experimental models of chronic renal failure and in humans with uraemia. Many patients currently receiving haemodialysis have subnormal values of plasma bicarbonate. However, the values can be normalised by using a dialysate bicarbonate concentration of 35-40 mmol/l and in continuous ambulatory peritoneal dialysis (CAPD), a similar increment in plasma bicarbonate can be achieved using a dialysate lactate content of 35-40 mmol/l. In short-term studies in haemodialysis patients there is evidence of an increase in body weight and other anthroprometric parameters when the plasma bicarbonate has been normalised by increasing the dialysate bicarbonate content. A long-term study in CAPD patients has demonstrated increased body weight, tricep skinfold thickness and midarm muscle circumference in those patients with a plasma bicarbonate of 27.2 +/- 0.3 mmol/l, compared to those with a value of 23.0 +/- 0.3 mmol/l. These studies strongly suggest that correction of acidosis by increased dialysate buffering capacity will improve nutritional status for patients with end-stage renal failure.     

Genetic basis of the MbrC "ploidy" phenotype in Escherichia coli

We measured the spin-lattice relaxation times (T1) of water protons and intermolecular cross-relaxation times (T(IS)) from irradiated protein protons (f2-irradiation at 1.95 or -4.00 ppm) of rabbit normal and monoiodoacetate-induced degenerated knee articular cartilages to observed water protons. The mean values of T1 (T1) for control and degenerated rabbit knee cartilages were 1.87+/-0.15 (mean+/-SD, n=29) and 1.82+/-0.13 s (n=34), respectively. The mean values of water content (W(H2O)) for control and degenerated rabbit knee cartilages were 82.9+/-2.09 (n=26) and 83.1+/-2.57% (n=28), respectively. These values were not statistically different from each other. However, the mean values of T(IS) (T(IS)) for normal knee articular cartilage were significantly different from those for degenerated cartilage: (normal), T(IS) (f2=1.95 ppm)=2.46+/-0.62 s (n=28), T(IS) (f2=-4.00 ppm)=4.25+/-1.26 s (n=26); (degenerated), T(IS) (f2=1.95 ppm)=1.99+/-0.76s (n=34), T(IS) (f2=-4.00 ppm)=3.33+/-0.76 s (n=31). Obtained results may be attributed to the reported switchover from type II to type I collagen syntheses in osteoarthritic cartilage, resulting in broad collagen fibers. This specificity of cross-relaxation effect may prove useful in the noninvasive and pathophysiological evaluation of cartilage tissues in vivo.     

Cabbage poisoning in ruminants

A complaint of poor productivity was investigated in a herd of Jersey cattle and a small flock of Dorper sheep that had been fed cabbage for 5 to 6 months per year, over a number of years. During that time a number of lambs were lost as a result of swayback, some cows aborted, milk production was down, and although the farmer was an experienced inseminator, the conception rate in the Jerseys was low. After rectal examination and consulting the records, 26% of the cows were found to have been open for more than 150 d and 28% had been inseminated more than 3 times. The body condition of the cows ranged from poor to moderate, the hair coats were dull and some cows were anaemia. The young lambs had visibly enlarged thyroids. Haematological investigations revealed a typical Heinz body type haemolytic anaemic. In the cattle the anaemia appeared to be macrocytic, hypochromic and associated with thrombocytosis, while in the sheep it seemed to be normochromic and slightly microcytic. Plasma copper concentrations were severely depressed in all cases. Most thyroxine concentrations were within the normal range, although some were on the low side. Analysis of cabbage revealed a high sulphur content and marginally low copper and zinc levels. The main factor in cabbage which is responsible for poor animal performance, is the high sulphur content. High levels of this mineral exert detrimental effects, in order of priority, by elevating s-methyl cystine sulphoxide, diminishing the availability of copper and raising the glucosinolate content of the plant.     

Efficacies of KY62 against Leishmania amazonensis and Leishmania donovani in experimental murine cutaneous leishmaniasis and visceral leishmaniasis

Carcass measurements of 12th-rib fat thickness (CARCFAT), longissimus muscle area (CARCLMA), and weight (CARCWT) on 2,028 Brangus and Brangus-sired fed steers and heifers, as well as yearling weights (YWT) and ultrasound measures of 12th-rib fat thickness (USFAT) and longissimus muscle area (USLMA) on 3,583 Brangus bulls and heifers were analyzed to estimate genetic parameters. Data were analyzed using a six-trait animal model and an average information REML algorithm. The model included fixed effects for contemporary group and breed of dam, covariates for age at slaughter or measurement, and random animal and residual effects. Heritabilities for CARCFAT, CARCLMA, CARCWT, USFAT, USLMA, and YWT were .27+/-.05, .39+/-.05, .59+/-.06, .11+/-.03, .29+/-.04, and .40+/-.04, respectively. Genetic correlations between CARCFAT and USFAT, CARCLMA and USLMA, and CARCWT and YWT were .69+/-.18, .66+/-.14, and .61+/-.11, respectively. The favorable and moderately strong genetic correlations between carcass measurements and similar yearling breeding-animal ultrasound measurements indicate that such measurements of 12th-rib fat and longissimus muscle area are useful in predicting genetic values for carcass leanness and longissimus muscle area. Selection using yearling ultrasound measurements of breeding cattle should result in predictable genetic improvement for carcass characteristics. Inclusion of yearling ultrasound measurements for fat thickness and longissimus muscle area should enhance national cattle evaluation programs.     

Changes in crystallinity by sterilization and processing of ultrahigh molecular polyethylene used in endoprosthetics]

Research in animals shows that the levels of neuropathic pain expression is genetically associated with a characteristic response profile to sensory stimuli. The aim of the present investigation was to examine if pressure algometry can identify a specific pain sensitivity profile in patients with complex regional pain syndrome, Type I (reflex sympathetic dystrophy), and to distinguish complex regional pain syndromes from other chronic pain dysfunction syndromes. Pressure pain threshold and pain tolerance measured at the sternum in 17 patients with complex regional pain syndrome, Type I (reflex sympathetic dystrophy), were compared with values obtained in 13 patients suffering from other chronic pain dysfunction syndromes and in a control group of 24 pain-free volunteers. The pressure algometer consisted of a force displacement transducer with a 0.25 cm2 tip connected to a recorder. The rate of force application was 1 kg/0.25 cm2/s. The difference between threshold and tolerance was defined as the pain sensitivity range. Young patients with complex regional pain syndrome (<40 yr) demonstrated a significantly higher mean pain sensitivity range compared with young subjects who had chronic pain or who were pain-free. Mean threshold and tolerance values were significantly lower in patients with complex regional pain syndrome (2.7+/-1.0 kg (mean +/- standard deviation) and 5.4+/-2.0 kg, respectively) and in patients suffering from other chronic pain syndromes (2.6+/-1.1 and 4.6+/-1.7 kg) than in healthy subjects (5.4+/-2.3 and 8.4+/-2.6 kg). Women in the chronic pain group exhibited a significantly lower pressure pain threshold than all other subgroups. Regardless of group, women exhibited lower pressure pain tolerance than men. In conclusion, the study contained herein shows a specific pain sensitivity profile to experimental stimuli behavior in young patients with complex regional pain syndrome expressed by a large pressure pain sensitivity range, at a location away from the painful area. However, one single pressure pain measurement over the sternum is insufficient for differentiation of patients with complex regional pain syndrome from those with chronic pain because of intersubject variation.     

Selenite and selenium yeast as feed supplements for dairy cows

The availability of inorganic and organic forms of selenium to dairy cows was studied by giving 25 cows supplementary selenium for 9 months either as sodium selenite or as a selenium-containing yeast product. Group I (eight cows) received 3.0 mg selenium as sodium selenite daily, group II (nine cows) received 3.0 mg selenium as the selenium yeast product, and group III (eight cows) received 0.75 mg selenium as the selenium yeast product. The total selenium contents of the ration were 0.26-0.32 mg/kg feed dry matter for groups I and II, and 0.16-0.18 mg/kg for group III. The supplement of 0.75 mg selenium daily from the yeast product maintained the selenium concentrations of whole blood and milk at the same levels as 3.0 mg selenium as sodium selenite, and 3.0 mg selenium from the yeast product increased the selenium concentration of whole blood by approximately equal to 40% and that of milk by approximately equal to 100%. The activity of glutathione peroxidase in erythrocytes of the group given selenite was not significantly different from that in either of the groups given the yeast product. The concentrations of selenium in the tissues of two cows from each group were marginal to adequate, and there was a trend for the concentrations to be higher in the tissues of the cows supplemented with the yeast product.     

Selenium regulation of hepatic heme metabolism: induction of delta-aminolevulinate synthase and heme oxygenase

Selenium was found to be a novel regulator of cellular heme methabolism in that the element induced both the mitochondrial enzyme delta-aminolevulinate synthase [succinyl-CoA:glycine C-succinyltransferase (decarboxylating); EC 2-3-1-37] and the microsomal enzyme heme oxygenase [heme, hydrogen-donor:oxygen oxidoreductase(alpha-methene-oxidizing, hydroxylating); EC 1-14-99-3] in liver. The effect of selenium on these enzyme activities was prompt, reaching a maximum within 2 hr after a single injection. Other changes in parameters of hepatic heme metabolism occurred after administration of the element. Thirty minutes after injection the cellular content of heme was significantly increased; however, this value slightly decreased below control values within 2 hr, coinciding with the period of rapid induction of heme oxygenase. At later peroids heme content returned to normal values. Selenium treatment caused only a slight decrease in microsomal cytochrome P-450 content. However, drug-metabolizing activity was severely inhibited by higher doses of the element. Unlike other inducers of delta-aminolevulinate synthase, which as a rule are also porphyrinogenic agents, selenium induction of this enzyme was not accompanied by an increase in the cellular content of prophyrins. When rats were pretreated with selenium 90 min before administration of heme, a potent inhibitor of delta-aminolevulinate synthase production, the inhibitory effect of heme of formation of this mitochondrial enzyme was completely blocked. Selenium, at high concentrations in vitro, was inhibitory to delta-aminolevulinate synthase activity. It is postulated that selenium may not be a direct inducer of heme oxygenase as is the case with trace metals such as cobalt, but may mediate an increase in heme oxygenase through increased production and cellular availability of "free" heme, which results from the increased heme synthetic activity of hematocytes. Subsequently, the increased heme oxygenase activity is in turn responsible for the lack of increase in the microsomal heme content, thus maintaining heme levels at normal values despite the highly increased activities of both heme oxygenase and delta-aminolevulinate synthase. It is further suggested that the increase in delta-aminolevulinate synthase activity is not due to a decreased rate of enzyme degradation or an activation of preformed enzyme, but to increased rate of synthesis of enzyme protein. Although selenium in trace amounts has been postulated to be involved in microsomal electron transfer process, the data from this study indicate that excess selenium can substantially inhibit microsomal drug metabolism.