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Biomedical subjects

L Krook

Publications and source records attributed to L Krook.

At least 19 recordsLinked to original sources

Response to dietary fat and cholesterol in young adult boars genetically selected for high or low plasma cholesterol.

Twenty-eight young adult boars (age 7 to 8 mo) genetically selected for four generations for high (HG) or low (LG) plasma cholesterol were studied to assess dietary and genetic effects and their interactions on cholesterol metabolism. Boars within a genetic group were paired according to their plasma cholesterol concentration at 8 wk of age and were fed for 15 wk (2.7 kg/d) one of two diets (16.5% fat and 1,156 mg of cholesterol/kg diet, HD; or 3.1% fat and 0 cholesterol diet, LD) in a 2 x 2 factorial arrangement. Plasma total cholesterol (P < .01) and HDL-cholesterol (P < .01) concentrations were higher in boars fed HS (P < .01) and in HG boars (P < .01). There was a trend toward a diet x genotype interaction for plasma HDL-cholesterol (P < .06). Plasma insulin concentration tended to be lower in boars fed HD (P < .09) or HG boars (P < .10). There was a diet x genotype interaction for plasma glucagon (P < .04) concentration and a trend toward an interaction for insulin (P < .07). After 15 wk, all boars were killed by electrocution and exsanguination and measurements were taken. Backfat thickness was greater (P < .01) and carcass length (P < .01) and weights of the four lean cuts (P < .02) were lower in LG than in HG boars. No microscopic atherosclerotic plaques were observed in aorta or coronary arteries. Cholesterol concentration in subcutaneous fat was lower (P < .04) in LG boars, suggesting that cholesterol content of depot fat can be reduced by genetic selection in swine.

Adipose Tissue

Effects of exercise and polysulfated glycosaminoglycan on repair of articular cartilage defects in the equine carpus.

Our aim was to determine if mild to moderate postoperative exercise and intra-articular polysulfated glycosaminoglycan result in improved repair of large, experimentally induced osteochondral defects in a weight-bearing surface of equine joints. Arthroscopic debridement was used to produce full-thickness defects in a weight-bearing area of the radial carpal bones in 18 ponies. The ponies were randomly assigned to two groups balanced for age: nine animals in the exercise and nine in the no exercise group. Six ponies in each group were medicated weekly for 5 weeks with an intra-articular injection of polysulfated glycosaminoglycan in one middle carpal joint beginning at the time of operation. Walking (twice daily) was begun 6 days postoperatively, and by the twelfth week postoperatively the ponies were trotting for 25 min and walking for 15 min twice daily. At the time of the ponies' death, 17 weeks postoperatively, each defect had an average of 50-75% coverage with repair tissue. Exercised, medicated joints had a significantly smaller area of coverage with repair tissue than exercised, nonmedicated joints. Cartilaginous repair tissue from exercised ponies contained significantly more glycosaminoglycan and type-II collagen (r = 0.53, p < 0.05). The ratio of hydroxylysine to hydroxyproline was significantly lower and the ratio of collagen content to total protein was significantly higher in the repair tissue of medicated joints than in the repair tissue of nonmedicated joints; this is consistent with the presence of less type-II collagen in the repair tissue in medicated joints. We concluded that postoperative exercise was beneficial and that the immediate postoperative use of intra-articular polysulfated glycosaminoglycan was detrimental to the development of cartilaginous repair tissue in large osteochondral defects of equine joints.

Amino Acids

Studies of collagen in bone and dentin matrix of a Columbian mammoth (late Pleistocene) of central Utah.

A Columbian mammoth, Mammuthus columbi, was excavated at an elevation of 9000 feet in Huntington Canyon, Emery County, Utah. Radiocarbon dates on the skeleton indicated death approximately 11,200 years ago. The skeleton was removed from postglacial, Late Quaternary, lake sediments deposited as glacial runoff approximately 9500 years ago. The bones and teeth were especially well preserved in a saturated lake bed. After excavation the bones and teeth were preserved by controlled desiccation, without hardeners, over a period of 9 months. Microradiography, light and electron microscopy, medium and high angle X-ray diffraction, amino acid analysis and cyanogen bromide peptide mapping were undertaken to evaluate the packing, organization, and preservation of collagen in bone and dentin of this mammoth. Microradiography and light microscopy showed that the bone consisted of especially well preserved compact and trabecular bone, and electron microscopy of demineralized bone and tusk showed that the matrix consisted of lamellae of densely packed cylindrical collagen fibrils. Cell remnants with intact nuclei, with or without a nucleolus, as well as variable lengths of plasma membrane were occasionally present on the surface of bony trabecula. Remnants of odontoblast processes were present in some dentin tubules. High and low angle X-ray diffraction demonstrated that the demineralized matrix contained native collagen molecules and amino acid analysis showed that the composition was comparable to that of type I collagen. Cyanogen bromide peptide mapping indicated that the major peptides of type I collagen were present and had the same electrophoretic mobility as that of type I collagen of demineralized Asian elephant bone and rat tail tendon.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

Immunohistochemical localization of a calcium pump and calbindin-D28k in the oviduct of the laying hen.

The localization of a plasma membrane calcium pump in the oviduct of the laying hen was investigated by immunohistochemical techniques, utilizing a monoclonal antibody (5F10) produced against the human erythrocyte calcium pump. This antibody was shown to react with an epitope of the pump in oviductal tissue, and prominent staining was observed on the microvilli of the tubular gland cells of the hen shell gland (uterus) and the isthmus. The Ca2+ pump was not detectable in the infundibulum or the magnum. Calbindin-D28k, also localized by immunohistochemical means, was observed to be present in the tubular gland cells of the shell gland and the distal isthmus (adjacent to shell gland) but not in either the proximal isthmus (adjacent to the magnum), the magnum or the infundibulum. The localization of the Ca2+ pump in the oviduct corresponds to known sites of mineral deposition during egg shell formation. The distribution of calbindin-D28k differed, co-localizing with the Ca2+ pump in the shell gland and distal isthmus but not in the proximal isthmus. This might reflect a greater rate of active Ca2+ secretion in the distal isthmus and shell gland as compared to the proximal isthmus.

Animals

Osteochondrosis in fetuses of ewes overfed calcium.

Ewes were fed ad libitum (up to maximum of 2.5 kg/day) a complete feed containing either 1.52% calcium (High Ca) or 0.59% calcium (Normal Ca) on a dry matter basis from day 50 of pregnancy, and the fetuses were removed at 133-135 days. Thyroid C cells, identified by indirect immunofluorescence, were more numerous (P less than 0.001) and plasma levels of 24,25-dihydroxycholecalciferol [24,25(OH)2D] were higher (P less than 0.09) in fetuses of High Ca ewes. These fetuses also had retarded cartilage differentiation in the proximal humeral epiphysis and metaphysis as well as transverse trabeculation in the epiphysis. These entities are two of the hallmarks of osteochondrosis. It was shown that feeding high dietary calcium to pregnant ewes caused osteochondrosis in their fetuses. Hypercalcitoninism and/or an adverse effect of supraphysiological levels of 24,25-dihydroxycholecalciferol may have been contributory to the skeletal abnormalities.

24,25-Dihydroxyvitamin D 3

Prolonged gestation in a Holstein cow: adenohypophyseal aplasia and skeletal pathology in the offspring.

A Holstein fetus was delivered by Caesarean section at a gestational age of 441 days. The pituitary pars distalis was aplastic and the adrenal and thyroid glands were severely hypoplastic. Arrested or retarded cartilage cell maturation resulted in absence or minimal development of epiphyseal ossification centers, delayed ossification of carpal bones, and arrest of longitudinal growth of bones. The pathophysiology of prolonged gestation and of skeletal pathology is discussed.

Adrenal Glands

The effects of phenylbutazone on the intestinal mucosa of the horse: a morphological, ultrastructural and biochemical study.

Phenylbutazone, a non-steroidal anti-inflammatory drug known to produce intestinal erosions, was administered intravenously (13.46 mg/kg bodyweight) to 12 horses which were killed after 24, 48, 72 and 96 h. Eight untreated horses served as controls. Annular erosions in the duodenum and mucosal necrosis in the colon were seen after 48 h which progressed in severity. The erosions were characterised by sloughing of the surface epithelium, subepithelial cleft and bleb formation, necrosis of the lamina propria, degeneration of the walls of subsurface capillaries and microthrombosis. Large numbers of neutrophils with abundant fibrin and cellular debris were present at the erosion sites. Ultrastructurally, there was swelling of the endothelium of capillaries and small vessels, and of pericyte and smooth muscle cytoplasm in arterioles. In capillaries and post capillary venules, the endothelium ranged from swollen to lysed and necrotic. Extensive extravasation of erythrocytes and oedema were seen. These lesions were not seen in the control horses. Phenylbutazone produces a microvascular injury associated with the formation of duodenal and colonic erosions in horses. The duodenal and colonic mucosa were assayed at 48 and 96 h for prostacyclin and PGE2. There was no statistically significant difference between prostaglandin levels in the mucosa of control and treated horses. It was concluded that there was no correlation between mucosal prostaglandin levels and intestinal erosions after 48 h.

Animals

The effects of phenylbutazone on the morphology and prostaglandin concentrations of the pyloric mucosa of the equine stomach.

Phenylbutazone, a nonsteroidal anti-inflammatory drug known to produce gastric ulcers, was administered intravenously (13.46 mg/kg body weight) daily to 12 horses. Horses were euthanatized daily after 24, 48, 72, and 96 hours following the initial injection. Eight untreated horses served as controls. Small multifocal pyloric erosions were seen after 24 hours and then progressed in severity over time. The erosions were characterized by sloughing of the surface epithelium, subepithelial bleb formation, necrosis of the lamina propria, degeneration of the walls of subsurface capillaries, and microthrombosis of the capillaries of the pyloric mucosa. Large numbers of neutrophils with abundant fibrin and cellular debris were present at the erosion sites. Eroded pyloric mucosa and adjacent macroscopically intact mucosa were examined ultrastructurally. In both the macroscopically eroded mucosa and multifocally in the adjacent macroscopically uneroded mucosa, there was cellular swelling of the endothelium, pericytes, and smooth muscle cells of arterioles. In capillaries and post-capillary venules, the endothelium ranged from swollen to lysed and necrotic. Extensive extravasation of erythrocytes and edema were seen. These lesions were not seen in the control horses. Phenylbutazone produces a microvascular injury that is associated with the formation of pyloric erosions in horses. The pyloric mucosa of six horses was assayed for prostacyclin and prostaglandin E2 at 48 and 96 hours following the initial injection. There was no statistically significant difference between prostaglandin concentrations in the mucosa of control and treated horses. It was concluded that there was little correlation between pyloric mucosal prostaglandin concentrations and pyloric erosions after 48 hours.

Animals

An experimental model of chronic renal disease in dogs by infusion of microspheres into the renal arterial circulation.

The feasibility of renal arterial infusion of nonbiodegradable microspheres as a model of chronic renal disease in dogs was evaluated. Resin-coated, styrene-divinyl benzene copolymer microspheres were infused into the kidneys of healthy adult Beagles by direct injections of both renal arteries in a single surgical procedure. Injections of 25-microns diameter microspheres had minimal effect on either the clinical status or serum values of the dogs. Histologic examination revealed the majority of the microspheres lodged within the capillary beds of the glomeruli, and little change to the kidneys. However, injections of 50-microns diameter microspheres caused significant increases in serum concentrations of urea nitrogen and creatinine. Histologically, the larger microspheres obstructed afferent arterioles and small arteries, which caused diffuse glomerular necrosis and nephron damage. With doses ranging from 1 to 3 million microspheres/dog, a correlation between the quantity of microspheres injected and severity of renal damage was observed. The optimal dose for producing a model of moderate renal disease was determined to be 1.8 million microspheres/dog (0.9 million microspheres/kidney). During long-term studies, microsphere-injected dogs fed a moderately restricted protein ration remained relatively azotemic, compared with control dogs on the identical ration. During the 5-month postsurgical period, the serum urea nitrogen concentration averaged 18.41 +/- 1.59 mg/dl (mean +/- SE) for the microsphere-injected dogs vs 9.31 +/- 0.38 for the control dogs (P less than 0.001). Similarly, the mean serum creatinine value was significantly higher (P = 0.020) for the microsphere-injected dogs, compared with the controls (1.23 +/- 0.12 mg/dl vs 0.94 +/- 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Endocrine and histologic correlates of the dynamics of the metacarpal growth plate in growing rams.

The objective was to study control of mature size by characterizing metacarpal growth plate closure in relation to relevant bone growth-regulating hormones in two breeds exhibiting distinct differences in mature frame size. Thirty-four Suffolk and 34 Dorset ram lambs were slaughtered in pairs within breed at birth, weaning and monthly intervals until 420 d and then bimonthly to 600 d. Plasma growth hormone was depressed to undetectable levels due to the high-energy, ad libitum-fed diet. Plasma insulin-like growth factor-I (IGF-I) rose over the growth period from 116 ng/ml (newborn Suffolk) to a high of 451 ng/ml (420-d Dorset); it appeared to peak at approximately 400 d and then declined to a stable level. Dorsets consistently exhibited higher IGF-I levels. The thyroid hormones exhibited no apparent age association. An age-associated rise was detected for testosterone, but not for estradiol. Mature metacarpal lengths were estimated to be 147.2 and 127.4 mm for Suffolks and Dorsets, respectively. Ninety-five percent of mature length was attained in Suffolks by 226 d and in Dorsets by 165 d. Growth plates, however, did not begin to appear closed until 390 d and closure was not complete in all animals until 480 d, suggesting that metacarpal growth rate was dissociated temporally from growth plate closure. Although growth plate closure likely is controlled by the endocrine system, there were no apparent relationships between circulating hormones and growth plate width, age at closure or zonal divisions within the growth plate, suggesting that the growth plate experiences a very different hormonal environment than what can be measured in the circulating blood.

Animals

Dietary calcium and metacarpal growth in ewes.

The effects of excess dietary calcium on bone growth were quantified in 44 ewes fed ad libitum diets that contained one of four levels of dietary calcium (0.37, 0.56, 1.13 and 1.80%) and 0.42% phosphorus. Animals were slaughtered at one of six ages, circulating concentrations of hormones and minerals were measured and bone morphometry was evaluated. None of the diets impaired normal bone growth of the metacarpal as evaluated by overall length, cortical index and growth plate width. Circulating plasma concentrations of calcium and gastrin increased as dietary calcium levels increased, but all values were within the normal range for sheep. Plasma phosphorus was unaffected by the level of dietary calcium. Diet had no affect on T3, T4 or estradiol-17 beta. Age significantly (P less than 0.05) affected the metacarpal length, growth plate width and circulating calcium and phosphorus. The metacarpal in these ewes was 95% of mature length by 172 d of age. Attainment of mature length preceded growth plate closure by slightly over 300 d. These results demonstrate that elevated dietary calcium levels do not adversely influence bone growth and that the presence of an intact growth plate does not infer that further bone growth will occur.

Age Factors

The granular layer of Tomes in experimental caries in rats.

In examination of ground sections of human third maxillary molar teeth, the granular layer of Tomes was shown to consist of expansion of dentinal tubules. The microradiographic density was decreased well inside the layer. It was postulated that the findings were expressions of dentin resorption. The theory was tested experimentally in rats fed a cariogenic diet with low calcium and phosphorus. The morphology of mandibular molar teeth was studied by electron probe microanalysis and by microradiography. It was concluded that the primary event in cariogenesis was an expansion of peripheral dentinal tubules with formation of confluent microcavities and, thus, an unmasking of the granular layer of Tomes, which normally is only potential. A subsequent loss of mineral density in the outer enamel eventually caused breakdown of the outer enamel with caries visible from the surface. The loss of density within the enamel was postulated to result from interruption of the normal flux of nutrients, metabolites and ions between the dentin and enamel. Whereas an increase in dietary calcium and phosphorus delayed and reduced significantly, but did not prevent cariogenesis, it supported the theory that experimental caries in rats is a metabolic disease with the peripheral dentin the primary target.

Adult

Annual skeletal changes in the little brown bat, Myotis lucifugus lucifugus, with particular reference to pregnancy and lactation.

Studies of bone from summer-active little brown bats, Myotis lucifugus lucifugus, have demonstrated sex differences in the renewal of skeletal mineral reserves following spring-arousal from hibernation. Patterns of bone remodeling in both sexes of bats indicate that new bone formation does not occur during hibernation: All new bone formation occurs during the summer-active season. Results show that a short period of time elapses after hibernation before the initial demands of a large fetus and rapidly growing neonate are expressed on maternal skeletal reserves. Bone loss in summer-active females was associated with pregnancy and lactation, whereas summer-active males did not show evidence of bone loss but, instead, uninterrupted bone accretion throughout the summer-active season. Osteoclasts and bone-forming osteoblasts, absent during the hibernation period, reappeared on bone surfaces following spring-arousal from hibernation. There was no apparent increase in osteoclast numbers or activity during lactation but resorption cavities were found in deep cortical lamellae distant from bone surfaces. The increase in bone resorption in lactating bats appeared to be by osteocytic osteolysis, suggesting that it might be a significant mechanism of bone/calcium regulation in this hibernating mammal throughout the year.

Animals

Morphology of thyroid C-cells and parathyroid glands in summer-active little brown bats, Myotis lucifugus lucifugus, with particular reference to pregnancy and lactation.

Morphological studies of thyroid C-cells and morphometric analyses of parathyroid glands in summer-active little brown bats indicated concomitant regulatory endocrine functions correlating with bone remodeling. C-cells apparently maintain maximal activity throughout the summer-active period in all bats. However, the hyperactivity of the parathyroid glands in summer-active female bats can be correlated with the maintenance of plasma calcium concentrations during lactation, when the female skeleton undergoes a period of bone demineralization. In summer-active male bats, which did not lose bone, the parathyroid glands did not show morphological evidence of hyperactivity; instead they were found to exhibit moderate parathyroid activity.

Animals

Fluoride intoxication in dairy calves.

Chronic fluoride intoxication in dairy cattle, caused by feeding fluoride contaminated commercial feed, was previously described in a dairy herd. Dental fluorosis and a catastrophic decrease in milk yield were the foremost findings. In calves born to the fluoride intoxicated cows, congenital fluorosis was manifested by brown discoloration of enamel, enamel hypoplasia, brown mottling of bone, severe retardation of cartilage cell differentiation, atrophy of osteoblasts, osteopenia, atrophy of bone marrow cells, serous atrophy of bone marrow fat and severely stunted growth.

Animal Feed