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1

1935-, Bock K. W., ed. Hepatic metabolism and disposition of endo- and xenobiotics: Proceedings of the 57th Falk Symposium held in Freiburg-im-Breisgau, Germany, October 8-10, 1990. Dordrecht: Kluwer Academic Publishers, 1991.

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2

Ahlström, Marie. Cytochrome P450, metabolism and inhibition: Computational and experimental studies. Göteborg: Göteborg University, 2007.

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3

Cozza, Kelly L. Quick guide to the Cytochrome P450 system: Overview of drug interaction principles. Washington, DC: American Psychiatric Pub., 2002.

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4

S, Lee Jae, Obach R. Scott, and Fisher Michael B, eds. Drug metabolizing enzymes: Cytochrome P450 and other enzymes in drug discovery and development. Lausanne, Switzerland: FontisMedia SA, 2003.

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5

Cozza, Kelly L. Concise guide to the cytochrome P450 system: Drug interaction principles for medical practice. Washington, DC: American Psychiatric Pub., 2001.

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6

Emel, Arinç, Schenkman John B, Hodgson Ernest 1932-, and NATO Advanced Study Institute on Molecular Aspects of Drug Metabolizing Enzymes (1993 : Kus̜adası, Turkey), eds. Molecular aspects of oxidative drug metabolizing enzymes: Their significance in environmental toxicology, chemical carcinogenesis, and health. Berlin: Springer-Verlag, 1995.

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7

B, Matchar David, United States. Agency for Healthcare Research and Quality., and Duke University Evidence-based Practice Center., eds. Testing for cytochrome P450 polymorphisms in adults with non-psychotic depression treated with selective serotonin reuptake inhibitors (SSRIs). Rockville, MD: Agency for Healthcare Research and Quality, 2007.

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8

(Editor), Karl-Walter Bock, W. Gerok (Editor), and S. Matern (Editor), eds. Hepatic Metabolism and Disposition of Endo- and Xenobiotics (Falk Symposium). Springer, 1991.

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9

Drug Metabolism Enzymes. Marcel Dekker, 2003.

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10

Neil B., M.d. Sandson. Drug Interactions Casebook: The Cytochrome P450 System and Beyond. American Psychiatric Publishing, 2003.

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11

Armstrong, Neil, and Alison M. McManus. Aerobic fitness. Edited by Neil Armstrong and Willem van Mechelen. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198757672.003.0012.

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Peak oxygen uptake (V̇O2) is the criterion measure of young people's aerobic fitness, and blood lactate accumulation (BLA) is a useful indicator of aerobic fitness with reference to the ability to sustain submaximal exercise. In sport and in everyday life it is the pulmonary (p)V̇O2 kinetics of the non-steady state which best assess the integrated responses of the oxygen delivery system and the metabolic demands of the exercising muscle. Data analysis using sophisticated modelling techniques has enhanced understanding of sexual dimorphism and the independent effects of chronological age, body size, and biological maturity on peak V̇O2 and BLA. The extant data on young people's pV̇O2 kinetic responses to step changes in exercise intensity are sparse, but describe intriguing chronological age and sex differences across exercise domains. However, independent effects of biological maturation are yet to be revealed.
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12

Ruckpaul, Klaus. Medicinal Implications in Cytochrome P-450 Catalyzed Biotransformations (Frontiers in Biotransformation, Vol 8). Vch Pub, 1993.

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13

Lee, Jae, R. Scott Obach, and Michael B. Fisher. Drug Metabolizing Enzymes: Cytochrome P450 and Other Enzymes in Drug Discovery and Development. Taylor & Francis Group, 2003.

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14

Lee, Jae, R. Scott Obach, and Michael B. Fisher. Drug Metabolizing Enzymes: Cytochrome P450 and Other Enzymes in Drug Discovery and Development. Taylor & Francis Group, 2003.

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15

(Editor), C. R. Elecombe, ed. Microsomes and Drug Oxidations: Proceedings of the 6th International Symposium (Microsomes & Drug Oxidations). Taylor & Francis Group, 1985.

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16

P450 Chem Carcinogen (Gann Monograph on Cancer Research). Plenum Press, 1985.

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17

Relationships between structure and function of Cytochrome P-450: Experiments, calculations, models. Berlin: Akademie Verlag, 1992.

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18

Cozza, Kelly L., C. M. D. Armstrong Scott, and R. M. D. Oesterheld Jessica. Concise Guide to Drug Interaction Principles for Medical Practice: Cytochrome P450s, Ugts, P-Glycoproteins (Concise Guides). 2nd ed. American Psychiatric Publishing, Inc., 2003.

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19

MD, Kelly L. Cozza, and Scott C. Armstrong MD. Concise Guide to the Cytochrome P450 System: Drug Interaction Guidelines for Medical Practice. 4th ed. American Psychiatric Association, 2001.

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20

Cohen, Jeffrey A., Justin J. Mowchun, Victoria H. Lawson, and Nathaniel M. Robbins. A 68-Year-Old Female with Progressive Pain and Weakness. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190491901.003.0027.

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Statin myopathy can occur at anytime during use. This chapter discusses an approach to diagnosis, and emphasizes management considerations, including awareness of statin metabolism by the cytochrome P-450 system. A statin must be discontinued in any patient with evidence of myopathy or myalgias. A muscle biopsy should be done in cases that do not improve clinically or by creatine kinase level. It is important to note that there are cases of apparent statin myopathy which transform into a chronic autoimmune inflammatory myopathy. Antibodies to hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase have recently been identified in the majority of patients with autoimmune statin myopathy and this test may give further weight to treat with immunotherapy.
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21

Schenkman, John B. Molecular Aspects of Oxidative Drug Metabolizing Enzymes: Their Significance in Environmental Toxicology, Chemical Carcinogenesis and Health (Nato a S I Series Series H, Cell Biology). Springer-Verlag Telos, 1995.

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22

Arinc, Emel, John B. Schenkman, and Ernest Hodgson. Molecular Aspects of Oxidative Drug Metabolizing Enzymes: Their Significance in Environmental Toxicology, Chemical Carcinogenesis and Health. Springer London, Limited, 2013.

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23

Testing for cytochrome P450 polymorphisms in adults with non-psychotic depression treated with selective serotonin reuptake inhibitors (SSRIs). Rockville, MD: AHRQ, 2007.

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24

Skiba, Grzegorz. Fizjologiczne, żywieniowe i genetyczne uwarunkowania właściwości kości rosnących świń. The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 2020. http://dx.doi.org/10.22358/mono_gs_2020.

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Bones are multifunctional passive organs of movement that supports soft tissue and directly attached muscles. They also protect internal organs and are a reserve of calcium, phosphorus and magnesium. Each bone is covered with periosteum, and the adjacent bone surfaces are covered by articular cartilage. Histologically, the bone is an organ composed of many different tissues. The main component is bone tissue (cortical and spongy) composed of a set of bone cells and intercellular substance (mineral and organic), it also contains fat, hematopoietic (bone marrow) and cartilaginous tissue. Bones are a tissue that even in adult life retains the ability to change shape and structure depending on changes in their mechanical and hormonal environment, as well as self-renewal and repair capabilities. This process is called bone turnover. The basic processes of bone turnover are: • bone modeling (incessantly changes in bone shape during individual growth) following resorption and tissue formation at various locations (e.g. bone marrow formation) to increase mass and skeletal morphology. This process occurs in the bones of growing individuals and stops after reaching puberty • bone remodeling (processes involve in maintaining bone tissue by resorbing and replacing old bone tissue with new tissue in the same place, e.g. repairing micro fractures). It is a process involving the removal and internal remodeling of existing bone and is responsible for maintaining tissue mass and architecture of mature bones. Bone turnover is regulated by two types of transformation: • osteoclastogenesis, i.e. formation of cells responsible for bone resorption • osteoblastogenesis, i.e. formation of cells responsible for bone formation (bone matrix synthesis and mineralization) Bone maturity can be defined as the completion of basic structural development and mineralization leading to maximum mass and optimal mechanical strength. The highest rate of increase in pig bone mass is observed in the first twelve weeks after birth. This period of growth is considered crucial for optimizing the growth of the skeleton of pigs, because the degree of bone mineralization in later life stages (adulthood) depends largely on the amount of bone minerals accumulated in the early stages of their growth. The development of the technique allows to determine the condition of the skeletal system (or individual bones) in living animals by methods used in human medicine, or after their slaughter. For in vivo determination of bone properties, Abstract 10 double energy X-ray absorptiometry or computed tomography scanning techniques are used. Both methods allow the quantification of mineral content and bone mineral density. The most important property from a practical point of view is the bone’s bending strength, which is directly determined by the maximum bending force. The most important factors affecting bone strength are: • age (growth period), • gender and the associated hormonal balance, • genotype and modification of genes responsible for bone growth • chemical composition of the body (protein and fat content, and the proportion between these components), • physical activity and related bone load, • nutritional factors: – protein intake influencing synthesis of organic matrix of bone, – content of minerals in the feed (CA, P, Zn, Ca/P, Mg, Mn, Na, Cl, K, Cu ratio) influencing synthesis of the inorganic matrix of bone, – mineral/protein ratio in the diet (Ca/protein, P/protein, Zn/protein) – feed energy concentration, – energy source (content of saturated fatty acids - SFA, content of polyun saturated fatty acids - PUFA, in particular ALA, EPA, DPA, DHA), – feed additives, in particular: enzymes (e.g. phytase releasing of minerals bounded in phytin complexes), probiotics and prebiotics (e.g. inulin improving the function of the digestive tract by increasing absorption of nutrients), – vitamin content that regulate metabolism and biochemical changes occurring in bone tissue (e.g. vitamin D3, B6, C and K). This study was based on the results of research experiments from available literature, and studies on growing pigs carried out at the Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences. The tests were performed in total on 300 pigs of Duroc, Pietrain, Puławska breeds, line 990 and hybrids (Great White × Duroc, Great White × Landrace), PIC pigs, slaughtered at different body weight during the growth period from 15 to 130 kg. Bones for biomechanical tests were collected after slaughter from each pig. Their length, mass and volume were determined. Based on these measurements, the specific weight (density, g/cm3) was calculated. Then each bone was cut in the middle of the shaft and the outer and inner diameters were measured both horizontally and vertically. Based on these measurements, the following indicators were calculated: • cortical thickness, • cortical surface, • cortical index. Abstract 11 Bone strength was tested by a three-point bending test. The obtained data enabled the determination of: • bending force (the magnitude of the maximum force at which disintegration and disruption of bone structure occurs), • strength (the amount of maximum force needed to break/crack of bone), • stiffness (quotient of the force acting on the bone and the amount of displacement occurring under the influence of this force). Investigation of changes in physical and biomechanical features of bones during growth was performed on pigs of the synthetic 990 line growing from 15 to 130 kg body weight. The animals were slaughtered successively at a body weight of 15, 30, 40, 50, 70, 90, 110 and 130 kg. After slaughter, the following bones were separated from the right half-carcass: humerus, 3rd and 4th metatarsal bone, femur, tibia and fibula as well as 3rd and 4th metatarsal bone. The features of bones were determined using methods described in the methodology. Describing bone growth with the Gompertz equation, it was found that the earliest slowdown of bone growth curve was observed for metacarpal and metatarsal bones. This means that these bones matured the most quickly. The established data also indicate that the rib is the slowest maturing bone. The femur, humerus, tibia and fibula were between the values of these features for the metatarsal, metacarpal and rib bones. The rate of increase in bone mass and length differed significantly between the examined bones, but in all cases it was lower (coefficient b <1) than the growth rate of the whole body of the animal. The fastest growth rate was estimated for the rib mass (coefficient b = 0.93). Among the long bones, the humerus (coefficient b = 0.81) was characterized by the fastest rate of weight gain, however femur the smallest (coefficient b = 0.71). The lowest rate of bone mass increase was observed in the foot bones, with the metacarpal bones having a slightly higher value of coefficient b than the metatarsal bones (0.67 vs 0.62). The third bone had a lower growth rate than the fourth bone, regardless of whether they were metatarsal or metacarpal. The value of the bending force increased as the animals grew. Regardless of the growth point tested, the highest values were observed for the humerus, tibia and femur, smaller for the metatarsal and metacarpal bone, and the lowest for the fibula and rib. The rate of change in the value of this indicator increased at a similar rate as the body weight changes of the animals in the case of the fibula and the fourth metacarpal bone (b value = 0.98), and more slowly in the case of the metatarsal bone, the third metacarpal bone, and the tibia bone (values of the b ratio 0.81–0.85), and the slowest femur, humerus and rib (value of b = 0.60–0.66). Bone stiffness increased as animals grew. Regardless of the growth point tested, the highest values were observed for the humerus, tibia and femur, smaller for the metatarsal and metacarpal bone, and the lowest for the fibula and rib. Abstract 12 The rate of change in the value of this indicator changed at a faster rate than the increase in weight of pigs in the case of metacarpal and metatarsal bones (coefficient b = 1.01–1.22), slightly slower in the case of fibula (coefficient b = 0.92), definitely slower in the case of the tibia (b = 0.73), ribs (b = 0.66), femur (b = 0.59) and humerus (b = 0.50). Bone strength increased as animals grew. Regardless of the growth point tested, bone strength was as follows femur > tibia > humerus > 4 metacarpal> 3 metacarpal> 3 metatarsal > 4 metatarsal > rib> fibula. The rate of increase in strength of all examined bones was greater than the rate of weight gain of pigs (value of the coefficient b = 2.04–3.26). As the animals grew, the bone density increased. However, the growth rate of this indicator for the majority of bones was slower than the rate of weight gain (the value of the coefficient b ranged from 0.37 – humerus to 0.84 – fibula). The exception was the rib, whose density increased at a similar pace increasing the body weight of animals (value of the coefficient b = 0.97). The study on the influence of the breed and the feeding intensity on bone characteristics (physical and biomechanical) was performed on pigs of the breeds Duroc, Pietrain, and synthetic 990 during a growth period of 15 to 70 kg body weight. Animals were fed ad libitum or dosed system. After slaughter at a body weight of 70 kg, three bones were taken from the right half-carcass: femur, three metatarsal, and three metacarpal and subjected to the determinations described in the methodology. The weight of bones of animals fed aa libitum was significantly lower than in pigs fed restrictively All bones of Duroc breed were significantly heavier and longer than Pietrain and 990 pig bones. The average values of bending force for the examined bones took the following order: III metatarsal bone (63.5 kg) <III metacarpal bone (77.9 kg) <femur (271.5 kg). The feeding system and breed of pigs had no significant effect on the value of this indicator. The average values of the bones strength took the following order: III metatarsal bone (92.6 kg) <III metacarpal (107.2 kg) <femur (353.1 kg). Feeding intensity and breed of animals had no significant effect on the value of this feature of the bones tested. The average bone density took the following order: femur (1.23 g/cm3) <III metatarsal bone (1.26 g/cm3) <III metacarpal bone (1.34 g / cm3). The density of bones of animals fed aa libitum was higher (P<0.01) than in animals fed with a dosing system. The density of examined bones within the breeds took the following order: Pietrain race> line 990> Duroc race. The differences between the “extreme” breeds were: 7.2% (III metatarsal bone), 8.3% (III metacarpal bone), 8.4% (femur). Abstract 13 The average bone stiffness took the following order: III metatarsal bone (35.1 kg/mm) <III metacarpus (41.5 kg/mm) <femur (60.5 kg/mm). This indicator did not differ between the groups of pigs fed at different intensity, except for the metacarpal bone, which was more stiffer in pigs fed aa libitum (P<0.05). The femur of animals fed ad libitum showed a tendency (P<0.09) to be more stiffer and a force of 4.5 kg required for its displacement by 1 mm. Breed differences in stiffness were found for the femur (P <0.05) and III metacarpal bone (P <0.05). For femur, the highest value of this indicator was found in Pietrain pigs (64.5 kg/mm), lower in pigs of 990 line (61.6 kg/mm) and the lowest in Duroc pigs (55.3 kg/mm). In turn, the 3rd metacarpal bone of Duroc and Pietrain pigs had similar stiffness (39.0 and 40.0 kg/mm respectively) and was smaller than that of line 990 pigs (45.4 kg/mm). The thickness of the cortical bone layer took the following order: III metatarsal bone (2.25 mm) <III metacarpal bone (2.41 mm) <femur (5.12 mm). The feeding system did not affect this indicator. Breed differences (P <0.05) for this trait were found only for the femur bone: Duroc (5.42 mm)> line 990 (5.13 mm)> Pietrain (4.81 mm). The cross sectional area of the examined bones was arranged in the following order: III metatarsal bone (84 mm2) <III metacarpal bone (90 mm2) <femur (286 mm2). The feeding system had no effect on the value of this bone trait, with the exception of the femur, which in animals fed the dosing system was 4.7% higher (P<0.05) than in pigs fed ad libitum. Breed differences (P<0.01) in the coross sectional area were found only in femur and III metatarsal bone. The value of this indicator was the highest in Duroc pigs, lower in 990 animals and the lowest in Pietrain pigs. The cortical index of individual bones was in the following order: III metatarsal bone (31.86) <III metacarpal bone (33.86) <femur (44.75). However, its value did not significantly depend on the intensity of feeding or the breed of pigs.
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