Human tissue is structured mainly of self-assembled polymers (proteins) and ceramics (bone minerals), with metals present as trace elements with molecular scale functions. However, metals and their alloys have played a predominant role as structural biomaterials in reconstructive surgery, especially orthopedics, with more recent uses in non-osseous tissues, such as blood vessels. With the successful routine use of a large variety of metal implants clinically, issues associated with long-term maintenance of implant integrity have also emerged. This review focuses on metallic implant biomaterials, identifying and discussing critical issues in their clinical applications, including the systemic toxicity of released metal ions due to corrosion, fatigue failure of structural components due to repeated loading, and wearing of joint replacements due to movement. This is followed by detailed reviews on specific metallic biomaterials made from stainless steels, alloys of cobalt, titanium and magnesium, as well as shape memory alloys of nickel–titanium, silver, tantalum and zirconium. For each, the properties that affect biocompatibility and mechanical integrity (especially corrosion fatigue) are discussed in detail. Finally, the most critical challenges for metallic implant biomaterials are summarized, with emphasis on the most promising approaches and strategies.

Metallic implant biomaterials

Objective: The intent of this review is to evaluate the scientific evidence for the assessment of adequacy of selenium status and of the requirements for selenium. From this evidence, attempts have been made to define levels of plasma selenium and dietary selenium intake, which could be used for the assessment of deficiency or adequacy of selenium status. Method: The first section briefly reviews the methods for assessment of selenium status. The second section outlines the requirements for selenium based on a number of criteria, and how these have been translated into recommended intakes of selenium. In the final section, levels of plasma selenium and dietary intake based on different criteria of adequacy have been proposed. Results and conclusion: The minimum requirement for selenium is that which prevents the deficiency disease, Keshan disease. The recommended intakes of selenium have been calculated from the requirement for optimum plasma glutathione peroxidase (GPx) activity that must, because of the hierarchy of selenoproteins, also take account of the amounts needed for normal levels of other biologically necessary selenium compounds. Whether optimal health depends upon maximization of GPx or other selenoproteins, however, has yet to be resolved, and the consequences of less-than-maximal GPx activities or mRNA levels need investigation. Intakes, higher than recommended intakes, and plasma selenium concentrations that might be protective for cancer or result in other additional health benefits have been proposed. There is an urgent need for more large-scale trials to assess any such beneficial effects and to provide further data on which to base more reliable estimates for intakes and plasma selenium levels that are protective.

Assessment of requirements for selenium and adequacy of selenium status: a review

There are many reasons for reviewing the neurology of vitamin-B12 and folic-acid deficiencies together, including the intimate relation between the metabolism of the two vitamins, their morphologically indistinguishable megaloblastic anaemias, and their overlapping neuropsychiatric syndromes and neuropathology, including their related inborn errors of metabolism. Folates and vitamin B12 have fundamental roles in CNS function at all ages, especially the methionine-synthase mediated conversion of homocysteine to methionine, which is essential for nucleotide synthesis and genomic and non-genomic methylation. Folic acid and vitamin B12 may have roles in the prevention of disorders of CNS development, mood disorders, and dementias, including Alzheimer's disease and vascular dementia in elderly people.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(06)70598-1.pdf

Vitamin B12, folic acid, and the nervous system

Increase in Plasma Homocysteine Associated with Parallel Increases in Plasma S-Adenosylhomocysteine and Lymphocyte DNA Hypomethylation*

Transfer Requirements The following requirements for the major are subject to change without notice. To assure accuracy of the information on this sheet, you should consult with a counselor, the articulation officer, or review articulation agreements via the internet at www.assist.org Veterinary medicine uses problem-solving skills and in-depth knowledge to diagnose, treat and prevent animal diseases. It is the broadest and most comprehensive of all the health professions. The profession is concerned with enhancing the health, welfare, and productivity of animals and assuring the safety of animal products used by people. Veterinarians are highly trained medical professionals who provide for the health needs of all kinds of animals while maintaining sensitivity to human health and well-being. Most veterinarians in the United States are engaged in private practice. Other veterinarians work in a wide range of fields relating to public health, animal disease control, environmental protection, the biotechnology industry, higher education and research. Academic preparation for veterinary school takes place at the undergraduate level through a comprehensive educational experience with special emphasis in the sciences. In order to succeed academically, in the rigorous veterinary school curriculum, veterinary schools are looking for individuals with a highly developed science background. Since Pre-Veterinary is not a major, it is important to meet with a counselor during your first semester at El Camino College to help with the selection of classes. 1. Academic preparation and grade point average is critical for admission. Cumulative GPA, strong grades in science courses, and GPA in the last two years of undergraduate study are critical in the selection process. 2. Many, but not all veterinary schools require a bachelor's degree. In some instances, a bachelor's degree may make an applicant more competitive in the admission process. 3. Score on a standardized graduate admissions test (e.g. GRE, MCAT, and VCAT). Check with the individual program for the specific test required. 4. Strong letters of recommendation-Most schools require a minimum of three letters of recommendation. Some schools require on letter from a Doctor of Veterinary Medicine. 5. Undergraduate course of study-Veterinary schools are looking for both lower and upper division preparation. 6. Applicant's personal statement or narrative. 7. Extracurricular activities, work experience, community activities, motivation, individual character, personality, and other post-undergraduate experiences. 8. Animal related activities and/or animal related work experience-Most colleges are looking for a strong commitment to working with animals. Some require employment by a Veterinarian. 9. Personal interview. …

What is Veterinary Medicine

Pigs were treated with N2O which is known to impair vitamin B12 function in vivo. Such pigs demonstrated an inability to gain weight, progressive ataxia, and spinal neuropathy. The ataxia was totally and the neuropathy partially preventable by dietary methionine supplementation. Methionine synthase activity was inhibited in both the liver and brain. There was a marked elevation of S-adenosylhomocysteine in the neural tissues and a concomitant failure of S-adenosylmethionine to rise and thus maintain the methylation ratio, except when supplementary dietary methionine was added. In contrast, the methylation ratio in the rat was affected to a lesser extent. The neuropathy, it is suggested, is caused by raised S-adenosylhomocysteine levels in neural tissue; as a result, the methylation ratio is inverted and S-adenosylmethionine-dependent methylation reactions are inhibited.

Methylation deficiency causes vitamin B12-associated neuropathy in the pig.

The changes in the activities of the two vitamin B12-dependent enzymes methylmalonyl-CoA mutase (EC 5.4.99.2) and methionine synthetase (5-methyltetrahydrofolate-homocysteine methyltransferase, EC 2.1.1.13) are described in two groups of sheep maintained for 20 weeks on either a cobalt-deficient or a Co-sufficient whole-barley diet. At the end of that period, the plasma concentrations of vitamin B12 were depressed and those of methylmalonic acid were raised in the Co-deficient group. During the course of the experiment hepatic holo-mutase activity, measured on biopsy samples, declined in Co-deficient animals with a half-life of 73 d. There was a similar, but slower decline in lymphocyte holo-mutase activity which fell with a half-life of 125 d. At slaughter, there was no difference between Co-sufficient and Co-deficient animals in total mutase activity in liver, kidney, brain and spinal cord. In contrast, the total-synthetase activity of liver and kidney was reduced by 60 and 30% respectively in the Co-deficient animals. There was no change in either group of animals in total-synthetase activity, or in either holo-mutase or holo-synthetase activity, in brain and spinal cord. In the Co-deficient animals, holo-mutase and holo-synthetase activities in liver, the tissue with the greatest activity of both enzymes, fell to 25 and 39% respectively, of that of Co-sufficient animals. The corresponding reductions for kidney were 12 and 51% respectively. These results indicated that activity of both holoenzymes is greatly reduced in Co-deficient sheep.

/pdf/methylmalonyl-coa-mutase-ec-5-4-99-2-and-methionine-3mafqglosc.pdf

Methylmalonyl-CoA mutase (EC 5.4.99.2) and methionine synthetase (EC 2.1.1.13) in the tissues of cobalt-vitamin B12 deficient sheep.

Feeding diets depleted of vitamin E and Se to cattle can induce a disease known as nutritional degenerative myopathy. It is believed that an increased peroxidative challenge in muscle is involved in the pathogenesis of this disease. A number of species can up-regulate the activity of some antioxidant enzymes, including glutathione reductase (EC 1.6.4.2), glutathione transferase (EC 2.5.1.18), glucose-6-phosphate dehydrogenase (EC 1.1.1.49), catalase (EC 1.11.1.6), and superoxide dismutase (EC 1.15.1.1), in an attempt to mitigate the effects of a peroxidative challenge. A 2 x 2 factorial study was set up to examine possible changes in the activities of these antioxidant enzymes in muscles of ruminant calves fed on diets low in either vitamin E or Se. Four groups of four calves each were fed on a basal diet of NaOH-treated barley which was supplemented with alpha-tocopherol or Se or both for a total of 50 weeks. Calves fed on diets depleted of vitamin E, but not those fed on diets low in Se, developed subclinical myopathy, as judged by increases in the activity of plasma creatinine kinase (EC 2.7.3.2), and had increased muscle concentrations of two indices of lipid peroxidation, namely thiobarbituric acid-reactive substances, with and without ascorbate activation. Feeding diets depleted of vitamin E and diets low in Se both increased muscle activities of glucose-6-phosphate dehydrogenase in heart, biceps and supraspinatus. This change may have occurred in an attempt to maintain intracellular pools of reduced glutathione. No other changes in antioxidant enzyme activity were observed.

/pdf/antioxidant-enzyme-activity-in-the-muscles-of-calves-wjcx2ydhzm.pdf

Antioxidant enzyme activity in the muscles of calves depleted of vitamin E or selenium or both

Lipid peroxidation induced in vivo by hyperhomocysteinaemia in pigs

Introduction - Central nervous system (CNS) methyltransferases methylate a wide range of substrates including proteins, lipids, nucleic acids and hormones In every instance the methyl donor is S-adenosylmethionine (SAMe) and the demethylated product is S-adenosylhomocysteine (SAH)Methylation can be disrupted when there is an inadequate supply of methionine synthase (following vitamin B12 deficiency or folate deficiency), SAMe synthetase (due to ethanol), or SAH hydrolase (for unknown reasons) Material and Methods 5-week-old pigs were maintained in an environment of either air or nitrous oxide, which inhibits methionine synthase, and were fed eithera methionine-unsupplemented or methionineenriched diet After 3 to 10 weeks, pigs were killed by pentabarbitone injection and the levels of methionine and SAMe in the pigs' brain, spinal cord, plasma, liver, and kidney assessed Results - Pigs maintained in nitrous oxide displayed a dramatic fall in methionine levels in plasma and brain tissues but maintained relatively normal SAMe levels in these tissues Brain and spinal cord cystathionine levels were markedly elevated, especially in those animals receiving oral methionine, as in the absence of methionine synthase homocysteine can be metabolized only through the catabolic pathway to cystathionine and cysteine Conclusion - Disorders such as vitamin B12 deficiency or folate deficiency inhibit methylation by limiting the availability of SAMe or by elevating levels of the inhibitor SAH In either case, the disruption of a wide range of methylation reactions can cause clinical sequelae ranging from structural abnormalities such as myelopathy to functional abnormalities such as depression

S. Kennedy

Papers

Methylation deficiency causes vitamin B12-associated neuropathy in the pig.

Methylmalonyl-CoA mutase (EC 5.4.99.2) and methionine synthetase (EC 2.1.1.13) in the tissues of cobalt-vitamin B12 deficient sheep.

Antioxidant enzyme activity in the muscles of calves depleted of vitamin E or selenium or both

Lipid peroxidation induced in vivo by hyperhomocysteinaemia in pigs

Effects of the disruption of transmethylation in the central nervous system: an animal model.