An elevated level of total homocysteine (tHcy) in blood, denoted hyperhomocysteinemia, is emerging as a prevalent and strong risk factor for atherosclerotic vascular disease in the coronary, cerebral, and peripheral vessels, and for arterial and venous thromboembolism. The basis for these conclusions is data from about 80 clinical and epidemiological studies including more than 10,000 patients. Elevated tHcy confers a graded risk with no threshold, is independent of but may enhance the effect of the conventional risk factors, and seems to be a particularly strong predictor of cardiovascular mortality. Hyperhomocysteinemia is attributed to commonly occurring genetic and acquired factors including deficiencies of folate and vitamin B12. Supplementation with B-vitamins, in particular with folic acid, is an efficient, safe, and inexpensive means to reduce an elevated tHcy level. Studies are now in progress to establish whether such therapy will reduce cardiovascular risk.

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Homocysteine and Cardiovascular Disease

Preface.- Contributors.- List of Abbreviations.- Section 1: Basic Principles: Introduction.-Sources of Heavy Metals and Metalloids in Soils.- Chemistry of Heavy Metals and Metalloids in Soils.- Methods for the Determination of Heavy Metals and Metalloids in Soils.- Effects of Heavy Metals and Metalloids on Soil Organisms.- Soil-Plant Relationships of Heavy Metals and Metalloids.- Heavy Metals and Metalloids as Micronutrients for Plants and Animals.-Critical Loads of Heavy Metals for Soils.- Section 2: Key Heavy Metals And Metalloids: Arsenic.- Cadmium.- Chromium and Nickel.- Cobalt and Manganese.- Copper.-Lead.- Mercury.- Selenium.- Zinc.- Section 3: Other Heavy Metals And Metalloids Of Potential Environmental Significance: Antimony.- Barium.- Gold.- Molybdenum.- Silver.- Thallium.- Tin.- Tungsten.- Uranium.- Vanadium.- Glossary of Specialized Terms.- Index.

Heavy metals in soils : trace metals and metalloids in soils and their bioavailability

This book is one of our contemporary medical bibles. It needs no introduction; those who have frequent need of it know it very well, and those who use it less often seek it out on the library shelf when problems arise. The book is truly encyclopedic. Everything relevant discovered during the six-year intervals between publication finds its way into these pages. By today's standards, its 1,778 closely packed small-print pages are a bargain. The mutant gene is both hero and villain in this book. It is reponsible for the biochemical abnormality that results in disease, no matter how rare a given abnormality may be. By the same token, however, it is truly an experiment of nature, shedding light on fundamental metabolic sequences and biologic mechanisms. This volume, more than most, explains the contributions of the laboratory to clinical medicine. Each chapter seems to have been rewritten, so that the exciting

The Metabolic Basis Of Inherited Disease.

Total homocysteine is defined as the sum of all homocysteine species in plasma/serum, including free and protein-bound forms. In the present review, we compare and evaluate several techniques for the determination of total homocysteine. Because these assays include the conversion of all forms into a single species by reduction, the redistribution between free and protein-bound homocysteine through disulfide interchange does not affect the results, and total homocysteine can be measured in stored samples. Total homocysteine in whole blood increases at room temperature because of a continuous production and release of homocysteine from blood cells, but artificial increase is low if the blood sample is centrifuged within 1 h of collection or placed on ice. Different methods correlate well, and values between 5 and 15 mumol/L in fasting subjects are considered normal. Total homocysteine in serum/plasma is increased markedly in patients with cobalamin or folate deficiency, and decreases only when they are treated with the deficient vitamin. Total homocysteine is therefore of value for the diagnosis and follow-up of these deficiency states and may compensate for weaknesses of the traditional laboratory tests. In addition, total homocysteine is an independent risk factor for premature cardiovascular diseases. These disorders justify introduction of the total homocysteine assay in the routine clinical chemistry laboratory.

https://www.folk.uib.no/mfapu/Pages/papers%20pdf/1993/ueland_2000_cc_39_1764.pdf

Total homocysteine in plasma or serum: methods and clinical applications.

Background: Measurement of plasma total homocysteine has become common as new methods have been introduced. A wide range of disorders are associated with increased concentrations of total homocysteine. The purpose of this review is to provide an international expert opinion on the practical aspects of total homocysteine determinations in clinical practice and in the research setting and on the relevance of total homocysteine measurements as diagnostic or screening tests in several target populations. Methods: Published data available on Medline were used as the basis for the recommendations. Drafts of the recommendations were critically discussed at meetings over a period of 3 years. Outcome: This review is divided into two sections: (a) determination of homocysteine (methods and their performance, sample collection and handling, biological determinants, reference intervals, within-person variability, and methionine loading test); and (b) risk assessment and disease diagnosis (homocystinuria, folate and cobalamin deficiencies, cardiovascular disease, renal failure, psychiatric disorders and cognitive impairment, pregnancy complications and birth defects, and screening of elderly and newborns). Each of these subsections concludes with a separate series of recommendations to assist the clinician and the research scientist in making informed decisions. The review concludes with a list of unresolved questions.

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Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion

We have investigated the effect of low-dose methotrexate (25 mg weekly) on plasma homocysteine in 13 patients who had psoriasis. Total, free, and protein-bound homocysteine were determined both during fasting and after methionine loading. Psoriasis patients had significantly higher basal plasma homocysteine levels than age-matched control subjects. In addition, the methionine loading test was abnormal in four of the patients, but this was not significant. Psoriasis patients, although not folate deficient, did have lower serum folate levels than control subjects. There was a significant and transient increase in fasting plasma homocysteine levels within 48 hours after administration of low-dose methotrexate. This response was repeated after each administration and was observed eight to 20 times in three patients whose progress was monitored for 2 to 6 months. Notably, methotrexate did not affect the plasma profile for homocysteine after methionine loading. This study showed the level of fasting plasma homocysteine to be a sensitive and responsive parameter of antifolate drug treatment.

Fasting plasma homocysteine as a sensitive parameter of antifolate effect: a study of psoriasis patients receiving low-dose methotrexate treatment.

Feeding Artemia to larvae of Atlantic halibut (Hippoglossus hippoglossus L.) results in lower larval vitamin A content compared with feeding copepods

Homocysteine in tissues of the mouse and rat.

Background Although potent, topical corticosteroids offer effective and rapid healing of psoriatic lesions. Their long term use is limited because of the risk of side effects. Calcipotriol is safe for long-term treatment, but its initial efficacy is lower than with topical corticosteroids. Objectives To investigate whether 2 weeks of treatment with clobetasol propionate 0.05% ointment bd followed by 4 weeks of treatment with calcipotriol 50 μg/g bd would offer therapeutic advantages over 6 weeks of continuous treatment with calcipotriol. Methods Forty-nine patients with moderate to severe plaque psoriasis were recruited from five centres in Norway. In a randomised, double-blind, right- versus left-side comparison, ointments were applied to two symmetrically-located areas. Results Two weeks of treatment with clobetasol propionate produced a significantly greater decrease in total symptom score (combined scores of erythema, induration and scaling) than calcipotriol treatment (P Conclusions Clobetasol propionate ointment bd for 2 weeks followed by treatment with calcipotriol ointment bd for 4 weeks was superior to calcipotriol ointment alone in the treatment of plaque psoriasis.

Clobetasol propionate followed by calcipotriol is superior to calcipotriol alone in topical treatment of psoriasis

Free amino acid (FAA) and protein content were measured in various developmental stages of Artemia franciscana, from cysts to Instar III metanauplii. In addition, decapsulated cysts of 15 Artemia populations from different localities were compared with respect to their FAA and protein content. Furthermore, the content and composition of the FAA pool were modulated by hatching the cysts at various salinities, and by enriching the nauplii with algae or a lipid-enrichment emulsion. The FAA content increased threefold from cysts to nauplii, and Instar III metanauplii contained nearly 50% taurine of total FAA. Cysts of A. franciscana were found to contain one-third the amount of FAA compared to the other Artemia species investigated. The content and pool composition of FAA was successfully modulated in 11 of 13 populations, where by the content of FAA was significantly increased when hatched at high salinity. Finally, enrichment elevated the content of FAA and changed the pool composition, thereby showing a dietary effect. Algal enrichment also increased the protein content.

Svein Helland

Papers

Fasting plasma homocysteine as a sensitive parameter of antifolate effect: a study of psoriasis patients receiving low-dose methotrexate treatment.

Feeding Artemia to larvae of Atlantic halibut (Hippoglossus hippoglossus L.) results in lower larval vitamin A content compared with feeding copepods

Homocysteine in tissues of the mouse and rat.

Clobetasol propionate followed by calcipotriol is superior to calcipotriol alone in topical treatment of psoriasis

Modulation of the free amino acid pool and protein content in populations of the brine shrimp Artemia spp.