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- Almquist, Martin, et al.
(författare)
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Reproductive history, lifestyle factors and season as determinants for serum calcium concentrations in women.
- 2008
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68, s. 777-785
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Serum calcium concentrations have been associated with the risk of malignant disease, especially breast cancer. Thus, determinants of serum calcium concentrations, with special regard to risk factors of breast cancer, are of great interest. Material and methods. Previous studies have either been small or they have not focused on reproductive factors. The present study examined serum calcium concentrations in relation to reproductive history, selected lifestyle factors and screening season in a large population-based cohort study comprising 8,114 women. ANOVA followed by the Bonferroni t-test were used for comparison of means, and logistic regression and multiple regression analysis were used to test associations. Results. Serum calcium concentrations were lower in hormone replacement therapy users versus non-users (2.321 mmol/L versus 2.364; p<0.001) and in users of oral contraceptives versus non-users (2.304 versus 2.348; p<0.001). They were higher in peri-/postmenopausal versus premenopausal women (2.357 versus 2.319; p<0.001). Overweight and obese women had higher mean calcium concentrations (2.350 and 2.355) than women with body mass index between 20 and 25 (2.342; p<0.001). Serum calcium concentrations were higher in spring and autumn than in winter (2.352 and 2.353 versus 2.343; p = 0.002). Both younger (40-45 years) (2.334; p = 0.001) and older age groups (>55 years) (2.363; p<0.001) had higher mean calcium concentrations compared to those of women aged 45-50 years (2.320), even when adjusting for menopausal status, suggesting that age has an independent influence on calcium concentrations. Conclusions. It is concluded that reproductive factors such as menopausal status, use of oral contraceptives or hormone-replacement therapy, and age, BMI and season are associated with serum calcium concentrations.
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- Andersson, Christer, 1945-, et al.
(författare)
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The W198X and R173W mutations in the porphobilinogen deaminase gene in acute intermittent porphyria have higher clinical penetrance than R167 : a populations-based study
- 2000
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 60:7, s. 643-648
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Tidskriftsartikel (refereegranskat)abstract
- The biosynthesis of porphyrins is one of the most conserved parthways known, about the same sequence of reactions taking place in all species. By associating different metals, porphyrins give rise to the “pigments of life”: chlorophyll, haem and cobalamin. The unique tetrapyrrolic structure enables it to function in an array of reactions as a single electron carrier and as a catalyst for redox reactions. In this capacity, it constitutes the prosthetic group of enzymes participating in cellular respiration, in conversion reactions involving steroids and lipophilic xenobiotics, in protective mechanisms directed against oxidative stress and in pathways providing central messenger molecules. The formation of haem is accomplished by a sequence of eight dedicated enzymes encoded by different genes, some being active in ubiquitous as well as in erythroid isoforms. Large differences between the participating enzymes with regard to catalytic power, with low capacity steps positioned early in the catalytic chain, constitute a bar against substrate overloading of enzymes processing porphyrins, thus preventing accumulation in the body of these phototoxic compounds under physiological conditions. Most of the haem in the body is produced by the liver and bone marrow, but the mechanisms applied for the control of the synthesis differ between the two organs. The extremely potent hemeprotein enzymes formed in the liver are rapidly turned over in response to current metabolic needs. They have half-lives in the order of minutes or hours and are restored by fast-acting mechanisms for the de novo synthesis, when needed. Uninterrupted and instant availability of the compound is secured by acute deinhibition of the initial enzyme of the synthetic chain, ubiquitous 5-aminolevulinate synthase (ALAS-1), in response to drain of the free cellular haem pool caused by prevailing demands for hemeproteins or by increased catabolism of the compound. In contrast, in the erythroid progenitor cell the haem synthetic machinery is designed for uninterrupted production of huge amounts of haem for combination with globin chains to form hemoglobin at a steady rate. In the erythron the synthesis of the enzymes participating in the formation of haem is under control of erythropoietin, formed under hypoxic conditions. In the absence of iron, to be incorporated in the porphyrin formed in the last step of the synthesis, the mRNA of erythroid 5-aminolevulinate synthase (ALAS-2) is blocked by attachment of an iron-responsive element (IRE) binding cytosolic protein, and transcription of this key enzyme is inhibited. In humans, the genes for each of the haem synthetic enzymes may become the target of mutations that give rise to impaired cellular enzyme activity. Seven of the enzyme deficiencies are associated with accumulation of toxic intermediaries and with disease entities termed porphyrias. The acute porphyrias are characterized by attacks of neuropsychiatric symptoms, which may be due to a toxic surplus of the porphyrin presursor 5-aminolevulinic acid, or a consequence of a deficit of vital hemeproteins resulting from impaired synthesis of haem. In the cutaneous porphyrias, impairment of enzymatic steps where porphyrins are processed gives rise to solar hypersensitivity due to accumulation of phototoxic porphyrins in the skin. Early diagnosis, information to the patient regarding the nature of the illness and counselling aimed at avoidance of triggering factors are cornerstones in the handling of the porphyric diseases. Gene analysis is of incomparable diagnostic reliability in carrier detection, but biochemical methods must be applied in the important task of monitoring porphyric disease activity. In most forms of porphyria the gene carriers run the risk of development of associated diseases in liver or kidneys, a circumstance that prompts application of well-structured surveillance programs.
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