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- Bjellerup, P, et al.
(författare)
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Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours
- 2000
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Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 83:2, s. 171-176
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide Y (NPY) is found at high concentrations in neural crest-derived tumours and has been implicated as a regulatory peptide in tumour growth and differentiation. Neuroblastomas, ganglioneuromas and phaeochromocytomas with significant concentrations of NPY-like immunoreactivity were investigated for different molecular forms of NPY and for significance of proNPY processing. Gel-permeation chromatography identified intact NPY (1-36) in all tumours, whereas proNPY (69 amino acids) was detected only in control adrenal tissue and malignant neuroblastomas. Purification of NPY-like immunoreactivity in tumour extracts and structural characterization revealed that both NPY (1-36) and the truncated form NPY (3-36) was present. The degree of processing of proNPY to NPY in tumour tissue was lower in advanced neuroblastomas with regional or metastatic spread (stage 3 and 4) (n = 6), (41%, 12-100%, median, range), compared to the less aggressive stage 1, 2 and 4S tumours (n = 12), (93%, 69-100%), (P = 0.012). ProNPY processing of less than 50% was correlated with poor clinical outcome (P = 0.004). MYCN oncogene amplification was also correlated to a low degree of proNPY processing (P = 0.025). In summary, a low degree of proNPY processing was correlated to clinical advanced stage and poor outcome in neuroblastomas. ProNPY/NPY processing generated molecular forms of NPY with known differences in NPY-receptor selectivity, implicating a potential for in vivo modulation of NPY-like effects in tumour tissue. (C) 2000 Cancer Research Campaign.
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| 11. |
- Akesson, A, et al.
(författare)
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Cadmium exposure in pregnancy and lactation in relation to iron status
- 2002
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Ingår i: American Journal of Public Health. - : American Public Health Association. - 1541-0048 .- 0090-0036. ; 92:2, s. 284-287
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The purpose of this study was to determine the impact of iron status on cadmium dose among pregnant women. Methods. Iron status and cadmium concentration in blood, urine, and placenta were determined among women followed for 2 years from early pregnancy. Results. Blood cadmium and urinary cadmium were correlated with iron status throughout the study period. Urinary cadmium increased longitudinally among women with exhausted iron stores during their pregnancy. The increase in urinary cadmium with age was more pronounced in multiparous than in nulliparous women. Conclusions. Iron deficiency during pregnancy leads to increased cadmium absorption and body burden. Multiparous women exhibit additional increases with increasing age.
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| 12. |
- Akesson, A, et al.
(författare)
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Cadmium-induced effects on bone in a population-based study of women
- 2006
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 114:6, s. 830-834
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Tidskriftsartikel (refereegranskat)abstract
- High cadmium exposure is known to cause bone damage, but the association between low-level cadmium exposure and osteoporosis remains to be clarified. Using a population-based women's health survey in southern Sweden [Women's Health in the Lund Area (WHILA)] with no known historical cadmium contamination, we investigated cadmium-related effects on bone in 820 women (53-64 years of age). We measured cadmium in blood and urine and lead in blood, an array of markers of bone metabolism, and forearm bone mineral density (BMD). Associations were evaluated in multiple linear regression analysis including information on the possible confounders or effect modifiers: weight, menopausal status, use of hormone replacement therapy, age at menarche, alcohol consumption, smoking history, and physical activity. Median urinary cadmium was 0.52 mu g/L adjusted to density (0.67 mu g/g creatinine). After multivariate adjustment, BMD, parathyroid hormone, and urinary deoxypyridinoline (U-DPD) were adversely associated with concentrations of urinary cadmium (p < 0.05) in all subjects. These associations persisted in the group of never-smokers, which had the lowest cadmium exposure (mainly dietary). For U-DPD, there was a significant interaction between cadmium and menopause (p = 0.022). Our results suggest negative effects of low-level cadmium exposure on bone, possibly exerted via increased bone resorption, which seemed to be intensified after menopause. Based on the prevalence of osteoporosis and the low level of exposure, the observed effects, although slight, should be considered as early signals of potentially more adverse health effects.
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| 17. |
- Akesson, AA, et al.
(författare)
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Tubular and glomerular kidney effects in Swedish women with low environmental cadmium exposure
- 2005
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 113:11, s. 1627-1631
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Tidskriftsartikel (refereegranskat)abstract
- Cadmium is a well-known nephrotoxic agent in food and tobacco, but the exposure level that is critical for kidney effects in the general population is not defined. Within a population-based women's health survey in southern Sweden (Women's Health in the Lund Area, WHILA), we investigated cadmium exposure in relation to tubular and glomerular function, from 1999 through early 2000 in 820 women (71% participation rate) 53-64 years of age. Multiple linear regression showed cadmium in blood (median, 0.38 mu g/L) and urine (0.52 mu g/L; density adjusted = 0.67 mu g/g creatinine) to be significantly associated with effects on renal tubules (as indicated by increased levels of human complex-forming protein and N-acetyl-beta-D-glucosaminidase in urine), after adjusting for age, body mass index, blood lead, diabetes, hypertension, and regular use of nephrotoxic drugs. The associations remained significant even at the low exposure in women who had never smoked. We also found associations with markers of glomerular effects: glomerular filtration rate and creatinine clearance. Significant effects were seen already at a mean urinary cadmium level of 0.6 mu g/L (0.8 mu g/g creatinine). Cadmium potentiated diabetes-induced effects on kidney. In conclusion, tubular renal effects occurred at lower cadmium levels than previously demonstrated, and more important, glomerular effects were also observed. Although the effects were small, they may represent early signs of adverse effects, affecting large segments of the population. Subjects with diabetes seem to be at increased risk.
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| 18. |
- Berglund, M, et al.
(författare)
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Metal-bone interactions
- 2000
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Ingår i: Toxicology letters. - : Elsevier BV. - 0378-4274. ; 112112-113, s. 219-225
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Tidskriftsartikel (refereegranskat)
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| 19. |
- Bergman, ASF, et al.
(författare)
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Diltiazem infusion for renal protection in cardiac surgical patients with preexisting renal dysfunction
- 2002
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1532-8422 .- 1053-0770. ; 16:3, s. 294-299
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate if the calcium channel blocker diltiazem protects postoperatively renal function in cardiac surgical patients with preexisting mild-to-moderate renal dysfunction. Design: Prospective, randomized, placebo-controlled, double-blind, clinical study. Setting: Cardiothoracic anesthesia department at a university hospital. Participants: Adult patients undergoing elective cardiac surgery using cardiopulmonary bypass, with a preoperatively elevated serum creatinine level (n = 24). Interventions: Randomized infusions of diltiazem (bolus 0.25 mg/kg followed by a continuous infusion of 1.7 pg/kg/min) (DTZ, n = 12) or placebo (C, n = 12) were started 30 minutes before induction of anesthesia and continued for 24 hours. Measurements and Main Results: Median plasma concentrations of diltiazem (DTZ group) were 79 mug/L before cardiopulmonary bypass, 67 mug/L at the end of cardiopulmonary bypass, and 164 mug/L at 24 hours postoperatively. Serum creatinine levels; on postoperative days 1, 3, and 5; and 3 weeks postoperatively were similar between groups. lohexol clearance did not differ between the groups on day 5 but was higher in the DTZ group than in the placebo group 3 weeks after surgery (median, 51 v 40 mL/min/1.73 m(2); p < 0.05). Urinary N-acetyl-β-glucosamidase concentrations were similar between the groups during the study but were increased from baseline on days 2 and 4 and 3 weeks postoperatively. Conclusion: Diltiazem can be safely used in patients who have mild-to-moderate renal dysfunction and undergo cardiac surgery using cardiopulmonary bypass. Within the limits of this study, the data suggest that addition of prophylactic diltiazem may prevent further glomerular damage resulting from cardiopulmonary bypass and may improve glomerular function 3 weeks after cardiac surgery.
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| 21. |
- Funkquist, Anders, 1977-, et al.
(författare)
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Higher CSF/serum free-T4 ratio is associated with improvement of quality of life during treatment with L-thyroxine
- 2023
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Ingår i: Journal of Neuroendocrinology. - : Wiley-Blackwell Publishing Inc.. - 0953-8194 .- 1365-2826. ; 35:5
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Tidskriftsartikel (refereegranskat)abstract
- Up to 20% of individuals with primary hypothyroidism treated with L-thyroxine still suffer from severe symptoms. These are supposedly brain derived and involve both cognitive and emotional domains. Previously, no consistent relationship has been found between thyroid hormones (TH) or TSH levels in blood and quality of life (QoL). Recently, we reported an association between cerebrospinal fluid (CSF)/serum free-thyroxine (f-T4) ratio and QoL, in juvenile hypothyroid patients. Here, we investigated if CSF/serum f-T4 ratio and QoL estimates correlate also during L-thyroxine treatment. Moreover, the CSF biomarker neurogranin (Ng) was used as a biomarker for synaptic function and integrity in clinical research. Ng is partially controlled by TH and therefore we investigated the relationship between QoL parameters and Ng levels. Patients diagnosed with primary hypothyroidism were investigated using vital parameters, serum and CSF analyses of TH, TSH, Ng and QoL questionnaires. Similar procedures were performed after 6 months of treatment. The most marked associations with QoL were found for CSF/serum f-T4 ratio, which was strongly related to several QoL parameters such as the mental subscore of SF-36 (r = 0.83, p < .0005). Ng, which did not differ from that in our healthy controls, was lower in some patients during treatment and higher in others. However, the change in Ng during treatment was significantly correlated with QoL parameters including the mental subscore of SF-36 (r = -0.86, p < .0001). In addition, the CSF/serum f-T4 ratio correlated with the change in Ng (r = -0.75, p = .001). Our results suggest that the ratio between CSF and serum f-T4 is an important biomarker for QoL during treatment of patients with primary hypothyroidism, so far in research, but in the future maybe also in clinical settings. Moreover, this ratio also correlates with the changes in Ng levels during L-thyroxine treatment, further supporting the impact of the TH balance between serum and CSF on QoL.
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| 22. |
- Funkquist, Anders, 1977-, et al.
(författare)
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Low CSF/serum ratio of free T4 is associated with decreased quality of life in mild hypothyroidism – A pilot study : CSF/s-T4 associated with QoL in hypothyroidism
- 2020
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Ingår i: Journal of Clinical and Translational Endocrinology. - Netherlands : Elsevier BV. - 2214-6237. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background & Objective: Patients with mild hypothyroidism often are depressed and have impaired quality of life despite serum free-T4 and T3 within reference values. Therefore, we investigated whether their symptoms were dependent on the concentrations of free -T4 and T3 in the circulation and cerebrospinal fluid (CSF). Methods: Twenty-five newly diagnosed, untreated hypothyroid subjects and as many age- and sex-matched healthy controls were investigated. Blood and CSF sampling was performed in the morning after an overnight fast. Quality of life (QoL) was assessed by a Likert scale. In the hypothyroid subjects, the MADRS rating scale was also used to evaluate symptoms of depression. Furthermore, the results obtained by the questionnaires were related to serum and CSF levels of free- T4 and T3 as well as the ratios between them in CSF and in serum. Results: Self-reported health was considerably lower in hypothyroid subjects. MADRS was considerably higher than the normal range for healthy individuals. Low CSF/serum free-T4 ratio was correlated with an increased depressed state according to MADRS (p < 0.01), and in addition, CSF/serum free-T4 ratio correlated positively with the self-reported general health Likert scale (p < 0.05). Concentrations of TSH, or free-T3 in serum or CSF, were not associated with an increased depressed state or self-reported general health. Conclusions: Low CSF/serum ratio of free-T4 was correlated with impaired general health and mood, in contrast to serum measurements not showing any correlations. These findings might partly explain why some patients with hypothyroidism suffer from mental symptoms, despite adequate serum levels of free-T4. However, the findings need to be confirmed in further and larger studies.
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| 23. |
- Grenback, E, et al.
(författare)
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Galanin in pituitary adenomas
- 2004
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Ingår i: Regulatory peptides. - : Elsevier BV. - 0167-0115. ; 117:2, s. 127-139
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Tidskriftsartikel (refereegranskat)
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| 24. |
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| 25. |
- Rignell-Hydbom, Anna, et al.
(författare)
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Exposure to cadmium and persistent organochlorine pollutants and its association with bone mineral density and markers of bone metabolism on postmenopausal women
- 2009
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 109:8, s. 991-996
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Tidskriftsartikel (refereegranskat)abstract
- Environmental contaminants such as cadmium and persistent organochlorine pollutants have been proposed as risk factors of osteoporosis, and women may be at an increased risk. To assess associations between exposure to cadmium and two different POPs (2,2',4,4',5,5'-hexachlorobiphenyl CB-153, 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene p,p'-DDE), on one hand, and bone effects, on the other, in a population-based study among postmenopausal (60-70 years) Swedish women with biobanked blood samples. The study included 908 women and was designed to have a large contrast of bone mineral densities, measured with a single photon absorptiometry technique in the non-dominant forearm. Biochemical markers related to bone metabolism were analyzed in serum. Exposure assessment was based on cadmium concentrations in erythrocytes and serum concentrations of CB-153 and p,p'-DDE. Cadmium was negatively associated with bone mineral density and parathyroid hormone, positively with the marker of bone resorption. However, this association disappeared after adjustment for smoking. The major DDT metabolite (p.p'-DDE) was positively associated with bone mineral density, an association which remained after adjustment for confounders, but the effect was weak. There was no evidence that the estrogenic congener (CB-153) was associated with any of the bone markers. In conclusion, no convincing associations were observed between cadmium and POPs, on one hand, and bone metabolism markers and BMD, on the other. (C) 2009 Elsevier Inc. All rights reserved.
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