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Biomedical subjects

E Nexø

Publications and source records attributed to E Nexø.

At least 19 recordsLinked to original sources
PubMed2006

A longitudinal study of serum cobalamins and its binding proteins in lactating women.

OBJECTIVE: To examine longitudinal changes in serum cobalamins, transcobalamin (TC) and haptocorrin (HC) during lactation and to investigate the influence of vitamin B12 supplementation on these parameters. DESIGN: A 9-month follow-up study. SUBJECTS AND METHODS: Lactating mothers (N=89) including 23 supplemented with vitamin B12 (1-18 microg/daily), 41 partly supplemented and 25 not supplemented. Blood samples collected 3 weeks (baseline) and 4 and 9 months post-partum were analysed for cobalamins, TC and HC. Both the total concentration and the cobalamin-saturated form (holo) of TC and HC were analysed. RESULTS: No significant differences were observed in serum cobalamins or its binding proteins related to supplementation with vitamin B12 or the duration of lactation. Serum cobalamins remained unchanged from 3 weeks to 9 months post-partum. Total TC (holoTC) (median+/-s.e. pmol/l) decreased between 3 weeks (710+/-23 (85+/-12)) and 9 months (602+/-21 (76+/-11)) (P<0.0001 (P=0.0002)), whereas total HC (holoHC) increased from (422+/-11 (300+/-9)) at 4 months to (455+/-13 (317+/-10)) to 9 months post-partum (P<0.0001 (P<0.0001)). CONCLUSION: We report a decrease in TC and an increase in HC during a 9-month period post-partum. No differences were observed between the vitamin B12-supplemented and the unsupplemented groups. Thus, supplementation with vitamin B12 has no impact on the circulating level of serum cobalamins or its binding proteins in a Danish population of lactating mothers.

Adult↗
PubMed2006

Systemically administered trefoil factors are secreted into the gastric lumen and increase the viscosity of gastric contents.

BACKGROUND AND PURPOSE: Trefoil factors (TFFs) secreted by mucus-producing cells are essential for the defence of the gastrointestinal mucosa. TFFs probably influence the viscoelastic properties of mucus, but this has not been demonstrated in vivo. We therefore studied the gastric secretion of systemically administered TFF2 and TFF3, and their influence on the viscosity of the secretions. EXPERIMENTAL APPROACH: Mice and rats under general anaesthesia were injected intravenously with human (h) TFF2, hTFF3 (5 mg kg(-1) to mice and 25 mg kg(-1) to rats), murine (m) (125)I-TFF3, or (125)I-hTFF3 (300,000 cpm, mice only). The appearance of TFFs in the gastric mucosa and luminal secretions was analysed by autoradiography, gamma-counting, and ELISA, and the viscosity by rheometry. KEY RESULTS: (125)I-mTFF3 and (125)I-hTFF3 were taken up by secretory cells of the gastrointestinal tract and detected at the gastric mucosal surface 15 min after injection. Stressing the stomach by carbachol (3.5 microg kg(-1)) and pyloric ligation significantly increased the uptake. Injected hTFF2, hTFF3, and mTFF3 were retrieved from the gastric contents after 4 h. In rats, an approximately seven-fold increase in the viscosity was detected after injection of TFF2 compared to the controls, whereas TFF3 did not increase the viscosity. In mice, TFF2 increased the viscosity approximately 4-fold. CONCLUSIONS: These data indicate that systemically administered TFFs are transferred to the gastric lumen in a biologically active form.

Animals↗
PubMed2006

Folate and vitamin B12 in relation to lactation: a 9-month postpartum follow-up study.

OBJECTIVE: To investigate the relation between lactation and markers of folate and vitamin B12 (B12) deficiency in women with and without vitamin supplementation. DESIGN: A 9-month follow-up study. SUBJECTS AND METHODS: Blood samples from 91 women, who gave birth to a single healthy child, were collected 3 weeks, 4 and 9 months postpartum and analysed for circulating level of homocysteine (tHcy), methylmalonic acid (MMA), folate and B12. The participants were categorized as exclusively, partly or not breast-feeding dependent on the degree of lactation 4 months postpartum. During follow-up, lifestyle factors were recorded by structured interviews. RESULTS: Among 72 exclusively breast-feeding women, the median (10-90% percentile) tHcy was 5.8 (3.1-8.3) micromol/l 3 weeks postpartum, 6.1 (4.1-10.3) micromol/l 4 months postpartum and 5.3 (3.6-8.7) micromol/I 9 months postpartum. At 9 months postpartum, none of the women breast-fed exclusively. No significant change occurred in the concentration of B12 and folate. Exclusively breast-feeding women without vitamin supplementation had higher median tHcy than supplemented exclusively breast-feeding women 4 and 9 months postpartum (7.0 vs 5.4 micromol/l (P < 0.001) and 5.8 vs 4.5 micromol/l (P = 0.003), respectively). Six women had increased (>15 micromol/l) tHcy; four of these were unsupplemented and exclusively breast-feeding. CONCLUSION: We found no overall indication of depletion of the folate and B12 stores during the lactation period in this population. However, folate-supplemented women had lower tHcy and higher folate levels, suggesting a beneficial effect of supplementation with folate throughout lactation.

Adult↗
PubMed2005

Expression of the epidermal growth factor system in human endometrium during the menstrual cycle.

The epidermal growth factor (EGF) system is ubiquitous in humans and plays fundamental roles in embryogenesis, development, proliferation and differentiation. As the endometrium of fertile women is characterized by proliferation and differentiation, we hypothesize a role for the EGF system. Fourteen premenopausal women had endometrial samples removed on day 6 +/- 1 and day 6 +/- 1 and 12 +/- 1 after ovulation during one menstrual cycle. RNA was extracted and analysed by real-time PCR, and immunohistochemistry was performed to localize the components of the EGF system. Human EGF Receptor 1 (HER1) showed highest expression during the proliferative phase, HER2 and HER4 during the early and HER3 during the late secretory phase. Amphiregulin (AR) and transforming growth factor alpha (TGFalpha) expression is highest in proliferative phase. Heparin binding (HB)-EGF and betacellulin (BCL) show no variation. Epiregulin (EP) is detectable in some samples. EGF is undetectable. HER1, HER2, HER3 and HER4 were localized to the epithelium and glands HER3 and HER4 solely in the secretory phase. Amphiregulin was seen in leucocytes and stromal cells, TGFalpha and betacellulin in the epithelial lining, epiregulin in stromal cells whereas HB-EGF and EGF are undetectable. In conclusions, we observed cyclical expression of the four EGF receptors and two ligands and localized all four receptors and four ligands in endometrial biopsies. This suggests a role for the EGF system in growth of the endometrium.

Adolescent↗
PubMed2004

Immunoassays of human trefoil factors 1 and 2: measured on serum from patients with inflammatory bowel disease.

BACKGROUND: The trefoil factors (TFF1-3) are cysteine-rich peptides expressed in the gastrointestinal tract where they play a critical role in mucosal protection and repair. The expression is up-regulated at sites of ulceration in various chronic inflammatory diseases. Recently, we presented an ELISA method for measurement of TFF3. The aims of the present study were to develop and evaluate ELISAs for the other two known human trefoil peptides, TFF1 and TFF2, and to carry out a cross-sectional study on serum TFF levels in patients with inflammatory bowel disease (IBD). METHODS: The TFF1-ELISA was based on two polyclonal rabbit antibodies and the TFF2-ELISA on a monoclonal mouse antibody and a polyclonal rabbit antibody. RhTFF1 and 2 were employed to prepare the calibrators. TFF1-3 were assayed in serum from IBD patients (n=41) and controls (n=13). RESULTS: The TFF1- (TFF2-) ELISA had a detection limit of 3 pmol/L (6 pmol/L) and an analytical imprecision (CV(A)) of 7.0-8.8 for mean concentrations of 24-120 pmol/L (6.1-8.0 for mean concentrations of 17-77 pmol/L). The central reference intervals (n=300) were 140-1400 pmol/L (37-190 pmol/L). There was no variation with age and menstrual cycle. Food intake reduced concentrations of TFF1 by approximately 15%, but did not influence concentrations of TFF2. TFF1 and TFF3 were increased in serum from IBD patients. CONCLUSIONS: We have developed assays for measuring TFF1 and TFF2. Finding increased TFF concentrations in serum from IBD patients suggests that measurements of trefoil peptides may be of clinical relevance in IBD.

Adolescent↗
PubMed2003

Injected TFF1 and TFF3 bind to TFF2-immunoreactive cells in the gastrointestinal tract in rats.

Peptides of the trefoil factor family (TFF1, TFF2 and TFF3) are co-secreted with mucus in most organ systems and are believed to interact with mucins to produce high-viscosity, stable gel complexes. We have previously demonstrated that cells in the GI tract possess binding sites to TFF2 and that injected TFF2 ends up in the mucus layer. In the present study, tissue binding and metabolism of parenterally administered human TFF1 and TFF3 in rats were described and compared to the immunohistochemical localization of the TFF peptides. 125I-TFF1 monomer and 125I-TFF3 mono- and dimer were given intravenously to female Wistar rats. The tissue distribution was assessed by gamma counting of organ samples and by autoradiography of histological sections. The degradation of 125I-TFF3 was studied by means of trichloracetic acid (TCA) precipitation and the saturability of the binding by administration of excess unlabelled peptide. The TFF peptides were localized in histologic sections from the GI tract by immunohistochemistry. Injected TFF3 dimer (12%) was taken up by the GI tract. At autoradiography, grains were localized to the same cells that were immunoreactive to TFF2. The binding could be displaced by excess TFF3. Similar binding was observed for the TFF1 and TFF3 monomers apart from binding in the stomach, where the uptake was only 15% in comparison to the dimer. There was no specific binding outside the GI tract and no binding to TFF1 or TFF3 immunoreactive cells. In conclusion, the TFF2-binding cells in the gastrointestinal tract seem to have basolateral, receptor-like activity to all three TFF peptides. The mucous neck cells of the stomach predominantly take up TFFs with two trefoil domains, indicating a different receptor-like activity in the stomach compared to the rest of the GI tract.

Animals↗
PubMed2003

Vitamin B-12 treatment has limited effect on health-related quality of life among individuals with elevated plasma methylmalonic acid: a randomized placebo-controlled study.

OBJECTIVE: To examine the hypothesis that treatment with vitamin B-12 improves health-related quality of life (HRQOL) in individuals with biochemical signs of vitamin B-12 deficiency. DESIGN: A randomized placebo-controlled study. SETTING: Municipality of Aarhus, Denmark. SUBJECTS: Nonhospitalized individuals (n = 140) with a modest increase in plasma methylmalonic acid (0.40-2.00 micromol L-1) not previously treated with vitamin B-12. INTERVENTION: The participants were randomized to vitamin B-12 injection treatment or placebo weekly for 4 weeks and re-examined 3 months later. The investigator and the participants were blinded to the intervention. MAIN OUTCOME MEASURE: Change in HRQOL assessed by the SF-36 questionnaire from baseline to follow-up examination 3 months later. RESULTS: The participants reported a significantly worser HRQOL than the age- and sex-matched Danish general population (P < 0.001). However, no change was observed after treatment with vitamin B-12 for seven of eight health dimensions. A significant improvement was found only in general health when compared with the placebo group (P = 0.03). CONCLUSIONS: Vitamin B-12 treatment influenced only one of eight dimensions of HRQOL amongst participants with biochemical signs of vitamin B-12 deficiency. We therefore question the benefit of vitamin B-12 treatment amongst elderly with a modestly increased plasma methylmalonic acid as the only sign of vitamin B-12 deficiency.

Aged↗
PubMed2003

Health technology assessment in clinical biochemistry. Methylmalonic acid: a Danish showcase.

In 1992 plasma methylmalonic acid (MMA) was introduced in Denmark for diagnosing vitamin B-12 deficiency. Now, 10 years later, we report on a health technology assessment (HTA) suggesting that the clinical usefulness of MMA is uncertain. MMA is an obvious component for measurement in the diagnosis of vitamin B-12 deficiency because MMA accumulates when there is a lack of vitamin B-12, and technologically the analysis is of high quality. The diagnostic sensitivity of MMA is high, whereas the diagnostic specificity is debatable, and our results suggest it to be relatively low. The organizational aspect implies that both MMA and P-cobalamins have been increasingly employed, though no consensus on the use of the analyses has emerged. The benefit to the patient is not obvious. An increased level of MMA does not predict further increases over time, and vitamin B-12 treatment shows limited clinical benefit in individuals with a moderately increased MMA. The economic consequences of introducing MMA were an increase in the costs of MMA and P-cobalamins of 12% per year during 1992-2000 and an increase in the turnover of vitamin B-12 preparations of 9% per year. In conclusion, MMA was introduced on sound grounds for both pathophysiological considerations and analytical quality. Our HTA shows that the resources employed to diagnose and to treat vitamin B-12 deficiency have increased considerably, but yet we have no evidence to suggest the clinical benefit.

Biomarkers↗
PubMed2002

Possible autocrine loop of the epidermal growth factor system in patients with benign prostatic hyperplasia treated with finasteride: a placebo-controlled randomized study.

OBJECTIVE: To analyse the expression of the epidermal growth factor (EGF) system in prostate tissue and secretions obtained from patients with benign prostatic hyperplasia (BPH) treated with or without finasteride (which primarily targets the androgen-sensitive secretory epithelial cells in the prostate, with little effect on basal epithelial and stromal cells). PATIENTS AND METHODS: The expression of the EGF system was evaluated by enzyme-linked immunosorbent assay and immunohistochemistry in samples of prostate tissue and secretions from patients with BPH randomized for treatment with finasteride or placebo for 3 months before surgery. RESULTS: Prostate tissue expressed the EGF receptor (HER1) and HER2, and the ligands EGF, transforming growth factor alpha (TGFalpha), heparin-binding (HB) EGF, betacellulin and amphiregulin. Treatment with finasteride produced greater concentrations of amphiregulin (P < 0.05) than did placebo, did not change the level of TGFalpha, HER1 and HER2, and tended to decrease the concentration of EGF, betacellulin and HB-EGF in prostate tissue. Using immunohistochemistry, HER1 and TGFalpha were both localized to the basal epithelial cells, and there was a strong positive correlation among the tissue concentrations of HER1, HER2 and TGFalpha. Amphiregulin localized to the luminal secretory epithelium. Prostate secretions contained only EGF, which was at levels approximately 150 times higher than in prostate tissue; treatment with finasteride did not affect the concentration of EGF in prostate secretion. CONCLUSIONS: There were only minor changes in the expression of TGFalpha, HER1 and HER2 after finasteride treatment. This may represent an important system for the continuous growth and homeostasis of the androgen-independent basal epithelial cells in the prostate.

Amphiregulin↗
PubMed2001

Increased plasma methylmalonic acid level does not predict clinical manifestations of vitamin B12 deficiency.

BACKGROUND: The prevalence of vitamin B(12) deficiency, defined as an elevated concentration of plasma methylmalonic acid (P-MMA), has been estimated to be 15% to 44% in the elderly. However, we do not know whether an increased P-MMA level actually indicates or predicts a clinical condition in need of treatment. PARTICIPANTS AND METHODS: In a follow-up study, 432 individuals not treated with vitamin B(12) were examined 1.0 to 3.9 years after initial observation of an increased P-MMA concentration (>0.28 micromol/L). The examination included laboratory tests, a structured interview to disclose symptoms, a food frequency questionnaire, and a clinical examination including a Neurological Disability Score. RESULTS: Variation in P-MMA levels over time was high (coefficient of variation, 34%). In only 16% of participants, P-MMA levels increased substantially, whereas 44% showed a decrease. Level of P-MMA was significantly but not strongly associated with levels of plasma cobalamins (r = -0.22, P<.001) and plasma total homocysteine (r = 0.37, P<.001). After adjustment for age and sex, we found no associations between P-MMA concentration and the total symptom score (P =.61), the total Neurological Disability Score (P =.64), or other clinical manifestations related to vitamin B(12) deficiency. CONCLUSIONS: An increased level of P-MMA did not predict a further increase with time and clinical manifestations related to vitamin B(12) deficiency. We therefore challenge the use of an increased P-MMA concentration as the only marker for diagnosis of vitamin B(12) deficiency.

Adolescent↗
PubMed2001

[Homocysteine and cardiovascular disease].

Treatment of highly increased plasma concentrations of homocysteine in patients with rare inborn errors of metabolism reduces their risk of vascular thromboses. Many, but not all, epidemiological studies show a relation between slightly increased plasma homocysteine and ischaemic cardiovascular disease. Folic acid supplements reduce plasma homocysteine. The results of ongoing studies of the effect of folic acid and other vitamins on the incidence of cardiovascular disease are expected within the next five years. The available data support the measurement of plasma homocysteine as a part of screening of patients with early and/or frequent vascular thromboses and a disparity between established risk factors and symptoms. Plasma homocysteine > 30 mumol/l in such patients should prompt a search for an inborn error of metabolism.

Amino Acid Metabolism, Inborn Errors↗
PubMed2001

Early urinary changes in Tamm-Horsfall protein and epidermal growth factor in diabetic children.

Both glomerular and tubular markers have been used to follow diabetic nephropathy. However, neither albumin nor proximal tubular markers have proven useful in prepubertal diabetes. Hence we studied two markers derived from the distal tubular cells, Tamm-Horsfall protein (THP) and epidermal growth factor (EGF). The urinary excretion of THP and EGF was examined in samples obtained during the first 20 days and 1 year after diagnosis of diabetes in children aged 4-15 years. Fourteen children without and 18 with ketonuria were examined, and 17 age-matched healthy children participated as controls. The excretion rate of EGF was increased at diagnosis, while that of THP was not. After 20 days of treatment the excretion of EGF had normalized, while the excretion of THP was decreased. Similar results were obtained after 1 year. In conclusion, in spite of good metabolic control a reduced excretion of THP persisted for at least 1 year after the diagnosis of diabetes. Whether the finding of reduced excretion of THP has any biological significance awaits further study.

Adolescent↗
PubMed2001

Chronic treatment with epidermal growth factor induces growth of the rat ventral prostate.

OBJECTIVE: The epidermal growth factor (EGF) system is expressed in the rat prostate, and growth factors from this system induce proliferation in prostate epithelial and stromal cell cultures. The aim of the study was to investigate the possible growth-promoting effects of the system during the hyperplastic growth phase of the prostate in newborn rats. MATERIAL AND METHODS: Newborn rats were treated for 8 weeks with EGF (150 microg/kg body weight per day), administered as daily subcutaneous injections. Sections of the prostate tissue were examined by a stereological technique to determine tissue composition. RESULTS: Treatment with EGF increased the weight of the ventral prostate, relative to body weight, by 50% compared with placebo (p < 0.005). Neither the dorsolateral prostate, seminal vesicles nor coagulating glands were affected by EGF. Prostate tissue showed a significant increase in the volume of the prostate epithelium, the stroma and the lumen following EGF treatment, in a pattern resembling physiological growth of the ventral prostate. A significant correlation (r = 0.78, p < 0.0001) of the volume fraction of the lumen with the glandular weight of the ventral prostate was seen. Serum testosterone was not affected by chronic EGF administration. CONCLUSIONS: EGF selectively induces growth of the ventral lobe of the prostate in newborn rats, in a pattern comparable to normal physiological growth. It may be hypothesized that the physiological growth of the prostate is directly correlated to endogenous activity of the EGF system in the rat prostate gland.

Animals↗
PubMed2001

Vitamin B12 treatment normalizes metabolic markers but has limited clinical effect: a randomized placebo-controlled study.

BACKGROUND: The clinical significance of increased plasma methylmalonic acid (P-MMA) is unclear. We assessed the efficacy of vitamin B12 treatment in reducing P-MMA and plasma total homocysteine compared with the clinical benefits of treatment. METHODS: We studied 140 individuals with mildly to modestly increased P-MMA (0.40-2.00 micromol/L), not previously treated with vitamin B12, in a randomized, placebo-controlled study. A detailed medical history was obtained, and laboratory tests as well as an objective neurologic disability score were performed at baseline and 3 months after the start of intervention. RESULTS: P-MMA (P <0.001) or plasma total homocysteine (P <0.001) decreased in the treatment group vs the placebo group, but no significant difference was found in the change of blood hemoglobin (P = 0.18) and mean cell volume (P = 0.71). Changes in symptom scores did not differ between the groups for symptoms of anemia (P = 0.63), neurologic symptoms (P = 0.21), gastroenterologic symptoms (P = 0.32), or the Neurological Disability Score (P = 0.85). CONCLUSIONS: Treatment with vitamin B12 reduces P-MMA and plasma total homocysteine, but individuals with a mild to modest increase in P-MMA may have only limited clinical benefit from vitamin B12 treatment, at least in the short term.

Adolescent↗
PubMed2000

Renal content and output of epidermal growth factor in long-term adrenergic agonist-treated rats.

This study investigates the renal and urinary levels of epidermal growth factor (EGF) in rats under long-term treatment with alpha- or beta-adrenergic agonists. Urine samples were obtained on days 7, 14 and 21, and renal tissue samples on day 21. EGF was quantified by ELISA and tissue sections were used for immunohistochemistry and in situ hybridization. Fractional kidney weight was increased in the alpha-adrenergic agonist-treated group by 35% when compared with controls. Histological examination of the kidney revealed well-defined wedge-shaped areas of tubular dilatations and luminal amorphous material in the distal tubules. Concomitantly, reduced levels of EGF and EGF mRNA were observed, and also the urinary levels of EGF were reduced. Together, these observations indicate alpha-adrenergic treatment to affect the distal tubules. Treatment with the beta-adrenergic agonist did not change fractional kidney weight, but initially the urinary excretion of EGF was reduced. The data add further evidence to the suggestion that activity of the sympathetic nervous system influences renal homeostasis of EGF, either directly or indirectly through renal histopathological changes.

Adrenergic alpha-Agonists↗