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U Syversen

Publications and source records attributed to U Syversen.

At least 19 recordsLinked to original sources
PubMed2007

Long-term fluoxetine administration does not result in major changes in bone architecture and strength in growing rats.

Many studies have indicated that serotonin and its transporter play a role in bone metabolism. In this study we investigated the effect of selective serotonin re-uptake inhibitor (SSRI), fluoxetine (Prozac) on bone architecture and quality in growing female rats. We therefore administrated rats with clinically relevant doses of fluoxetine for a period of 6 months. DXA scans were performed during the treatment period in order to follow parameters as body weight, fat percentage and BMD. After 6 months of treatment, femurs were used to analyze bone architecture and bone strength, by means of microCT scans and three-point bending assays, respectively. We found a slightly diminished bone quality, reflected in a lower bone tissue strength, which was compensated by changes in bone geometry. As leptin and adiponectin could be possible factors in the serotonergic regulation of bone metabolism, we also determined the levels of these factors in plasma samples of all animals. Leptin and adiponectin levels were not different between the control group and fluoxetine-treated group, indicating that these factors were not involved in the observed changes in bone geometry and quality.

Adiponectin↗
PubMed2006

Serotonin and fluoxetine modulate bone cell function in vitro.

Recent studies have proposed a role for serotonin and its transporter in regulation of bone cell function. In the present study, we examined the in vitro effects of serotonin and the serotonin transporter inhibitor fluoxetine "Prozac" on osteoblasts and osteoclasts. Human mononuclear cells were differentiated into osteoclasts in the presence of serotonin or fluoxetine. Both compounds affected the total number of differentiated osteoclasts as well as bone resorption in a bell-shaped manner. RT-PCR on the human osteoclasts demonstrated several serotonin receptors, the serotonin transporter, and the rate-limiting enzyme in serotonin synthesis, tryptophan hydroxylase 1 (Tph1). Tph1 expression was also found in murine osteoblasts and osteoclasts, indicating an ability to produce serotonin. In murine pre-osteoclasts (RAW264.7), serotonin as well as fluoxetine affected proliferation and NFkappaB activity in a biphasic manner. Proliferation of human mesenchymal stem cells (MSC) and primary osteoblasts (NHO), and 5-HT2A receptor expression was enhanced by serotonin. Fluoxetine stimulated proliferation of MSC and murine preosteoblasts (MC3T3-E1) in nM concentrations, microM concentrations were inhibitory. The effect of fluoxetine seemed direct, probably through 5-HT2 receptors. Serotonin-induced proliferation of MC3T3-E1 cells was inhibited by the PKC inhibitor (GF109203) and was also markedly reduced when antagonists of the serotonin receptors 5-HT2B/C or 5-HT2A/C were added. Serotonin increased osteoprotegerin (OPG) and decreased receptor activator of NF-kappaB ligand (RANKL) secretion from osteoblasts, suggesting a role in osteoblast-induced inhibition of osteoclast differentiation, whereas fluoxetine had the opposite effect. This study further describes possible mechanisms by which serotonin and the serotonin transporter can affect bone cell function.

3T3 Cells↗
PubMed2006

Osteoporosis in a population from medieval Norway.

Modern populations from Norway and England differ in their experience of osteoporosis, the former showing lower bone mineral density (BMD) and a higher fragility fracture rate. The aim of the present work was to investigate whether this was also the case during the Middle Ages. Age-dependent loss of BMD in the proximal femur was assessed using dual X-ray absorptiometry (DXA) in male and female adult skeletons from a cemetery in the medieval town of Trondheim, Norway. Fracture prevalence was also investigated. Results were compared with those previously reported for a skeletal series from Wharram Percy, a deserted medieval village in England. Results indicate that peak BMD and patterns of age-related loss of BMD in the Norwegian and the English group were similar. Among females, the prevalence of osteoporotic fractures was greater in the Norwegian than in the English population. The BMD results suggest that differences in BMD between English and Norwegians are of recent origin, although given the fairly modest sample sizes, further work is needed to confirm this. Reasons for the greater prevalence of osteoporotic fractures in women in the Norwegian skeletal series are unclear, but the colder climate and greater frequency of hard surfaces may have meant that falls were more frequent, and when they occurred, were more likely to result in fractures than in the rural English group.

Adolescent↗
PubMed2004

The need for clinical guidance in the use of calcium and vitamin D in the management of osteoporosis: a consensus report.

A European Union (EU) directive on vitamins and minerals used as ingredients of food supplements with a nutritional or physiological effect (2002/46/EC) was introduced in 2003. Its implications for the use of oral supplements of calcium and vitamin D in the prevention and treatment of osteoporosis were discussed at a meeting organized with the help of the World Health Organization (WHO) Collaborating Center for Public Health Aspects of Rheumatic Diseases (Liège, Belgium) and the support of the WHO Collaborating Center for Osteoporosis Prevention (Geneva, Switzerland). The following issues were addressed: Is osteoporosis a physiological or a medical condition? What is the evidence for the efficacy of calcium and vitamin D in the management of postmenopausal osteoporosis? What are the risks of self-management by patients in osteoporosis? From their discussions, the panel concluded that: (1) osteoporosis is a disease that requires continuing medical attention to ensure optimal therapeutic benefits; (2) when given in appropriate doses, calcium and vitamin D have been shown to be pharmacologically active (particularly in patients with dietary deficiencies), safe, and effective for the prevention and treatment of osteoporotic fractures; (3) calcium and vitamin D are an essential, but not sufficient, component of an integrated management strategy for the prevention and treatment of osteoporosis in patients with dietary insufficiencies, although maximal benefit in terms of fracture prevention requires the addition of antiresorptive therapy; (4) calcium and vitamin D are a cost-effective medication in the prevention and treatment of osteoporosis; (5) it is apparent that awareness of the efficacy of calcium and vitamin D in osteoporosis is still low and further work needs to be done to increase awareness among physicians, patients, and women at risk; and (6) in order that calcium and vitamin D continues to be manufactured to Good Manufacturing Practice standards and physicians and other health care professionals continue to provide guidance for the optimal use of these agents, they should continue to be classified as medicinal products.

Aged↗
PubMed2004

Clinical significance of elevated serum chromogranin A levels.

BACKGROUND: Chromogranin A (CgA) has been shown to be a useful marker in the diagnosis of neuroendocrine (NE) tumours. The clinical significance of CgA has been studied mostly in patients with known NE tumours. The diagnosis was evaluated in 153 consecutive patients in whom CgA was measured in a given time interval. METHODS: CgA in serum was measured by radioimmunoassay. Immunohistochemistry with an antibody against CgA was performed in tumours from patients with adenocarcinoma and elevated CgA levels using a conventional method and the more sensitive tyramide signal amplification (TSA) technique. RESULTS: Elevated serum CgA levels were found in 44 patients; 19 had NE tumours and 6 had tumours classified as adenocarcinomas. With the TSA technique, a high proportion of CgA-positive cells were disclosed in five of the adenocarcinoma patients. Patients with atrophic gastritis (no. 2) and patients treated with inhibitors of gastric acid secretion (no. 6) also had elevated levels of CgA. A modest increase in CgA levels was observed in 2 patients with renal impairment, and in 9 patients without any obvious cause. CONCLUSION: The current study confirms that serum CgA is a sensitive marker for the detection of NE neoplasia. Elevated levels found in patients with adenocarcinoma may indicate NE differentiation in the tumour. CgA is a useful tool in the monitoring of enterochromaffin-like (ECL) hyperplasia secondary to treatment with acid secretion inhibitors or atrophic gastritis.

Adenocarcinoma↗
PubMed2004

Treatment of ECL cell carcinoids with octreotide LAR.

BACKGROUND: Patients with chronic atrophic gastritis (CAG) and hypergastrinaemia are at risk of developing hyperplasia of the enterochromaffin-like (ECL) cells and ECL-cell-derived tumours. The effect of the somatostatin analogue octreotide on ECL cell carcinoids is examined. METHODS: Five patients with hypergastrinaemia and ECL cell carcinoids were enrolled in a 1-year study of octreotide LAR (long-acting release) 20 mg given at monthly intervals. Biopsies from tumours and from flat oxyntic mucosa were done at the start and 3, 6 and 12 months thereafter. Sections were stained with haematoxylin-erythrosin, immunostained with chromogranin A (CgA) and doublestained with CgA and Ki-67. Serum gastrin and CgA were measured. RESULTS: The number of visible tumours was reduced by more than 50 %. Sections from both tumours and flat mucosa showed a reduced number of CgA immunoreactive cells. Mean serum gastrin decreased from 421 to 186 pM (normal <40 pM); P > 0.05, and serum CgA from 73 to 25 ng/ml (normal < 30 ng/ml); P < 0.001. CONCLUSIONS: During treatment the patients were still markedly hypergastrinaemic, whereas the serum CgA showed normalization. A diminished tumour load and reduced ECL cell density were found, indicating an antiproliferative effect of octreotide directly on the ECL cells.

Aged↗
PubMed2003

The effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone density in men with osteoporosis.

Teriparatide [rhPTH(1-34)] increases bone mineral density and reduces the risk of vertebral fracture in women. We randomized 437 men with spine or hip bone mineral density more than 2 SD below the young adult male mean to daily injections of placebo, teriparatide 20 microg, or teriparatide 40 microg. All subjects also received supplemental calcium and vitamin D. The study was stopped after a median duration of 11 months because of a finding of osteosarcomas in rats in routine toxicology studies. Biochemical markers of bone formation increased early in the course of therapy and were followed by increases in indices of osteoclastic activity. Spine bone mineral density was greater than in placebo subjects after 3 months of teriparatide therapy, and by the end of therapy it was increased by 5.9% (20 microg) and 9.0% (40 microg) above baseline (p < 0.001 vs. placebo for both comparisons). Femoral neck bone mineral density increased 1.5% (20 microg; p = 0.029) and 2.9% (40 microg; p < 0.001), and whole body bone mineral content increased 0.6% (20 microg; p = 0.021) and 0.9% (40 microg;p = 0.005) above baseline in the teriparatide subjects. There was no change in radial bone mineral density in the teriparatide groups. Bone mineral density responses to teriparatide were similar regardless of gonadal status, age, baseline bone mineral density, body mass index, smoking, or alcohol intake. Subjects experienced expected changes in mineral metabolism. Adverse events were similar in the placebo and 20-microg groups, but more frequent in the 40-microg group. This study shows that teriparatide treatment results in an increase in bone mineral density and is a potentially useful therapy for osteoporosis in men.

Adult↗
PubMed2001

Long-term omeprazole treatment suppresses body weight gain and bone mineralization in young male rats.

BACKGROUND: The stomach is rich in endocrine cells, including those producing ghrelin, which is thought to play a role in the control of body growth. Omeprazole treatment is associated with hypergastrinaemia, resulting in growth of the oxyntic mucosa in general and the enterochromaffin-like (ECL) cells in particular. In the present study, we examined the effects of long-term omeprazole treatment on young male rats with respect to body growth and stomach. METHODS: Male rats (24 days old) were treated with omeprazole (400 micromol/kg/day) or vehicle for 77 days. The body weight was recorded twice per week. At sacrifice, dual-energy X-ray absorptiometry (DXA) was used to assess total bone area, bone mineral content (BMC), bone mineral density (BMD) and body composition (fat and lean body mass). The lengths of the spine and the femur were recorded. The plasma concentrations of gastrin and histamine were determined by radioimmunoassays. The endocrine cells of the stomach were examined by immunocytochemistry. RESULTS: The body weight gain was suppressed by omeprazole treatment. The bone area, BMC and BMD were reduced, while the lengths of the spine and the femur and the body composition were unchanged. Omeprazole-induced hypergastrinaemia was associated with enlargement of the oxyntic area and with hyperplasia of ECL cells but not of A-like cells and D cells. In contrast, the enterchromaffin (EC) cell density in the antrum was reduced. CONCLUSIONS: Omeprazole treatment of young male rats reduces body weight and bone mass gain. The densities of ECL cells in the oxyntic mucosa was increased and of the EC cells in the antral mucosa reduced.

Age Factors↗
PubMed2001

Hypergastrinemia as a cause of chromogranin a increase in blood in patients suspected to have neuroendocrine tumor.

BACKGROUND: Chromogranin A (CgA) is a sensitive marker for neuroendocrine neoplasia. Enterochromaffin-like cell hyperplasia secondary to hypergastrinemia also leads to CgA increase in blood. Treatment with inhibitors of acid secretion, atrophic gastritis and infection with Helicobacter pylori are prevalent conditions leading to hypergastrinemia. We therefore wanted to study whether concomitant determination of gastrin could increase the utility of CgA as a marker of neuroendocrine neoplasia. METHODS: CgA and gastrin concentrations were determined by radioimmunoassay methods, while pepsinogen I (used to diagnose severe atrophic gastritis) was determined by a commercial immunoenzymatic assay. RESULTS: Among 100 patients with elevated CgA, we found that 29% had hypergastrinemia. Vice versa, CgA was elevated in 23 out of 26 (88.5%) in a population of patients with hypergastrinemia. By determining pepsinogen I in blood in patients with hypergastrinemia, a proportion of them was diagnosed as having severe atrophic gastritis. CONCLUSION: We conclude that determination of gastrin in blood in patients with CgA elevation will increase the utility of CgA in the diagnosis of neuroendocrine tumors.

Biomarkers, Tumor↗
PubMed2001

Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization.

The adipose hormone leptin and its receptor are important for regulation of food intake and energy metabolism. Leptin also is involved in the growth of different tissues. In this study, we show the expression of leptin in primary cultures of normal human osteoblasts (hOBs) as evidenced by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry. Release of leptin into the medium also was found. Leptin was not detected in commercially available hOBs (NHOst) or in three different human monoclonal osteosarcoma cell lines. Leptin expression was observed in OBs in the mineralization and/or the osteocyte transition period but not during the matrix maturation period. Furthermore, hOBs and osteosarcoma cell lines expressed the long signal-transducing form of the leptin receptor (OB-Rb) as shown by RT-PCR. We observed no significant changes in leptin or OB-Rb genes in hOBs after incubation with recombinant leptin, indicating no autoregulation of the leptin expression. Incubation of both hOBs entering the mineralization phase and osteosarcoma cell lines with recombinant leptin markedly increased the number of mineralized nodules as shown by alizarin S staining. These findings indicate that leptin may be of importance for osteoblastic cell growth and bone mineralization.

3T3 Cells↗
PubMed2000

Anorexia nervosa: slow regain of bone mass.

In a retrospective study of women aged 18-30 years, aimed at assessing factors associated with peak bone mass (PBM), 13 of 239 study cases reported having had anorexia nervosa. The mean total femoral and lumbar bone mineral density (BMD) values were not significantly lower in women who had had anorexia than in the pooled group (mean Z-scores of -0.60 and -0.48). Cases with less than 6 years since the anorexia had on average a present weight 5.7 kg less than their premorbid weights, while cases with more than 6 years since the eating disorder had an average weight 22.5 kg above their pre-morbid weights. The cases who had not regained their weight had BMD values significantly lower than the pooled material (mean Z-scores -1.15 and -0.9 in the lumbar spine and total femur respectively). Those who had regained their weight had BMD values as predicted from their present anthropometric data, while those who had not regained their weight had BMD values that were substantially below that predicted from their present weight. Anorexia nervosa seems to be associated with a low BMD which is even lower than that which can be predicted from the weight loss alone. This suggests that weight loss and other factors, such as menstrual dysfunction and estrogen deficiency, are independent and thus additive causes of bone loss in anorexia nervosa. Recovery of BMD seems slow, but the BMD may become as predicted from the anthropometric data after restoration of body weight and menses. The potential for recovery of BMD seems intact for several years after menarche.

Adolescent↗
PubMed1999

Effect of lifelong nicotine inhalation on bone mass and mechanical properties in female rat femurs.

As tobacco smoking has been identified as a risk factor in the development of osteoporosis, possible deleterious effects of nicotine inhalation on bone mineral density (BMD) and mechanical properties of the femur in female rats were studied. Female Sprague Dawley rats were exposed to nicotine vapour 20 hours a day 5 days a week for 2 years. The nicotine concentration in the inhaled air was kept at a level, giving a plasma nicotine concentration exceeding that of heavy smokers. Throughout the study, the nicotine-exposed rats weighed approximately 10% less than the control rats. At the end of the study the rats were anesthesized and blood was collected by heart puncture for determination of nicotine in plasma. Both femurs were resected and scanned by dual X-ray absorptiometry (DXA). There was no difference in BMD between control rats (n = 7) and nicotine-exposed rats (n = 23) (mean 0.216 +/- 0.021 g/cm(2) and 0. 210 +/- 0.014 g/cm(2), respectively (P = 0.19)). The left femur was used for mechanical testing of the shaft and the neck. No significant difference could be demonstrated in ultimate bending moment, ultimate energy absorbtion, stiffness, or deflection between the two groups. In conclusion, no negative effects of nicotine inhalation on the femurs of female rats were found.

Absorptiometry, Photon↗
PubMed1998

Neuroendocrine differentiation in human gastric carcinoma.

BACKGROUND: Distinguishing between neuroendocrine carcinoma and adenocarcinoma may be difficult. METHODS: In the current prospective study blood and tumor tissue from patients with gastric carcinoma were collected. The tissue was fixed in different ways to allow examination for neuroendocrine markers by multiple methods such as various histochemical and immunohistochemical methods and electron microscopy. Blood and tumor homogenates were examined by radioimmunoassay for specific hormones and general neuroendocrine markers. RESULTS: Based on examination of general neuroendocrine markers such as chromogranin A (by immunohistochemistry, Northern blot analysis, and tissue concentration), neuron specific enolase (immunohistochemistry) as well as electron microscopy, it was possible to conclude that approximately 10% of the tumors were actually neuroendocrine malignant tumors. Among these tumors, the enterochromaffin-like (ECL) cell was the most preponderant cell of origin (Sevier-Munger positive and serotonin negative immunoreactive tumor cells with secretory granules resembling those observed in normal ECL-cells). As reported previously, tumors of the diffuse type (according to the classification of Laurén) most often were reclassified as neuroendocrine carcinomas. CONCLUSIONS: The current study shows that neuroendocrine and particularly ECL cell-derived tumors are more common in the stomach than previously recognized.

Adenocarcinoma↗
PubMed1998

[Diphosphonates--pharmacology and clinical use].

Based upon recent research, bisphosphonates have now attained a ranking as the first alternative to oestrogen replacement therapy in women with postmenopausal osteoporosis. The efficacy of these drugs has been clearly documented in recent years, particularly as a result of extensive clinical trials with alendronate. The studies have also confirmed the favourable risk/benefit ratio. The specific affinity of bisphosphonates for bone tissue has been recognized for many years, and explains the diagnostic use of radio-labelled species in skeleton scintigraphy. Bisphosphonates deposited in bone tissue reverse the osteoporotic process by inhibiting osteoclastic bone resorption. This mechanism also explains their role as the treatment of choice in patients with Paget's disease and cancer induced hypercalcaemia. In addition, the same drugs are useful adjuvants in the treatment of patients with multiple myeloma or bone metastases to lessen the pain and risk of fracture. A possible role of bisphosphonates in the management of cancer patients without detectable bone metastases or patients with rheumatoid arthritis has been discussed, but further research is needed in these areas.

Diphosphonates↗
PubMed1998

NGF-beta, NE-cells and prostatic cancer cell lines. A study of neuroendocrine expression in the human prostatic cancer cell lines DU-145, PC-3, LNCaP, and TSU-pr1 following stimulation of the nerve growth factor-beta.

Neuroendocrine (NE) cells are present in both benign and malignant human prostate. However, their function is poorly understood, mainly due to the lack of suitable experimental models. The nerve growth factor-beta (NGF-beta) promotes the rat pheochromocytoma cell line PC-12 to differentiate into neuronal like cells. We have studied the effect of NGF-beta on four human prostate cancer cell lines, LNCaP, DU-145, PC-3, and TSU-pr1. NGF-beta stimulates the growth rate in all these cell lines, but does not induce a neuronal phenotype. NE tumour markers (chromogranin A [CgA] and chromogranin B[CgB]) could not be demonstrated by immunocytochemistry (CgA and CgB), Northern blotting (CgA), or ELISA techniques (CgA), neither in control nor in NGF-beta stimulated cells. Consequently, other experimental models have to be sought in the study of NE cells in the human prostate.

Blotting, Northern↗