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Biomedical subjects

Per Ole Iversen

Publications and source records attributed to Per Ole Iversen.

At least 19 recordsLinked to original sources
PubMed2007

A murine model for studying hematopoiesis and immunity in heart failure.

Recent epidemiological research indicates that a coexistent anemia among patients with heart failure might worsen their prognosis. However, whether the reduced synthesis of red blood cells is a contributing factor to the development and progression to overt heart failure, or whether it simply is a mere consequence of a dysfunctional heart, remains to be elucidated. Studies in mice with experimentally induced acute myocardial infarction leading to subsequent development of a postinfarction congestive heart failure have shed some light on this problem. Careful analyses of the number and of the functions of various hematopoietic cells residing in either blood or bone marrow point to a possible inhibitory role of cytokines, such tumor necrosis factor alpha, on hematopoiesis. The present protocols will hopefully encourage further studies of hematopoiesis and immunity in heart failure by using a combination of animal models with state-of-the-art techniques in molecular biology to define and validate possible targets for therapy.

Animals↗
PubMed2006

Increase in matrix metalloproteinases from endothelial cells exposed to umbilical cord plasma from high birth weight newborns.

Large for gestational age infants have increased risk of developing the metabolic syndrome and cardiovascular disease in child- and adulthood. The vascular endothelium is a target site in the pathogenesis of many cardiovascular disorders. The matrix metalloproteinases (MMP) are important modulators of the extracellular matrix and serve as markers of these disorders. Here, we asked whether umbilical cord plasma of high birth weight (HBW; >4 kg) infants could modulate functional properties of human umbilical vein endothelial cells (HUVEC) compared with plasma from normal birth weight (NBW; 3.1-3.6 kg) infants. To test this, HUVECs were exposed for 48 h to 20% venous cord plasma from HBW or NBW infants. The MMP activity in supernatants of HUVECs exposed to HBW plasma was nearly three times higher (P < 0.05) than that obtained with NBW plasma. MMP-9, but not MMP-2, protein concentration and mRNA expression were enhanced in HBW (P < 0.05). With specific blockers, MMP activity and mRNA-MMP-9 were inhibited by approximately 60-70%. Cord lipid and insulin concentrations were similar (P > 0.05) among the two groups. We could not detect any significant differences between the two groups in the concentrations of proinflammatory cytokines or specific tissue inhibitors of MMP in plasma or HUVEC supernatants. In conclusion, cord plasma from HBW infants induced more MMP-9 in HUVECs compared with cord plasma from NBW infants. Although not identified, cord plasma of HBW infants may contain factors that increase endothelial cell MMP. These findings may indicate an association between fetal nutritional conditions and endothelial cell functions.

Adult↗
PubMed2006

[Gestational diabetes in women from South Asia].

BACKGROUND: The number of patients with diabetes is growing worldwide. In particular this increase, most pronounced for type 2 diabetes, affects South-Asians. In Norway pregnant women originating from this region are more prone to gestational diabetes than ethnic Norwegians. More knowledge is needed to prevent and treat this disease effectively. Here we give a brief overview of the epidemiology and risk factors associated with gestational diabetes. MATERIALS AND METHODS: Information related to gestational diabetes was obtained from various databases, including PubMed, HighWire and Ovid, in addition to our own experience. RESULTS AND INTERPRETATION: Some methodological aspects preclude a definite assessment of the true extent of gestational diabetes nationally as well as internationally. About 0.01 3% of Caucasian pregnancies are affected while the corresponding number among South-Asian women is 5 to 10 times higher. Most studies identify obesity as an important risk factor. Generally, advice on diet and physical activity can prevent diabetes. Similar interventions might also be useful among the increasing population of immigrant fertile women in Norway.

Asia↗
PubMed2006

Marked changes in plasma lipids and lipoproteins during pregnancy in women with familial hypercholesterolemia.

Serum lipids increase during pregnancy. However, data are scarce for lipid changes in pregnant women with heterozygous familiar hypercholesterolemia (FH). The purpose of the present study was to examine plasma lipids and lipoproteins during pregnancy in women with FH. In 22 pregnant women blood samples were collected at gestational weeks 17-20 (baseline), 24, 30 and 36. Total- and LDL cholesterol increased significantly between baseline and gestational week 36 by 29% and 30%, respectively, compared to 25% and 34% in a reference group of 149 healthy pregnant women. Notably, the plasma lipid concentrations in the FH women were much higher than in the reference women. Triglycerides increased (P<0.05) by 116% and 103%, in the FH group and reference group, respectively. HDL cholesterol was unchanged in both groups. Moreover, apolipoprotein B increased significantly during pregnancy in the FH women, whereas apolipoprotein A1 and lipoprotein (a) were unchanged. Pregnancy outcomes in the FH group did not differ significantly from those in the reference group. In conclusion, the relative increase in plasma lipids was similar in pregnant women with FH and in healthy women, but the absolute magnitude was considerably larger in pregnant FH women.

Adult↗
PubMed2005

Tumor necrosis factor alpha and adiponectin in bone marrow interstitial fluid from patients with acute myeloid leukemia inhibit normal hematopoiesis.

PURPOSE: Locally residing cytokines may inhibit bone marrow hematopoiesis in acute myeloid leukemia (AML). Using a novel method to isolate bone marrow interstitial fluid, we examined if this fluid from 10 adult AML patients could affect normal bone marrow hematopoiesis. EXPERIMENTAL DESIGN: Bone marrow interstitial fluid was isolated by centrifugation of bone marrow biopsies obtained at time of diagnosis and 2 to 4 weeks after start of induction therapy. The isolated fluid was added to normal bone marrow CD34 hematopoietic progenitor cells sampled from five healthy subjects. RESULTS: Unlike plasma, AML-derived bone marrow interstitial fluid clearly repressed hematopoietic progenitor cell growth as determined by an in vitro colony assay, an effect that was lost after successful induction treatment. Antibodies against tumor necrosis factor alpha (TNFalpha) and adiponectin abolished growth inhibition by bone marrow interstitial fluid, suggesting a mechanistic role of these cytokines in impairing normal hematopoiesis in AML. The plasma levels of adiponectin and TNFalpha were unaffected by therapy whereas bone marrow interstitial fluid levels of both cytokines fell significantly in patients entering remission. Transcripts for TNFalpha, but not for adiponectin, were found in AML blast cells. Neither the plasma levels nor the bone marrow interstitial fluid levels of the proangiogenic factors vascular endothelial growth factor or basic fibroblast growth factor were appreciably elevated in the patients nor did they change with treatment. CONCLUSIONS: Specific analyses of bone marrow interstitial fluid may give novel information on normal and malignant hematopoietic activity and thus form the basis for mechanism-based therapy.

Adiponectin↗
PubMed2005

Differences in circadian variations of tissue factor pathway inhibitor type 1 between able-bodied and spinal cord injured.

INTRODUCTION: Tissue factor pathway inhibitor type 1 (TFPI) is the physiological inhibitor of the tissue factor pathway of coagulation. TFPI is produced by endothelial cells, and most intravascular TFPI is composed of full-length TFPI associated with the endothelium. Circulating TFPI is mainly truncated and lipoprotein-associated, but a small fraction circulates in a free full-length form. Although hormonal state influences the plasma variation of TFPI between individuals, other factors like temporal variation may be important. Hence, in the current study we aimed at exploring the intra-individual variation with focus on the possible circadian variations of TFPI. MATERIALS AND METHODS: TFPI free and total antigen from 8 able-bodied and 6 tetraplegic men were measured at 12 time points during a 24 h period. RESULTS: TFPI free antigen in the able-bodied exhibited circadian variation with the highest levels (approximately 20% above mean) from 12:00 to 18:00 h and the lowest levels (approximately 15% below mean) at 09:00 and 02:00 h. In contrast, TFPI free antigen in the tetraplegic group showed no circadian variation. TFPI total antigen exhibited circadian variation in neither group, but mean TFPI total antigen was lower in the tetraplegic group compared with the able-bodied (80 versus 110 ng/mL, respectively). Notably, even if TFPI total antigen in both groups did not vary according to any specific circadian rhythm, the intra-individual variation was higher than the assay variation. CONCLUSION: TFPI free antigen exhibited circadian variations in able-bodied, but not in tetraplegic subjects and the able-bodied had higher levels of TFPI total antigen than the tetraplegic group.

Adult↗
PubMed2005

[Fetal nutrition and future health].

Fetal nutrition may permanently affect physiological properties of the new individual and hence the risk of future disease. Epidemiological studies indicate that fetal nutrition may significantly influence the risk of diabetes, cardiovascular disease, and cancer. Controlled animal studies show that even properties traditionally considered as exclusively genetic, like fur colour, may be modified by altered maternal nutrition. The expression "fetal programming" has been introduced to describe permanent effects of environmental conditions in fetal life. An important mechanism of fetal programming seems to be epigenetic regulation. One example of epigenetic regulation is methylation of the DNA base cytosine in promoter regions of some genes. DNA methylation will lead to decreased gene expression. Over the last two decades, marked changes in dietary habits and other life style features have taken place among young Norwegian women. This is particularly reflected in the increasing prevalence of obesity. Maternal weight and metabolic status is closely associated with the growth and development of the fetus. Thus, diet and physical activity become particularly important aspects of the health of young women.

Animals↗
PubMed2005

Ribozymes, DNAzymes and small interfering RNAs as therapeutics.

Selective gene silencing by nucleic acid enzymes has provided researchers with a new strategy to block gene expression and drug target validation. Ribozymes, DNAzymes and small interfering RNAs (siRNAs) are being explored as genetic inhibitors of gene expression as well as potential therapeutics against viral infections, inflammatory disorders, haematological diseases and cancers. We review the mode of action of these molecules, with special emphasis on their construction and the possibility to enhance their serum half-lives via specific chemical modifications. Their potential use in cell cultures and in animal models for disease is also highlighted.

Animals↗
PubMed2004

[Salt and hypertension--100 years of unresolved issues].

BACKGROUND: In recent years, criticism against the so-called "salt hypothesis" has gained momentum. We give a brief review of important data related to this issue, in particular of the evidence-based documentation supporting a general recommendation of reduced salt intake. MATERIAL AND METHODS: We searched in PubMed, Ovid and HighWire for papers relating to salt intake, blood pressure and cardiovascular disease. RESULTS: Most studies in favour of the salt hypothesis rely on short-term (about 30 days) intervention trials. The possible benefit of salt restriction on hypertension and hypertension-related morbidity and mortality is not firmly established. INTERPRETATION: A general recommendation of a reduction in salt intake among Norwegians to 5 g/day or less is not scientifically justified. More studies on salt intake in the general Norwegian population as well as intervention trials spanning years are warranted.

Animals↗
PubMed2004

[Nutrition for preterm infants].

BACKGROUND: Each year about 630 infants are born with very low birth weight (below 1500 g) in Norway. In spite of an increased survival rate over the past 30 years, many challenges remain in the treatment of premature infants; their nutritional need is an important aspect. MATERIAL AND METHODS: This review is based on searches in the Medline database. RESULTS AND INTERPRETATION: Human milk is the first choice for premature babies in Norway. The beneficial effects of human milk for premature babies are well documented, but unfortified human milk does not meet the nutritional needs of very low birth weight infants. Infants fed human milk grow slower than babies fed preterm formula. Fortification is necessary. There are many unsolved problems concerning nutrition for premature babies. What is the best rate of advancement in parenteral and enteral nutrition? How to improve the energy and protein fortification of human milk? Does human milk meet the need for long-chain polyunsaturated fatty acids or is a supplement indicated? What are the optimal doses of vitamin and mineral supplements? What is the recommended nutrition after discharge? More clinical trials are needed to establish evidence-based practice.

Dietary Supplements↗
PubMed2004

Demonstration of altered signaling responses in bone marrow extracellular fluid during increased hematopoiesis in rats using a centrifugation method.

The composition and characteristics of the bone marrow extracellular fluid supposedly modify the transport of cytokines, drugs, and other signaling molecules involved in the regulation of bone marrow function. Direct access to the bone marrow extracellular fluid surrounding hematopoietic cells is complicated by the virtually noncompliant surrounding bone tissue. We examined the applicability of a centrifugation method to obtain representative samples of bone marrow extracellular fluid from rats and humans. Perforated rat bones or human bone marrow biopsies were wrapped in nylon mesh baskets before being centrifuged at 180-239 g. In the rats, we found an only minor contribution of fluid from other sources than the bone marrow extracellular fluid as indicated by the average ratio of centrifugate-to-plasma activity of the extracellular tracer fluid 51Cr-labeled EDTA of 0.85. The colloid osmotic pressure in the centrifugate was consistently lower than that in the corresponding plasma in both species. In rats and humans, high-performance liquid chromatography showed a protein elution pattern from the bone marrow fluid similar to that of plasma, except for a peak eluting in the approximately 40-kDa molecular mass range. Western blotting of the cytokines erythropoietin and granulocyte colony-stimulating factor revealed generally higher amounts in the centrifugate than in the plasma. This difference was augmented during increased hematopoietic activity induced by inflammation or bleeding in rats. We conclude that the centrifugation method provides representative samples of bone marrow extracellular fluid and that extracellular signaling responses to altered hematopoiesis are more clearly reflected locally in the bone marrow interstitium than in plasma.

Adult↗
PubMed2004

Preserved granulocyte formation and function, as well as bone marrow innervation, in subjects with complete spinal cord injury.

Patients with a spinal cord injury are at risk of infections and is partly attributed to immobilization. Their lymphocyte-mediated immunity is impaired and the growth of blood progenitor cells is reduced. An adequate immune response depends on granulocytes being mobilized rapidly and activated properly, at the inflammatory site. Possibly this requires a coordinated interaction between the autonomous nervous system and cells within the haematopoietic bone marrow. Granulocyte function in the spinal cord injured has not been evaluated. Although there is evidence that the bone marrow in rodents is innervated, it is uncertain whether human bone marrow is similarly affected. Microscopy and immunolabelling followed by flow cytometry, showed that blood and bone marrow counts of leucocyte subsets were similar in paraplegic, tetraplegic and control subjects (P > 0.05). Neutrophilic migration and oxygen consumption, as well as eosinophil activation, assayed as release of eosinophilic cationic protein or CD69 expression, were not altered after spinal cord injury (P > 0.05). Cryostat sections of human bone marrow biopsies stained positive with glyoxylic acid, indicating the presence of catecholamine-containing nerves in both the patients and the controls. We conclude that terminal differentiation and formation of granulocytes, as well as their functional capacity, do not depend appreciably on supraspinal nervous regulation.

Adrenergic Fibers↗
PubMed2004

Inhibition of gene expression by nucleic acid enzymes in rodent models of human disease.

Nucleic acid enzymes have emerged as a versatile technique for sequence-specific gene silencing in a wide range of cells. However, the question remains as to whether, for example, DNA enzymes and ribozymes are functional in animals. In this chapter, we describe two different rodent models of human diseases--namely, leukemia and chronic heart failure. We specifically reduced Raf-1 expression in leukemic mice using an anti-Raf-1 DNA enzyme. A continuous supply of this catalytic molecule led to a substantial reduction in leukemic-cell burden and survival. Rats with postinfarction heart failure were treated with a DNA enzyme targeting TNFa, and this led to a substantial improvement of cardiac function concomitant with a restoration of the hemodynamic status of the animals. The described protocols should facilitate the in vivo evaluation of other oligonucleotide-based therapy such as small interfering RNAs (siRNAs).

Animals↗
PubMed2003

[Water--for life].

BACKGROUND: Water is an indispensable nutrient because of its physicochemical properties. People seem to consume more water than before although the scientific basis for this has not been firmly established. MATERIAL AND METHODS: We present a short overview of data retrieved from the databases PubMed and Ovid, with particular emphasis on the regulation of water intake and water excretion in adults. RESULTS: Water excretion is mainly regulated through the production of urine. Anti-diuretic hormone plays a key role. The intake of water is mainly governed via the poorly defined sense of thirst. Circumstantial evidence supports an increased intake of water to prevent certain cancers and cardiovascular diseases. INTERPRETATION: Both excessive hydration and dehydration can cause serious illness, in particular in the elderly. There is a lack of firm scientific support for the beneficial health effects of increased water intake.

Adult↗
PubMed2003

[Angiogenesis and hematological malignancies].

BACKGROUND: It is fairly well documented that the growth and metastasis of solid tumours is accompanied by increased formation of new blood vessels emanating from a pre-existing vascular bed. Recent findings suggest that angiogenesis also takes place in haematological malignancies. These findings suggest that angiogenesis might be a potential target for therapy. MATERIALS AND METHODS: A short review is presented on the basis of literature identified on PubMed and Medline as well as our own data. RESULTS: When surrogate markers are used, such as the plasma concentration of angiogenic growth factors or the density of blood vessels within the bone marrow, angiogenesis is associated with poor prognosis and treatment outcome in haematopoietic malignancy. While human treatment data are scarce, findings in animal experiments suggest that anti-angiogenesis might retard leukemogenesis. INTERPRETATION: The proliferation and dissemination of malignant blood cells seems to be related to increased angiogenesis in the bone marrow. Targeting components of the angiogenic process might offer adjunct treatment modalities in haematopoietic malignancy.

Angiogenesis Inhibitors↗
PubMed2002

Prevention of leptin binding to its receptor suppresses rat leukemic cell growth by inhibiting angiogenesis.

Leptin promotes the growth and viability of hematopoietic cells, and it also stimulates microvessel formation, indicating a role for leptin in angiogenesis. Acute myelocytic leukemia (AML) remains a disease with poor prognosis. Similar to solid tumors, it probably requires angiogenesis to ensure adequate supplies of nutrients. We studied rats with transplanted AML to test if a neutralizing anti-leptin receptor monoclonal antibody (mAb) (anti-OB-R) could inhibit leukemogenesis. At 4 weeks after transplantation, the bone marrow contained about 80% leukemic cells as assayed with a specific mAb and flow cytometry. Microscopic examination of bone marrow sections stained with an anti-von Willebrand mAb revealed a marked increase in microvessel density in the leukemic rats compared with controls. Treatment with anti-OB-R for 3 weeks more than halved the content of bone marrow leukemic cells with a concomitant, substantial decrease in angiogenesis. A parallel experiment using an irrelevant anticasein mAb showed no effect on either leukemic cell growth or angiogenesis. We could not detect surface expression of the leptin receptor on the leukemic cells, but on mononuclear cells from healthy rats. The anti-OB-R did not affect in vitro proliferation of leukemic cells whereas proliferation of the mononuclear cells was markedly impaired. The anti-OB-R had no effect on either leukemic cell growth or angiogenesis in leukemic fa/fa rats with a mutated leptin receptor. We conclude that leptin stimulates leukemic cell growth in vivo by promoting angiogenesis. Inhibition of binding of leptin to its receptor might be a new adjunct therapy in AML.

Animals↗