Biomedical subjects

K Sjögren

Publications and source records attributed to K Sjögren.

At least 19 recordsLinked to original sources

PubMed2002

A transgenic model to determine the physiological role of liver-derived insulin-like growth factor I.

Insulin-like growth factor-I (IGF-I) has important growth promoting and metabolic effects and is expressed in virtually every tissue of the body. The highest expression is found in the liver but the physiological role of liver-derived IGF-I is unknown. It has been difficult to separate the endocrine effects of liver-derived IGF-I from the autocrine/paracrine effects of locally produced IGF-I in peripheral tissues. Therefore, we have developed a mouse model with a liver-specific inducible deletion of the IGF-I gene. The liver-IGF-I deficient mouse have dramatically reduced (>80%) serum IGF-I levels, demonstrating that the major part of serum IGF-I is liver-derived. Surprisingly, liver-IGF-I deficient mice demonstrate a normal appendicular skeletal growth up to at least 12 months of age despite the dramatic decrease in circulating IGF-I levels, indicating that liver-derived IGF-I is not required for appendicular skeletal growth. However, the adult axial skeletal growth is clearly reduced in the liver-IGF-I deficient mice. Furthermore, the amount of cortical bone is reduced due to decreased radial growth of the cortical bone while the amount of trabecular bone is unchanged in the liver-IGF-I deficient mice. The decreased levels of circulating IGF-I are associated with increased serum levels of growth hormone (GH), indicating a role for liver-derived IGF-I in the negative feedback regulation of GH secretion. Measurements of factors regulating GH-secretion in the pituitary and in the hypothalamus revealed an increased expression of growth hormone releasing hormone (GHRH) and growth hormone secretagogue (GHS) receptors in the pituitary of liver-IGF-I deficient mice. This in turn results in an increased sensitivity to systemically administered GHRH and GHS, demonstrating that the regulatory action of liver-derived IGF-I on GH secretion is at the pituitary rather than at the hypothalamic level. The liver is an important metabolic organ and liver-IGF-I deficient mice are markedly hyperinsulinemic and yet normoglycemic, consistent with an adequately compensated insulin resistance. Interestingly, liver-IGF-I deficient mice display a reduced age-dependent fat mass accumulation compared with control mice. In conclusion, liver-derived IGF-I is important for carbohydrate- and lipid-metabolism and for the regulation of GH-secretion at the pituitary level. Furthermore, it regulates adult axial skeletal growth and cortical radial growth while it is not required for appendicular skeletal growth.

Adipose Tissue↗

PubMed2001

The somatomedin hypothesis revisited in a transgenic model.

Studies of insulin-like growth factor I (IGF-I) gene knockout mice models have clearly shown that IGF-I is necessary for prenatal as well as postnatal body growth in mice. Clinical studies of a patient with an IGF-I gene defect which caused complete absence of IGF-I, verified that it is important for intrauterine and postnatal growth. Recent studies of mice with liver-specific and inducible IGF-I gene knockout indicated that liver-derived IGF-I is not necessary for postnatal body growth, although serum IGF-I levels are decreased by more than 80% in these mice. Therefore, extrahepatic IGF-I is sufficient for maintenance of postnatal body growth in mice. Further investigations are needed to assess whether liver-derived circulating IGF-I is essential for other biological functions.

Animals↗

PubMed2001

Body fat content can be predicted in vivo in mice using a modified dual-energy X-ray absorptiometry technique.

The introduction of transgenic mice as animal models in medical research has increased the need for methods to study the phenotype of mice. The aim of the present study was to develop and evaluate a method for in vivo prediction of fat content in living mice. We combined a modified dual-energy X-ray technique with an image analysis procedure. This combined procedure calculates the percentage of fat area, defined as the percentage of the total area of the mice consisting of >50% fat. A high correlation between the percentage of fat area and dissected adipose tissue was seen in both male and female mice (males, r = 0.92, P < 0.001; females, r = 0.88, P < 0.001). A high correlation was also seen between the percentage of fat area and serum levels of leptin (males, r = 0.95, P < 0.001; females, r = 0.86, P < 0.001). An additional experiment demonstrated a very strong correlation between the percentage of fat area and total body fat as determined by chemical extraction (r = 0.97, P < 0.001). In summary, the percentage of fat area, as measured with the dual-energy X-ray/image combined procedure, provides a good in vivo estimation of total body fat content in mice.

Absorptiometry, Photon↗

PubMed2001

The influence of rinsing routines on fluoride retention after toothbrushing.

OBJECTIVE: An important determinant of the anticaries effect of brushing with a fluoride dentifrice is the retention of fluoride in the oral fluids. This study measured the influence of various post-brushing rinsing routines on fluoride retention. SETTING: The Faculty of Odontology, Göteborg University, Sweden. SUBJECTS: Twenty-one healthy dental students, aged 23 +/- 2 yr. DESIGN: A randomised, cross-over protocol, comparing various post-brushing rinsing procedures, with the following variables: volume of rinsing water (5 mL vs. 10 x 3 mL) and duration of rinsing (10 vs. 60 s). Samples of whole saliva, interdental fluid and interdental plaque were analysed for fluoride content. RESULTS: The duration of rinsing did not influence fluoride retention in whole saliva, interdental fluid or interdental plaque. Rinsing with a higher volume of water substantially decreased fluoride retention in all samples. CONCLUSION: Brushing with a fluoride dentifrice should be followed by rinsing procedures which enhance the retention of fluoride. Rinsing with large volumes of water decreases fluoride retention in the oral fluids, and should be discouraged.

Adult↗

PubMed2001

How to improve oral fluoride retention?

This paper reviews current ideas relating to oral fluoride retention after topical applications of various fluoride preparations. The oral fluoride reservoirs, which serve as a store for fluoride, gradually releasing its content into saliva, will be discussed. The present paper also deals with fluoride kinetics in the oral cavity. The answer to the title of the paper has, however, not yet been found but remains a goal for researchers studying caries prophylaxis worldwide in the search for possible ways of increasing and improving oral fluoride retention.

Cariostatic Agents↗

PubMed2001

Possible roles of insulin-like growth factor in regulation of physiological and pathophysiological liver growth.

BACKGROUND/AIMS: Almost all circulating insulin-like growth factor-1 (IGF-1) is produced and secreted from the liver. However, the possible role of IGF-1 in local regulation of liver functions including liver growth is unclear. In the present study, we investigated the role of IGF-1 on liver growth in vivo and in hepatic stellate cell function in vitro. RESULTS: Liver-specific knock-out of the IGF-1 gene by use of the cre-loxP system caused enhanced liver growth, possibly reflecting increased growth hormone (GH) secretion due to decreased negative feedback by IGF-1. Studies on cultured rat hepatic stellate cells (HSC) showed that IGF-1 and hepatocyte-conditioned medium (PCcM) time- and dose-dependently increased hepatocyte growth factor (HGF) mRNA and HGF immunoreactivity. IGF-1 and PCcM also enhanced DNA synthesis in the HSC cultures. The PCcM did not contain bioactive IGF-1 and was also able to stimulate proliferation when prepared under serum- and hormone-free conditions. CONCLUSION: In vivo results show that IGF-1 is not essential for normal growth of the intact liver. The in vitro results indicate that both IGF-1 and IGF- 1-independent factor(s) from hepatocytes can stimulate HGF production by HSC. It remains to be investigated whether these effects are of importance for liver regeneration or pathological conditions.

Animals↗

PubMed2001

Metabolic functions of liver-derived (endocrine) insulin-like growth factor I.

Until now it has been difficult to determine the relative importance of locally produced (autocrine/paracrine) versus systemically derived (endocrine) insulin-like growth factor I (IGF-I) in the intact organism. We recently eliminated IGF-I production in the livers of mice using the Cre/loxP recombination system. These mice displayed a reduction in serum IGF-I levels of more than 80%, but demonstrated normal body growth, suggesting that autocrine/paracrine-acting IGF-I, but not endocrine-acting IGF-I, regulates body growth. Long-term metabolic studies of mice in which IGF-I production had been inactivated in the liver, have shown that the mice have decreased fat mass, but increased serum levels of insulin and cholesterol. Despite the marked increase in plasma insulin following glucose administration, the glucose elimination was not altered in these animals. Thus, the mice showed an adequately compensated insulin resistance. In conclusion, liver-derived or endocrine IGF-I is not required for post-natal statural growth, but seems to be of vital importance for normal carbohydrate and lipid metabolism.

Animals↗

PubMed2001

Liver-derived IGF-I regulates GH secretion at the pituitary level in mice.

We have reported that liver-specific deletion of IGF-I in mice (LI-IGF-I-/-) results in decreased circulating IGF-I and increased GH levels. In the present study, we determined how elimination of hepatic IGF-I modifies the hypothalamic-pituitary GH axis to enhance GH secretion. The pituitary mRNA levels of GH releasing factor (GHRF) receptor and GH secretagogue (GHS) receptor were increased in LI-IGF-I-/- mice, and in line with this, their GH response to ip injections of GHRF and GHS was increased. Expression of mRNA for pituitary somatostatin receptors, hypothalamic GHRF, somatostatin, and neuropeptide Y was not altered in LI-IGF-I-/- mice, whereas hypothalamic IGF-I expression was increased. Changes in hepatic expression of major urinary protein and the PRL receptor in male LI-IGF-I-/- mice indicated an altered GH release pattern most consistent with enhanced GH trough levels. Liver weight was enhanced in LI-IGF-I-/- mice of both genders. In conclusion, loss of liver-derived IGF-I enhances GH release by increasing expression of pituitary GHRF and GHS receptors. The enhanced GH release in turn affects several liver parameters, in line with the existence of a pituitary-liver axis.

Animals↗

PubMed2001

Liver-derived IGF-I is of importance for normal carbohydrate and lipid metabolism.

IGF-I is important for postnatal body growth and exhibits insulin-like effects on carbohydrate metabolism. The function of liver-derived IGF-I is still not established, although we previously demonstrated that liver-derived IGF-I is not required for postnatal body growth. Mice whose IGF-I gene in the liver was inactivated at 24 days of age were used to investigate the long-term role of liver-derived IGF-I for carbohydrate and lipid metabolism. Serum levels of leptin in these mice were increased by >100% at 3 months of age, whereas the fat mass of the mice was decreased by 25% at 13 months of age. The mice became markedly hyperinsulinemic and yet normoglycemic, indicating an adequately compensated insulin resistance. Furthermore, they had increased serum levels of cholesterol. We conclude that liver-derived IGF-I is of importance for carbohydrate and lipid metabolism.

Absorptiometry, Photon↗

PubMed2000

Disproportional skeletal growth and markedly decreased bone mineral content in growth hormone receptor -/- mice.

Growth hormone (GH) is important for skeletal growth as well as for a normal bone metabolism in adults. The skeletal growth and adult bone metabolism was studied in mice with an inactivated growth hormone receptor (GHR) gene. The lengths of femur, tibia, and crown-rump were, as expected, decreased in GHR-/- mice. Unexpectedly, GHR-/- mice displayed disproportional skeletal growth reflected by decreased femur/crown-rump and femur/tibia ratios. GHR-/- mice demonstrated decreased width of the growth plates in the long bones and disturbed ossification of the proximal tibial epiphysis. Furthermore, the area bone mineral density (BMD) as well as the bone mineral content (BMC)/body weight were markedly decreased in GHR-/- mice. The decrease in BMC in GHR-/- mice was not due to decreased trabecular volumetric BMD but to a decreased cross-sectional cortical bone area In conclusion, GHR-/- mice demonstrate disproportional skeletal growth and markedly decreased bone mineral content.

Animals↗

PubMed2000

The relative importance of endocrine versus autocrine/paracrine insulin-like growth factor-I in the regulation of body growth.

Body growth is regulated by growth hormone (GH) and insulin-like growth factor-I (IGF-I). The classical somatomedin hypothesis of this regulation is that most IGF-I in the blood originates in the liver and that body growth is controlled by the concentration of IGF-I in the blood. We have recently abolished IGF-I production in the livers of mice by using the Cre/loxP recombination system. These mice displayed a more than 75% reduction in serum IGF-I associated with increased serum levels of GH. In contrast, they demonstrated a normal postnatal growth, indicating that extrahepatic, autocrine/paracrine-acting IGF-I is the main determinant of postnatal growth. Thus, the "classical" somatomedin hypothesis needs revision. We propose the "dual somatomedin hypothesis" according to which: (1) autocrine/paracrine IGF-I is the main determinant of postnatal body growth and (2) liver-derived, endocrine-acting, IGF-I exerts negative feedback on GH secretion and possibly also exerts other effects on carbohydrate and lipid metabolism.

Animals↗

PubMed1999

Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice.

The body growth of animals is regulated by growth hormone and IGF-I. The classical theory of this regulation is that most IGF-I in the blood originates in the liver and that body growth is controlled by the concentration of IGF-I in the blood. We have abolished IGF-I production in the livers of mice by using the Cre/loxP recombination system. These mice demonstrated complete inactivation of the IGF-I gene in the hepatocytes. Although the liver accounts for less than 5% of body mass, the concentration of IGF-I in the serum was reduced by 75%. This finding confirms that the liver is the principal source of IGF-I in the blood. However, the reduction in serum IGF-I concentration had no discernible effect on postnatal body growth. We conclude that postnatal body growth is preserved despite complete absence of IGF-I production by the hepatocytes.

Aging↗

PubMed1998

Osteoprotegerin mRNA is increased by interleukin-1 alpha in the human osteosarcoma cell line MG-63 and in human osteoblast-like cells.

Osteoprotegerin (OPG) is a soluble receptor for the Osteoprotegerin-Ligand (OPGL) which is expressed on osteoblasts and mediates the signal for osteoclast differentiation. In the present study we demonstrate that OPG mRNA levels in MG-63 cells are increased in a dose-dependent manner after 8 h of treatment with IL-1 alpha (338 +/- 53% over control at 25 U/ml). Interleukin-6 (IL-6), under similar culture conditions, does not affect OPG mRNA levels. Time-course studies show that IL-1 alpha (25 U/ml) causes a transient increase of OPG mRNA levels in MG-63 cells, peaking after 4 h of treatment. An increase of the OPG transcript occurs in hOB cells at 0.5 h which is still present after 24 h of IL-1 alpha treatment. In MG-63 cells neither basal-nor IL-1 alpha-induced OPG mRNA levels are altered by the translational inhibitor cycloheximide. These results suggest that expression of OPG in osteoblasts may be regulated by IL-1 alpha.

Bone Neoplasms↗

PubMed1997

Salivary fluoride concentration and plaque pH after using a fluoride-containing chewing gum.

The aim was to study the salivary fluoride (F) concentration and plaque pH recovery on the chewing and the non-chewing side of the dentition during and after chewing 1 piece of chewing gum containing 0.25 mg F as NaF. Ten subjects refrained from toothbrushing for 3 days. On the fourth day, they rinsed for 1 min with 10 ml of a 10% sucrose solution. When plaque pH had reached a low value, they started to chew for either 5, 10, 15, 20, 30 or 45 min. Measurements of F concentration in saliva and of pH of approximal plaque were carried out at 2 contralateral sites for up to 60 min. In each individual, the chewing and non-chewing side were registered. Two to 3 times higher salivary F concentrations (expressed as area under the curve, AUC) were found on the chewing than on the non-chewing side (p < 0.05 or p < 0.01). The most pronounced recovery of plaque pH after the sucrose rinse was also registered for the chewing side, but the difference between the chewing and the non-chewing side was not so obvious as for the salivary F concentration. Significantly higher values of plaque pH (expressed as AUC) were found during prolonged chewing (p < 0.05 or p < 0.01), while only small numerical differences in salivary F concentration were noted between short and long chewing times. Thus, this study showed: (1) that the F concentrations in saliva after chewing a F-containing chewing gum were highest on the chewing side, and (2) that a prolonged chewing time increased the plaque pH recovery after a sucrose rinse, but had only a minor effect on the salivary F concentration.

Adult↗

PubMed1996

Estimation of prophylactic measures in Swedish public dental health care. Results from a questionnaire.

The aim of the present investigation was to map the presence of prophylactic measures in organized Swedish dental health care systems, focusing on personnel working with children and adolescents. The study was conducted by sending a questionnaire to all public dental clinics in Sweden (830 clinics in all). The results showed that collectively-performed prophylactic measures were given at 66% of the child health centers/ child day care centers and at 63% of the pre-schools. 57% of all clinics replied that they performed some kind of fluoride administration collectively (mainly fluoride varnish application or fluoride mouthrinses). 34% of all clinics used fluoride varnishes at the ages from 6 to 12 years, and collectively-performed fluoride mouthrinsing in schools at these ages was carried out by 16% of the clinics. 26% of all the clinics answered that they aimed at increasing the time spent on prophylactic measures compared to only 2% that were planning to decrease this time. The remaining 72% aimed at maintaining the time spent at the present. Prophylactic measures were performed individually by 49% of the clinics, whereas 50% of the clinics preferred a combination of individually and collectively performed measures. It can be concluded that the preventive measures against dental caries in Swedish public dental care is mainly focused on individually performed prophylaxis.

Adolescent↗

PubMed1996

Fluoride in the interdental area after two different post-brushing water rinsing procedures.

The aim of the present investigation was to study two post-brushing water rinsing procedures: (1) on fluoride (F) accumulation in approximal dental plaque, and (2) on F clearance in the interdental area. Twenty subjects participated first in the accumulation study, including three experimental periods (A, B and C), each lasting for 7 days. During period A, they brushed with a 0.32% NaF dentifrice for 2 min, followed by a 1-min active mouth rinse with the toothpaste foam combined with 5 ml of water. During period B, the 2-min brushing was followed by three quick water rinses with 15 ml each. During period C, toothbrushing, which was carried out without any toothpaste, was followed by a 2-min active mouthrinse with 10 ml of a 0.05% NaF solution. All three procedures were performed in the morning (after breakfast) and in the evening (just before bedtime). The results showed that the accumulation of F in pooled approximal plaque after 7 days reached on average 2.7 times higher values after procedure A than B (p<0.001). Procedure C also resulted in more F in plaque than B (p<0.001). The same 20 subjects participated in the clearance study on a separate occasion. When measuring the F concentration in the interdental area at 3 h after the application, procedure A resulted in a significantly higher F concentration than both toothbrushing B and mouth rinse C; the AUC was 2.2 times larger for A than for B (p <0.001). Thus, both the accumulation of F in approximal plaque and the clearance of F in the interdental area are related to the mode of water rinsing after toothbrushing.

Adult↗

PubMed1995

Effect of post-brushing water rinsing on caries-like lesions at approximal and buccal sites.

The aim was to study the effect of two different water rinsing procedures after toothbrushing with an NaF-containing dentifrice on the degree of de- or remineralization of enamel and dentine at approximal and buccal sites. Seven adults, wearing complete dentures, participated in two experimental periods (A and B) in a randomised order. During period A, they brushed with the dentifrice for 2 min, followed by 1-min active mouthrinse with the toothpaste-foam combined with 10 ml of water. No more water was used after the slurry had been spat out. During period B, the brushing was followed by 3 thorough rinsings of approximately 15 ml water each. These two procedures were carried out twice daily, i.e. in the morning (after breakfast) and in the evening (just before bedtime), during 3 months. Demineralized enamel and dentine samples were mounted at two locations--approximally and buccally--in the first molar region of the upper prostheses. Quantitative microradiography (TMR) was used to assess the lesion depth (ld) and the mineral loss (delta Z). The results showed that the approximally located samples continued to lose mineral during both periods A and B. However, the ld and delta Z values for enamel (p < 0.01) and dentine (p < 0.05) increased less during A than B. The buccally located enamel and dentine samples remineralized during the experiment, but no statistically significant differences were found for the ld and delta Z values of either enamel or dentine between periods A and B.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

Effect of a modified toothpaste technique on approximal caries in preschool children.

A 3-year, double-blind caries trial was conducted to evaluate the caries-reducing effect of a modified technique to use toothpaste. At the outset, 369 children, 4 years of age, were randomly assigned to four groups. At the end of the study, when the children were 7 years old, 281 (76%) had completed the trial. Two of the groups (test groups, n = 131) were given the following instructions regarding 'toothpaste technique': (1) to spread the paste evenly on the teeth prior to brushing, (2) not to expectorate more than necessary during brushing, (3) to filter the remaining dentifrice foam in the dentition, together with a sip of water, by active cheek movements for 1 min before expectorating, and (4) not to carry out any further water rinsings afterwards, and not to eat or drink for 2 h after brushing. The children in the other two groups (control groups, n = 150) were not given any instruction how to use the dentifrice and how to rinse after the brushing, but were, as the children in the test groups, encouraged to use the test dentifrice and to brush their teeth twice daily. Two commercial fluoride dentifrices (A and B) were compared: one of the test groups and one of the control groups used each product. Approximal carious lesions were scored on bite-wing radiographs at baseline and at the end of the study on the distal surface of the first and on the mesial surface of the second primary molars. No difference in caries increment was found between toothpastes A and B. The children in the two test groups developed a mean of 1.14 new dfs during the 3 years compared to 1.55 in the two control groups (p < 0.05). Thus, the results indicate that the modified toothpaste technique reduced approximal caries in preschool children by an average of 26%.

Analysis of Variance↗