Ontogeny and sexual dimorphic expression of mouse type 2 11beta-hydroxysteroid dehydrogenase

During early neonatal life, important changes occur in the gut. The intestine is challenged by both milk and a microbial flora. Later on, at weaning, the diet of mice changes from milk to pelleted food leading to changes in microbial contents. This period seems essential for a complete development of the mucosal immune system. We investigated the development of both intraepithelial (IEL) and lamina propria lymphocytes (LPL), from day 5, and every 5 days, up to day 30 after birth. IEL and LPL were isolated from the small intestine and the phenotype was assessed by FACS analyses, using antibodies for detection of T-cell markers CD3, TCR alpha beta, TCR gamma delta, CD4, CD8 alpha, CD8 beta, CD5, CD18, CD54, and CD49d. Our data show a clear increase in the number of LPL just before weaning, while the number of IEL increased after day 15. A more mature pattern of membrane antigen expression of both IEL and LPL was observed at weaning. The adhesion molecules CD18, CD54, and CD49d, essential for cellular communication of lymphocytes, showed an expression peak at weaning. In conclusion, the mouse mucosal immune system develops during the first 3 weeks of neonatal life leading to the formation of a more mature immune system at weaning.     

Reduced 11beta-hydroxysteroid dehydrogenase activity in the remaining kidney following nephrectomy

Intracellular access of steroids to gluco- and mineralocorticoid receptors is regulated by reduced 11beta-hydroxysteroid dehydrogenase (OHSD) 1 and 2. These enzymes convert active 11beta-OH-steroids into inactive 11-keto-steroids. The purpose of the present study was to establish whether the 11beta-OHSD1 and 11beta-OHSD2 are modulated in the remnant kidney 24 h or 14 days after uninephrectomy (UNX) in rats. Overall, 11beta-OHSD activity was analyzed by measuring the ratio of the exogenous 11beta-OH-steroid prednisolone to its 11-keto metabolite prednisone in vivo in kidney tissue using high performance liquid chromatography. To determine which isoenzyme accounts for the changed activity 24 h after UNX, the oxidation and reduction attributable to 11beta-OHSD1 and oxidation to 11beta-OHSD2 were analyzed in total renal extracts and in isolated glomeruli, proximal convoluted tubules (PCT), cortical ascending limbs, and cortical convoluted tubules (CCT). The messenger RNA content of 11beta-OHSD1 and 11beta-OHSD2 was measured by RT-PCR in renal tissues and single segments, using glyceraldehyde-3-phosphate-dehydrogenase as an internal standard. Protein amounts of 11beta-OHSD1 and 11beta-OHSD2 were assessed by Western blot. The prednisolone/prednisone ratio increased 24 h after UNX in 9 out of 10 animals (P < or = 0.0011), and was unchanged 14 days after UNX. 11Beta-OHSD1 oxidation (P < or = 0.032) and reduction activity (P < or = 0.002) declined 24 h after UNX in total extracts. 11Beta-OHSD1 oxidase activity was more than 3 times higher in PCT than in glomeruli, cortical ascending limbs, and CCT, and declined by 50% after UNX (P < or = 0.001). The reductase activity did not change following UNX in PCT. 11Beta-OHSD2 activity was 5-15 times higher in CCT than in the other segments, and decreased significantly after UNX (P < or = 0.008). UNX did not affect messenger RNA and protein levels of both enzymes in total renal extracts. In conclusion, 11beta-OHSD1 and 11beta-OHSD2 are predominantly expressed in PCT and CCT, respectively, and their corresponding oxidative activities decline after UNX. Thus, the access of 11beta-glucocorticosteroids to gluco- and mineralocorticoid receptors in the remaining kidney is facilitated after UNX.     

Pharmacology of 11 beta-hydroxysteroid dehydrogenase

In a retrospective study of 73 girls and women treated in a psychiatric inpatient unit in Cape Town between 1979 and 1989, follow-up data were available for 49 (67%) of them. Internationally recommended measures were used to obtain further data, where possible, from 17 subjects (14 with anorexia, 3 with bulimia) who were 4 and more years post-hospitalisation, as well as 19 subjects (9 with anorexia, 10 bulimia) who had been out of hospital less than 4 years. Indirect information was available from 13 subjects. With regard to long-term outcome, 15 of the 17 subjects fell into the Morgan-Russell categories 'good' or 'intermediate'; in the short-term follow-up group, 14 of the 19 fell into these categories. Indirectly, we also discovered that 3 of the original subjects had died, 4 had remained ill, and 6 had recovered. These findings were similar to those from a previous study from this department and are useful feedback on the comprehensive treatment programme. They also throw light on what appears to be a culture-bound syndrome; at the time of study, the eating disorder affected mainly the middle-class white population, a pattern similar to that found elsewhere in the world.     

Clinical investigation of 11 beta-hydroxysteroid dehydrogenase

At least two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) have been identified, and clinical studies have illustrated their physiological and pathological significance. In the kidney, a high affinity 11 beta-OHSD2 inactivates cortisol to cortisone and protects mineralocorticoid receptors from cortisol. In the liver, a low affinity 11 beta-OHSD1 converts cortisone to cortisol, and may ensure that glucocorticoid receptors are adequately exposed to cortisol. In vascular smooth muscle, the conversion of cortisol to cortisone influences vascular tone. Defects in 11 beta-OHSD2 probably account for mineralocorticoid excess in the syndromes of Apparent Mineralocorticoid Excess, licorice administration, and ectopic ACTH syndrome. Defects in 11 beta-OHSD1 may be important in essential hypertension, and polycystic ovarian syndrome. The underlying mechanism for all of these defects, and the putative role of endogenous inhibitors of 11 beta-OHSD, remains unclear. In future, the measurement of the activity of individual isoforms should resolve this uncertainty.     

Ontogeny of innervation of rat and ovine fetal adrenals

The formation of adrenocortical zonation occurs in rats during late gestation. Since adult cortical function is modulated by neural mediators, it is possible that the development of differentiated function is dependent on cortical innervation. The goal of this study was to compare the pattern and timing of rodent and ovine adrenal innervation during late organogenesis by staining with antibodies directed against the neuropeptides vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and neuropeptide tyrosine (NPY) and the catecholamine biosynthetic enzyme, tyrosine hydroxylase (TOH). Rat adrenals were collected from fetal days 17-21 (term=21 days) and ovine adrenals from fetal days 101-136 (term=145 days). Adrenals were fixed, cryosectioned at 100 microns and immunostained using Cy3-conjugated secondary antibodies. In both species, staining of VIP, CGRP, NPY and TOH fibers was observed in the capsule and subcapsular layers of the cortex during gestation. In late gestation, VIP- and NPY-positive ganglions cells were observed near the medulla extending processes toward the outer cortex; in ovine adrenals, fibers from ganglion cells appeared to surround nests of outer cortical (presumably, zona glomerulosa) cells. These data show that phenotypically distinct neural elements appear at different stages of adrenocortical development. The presence of neural elements in contact with adrenal cortical cells supports the possibility for neural control of adrenocortical development.     

Expression of type 2 11beta-hydroxysteroid dehydrogenase and corticosteroid hormone receptors in early human fetal life

In adult life, the type 2 isozyme of 11beta-hydroxysteroid dehydrogenase (11betaHSD2) protects the mineralocorticoid receptor (MR) from glucocorticoid by inactivating cortisol to cortisone. 11betaHSD2 activity has been reported in human fetal tissues, where glucocorticoids may impair fetal growth yet are also required for normal fetal development. Using digoxigenin-labeled complementary ribonucleic acid (RNA) probes and an in-house 11betaHSD2 antiserum, we have analyzed the expression of 11betaHSD2, MR, and glucocorticoid receptor (GR) in human fetal tissues of gestational age 6-17 weeks (n=15). 11BetaHSD2 expression was absent at gestational age 6+ weeks, but was expressed in abundance in many fetal tissues between 8-12 weeks. At this time, 11betaHSD2 colocalized with GR messenger RNA (mRNA) expression in metanephros, gut, muscle, spinal cord and dorsal root ganglia, periderm, sex chords of testis, and adrenal. In particular within fetal kidney, intense expression of 11betaHSD2 and GR mRNA was observed over Bowman's capsule and the vascular tufts of developing glomeruli as they migrated from the surface of the kidney to the inner cortex. Only lung and adrenal medullary rests demonstrated high levels of GR mRNA but low levels of 11betaHSD2. 11BetaHSD2 mRNA and immunoreactivity staining patterns were similar, with the exception of the fetal adrenal, where mRNA was localized to the outer definitive zone but immunoreactivity was localized to the inner fetal zone. Colocalization of 11betaHSD2 (and GR mRNA) with MR mRNA was observed principally within epithelial cells of collecting ducts, particularly after 16 weeks gestation when the pattern of distribution of 11betaHSD2 became more adult in nature. High levels of MR mRNA were observed within developing bone. The data indicate that 11betaHSD2 in fetal life principally modulates ligand access to the GR in most fetal tissues, notably glomeruli and tubules in the developing kidney, testis, and periderm, and this may be have ramifications for fetal sodium homeostasis and differentiation. The development of tissues previously shown to have a critical requirement for glucocorticoids, such as lung and adrenal medulla, is facilitated by the expression of GR mRNA, but not 11betaHSD2. The expression of MR mRNA in high abundance in bone suggests a role for corticosteroids in human bone development, and the low/absent expression of 11betaHSD2 at this site suggests that it is functionally acting as a GR.     

Hormonal regulation of intestinal 11beta-hydroxysteroid dehydrogenase

We have previously demonstrated the developmental increase of the activity of 11beta-hydroxysteroid dehydrogenase (11betaHSD) in the rat ileum which correlated with the developmental surge of plasma concentrations of corticosteroids, thyroid hormones and insulin. To ascertain whether these hormones directly stimulate 11betaHSD activity we used explant cultures of ileum and distal colon. The intestinal segments of young, 7-day-old rats, were cultured 48 hours in the presence of aldosterone (10[-7] M), dexamethasone (10[-7] M), triiodothyronine (10[-7] M) or insulin (10[-7] M) and 11betaHSD activity was evaluated by measuring the conversion of [3H]corticosterone to [3H]11-dehydrocorticosterone. The activity of 11betaHSD was significantly increased following 48 h treatment with dexamethasone and aldosterone, whereas insulin and triiodothyronine were without any effect. Corticosterone oxidation was inhibited by carbenoxolone and progesterone. It is being concluded, that both glucocorticoids and mineralocorticoids but not insulin or triiodothyronine induce intestinal 11betaHSD activity.     

Placental 11 beta-hydroxysteroid dehydrogenase activity in normotensive and pre-eclamptic pregnancies

Apparent mineralocorticoid excess and licorice induced hypertension, both hypertensive disorders, have been attributed to a defect in the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which interconverts cortisol to cortisone. Therefore, we undertook this study to determine the role of human placental 11 beta-HSD activity in preeclampsia, which is a hypertensive disorder in pregnancy. 11 beta-HSD activities were determined in placentas of 17 normotensive and 11 preeclamptic patients matched for gestational age at 34-42 weeks. Cortisol levels in umbilical venous and arterial sera were also determined for both groups. Statistical analysis was performed using Student's t-test, significance at p < 0.05. 11 beta-dehydrogenase (oxidation activity of 11 beta-HSD) activity was significantly lower in placentas of preeclamptic compared to normotensive patients (0.19 +/- 0.09 vs. 0.26 +/- 0.08 mmoles/min/placenta, p = 0.02). Cortisol level in umbilical cord blood was significantly higher in the preeclamptic group (14.99 +/- 14.08 vs. 6.71 +/- 3.69 g/dL, p = 0.02). The decreased 11 beta-HSD activity is accompanied by an expected increase in umbilical cord blood cortisol level and decrease in fetal weight. This enzyme may play an important role in influencing fetal growth.     

Renal 11beta-hydroxysteroid dehydrogenase in genetically salt-sensitive hypertensive rats

-Renal 11beta-hydroxysteroid dehydrogenase II (11beta-HSDII) converts glucocorticoids into inactive metabolites and plays an important role in controlling blood pressure and sodium retention. To examine whether this enzyme may be involved in the pathophysiology of salt-sensitive hypertension, we determined 11beta-HSDII activity and mRNA levels in the blood vessel and kidney of Dahl Iwai salt-sensitive (DS) rats and Dahl Iwai salt-resistant (DR) rats. Urinary free corticosterone:free 11-dehydrocorticosterone ratio was measured to estimate renal 11beta-HSD activity. Vascular 11beta-HSDII activity was expressed as percent conversion of [3H]corticosterone to [3H]11-dehydrocorticosterone in homogenized mesenteric arteries. 11beta-HSDII mRNA was estimated with the use of competitive polymerase chain reaction (PCR). Renal 11beta-HSDII activity and mRNA levels were significantly decreased in 8- and 12-week-old high salt DS rats compared with DR, Sprague-Dawley (SD), or low salt DS rats of the same age. Decreased 11beta-HSDII activity and mRNA levels in mesenteric arteries were observed in 8- and 12-week-old high salt DS rats. Urinary excretion of 11beta-HSDII inhibitory factors was measured by inhibition of enzyme activity in microsomes from human kidney. The urinary inhibitors were significantly increased in 8- and 12-week-old high salt DS rats compared with DR, SD, or low salt DS rats of the same age. There were no significant differences in 11beta-HSDII activity and mRNA levels in mesenteric arteries and kidney or in urinary inhibitors between 4-week-old DS, DR, and SD rats. These results indicate that 11beta-HSDII may play a role in salt sensitivity and development of hypertension in the DS rat.     

Pattern of 11 beta-hydroxysteroid dehydrogenase type 1 messenger ribonucleic acid expression in the ovine uterus during the estrous cycle and pregnancy

The present study was designed to examine the pattern and cellular localization of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) gene expression in the ovine uterus during pregnancy and at 3 mo postpartum. High levels of 11 beta-HSD1 mRNA were detected in the endometrium from Days 60 to 143 (term = 145 days), and the levels did not change significantly during that time. The level of 11 beta-HSD1 mRNA in the endometrium was always much higher than that in the myometrium, in which the mRNA was not readily detectable throughout pregnancy; at 3 mo postpartum, 11 beta-HSD1 mRNA became undetectable in both endometrium and myometrium. Within the endometrium, intense immunoreactive 11 beta-HSD1 was localized exclusively to the luminal epithelium, and the intensity of 11 beta-HSD1 immunostaining closely followed the level of 11 beta-HSD1 mRNA. To determine whether the level of endometrial 11 beta-HSD1 mRNA was related to the status of ovarian function, tissues from non-pregnant animals at different stages of their reproductive cycle were also examined. It was found that 11 beta-HSD1 mRNA was undetectable in the endometrium of cycling animals up to Day 9 of the estrous cycle but was detectable thereafter. Taken together, these results demonstrate that within the ovine uterus the endometrium is always the dominant site of 11 beta-HSD1 gene expression in relation to the myometrium. Furthermore, the expression of 11 beta-HSD1 mRNA in the endometrium is closely related to the status of the reproductive cycle. The mRNA for 11 beta-HSD1 is highly expressed only during pregnancy and in non-pregnant animals during the late luteal phase. Since circulating levels of progesterone are elevated during both of these periods, the present findings suggest a progesterone effect on uterine 11 beta-HSD1 gene expression.     

The role of 11beta-hydroxysteroid dehydrogenase in steroid hormone specificity

11Beta-hydroxysteroid dehydrogenase (11beta-HSD) is thought to confer aldosterone specificity to mineralocorticoid target cells by protecting the mineralocorticoid receptor (MR) from occupancy by endogenous glucocorticoids. In aldosterone target cells the type 2 11beta-HSD is present, which, in contrast to the type 1 11beta-HSD, has very high affinity for its substrate, is unidirectional and prefers NAD as cofactor. cDNAs encoding 11beta-HSD2 have been recently cloned from different species, and the cell-specific expression of its mRNA and protein were determined. 11Beta-HSD2 is expressed in every aldosterone target tissue. Northern analysis revealed that the rabbit 11beta-HSD2 is expressed at high levels in the renal collecting duct and at much lower levels in the colon. RT-PCR experiments demonstrated that 11beta-HSD2 mRNA is present only in aldosterone target cells within the kidney. We determined the subcellular localization of the rabbit 11beta-HSD2 using a chimera encoding 11beta-HSD2 and the green fluorescent protein (GFP). This construct was stably transfected into CHO and MDCK cells. The expressed 11beta-HSD2/GFP protein retained high enzymatic activity, and its characteristics were undistinguishable from those of the native enzyme. The intracellular localization of this protein was determined by fluorescence microscopy. 11Beta-HSD2-associated fluorescence was observed as a reticular network over the cytoplasm whereas the plasma membrane and the nucleus were negative, suggesting endoplasmic reticulum (ER) localization. Co-staining with markers for ER proteins, the Golgi membrane, mitochondria and nucleus confirmed that 11beta-HSD2 is localized exclusively to the ER. To determine what structural motifs are responsible for the ER localization, we generated deletion mutants missing the C-terminal 42 and 118 amino acids, and fused them to GFP. Similarly as with the intact 11beta-HSD2, these mutants localized exclusively to the ER. Both C-terminal deletion mutants completely lost dehydrogenase activity, independently whether activity was determined in intact cells or homogenates. These results indicate that 11beta-HSD2 has a novel ER retrieval signal which is not localized to the C-terminal region. In addition, the C-terminal 118 amino acids are essential for NAD-dependent 11beta-HSD activity.     

Development of 11 beta-hydroxysteroid dehydrogenase expression in the rat cochlea

Spontaneous coronary dissection is rare and the diagnosis is usually post-mortem. Less than 60 cases have been diagnosed at coronary angiography. The authors report, to the best of their knowledge, the first case of multiple spontaneous coronary artery dissections in a type IV Ehlers-Danlos syndrome in a young woman admitted to hospital for acute myocardial infarction. She had a previous history of regressive complete tetraplegia due to dissection of the basilar artery and episodes of dizziness related to a dissecting aneurysm of the left vertebral artery. The diagnosis of type IV Ehlers-Danlos syndrome was established after skin biopsy had shown typical histological changes. The patient died several months later after an acute abdominal syndrome probably related to dissection of the aorta. An autopsy was refused by her family. The authors believe this to be the first case of spontaneous coronary dissection related to a type IV Ehlers-Danlos syndrome.     

11beta-hydroxysteroid dehydrogenase expression and activity in the human adrenal cortex

Although oxidation of cortisol or corticosterone by 11beta-hydroxysteroid dehydrogenase (11beta-HSD) represents the physiological mechanism conferring specificity for aldosterone on the mineralocorticoid receptor in mineralocorticoid target tissues, little attention has been paid until now to the expression and activity of this enzyme in human adrenals. We have shown that human adrenal cortex expresses 11beta-HSD type 2 (11beta-HSD2) gene, and found a marked 11beta-HSD2 activity in microsomal preparations obtained from slices of decapsulated normal human adrenal cortices. Under basal conditions, adrenal slices secreted, in addition to cortisol and corticosterone (B), sizeable amounts of cortisone and 11-dehydrocorticosterone (DH-B), the inactive forms to which the former glucocorticoids are converted by 11beta-HSD. Addition of the 11beta-HSD inhibitor glycyrrhetinic acid elicited a moderate rise in the production of cortisol and B and suppressed that of cortisone and DH-B. ACTH and angiotensin II evoked a marked rise in the secretion of cortisol and B, but unexpectedly depressed the release of cortisone and DH-B. ACTH also lowered the capacity of adrenal slices to convert [3H]cortisol to [3H]cortisone. This last effect of ACTH was concentration-dependently abolished by both aminoglutethimide and cyanoketone, which blocks early steps of steroid synthesis, but not by metyrapone, an inhibitor of 11beta-hydroxylase. Collectively, these findings indicate that the human adrenal cortex possesses an active 11beta-HSD2 engaged in the inactivation of newly formed glucocorticoids. The activity of this enzyme is negatively modulated by the main agonists of glucocorticoid secretion through an indirect mechanism, probably involving the rise in the intra-adrenal concentration of non-11beta-hydroxylated steroid hormones.     

Regulation of 11beta-hydroxysteroid dehydrogenase type II in rat adrenocortical cells

The regulation of 11beta-hydroxysteroid dehydrogenase type II (11beta-HSD2) gene expression was studied in primary cultures of rat adrenocortical cells. The protein kinase A (PKA) pathway agonists forskolin, dibutyryl cAMP and ACTH caused a 5-10 fold increase in 11beta-HSD2 mRNA as determined by semiquantitative PCR. The effect of forskolin could be partially inhibited by the addition of the phorbol ester TPA, an activator of the protein kinase C (PKC) pathway. The increase in mRNA encoding 11beta-HSD2 was accompanied by increased synthesis of 11beta-HSD2 as measured by immunoprecipitation of labeled protein. It is concluded that both the PKA and PKC pathways are involved in the regulation of rat adrenal 11beta-HSD2 gene expression.     

Renal 11 beta-hydroxysteroid dehydrogenase activity is enhanced by ramipril and captopril

Changes of renal 11 beta-hydroxysteroid dehydrogenase activity may contribute to variations of sodium excretion by modulating inactivation of cortisol or corticosterone and thus their access to mineralocorticoid receptors. Angiotensin-converting enzyme inhibitors enhance sodium excretion but by mechanisms still incompletely understood. To test the hypothesis that the angiotensin-converting enzyme inhibitors ramipril and captopril act in part by enhancing renal 11 beta-hydroxysteroid dehydrogenase activity, the effects of these agents in slices of rat renal outer medulla were examined. Conversion of 3H-corticosterone to 3H-11-dehydrocorticosterone was 58% greater in tissue from fasted rats than from fed rats (mean +/- SE 2467 +/- 146 vs. 1584 +/- 102 pmol/mg protein.h, P < 0.01). Incubation of tissue from fed rats with physiological concentrations of ramiprilat, the active form of ramipril, enhanced activity (1497 +/- 76) to fasted levels (2323 +/- 120, P < 0.02). Captopril had a similar in vitro effect (1557 +/- 92 to 2109 +/- 116, P < 0.01). Ramipril given in vivo to fed rats also increased activity to fasted levels (1716 +/- 101 to 2737 +/- 396, P < 0.05). Angiotensin II incubated with renal tissue from fasted rats suppressed activity to fed levels, but this effect was prevented by the presence of ramiprilat. Both ramipril and captopril enhance renal 11 beta-hydroxysteroid dehydrogenase activity, and this effect is only partly explained by limitation of endogenous angiotensin II production.     

Down-regulation of hepatic and renal 11 beta-hydroxysteroid dehydrogenase in rats with liver cirrhosis

Twenty-four crossbred primiparous sows were used to investigate the influence of insulin administration after weaning on the intrafollicular insulin-like growth factor i (IGF-I) system. Sows received 0.4 i.u. insulin kg-1 bodyweight or an equivalent volume of saline for 3 days (n = 5 insulin; n = 4 saline) or 5 days (n = 5 insulin; n = 6 saline) after weaning or served as untreated controls on day 1 (n = 4). The number and diameters of ovarian follicles were recorded, and fluid was aspirated from the 20 largest follicles for determination of oestradiol and IGF-I by radioimmunoassay and of insulin-like growth factor-binding proteins (IGFBPs) by western ligand blotting. The walls of the follicles were collected for mRNA analysis by RNase protection assay or granulosa cells were collected for estimation of apoptosis by flow cytometry. Insulin treatment resulted in smaller diameters of all follicles (P < 0.05) and tended (P < 0.07) to increase the number of follicles available on day 5 compared with saline-treated animals (19.8 versus 17.8). The concentration of oestradiol in follicular fluid from large (7-10 mm) follicles on days 3 and 5 was reduced (treatment by size class interaction; P < 0.05) by insulin treatment. Insulin also reduced intrafollicular concentrations of IGF-I at days 3 and 5 after weaning (treatment by day interaction; P < 0.02) while the amounts of IGFBP-3 and IGFBPs of molecular mass 30 and 22 kDa decreased from day 3 to day 5 in saline-treated animals only (treatment by day interaction; P < 0.05). Gene expression for IGF-I increased in saline-treated animals but decreased fourfold in insulin-treated sows from day 3 to day 5 (treatment by day interaction; P < 0.002). Gene expression for IGFBP-d decreased (P < 0.04) from day 3 to day 5, while expression of IGFBP-2 was unaffected by treatment or day. Overall, insulin influenced the IGF-I system in a manner consistent with slowing follicular growth and possibly allowed more follicles to become available for ovulation.     

Leukocytes modulate 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity in human granulosa-lutein cell cultures

A randomised clinical trial was performed to investigate whether there is a need or advantage to splint two implants in the mandible retaining a hinging overdenture. Furthermore, patient satisfaction was evaluated for different attachment systems retaining the overdenture. Thirty-six edentulous patients were randomised into three groups of equal size and treated with either magnets, ball attachments or straight bars (reference group). After 3 years of observation no implants were lost in any of the groups. Besides, no statistically significant differences were noted for the peri-implant outcome. Although the bar group presented the highest retention force, the general satisfaction of the patients in the three groups did not differ. The patients with bar retentions showed less prosthetic complications of the retention elements but more at the level of the denture-supporting mucosa. Finally, the clinical outcome of all groups confirms that overdenture treatment demands regular controls with limited time intervals.