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Biomedical subjects

S Lindskog

Publications and source records attributed to S Lindskog.

At least 109 records · Page 6Linked to original sources
PubMed1991

Osteoclasts: structure and function.

Osteoclasts are multinucleated giant cells showing specialized membrane structures, clear zones and ruffled borders, which are responsible for the process of bone resorption. These cells arrive at the resorption site via the bloodstream as mononuclear cells, derived from haemopoietic precursors in the spleen or bone marrow, which fuse prior to resorption. The osteoclast may share an early progenitor cell, the granulocyte macrophage colony-forming unit (GM-CFU) with monocytes, macrophages and granulocytes, implying that osteoclasts share the pluripotent haemopoietic stem cell with all other haemopoietic cells. In the past, elucidation of the structure of these cells relied upon traditional ultrastructural techniques. Transmission electron microscopic studies revealed details of the unique ultrastructure of these cells and, in combination with stereological techniques, showed the response of cells to various hormonal stimuli. Scanning electron microscopy not only demonstrated the surface appearance of osteoclasts, and their predilection for spreading on various substratum components, but has also been used as an adjunct in resorption assays in which areas of resorption lacunae are measured as indicators of cell activity. Recent advances in fields such as immunocytochemistry and freeze fracture techniques have contributed towards a more detailed delineation of antigenic profile, cytoskeletal structure and localization of enzymatic pathways. The osteoclast is subject to extensive regulatory mechanisms and it has been established that the osteoblast plays a major rôle in mediating the effects of osteotropic hormones and local mediators on these cells. Hence, research aimed at elucidating the coupling mechanisms between these two cells may result in new therapies for bone disease.

Animals↗
PubMed1991

A morphometric study of bone surfaces and skin reactions after stimulation with static magnetic fields in rats.

The present investigation was undertaken to measure any bone surface changes after stimulation with orthodontic magnets and, furthermore, to examine the soft tissue in immediate contact with the magnets. Both distal parts of the tibial hind legs in six groups of young rats were fitted with devices holding two orthodontic magnets in the experimental legs and similar devices without magnets in the control legs. The animals were killed after 2, 3, and 4 weeks. Morphometric evaluation showed significant increases in resorbing areas after 3 and 4 weeks. Similarly, a reduction was evident in the number of epithelial cells under the areas where the magnets had been applied. These findings indicate that the stimulation of bone resorption in the present study may have been caused by inhibition of the bone-lining osteoblasts. This proposition is supported by the apparent inhibitory effect of the magnetic fields on epithelial recycling that was seen as a reduced thickness of the epithelium under the magnets. Consequently, static magnetic fields should be used with care in orthodontic practice until a more complete understanding of their mechanism of action has been established.

Animals↗
PubMed1991

Effect of immediate calcium hydroxide treatment and permanent root-filling on periodontal healing in contaminated replanted teeth.

The effect of immediate permanent root-filling and immediate intracanal calcium hydroxide treatment on experimentally contaminated and necrotized periodontal membranes (PDM) in avulsed and subsequently replanted monkey teeth was studied. Almost the entire root surface in the non-endodontically treated control teeth were covered with inflammatory resorption. A significant shift towards ankylosis not associated with root resorption (greater than 80% of the total root surface area) was noted following calcium hydroxide treatment. About two thirds of the root surfaces from the teeth with permanent root fillings showed surface resorptions or ankylosis preceded by root resorption. The root surface area which would have been covered by inflammatory resorption, unless endodontic treatment had been implemented, were instead predominantly covered by either surface resorption (permanent root filling) or ankylosis (calcium hydroxide treatment). Ankylosis compared with surface resorption may in the long term lead to progressive loss of root substance due to replacement resorption. It was concluded that calcium hydroxide may be an excellent initial intracanal treatment in teeth with healthy PDM, but care should be taken not to risk unnecessary development of ankylosis by prolonged treatment of teeth with compromised PDM.

Alveolar Process↗
PubMed1991

Effect of delayed calcium hydroxide treatment on periodontal healing in contaminated replanted teeth.

The effect of delayed intracanal calcium hydroxide treatment on experimentally induced extensive inflammatory root resorption in monkeys was studied. A significant shift from inflammatory resorption to ankylosis was noted following calcium hydroxide treatment. Furthermore, calcium hydroxide treatment appeared to change the pattern of ankylosis over time, although the total ankylotic area remained the same. Ankylosis preceded by root resorption (replacement resorption) increased, while ankylosis not associated with root resorption decreased. It was concluded that intracanal calcium hydroxide treatment of teeth with compromised PDM may cause unnecessary replacement resorption if left in the root canal for a long time or changed repeatedly.

Alveolar Process↗
PubMed1990

Fine tuning of the catalytic properties of carbonic anhydrase. Studies of a Thr200----His variant of human isoenzyme II.

The active sites of carbonic anhydrases I contain a unique histidine residue at sequence position 200. To test the hypothesis that His200 is essential for the isoenzyme-specific catalytic and inhibitor-binding properties of carbonic anhydrases I, a variant of human carbonic anhydrase II, having His200 for Thr200, was prepared by oligonucleotide-directed mutagenesis. The variant has a circular dichroic spectrum that is indistinguishable from that of the parent enzyme. The kinetics of CO2 hydration and HCO3- dehydration has been investigated. The results show that the amino acid substitution has led to changes of catalytic parameters as well as Ki values for anion inhibition in the expected directions towards the values for isoenzyme I. However, the maximal 4-nitrophenyl acetate hydrolase activity of the variant is higher than for any naturally occurring carbonic anhydrase studied so far. A detailed analysis of the kinetic observations suggests that the modification has resulted in a change of the step that limits the maximal rate of CO2 hydration at saturating buffer concentrations. This rate-limiting step is an intramolecular proton transfer in unmodified isoenzyme II and, presumably, HCO3- dissociation in the variant and in human isoenzyme I. A free-energy profile for the dominating pathway of CO2 hydration at high pH was constructed. The results suggest that the major effect of His200 is a stabilization of the enzyme-HCO3- complex by about 7.5 kJ/mol (variant) and 6.1 kJ/mol (human isoenzyme I) relative to unmodified isoenzyme II, while proton transfer between the metal site and the reaction medium is only marginally affected by the amino acid replacement.

Anions↗
PubMed1990

A longitudinal comparative histometric study of the biocompatibility of three local hemostatic agents.

The biocompatibility was studied of 3 hemostatic agents (Astroplast, Hemastogen and bone wax) implanted into experimental bone cavities together with their clearance from the implantation sites. The 3 agents had an acceptable hemostatic effect during the surgical procedure. However, marked differences regarding tissue reactions in the experimental bone cavities, as well as at the internal bone surfaces, were found between them. Astroplast and Hemastogen appear to provoke more adverse tissue reactions, including foreign body giant cell formation, compared with bone wax. All 3 hemostatic implants showed markedly delayed bone healing. It was concluded that their biocompatibility was not ideal but acceptable in view of the clinical advantages.

Alginates↗
PubMed1990

Cellular reactions in pulpal and periodontal tissues after periodontal wound debridement.

Periodontal wounds in monkeys were prepared with a bur followed by the application of microbially contaminated cotton pellets. 3 weeks later, the wounds were debrided by scaling followed by etching with citric acid or by treatment with carbonate/peroxidate. The cellular reactions in the periodontal tissues and in the pulp 4, 11, 25, 39 and 53 days after treatment were followed with light microscopy. The marginal periodontium showed heavy inflammatory reactions immediately after treatment, regardless of the debridement procedure. 25 days after debridement, a long epithelial junction had been formed. The apical part of the epithelium deviated from the root surface into the connective tissue, delineating a heavily inflamed part of the connective tissue. After 39 to 53 days, most of the experimental wounds were covered by an epithelial lining. The pulpal reactions were generally limited to a production of irregular dentin on the pulpal wall facing the periodontal wound. It was concluded that the marginal healing pattern following various chemical treatments to the root surface followed, in all essential aspects, conventional treatment with scaling and root planing.

Animals↗
PubMed1990

Mineralization of and cementoblast attachment to original and reparative cementum.

Cementoblast attachment to original and reparative cementum as well as the mineralization pattern of the two tissues were studied ultrastructurally. Although differences were found in the mineralization pattern between the two types of cementum, cementoblasts attached to both with focal contacts, indicating a non-motile synthesizing state of the cells. It was concluded that the differences in morphology between the two types of cementum are only reflections of the rate with which they are formed.

Animals↗
PubMed1990

Galanin of the homologous species inhibits insulin secretion in the rat and in the pig.

It is known that pig galanin inhibits insulin secretion in dogs, rats and mice. The present study examined whether species-specific, homologous, galanin inhibits insulin secretion. Thus, the effects of rat galanin were examined in the rat, and the effects of pig galanin were examined in the pig, both in vivo and in vitro. In conscious rats, synthetic rat galanin (2 nmol kg-1) abolished the glucose- (0.56 mmol kg-1) induced increase in plasma insulin levels. In vitro, rat galanin (10(-9) to 10(-6) mol l-1) inhibited glucose- (8.3 mmol l-1) stimulated insulin release from isolated rat islets. In anaesthetized pigs, 15 min infusion of synthetic pig galanin (207 pmol min-1) into the pancreatic artery decreased the insulin output with a subsequent recovery. In vitro, pig galanin (10(-6) mol l-1) inhibited glucose- (8.3 mmol l-1) stimulated insulin release from isolated pig islets. We conclude that homologous galanin inhibits insulin secretion in both the rat and the pig.

Animals↗
PubMed1989

Role of histidine 64 in the catalytic mechanism of human carbonic anhydrase II studied with a site-specific mutant.

To test the hypothesis that histidine 64 in the active site of human carbonic anhydrase II functions as a proton-transfer group in the catalysis of CO2 hydration, we have studied a site-specific mutant having histidine 64 replaced by alanine, which cannot transfer protons. The steady-state kinetics of CO2 hydration has been measured as well as the exchange of 18O between CO2 and water at chemical equilibrium. The results show that the rate of exchange between CO2 and HCO3- at chemical equilibrium is essentially unaffected by the amino acid substitution at pH greater than 7.0 and slightly decreased in the mutant at pH less than 7.0 (by a factor of 2 at pH 6.0). However, in the absence of buffer the rate of release from the active site of water bearing substrate oxygen is smaller by as much as 20-fold for the mutant as compared to unmodified enzyme. Furthermore, in the unmodified enzyme water release is inhibited by micromolar concentrations of Cu2+ ions, but no such inhibition is observed with the alanine 64 variant. These results suggest that the mutation has specifically affected the rate of proton transfer between the active site and the reaction medium. This kinetic defect in the mutant can be overcome by increasing the concentration of certain buffers, such as imidazole and 1-methylimidazole, but not by others buffers, such as MOPS or HEPES. Similarly, the maximal rate of CO2 hydration at steady state catalyzed by the alanine 64 variant is very low in the presence of MOPS or TAPS buffers but considerably higher in the presence of imidazole derivatives.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1989

Effects of galanin on insulin and glucagon secretion in the rat.

Galanin-like immunoreactivity has been visualized in nerve fibers in the islets of Langerhans, suggesting an involvement of galanin in the neural regulation of islet function. In this study, we investigated the effects of galanin on basal and stimulated insulin and glucagon secretion by infusing the peptide at three different dose rates in rats. We also studied the direct effect of galanin on insulin secretion from freshly isolated rat islets. At 320 pmol/kg/min, but not at 20 or 80 pmol/kg/min, galanin lowered basal plasma insulin levels. In contrast, basal plasma glucagon levels were lowered by galanin already at 20 and 80 pmol/kg/min. Furthermore, galanin inhibited both glucose- and arginine-induced insulin release at all three dose levels, whereas arginine-induced glucagon release was not affected by galanin. Glucose-stimulated insulin secretion from isolated rat islets was dose-dependently suppressed by galanin (10(-6)-10(-8) M). Therefore, it is concluded that galanin in rats inhibits insulin secretion, both in vivo and in vitro, and that at lower dose levels, the peptide also inhibits basal glucagon release.

Animals↗
PubMed1989

Influence of granulation tissue, dental calculus and contaminated root cementum on periodontal wound healing. An experimental study in monkeys.

The rôle of gingival granulation tissue, dental calculus and contaminated root cementum in marginal periodontal formation of new attachment was studied experimentally after chemical conditioning of the root surfaces of premolars and molars in 8 monkeys. Each treatment procedure was carried out in 4 monkeys. The other 4 monkeys served as controls. A morphometrical method was used to evaluate the results. It was concluded that a significant amount of new attachment including formation of new adhering cementum will result only on chemically-conditioned cementum surfaces. Small amounts of calculus or granulation tissue left in situ do not seem to influence healing, provided the cementum is left intact after chemical cleansing.

Alveolar Process↗
PubMed1989

Effect of a high dose of fluoride on resorbing osteoclasts in vivo.

Histomorphometric analysis of osteoclasts resorbing bone above the erupting first rat molar tooth germ was made at 1, 2, 6, 24, and 48 h following systemic administration of a single high dose of sodium fluoride. Compared to the number of osteoclasts in control rats, a significant reduction was observed in the number of actively resorbing osteoclasts in fluoride-injected rats at 2 and 6 h after dose administration, after which a gradual increase to control levels was observed. A locally increased number of inactive osteoclasts, not attached to bone surfaces, accompanied the reduced number of active osteoclasts.

Animals↗
PubMed1989

Dynamics of dentoalveolar ankylosis and associated root resorption.

The present experimental studies in monkeys were undertaken to study the initiation and progression of dentoalveolar ankylosis of replanted teeth and associated root resorption. Maxillary and mandibular lateral incisors were extracted and replanted after an extraoral period of 15 min or 1 h. Teeth with an extraoral period of 1 h were endodontically treated. Half the number of monkeys were given antibiotics at the time of replantation. The observation periods varied from 2 days to 40 weeks. Irrespective of the length of the extraoral period, initial root resorption and minor areas of ankylosis were found 1 week after replantation. The initial ankylosis was not preceded by root resorption. In teeth replanted after an extraoral period of 15 min the ankylotic area did not increase with increasing time after replantation. Instead the periodontal membrane was re-established, separating the root surface from the alveolar bone. In teeth replanted after an extraoral period of 1 h, the initial ankylotic area increased with increasing time after replantation. Eight weeks and more after replantation, most of the periodontal membrane was replaced by bone covered by osteoblasts and occasional osteoblasts that were in continuity with the endosteal cells outlining the marrow spaces of the alveolar bone. The cementum and dentin were then gradually resorbed with increasing time after replantation. Antibiotics given at the time of replantation reduced the initial inflammation in the periodontal membrane and the inflammatory root resorption after all observation periods and it also seemed to some extent to prevent bacteria from entering the necrotic pulp tissue. Based on the present results it is suggested that root resorption associated with dentoalveolar ankylosis is initiated by endosteal osteoblasts and is thus a hormonally regulated process. This is in contrast to inflammatory root resorption, which seems to be triggered by inflammatory cells.

Animals↗
PubMed1989

Early responses by osteoclasts in vivo and dentinoclasts in vitro to corticosteroids.

The results of previous investigations examining the association between corticosteroids and bone resorption in vitro have been conflicting. Recent studies have shown that application of a triamcinolone-containing medicament to the dental pulp cavity inhibits dentinoclast-mediated tooth resorption in vivo and in vitro. The aims of this study were to quantitate early ultrastructural changes in osteoclasts in vivo in response to a single steroid dose, and to examine the attachment of dentinoclasts grown in steroid-supplemented cultures in vitro. Resorbing bone around erupting rat molars was examined using TEM and morphometrically quantitated for changes in ruffled border and clear zone areas 1 and 4 h after injections of NaCl, calcitonin, hydrocortisone and prednisolone. Dentinoclasts were harvested from resorption areas in mature rat molars, grown in cultures with calcitonin, hydrocortisone or prednisolone, and fixed and viewed with SEM after 30 min and 2 h. Results of TEM studies showed a significant reduction in areas of resorbing structures in osteoclasts treated with calcitonin at 1 and 4 h, and prednisolone at 4 h. At 1 and 4 h, hydrocortisone showed an increase in resorbing structure areas. SEM results indicated all experimental substances reduced dentinoclast spreading and attachment. It was concluded that the direct effect of steroids on clastic cells may be one of inhibition (the degree of which depends on the nature and dose of the steroid) whereas, in vivo, systemic administration may cause more secondary effects (such as PTH stimulation) to compete with this inhibition. The efficacy of steroid-containing medicaments in inhibiting dentinoclastic resorption may be due to their relatively localized area of application.

Adrenal Cortex Hormones↗
PubMed1988

Rapid-scan stopped-flow studies of the flavoenzyme mercuric reductase during catalytic turnover.

Time-resolved absorption spectra of the FAD-containing enzyme mercuric reductase were recorded during the catalytic reaction at 25 degrees C, pH 7.3. With an excess of NADPH over Hg2+ there was a rapid (k = 43 s-1) initial formation of a spectral species similar to that previously assigned to an NADPH complex of two-electron-reduced enzyme, EH2-NADPH. This spectrum persisted during the quasisteady-state phase of the reaction suggesting that EH2-NADPH is a true catalytic intermediate and that the rate of catalysis is limited by the oxidation of EH2-NADPH by Hg2+. Also with an excess of Hg2+ over NADPH a spectrum similar to that of EH2-NADPH was rapidly formed. As the NADPH was exhausted, the spectrum of oxidized enzyme, E, did not reappear but rather a spectrum similar to that previously assigned to an NADP+ complex of two-electron-reduced enzyme, EH2-NADP+. These results suggest that EH2-HADP+ cannot rapidly reduce the Hg2+ substrate. However, eventually all reducing equivalents from NADPH added to oxidized, activated enzyme are utilized for the reduction of Hg2+. A mechanism model is proposed that does not involve the free, oxidized enzyme in the catalytic cycle.

Catalysis↗