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Biomedical subjects

R P Happonen

Publications and source records attributed to R P Happonen.

At least 19 recordsLinked to original sources

Osteoblast differentiation of bone marrow stromal cells cultured on silica gel and sol-gel-derived titania.

Primary cultures of osteogenic precursor cells derived from rat bone marrow stroma were performed on commercially available pure titanium discs (Ti c.p.) and surface modified Ti c.p.using a sol-gel technique (Ti sol). In separate repeated experimental runs, cell behavior and in vitro mineralization were compared with cultures on silica gel bioactive glass discs (S53P4). All substrates were incubated in simulated body fluid prior to the experiment. Overall, variable effects between experimental runs were seen. Apparently, this was due to the heterogeneous nature of the used cell population. Therefore, only careful conclusions can be made. Initial cell adhesion and growth rates between 3 and 5 days of culture--analyzed by cell numbers--were in general comparable for the two titanium substrates, while initial growth up to day 3 is suggested to be higher in Ti c.p. compared to Ti sol. Although initial cell adhesion on the S53P4 glass discs was lower than the titanium substrates, cell growth rates appeared to be higher on the silica gel compared to the two titanium substrates. Further, there were some indications that the early and late osteoblast differentiation markers, alkaline phosphatase and osteocalcin, monitored up to day 24, were elevated in Ti c.p cultures compared to Ti sol cultures. There were no differences observed in in vitro mineralization between the titanium groups. S53P4 seemed to display a substantially higher differentiating capacity for both osteogenic cell markers as well as in vitro mineralization compared to the two titanium substrates.

Alkaline Phosphatase↗

Osteodistraction of a previously irradiated mandible with or without adjunctive hyperbaric oxygenation: an experimental study in rabbits.

The purpose of this study was to analyse the effects of irradiation and hyperbaric oxygenation (HBO) on mandibular osteodistraction (OD). Eighteen rabbits were divided into three groups: 1. Irradiation (R), 2. Irradiation+HBO (R-HO), and 3. Control group (C). Animals of groups R and R-HO received in the mandible irradiation 22.4 Gy in four 5.6 Gy fractions (equivalent to 50 Gy/25 fractions). In addition, group R-HO was given HBO at 2.5 ATA for 90 min per day 18 times preoperatively. Unilateral osteotomy was made 1 month after completion of radiotherapy. After a 1 week latency period bone distraction was started at rate of 1 mm per day, continued for 2 weeks, and left to consolidate for 4 weeks. Amount of new bone was measured histomorphometrically from midsagittal sections. Area of new bone was equal in all groups. Bone was more mature and bone spicules better organized in group C than in groups R and R-HO. Cartilaginous cells were found in distracted bone in all groups but larger chondroid islands were evident only in group R. It seems that despite delayed bone formation, OD can be performed after radiotherapy. HBO had a beneficial effect on bone quality of a previously irradiated mandible.

Animals↗

Effect of mandibular distraction osteogenesis on temporomandibular joint after previous irradiation and hyperbaric oxygenation.

The purpose was to evaluate the effect of mandibular distraction osteogenesis (DO) on condylar cartilage after radiotherapy and hyperbaric oxygenation (HBO). Unilateral DO was performed on low- and high-dose irradiated rabbits with or without accompanying HBO, and non-irradiated animals. High-dose irradiated animals were given irradiation in the temporomandibular joint (TMJ) equivalent to 50 Gy in 25 fractions. Low-dose irradiated rabbits received scattered irradiation of 10% of that of high-dose irradiated animals. After radiotherapy, some of the animals were given HBO 18 times at 2.5 ATA for 90 min/day. One month after completion of radiotherapy, distraction osteotomy with distractor placement was performed. After a latency period, distraction was started at the rate of 1 mm/day, continued for 2 weeks, and the regenerate was allowed to consolidate for 1 month. Condyles of non-operated rabbits served as controls. Histological changes were more evident on the distracted than on the non-distracted side. In distracted, non-irradiated animals, condylar cartilage changes were minor and probably clinically insignificant. In irradiated rabbits, condylar cartilage changes on the lengthened side were severe, and often cartilage was either totally or partially sealed off by bone. Condylar heads were morphologically deformed. Even low doses of irradiation resulted in notable changes on the operated side, and HBO did not prevent disadvantageous effects.

Animals↗

Craniofacial morphology in preschool children with sleep-related breathing disorder and hypertrophy of tonsils.

UNLABELLED: The purpose of this study was to examine craniofacial morphology, pharyngeal airway space and hyoid bone position in preschool children with sleep-related breathing disorder associated with hypertrophy of tonsils (SBDT). Thirty-eight preschool children, mean age 4.7 y, with SBDT and with an apnoea index (AI) of 0 < AI < 5, were divided into two groups. One consisted of 15 children with sleep-related breathing disorder (SBD) and more than 75% of the tonsils visible (GIII) and the other of 23 children with SBD and 25-75% of the tonsils visible (GII). The control group consisted of 31 children without ear, nose and throat disease and with GI (barely visible) tonsils. Compared with the controls, GIII children had a retrognathic mandible, a large posterior facial height, a large interincisal angle with retroclined lower incisors, a narrow pharyngeal airway space, an anterior tongue base position and a long soft palate. Compared with the controls, GII children had a large anterior lower facial height and a short nasal floor. However, like the controls, GII children did not have a retrognathic mandible. CONCLUSION: The findings show that children with SBDT display a characteristic facial appearance at an early age. Since the condition has an effect on growth, it needs to be prevented by controlling morphology and function at the preschool age.

Case-Control Studies↗

Reduction of syndecan-1 expression is associated with dysplastic oral epithelium.

Syndecans are a family of integral membrane proteoglycans that participate in cell-matrix interactions and growth factor binding. Syndecan-1 expression is induced during keratinocyte differentiation and reduced in squamous cell carcinomas. The purpose of this study was to examine the alteration in syndecan-1 expression in dysplastic oral epithelium. Sixty-six oral biopsy specimens (43 epithelial dysplasias, 3 carcinoma in situ and 20 squamous cell carcinomas) were studied using immunohistochemical methods. The normal epithelium specimens were highly positive for syndecan-1. Fifteen of 46 dysplasias or carcinoma in situ specimens showed negative or weak staining for syndecan-1, two of which were totally negative. Intermediate and strong staining were observed in 17 and 14 dysplasias or carcinoma in situ specimens, respectively. Thirteen (65%) squamous cell carcinomas showed negative or weak staining for syndecan-1, seven of which were totally negative. Only three carcinomas had a strong syndecan-1 expression. Four of the 34 patients with dysplasia who were followed up developed squamous cell carcinoma. All these dysplasias had weak or totally negative syndecan-1 expression. The results suggest that the loss of syndecan-1 is associated with dysplastic changes in oral epithelium.

Adult↗

The effect of PUVA on langerhans cells in rat oral epithelium photosensitized with systemic methoxsalen or topical trioxsalen.

BACKGROUND/PURPOSE: Ultraviolet-A radiation (UVA) of the oral mucosa after photosensitization with either systemic methoxsalen (8-MOP) or topical trioxsalen (TMP), i.e. mouth-PUVA, has been reported to be successful in the treatment of oral lichenoid lesions. In the case of PUVA treatment of skin disorders, local immune suppressive effects have been demonstrated, and the antigen presenting epithelial Langerhans cells (LCs) have been shown to be especially sensitive to ultraviolet treatments. Our aim was to compare the photobiological effects of PUVA in oral mucous membrane (OMM) using topical TMP or systemic 8-MOP photosensitization. METHODS: Rat OMM photosensitized with topical TMP or systemic 8-MOP was treated with PUVA using UVA doses of 1-8 J/cm2. The LCs were demonstrated in epithelial sheets of the treated OMM with ATPase staining. RESULTS: Both treatments caused a sim ilar, dose-dependent depletion of ATPase-positive LCs, with a maximal depletion of 80% or 73% with 8 J/cm2 at 2 days after irradiation as photosensitized with TMP or 8-MOP, respectively. This contrasts with earlier published findings in human skin, where topical TMP is an order of magnitude greater a sensitizer than 8-MOP, and PUVA-induced depletion of LCs occurs maximally 5 days after irradiation. CONCLUSION: The depletion of LCs of rat OMM after PUVA treatment is greater using topical TMP compared to systemic 8-MOP, but the difference is significantly smaller than reported earlier in human skin.

Administration, Oral↗

Intraocular lens bioactivity tested using rabbit corneal tissue cultures.

PURPOSE: To evaluate the effects of different intraocular lens (IOL) materials on epithelial cell growth to test the sandwich theory; i.e., a bioactivity-based explanation of posterior capsule opacification (PCO) after cataract surgery. SETTING: Central Hospital, Vaasa, and Institute of Dentistry and Turku Center for Biomaterials, University of Turku, Finland. METHODS: Rabbit corneal tissue cultures were set up on poly(methyl methacrylate) (PMMA), heparin-surface-modified (HSM) PMMA, silicone, acrylate, and hydrogel IOLs for 1 week. The tissue consisted of intact epithelium and half the thickness of the corneal stroma, which was placed against the IOL. The growth of the epithelium was examined by light microscopy to evaluate the attachment of the corneal explant to the IOL surface. RESULTS: All tissue samples grew well under the culture conditions. When grown on PMMA, HSM PMMA, silicone, and hydrogel, the tissue did not attach to the IOL or the epithelium grew around the explant, suggesting that the attachment of the stroma to the IOL was poor or nonexistent. Some explants on acrylate IOLs attached directly to the IOL surface with no epithelial ingrowth between the stroma and the IOL. CONCLUSIONS: This tissue culture method can be used to examine the behavior of corneal tissue in contact with different IOL materials. The results suggest that the acrylate IOL may have bioactive properties. This, with the lens optic's square edge, may hinder lens epithelial cell proliferation and thus prevent PCO.

Animals↗

Osteopontin (OPN) distribution in premalignant and malignant lesions of oral epithelium and expression in cell lines derived from squamous cell carcinoma of the oral cavity.

The objectives of this study were to assess the immunolocalization of human osteopontin (OPN) in oral lesions and to identify human cell lines of oral squamous cell carcinoma (OSCC) origin that express OPN mRNA. OPN was localized using immunohistochemistry in the following oral specimens: normal epithelium (n=6), epithelial hyperplasia (n=4), epithelial dysplasia (n=28), carcinoma in situ (n=11) and squamous cell carcinoma (n=43). Cell lines UMSCC-1, MDA TU 138, MDA 686LN, SCC4, SCC9, SCC25, CAL 27 and MDA 1483 were characterized for OPN mRNA expression using Northern blotting. OPN was not detected in normal oral epithelium. Intracellular and intercellular immunoreactivity was seen in 75% of hyperplasias, 57% of dysplasias, 54% of carcinoma in situ and 67% of squamous cell carcinomas. UMSCC-1 expressed high levels of OPN mRNA. We conclude that OPN protein is detectable in premalignant and malignant lesions arising from oral epithelium. UMSCC-1 may be a useful cell line in which to conduct in vitro studies designed to clarify the role of OPN in OSCC.

Adolescent↗

Immunocompetent cells in amalgam-associated oral lichenoid contact lesions.

Inflammatory cells in amalgam-associated, oral lichenoid contact lesions (OLL) were studied in 19 patients by immunocytochemistry using monoclonal antibodies. Ten of the patients displayed allergic patch test (PT) reactions to several mercury compounds and nine were negative. The immunocytochemical quantification showed a uniform composition of the inflammatory mononuclear cells in the two study groups. The number of HLA-D/DR-positive dendritic cells (P<0.001) and CD1a-positive Langerhans cells (P=0.035) was significantly lower in the PT-negative than PT-positive patients. HLA-D/DR expression on keratinocytes varied from negative to full thickness staining of the epithelium. HLA-D/DR expression in the full thickness of epithelium (3) or through the basal and spinous cell layers (2) was seen in 5 of 8 PT-positive patients, whereas none of the PT-negative patients had this staining pattern (P=0.045). These patients also showed a good clinical response after amalgam removal. Consequently, OLL may represent a true delayed hypersensitivity reaction with a trans-epithelial route of entrance of the metal haptens released from dental restorative materials.

Adult↗

Obliteration of the frontal sinus cavity with bioactive glass.

BACKGROUND: Bioactive glass (BG) is a glass ceramic material. It has been used as surgical bone replacement material in ear and oral surgery, orthopedics, and dentistry. METHODS: Bioactive glass was used as obliteration material in a series of osteoplastic frontal sinus operations on 10 patients suffering from chronic frontal sinusitis, which other, more-conservative treatment modalities had failed to cure. RESULTS: Bioactive glass is easy to handle, and complete obliteration of all sinusal recesses and excavations is easily achieved. No adverse effects of the implant material have been seen over a mean follow-up period of 5.0 years. One patient with a local recurrent infection in the outer table of the sinus was reoperated on 5 months after primary surgery. Repeated postoperative computed tomographic scans analyzed by digital region-of-interest (ROI) selection showed no remarkable changes in the frontal sinus cavities but a slight, yearly decrease in the density of the occlusion material. Laboratory monitoring of patients and histopathologic examination of two postoperative biopsy specimens indicated that the material is well tolerated and stable. CONCLUSIONS: Bioactive glass is a promising and well-tolerated bone graft suitable for osteoplastic frontal sinus operations. Total accurate obliteration of the sinus is achieved with different sizes of granules and blocks. The results of the obliteration are maintained owing to the stability of the material.

Adult↗

Compositional dependence of bioactivity of glasses in the system Na2O-K2O-MgO-CaO-B2O3-P2O5-SiO2.

The bioactivity, i.e., bone-bonding ability, of 26 glasses in the system Na2O-K2O-MgO-CaO-B2O3-P2O5-SiO2 was studied in vivo. This investigation of bioactivity was performed to establish the compositional dependence of bioactivity, and enabled a model to be developed that describes the relation between reactions in vivo and glass composition. Reactions in vivo were investigated by inserting glass implants into rabbit tibia for 8 weeks. The glasses and the surrounding tissue were examined using scanning electron microscopy (SEM), light microscopy, and energy-dispersive X-ray analysis (EDXA). For most of the glasses containing < 59 mol % SiO2, SEM and EDXA showed two distinct layers at the glass surface after implantation, one silica-rich and another containing calcium phosphate. The build-up of these layers in vivo was taken as a sign of bioactivity. The in vivo experiments showed that glasses in the investigated system are bioactive when they contain 14-30 mol % alkali oxides, 14-30 mol % alkaline earth oxides, and < 59 mol % SiO2. Glasses containing potassium and magnesium bonded to bone in a similar way as bioactive glasses developed so far.

Animals↗

An open clinical trial of a new mouth-PUVA variant in the treatment of oral lichenoid lesions.

OBJECTIVE: To investigate the feasibility of topical psoralen PUVA (sensitization in photosensitizing psoralen drug + UVA radiation) treatment of oral lichenoid lesions (OLL). STUDY DESIGN: A total of 16 patients with OLL were treated using a 0.01% trioxsalen ointment and UVA doses in the 0.09 to 1.80 J/cm2 range. The average number of sessions was 8.7 and a mean cumulative irradiation dose was 4.25 J/cm2. RESULTS: A marked-to-complete healing occurred in 3 to 16 (19%) patients immediately after therapy, in 4 of 14 (29%) after 3 months, and in 5 of 14 (38%) after 14 months, respectively. Of the 16 subjects with OLL, five were diagnosed as oral lichen planus (OLP) and 11 were classified as oral lichenoid reaction (OLR). Post-PUVA amelioration rate in patients with genuine OLP (4 of 5, 80%) was superior to that in patients with OLR (1 of 9, 11%). CONCLUSION: Topical trioxsalen photosensitization can be used in mouth-PUVA treatment, and lichen planus is a main indication for this therapy.

Administration, Topical↗

Bioactive glass and calcium carbonate granules as filler material around titanium and bioactive glass implants in the medullar space of the rabbit tibia.

The effect of bioactive glass (BG) and calcium carbonate (CC) granules on bone formation around titanium and BG implants projecting into the medullary space of rabbit tibia was studied. The bone marrow tissue was removed and the medullary space was filled either with BG or CC (Biocoral) granules (phi 630-800 microns). Conical titanium and BG implants were inserted into the holes drilled in compact bone using the press fit-technique. Histomorphometry was used to measure the bone-biomaterial area in a 1.0 mm wide zone around the head of the implant and the contact between formed bone and implant. Significantly larger bone-biomaterial area was obtained around titanium implants using BG than CC granules while no difference was found in connection of BG implants. Better bone-implant contact was achieved with BG implants than with titanium implants regardless of the type of granules used. The results indicate that BG may prove to be useful as filler and coating material in connection of implants projecting into bone cavities.

Animals↗

Contact allergy to dental restorative materials in patients with oral lichenoid lesions.

118 patients with oral lichenoid lesions (OLL) topographically related to dental fillings were patch tested (PT) to reveal contact allergy to restorative materials. 80 (67.8%) patients displayed positive PT reactions to metals of dental filling materials: 76 reactions were found to various mercury compounds, 4 to sodium aurothiosulphate, 3 to stannic chloride and 2 to silver nitrate. The positive patch test reactions appeared more commonly in patients with restricted contact lesions (85.1%, type-1 lesions) as compared to patients with lesions exceeding to the adjacent areas (38.6%, type-2 lesions). The replacement of dental fillings was carried out in 62/80 PT-positive and 15/38 PT-negative patients. 28 out of 62 (45.2%) PT-positive and 3/15 (20%) PT-negative patients showed complete healing of OLL after a mean follow-up time of 16 months. Complete healing occurred in 29/54 (54.0%) type-1 and 2/23 (8.7%) type-2 lesions. Topographical relation between the lesion and the filling material (restricted versus exceeding the contact area) indicated association of OLL lesion and the filling material, which could be further confirmed by patch testing in the majority of patients. The patch test series should include mercuric chloride (0.1%), mercury (0.5%) and mercury ammonium chloride (1.0%), each in pet.

Adult↗

Effect of snuff on cytokeratin expression in oral vestibular sulcus epithelium.

Differences in the expression of cytokeratins (CK) in specimens obtained from snuff-affected oral epithelium of the maxillary vestibular sulcus and clinically normal sulcular epithelium were studied by indirect immunofluorescence staining with a panel of monoclonal antibodies (MAbs). CK 14, a marker of stratified squamous epithelium was not seen expressed in 3/11 of the snuff user's specimens. Terminal differentiation markers, typical of cornified epithelia (CK 1, 9, 10 and 11), were detected suprabasally in the snuff user's keratosis but not in the normal control epithelium. The use of snuff seemed to change the CK staining pattern of the mucosa so that it resembles more that of a cornified type of epithelium. Simple epithelial-type CK were included in the study in order to establish the CK profile of the snuff-induced keratosis, for comparison with normal and dysplastic lesions. MAb to CK 7 and 19 showed reactivity in the basal cells and suprabasally whereas the monospecific MAb anti-CK 7 showed suprabasal staining both in the control and affected epithelia. By using MAbs, we found no immunoreactivity against CK 18 either in normal or affected epithelia, whereas we found suprabasal reaction (5/11) against CK 8 in the snuff user's epithelia. The two MAbs demonstrating the expression of CK 19, normally confined to the basal cells of the stratified squamous epithelium, showed variable patterns of expression both in basal cells and suprabasally in the snuff lesions. The results show that use of oral snuff causes some alterations in the CK expression pattern of the affected epithelium. Whether the alterations are indicative of a premalignant change is, however, uncertain. The results encourage further studies on the subject.

Adult↗

Effect of snuff and smoking on tenascin expression in oral mucosa.

We have shown, by using two monoclonal antibodies (143DB7 and 100EB2), that the expression of the extracellular matrix protein tenascin (Tn) is increased in the connective tissue of biopsies taken from snuff users' and tobacco smokers' oral mucosa. In normal oral mucosa Tn was seen to underlie the epithelium as a thin delicate band. The most increase in Tn reaction was observed in snuff users' mucosa while the immunoreaction in smokers' mucosa was less conspicuous. Often the most prominent Tn reaction took place in association with round cell inflammatory infiltration, indicating epithelial irritation. Tn has been shown to take part in epithelial-mesenchymal interactions during embryogenesis, wound healing and tumorigenesis. Here, a superficial epithelial irritant has been shown to cause conspicuous alterations not only in the epithelial cell layers but also in the underlying connective tissue by increasing its Tn content. As a result of our findings we suggest a further link for Tn in a dynamic epithelial-mesenchymal interplay by virtue of this marked connective tissue reaction in snuff users' and smokers' oral mucosa.

Adult↗

In vitro lymphocyte proliferation test in the diagnosis of oral mucosal hypersensitivity reactions to dental amalgam.

Patch testing was carried out in 23 patients with oral lichenoid lesions (OLL) topographically related to dental amalgam fillings. Twelve patients displayed positive reactions to several mercury compounds, whereas 11 patients were negative. An in vitro lymphocyte proliferation (LyPro) test was carried out using different mercury compounds and other metal salts. Mercuric chloride and phenyl mercuric acetate caused positive proliferation in 3/12 patch test-positive and in 5/11 negative patients. One out of seven healthy control subjects had a positive LyPro result. The mean stimulation index (SI) values between the patient groups or compared with the control subjects did not differ significantly. Zinc, tin, copper or silver salts caused in vitro lymphocyte stimulation in most of the patients and in healthy control people. Total (14) or partial (4) replacement of amalgam fillings was carried out in 18 patients. Complete healing of lichenoid lesions was seen in 4/6 LyPro test-positive and in 5/10 patch test-positive patients at follow-up examinations 12 months after the replacement of amalgam fillings. The in vitro proliferation assay seems not to be a specific test for identifying the patients who would benefit from amalgam replacement.

Adult↗

Titanium and bioactive glass-ceramic coated titanium as materials for keratoprosthesis.

The current problem with keratoprosthesis is the ingrowth of corneal or conjunctival epithelium into the anterior chamber. This may lead to infections and extrusion of the prosthesis as well as to the development of retroprosthetic membrane and secondary glaucoma. Glass-ceramic coated and uncoated titanium has been tested as material for the keratoprosthesis to prevent epithelial ingrowth. Twenty-two Supra-Descemet's membrane keratoprostheses were inserted in the eyes of 22 rabbits for 1, 2, 4, 8, or 12 months. The prosthesis had an optic part made of polymethylmetacrylate (PMMA). The support for the optic part and the flange of the prosthesis were made of titanium. Eleven of the prostheses were coated with glass-ceramic. The histological sections of the enucleated eyes were prepared through the central part of the cornea and the prosthesis using a cutting-grinding method. The histological analysis was made on both halves of the implants separately giving two analysis areas in each eye. All 11 titanium prostheses were retained for the time period planned. Two glass-ceramic coated prostheses were lost at 2 and 4 weeks, respectively. This was caused by difficulties at surgery due to a thick coating. These eyes were excluded from the histological analysis. No significant ingrowth of epithelium was seen in 15/18 (83%) and in 16/22 (73%) of the analysed areas of the glass-ceramic coated and titanium prostheses, respectively. Titanium appears to be a suitable material for the keratoprosthesis. The ingrowth of the epithelium may be hindered further by coating the titanium with bioactive glass-ceramic.

Animals↗