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Insulin-like growth factor system components in the periodontium during tooth root resorption and early repair processes in the rat.

There is evidence that growth factors, such as the insulin-like growth factors (IGFs), are involved in biological and pathological processes in oro-dento-facial tissues. To investigate their roles in tooth movement, root resorption, and repair, the occurrence of components of the IGF system, including the ligands IGF-I and -II, the IGF receptor 1 (IGF1R) and six IGF-binding proteins (IGFBP-1 to -6), was investigated by immunohistochemistry on sections from rat maxillae where the first molar had been moved mesially by means of an orthodontic appliance for 9 d to induce root resorption. After force deactivation on day 0, early repair was studied after a further 5, 7, 10, 12, 14, and 17 d. The immunostaining pattern in the periodontal ligament, cementum, and bone of control animals showed similarities known from studies in human teeth. Increased immunostaining for nearly all components in pressure sides and resorption lacunae indicated an involvement in resorption processes and clastic activities. During early stages of repair, the occurrence of several components (e.g. IGF-II, IGFBP-5 or -6) within lacunae and in cementoblasts showed an involvement in the resorption-repair sequence, which is considered to be a coupling process as known from bone.

Alveolar Process↗

Bone formation in tricalcium phosphate-filled periodontal intrabony lesions. Histological observations in humans.

The capacity of a tricalcium phosphate (TCP) ceramic to promote bone formation after grafting in intrabony defects was studied in humans. Five biopsies were collected from 4 patients during reentry surgery 16 to 40 months after implantation. They were processed without demineralization for histological examination. In the less mature samples, the grafted material was surrounded by a highly fibrous, highly cellular, and poorly vascularized connective tissue. Howship's lacuna-like cavities were clearly visible at the surface of the material. They contained resorbing mononuclear phagocytes. At a more mature stage, TCP granules were embedded in an acellular fibrous material which underwent mineralization from the medullary spaces towards the granules. The bone formed was subsequently remodeled. The implanted material itself was progressively modified. It first acquired the staining appearance of bone. After its structure became loose and vacuolated, it was invaded by cells and vessels. The present data indicate that TCP has osteogenic potential and is subject to degradation. Unlike in experimental wounds, these processes are of long duration in human defects.

Adult↗

Hyperoxic injury decreases alveolar epithelial cell expression of vascular endothelial growth factor (VEGF) in neonatal rabbit lung.

Normal neonatal lung growth requires a substantial increase in microvascular endothelial cells. Oxygen injury to neonatal lung destroys endothelial cells and alters the normal process of alveolarization, including development of the microvasculature. The mechanisms that regulate lung alveolar capillary growth and development are not known. Vascular endothelial growth factor (VEGF) is a specific mitogen for endothelial cells that is often expressed by epithelial cells in close proximity to capillary beds. VEGF expression is induced by hypoxia and may be inhibited by hyperoxia. We examined the cell-specific expression of VEGF during normal postnatal lung development and the effects of hyperoxic lung injury on VEGF mRNA and protein in vivo. Normal newborn rabbits between 1 day and 5 wk of age had VEGF transcripts located mainly in alveolar epithelial cells, with little or no VEGF mRNA noted in smooth muscle or endothelial cells. A subpopulation of freshly isolated, normal type II cells, but not mesenchymal cells, expressed VEGF mRNA. Newborn rabbits exposed to 100% oxygen for 4 days had no change in VEGF mRNA abundance, transcript location, or immunostaining. Animals exposed to 100% oxygen for an average of 9 days had an 80% decrease in lung VEGF mRNA abundance, decreased alveolar epithelial cell VEGF expression, and decreased VEGF immunostaining. Recovery of VEGF expression to control levels occurred during a 5-day recovery period. We conclude that alveolar epithelial cells in postnatal lung express VEGF, suggesting epithelial regulation of alveolar capillary formation. Furthermore, hyperoxic injury decreases neonatal lung VEGF mRNA and protein, which may be a contributory mechanism of impaired postnatal microvascular development in oxygen injury.

Animals↗

Repair of periodontal furcation defects in beagle dogs following reconstructive surgery including root surface demineralization with tetracycline hydrochloride and topical fibronectin application.

This study examines the effects of root surface demineralization and topical fibronectin as adjuncts to reconstructive periodontal surgery. In 14 beagle dogs, horizontal periodontal defects were surgically induced around the mandibular premolars followed by a 6-week period without plaque control. Reconstructive surgery of the defects was subsequently carried out. The root surfaces were debrided and superficially demineralized with citric acid or tetracycline hydrochloride, with or without subsequent application of fibronectin. Mucoperiosteal flaps were raised to cover most of the crowns and sutured. The animals were sacrificed 12 weeks after surgery and block sections of the teeth and surrounding tissues were processed for histology. Analysis included incidence of furcation defects presenting with an epithelial lining, quantification of connective tissue repair relative to the furcation circumference, and regeneration of alveolar bone relative to the furcation defect height. The incidence of root resorption and ankylosis was also analyzed. Within the limitations of this study it was concluded that: (1) citric acid conditioning of the root surface frequently resulted in complete connective tissue repair of the furcation defect; (2) root resorption and ankylosis were prevalent features of the healing response; (3) citric acid and tetracycline treatment had similar potential to induce connective tissue repair and resulted in corresponding incidences of root resorption and ankylosis; (4) application of fibronectin to demineralized root surfaces did not enhance the amount of connective tissue repair and did not alter the pattern of root resorption and ankylosis.

Administration, Topical↗

Histometric and ultrastructural studies of tissues surrounding Astra dental implants in dogs.

Twenty-four Astra titanium dental implants were inserted bilaterally, three on each side, into the mandibles of four dogs to study mucosal and bone-implant junctions. After a healing period of 6 months, the dogs were sacrificed and bone sections with implants were removed and processed for histologic evaluation. All implants were stable, and radiographs disclosed complete bone healing. The surrounding mucosa closely resembled that surrounding natural teeth. Histometric analysis of the alveolar bone revealed that, on average, 61.3% of the implant surface interface was integrated in the bone at the light-microscopic level.

Alveolar Process↗

Assessment of the severity of pulmonary emphysema by computed tomography.

Pulmonary emphysema is defined as an abnormal enlargement of alveolar spaces distal to the terminal bronchioles, with alveolar wall disruption and without obvious fibrosis. Clinico-functional evaluation and chest radiographic diagnosis are not highly accurate in detecting emphysema and in establishing the extent of the process of alveolar destruction. Several computed tomography (CT) techniques are now available for detection and quantitative assessment of emphysema. The results appear to correlate significantly better than chest radiography with functional impairment and pathological score. Many options have been proposed by different authors regarding CT technique. The choice, however, is essentially between inspiratory high resolution CT (HRCT) with a visual scoring system, and automated quantitative evaluation by means of a "density mask" (DM) program. This paper presents the state of the art on CT quantification of pulmonary emphysema and briefly discusses the technical options and parameters to be used, together with the problems to be solved.

Humans↗

[Clinical evaluation, radiologic and histologic analysis in mandibular alveolar distraction procedures. Preliminary study].

BACKGROUND: Alveolar distraction osteogenesis is a process to form new alveolar bone to correct alveolar deformities in ridge height and width. Aim of this work is to study the bone processes to optimize the implantoprosthetic rehabilitation. METHODS: Alveolar distraction osteogenesis was applied in 7 patients with ridge deformities to obtain the desired ridge augmentation. Clinical and radiological evaluations were performed during the following 12 weeks, before implant insertion. Biopsies at 40, 60 and 88 days were studied after general, specific and histochemical staining of slides; microradiographs were analyzed to evaluate the trabecular bone volume. RESULTS: Forty days after the end of distraction, soft callus shows the start of ossification. Sixty days after the end of distraction, soft callus was widely converted into a network of trabecular woven bone; osteogenic activities were low; trabecular bone volume was about 50%. Eighty-eight days after the end of distraction bone amount appeared reduced, with a more ordered structure, further reduction of bone formation activity, whereas osteoclast erosion was active. CONCLUSIONS: Results show an almost steady-state bone deposition processes 60 days after the end of distraction and a regress with longer time. The results suggest the possibility of an early implant insertion to avoid bone loss due to mechanical unloading.

Adolescent↗

Expression of genes for gelatinases and tissue inhibitors of metalloproteinases in periodontal tissues during orthodontic tooth movement.

Orthodontic tooth movement progresses by a combination of periodontal ligament (PDL) tissue and alveolar bone remodeling processes. Besides the remodeling of alveolar bone around the moving teeth, the major extracellular matrix (ECM) components of PDLs, collagens, are degenerated, degraded, and restructured. Matrix metalloproteinases (MMPs) and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs), act in a co-ordinated fashion to regulate the remodeling of periodontal tissues. We hypothesized that the expression levels of the genes for MMP-2, MMP-9, and TIMPs 1-3 are increased transiently in the periodontal tissue during orthodontic tooth movement. To test this hypothesis, we employed an animal model of tooth movement using rats, as well as in situ hybridization to analyze the expression levels of Mmp-2, Mmp-9, and Timps 1-3. The expression levels of these genes increased transiently in cells of periodontal tissues, which include cementoblasts, fibroblasts, osteoblasts, and osteoclasts, at the compression side of the moving teeth. The transient increases in gene expression at the tension side were mainly limited to osteoblasts and cementoblasts. In conclusion, the expression levels of Mmp-2, Mmp-9, and Timps 1-3 increase transiently during orthodontic tooth movement at both the tension and compression sides. The expression of these genes is regulated differentially in the periodontal tissue of the tension side and compression side. This altered pattern of gene expression may determine the rate and extent of remodeling of the collagenous ECM in periodontal tissues during orthodontic tooth movement.

Animals↗

Pulmonary surfactant phosphatidylcholine transport bypasses the brefeldin A sensitive compartment of alveolar type II cells.

Brefeldin A (BFA) causes disassembly of the Golgi apparatus and blocks protein transport to this organelle from the endoplasmic reticulum. However, there still remains considerable ambiguity regarding the involvement of the Golgi apparatus in glycerolipid transport pathways. We examined the effects of BFA upon the intracellular translocation of phosphatidylcholine in alveolar type II cells, that synthesize, transport, store and secrete large amounts of phospholipid for regulated exocytosis. BFA at concentrations as high as 10 microg/ml failed to alter the assembly of phosphatidylcholine into lamellar bodies, the specialized storage organelles for pulmonary surfactant. The same concentration of BFA was also ineffective at altering the secretion of newly synthesized phosphatidylcholine from alveolar type II cells. In contrast, concentrations of the drug of 2.5 microg/ml completely arrested newly synthesized lysozyme secretion from the same cells, indicating that BFA readily blocked protein transport processes in alveolar type II cells. The disassembly of the Golgi apparatus in alveolar type II cells following BFA treatment was also demonstrated by showing the redistribution of the resident Golgi protein MG-160 to the endoplasmic reticulum. These results indicate that intracellular transport of phosphatidylcholine along the secretory pathway in alveolar type II cells proceeds via a BFA insensitive route and does not require a functional Golgi apparatus.

Animals↗

Recurrent pneumothorax in AIDS patients with Pneumocystis pneumonia. A clinicopathologic report of three cases and review of the literature.

Spontaneous pneumothorax associated with Pneumocystis carinii pneumonia (PCP) in AIDS patients has been reported with increasing frequency; however, little is known about the causative histopathology. In the past year, we treated three patients with documented PCP subsequently complicated by multiple spontaneous pneumothoraces. All patients underwent open surgical repair. In contrast to traditional pathologic findings of PCP in AIDS, histologic sections of lung from each patient consistently demonstrated an extensive interstitial inflammatory process with destruction of lung tissue primarily involving the periphery of the lung. Subpleural necrosis with bleb formation as well as bullous changes persisted even in the absence of an alveolar filling process. We conclude that the mechanism for pneumothorax in PCP is spontaneous rupture of necrotic lung tissue occurring in a subgroup of AIDS patients in which the interstitial inflammatory response to Pneumocystis has been accelerated.

Acquired Immunodeficiency Syndrome↗

Microvascular response in the periosteum following mucoperiosteal flap surgery in dogs: 3-dimensional observation of an angiogenic process.

BACKGROUND: An increase in blood flow from the periosteum after mucoperiosteal flap surgery is essential for healing and angiogenesis and repair may work in close cooperation to facilitate this process. To investigate the role of the periosteal vascular plexus in the healing process, we used 3-dimensional (3-D) and ultrastructural monitoring of the angiogenic process after elevation of the mucoperiosteal flap. METHODS: Mucoperiosteal flap surgery was performed on nine adult beagle dogs. The periosteal vascular plexus was observed 3, 5, and 7 days after surgery in histological specimens in which blood vessels were injected with India ink under a light microscope, in ultrathin sections under a transmission electron microscope, and in acryl plastic vascular cast specimens under a scanning electron microscope. RESULTS: On day 3 after surgery, new blood vessels, formed through sprouting, bridging, and intussusception, were observed in ultrathin sections and vascular casts. In addition, blood island-like structures consisting of clustered immature endothelial cells were noted in the repaired tissue. On days 5 to 7 after surgery, 3-D observation of vascular casts clarified that these new blood vessels had a sinus-like morphology in the interstitium of the periosteal vascular plexus. These new sinusoidal vessels exhibited a stereoscopic structure with increased continuity as the blood vessels matured and ultrastructurally the vascular endothelium was thinned. CONCLUSIONS: After mucoperiosteal flap elevation, the periosteal vasculature exhibited potent blood vessel-forming activity through various angiogenic mechanisms and through repair activity. Our results provide a 3-dimensional clarification that the periosteal vascular plexus has an important role in the healing process after flap surgery.

Alveolar Process↗

Geometric alignment and chromatic calibration of serial radiographic images.

OBJECTIVE: To develop software for automated registration and intensity calibration of serial dental radiographs for the analysis of longitudinal changes in bone density. METHODS: Serial dental radiographs were acquired using a positioning device designed to minimize projection divergence. Each radiograph included an image of a standardized aluminium wedge. The radiographs were scanned on a flatbed scanner (AGFA Duo Scan) with a spatial resolution of 300 dpi, and pixel intensity coded in 16-bit grey scale. The intensity was calibrated using serial images of selected areas with defined thickness of the aluminium wedge. A robust B-splines multiresolution registration algorithm was implemented to overcome the acquisition misalignment. Radiographs, taken before and after periodontal therapy, were subtracted to assess bone density evolution. RESULTS: The intensity calibration decreased the maximum intensity variations between serial radiographs from 30+/-17% to 1+/-1% (mean+/-standard deviation), and improved the visual comparison between the radiographs. The registration stage allowed correcting the misalignment of the radiographs on the scanner screen and superimposing the radiography contents. The observed residual motion was about 0.02+/-0.01 mm. CONCLUSION: Very user-friendly software was developed. The manipulator needs to scan the radiographs only one time. The software performs all subsequent processing steps.

Absorptiometry, Photon↗

Subtraction radiography for the diagnosis of periodontal bone lesions.

Subtraction radiography permits reduction of structured noise from sequentially obtained images containing changes of diagnostic interest. It is particularly well suited for the detection of small periodontal changes, because the teeth provide stable bases for standardization of projection geometry from one exposure to the next and because structured noise is prevalent in unprocessed images of the periodontium. Multiple lesions were selectively induced in the tooth-supporting bone of dry mandibles. A significant improvement was unequivocally demonstrated in the visual detectability of the resulting changes after digital subtraction of pre- and postinduction standardized radiographs. The data indicate a significant increase in diagnostic accuracy as a result of the digital subtraction process used in this study. Hence, further application of this technique is warranted in controlled clinical trials.

Alveolar Process↗

Distinctions between microglial cells and peripheral macrophages with regard to adhesive activities and morphology.

Activated microglial cells and peripheral macrophages are hardly distinguishable from the viewpoints of morphology and function. There are various immunological markers common to both microglial cells and peripheral macrophages. In the present study, however, we found that microglial cells have distinct characters in terms of adhesion and morphology. By using a "rheoscope," that is an apparatus to rheologically measure the strength of cell adhesion to substrates, rat microglial cells were found to attach to polystyrene dishes much more weakly than alveolar and peritoneal macrophages. Interferon-gamma (IFNgamma) strengthened the adhesion of alveolar and peritoneal macrophages, whereas it weakened that of microglial cells. Morphological changes of microglial cells induced by IFNgamma were also different from those of peripheral macrophages. Furthermore, alveolar and peritoneal macrophages produced NO in response to IFNgamma, while microglial cells did not. When cultured on astrocyte-derived extracellular matrix (AsECM) in serum-free medium, only microglial cells extended multiple ramified processes. Conversely, alveolar and peritoneal macrophages on AsECM shrunk their ruffling membrane and rounded up. These distinctions between microglial cells and macrophages may reflect differences in cell lineages as well as environments in which individual cells reside.

Animals↗

Effects of dietary consistency on the mandible of rats at the growth stage: computed X-ray densitometric and cephalometric analysis.

Thirty 3-week-old male Wistar rats were grouped into a hard diet control group, a kneaded-diet group, and a powdered-diet group. After 6 weeks of growth, all rats were killed under deep anesthesia. The effects of dietary physical consistency on the mandible were investigated with respect to morphology and bone mineral content using lateral cephalometric analysis and computed X-ray densitometry. Significant differences between the experimental and control groups were determined by measuring the means and standard deviation of the coordinates and differences between 15 points selected on the mandibles. Gonion (Go), which is a measurement of depth to the X-axis, was significantly less in the powdered-diet group, while the kneaded-diet group showed no significant differences. The most posterior point of the coronoid process (Cr) and the most posterior point of condylar process (Cd), which are measures of height to the Y-axis, were less in the kneaded-diet group than in the control group. In the powdered-diet group, Cr, Cd, Go and Infradentale were significantly less than in the control group. On the other hand, the bone mineral content was significantly lower in the coronoid process and angle of mandible in only the powdered-diet group.

Absorptiometry, Photon↗

Loss of PECAM-1 function impairs alveolarization.

The final stage of lung development in humans and rodents occurs principally after birth and involves the partitioning of the large primary saccules into smaller air spaces by the inward protrusion of septae derived from the walls of the saccules. Several observations in animal models implicate angiogenesis as critical to this process of alveolarization, but all anti-angiogenic treatments examined to date have resulted in endothelial cell (EC) death. We therefore targeted the function of platelet endothelial cell adhesion molecule, (PECAM-1), an EC surface molecule that promotes EC migration and has been implicated in in vivo angiogenesis. Administration of an anti-PECAM-1 antibody that inhibits EC migration, but not proliferation or survival in vitro, disrupted normal alveolar septation in neonatal rat pups without reducing EC content. Three-dimensional reconstruction of lungs showed that pups treated with a blocking PECAM-1 antibody had remodeling of more proximal branches resulting in large tubular airways. Subsequent studies in PECAM-1-null mice confirmed that the absence of PECAM-1 impaired murine alveolarization, without affecting EC content, proliferation, or survival. Further, cell migration was reduced in lung endothelial cells isolated from these mice. These data suggest that the loss of PECAM-1 function compromises postnatal lung development and provide evidence that inhibition of EC function, in contrast to a loss of viable EC, inhibits alveolarization.

Animals↗