Proliferation of rat molar pulp cells after direct pulp capping with dentine adhesive and calcium hydroxide.

The aim was to evaluate the proliferation of pulp cells 1, 3 and 7 days after direct pulp capping with the dentine adhesive Gluma Comfort Bond (GCB) and to compare it with calcium hydroxide (Ca(OH)(2)). An occlusal cavity was prepared in 72 molar teeth of 36 Wistar rats. Then GCB or Ca(OH)(2) was placed on the exposed pulp. All cavities were restored with composite. After 1, 3 and 7 days, the animals were sacrificed. One hour prior sacrification, 5-bromo-2'-desoxyuridine (BrdU) was injected into the intraperitoneal cavity for immunohistological analysis of 18 animals. BrdU was incorporated into the DNA to tag proliferating cells using an antibody staining. Three animals served as controls and were not further treated. The number of the tagged cells was statistically analysed by comparing the results of the three groups. In 18 rats, routine histological analysis was performed in order to evaluate the pulp tissue for bacterial infection, inflammatory cells and necrosis. The marked cells were identified as fibroblasts, endothelial cells (after 1, 3 and 7 days) and Höhl cells (after 7 days). One day after capping, significantly more cells were stained in the GCB than in the Ca(OH)(2) group (p < 0.05). After 3 days, significantly more cells were stained in the GCB than in the Ca(OH)(2) and the control group (p < 0.016). Direct contact of GCB with pulp tissue leads to an increased formation of granulation tissue (fibroblasts, endothelial cells) because of an inflammatory reaction. This may be explained by missing antibacterial effect and foreign body reactions. Also, GCB may have a negative effect on Höhl cells.

ATIII attenuates endotoxemia induced healing impairment in the colon.

BACKGROUND: Intra-abdominal infections are considered a contributing factor to the impairment of anastomotic healing in patients undergoing surgical procedures of digestive system. Antithrombin (ATIII) is known to improve the microcirculation in sepsis. We hypothesized that it may also positively influence the healing of the colon anastomoses under endotoxemia. MATERIALS AND METHODS: Ninety Balb/c mice (n = 10 per group on day 2, 4, and 7) were randomly assigned to three groups: Control (N), Sepsis (S) (administration of lipopolysaccharides (LPS) dosed at 2 mg/kg bodyweight, 18 h before colon surgery), and Sepsis with ATIII therapy (SIII) (administration of LPS and ATIII). All the animals underwent colonic anastomoses. Immediately after their completion, microcirculatory parameters were measured, and both macroscopic and histological parameters were assessed on day 2, 4, and 7 postoperation. Additionally, immunohistology studies were performed for CD31, ssDNA, and iNOS, along with an examination for bacterial translocation to the mesenteric lymph nodes. RESULTS: Compared with group S, the functional capillary network was denser in the control group N (P < 0.001) and group SIII (P < 0.01). Mean bursting pressures were significantly lower in group S compared with group N, on day 2, 4, and 7, and with group SIII on day 2 and 7. At the anastomosis, the inflammatory infiltrate in group S was denser compared with groups N (P < 0.001) and SIII (P < 0.01). Furthermore, the apoptotic rate was higher, and the vascular density was lower on day 7 in group S compared with groups SIII and N (P < 0.05). Bacterial translocation decreased over time (P < 0.05) with no significant differences between the groups. CONCLUSION: ATIII improved the anastomotic microcirculatory parameters and anastomotic healing in mice with endotoxemia, though the improvement failed to achieve the levels of the control mice.

Microcirculatory dysfunction in endotoxemic bowel anastomosis: the pathogenetic contribution of microcirculatory dysfunction to endotoxemia-induced healing impairment.

BACKGROUND: An established intra-abdominal infection as in perforated diverticulitis is considered to contribute to anastomotic healing impairment. Since microvascular dysfunction in sepsis is known to be due to organ failure, the influence of inflammation on the anastomotic microcirculation needs further investigation. MATERIAL AND METHODS: Sixty BALB/c mice (n = 10 per group and day 2, 4, and 7) were randomized to two groups: Control and Sepsis (lipopolysaccharide administration 2 mg/kg bodyweight 18 h before colon surgery). All animals underwent colonic anastomosis. Immediately after its completion intravital fluorescence microscopy of the anastomosis was performed, and both macroscopic and histological parameters were assessed on days 2, 4, and 7 postoperatively. Additionally, immunohistology was performed for CD31 (platelet endothelial cell adhesion molecule-1), single-strand DNA, and inducible nitric oxide synthase. RESULTS: As compared to Control the functional capillary network of the perianastomotic region was decreased in Sepsis (P < 0.001) as well as the hemoglobin O(2) saturation in the antimesenteric region of the anastomosis (P < 0.05). Bursting pressure was significantly decreased in Sepsis compared to Control at days 2, 4, and 7. On day 7 there were significant differences between the two groups in the anastomotic region: neutrophil infiltration in Sepsis was higher (P < 0.001); vascular density and differentiation in Sepsis was lower (P < 0.01, P < 0.05, respectively); and apoptosis was higher in Sepsis (P < 0.05). CONCLUSION: The inflammatory state increases microvascular dysfunction at the anastomosis resulting in healing impairment.

Effect of glycine powder air-polishing on the gingiva.

OBJECTIVES: Safety and efficacy of glycine powder air-polishing (GPAP) in removing subgingival biofilm have been previously demonstrated. The hypothesis that GPAP results in less gingival erosion than sodium bicarbonate air-polishing (SBAP) or hand-instrumentation was assessed. MATERIAL AND METHODS: In each of 10 patients, eight teeth with a residual probing depth of at least 5 mm following initial periodontal therapy were randomly assigned to the following interventions: GPAP (test), SBAP (positive control), hand-instrumentation (positive control), or no treatment (negative control). In each group, gingival biopsies were taken immediately after instrumentation and one 14 days later. Damaged gingival epithelium (GE) was assessed by light microscopy and quantified by a histological score (values 1-4). Differences between groups were evaluated using the marginal homogeneity test. RESULTS: GPAP resulted in minor erosions of the GE (scores 1 and 2), whereas positive control specimens displayed moderate to severe erosions (scores 2-4). Differences between GPAP and positive controls were significant (p<0.05). Fourteen days following instrumentation GE under assessment was found to be intact in all groups. CONCLUSION: The data indicated that GPAP results in less gingival erosion than SBAP or hand instrumentation, further supporting the safety of this new debridement technique.

Morphologic features in the regenerating liver--a comparative intravital, lightmicroscopical and ultrastructural analysis with focus on hepatic stellate cells.

Different cell types play a role in the liver regeneration. The present study reveals morphological key steps of liver regeneration by correlating intravital, light, and electron microscopic with immunohistochemistry results focusing on hepatic stellate cells (HSCs). In Lewis rats, liver regeneration was induced by a 2/3-hepatectomy. Animals (n = 7 each) were killed after 0, 1, 2, 3, 4, 7, and 14 days. Morphological features were investigated by light microscopy, immunohistochemistry [alpha-smooth muscle actin (alpha-SMA), Desmin, vascular endothelial growth factor (VEGF)/VEGF receptor, Ki-67, ssDNA], intravital microscopy (sinusoid density, number of hepatocytes, and HSC), and electron microscopy focussed on cell-to-cell interactions. During liver regeneration, HSC were activated at day 3 showing a loss of autofluorescence and simultaneously an increased alpha-SMA expression and direct cell contact to hepatocytes. HSC activation was followed by increasing VEGF expression and sinusoid density. After 14 days, liver architecture and ultrastructure was restored and HSCs were deactivated showing decreased alpha-SMA expression as well as increased apoptosis and no more direct cell contact to hepatocytes. HSCs play a central role in the regenerating liver by governing angiogenesis and extracellular matrix remodeling. A direct cell contact to hepatocytes seems to be essential for HSC activation, whereas deactivation is accompanied by loosening of hepatocyte contact and increased apoptosis.

A new technique for reconstruction of the common bile duct by an autologous vein graft and a biodegradable endoluminal stent.

The incidence of severe bile duct injuries has significantly increased since the introduction of laparoscopic cholecystectomy. The ideal reconstruction procedure for traumatic defects of the bile duct should be technically simple and should preserve both the physiological passage of bile and the sphincter of Oddi. In this article we describe a new technique for bile duct reconstruction in a pig model by means of an autologous vein graft that is splinted by a endoluminal biodegradable polylactate acid stent. In 12 pigs the external jugular vein was removed and used as an autologous vein graft. After performing a median laparotomy a 2-cm segment was resected from the bile duct. The common bile duct was reconstructed by a venous interponate that had been endoluminally stented by a biodegradable polylactate acid stent. For the examination of stent degradation, 2 pigs were sacrificed at 3, 4, and 5 months (stent degradation group) and the remaining 6 pigs at 6 months (survival group). All the pigs in the survival group survived for 6 months before being sacrificed. After 4 months the stent material had been completely broken down and the vein graft had been relined with bile duct epithelium. Thus, this new technique for bile duct reconstruction using an autologous vein graft with an endoluminal stent is simple to perform and reliable, and constitutes an interesting alternative to bilodigestive anastomosis due to the preservation of the papilla of Vateri.

The endothelin/nitric oxide balance determines small-for-size liver injury after reduced-size rat liver transplantation.

Small-for-size (SFS) liver graft injury is probably related to microcirculatory disorders due to an imbalance of vasoconstricting, e.g. endothelin (ET)-1, and vasorelaxing mediators, e.g. nitric oxide (NO). We studied the role of ET-1/NO balance and the effect of an endothelin A receptor (ETAR) antagonist on SFS injury after liver resection and reduced-size liver transplantation (RSLT). One hundred twenty-six Lewis rats were divided into five groups: (I) 70% liver resection, (II) 70% liver resection treated with the ETAR antagonist LU 135252 (1 mg/kg b.w. i.v.), (III) RSLT (30% residual liver volume), (IV) RSLT treated with the ETAR antagonist, (V) sham operation. Liver microcirculation was measured by intravital microscopy. ET-1, ETAR, endothelial NO-synthase (eNOS), activation of Kupffer cells (KCs) and parenchymal injury were studied by immunohistology. Survival and liver function were followed up to 14 days. RSLT led to increased ET-1, ETAR and decreased eNOS protein expression, accompanied by activation of KC, reduced perfusion rate, vasoconstriction and elevated sinusoidal blood flow, as well as hepatocellular damage, impaired liver function and impaired survival. ETAR blockade (groups II + IV) improved the ET-1/NO balance, attenuated microcirculatory disorders and improved hepatocellular apoptosis and liver function. Microcirculatory disorders related to an ET-1/NO imbalance may contribute to SFS liver injury. Maintenance of ET-1/NO balance by blocking ETAR reduces SFS injury by protecting liver microcirculation, thus reducing hepatocellular damage.

TCP is hardly resorbed and not osteoconductive in a non-loading calvarial model.

Tricalciumphosphate (TCP) has been used as a ceramic bone substitute material in the orthopedic field as well as in craniofacial surgery. Some controversies exist concerning the osteoconductive potential of this material in different implantation sites. This study was designed to evaluate the biological response of calvarial bone towards TCP granules under non-loading conditions to assess the potential of TCP as a biodegredable and osteoconductive bone substitue material for the cranial vault. Full-thickness non-critical size defects were made bilaterally in the calvaria of 21 adult Wistar rats. One side was filled by TCP granules, the contralateral side was left empty and used as a control. Animals were sacrified in defined time intervals up to 6 months. Bone regeneration was analyzed with special respect toward the micromorphological and microanalytical features of the material-bone interaction by electron microscopy and electron diffraction analysis. Histologic examination revealed no TCP degradation even after 6 months of implantation. In contrast, a nearly complete bone regeneration of control defects was found after 6 months. At all times TCP was surrounded by a thin fibrous layer without presence of osteoblasts and features of regular mineralization. As far as degradation and substitution are concerned, TCP is a less favourable material tinder conditions of non-loading.

Reaction of sound and demineralised dentine to Carisolv in vivo and in vitro.

OBJECTIVES: The aim of the present study was to assess the structural reaction of intact dentine to Carisolv in vivo and in vitro. METHODS: For the in vivo study occlusal cavities were prepared in 48 caries-free molars in Wistar rats (age: three months) and Carisolv-solution was placed into the cavities of 24 M for 1, 10 and 20 min. Twenty four contralateral molars served as controls and were treated with an inert liquid containing purified water, carmellose and erythrosin for corresponding periods. For the in vitro study 24 rat molars were resected en bloc and fractured to expose an area of crown dentine area. Molars were demineralised with EDTA for eight weeks to expose the collagenous dentinal matrix. One half of the specimens was then coated with Carisolv-solution for 20 min. The other half served as a control and was coated with an inert solution for 20 min. RESULTS: In the in vivo specimens no signs of pulp cell damage were observed in the experimental group. The odontoblastic processes were destroyed in proximity to the floor of the cavity but were intact in the inner portion of dentinal tubules in experimental molars and a mechanical damage was noted in the control molars. In the in vitro specimens no structural discrepancy was detected between the experimental molars and the control molars in collagen fibrils of demineralised dentine. CONCLUSIONS: Carisolv causes destruction of cellular components of odontoblastic processes but does not attack healthy collagen fibrils.

The influence of different registration positions on condyle displacement in symptomatic patients.

OBJECTIVE: This study aimed to evaluate effects of different registration positions on the condyle-disk position changes in the mandibular fossa in symptomatic individuals. STUDY DESIGN: Vertical and sagittal condyle position and thickness of the bilaminar zone were measured by magnetic resonance imaging during maximal intercuspation (MI) and with jigs in Gothic arch tracing guided centric relation (DIR method [Dynamics and Intraoral Registration]) and retruded contact position (RCP). Participants were 26 patients seeking treatment for temporomandibular disorders. Condyle and disk position in the fossa were calculated in the parasagittal plane. RESULTS: Significant differences were found for MI, DIR, and RCP for thickness of bilaminar zone and sagittal condyle position, dependent on diagnosis and registration position for vertical and sagittal condyle position and thickness of bilaminar zone. CONCLUSIONS: DIR position ensures the widest posterior space for the retrodiskal tissues and the slightest sagittal difference between condyle zenith and glenoid fossa.

Direct pulp capping with mineral trioxide aggregate: an immunohistologic comparison with calcium hydroxide in rodents.

INTRODUCTION: The aim was to evaluate the proliferation of pulp cells 1, 3, and 7 days after direct pulp capping with ProRoot MTA (MTA) and to compare the results with calcium hydroxide (Ca(OH)(2)). METHODS: An occlusal cavity was prepared in 36 molar teeth of 18 Wistar rats. Then MTA or Ca(OH)(2) was placed on the exposed pulp. All cavities were restored with composite. After 1, 3, and 7 days the animals were killed. One hour before scarification 5-bromo-2'-deoxyuridine (BrdU) was injected into the intraperitoneal cavity for immunohistologic analysis. BrdU was incorporated into the cell nucleus during the S phase of the cell cycle. Proliferating cells were tagged and counted by using alkaline phosphatase and anti-alkaline phosphatase antibody staining. Three animals (6 molar teeth) served as controls and were not further treated. The number of the tagged cells was statistically analyzed by comparing the results of the 3 groups. A Bonferroni correction was performed, because the data of the Ca(OH)(2)- group was used 3 times for pairwise comparison. RESULTS: The marked cells were identified as fibroblasts, endothelial cells (after 1, 3, and 7 days), and Höhl cells (after 7 days). The MTA group showed a similar amount of Höhl cells when compared with the Ca(OH)(2) group (P > .05). One day and 7 days after capping, no significant differences were observed between the 2 tested groups and the controls (P > .05). After 3 days, significantly more cells were stained in the MTA and Ca(OH)(2) groups than in the control group (P < .016). CONCLUSIONS: Immunohistologic analysis demonstrated that MTA showed similar results when compared with Ca(OH)(2) within the first week after direct pulp capping.

Mineral trioxide aggregate for direct pulp capping: a histologic comparison with calcium hydroxide in rat molars.

OBJECTIVES: Several studies reported superior healing results for ProRoot mineral trioxide aggregate (MTA; Dentsply Tulsa) cement in direct pulp capping when compared to calcium hydroxide. However, this could not be confirmed by other authors. The aim of this study was to compare the reaction of MTA-treated rat pulp tissue to calcium hydroxide [Ca(OH)2]-treated rat pulp tissue in direct pulp capping after 1 to 70 days. METHOD AND MATERIALS: Seventy-two caries- free, maxillary right and left first molars of 36 Wistar rats were prepared with an occlusal cavity. The pulp chambers were then perforated with a sharp probe. For each of four time periods, MTA was placed on the exposed pulp of 10 molars according to the manufacturer's instructions, and Ca(OH)2 was placed on 8 molars. All cavities were then filled with dentin adhesive and flowable composite. The animals were sacrificed 1, 3, 7, and 70 days after pulp capping. The pulps were histologically analyzed (light and transmission electron microscopic) for bacterial infection, inflammatory cells, necrosis, and reparative dentin and classified according to occurrence in scores from 1 to 4. To ensure that the coronal restorations did not leak, occlusal cavities were prepared in four maxillary molars of one rat. The coronal cavity was then sealed with resin. After 70 days, the rat was sacrificed, and the molars were immersed in new fuchsin. Data were statistically evaluated with the Kruskal-Wallis test (P<.05). RESULTS: The MTA group showed statistically significantly lower signs of necrosis 1 and 3 days after pulp capping when compared with the Ca(OH)2 group (P<.05). No other statistically significant differences were found (P>.05). After 70 days, all pulps displayed healthy tissue. In the leakage test no specimens revealed any dye penetration. CONCLUSION: MTA showed equally good results as Ca(OH)2 and can berecommended clinically for direct pulp capping.

A histologic investigation of direct pulp capping in rodents with dentin adhesives and calcium hydroxide.

OBJECTIVE: To investigate reactions of pulp tissue when in contact with the dentin adhesives Resulcin AquaPrime + MonoBond (RAPMB, Merz Dental), Scotchbond 1 (SB1, 3M ESPE), and Gluma Comfort Bond (GCB, Heraeus Kulzer) in comparison with calcium hydroxide after 1 to 70 days. METHOD AND MATERIALS: An occlusal cavity was prepared in 152 molars of 76 Wistar rats. The pulps were exposed and dentin adhesives placed on the pulp tissue of 10 molars for each dentin adhesive group and time period. Eight molars per time period served as controls and were capped with calcium hydroxide. All cavities were restored with composite resin. The animals were sacrificed 1, 3, 7, and 70 days after pulp capping. Pulp tissue was histologically evaluated for the following criteria: bacterial infection, inflammatory cells, necrosis, and reparative dentin. The data were statistically evaluated using the Kruskal-Wallis test (P < .05). RESULTS: Overall, significantly more bacterial infections were detected 1, 3, 7, and 70 days after pulp capping with dentin adhesive (P < .05). In all dentin adhesive groups, 1 day after direct pulp capping, significantly more inflammatory cells were found, whereas after 7 days, this was only the case for the SB1 group (P < .05). After 70 days, capping with calcium hydroxide resulted in significantly less necrosis than with RAPMB and SB1 (P < .05). Regarding necrosis, SB1 showed the worst results: Pulp necrosis occurred significantly more often than with calcium hydroxide and GCB (P < .05). After the application of calcium hydroxide, significantly more reparative dentin formation occurred (P < .05). CONCLUSION: Direct pulp capping with calcium hydroxide seems to produce remarkably better results than with dentin adhesive.

Attenuated cold storage injury of rat livers using a modified HTK solution.

BACKGROUND: Preservation injury is a main factor leading to graft failure in liver transplantation. The aim of the study was to minimize preservation injury by modifications of the histidine-tryptophan-ketoglutarate (HTK) solution (incorporation of N-acetyl-histidine, aspartate, glycine, alanine, and arginine). MATERIALS AND METHODS: The study was carried out in rats and subdivided into four parts. (1) Systemic toxicity of the modified HTK solution in comparison to the standard HTK solution was tested. (2) Hemodynamic and microcirculatory parameters were analyzed after i.v. injection of the respective solution. (3) Preservation injury after cold storage for different periods of time was assessed microscopically. (4) Reperfusion injury was analyzed in the isolated perfused liver by enzyme release and bile production. RESULTS: Blood values, hemodynamic and microcirculatory parameters after i.v. and i.p. application did not significantly differ from control. The modified HTK solution led to an attenuated preservation injury after cold preservation for 24 h compared with standard HTK solution. There was a significantly decreased lactate dehydrogenase release after ischemia for 72 h and reperfusion using the modified solution. After 24 h cold storage and reperfusion the apoptosis index was reduced and bile production significantly increased. CONCLUSION: Optimizing the HTK solution may be a promising therapeutic strategy for attenuation of cold storage injury.

Bromelain ameliorates hepatic microcirculation after warm ischemia.

BACKGROUND: Because of its immunomodulatory action, the protease bromelain represents a novel strategy for the treatment of hepatic ischemia/reperfusion (I/R) injury. A dose-response study was performed to investigate the effect of bromelain on liver function, microcirculation, and leukocyte-endothelium interactions in hepatic I/R injury. MATERIALS AND METHODS: One hundred forty rats were randomized to 8 short-term or 12 long-term groups (n=7 each). A 30 min normothermic hepatic ischemia was induced by Pringle maneuver with a portocaval shunt. Animals were treated 60 min prior to ischemia with either no therapy, 0.1, 1.0, or 10 mg/kg b.w. bromelain i.v. In the short-term experiments, microcirculation was investigated 30 min after sham operation or ischemia using intravital microscopy. In the long-term experiments AST, ALT, and bradykinin levels were determined for 14 d after central venous catheter (CVC) placement only, sham operation, or ischemia. Additionally, apoptosis rate, Kupffer cell activation, endothelial cell damage, and eNOS expression were analyzed. RESULTS: In sham-operated animals, treatment with 10 mg/kg b.w. bromelain led to a disturbed microcirculation with increased leukocyte adherence, apoptosis rate, Kupffer cell activation, and endothelial cell damage. Six h after CVC placement and administration of 10 mg/kg b.w. bromelain, AST and ALT levels were significantly increased. After I/R, rats treated with 0.1 mg/kg b.w. bromelain showed an improved microcirculation, reduction in leukocyte adhesion, apoptosis rates, Kupffer cell activation and endothelial cell damage, increased eNOS expression, and significantly lower AST levels compared with untreated animals. CONCLUSION: Bromelain represents a novel approach to the treatment of hepatic I/R injury with a limited therapeutic window.

VEGF-activated angiogenesis during bone regeneration.

PURPOSE: The aim of this study was to investigate the influence of controlled release of recombinant human vascular endothelial growth factor (rhVEGF(165)) on angiogenesis and osteogenesis in a mandibular defect model. MATERIAL AND METHODS: A total of 56 rabbits were operated and bicortical holes were placed at the lower border of the mandible. The defects were filled with type-I collagen, with collagen complexed with 0.8 mug rhVEGF(165), or left without any filling. After 3, 7, 14, and 28 days, specimens were taken and histologic, histomorphometric, and immunohistologic analyses were carried out concerning number of vessels, cross-sectional area of vessels, and area and density of regenerated bone. RESULTS: Bone formation occurred in a typical centripetal direction and showed all stages of bone regeneration and maturation. New vessel formation took place in front of the osteogenic regeneration front. The number of vessels increased in all groups until day 14, followed by physiologic regression in the control groups as opposed to persisting high numbers in the study group. The area of newly formed bone showed no difference to the control group but the density of regenerated bone was significantly higher in the study group. CONCLUSION: Blood vessels are an important component of bone formation and maintenance and the bone tissue differentiation is related to the local presence of blood vessels. The activation of angiogenesis using rhVEGF(165) leads to more intensive angiogenesis and bone regeneration.

Detrimental effect of sinusoidal overperfusion after liver resection and partial liver transplantation.

Liver resection exposes the remaining sinusoids to an over-proportional blood flow. This mechanism may aggravate ischaemia/reperfusion damage and rejection in partial liver transplants. We studied the potential relevance of this mechanism for the pathogenesis of partial liver transplant dysfunction. Eighty-four isogeneic Lewis rats were divided into four groups: (I) sham operation; (II) partial liver resection (30% residual liver volume); (III) orthotopic transplantation of a full-size liver; (IV) transplantation of a reduced-size liver (30% transplant volume). Microcirculation was determined by intravital microscopy 90 min after surgery. Survival rates, liver function and morphology were monitored over a period of 14 days. Lowest survival rates and impaired liver function were observed after partial liver transplantation (group IV). These transplants displayed the lowest perfusion rate and an increased rate of leukocyte-endothelium interactions in the presence of a significantly increased sinusoidal blood flow velocity compared with those in groups I and III. Sinusoidal overperfusion in groups II and IV resulted in widespread endothelium lesions. Sinusoidal overperfusion seems to be a significant factor impairing liver function after liver resection. In addition to other adverse factors, such as ischaemia/reperfusion injury, it can contribute to the pathogenesis of postoperative dysfunction of partial liver transplants.

Amelioration of microcirculatory damage by an endothelin A receptor antagonist in a rat model of reversible acute liver failure.

BACKGROUND/AIMS: Hepatocellular damage in acute liver failure (ALF) is aggravated by proinflammatory and cytotoxic mediators released from sinusoidal-lining cells. We studied a selective endothelin A receptor (ETAR) antagonist for its potential influence on the microcirculation in the setting of ALF. METHODS: Seventy Wistar rats were divided into five groups: (I) induction of ALF by a 70% liver resection combined with injection of 400 microg/kg endotoxin, (II) ALF treated with the ETAR antagonist LU 135252 (1 mg/kg b.w. i.v.), (III) sham operation, (IV) injection of endotoxin, (V) 70% liver resection. Liver microcirculation was measured by intravital microscopy. Parenchymal injury, growth fractions, endothelin (ET)-1 and ETAR were studied by histology and immunohistology. Survival, liver function, and morphology were followed up to 14 days. RESULTS: 100% mortality, impaired liver function, widespread endothelial lesions, highest ET-1 and ETAR levels, a decreased perfusion rate, reduced sinusoidal diameter, as well as an increase in both leukocyte-endothelium interactions and sinusoidal blood flow were observed after induction of ALF. ETAR antagonist-treated rats showed decreased ET-1 and ETAR levels as well as improved microcirculatory function, morphology, liver function, and 85% survival. CONCLUSIONS: Microcirculatory disturbances correlate with liver dysfunction in ALF. ETAR blockade represents a new therapeutic approach to ALF by reducing microcirculatory lesions and their sequelae.

Histologic, histomorphometric and immunohistologic changes of the gingival tissues immediately following mandibular osteodistraction.

OBJECTIVES: Even though osteogenesis after osteodistraction has been investigated in numerous experimental studies, there is limited information focusing on the influence of well-defined mechanical distraction forces on the associated gingival tissues. MATERIAL AND METHODS: In a study including 48 rabbits, mandibular osteodistraction was performed in vertically osteotomized mandibular body, using defined distraction protocols with physiologic, moderate and hyperphysiologic forces. The soft tissues overlying the distraction gap were harvested finally for histologic, immunohistologic and histomorphometric investigations. RESULTS: The control group without distraction showed the typical architecture and thickness of normal gingiva. In groups with distracted mandibles, an accelerating atrophy of gingiva depending on the degree of mechanical loading was obvious, characterized by decreasing thickness of epithelial layer, loss of rete ridges and disorganization of the different cell layers with a high number of apoptotic cells. In lamina propria collagen fibres were reduced and elastic fibres increased. Histomorphometric analysis revealed significant correlation between degree of distraction and atrophy in overlying soft tissues. CONCLUSION: This rabbit model of mandibular lengthening shows an accelerating atrophy in the covering soft tissues following hyperphysiologic distraction. The long-term outcome of these distraction-related soft-tissue alterations remains unclear. The atrophic changes may likely be of temporary nature.

Effect of root canal dressings on the regeneration of inflamed periapical tissue.

The aim of this study was to evaluate the effects of chlorhexidine and calcium hydroxide on apical periodontitis in rats. Experimentally induced apical periodontitis was established on the mesial roots of maxillary molars of Wistar rats by leaving the root canals exposed to the oral cavity for 14 d. In the positive control group (n=10 teeth), the root canals were not further treated, but the coronal access openings were filled with composite. In the negative control group (n=10 teeth), partial pulpotomies were performed aseptically and the coronal access openings were sealed immediately. In a third control group (n=10 teeth) the canals were instrumented, left empty, and the coronal access openings were sealed. In the experimental groups, the root canals were instrumented and filled with either 2% chlorhexidine gel or calcium hydroxide paste (n=10 teeth per group). After 7 d all rats were killed and the histological sections were stained for microscopic analysis of periapical regeneration. The data of the subjective evaluation were analyzed with the Kruskal-Wallis test. Lesion sizes were measured and statistically analyzed using the ANOVA and post-hoc Scheffé test. The two treatment groups showed significantly lower average inflammatory scores and smaller lesion sizes than the positive and third control group (p<0.05). No statistically significant differences were obtained between the two treatment groups (p>0.05). Chlorhexidine used as an intra-canal medicament showed good periapical regeneration, suggesting that this may be an alternative to calcium hydroxide root canal dressing.