Establishment of the epithelial attachment and connective tissue adaptation to implants installed under the concept of "platform switching": a histologic study in minipigs

Aim: To validate the platform switching concept at oral implants with respect to the preservation of the alveolar crestal bone levels in an animal model. Material & methods: Five minipigs received three implants each with a 0.25mm implant/ abutment mismatch and were placed flush (T(0)), 1 mm below (T(1)) and 1 mm above (T(+1)) the alveolar bony crest, and as a control, one conventionally restored implant placed at the bone level. The implants were randomly inserted flapless into the mandible. Four months after implant insertion, the animals were sacrificed, and undecalcified block sections were obtained and used for histological analyses. Results: The mean values for peri- implant bone resorption were 1.09 +/- 0.59mm (Control), 0.51 (+/- 0.27 mm, T(0)), 0.50 (+/- 0.46 mm, T(1)) and 1.30 (+/- 0.21 mm, T (+1)), respectively. Statistically significant differences (P< 0.05) were found among the test (T(0), T(-1)) and the control sites. Control implants presented an average biologic width length of 3.20mm (+/- 0.33), with a connective tissue adaptation compartment of 1.29mm (+/- 0.53) and an epithelial attachment of 1.91 mm (+/- 0.71). T(0), T(1) and T(+1) implants presented with a mean biologic width of 1.97mm (+/- 1.20), 2.70 mm (+/- 1.36) and 2.84mm (+/- 0.90), respectively, with a connective tissue adaptation compartment of 1.21mm (+/- 0.97), 1.21 mm (+/- 0.65) and 1.50 mm (+/- 0.70) and an epithelial attachment of 0.84 mm (+/- 0.93), 1.66 mm (+/- 0.88) and 1.35 mm (+/- 0.44), respectively. Differences between the configurations were mainly associated with the length of the epithelial attachment. The epithelial attachment was significantly longer in the C sites than in T(0) (P = 0.014). However, no other differences between configurations were detected. Conclusion: If the implants are positioned at the level of the alveolar bony crest, the platform switching concept may have a minor impact on the length of the epithelial attachment (0.84 vs. 1.91 mm), while the connective tissue adaptation compartment remains relatively unaffected. Moreover, platform switching resulted in less resorption of the alveolar crest (0.58 mm).

Experimental hyperprolinemia induces mild oxidative stress, metabolic changes, and tissue adaptation in rat liver

The present study investigated the effects of chronic hyperprolinemia on oxidative and metabolic status in liver and serum of rats. Wistar rats received daily subcutaneous injections of proline from their 6th to 28th day of life. Twelve hours after the last injection the rats were sacrificed and liver and serum were collected. Results showed that hyperprolinemia induced a significant reduction in total antioxidant potential and thiobarbituric acid-reactive substances. The activities of the antioxidant enzymes catalase and superoxide dismutase were significantly increased after chronic proline administration, while glutathione (GSH) peroxidase activity, dichlorofluorescin oxidation, GSH, sulfhydryl, and carbonyl content remained unaltered. Histological analyses of the liver revealed that proline treatment induced changes of the hepatic microarchitecture and increased the number of inflammatory cells and the glycogen content. Biochemical determination also demonstrated an increase in glycogen concentration, as well as a higher synthesis of glycogen in liver of hyperprolinemic rats. Regarding to hepatic metabolism, it was observed an increase on glucose oxidation and a decrease on lipid synthesis from glucose. However, hepatic lipid content and serum glucose levels were not changed. Proline administration did not alter the aminotransferases activities and serum markers of hepatic injury. Our findings suggest that hyperprolinemia alters the liver homeostasis possibly by induction of a mild degree of oxidative stress and metabolic changes. The hepatic alterations caused by proline probably do not implicate in substantial hepatic tissue damage, but rather demonstrate a process of adaptation of this tissue to oxidative stress. However, the biological significance of these findings requires additional investigation. J. Cell. Biochem. 113: 174183, 2012. (C) 2011 Wiley Periodicals, Inc.

The platform switching concept revisited. An experimental study in dogs

Objective: To evaluate the influence of the configuration of the marginal aspect of implants placed immediately into extraction sockets on peri-implant hard tissue adaptation. Material and methods: In 6 Labrador dogs, endodontic treatments of the mesial roots of 1M1 were performed and the distal roots were removed. 2P2 was extracted as well. Implants were immediately placed in the center of the distal alveoli. Cylindrical straight implants were installed in the right side of the mandible (Control), while, in the left side, implants with a reduced diameter in the coronal portion, yielding an indentation in the surface continuity (Test), were installed. Cover screws were affixed, and the flaps were sutured to allow non-submerged healing. After 4 months of healing, histological slides were obtained for assessments. Results: A buccal resorption of 1.58 ± 1.28 and 1.90 ± 1.93 mm at the control and of 0.26 ± 0.90 and 0.14 ± 0.66 mm at the test sites was observed at the premolar and molar regions, respectively. The buccal coronal level of osseointegration was located apically to the margin of the smooth/rough surface border by 2.40 ± 0.90 and 3.70 ± 0.87 mm at the control sites and 1.19 ± 0.45 and 2.16 ± 0.96 mm at the test sites at the premolar and molar sites, respectively. All differences yielded statistical significance. Conclusions: The use of implants with a reduced diameter in their coronal aspect may contribute to preservation of the buccal bony crest in a more coronal level compared with conventional implants. Thus, the study confirmed the efficacy of the platform switching concept. © 2013 John Wiley & Sons A/S.

Utilização da matriz dérmica acelular associada ou não à proteína derivada da matriz do esmalte em recessões gengivais. Estudo histológico em cães

Pós-graduação em Odontologia - FOAR

A digital evaluation of alveolar ridge preservation at implants placed immediately into extraction sockets: an experimental study in the dog

Objective: To compare with pristine sites bone resorption and soft tissue adaptation at implants placed immediately into extraction sockets (IPIES) in conjunction with deproteinized bovine bone mineral (DBBM) particles and a collagen membrane.Material and methods: The mesial root of the third premolar in the left side of the mandible was endodontically treated (Test). Flaps were elevated, the tooth hemi-sectioned, and the distal root removed to allow the immediate installation of an implant into the extraction socket in a lingual position. DBBM particles were placed into the defect and on the outer contour of the buccal bony ridge, concomitantly with the placement of a collagen membrane. A non-submerged healing was allowed. The premolar on the right side of the mandible was left in situ (control). Ground sections from the center of the implant as well as from the center of the distal root of the third premolar of the opposite side of the mandible were obtained. The histological image from the implant site was superimposed to that of the contralateral pristine distal alveolus, and dimensional variation evaluated for the hard tissue and the alveolar ridge.Results: After 3 months of healing, both histological and photographic evaluation revealed a reduction of hard and soft tissue dimensions.Conclusion: The contour augmentation performed with DBBM particles and a collagen membrane at the buccal aspects of implants placed IPIES was not able to maintain the tissue volume.

Sequential healing at implants with different configuration and modified surfaces: an experimental study in the dog

To evaluate the peri-implant soft and hard tissue adaptation at implants with different modified surfaces and configurations. Six Beagle dogs were used. Mandibular premolars and first molars were extracted bilaterally. After 3 months, full-thickness flaps were elevated, and two different types of trans-mucosal implants (ICX-Gold®, Medentis Medical GmbH, Dernau, Germany and SLActive®, Institute Straumann, Bern, Switzerland) and two different surfaces were randomly installed in the distal regions of one side of the mandible. Abutments were applied, and a nonsubmerged healing was allowed. After 1 month, the procedures were performed in the other side of the mandible, and after a further month, the animals were sacrificed, biopsies were collected, and ground sections prepared for histological examination. Similar results in marginal bone and soft tissues dimensions were observed after 1 month of healing at the two implant systems used, and no major changes could be observed after 2 months of healing. After 1 month, the percentage of new bone was 69.0% and 68.8% at ICX-Gold and SLActive surfaces, respectively. After 2 months, the percentage of new bone was 67.8% and 71.9% at ICX-Gold Medentis and SLActive surfaces, respectively. No statistically significant differences in osseointegration were found. The two implant systems used resulted in similar osseointegration after 1 and 2 months of healing.

Adaptation of rubella to avian tissue culture

Sponsored by the National Institute of Allergy and Infectious Diseases.

Growth hormone is permissive for skeletal adaptation to mechanical loading

The Lewis dwarf (DW) rat was used as a model to test the hypothesis that growth hormone (GH) is permissive for new bone formation induced by mechanical loading in vivo. Adult female Lewis DW rats aged 6.2 +/- 0.1 months (187 +/- 18 g) were allocated to four vehicle groups (DW), four GH treatment groups at 32.5 mug/100 g body mass (DWGH1), and four GH treatment groups at 65 mug/100 g (DWGH2). Saline vehicle or GH was injected intraperitoneally (ip) at 6:30 p.m. and 6:30 a.m. before mechanical loading of tibias at 7:30 a.m. A single period of 300 cycles of four-point bending was applied to right tibias at 2.0 Hz, and magnitudes of 24, 29, 38, or 48N were applied. Separate strain gauge analyses in 5 DW rats validated the selection of loading magnitudes. After loading, double-label histomorphometry was used to assess bone formation at the periosteal surface (Ps.S) and endocortical surface (Ec.S) of tibias. Comparing left (unloaded) tibias among groups, GH treatment had no effect on bone formation. Bone formation in tibias in DW rats was insensitive to mechanical loading. At the Ec.S, mechanically induced lamellar bone formation increased in the DWGH2 group loaded at 48N (p < 0.05), and no significant increases in bone formation were observed among other groups. The percentage of tibias expressing woven bone formation (Wo.B) at the Ps.S was significantly greater in the DWGH groups compared with controls (p < 0.05). We concluded that GH influences loading-related bone formation in a permissive manner and modulates the responsiveness of bone tissue to mechanical stimuli by changing thresholds for bone formation.

Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat diet.

C57BL/6J mice were fed a high-fat, carbohydrate-free diet (HFD) for 9 mo. Approximately 50% of the mice became obese and diabetic (ObD), approximately 10% lean and diabetic (LD), approximately 10% lean and nondiabetic (LnD), and approximately 30% displayed intermediate phenotype. All of the HFD mice were insulin resistant. In the fasted state, whole body glucose clearance was reduced in ObD mice, unchanged in the LD mice, and increased in the LnD mice compared with the normal-chow mice. Because fasted ObD mice were hyperinsulinemic and the lean mice slightly insulinopenic, there was no correlation between insulin levels and increased glucose utilization. In vivo, tissue glucose uptake assessed by 2-[(14)C]deoxyglucose accumulation was reduced in most muscles in the ObD mice but increased in the LnD mice compared with the values of the control mice. In the LD mice, the glucose uptake rates were reduced in extensor digitorum longus (EDL) and total hindlimb but increased in soleus, diaphragm, and heart. When assessed in vitro, glucose utilization rates in the absence and presence of insulin were similar in diaphragm, soleus, and EDL muscles isolated from all groups of mice. Thus, in genetically homogenous mice, HFD feeding lead to different metabolic adaptations. Whereas all of the mice became insulin resistant, this was associated, in obese mice, with decreased glucose clearance and hyperinsulinemia and, in lean mice, with increased glucose clearance in the presence of mild insulinopenia. Therefore, increased glucose clearance in lean mice could not be explained by increased insulin level, indicating that other in vivo mechanisms are triggered to control muscle glucose utilization. These adaptive mechanisms could participate in the protection against development of obesity.

RV contractility and exercise-induced pulmonary hypertension in chronic mountain sickness: a stress echocardiographic and tissue Doppler imaging study.

OBJECTIVES: The aim of this study was to evaluate right ventricular (RV) and left ventricular function and pulmonary circulation in chronic mountain sickness (CMS) patients with rest and stress echocardiography compared with healthy high-altitude (HA) dwellers. BACKGROUND: CMS or Monge's disease is defined by excessive erythrocytosis (hemoglobin >21 g/dl in males, 19 g/dl in females) and severe hypoxemia. In some cases, a moderate or severe increase in pulmonary pressure is present, suggesting a similar pathogenesis of pulmonary hypertension. METHODS: In La Paz (Bolivia, 3,600 m sea level), 46 CMS patients and 40 HA dwellers of similar age were evaluated at rest and during semisupine bicycle exercise. Pulmonary artery pressure (PAP), pulmonary vascular resistance, and cardiac function were estimated by Doppler echocardiography. RESULTS: Compared with HA dwellers, CMS patients showed RV dilation at rest (RV mid diameter: 36 ± 5 mm vs. 32 ± 4 mm, CMS vs. HA, p = 0.001) and reduced RV fractional area change both at rest (35 ± 9% vs. 43 ± 9%, p = 0.002) and during exercise (36 ± 9% vs. 43 ± 8%, CMS vs. HA, p = 0.005). The RV systolic longitudinal function (RV-S') decreased in CMS patients, whereas it increased in the control patients (p < 0.0001) at peak stress. The RV end-systolic pressure-area relationship, a load independent surrogate of RV contractility, was similar in CMS patients and HA dwellers with a significant increase in systolic PAP and pulmonary vascular resistance in CMS patients (systolic PAP: 50 ± 12 mm Hg vs. 38 ± 8 mm Hg, CMS vs. HA, p < 0.0001; pulmonary vascular resistance: 2.9 ± 1 mm Hg/min/l vs. 2.2 ± 1 mm Hg/min/l, p = 0.03). Both groups showed comparable systolic and diastolic left ventricular function both at rest and during stress. CONCLUSIONS: Comparable RV contractile reserve in CMS and HA suggests that the lower resting values of RV function in CMS may represent a physiological adaptation to chronic hypoxic conditions rather than impaired RV function. (Chronic Mountain Sickness, Systemic Vascular Function [CMS]; NCT01182792).

Role of the circadian clock gene Per2 in adaptation to cold temperature.

Adaptive thermogenesis allows mammals to resist to cold. For instance, in brown adipose tissue (BAT) the facultative uncoupling of the proton gradient from ATP synthesis in mitochondria is used to generate systemic heat. However, this system necessitates an increase of the Uncoupling protein 1 (Ucp1) and its activation by free fatty acids. Here we show that mice without functional Period2 (Per2) were cold sensitive because their adaptive thermogenesis system was less efficient. Upon cold-exposure, Heat shock factor 1 (HSF1) induced Per2 in the BAT. Subsequently, PER2 as a co-activator of PPARα increased expression of Ucp1. PER2 also increased Fatty acid binding protein 3 (Fabp3), a protein important to transport free fatty acids from the plasma to mitochondria to activate UCP1. Hence, in BAT PER2 is important for the coordination of the molecular response of mice exposed to cold by synchronizing UCP1 expression and its activation.

Tissue homing and persistence of defined antigen-specific CD8+ tumor-reactive T-cell clones in long-term melanoma survivors.

Tumor antigen-specific cytotoxic T cells (CTLs) play a major role in the adaptive immune response to cancers. This CTL response is often insufficient because of functional impairment, tumor escape mechanisms, or inhibitory tumor microenvironment. However, little is known about the fate of given tumor-specific CTL clones in cancer patients. Studies in patients with favorable outcomes may be very informative. In this longitudinal study, we tracked, quantified, and characterized functionally defined antigen-specific T-cell clones ex vivo, in peripheral blood and at tumor sites, in two long-term melanoma survivors. MAGE-A10-specific CD8+ T-cell clones with high avidity to antigenic peptide and tumor lytic capabilities persisted in peripheral blood over more than 10 years, with quantitative variations correlating with the clinical course. These clones were also found in emerging metastases, and, in one patient, circulating clonal T cells displayed a fully differentiated effector phenotype at the time of relapse. Longevity, tumor homing, differentiation phenotype, and quantitative adaptation to the disease phases suggest the contribution of the tracked tumor-reactive clones in the tumor control of these long-term metastatic survivor patients. Focusing research on patients with favorable outcomes may help to identify parameters that are crucial for an efficient antitumor response and to optimize cancer immunotherapy.

T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?

Chronic viral infections and malignant tumours induce T cells that have a reduced ability to secrete effector cytokines and have upregulated expression of the inhibitory receptor PD1 (programmed cell death protein 1). These features have so far been considered to mark terminally differentiated 'exhausted' T cells. However, several recent clinical and experimental observations indicate that phenotypically exhausted T cells can still mediate a crucial level of pathogen or tumour control. In this Opinion article, we propose that the exhausted phenotype results from a differentiation process in which T cells stably adjust their effector capacity to the needs of chronic infection. We argue that this phenotype is optimized to cause minimal tissue damage while still mediating a critical level of pathogen control. In contrast to the presently held view of functional exhaustion, this new concept better reflects the pathophysiology and clinical manifestations of persisting infections, and it provides a rationale for emerging therapies that enhance T cell activity in chronic infection and cancer by blocking inhibitory receptors.

Fetal programming of adipose tissue function: an evolutionary perspective

Obesity is an escalating threat of pandemic proportions and has risen to such unrivaled prominence in such a short period of time that it has come to define a whole generation in many countries around the globe. The burden of obesity, however, is not equally shared among the population, with certain ethnicities being more prone to obesity than others, while some appear to be resistant to obesity altogether. The reasons behind this ethnic basis for obesity resistance and susceptibility, however, have remained largely elusive. In recent years, much evidence has shown that the level of brown adipose tissue thermogenesis, which augments energy expenditure and is negatively associated with obesity in both rodents and humans, varies greatly between ethnicities. Interestingly, the incidence of low birth weight, which is associated with an increased propensity for obesity and cardiovascular disease in later life, has also been shown to vary by ethnic background. This review serves to reconcile ethnic variations in BAT development and function with ethnic differences in birth weight outcomes to argue that the variation in obesity susceptibility between ethnic groups may have its origins in the in utero programming of BAT development and function as a result of evolutionary adaptation to cold environments.