Bone repair and augmentation using block of sintered bovine-derived anorganic bone graft in cranial bone defect model

To histomorphometrically investigate the repair of critical size defects (CSDs) and bone augmentation in cranial walls using block of sintered bovine-derived anorganic bone (sBDAB) graft. Forty guinea-pigs were divided into test (n=20) and CSD control (n=20) groups. In each animal, a full-thickness bone defect with 9.5 mm diameter was made in the frontal bone. The defects were filled with an sBDAB block soaked in blood in the test group and with blood clot in the CSD control group. The skulls were collected at 0 h (n=2) and 30, 90 and 180 days (n=6/group and period) postoperatively. The volume density and total volume of newly formed bone, sBDAB, blood vessels and connective tissue, vertical thickness of removed bone plug, sBDAB block and graft area were evaluated. The vertical thickness of the adapted sBDAB block was 3.8 times higher than that of the removed bone plug and did not show significant difference between periods, filling in average 29.8% of the total graft region. The sBDAB block exhibited complete osseointegration with the borders of the defect at 90 days. At 90 and 180 days, the vertical thickness of the graft was 279% in the average, and the total volume of bone augmentation was, respectively, 78.8% and 148.5% higher compared with the removed bone plug. The defects of the CDS control group showed limited osteogenesis and filling by connective tissue plus tegument. The sBDAB block can be used to promote repair of CSDs and bone augmentation in the craniomaxillofacial region, due to its good osteoconductive and slow resorptive properties. To cite this article:Cestari TM, Granjeiro JM, de Assis GF, Garlet GP, Taga R. Bone repair and augmentation using block of sintered bovine-derived anorganic bone graft in cranial bone defect model.Clin. Oral Impl. Res. 20, 2009; 340-350.doi: 10.1111/j.1600-0501.2008.01659.x.

Effect of different surface treatments on the repair bond strength of indirect composites

Purpose: To evaluate the tensile bond strength of indirect composites repaired with different surface treatments and direct composites. Methods: 180 specimens were prepared with Targis, belleGlass HP and Sculpture indirect composites, light-activated and post-cured according to the manufacturers` recommendations. The specimens were stored in distilled water for 24 hours at 37 degrees C. The bonding surfaces were prepared with air abrasion, hydrofluoric acid or hydrofluoric acid followed by a neutralizing solution. All the treated surfaces were subject to the application of a silane and a bonding agent before the repair procedures with Tetric Ceram and Tetric Flow for the Targis specimens, Herculite XRV and Revolution for the belleGlass HP specimens and Sculp-It and Flow-It for Sculpture specimens. The tensile bond strength tests were carried out using a universal testing machine at cross-head speed of 0.5 mm/minute. The type of fracture was observed under a light microscope at x40 magnification. Data were analyzed by a two-way ANOVA and Tukey`s post-hoc tests (P<0.05). Results: Targis showed a statistically higher repair bond strength than belleGlass HP and Sculpture, which were not significantly different from each other. Air abrasion increased the repair bond strength of belleGlass HP and Sculpture. For Targis, all the surface treatments resulted in similar repair bond strength. The different viscosity of repair composites did not affect the repair of indirect composites. Fractured surfaces showed mostly adhesive failures, mainly with hydrofluoric acid treatment.

Morphometric evaluation of the repair of critical-size defects using demineralized bovine bone and autogenous bone grafts in rat calvaria

Objective: To evaluate the repair of critical-size bone defects in rats treated with demineralized bovine bone (DBB) compared with autogenous bone (AB). Material and method: A bone defect of 8 mm in diameter was created in the calvaria of 50 Rattus norvegicus, treated either with DBB or AB. Sub-groups of five rats of each group were killed at 7, 14, 21, 30 and 90 days post-operatively, and the skulls were removed and processed histologically. Histological sections were stained with hematoxylin and eosin. Result: Histological analysis showed complete closure of the defects with new bone at 90 days in group AB, and substitution of the biomaterial by fibrotic connective tissue in the DBB group at 21 days. Morphometric analysis showed that DBB was rapidly absorbed at 14 days, with its volume density decreasing from 47%+/- 0.8% at 7 days to 1.2%+/- 0.41% at 14 days. Subsequently, volume densities of the connective tissue and neoformed bone increased from 51.1%+/- 11.17% to 86.8%+/- 7.92% and from 1.9%+/- 1.13% to 12%+/- 8.02%, respectively, for the same time interval. The volume density of AB particles did not change throughout the experimental periods, but the amount of new bone increased markedly between 7 and 90 days, from 4.5%+/- 1.57% to 53.5%+/- 6.42% (P < 0.05). Conclusion: DBB did not provide complete repair of the defects, with significantly less new bone formation than in the AB group.

Influence of Antiplatelet Drugs in the Pathogenesis of Experimental Periodontitis and Periodontal Repair in Rats

Background: Platelets contain an array of biologic mediators that can modulate inflammation and repair processes including proinflammatory mediators and growth factors. Previous studies have shown that periodontitis and periodontal repair are associated with platelet activation. We hypothesized that drug-induced platelet inactivation may interfere in the processes of inflammation and repair in experimental periodontitis in rats by suppressing the release of biologic mediators from platelets to the site of injury. Methods: To measure the effects on periodontitis, ligatures were placed around first molars, and aspirin (Asp, 30 mg/kg) or clopidogrel (Clo, 75 mg/kg) was given intragastrically once daily for 15 days. Interleukin-6 (IL-6), tumor necrosis factor-a (TNF-alpha), and thromboxane A(2) levels were measured by enzyme-linked immunosorbent assay. To evaluate the effects of antiplatelet drugs on periodontal repair, ligatures were removed after 15 days of periodontitis induction, and Asp or Clo were administered beginning the following day for 15 days. Periodontal repair was assessed by microcomputed tomography. Results: On periodontitis phase, Asp and Clo significantly reduced levels of TNF-alpha and II-6 (P < 0.05), but only Asp decreased thromboxane A(2) (P < 0.05). Asp and Clo decreased inflammatory infiltration; however, this reduction was more pronounced with Clo treatment (P < 0.05). Histometric analysis showed that Asp and Clo impaired alveolar bone resorption. During the repair phase and after removal of the ligatures, microcomputed tomography analysis demonstrated that treatment with Asp and Clo did not impair alveolar bone repair. Conclusion: Systemic administration of Asp and Clo attenuates the inflammation associated with periodontitis without affecting the repair process when stimulus is removed. J Periodontol 2011;82:767-777.

Mice with genetic deletion of the heparin-binding growth factor midkine exhibit early preclinical features of Parkinson`s disease

There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson`s disease (PD) begin many years before the appearance of the characteristic motor symptoms and that impairments in olfactory, cognitive and motor functions are associated with time-dependent disruption of dopaminergic neurotransmission in different brain areas. Midkine is a 13-kDa retinoic acid-induced heparin-binding growth factor involved in many biological processes in the central nervous system such as cell migration, neurogenesis and tissue repair. The abnormal midkine expression may be associated with neurochemical dysfunction in the dopaminergic system and cognitive impairments in rodents. Here, we employed adult midkine knockout mice (Mdk(-/-)) to further investigate the relevance of midkine in dopaminergic neurotransmission and in olfactory, cognitive and motor functions. Mdk(/-) mice displayed pronounced impairments in their olfactory discrimination ability and short-term social recognition memory with no gross motor alterations. Moreover, the genetic deletion of midkine decreased the expression of the enzyme tyrosine hydroxylase in the substantia nigra reducing partially the levels of dopamine and its metabolites in the olfactory bulb and striatum of mice. These findings indicate that the genetic deletion of midkine causes a partial loss of dopaminergic neurons and depletion of dopamine, resulting in olfactory and memory deficits with no major motor impairments. Therefore, Mdk(-/-) mice may represent a promising animal model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.

Blocking systemic nitric oxide production alters neuronal activation in brain structures involved in cardiovascular regulation during polymicrobial sepsis

In a previous study, we concluded that overproduction of nitric oxide (NO) by inducible nitric Oxide synthase (iNOS) in the late phase of sepsis prevents hypothalamic activation, blunts vasopressin secretion and contributes to hypotension, irreversible shock and death. The aim of this follow-up study was to evaluate if the same neuronal activation pattern happens in brain structures related to cardiovascular functions. Male Wistar rats received intraperitoneal injections of aminoguanidine, an iNOS inhibitor, or saline 30 min before cecal ligation and puncture (CLP) or sham surgeries. The animals were perfused 6 or 24 h after the surgeries and the brains were removed and processed for Fos immunocytochemistry We observed an increase (P < 0.001) in c-fos expression 6 h after CLP in the area postrema (AP), nucleus of he tractus solitarius (NTS), ventral lateral medulla (VLM), locus coeruleus (LC) and parabrachial nucleus (PB). At 24 h after CLP, however, c-fos expression was strongly decreased in all these nuclei (P < 0.05), except for the VLM. Aminoguanidine reduced c-fos expression in the AP and NTS at 6 h after CLR but showed an opposite effect at 24 h, with an increase in the AP, NTS, and also in the VLM. No such effect was observed in the LC and PB at 6 or 24 h. In all control animals, c-fos expression was minimal or absent. We conclude that in the early phase of sepsis iNOS-derived NO may be partially responsible for the activation of brain structures related to cardiovascular regulation. During the late phase, however, this activation is reduced or abolished. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Brain monoaminergic neurons and ventilatory control in vertebrates

Monoamines (noradrenaline (NA), adrenaline (AD), dopamine (DA) and serotonin (5-HT) are key neurotransmitters that are implicated in multiple physiological and pathological brain mechanisms, including control of respiration. The monoaminergic system is known to be widely distributed in the animal kingdom, which indicates a considerable degree of phylogenetic conservation of this system amongst vertebrates. Substantial progress has been made in uncovering the participation of the brain monoamines in the breathing regulation of mammals, since they are involved in the maturation of the respiratory network as well as in the modulation of its intrinsic and synaptic properties. On the other hand, for the non-mammalian vertebrates, most of the knowledge of central monoaminergic modulation in respiratory control, which is actually very little, has emerged from studies using anuran amphibians. This article reviews the available data on the role of brain monoaminergic systems in the control of ventilation in terrestrial vertebrates. Emphasis is given to the comparative aspects of the brain noradrenergic, adrenergic, dopaminergic and serotonergic neuronal groups in breathing regulation, after first briefly considering the distribution of monoaminergic neurons in the vertebrate brain. (C) 2008 Elsevier B.V. All rights reserved.

Eag1 potassium channel immunohistochemistry in the CNS of adult rat and selected regions of human brain

Eag1 (K(v)10.1) is the founding member of an evolutionarily conserved superfamily of voltage-gated K+ channels. In rats and humans Eag1 is preferentially expressed in adult brain but its regional distribution has only been studied at mRNA level and only in the rat at high resolution. The main aim of the present study is to describe the distribution of Eag1 protein in adult rat brain in comparison to selected regions of the human adult brain. The distribution of Eag1 protein was assessed using alkaline-phosphatase based immunohistochemistry. Eag1 immunoreactivity was widespread, although selective, throughout rat brain, especially noticeable in the perinuclear space of cells and proximal regions of the extensions, both in rat and human brain. To relate the results to the relative abundance of Eag1 transcripts in different regions of rat brain a reverse-transcription coupled to quantitative polymerase chain reaction (real time PCR) was performed. This real time PCR analysis showed high Eag1 expression in the olfactory bulb, cerebral cortex, hippocampus, hypothalamus, and cerebellum. The results indicate that Eag1 protein expression greatly overlaps with mRNA distribution in rats and humans. The physiological relevance of potassium channels in the different regions expressing Eag1 protein is discussed. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

Rapid maxillary expansion causes neuronal activation in brain structures of rats

A correlation between pain sensation and neuronal c-fos expression has been analyzed following experimental rapid maxillar expansion (RME). Adult male Wistar rats were anaesthetized and divided into three groups: animals that received an orthodontic apparatus, which was immediately removed after the insertion (control), animals that received an inactivated orthodontic apparatus (without force), and animals that received an orthodontic apparatus previously activated (140 g force). After 6, 24, 48, or 72 h, the animals were re-anaesthetized, and perfused with 4% paraformaldehyde. The brains were removed, fixed, and sections containing brain structures related to nociception were processed for Fos protein immunohistochemistry (IHC). The insertion of the orthodontic apparatus with 140 g was able to cause RME that could be seen by radiography. The IHC results showed that the number of activated neurons in the different nuclei changed according to the duration of appliance insertion and followed a temporal pattern similar to that of sensations described in clinics. The animals that received the orthodontic apparatus without force did not show RME but a smaller c-fos expression in the same brain structures. In conclusion, we demonstrate that orthodontic force used for palate disjunction activates brain structures that are related to nociception, and that this activation is related to the pain sensation described during orthodontic treatment. (c) 2008 Elsevier Inc. All rights reserved.

Bone repair in mandibular body osteotomy after using 2.0 miniplate system - histological and histometric analysis in dogs

The objective of this study was to evaluate the bone repair along a mandibular body osteotomy after using a 2.0 miniplate system. Nine adult mongrel dogs were subjected to unilateral continuous defect through an osteotomy between the mandibular 3rd and 4th premolars. Two four-hole miniplates were placed in accordance with the Arbeitgeimeinschaft fur Osteosynthesefragen Manual. Miniplates adapted to the alveolar processes were fixed monocortically with 6.0-mm-length titanium alloy self-tapping screws, whereas miniplates placed near the mandible bases were fixed bicortically. At 2, 6 and 12 weeks, three dogs were sacrificed per period, and the osteotomy sites were removed, divided into three thirds (Tension Third, TT; Intermediary Third, IT; Compression Third, CT) and prepared for conventional and polarized light microscopy. At 6 weeks, while the CT repaired faster and showed bone union by woven bone formation, the TT and IT exhibited a ligament-like fibrous connective tissue inserted in, and connecting, newly formed woven bone overlying the parent lamellar bone edges. At 12 weeks, bone repair took place at all thirds. Histometrically, proportions of newly formed bone did not alter at TT, IT and CT, whereas significantly enhanced bone formation was observed for the 12-week group, irrespective of the third. The results demonstrated that although the method used to stabilize the mandibular osteotomy allowed bone repair to occur, differences in the dynamics of bone healing may take place along the osteotomy site, depending on the action of tension and compression forces generated by masticatory muscles.

Patterns of community integration 2-5 years post-discharge from brain injury rehabilitation

Outcome after traumatic brain injury (TBI) is characterized by a high degree of variability which has often been difficult to capture in traditional outcome studies. The purpose of this study was to describe patterns of community integration 2-5 years after TBI. Participants were 208 patients admitted to a Brain Injury Rehabilitation Unit between 1991-1995 in Brisbane, Australia. The design comprised retrospective data collection and questionnaire follow-up by mail. Mean follow-up was 3.5 years. Demographic, injury severity and functional status variables were retrieved from hospital records. Community integration was assessed using the Community Integration Questionnaire (CIQ), and vocational status measured by a self administered questionnaire. Data was analysed using cluster analysis which divided the data into meaningful subsets. Based on the CIQ subscale scores of home, social and productive integration, a three cluster solution was selected, with groups labelled as working (n = 78), balanced (n = 46) and poorly integrated (n = 84). Although 38% of the sample returned to a high level of productive activity and 22% achieved a balanced lifestyle, overall community integration was poor for the remainder. This poorly integrated group had more severe injury characterized by longer periods of acute care and post-traumatic amnesia (PTA) and greater functional disability on discharge. These findings have implications for service delivery prior to and during the process of reintegration after brain injury.

Glucose induced IEG expression in the thiamin-deficient rat brain

Glucose loading of rats made thiamin deficient by dietary deprivation of thiamin and the administration of pyrithiamin (40 mug/100 g, i.p.) precipitates an acute neuropathy, a model of Wernicke's encephalopathy in man (Zimitat and Nixon, Metab. Brain Dis. 1999;14:1-20). Immunohistochemical detection of Fos proteins was used as a marker to identify neuronal populations in the thiamin-deficient rat brain affected by glucose loading. As thiamin deficiency progressed, the extent and intensity of Fos-Like immunoreactivity (FLI) in brain structures typically affected by thiamin deficiency (the thalamus, mammillary bodies, inferior colliculus, vestibular nucleus and inferior olives) were markedly increased when compared to thiamin-replete controls. Glucose loading for 1-3 days further increased the intensity of FLI in these same regions, consistent with a dependence of Fos expression on carbohydrate metabolism as well as on thiamin deficiency. The timed acute changes that follow a bolus glucose load administered to thiamin-deficient animals may provide a sequential account of events in the pathogenesis of brain damage in this model of Wernicke's encephalopathy. (C) 2001 Elsevier Science B.V. All rights reserved.

Irrational schematic beliefs and psychological distress in caregivers of people with traumatic brain injury

Objective: To investigate the relation between irrational schematic beliefs and psychological distress in caregivers of persons with traumatic brain injury (TBI). Design: Cross-sectional mail survey. Participants: One hundred sixteen caregivers of persons with TBI living in the Australian states of Victoria and Queensland who were members of community support groups and brain injury associations. Measures: The Irrational Beliefs Inventory, Brief Symptom Inventory, income satisfaction, degree of personality and behavior change in the TBI individual, and injury severity. Results: Hierarchical regression analyses showed that after controlling for the effects of characteristics of the caregiving situation and the individual with TBI, greater adherence to irrational beliefs was related to higher levels of global psychological distress. Specifically, irrational beliefs related to Worrying were associated with all areas of psychological distress. Conclusion: Results support the cognitive theory proposal that irrational beliefs play an important role in the adaptation to TBI caregiving. Findings suggest the inclusion of cognitive therapy strategies in interventions for caregivers.

Ethanol and gene expression in brain

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Izuru Matusmoto and Peter A. Wilce. The presentations were (1) GABA receptor subunit expression in the human alcoholic brain, by Tracey Buckley and Peter Dodd; (2) NMDAR gene expression during ethanol addiction, by Jorg Puzke, Rainer Spanagel, Walther Zieglgansberger, and Gerald Wolf; (3) Differentially expressed gene in the nucleus accumbens from ethanol-administered rat, by Shuangying Leng; (4) Expression of a novel gene in the alcoholic brain, by Peter A. Wilce; and (5) Investigations of haplotypes of the dopamine Da-receptor gene in alcoholics, by Hans Rommelspacher, Ulrich Finckh, and Lutz G. Schmidt.