Social preference is maintained in mice with impaired startle reflex and glutamate/D-serine imbalance induced by chronic cerebral toxoplasmosis.

Toxoplasma gondii is an opportunistic protozoan pathogen with a wide geographic distribution. The chronic phase of toxoplasmosis is often asymptomatic in humans and is characterized by tissue cysts throughout the central nervous system and muscle cells. T. gondii and other pathogens with tropism for the central nervous system are considered risk factors in the etiology of several neuropsychiatric disorders, such as schizophrenia and bipolar disorder, besides neurological diseases. Currently, it is known that cerebral toxoplasmosis increases dopamine levels in the brain and it is related to behavioral changes in animals and humans. Here we evaluate whether chronic T. gondii infection, using the cystogenic ME-49 strain, could induce behavioral alterations associated with neuropsychiatric disorders and glutamatergic neurotransmission dysfunction. We observed that the startle amplitude is reduced in the infected animals as well as glutamate and D-serine levels in prefrontal cortical and hippocampal tissue homogenates. Moreover, we did not detect alterations in social preference and spontaneous alternation despite severe motor impairment. Thus, we conclude that behavioral and cognitive aspects are maintained even though severe neural damage is observed by chronic infection of C57Bl/6 mice with the ME-49 strain.

Genetic polymorphisms and periodontal disease in populations of African descent: A review.

Aggressive periodontitis is a rare but rapidly progressing form of periodontal disease that usually affects otherwise systemically healthy individuals, at a young age. It usually affects first molars and incisors, which are usually lost if treatment is not properly and early rendered. Although of low prevalence, it affects individuals of African descent at a higher prevalence, and usually multiple members within the same family. Several studies have been performed in the attempt to evaluate specific single nucleotide polymorphisms (SNPs) that could be associated with this disease. To the best of our knowledge, the present article provides the first review of the literature focusing on studies that evaluated SNPs in patients of African descent with aggressive periodontitis. Several SNPs have been evaluated in different genes according to their role in the pathogenesis of the disease, with positive and negative associations (such as IL1, FCGR3B, FPR1, LTF, CYBA, GLT6D1, TLR4) with both the localized and generalized forms of aggressive periodontitis. Given the complexity of periodontitis, the difficulty in gathering large cohorts diagnosed with this rare form of disease, and the fact that candidate gene studies may only determine part of the genetic risk of a disease, the search for specific SNPs associated with aggressive periodontitis seems to be a long one, most likely to result in the combination of multiple SNPs, in multiple genes.

LPS-induced inflammatory response after therapy of aggressive periodontitis.

We have reported a lipopolysaccharide (LPS)-induced hyper-inflammatory response in localized aggressive periodontitis (LAP). It is unknown whether treatment is able to modulate this LPS responsiveness. Fifty-nine individuals with LAP were treated by mechanical debridement and systemic antibiotics. Clinical parameters and cyto/chemokine responsiveness of whole blood stimulated with Porphyromonas gingivalis or Escherichia coli LPS were monitored at baseline and 3, 6, and 12 months post-treatment. Overall, clinical parameters were improved following treatment. Additionally, P. gingivalis LPS induction of eotaxin, IFNγ, IL10, IL12p40, IL1ß, IL6, IP10, MCP1, MIP1α, GM-CSF, and TNFα was significantly decreased (p < .05). Similarly, induction of eotaxin, INFγ, IL10, IL12p40, GM-CSF, and TNFα by E. coli LPS was also reduced post-treatment. These reductions correlated with decreases in clinical parameters. Importantly, these reductions in LPS responsiveness were most robust at 3 months, and some lost significance at 6 to 12 months post-treatment. In conclusion, LPS-induced hyper-inflammatory response in LAP can be partially modulated by periodontal therapy. Conversely, rebound in the hyper-responsiveness of some mediators, in the presence of improved clinical parameters, suggests that this phenotype could be partially influenced by a genetic trait and play a role in future disease recurrence (ClinicalTrials.gov, NCT01330719).

Impact of Porphyromonas gingivalis inoculation on ligature-induced alveolar bone loss. A pilot study in rats.

BACKGROUND AND OBJECTIVE: Periodontitis is a polymicrobial infection characterized by the loss of connective tissue attachment, periodontal ligament and alveolar bone. The aim of this study was to evaluate the impact of Porphyromonas gingivalis inoculation on the ligature-induced alveolar bone loss (ABL) model in rats. MATERIAL AND METHODS: Forty male Wistar rats were randomly assigned to the following groups: G1, control (n = 10); G2, ligature-induced ABL (n = 15); and G3, ligature-induced ABL + P. gingivalis inoculation (n = 15). Rats in G2 and G3 were killed 15, 21 and 30 d after ligature placement, and the following parameters were assessed: microbiological load; ABL; and interleukin (IL)-1ß (Il1beta)/Il1ra, Il6/Il10 and Rankl/osteoprotegerin (Opg) mRNA ratios in the gingival tissues, as determined by quantitative PCR. RESULTS: Microbiological analyses demonstrated that rats in G1, G2 and G3 were positive for the presence of bacteria (determined using PCR amplification of the 16S gene), but that only the treatment sites of rats in G3 were positive for P. gingivalis at all time-points investigated. Histometrically, significant bone loss (p<0.001) was observed for both ligated groups (G2 and G3) compared with the nonligated group (G1), with higher ABL observed for G2 at all the experimental time-points. Furthermore, gene-expression analysis demonstrated that the presence of P. gingivalis in the dentogingival area significantly decreased the Il1ß/Il1ra, Il6/Il10 and Rankl/Opg mRNA ratios compared with ligature alone. CONCLUSION: Within the limits of this pilot study, it was concluded that inoculation of P. gingivalis affected the ligature-induced ABL model by the induction of an anti-inflammatory and antiresorptive host response.

Protective effects of heparin on hepatic ischemia and reperfusion lesions in rabbits.

Because the role of heparin (HEP) in hepatic ischemia/reperfusion (I/R) injury is still not fully understood, we investigated the effects of treatment with HEP on hepatic I/R injury in rabbits. For I/R procedures, the portal vein and hepatic artery were occluded by a metallic clamp to promote ischemia. The clamp was removed after 30 minutes to allow reperfusion. Rabbits undergoing the I/R procedure were treated with HEP (100 U/kg) or saline solution 0.9% (SS). When compared with levels before I/R, the serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, levels were increased by the hepatic I/R procedure, among rabbits treated with SS or HEP. However, the increase in these enzymes was lower among rabbits treated with HEP. Histologic analysis of hepatic tissue of rabbits undergoing I/R and treated with SS showed marked lesions in the central lobule with significant inflammatory infiltration. In contrast, a significant reduction in lesions caused by I/R was observed in the livers of rabbits treated with HEP. After starting reperfusion, we visualized apoptotic cells with nuclear staining among rabbits submitted to I/R and treated with SS, but not those treated with HEP. These results suggested that HEP was able to attenuate hepatic lesions caused by I/R in the livers of rabbits.

Guided tissue regeneration may modulate gene expression in periodontal intrabony defects: a human study.

BACKGROUND AND OBJECTIVE: Guided tissue regeneration has been shown to lead to periodontal regeneration, however, the mechanisms involved remain to be clarified. The present study was carried out to assess the expression of genes involved in the healing process of periodontal tissues in membrane-protected vs. nonprotected intrabony defects in humans. MATERIAL AND METHODS: Thirty patients with deep intrabony defects (> or = 5 mm, two or three walls) around teeth that were scheduled for extraction were selected and randomly assigned to receive one of the following treatments: flap surgery alone (control group) or flap surgery plus guided tissue regeneration (expanded polytetrafluorethylene (e-PTFE) membrane) (test group). Twenty-one days later, the newly formed tissue was harvested and quantitatively assessed using the polymerase chain reaction assay for the expression of the following genes: alkaline phosphatase, receptor activator of nuclear factor-kappa B ligand, osteoprotegerin, osteopontin, osteocalcin, bone sialoprotein, basic fibroblast growth factor, interleukin-1, interleukin-4, interleukin-6, matrix metalloproteinase-2 and matrix metalloproteinase-9. RESULTS: Data analysis demonstrated that mRNA levels for alkaline phosphatase, receptor activator of nuclear factor-kappa B ligand, osteoprotegerin, osteopontin, bone sialoprotein, basic fibroblast growth factor, interleukin-1, interleukin-6, matrix metalloproteinase-2 and matrix metalloproteinase -9 were higher in the sites where guided tissue regeneration was applied compared with the control sites (p < 0.05), whereas osteocalcin mRNA levels were lower (p < 0.05). No difference was observed in interleukin-4 mRNA levels between control and test groups. CONCLUSION: Within the limits of this study, it can be concluded that genes are differentially expressed in membrane barrier-led periodontal healing when compared with flap surgery alone, and this may account for the clinical outcome achieved by guided tissue regeneration.

Platelet-rich plasma does not improve bone regeneration around peri-implant bone defects--a pilot study in dogs.

The purpose of the present study was to evaluate the influence of platelet-rich plasma (PRP) on bone regeneration in dehiscence-type bone defects around dental implants. Ten male adult mongrel dogs were used. Three months after teeth extractions, an osteotomie for implantation and a buccal dehiscence defect were prepared on both sides of the jaws. Two dental implants with machined surfaces were placed on each implant site of the mandible. Dehiscences were randomly assigned to the following groups: (1) test (PRP) and (2) control. After 3 months animals were sacrificed; implants and adjacent hard tissues were processed for undecalcified sections. Bone-to-implant contact (BIC), bone density (BD) within the limits of implant threads, bone density (BO) and new bone area (NB) in a zone lateral to the implant, corresponding to bone defects, were obtained and measured. Inter group analysis (paired Student's t-test, alpha = 5%) demonstrated no statistically significant differences for any of the parameters when PRP was used (P > 0.05). Within the limits of the present study, it was concluded that platelet-rich plasma alone did not enhance bone regeneration for peri-implant defects.

Effect of two different approaches for root decontamination on new cementum formation following guided tissue regeneration: a histomorphometric study in dogs.

BACKGROUND AND OBJECTIVE: The aim of the present study was to evaluate comparatively the effect of two different approaches for root decontamination on new cementum formation following guided tissue regeneration (GTR). MATERIAL AND METHODS: Nine mongrel dogs were used to obtain bilateral chronic class III furcation defects by placing cotton ligatures around both third mandibular premolars. The teeth were randomly assigned to receive one of the following treatments: scaling and root planing, by means of hand and rotatory instruments, in order to remove soft and hard deposits as well as all root cementum (group A); or removal of only soft microbial deposits, by polishing the root surface with rubber cups and polishing paste, aiming for maximum root cementum preservation (group B). Both groups were treated with GTR, with the use of resorbable polyglycolic-lactic acid membranes (RESOLUT XT). RESULTS: Four months later, data analysis showed that a superior length (mm) (3.59 +/- 1.67 and 6.20 +/- 2.26 for groups A and B, respectively; p = 0.004) and a thicker layer (microm) (18.89 +/- 9.47 and 52.29 +/- 22.48 for groups A and B, respectively; p = 0.001) of new cementum was achieved by keeping the root cementum in place during root decontamination (group B). Regardless of the treatment modality, the new cementum was predominantly of a reparative, cellular extrinsic and intrinsic fiber type. CONCLUSION: Within the limits of the present study, it may be concluded that root cementum preservation may affect the new cementum formation following GTR in class III furcation defects, and the treatment modality did not influence the type of newly formed cementum.