Sex-based differential regulation of bacterial-induced bone resorption.

BACKGROUND AND OBJECTIVE: Periodontal disease pathogenesis is comprised of the complex inflammatory immune response to oral bacterial dysbiosis. Like other inflammatory diseases, there is sexual dimorphism evident in periodontal diseases. During periodontitis, inflammatory chemokines direct neutrophils to migrate to the site of infection to neutralize the pathogen. Interestingly, these same chemokines are also involved in regulating pathogen-induced osteoclast formation. Previous reports show differences in bone turnover and lymphocyte recruitment between sexes. We hypothesize that chemokine expression is differentially regulated by sex and thus results in differential osteoclast formation. MATERIAL AND METHODS: Male and female mice were utilized to isolate neutrophils based on expression of Ly6G-specific, as well as defined osteoclast progenitors. Cells were stimulated with lipopolysaccharide (LPS; 100 ng/mL) then analyzed for neutrophil infiltration and gene expression. Defined osteoclast progenitors were primed: macrophage-colony stimulating factor (25 ng/mL), receptor activator of NF-κB ligand (50 ng/mL), then stimulated with LPS. Osteoclasts were enumerated via TRAP stain and mRNA isolated for gene expression analysis via quantitative polymerase chain reaction. RESULTS: In response to LPS, male neutrophils in vitro respond with increased chemokine expression and significantly more osteoclast formed in response to LPS compared to females. CONCLUSIONS: Findings support observations in humans regarding a sexual dimorphism in oral bacterial infections of alveolar bone loss. Males have a strong inflammatory response to bacterial infection, resulting in increased inflammatory microenvironment, reduced pathogenic bacteria clearance and increased osteoclast-driven bone loss in response to differential expression of key chemokines.

Aggregatibacter actinomycetemcomitans, a potent immunoregulator of the periodontal host defense system and alveolar bone homeostasis.

Aggregatibacter actinomycetemcomitans is a perio-pathogenic bacteria that has long been associated with localized aggressive periodontitis. The mechanisms of its pathogenicity have been studied in humans and preclinical experimental models. Although different serotypes of A. actinomycetemcomitans have differential virulence factor expression, A. actinomycetemcomitans cytolethal distending toxin (CDT), leukotoxin, and lipopolysaccharide (LPS) have been most extensively studied in the context of modulating the host immune response. Following colonization and attachment in the oral cavity, A. actinomycetemcomitans employs CDT, leukotoxin, and LPS to evade host innate defense mechanisms and drive a pathophysiologic inflammatory response. This supra-physiologic immune response state perturbs normal periodontal tissue remodeling/turnover and ultimately has catabolic effects on periodontal tissue homeostasis. In this review, we have divided the host response into two systems: non-hematopoietic and hematopoietic. Non-hematopoietic barriers include epithelium and fibroblasts that initiate the innate immune host response. The hematopoietic system contains lymphoid and myeloid-derived cell lineages that are responsible for expanding the immune response and driving the pathophysiologic inflammatory state in the local periodontal microenvironment. Effector systems and signaling transduction pathways activated and utilized in response to A. actinomycetemcomitans will be discussed to further delineate immune cell mechanisms during A. actinomycetemcomitans infection. Finally, we will discuss the osteo-immunomodulatory effects induced by A. actinomycetemcomitans and dissect the catabolic disruption of balanced osteoclast-osteoblast-mediated bone remodeling, which subsequently leads to net alveolar bone loss.

Anomalous patterns of response learning and transfer in decorticate rats.

Behavioural flexibility in decorticate rats was examined by testing response transfer in an obstructed alleyway. In the first experiment, rats were trained to push a ball out of a cylindrical alleyway in order to gain access to the goal box. When this 'push' habit was prevented by blocking forward movement of the ball, decorticate rats were much quicker than sham-operated rats in successfully developing the novel clearance response of pulling the ball into the start box. Both groups were subsequently able to reverse effectively between responses. In a second experiment, sham-operated and decorticate rats were first shaped to pull the ball clear from the alleyway, and then required to adopt a push-type clearance response when movement of the ball towards the start box was prevented. Here, the decorticates showed difficulty both in learning to pull the ball out of the alley and in transferring to a push-type clearance response, but having transferred they coped well with subsequent reversals. This asymmetrical pattern of transfer results is not readily attributed to response preference and raises the possibility that, in some situations at least, decorticated animals may show greater behavioural flexibility than had previously been supposed.

Infection by the hepatitis B virus in patients of a general hospital.

The prevalence of HBsAg and anti HBs was studied in 1062 inpatients in the city of Rio de Janeiro. HBsAg positivity rates were as follows: a) acute viral hepatitis: 37.8% b) chronic hepatitis 46.67% c) chronic liver disease without hepatitis: 7.69% d) diabetes 3.08% e) lepromatous leprosy 2.35% f) others 2.01%. The carrier state is emphasized. Anti HBs was less frequent in patients with acute viral hepatitis than in patients with other diseases (hepatic or not). The highest levels were: a) lepromatous leprosy: 57.65% b) drug addicts: 46.15% e) diabetes: 43.3%. The high anti HBs positivity is discussed.