Behavioral and physiological response to onset and termination of social instability in female mice.

Chronic stress has been associated with several negative health outcomes and psychopathological conditions. One source of chronic stress might be from ones social environment (e.g., being excluded from a group, losing a loved one, etc.). Specifically, social instability, or frequent changes in the social environment, can result in both physiological and behavioral stress responses. Corticosterone is the primary stress-responsive biomarker in rodents, and it reflects the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Historically, research on the effects of stress has relied on collection of blood, saliva, or other bodily fluids that yield information about moment-to-moment changes in stress physiology. Recently, new sampling techniques involving quantification of glucocorticoids in hair has allowed researchers to view patterns of stress physiology over extended periods of time. This study assessed the effects of chronic social instability on corticosterone levels in female mice. Mice that were subjected to social instability showed elevated hair corticosterone compared to baseline levels and as compared to controls. Additionally, when mice were returned to stable social environments, corticosterone levels returned to levels comparable to baseline and to control animals. This suggests that the corticosterone in hair from female mice can serve as a useful biomarker of chronic stress, and that social instability is a sufficient stressor to elicit an extended HPA response.

Intranasal vasopressin affects pair bonding and peripheral gene expression in male Callicebus cupreus.

Arginine vasopressin (AVP) is a neuropeptide hormone and neurotransmitter that has peripheral functions in water regulation, and central functions in the stress response and social bonding in male rodents. In this study, we investigated the role of AVP in partner preference behavior in a monogamous primate, the coppery titi monkey (Callicebus cupreus). Seven titi males each received three intranasal treatments: saline, low AVP (40 IU) and high AVP (80 IU) in random order, 1 week apart. They experienced a series of stimulus exposures to their female partner, a female stranger and an empty cage. Males were more likely to contact the stimulus and do so faster when either female stimulus was present. When pretreated with saline, males contacted the stranger more frequently than their partner; when pretreated with the high dosage of AVP, males contacted their partner more frequently than the stranger. We used microarray to measure peripheral changes in gene expression associated with intranasal AVP and found reduced expression of several genes coding for proinflammatory cytokines. The data presented here suggest that intranasally administered AVP has both central influences on social behavior and peripheral influences on inflammation in a nonhuman primate.

Plasma omega 3 polyunsaturated fatty acid status and monounsaturated fatty acids are altered by chronic social stress and predict endocrine responses to acute stress in titi monkeys.

Disturbances in fatty acid (FA) metabolism may link chronic psychological stress, endocrine responsiveness, and psychopathology. Therefore, lipid metabolome-wide responses and their relationships with endocrine (cortisol, insulin, and adiponectin) responsiveness to acute stress (AS) were assessed in a primate model of chronic social stress (CS). Compared to controls (not exposed to CS), CS increased (P≤0.05) circulating triacylglycerol (TG) and phosphatidylethanolamine (PE) n-6/n-3 and reduced (P≤0.05) cholesterol ester (CE) 16:1n7 and phosphatidylcholine (PC) 18:1n7, suggesting lower omega-3 FA status and stearoyl-CoA desaturase activity, respectively. Cortisol responses to AS positively correlated with TG n-6/n-3 (r=0.93; P=0.007), but only in CS monkeys. The adiponectin response to AS inversely correlated with CE n-6/n3 (r=-0.89; P=0.045) and positively with TG 16:1n7 (r=0.98; P=0.004), only in CS monkeys. Our results are consistent with previously reported FA profiles in stress-related psychopathology and suggest that compositional changes of specific lipid FAs may form new functional markers of chronic psychological stress.

Evaluation of hylan b gel as a soft-tissue augmentation implant material.

BACKGROUND: The ideal soft tissue augmentation material should be an inert, safe, volume-filling material that is easy to use and remains in place over time. Hylan b gel, a cross-linked hyaluronic acid, may have many of these characteristics. OBJECTIVE: We assessed the potential value of hylan b gel as a soft tissue augmentation material. METHODS: A 12-month guinea pig model was used to investigate the tissue effects of hylan b gel versus "collagen" controls. RESULTS: Hylan b gel was found to be biologically compatible and stable in dermal tissues. At 1 year, only hylan b gel implants were evident (12 of 16 test sites). CONCLUSION: In this model hylan b gel performed favorably when compared with the most commonly used soft-tissue augmentation products. The material possesses many desirable implant material characteristics.

Retrospective analysis of hydroxyapatite development for oral implant applications.

Ceramic forms of calcium phosphate, particularly HA, have been investigated extensively and used for hard-tissue implant applications for the past 20 years. HA ceramics still remain the most biocompatible bone implant material known and possess the added feature of becoming strongly bonded to living bone through natural-appearing bonding mechanisms. A variety of new or improved bone and tooth implant products have been developed using HA ceramics and thus this system has lead to overall improvements in dental hard-tissue repair and replacement. Because of HA's weak mechanical profile and relatively high chemical reactivity, however, bone implant devices composed in whole or in part of HA ceramics will fall short of being ideal permanent implant devices. Nevertheless, the development of a more fundamental and complete understanding of HA's bone-bonding mechanism could pave the way for a generation of surgical metals with permanent bone-bonding sites incorporated on their surfaces.

Biologic response to hydroxylapatite-coated titanium hips. A preliminary study in dogs.

Hydroxylapatite (HA)-coated and uncoated Ti-6A1-4V alloy femoral endoprostheses were evaluated in adult dogs. The femoral stems had proximal anterior, posterior, and medial pockets of either a commercially pure titanium porous coating or a grooved macrotexture. They also had a medial collar, with an inferior surface pocket of either the porous coating or the grooved macrotexture. HA-coated and uncoated specimens of each type were evaluated. The devices were placed as unilateral hemiarthroplasties in 12 dogs and remained in function for up to 52 weeks. Histologic sections from the uncoated grooved implants showed no direct bone-implant apposition in the proximal regions after up to 10 weeks; the HA-coated grooved implants demonstrated extensive direct bone-coating apposition after 5 weeks. Sections from uncoated porous implants evaluated after 10 weeks demonstrated approximately equivalent in-growth to those sections from the HA-coated devices after 6 weeks. All HA-coated implants demonstrated consistent bone-implant apposition with no fibrous tissue interposition. The HA-coated surfaces were associated with increased bone deposition and proliferation at early implantation periods. In no histologic section examined was there any evidence of deterioration of the HA coating, nor was any separation of the coating from the substrate material observed.

Hydroxyapatite-coated titanium for orthopedic implant applications.

The interface mechanical characteristics and histology of commercially pure (CP) titanium- and hydroxyapatite- (HA) coated Ti-6Al-4V alloy were investigated. Interface shear strength was determined using a transcortical push-out model in dogs after periods of three, five, six, ten, and 32 weeks. Undecalcified histologic techniques with implants in situ were used to interpret differences in mechanical response. The HA-coated titanium alloy implants developed five to seven times the mean interface strength of the uncoated, beadblasted CP titanium implants. The mean values for interface shear strength increased up to 7.27 megaPascals (MPa) for the HA-coated implants after ten weeks of implantation, and the maximum mean value of interface shear strength for the uncoated CP titanium implants was 1.54 MPa. For both implant types there was a slight decrease in mean shear strength from the maximum value to that obtained after the longest implantation period (32 weeks). Histologic evaluations in all cases revealed mineralization of interface bone directly onto the HA-coated implant surface, with no fibrous tissue layer interposed between the bone and HA visible at the light microscopic level. The uncoated titanium implants had projections of bone to the implant surface with apparent direct bone-implant apposition observed in some locations. Measurements of the HA coating material made from histologic sections showed no evidence of significant HA resorption in vivo after periods of up to 32 weeks.

Hydroxyapatite-coated porous titanium for use as an orthopedic biologic attachment system.

The biologic attachment characteristics of hydroxyapatite (HA)-coated porous titanium and uncoated porous titanium implants were investigated. The implants were placed transcortically in the femora of adult mongrel dogs and evaluated after periods of three, six, and 12 weeks. The HA coating was applied using a modified plasma spray process to samples with pore volume and pore size of the porous coating expanded to equal the pore morphology of uncoated porous specimens. Mechanical push-out testing revealed that the bone-porous material interface shear strength increased with time in situ for both the uncoated and HA-coated implants. The use of the HA coating on porous titanium, however, did not significantly increase attachment strength. Histologic and microradiographic sections yielded similar qualitative results in the amount of bone grown into each system. After three weeks, both systems displayed primarily woven bone occupying approximately 50% of the available porous structure. Six and 12 weeks postimplantation, each system displayed more extensive bone ingrowth, organization, and mineralization, with only limited areas of immature bone. Histologically, differences were noted at the ingrown bone-porous material interface between the two implant types. The HA coating supported mineralization directly onto its surface, and a thin osseous layer was found lining all HA-coated surfaces. An extremely thin fibrous layer was observed separating the uncoated titanium particle surface from ingrown bone. There was no extensive direct apposition or lining of the ingrown bone to the uncoated porous titanium particle surfaces.

The effect of surface macrotexture and hydroxylapatite coating on the mechanical strengths and histologic profiles of titanium implant materials.

A mechanical and histological evaluation of uncoated and hydroxylapatite-coated titanium implant materials was performed. Cylindrical implants of uncoated commercially pure (CP) titanium and hydroxylapatite-coated Ti-6Al-4V alloy were studied using a transcortical model, with implants evaluated after periods of 3, 5, 10, and 32 weeks. All implants had a surface macrotexture consisting of a series of semicircular annular grooves, approximately 750 micron in maximum depth. The attachment characteristics of interface shear stiffness and interface shear strength were determined by mechanical push-out testing. Nondecalcified histologic and microradiographic techniques, with implants in situ, were used to evaluate the response to the implant materials and the presence of the surface macrotexture. Mechanical testing results indicated that the hydroxylapatite-coated implants exhibited significantly greater values of maximum interface shear strength than the uncoated implants after all time periods. Interface shear stiffness was also significantly greater at all time periods for the hydroxylapatite-coated implants as compared to the uncoated implants. Histological evaluation after 3 weeks revealed an osteoid layer covering on all areas coated with the hydroxylapatite material; mineralization of this layer appeared to be complete after 10 weeks. In all cases, longer-term implants demonstrated mineralization of interface bone directly onto the hydroxylapatite coating, and in no case was a fibrous layer observed between the hydroxylapatite coating and the interface bone. Sections from the uncoated CP titanium implants revealed a thin fibrous layer present in nearly all areas. Only isolated regions of direct bone-implant apposition were observed for the uncoated implants. The presence of this fibrous tissue layer, however, apparently did not adversely affect the development of considerable attachment strength. The results from this study indicate that the hydroxylapatite coating can significantly increase the attachment strength of implants which rely upon bone apposition for fixation. In addition, the hydroxylapatite coating provides an osteophilic surface for bone deposition, and allows for a more rapid development of implant-bone attachment.

Hydroxylapatite blocks and particles as bone graft substitutes in orthognathic and reconstructive surgery.

A three-year clinical evaluation of 98 patients in whom dense hydroxylapatite in particle and block form had been placed in facial contour defects and osteotomy sites, and in cystic and reconstructive defects, alone or with autogenous bone, was conducted. The results indicate that the implants were effective in reducing operating time and potential for infection and relapse, as well as in reducing or eliminating the necessity of a donor site. The clinical response was excellent, and complications with both forms were minor, generally related to lack of initial fixation or failure to use autogenous bone in specific situations.

Evaluation of hydroxylapatite graft materials in canine cervical spine fusions.

The efficacy of ceramic hydroxylapatite implant materials as graft materials for cervical spine fusion was evaluated in canines. Bioresorbable and non-bioresorbable systems were evaluated at time periods ranging from 1 to 24 weeks. Implant interbody position and progression of fusion were evaluated radiographically and histologically. Implant fracture and extrusion into adjacent soft tissues occurred in nine of 23 cases. Implant fracture occurred in many of the remaining 14 cases, however, the implant materials remained within the interspace. Implant fracture occurred with both implant systems. Radiographically little evidence of fusion was observed at less than 6 weeks, however by 12 weeks evidence of fusion was noted and was confirmed histologically. No difference in fusion rate or degree of fusion was observed between the two implant systems.

Biomaterial aspects of calcium phosphates. Properties and applications.

Biomaterials composed of calcium phosphate ceramics are receiving increasing attention as potential bone graft substitutes. These substances have proved to be the most biocompatible hard-tissue implant materials discovered. The mechanical and biologic properties of the calcium phosphates, as well as their present and future applications, are discussed.

Fluoride uptake and dissolution behavior of a synthetic dental enamel-like substrate.

A new ceramic form of hydroxylapatite and enamel were found to behave similarly in regard to their acid dissolution behavior in the presence and absence of topically applied fluoride. Discrepancies between the two materials can be explained by morphological differences between the rough enamel and smooth ceramic particles.

Ceramic hydroxylapatite as a plaque growth and drug screening substrate.

A new polycrystalline form of hydroxylapatite, CHA, has been shown to closely mimic dental enamel, in vitro, in regard to rate and degree of plaque formation and effectiveness of antiplaque drugs. The material has successfully been exploited as a standardized hydroxylapatite plaque growth substrate in conjuntion with a mass antidental plaque drug screening program.

Tissue, cellular and subcellular events at a bone-ceramic hydroxylapatite interface.

A new polycrystalline form of hydroxylapatite, durapatite, has been examined as a cortical bone implant in dogs. Utilizing histological and electron optical techniques, it has been found that durapatite does not elicit a foreign body response and that all new bone surrounding the material is normally calcified. Bone was found to strongly adhere to durapatite and preliminary evidence suggests this bonding may be due to direct chemical attachment of bone to the material.