Assessing osseointegration of metallic implants with boronized surface treatment.

BACKGROUND: Modification of endosteal implants through surface treatments have been investigated to improve osseointegration. Boronization has demonstrated favorable mechanical properties, but limited studies have assessed translational, in vivo outcomes. This study investigated the effect of implant surface boronization on bone healing. MATERIAL AND METHODS: Two implant surface roughness profiles (acid etched, machined) in CP titanium (type II) alloy implants were boronized by solid-state diffusion until 10-15µm boron coating was achieved. The surface-treated implants were placed bilaterally into 5 adult sheep ilia for three and six weeks. Four implant groups were tested: boronized machined (BM), boronized acid-etched (BAA), control machined (CM), and control acid-etched (CAA). Osseointegration was quantified by calculating bone to implant contact (BIC) and bone area fraction occupancy (BAFO). RESULTS: Both implant types treated with boronization had BIC values not statistically different from machined control implants at t=3 weeks, and significantly less than acid-etched control (p<0.02). BAFO values were not statistically different for all 3-week groups except machined control (significantly less at p <0.02). BAFO had a significant downward trend from 3 to 6 weeks in both boronized implant types (p<0.03) while both control implant types had significant increases in BIC and BAFO from 3 to 6 weeks. CONCLUSIONS: Non-decalcified histology depicted intramembranous-like healing/remodeling in bone for controls, but an absence of this dynamic process in bone for boronized implants. These findings are inconsistent with in vitro work describing bone regenerative properties of elemental Boron and suggests that effects of boron on in vivo bone healing warrant further investigation.

Plant and herbivore ontogeny interact to shape the preference, performance and chemical defense of a specialist herbivore.

The amount of damage that herbivorous insects impose on plants varies as a function of plant ontogenetic trajectories in tissue quality and defenses, and the herbivores' own developmental trajectories in body size, mandible shape and detoxification enzymes, among others. However, little is known about how host plant and herbivore ontogeny interact. Using four ontogenetic stages of Plantago lanceolata (Plantaginaceae) and three to five larval stages of the specialist caterpillar Junonia coenia (Nymphalidae), we evaluated how ontogenies in both of these trophic levels shape: (i) caterpillar feeding choice, (ii) performance, and (iii) sequestration of plant allelochemicals. Plant physical (leaf toughness) and chemical (iridoid glycosides) defenses increased, while nutritional quality (water and nitrogen content) decreased, as plants aged. These plant ontogenetic trajectories strongly altered the behavior and physiology of this specialist herbivore, but the magnitude of the response varied with larval stage. In feeding experiments, while first instar larvae showed little preference among plant stages, older larvae significantly preferred juvenile over reproductive stages. In turn, larval consumption increased and digestive efficiency decreased, potentially explaining their decrease in relative growth rate, as larvae and host plant aged, but differences were greater for younger than older caterpillars. Finally, sequestration of plant allelochemicals increased through plant and larval development; however, the major differences due to diet occurred earlier during larval development. Our results highlight that changes in plant ontogeny most strongly influence early herbivore instars, emphasizing the need to consider the developmental stage of both trophic levels to better understand temporal variation in herbivore damage.

Pegloticase co-administered with high MW polyethylene glycol effectively reduces PEG-immunogenicity and restores prolonged circulation in mouse.

The interactions between polymers and the immune system remains poorly controlled. In some instances, the immune system can produce antibodies specific to polymer constituents. Indeed, roughly half of pegloticase patients without immunomodulation develop high titers of anti-PEG antibodies (APA) to the PEG polymers on pegloticase, which then quickly clear the drug from circulation and render the gout treatment ineffective. Here, using pegloticase as a model drug, we show that addition of high molecular weight (MW) free (unconjugated) PEG to pegloticase allows us to control the immunogenicity and mitigates APA induction in mice. Compared to pegloticase mixed with saline, mice repeatedly dosed with pegloticase containing different MW or amount of free PEG possessed 4- to 12- fold lower anti-PEG IgG, and 6- to 10- fold lower anti-PEG IgM, after 3 rounds of pegloticase dosed every 2 weeks. The markedly reduced APA levels, together with competitive inhibition by free PEG, restored the prolonged circulation of pegloticase to levels observed in APA-naïve animals. In contrast, mice with pegloticase-induced APA eliminated nearly all pegloticase from the circulation within just four hours post-injection. These results support the growing literature demonstrating free PEG may effectively suppress drug-induced APA, which in turn may offer sustained therapeutic benefits without requiring broad immunomodulation. We also showed free PEG effectively blocked the PEGylated protein from binding with cells expressing PEG-specific B cell receptors. It provides a template of how we may be able to tune the interactions and immunogenicity of other polymer-modified therapeutics. STATEMENT OF SIGNIFICANCE: A major challenge with engineering materials for drug delivery is their interactions with the immune system. For instance, our body can produce high levels of anti-PEG antibodies (APA). Unfortunately, the field currently lack tools to limit immunostimulation or overcome pre-existing anti-PEG antibodies, without using broad immunosuppression. Here, we showed that simply introducing free PEG into a clinical formulation of PEG-uricase can effectively limit induction of anti-PEG antibodies, and restore their prolonged circulation upon repeated dosing. Our work offers a readily translatable method to safely and effectively restore the use PEG-drugs in patients with PEG-immunity, and provides a template to use unconjugated polymers with low immunogenicity to regulate interactions with the immune system for other polymer-modified therapeutics.

Mandibular reconstruction using a titanium plate: the impact of radiation therapy on plate preservation.

PURPOSE: To evaluate the soft tissue and bone tolerance of radiation therapy (RT) in patients undergoing radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. METHODS AND MATERIALS: From 1990 to 1994, 47 patients with primary or recurrent oral cavity or oropharyngeal carcinomas were treated with radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. Eleven patients received no RT (no RT), 10 patients received RT greater than 10 months from the time of surgery (remote RT), and 26 patients received RT within 12 weeks of surgery (perioperative RT). The radiation dose to the reconstructed mandible ranged from 45 to 75 Gy (median 63 Gy). The effect of the titanium plate on the radiation dose was measured using film dosimetry and soft tissue and bone-equivalent materials. The median follow-up was 17 months (range: 3-50 months). RESULTS: Late complications included four patients with osteomyelitis or necrosis, two plate exposures requiring flap revision, one chronic infection, two cases of chronic pain, two fistulae, and one case of trismus and malocclusion. The crude incidence of late complications by treatment was: (a) no RT: 3 of 11 patients (27%); (b) remote RT: 2 of 10 patients (20%); and (c) perioperative RT: 9 of 26 patients (35%). One patient in the no-RT group lost the plate due to chronic pain. Five patients in the perioperative RT group also had plate loss, four due to osteomyelitis and/or necrosis, and one due to pain related to a recurrent tumor. No patients in the remote RT group had plate loss. The actuarial prosthesis preservation rate at 2 years was 88% for the no RT, 100% for the remote RT, and 57% for the perioperative RT groups (p = 0.05). Phantom dose measurements showed that for parallel opposed 6 MV photon beams, there was no significant increase in the dose proximal or distal to the plate in either a soft tissue- or bone-equivalent phantom. CONCLUSIONS: The impact of radiation therapy on plate preservation after mandibular reconstructive surgery using a titanium plate may be dependent on the timing of RT relative to surgery. Significantly more mandibular reconstruction plates were lost when the involved mandible received RT in the perioperative period than when RT was delivered beyond 10 months from surgery or when no RT was given. The use of alloplastic implants such as titanium plates in conjunction with myocutaneous flap coverage for mandibular reconstruction is attractive because it allows immediate reconstruction of the defect and promotes a good functional and cosmetic result; however, administration of perioperative RT may result in a higher plate failure rate.

Regional homovanillic acid levels and oral movements in rats following chronic haloperidol treatment.

Rats with more severe orofacial movements after 51 days of haloperidol administration showed lower levels of the dopamine metabolite homovanillic acid (HVA) in the caudate compared to animals who did not develop significant mouth movements. This effect was not observed in other brain regions sampled. This finding is consistent with the hypothesis that dopaminergic receptor supersensitivity in neostriatal structures plays some role in the development of orofacial movements in rats, in association with chronic neuroleptic administration.

Oral and sialochemical findings in patients with autoimmune rheumatic disease.

Forty-two patients with autoimmune rheumatic diseases were evaluated for oral-dental findings and a biopsy of labial minor salivary glands was obtained. Stimulated parotid salivary gland function was assessed and levels of total protein, chloride and albumin in these secretions measured. The patients were stratified into three groups according to the severity of labial gland histopathology (normal histology, 1+ and 2+). Individuals with chronic inflammatory disease of the minor salivary glands had no decrease in stimulated parotid salivary flow but were found to have a greater incidence of oral soft tissue changes commonly associated with salivary dysfunction. However, there were no statistically significant differences in total protein or chloride levels between the groups and no albumin was detected in any samples. These data suggest that stimulated parotid function may be a poor indicator of the extent of salivary involvement in individuals with autoimmune-mediated salivary gland disease.

Connective tissue-associated proteins in crevicular fluid: potential markers for periodontal diseases.

Tests for periodontal disease that are able to detect both ongoing and future loss of clinical attachment would be valuable assets in determining the diagnosis and treatment of periodontal diseases. We hypothesized that connective tissue-associated proteins could be detected in crevicular fluid and would reflect the biochemical activity of the periodontium in health and disease. To test this hypothesis, crevicular fluid samples obtained from patients with various states of periodontal disease were analyzed for the presence of several connective tissue-associated proteins using a dot blot assay. Two such proteins, osteonectin and N-propeptide alpha I type I collagen, were detected in crevicular fluid samples of patients with periodontal disease. Furthermore, the amount of these proteins detected in crevicular fluid appeared to increase with increased probing depth at the sampled site. These studies indicate that measurements of connective tissue-associated proteins in crevicular fluid may prove to be a valuable tool for diagnosing periodontal diseases.

A positive view of safe sex.

AIDS: HIV positive individuals can protect themselves and their partners from sexually transmitted diseases (STDs) while maintaining a healthy expression of sexuality. However, they must employ safer sex practices, as research has proven that seropositive individuals can be reinfected by strains of HIV other than the one that caused their positive HIV tests. The same protective measures apply to both seropositive and seronegative individuals. STDs, such as gonorrhea, syphilis, and chancroid, have been known to be cofactors in HIV transmission and progression. Therefore, HIV-infected individuals must work to avoid these diseases through the practice of safer sex which greatly reduces the risks of infection. Studies show that an HIV-positive individual is more at risk of contracting most infections from an HIV negative sexual partner than the reverse, with the exception of HIV infection itself. The wisest course of action is to always use some form of protection, such as condoms, dental dams, or latex gloves.^ieng

Uptake and secretion of technetium pertechnetate by the rat parotid gland.

The ability of acinar cells of the rat parotid gland to transport technetium pertechnetate (99mTcO-4) was examined. After intravenous injection, 99mTcO-4 was rapidly detected in parotid saliva. There was an excellent correlation between saliva and plasma 99mTcO-4 levels. The saliva to plasma ratio was always less than 1, consistent with the inability of rat parotid gland duct cells to concentrate the anion. Output of 99mTcO-4 by the parotid gland closely mimicked fluctuations in parotid saliva flow rate. In vitro, enzymatically dispersed parotid acinar cells accumulated 99mTcO-4 from the incubation medium in a biphasic manner. This uptake was partially blocked by 10(-4) M NaI. Cells which had accumulated 99mTcO-4 showed increased radionuclide efflux after exposure to 10(-5) M carbachol.

In vitro attachment of bacteria to extracts of cementum.

Cementum is a specialized mineralized tissue providing for the attachment of periodontal fibers to the root surface of a tooth. In periodontal disease this connective tissue attachment to the cemental surface is lost. The ability of bacteria to adhere to the root surface, an initial event in the disease process, may be influenced by the organic matrix of cementum. Therefore, an in vitro assay of cell attachment was modified to study bacterial adherence to protein extracts of cementum. Petri dishes coated with the extracts were pre-incubated in culture media and then bacteria were added. Using this assay, Capnocytophaga-like species, a gram negative bacterium implicated in periodontal disease, attached preferentially to dishes coated with cemental extracts when compared with Type I collagen or uncoated dishes. This assay system should prove beneficial for studying the attachment of various microorganisms to protein extracts of both normal and diseased cementum, as well as providing insight into the unique attachment properties of cementum.