Estrogens are known modulators of monocyte/macrophage functions; however, the underlying mechanism has not been clearly defined. Recently, a number of estrogen receptor molecules and splice variants were identified that exert different and sometimes opposing actions. We assessed the expression of estrogen receptors and explored their role in mediating estrogenic anti-inflammatory effects on human primary monocytes. We report that the only estrogen receptors expressed are estrogen receptor-α 36-kDa splice variant and G-protein coupled receptor 30/G-protein estrogen receptor 1, in a sex-independent manner. 17-β-Estradiol inhibits the LPS-induced IL-6 inflammatory response, resulting in inhibition of NF-κB transcriptional activity. This is achieved via a direct physical interaction of ligand-activated estrogen receptor-α 36-kDa splice variant with the p65 component of NF-κB in the nucleus. G-protein coupled receptor 30/G-protein estrogen receptor 1, which also physically interacts with estrogen receptor-α 36-kDa splice variant, acts a coregulator in this process, because its inhibition blocks the effect of estrogens on IL-6 expression. However, its activation does not mimic the effect of estrogens, on neither IL-6 nor NF-κB activity. Finally, we show that the estrogen receptor profile observed in monocytes is not modified during their differentiation to macrophages or dendritic cells in vitro and is shared in vivo by macrophages present in atherosclerotic plaques. These results position estrogen receptor-α 36-kDa splice variant and G-protein coupled receptor 30 as important players and potential therapeutic targets in monocyte/macrophage-dependent inflammatory processes.

SummaryBone deficits of the jaws are often attributed to accidents, surgical removal of benign lesions or malignant neoplasms, congenital abnormalities, periodontal inflammation, tooth abscess or extraction and finally jaw atrophy due to advanced age or general disease.These bone defects require rehabilitation for a variety of reasons, e.g. maintaining the normal anatomic outline, eliminating empty space, aesthetic restoration and placing dental implants. Today, several techniques have been developed to eliminate these bone deformities including bone grafting, guided bone regeneration, distraction osteogenesis, use of growth factors and stem cells.Bone grafts consist of materials of natural or synthetic origin, implanted into the bone defect site, documented to possess bone healing properties. Currently, a variety of bone restorative materials with different characteristics are available, possesing different properties.Despite years of effort the ‘perfect’ bone reconstruction material has not yet been developed, a further effort is required to make this objective feasible.The aim of this article is to provide a contemporary and comprehensive overview of the grafting materials that can be applied in dentoalveolar reconstruction, discussing their properties, advantages and disadvantages, enlightening the present and the future perspectives in the field of bone regeneration.

The aim of this study was to investigate the healing of human extraction sockets filled with β-tricalcium phosphate and type I collagen (β-TCP/Clg) cones with or without a barrier membrane. Twenty patients were divided in two groups: (A) β-TCP/Clg non-membrane and (B) β-TCP/Clg + barrier membrane. Clinical examination and biopsies from the grafted sites were collected 9 months later. Bone samples were analyzed using histomorphometry and immunohistochemistry. The horizontal dimension of the alveolar ridge was significantly reduced 9 months after socket preservation in the non-membrane group. There was bone formation with no significant differences between the two groups in the areas occupied by new bone (A = 42.4%; B = 45.3%), marrow (A = 42.7%; B = 35.7%), or residual graft (A = 9.7%; B = 12.5%). Immunohistochemistry revealed osteonectin expression in both groups. Both groups demonstrated sufficient amounts of vital bone and socket morphology to support dental implant placement after the 9-month healing period. A future trial to evaluate the alveolar outcomes at an earlier 6-month time point rather than the 9 months used in this study would be of interest.

Although these results need replication and further biomechanical research, PRP may promote tendon healing acceleration.

In our study, the mechanical properties of the regenerated tendon in the PRP group were significantly improved in relation to the control group. It appears that PRP has a strong effect in the early phase of tendon healing. This effect is probably due to the growth factors that are released from the platelets during activation.

Purpose:To describe the pharmacokinetics of intravitreal bevacizumab (Avastin®) in rabbits.Methods:The right eye of 20 rabbits was injected intravitreally with 1.25 mg/0.05 mL bevacizumab. Both eyes of four rabbits each time were enucleated at days 1, 3, 8, 15, and 29. Bevacizumab concentrations were measured in serum, aqueous humor, and vitreous.Results:Maximum vitreous (406.25 μg/mL) and aqueous humor (5.83 μg/mL) concentrations of bevacizumab in the right eye were measured at day 1. Serum bevacizumab concentration peaked at day 8 (0.413 μg/mL) and declined to 0.032 μg/mL at 4 weeks. Half-life values in right vitreous, right aqueous humor, and serum were 6.61, 6.51, and 5.87 days, respectively. Concentration of bevacizumab in the vitreous of the noninjected eye peaked at day 8 (0.335 ng/mL) and declined to 0.218 ng/mL at 4 weeks. In the aqueous humor of the noninjected eye, maximum concentration of bevacizumab was achieved at day 8 (1.6125 ng/mL) and declined (to 0.11 ng/mL) at 4 weeks.Conclusion:The vitreous half-life of 1.25 mg/0.05 mL intravitreal bevacizumab was 6.61 days in this rabbit model. Maximum concentrations of bevacizumab were reached at day 1 in both vitreous and aqueous humor of the right eye and at day 8 in the serum. Very low concentrations of bevacizumab were measured in the fellow noninjected eye.

Laboratory control animal study.

BackgroundAdvanced glycation end products (AGEs) and their receptor RAGE emerge as important pathogenic contributors in colorectal carcinogenesis. However, their relationship to the detoxification enzyme Glyoxalase (GLO)-I and Adiponectin receptors (AdipoR1, AdipoR2) in colorectal carcinoma (CRC) is currently understudied. In the present study, we investigated the expression levels of the above molecules in CRC compared to adjacent non-tumoral tissue and their potential correlation with clinicopathological characteristics and patients’ survival.MethodsWe analyzed the immunohistochemical expression of AGE, RAGE, GLO-1, AdipoR1 and AdipoR2 in 133 primary CRC cases, focusing on GLO-I. The tumour MSI status was further assessed in mucinous carcinomas. Western immunoblotting was employed for validation of immunohistochemical data in normal and tumoral tissues as well in three CRC cell lines. An independent set of 55 patients was also used to validate the results of univariate survival analysis regarding GLO-I.ResultsCRC tissue showed higher intensity of both AGE and RAGE expression compared with normal colonic mucosa which was negative for GLO-I in most cases (78 %). Western immunoblotting confirmed AGE, RAGE and GLO-I overexpression in tumoral tissue. GLO-I expression was directly related to RAGE and inversely related to AGE immunolabeling. There was a trend towards higher expression of all markers (except for RAGE) in the subgroup of mucinous carcinomas which, although of borderline significance, seemed to be more prominent for AdipoR1 and AGE. Additionally, AGE, AdipoR1 and Adipo R2 expression was related to tumor grade, whereas GLO-1 and AdipoR1 to T-category. In survival analysis, AdipoR2 and GLO-I overexpression predicted shortened survival in the entire cohort and in early stage cases, an effect which for GLO-I was reproduced in the validation cohort. Moreover, GLO-I emerged as an independent prognosticator of adverse significance in the patients’ cohort.ConclusionsWe herein provide novel evidence regarding the possible interactions between the components of AGE-RAGE axis, GLO-I and adiponectin receptors in CRC. AGE and AdipoR1 are possibly involved in colorectal carcinogenesis, whereas AdipoR2 and GLO-I emerged as novel independent prognostic biomarkers of adverse significance for patients with early disease stage. Further studies are warranted to extend our observations and investigate their potential therapeutic significance.