Adjuvant Therapy With Sodium Alendronate for the Treatment of Experimental Periodontitis in Rats

Background: This study assesses the effects of topical sodium alendronate (SA) as an adjuvant to the mechanical treatment of ligature‐induced periodontitis in rats. Methods: Ninety animals were subjected to the induction of periodontitis via the installation of a ligature around the mandibular left first molar. After 7 days, the ligature was removed, and the animals were distributed into the following groups: 1) NT group (n = 30), no treatment; 2) SRP group (n = 30), scaling and root planing (SRP) and local irrigation with physiologic saline solution; and 3) SRP/SA group (n = 30), SRP and local irrigation with SA (10^?5 M). Ten animals from each group were euthanized at 7, 15, and 30 days after treatment. Histologic and histometric analyses were performed in the furcation region. The percentage of bone in the furcation (PBF) was measured. Immunohistochemical analyses for detecting the receptor activator of nuclear factor‐κB ligand (RANKL), osteoprotegerin (OPG), tartrate‐resistant acid phosphatase (TRAP), and activated caspase‐3 were performed at the furcation region. Results: Compared with the other groups, the SRP/SA group showed less local inflammation and better tissue reparation during the entire experiment. There was more PBF in the SRP/SA group than in the other groups at days 7 and 15. Stronger OPG immunolabeling and weaker RANKL immunolabeling were observed in the SRP/SA group at 15 and 30 days. There were fewer TRAP‐positive cells in the SRP/SA group than in the NT group at all of the time points. There was no difference in the number of activated caspase‐3‐positive osteocytes among groups and time points. Conclusion: It can be concluded that topical use of SA as an adjuvant to SRP is effective in the treatment of experimental periodontitis.     

Immunophenotypic Profile and Increased Risk of Hospital Admission for Infection in Infants Born to Female Kidney Transplant Recipients

Children born to female kidney recipients are exposed to immunosuppressive drugs during gestation. Little is known about their immune system at birth or in the long term. Twenty‐eight children born to female kidney recipients and 40 full‐term children born to healthy mothers were evaluated. T, B, NK, NKT, γδT cells were assessed by flow cytometry and functional evaluation of T and dendritic cells after in vitro activation was performed at birth and at 8 months of age. At birth, infants born to female kidney recipients showed lower numbers of CD4+ T, NKT and intense reduction of B cells (median cells/mm³, transplant: 153.7 X control: 512.4; p < 0.001). There was also a reduced percentage of activated CD8+ T and of CD4+ regulatory T cells. Activated memory and exhausted memory B cells showed higher percentages among children exposed to immunosuppressors when compared to control group. At 8 months, most immune alterations were no longer observed, but four children still had low numbers of some lymphocyte subsets at this age. Children born to female kidney recipients had 4.351 (95% CI: 1.026–15.225; p = 0.046) higher risk of hospital admission in the first months of life—some, with severe clinical manifestations—than those born to healthy women.     

Restricted dendritic cell and monocyte progenitors in human cord blood and bone marrow

In mice, two restricted dendritic cell (DC) progenitors, macrophage/dendritic progenitors (MDPs) and common dendritic progenitors (CDPs), demonstrate increasing commitment to the DC lineage, as they sequentially lose granulocyte and monocyte potential, respectively. Identifying these progenitors has enabled us to understand the role of DCs and monocytes in immunity and tolerance in mice. In humans, however, restricted monocyte and DC progenitors remain unknown. Progress in studying human DC development has been hampered by lack of an in vitro culture system that recapitulates in vivo DC hematopoiesis. Here we report a culture system that supports development of CD34⁺ hematopoietic stem cell progenitors into the three major human DC subsets, monocytes, granulocytes, and NK and B cells. Using this culture system, we defined the pathway for human DC development and revealed the sequential origin of human DCs from increasingly restricted progenitors: a human granulocyte-monocyte-DC progenitor (hGMDP) that develops into a human monocyte-dendritic progenitor (hMDP), which in turn develops into monocytes, and a human CDP (hCDP) that is restricted to produce the three major DC subsets. The phenotype of the DC progenitors partially overlaps with granulocyte-macrophage progenitors (GMPs). These progenitors reside in human cord blood and bone marrow but not in the blood or lymphoid tissues.DCs, monocytes, and macrophages are closely related cell types whose interrelationship were long debated and only recently elucidated in the mouse (Geissmann et al., 2010; Merad et al., 2013). In mice, DCs and monocytes arise from a macrophage/dendritic progenitor (MDP; Fogg et al., 2006), which produces monocytes, and a common dendritic progenitor (CDP) that is restricted to the DC fate (Shortman and Naik, 2007; Liu et al., 2009; Geissmann et al., 2010; Merad et al., 2013). The CDP produces pre–plasmacytoid DCs (pDCs) and pre–conventional DCs (cDCs), the latter of which leaves the BM and circulates in the blood before entering tissues and developing into the different DCs subsets (Naik et al., 2006, 2007; Onai et al., 2007b, 2013; Ginhoux et al., 2009; Liu et al., 2009; Onai et al., 2013).In the mouse, DC differentiation is dependent on a hematopoietin, Flt3L, whose receptor, Flt3 (CD135), is expressed throughout DC development (McKenna et al., 2000; Karsunky et al., 2003; Waskow et al., 2008). In contrast, other hematopoietin receptors such as monocyte colony-stimulating factor receptor (M-CSFR or CD115) and granulocyte macrophage colony-stimulating factor receptor (GM-CSFR or CD116) are restricted to hematopoietic progenitors of DCs but not expressed on all mature DCs (Kingston et al., 2009).DC development in the human is far less well understood than in the mouse. Human monocytes can be induced to differentiate into potent antigen-presenting cells with some phenotypic features of DCs after in vitro culture with cocktails of cytokines (Sallusto and Lanzavecchia, 1994). However, these monocyte-derived DCs are more closely related to activated monocytes than to cDCs (Naik et al., 2006; Xu et al., 2007; Cheong et al., 2010; Crozat et al., 2010). Progress in defining the human DC lineage has been hampered, in part, by a paucity of reliable markers to distinguish these cells from monocytes, limited access to human tissues, the relatively small number of circulating DCs in blood, and the lack of a robust tissue culture system for the in vitro development of all DC subsets (Poulin et al., 2010; Ziegler-Heitbrock et al., 2010; Proietto et al., 2012).Here we report a stromal cell culture system that supports the development of CD34⁺ hematopoietic stem cell (HSC) progenitors into the three major subsets of human DCs, monocytes, granulocytes, and NK and B cells. Using this culture system, we have been able to define the sequential origin of human DCs from a human granulocyte-monocyte-DC progenitor (hGMDP), which develops into a more restricted human monocyte-dendritic progenitor (hMDP), which produces monocytes, and a human CDP (hCDP), which is restricted to produce the three major subsets of DCs.     

Successful Treatment of Carbapenemase-Producing Pandrug-Resistant Klebsiella pneumoniae Bacteremia

New antibiotic options are urgently needed for the treatment of carbapenem-resistant Enterobacteriaceae infections. We report a 64-year-old female with prolonged hospitalization following an intestinal transplant who developed refractory bacteremia due to a serine carbapenemase-producing pandrug-resistant isolate of Klebsiella pneumoniae. After failing multiple antimicrobial regimens, the patient was successfully treated.     

Preclinical In Vitro Assessment of Submicron-Scale Laser Surface Texturing on Ti6Al4V

Loosening of orthodontic and orthopedic implants is a critical and common clinical problem. To minimize the numbers of revision surgeries due to peri-implant inflammation or insufficient osseointegration, developments of new implant manufacturing strategies are indicated. Ultrafast laser surface texturing is a promising contact-free technology to modify the physicochemical properties of surfaces toward an anti-infectious functionalization. This work aims to texture Ti6Al4V surfaces with ultraviolet (UV) and green (GR) radiation for the manufacturing of laser-induced periodic surface structures (LIPSS). The assessment of these surface modifications addresses key aspects of topography, morphology and chemical composition. Human primary mesenchymal stromal cells (hMSCs) were cultured on laser-textured and polished Ti6Al4V to characterize the surfaces in terms of their in vitro biocompatibility, cytotoxicity, and metal release. The outcomes of the in vitro experiment show the successful culture of hMSCs on textured Ti6Al4V surfaces developed within this work. Cells cultured on LIPSS surfaces were not compromised in terms of their viability if compared to polished surfaces. Yet, the hMSC culture on UV-LIPSS show significantly lower lactate dehydrogenase and titanium release into the supernatant compared to polished. Thus, the presented surface modification can be a promising approach for future applications in orthodontics and orthopedics.     

The European Histamine Research Society43rd Annual Meeting,May 7–10, 2014Lyon,France

Idiopathic nephrotic syndrome (INS) is a multifactorial disease, characterized by proteinuria, hypoalbuminemia, edema and hyperlipidemia. Studies in humans and animal models have associated INS with changes in the immune response. The purpose of this article is to review clinical and experimental findings showing the involvement of the immune response in the pathogenesis of INS. The role of the immune system in INS has been shown by clinical and experimental studies. However, the pattern of immune response in patients with INS is still not clearly defined. Many studies show changes in the dynamics of T lymphocytes, especially the regulatory T cells. Alternatively, there are other reports regarding the involvement of the complement system and B lymphocytes in the pathophysiology of INS. Indeed, none of the immunological biomarkers evaluated were undeniably linked to changes in glomerular permeability and proteinuria. On the other hand, some studies suggest a link between urinary chemokines, such as IL-8/CXCL8 and MCP-1/CCL2, and changes in glomerular permeability and/or the deterioration of glomerulopathies. To understand the pathophysiology of INS, longitudinal studies are clearly needed. The characterization of the profile of the immune response might help the development of specific and individualized therapies, leading to clinical improvement and better prognosis.