This work explores the synthesis, physicochemical characterization, and in vivo biocompatibility of ironbased layered double hydroxides (LDHs) with molar ratio M 2+ /(Fe 3+ + Al 3+ ) equal to 2, Fe 3+ /Al 3+ equal to 1, and chloride anions as charge-compensating ion (abbreviated Mg 4 FeAl-Cl and Zn 4 FeAl-Cl) prepared by the coprecipitation method. The higher structural organization of Zn 4 FeAl-Cl in comparison to Mg 2+ analogous material was noticed by X-ray diffraction and scanning electron microscopy images. Biocompatibility of LDH was evaluated by intramuscular implantation in rats. Tablets of M 4 FeAl-Cl (M = Mg, Zn) were readily identified macroscopically after 7 and 28 days of implantation, denoting slow dissolution in the internal medium; adjacent to the tablets, blood flow was preserved without tortuosity or pathological dilatations, according to the Sidestream Dark Field Imaging technique. The histological analysis showed no inflammatory response and the presence of angiogenesis and tissue remodeling with the reconstruction of the extracellular matrix and cells around the tablets, besides the induction of collagen type-I formation. Prussian blue histochemical reaction suggested higher solubility of Mg 4 FeAl-Cl in the extracellular matrix compared to zinc LDH. Considering the positive biocompatibility results obtained for M 4 II FeAl-LDH materials, experiments were conducted to intercalate the anti-inflammatory naproxen, as a model drug, into the iron-based LDHs (M 4 II FeAl-NAP). The release profile of NAP in phosphate buffer showed 90% of the drug delivered after about 80 h. However, divalent metal leaching was verified mainly for Mg-LDH (around 50%) when compared to Zn 2+ (around 1%). Iron-based LDHs have great potential for medical and technological applications as local drug delivery biomaterials exhibiting biocompatibility and biointegration properties.

Biocompatibility of layered double hydroxides (LDHs), also known as hydrotalcite-like materials or double metal hydroxides, was investigated by in vivo assays via intramuscular tablets implantation in rat abdominal wall. The tablets were composed by chloride ions intercalated into LDH of magnesium/aluminum (Mg2Al-Cl) and zinc/aluminum (Zn2Al-Cl). The antigenicity and tissue integration capacity of LDHs were assessed histologically after 7 and 28 days post-implantation. No fibrous capsule nearby the LDH was noticed for both materials as well any sign of inflammatory reactions. Sidestream Dark Field imaging, used to monitor in real time the microcirculation in tissues, revealed overall integrity of the microcirculatory network neighboring the tablets, with no blood flow obstruction, bleeding and/or increasing of leukocyte endothelial adhesion. After 28 days Mg2Al-Cl promoted multiple collagen invaginations (mostly collagen type-I) among its fragments while Zn2Al-Cl induced predominantly collagen type–III. This work supports previous results in the literature about LDHs compatibility with living matter, endorsing them as functional materials for biomedical applications.

The effect of LDH samples comprised of chloride anions intercalated between positive layers of magnesium/aluminum (Mg-Al LDH) or zinc/aluminum (Zn-Al LDH) chemical composition on pre-osteoblast performance is investigated. Non-cytotoxic concentrations of both LDHs modulated pre-osteoblast adhesion by triggering cytoskeleton rearrangement dependent on recruiting of Cofilin, which is modulated by the inhibition of the Protein Phosphatase 2A (PP2A), culminating in osteoblast differentiation with a significant increase of osteogenic marker genes. The alkaline phosphatase (ALP) and bone sialoprotein (BSP) are significantly up-modulated by both LDHs; however, Mg-Al LDH nanomaterial promoted even more significance than both experimental controls, while the phosphorylations of mitogen-activated protein kinase (MAPKs)- extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinase (JNK) significantly increased. MAPK signaling is necessary to activate Runt-related transcription factor 2 (RUNX2) gene. Concomitantly, it is also investigated whether challenged osteoblasts are able to modulate osteoclastogenesis by investigating both osteoprotegerin (OPG) and Receptor activator of nuclear factor kappa-ligand (RANKL) in this model; a dynamic reprogramming of both these genes is found, suggesting LDHs in modulating osteoclastogenesis. These results suggest that LDHs interfere in bone remodeling, and they can be considered as nanomaterials in graft-based bone healing or drug-delivery materials for bone disorders.

The greater incidence of capsular contracture in smooth implants was correlated with the progressive increase in total capsule thickness, due to a higher concentration of collagenous fibers, when compared with textured implants (p = 0.011; mean difference, 6.61), and a higher concentration of thick fibers (p = 0.034; average, >5.51 percentage points per field of thick fibers than the textured implants in all periods). Pigs are good animal models for studying the healing process after breast augmentation with implants.

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Diarrhea is the second leading cause of death of children up to five years old in the developing countries. Among the etiological diarrheal agents are atypical enteropathogenic Escherichia coli (aEPEC), one of the diarrheagenic E. coli pathotypes that affects children and adults, even in developed countries. Currently, genotypic and biochemical approaches have helped to demonstrate that some strains classified as aEPEC are actually E. albertii, a recently recognized human enteropathogen. Studies on particular strains are necessary to explore their virulence potential in order to further understand the underlying mechanisms of E. albertii infections. Here we demonstrated for the first time that infection of fragments of rat intestinal mucosa is a useful tool to study the initial steps of E. albertii colonization. We also observed that an E. albertii strain can translocate from the intestinal lumen to Mesenteric Lymph Nodes and liver in a rat model. Based on our finding of bacterial translocation, we investigated how E. albertii might cross the intestinal epithelium by performing infections of M-like cells in vitro to identify the potential in vivo translocation route. Altogether, our approaches allowed us to draft a general E. albertii infection route from the colonization till the bacterial spreading in vivo.

Experimental models of sepsis-induced pulmonary alterations are important for the study of pathogenesis and for potential intervention therapies. The objective of the present study was to characterize lung dysfunction (low PaO 2 and high PaCO 2 , and increased cellular infiltration, protein extravasation, and malondialdehyde (MDA) production assessed in bronchoalveolar lavage) in a sepsis model consisting of intraperitoneal (ip) injection of Escherichia coli and the protective effects of pentoxifylline (PTX). Male Wistar rats (weighing between 270 and 350 g) were injected ip with 10 7 or 10 9 CFU/100 g body weight or saline and samples were collected 2, 6, 12, and 24 h later (N = 5 each group). PaO 2 , PaCO 2 and pH were measured in blood, and cellular influx, protein extravasation and MDA concentration were measured in bronchoalveolar lavage. In a second set of experiments either PTX or saline was administered 1 h prior to E. coli ip injection (N = 5 each group) and the animals were observed for 6 h. Injection of 10 7 or 10 9 CFU/100 g body weight of E. coli induced acidosis, hypoxemia, and hypercapnia. An increased (P < 0.05) cell influx was observed in bronchoalveolar lavage, with a predominance of neutrophils. Total protein and MDA concentrations were also higher (P < 0.05) in the septic groups compared to control. A higher tumor necrosis factor-alpha (P < 0.05) concentration was also found in these animals. Changes in all parameters were more pronounced with the higher bacterial inoculum. PTX administered prior to sepsis reduced (P < 0.05) most functional alterations. These data show that an E. coli ip inoculum is a good model for the induction of lung dysfunction in sepsis, and suitable for studies of therapeutic interventions. Correspondence

Sepsis is the result from a complex bacterial-host interaction, which is an often-fatal response when host protective molecular mechanisms designed to fight invading bacteria surpass the beneficial intensity to the point of causing injury to the host. Increasing evidences have implicated the bacterial translocation (BT) as the main source for the induction of sepsis, although the beneficial effect of BT process has been related to the development of the intestinal immune response by physiological interaction between bacteria and host. In this article, we examined evolving concepts concerning to BT and discussed about its potential role in the promotion of microcirculation injury, moreover, its possible participation in the sepsis induction. According to our data obtained from in-vivo BT animal-model, both bacterial overgrowth and bacterial pathogenic determinants seem to be major predisposing factors for the induction of BT. Besides, translocation of luminal bacteria through the lymphatic via elicits the activation of the GALT inflammatory response contributing to microcirculation injuries, and the haematological via of BT was responsible to the systemic bacterial spread. On other hand, the combination of BT process to the pre-existing host systemic infection played a crucial role in the worsening of the clinical outcome. In our understanding, studies concerning to intestinal immune response and the pathophysiology of bacterial-host interaction, under normal and disease conditions, seems to be the key elements to the development of therapeutic approaches towards sepsis.