Refractory esophagitis caused by Candida nivariensis: second description of this yeast in Brazil and a literature review.

Candida nivariensis caused refractory esophagitis in a 36-year-old Brazilian man coinfected with HIV and Leishmania. A literature review on this rare fungal pathogen is also presented. The diagnosis was made, and pathogen identification was performed using matrix-assisted laser desorption ionization-time of flight mass spectrometry and sequencing of the LSU/26S region. An antifungigram was performed using broth microdilution. A literature search of PubMed was performed. The causative agent, C. nivariensis, was resistant to fluconazole and voriconazole. The patient's condition worsened considerably, and he passed away. This is the second report of this Candida species in Brazil and the first case reported worldwide of refractory esophagitis in a patient coinfected with HIV and Leishmania. The case illustrates the importance of precise identification and antifungal susceptibility testing when isolating this emerging pathogen.

Enhancement of Bone Healing by Local Administration of Carbon Nanotubes Functionalized with Sodium Hyaluronate in Rat Tibiae.

It has been reported that carbon nanotubes (CNTs) serve as nucleation sites for the deposition of bone matrix and cell proliferation. Here, we evaluated the effects of multi-walled CNTs (MWCNTs) on bone repair of rat tibiae. Furthermore, because sodium hyaluronate (HY) accelerates bone restoration, we associated CNTs with HY (HY-MWCNTs) in an attempt to boost bone repair. The bone defect was created by a 1.6-mm-diameter drill. After 7 and 14 days, tibiae were processed for histological and morphometric analyses. Immunohistochemistry was used to evaluate the expression of vascular endothelial growth factor (VEGF) in bone defects. Expression of osteocalcin (OCN), bone morphogenetic protein-2 (BMP-2), and collagen I (Col I) was assessed by real-time PCR. Histomorphometric analysis showed a similar increase in the percentage of bone trabeculae in tibia bone defects treated with HY and HY-MWCNTs, and both groups presented more organized and thicker bone trabeculae than nontreated defects. Tibiae treated with MWCNTs or HY- MWCNTs showed a higher expression of VEGF. Treatment with MWCNTs or HY-MWCNTs increased the expression of molecules involved in the bone repair process, such as OCN and BMP-2. Also, HY- and MWCNT-treated tibiae had an increased expression of Col I. Thus, it is tempting to conclude that CNTs associated or not with other materials such as HY emerged as a promising biomaterial for bone tissue engineering.

Scale/topography of substrates surface resembling extracellular matrix for tissue engineering.

Biomaterial matrices are being developed that mimic the key characteristics of the extracellular matrix, including presenting adhesion sites and displaying growth factors in the context of a viscoelastic hydrogel. This review focuses on two classes of materials: those that are derived from naturally occurring molecules and those that recapitulate key motifs of biomolecules within biologically active synthetic materials. We also discussed some of the most significant biological features of the ECM, and several engineering methods currently being implemented to design and tune synthetic scaffolds to mimic these features. Understanding the cell-protein-material interaction is fundamental for developing more powerful tools in tissue engineering and regenerative medicine strategies. The design of model substrates including the presence of well-defined properties (chemistry, topography, stiffness) and even the gradient of these properties in three dimensional environments must lead in the near future to learn more about the specific roles of protein adsorption and the very dynamic process related to the cell fate of synthetic substrates: cell adhesion, matrix reorganisation, deposition and degradation at the cell-material interface. These materials will open new doors to biosurgical therapeutics in tissue engineering and regenerative medicine.

Human adult stem cells from diverse origins: an overview from multiparametric immunophenotyping to clinical applications.

Stem cells are known for their capacity to self-renew and differentiate into at least one specialized cell type. Mesenchymal stem cells (MSCs) were isolated initially from bone marrow but are now known to exist in all vascularized organ or tissue in adults. MSCs are particularly relevant for therapy due to their simplicity of isolation and cultivation. The International Society for Cellular Therapy (ISCT) has proposed a set of standards to define hMSCs for laboratory investigations and preclinical studies: adherence to plastic in standard culture conditions; in vitro differentiation into osteoblasts, adipocytes, and chondroblasts; specific surface antigen expression in which ≥95% of the cells express the antigens recognized by CD105, CD73, and CD90, with the same cells lacking (≤2% positive) the antigens CD45, CD34, CD14 or CD11b, CD79a or CD19, and HLA-DR. In this review we will take an historical overview of how umbilical cord blood, bone marrow, adipose-derived, placental and amniotic fluid, and menstrual blood stem cells, the major sources of human MSC, can be obtained, identified and how they are being used in clinical trials to cure and treat a very broad range of conditions, including heart, hepatic, and neurodegenerative diseases. An overview of protocols for differentiation into hepatocytes, cardiomyocytes, neuronal, adipose, chondrocytes, and osteoblast cells are highlighted. We also discuss a new source of stem cells, induced pluripotent stem cells (iPS cells) and some pathways, which are common to MSCs in maintaining their pluripotent state.

Altered responsiveness to extracellular ATP enhances acetaminophen hepatotoxicity.

BACKGROUND: Adenosine triphosphate (ATP) is secreted from hepatocytes under physiological conditions and plays an important role in liver biology through the activation of P2 receptors. Conversely, higher extracellular ATP concentrations, as observed during necrosis, trigger inflammatory responses that contribute to the progression of liver injury. Impaired calcium (Ca2+) homeostasis is a hallmark of acetaminophen (APAP)-induced hepatotoxicity, and since ATP induces mobilization of the intracellular Ca2+ stocks, we evaluated if the release of ATP during APAP-induced necrosis could directly contribute to hepatocyte death. RESULTS: APAP overdose resulted in liver necrosis, massive neutrophil infiltration and large non-perfused areas, as well as remote lung inflammation. In the liver, these effects were significantly abrogated after ATP metabolism by apyrase or P2X receptors blockage, but none of the treatments prevented remote lung inflammation, suggesting a confined local contribution of purinergic signaling into liver environment. In vitro, APAP administration to primary mouse hepatocytes and also HepG2 cells caused cell death in a dose-dependent manner. Interestingly, exposure of HepG2 cells to APAP elicited significant release of ATP to the supernatant in levels that were high enough to promote direct cytotoxicity to healthy primary hepatocytes or HepG2 cells. In agreement to our in vivo results, apyrase treatment or blockage of P2 receptors reduced APAP cytotoxicity. Likewise, ATP exposure caused significant higher intracellular Ca2+ signal in APAP-treated primary hepatocytes, which was reproduced in HepG2 cells. Quantitative real time PCR showed that APAP-challenged HepG2 cells expressed higher levels of several purinergic receptors, which may explain the hypersensitivity to extracellular ATP. This phenotype was confirmed in humans analyzing liver biopsies from patients diagnosed with acute hepatic failure. CONCLUSION: We suggest that under pathological conditions, ATP may act not only an immune system activator, but also as a paracrine direct cytotoxic DAMP through the dysregulation of Ca2+ homeostasis.