Hyaluronate Protects From Benzalkonium Chloride-Induced Ocular Surface Toxicity.

Purpose: The purpose of this study was to investigate the effect of sodium hyaluronate (SH) on benzalkonium chloride (BAK)-induced toxicity in the ocular surface epithelium and corneal nerves.

Methods: Ocular surface epithelial cells from Balb/c mice were cultured with 0.1% to 0.

Treatment of Chronic Haemophilic Synovitis with PRP: Clinical and Studies.

Intra-articular blood, iron and hemosiderin, hydroxyl radical cytokines, and neo-angiogenesis cause synovial inflammation, which leads to cartilage and joint damage. Platelet-rich plasma (PRP) inhibits most of the mediators that produce and maintain synovitis. We compile here our work showing the clinical effectiveness of intra-articular PRP injections and their potential role in stopping articular cartilage damage due to bleeding and its possible repair.

Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye.

Corneal nerve impairment contributes significantly to dry eye disease (DED) symptoms and is thought to be secondary to corneal epithelial damage. Transient receptor potential vanilloid-1 (TRPV1) channels abound in corneal nerve fibers and respond to inflammation-derived ligands, which increase in DED. TRPV1 overactivation promotes axonal degeneration in vitro, but whether it participates in DED-associated corneal nerve dysfunction is unknown.

An ocular Th1 immune response promotes corneal nerve damage independently of the development of corneal epitheliopathy.

Proper sight is not possible without a smooth, transparent cornea, which is highly exposed to environmental threats. The abundant corneal nerves are interspersed with epithelial cells in the anterior corneal surface and are instrumental to corneal integrity and immunoregulation. Conversely, corneal neuropathy is commonly observed in some immune-mediated corneal disorders but not in others, and its pathogenesis is poorly understood.

Ectopic lymphoid structures in the aged lacrimal glands.

Aging is a complex biological process in which many organs are pathologically affected. We previously reported that aged C57BL/6J had increased lacrimal gland (LG) lymphoid infiltrates that suggest ectopic lymphoid structures. However, these ectopic lymphoid structures have not been fully investigated.

DNA extracellular traps as potential biomarker of chronic haemophilic synovitis and therapeutic perspective in patients treated with PRP: A pilot study.

Introduction: Hemarthrosis causes chronic haemophilic synovitis (CHS). Although neutrophils are major immune cells infiltrating joints after bleeding, their role on the pathogenesis of CHS is unknown. Neutrophils release extracellular DNA traps (ETs), structures of DNA with bound granular enzymes that were associated with tissue damage.

PRP in wound healing applications.

Platelets play a crucial role in hemostasis, tissue regeneration and host defense. Based on these settings, platelet-rich plasma (PRP) and its derivatives are therapeutically used to promote wound healing in several scenarios. This review summarizes the biological mechanisms underlying the most traditional as well as innovative applications of PRP in wound healing.

SLAMF1 signaling induces Mycobacterium tuberculosis uptake leading to endolysosomal maturation in human macrophages.

Tuberculosis dates back to ancient times but it is not a problem of the past. Each year, millions of people die from tuberculosis. After inhalation of infectious droplet nuclei, Mycobacterium tuberculosis reaches the lungs where it can manipulate the immune system and survive within host macrophages, establishing a persistent infection.

Inhibition of Fenton reaction is a novel mechanism to explain the therapeutic effect of intra-articular injection of PRP in patients with chronic haemophilic synovitis.

Introduction And Aim: Haemarthroses cause major morbidity in haemophilia resulting in chronic haemophilic synovitis (CHS) and arthropathy. Oxidation of haemoglobin-coupled iron released in synovium after haemolysis induces chondrocytes death and cartilage damage, allowing postulate using iron-chelating drugs as potential therapeutic tool for haemophilic joint damage. Considering that albumin, the most abundant plasma protein, is a physiologic iron chelator, we aim to demonstrate that impediment of haemoglobin oxidation is exerted by plasma as a mechanism involved in the therapeutic effect of intra-articular injection of platelet-rich plasma in CHS.

Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages.

While tuberculosis (TB) is a risk factor in HIV-1-infected individuals, the mechanisms by which (Mtb) worsens HIV-1 pathogenesis remain scarce. We showed that HIV-1 infection is exacerbated in macrophages exposed to TB-associated microenvironments due to tunneling nanotube (TNT) formation. To identify molecular factors associated with TNT function, we performed a transcriptomic analysis in these macrophages, and revealed the up-regulation of Siglec-1 receptor.

Surveillance and characterization of drug-resistant isolated in a reference hospital from Argentina during 8 years' period.

Background: Argentina is considered a country with a middle tuberculosis (TB) incidence. However, according to the last national epidemiological report released in 2018, since 2013, the trends are steadily increasing. The aims of this study were to determine the drug-resistance (DR), multi-DR and extensively DR (MDR/XDR-TB), and rifampicin resistance (RIF-R) burden as a part of the local TB diagnosis (June 2010-August 2018); to detect the mutations associated to isoniazid (INH) and RIF-R and their geographical distribution; and to analyze the lineage relationship among the genetic patterns of the isolates circulating in the community.

Activation of toll-like receptors 2 and 4 on CD34 cells increases human megakaryo/thrombopoiesis induced by thrombopoietin.

Background: Platelet Toll-like receptor (TLR)2/4 are key players in amplifying the host immune response; however, their role in human megakaryo/thrombopoiesis has not yet been defined.

Objectives: We evaluated whether Pam3CSK4 or lipopolysaccharide (LPS), TLR2/4 ligands respectively, modulate human megakaryocyte development and platelet production.

Methods: CD34 cells from human umbilical cord were stimulated with LPS or Pam3CSK4 with or without thrombopoietin (TPO).

Tuberculosis Exacerbates HIV-1 Infection through IL-10/STAT3-Dependent Tunneling Nanotube Formation in Macrophages.

The tuberculosis (TB) bacillus, Mycobacterium tuberculosis (Mtb), and HIV-1 act synergistically; however, the mechanisms by which Mtb exacerbates HIV-1 pathogenesis are not well known. Using in vitro and ex vivo cell culture systems, we show that human M(IL-10) anti-inflammatory macrophages, present in TB-associated microenvironment, produce high levels of HIV-1. In vivo, M(IL-10) macrophages are expanded in lungs of co-infected non-human primates, which correlates with disease severity.

Role of neutrophils in CVB3 infection and viral myocarditis.

Coxsackievirus B3 (CVB3) is a globally prevalent enterovirus of the Picornaviridae family that is frequently associated with viral myocarditis (VM). Neutrophils, as first responders, may be key cells in determining viral disease outcomes; however, neutrophils have been poorly studied with respect to viral infection. Although neutrophils have been ascribed a relevant role in early cardiac inflammation, their precise role in CVB3 infection has not yet been evaluated.

String test: A new tool for tuberculosis diagnosis and drug-resistance detection in children.

Background: There is a critical need to improve the diagnostic accuracy of tuberculosis (TB) in children. Several techniques have been developed to improve the quality of sputum samples; however, these procedures are very unpleasant and invasive and require hospitalization and trained personnel. This study aims to explore the potential use of a new and noninvasive tool, "string test," for TB diagnosis in children and in adults not able to render sputum samples and at risk of developing multidrug-resistant TB (MDR-TB).

Detection of multidrug-resistant tuberculosis from stored DNA Samples: A multicenter study.

Background: In low-income countries, rapid detection of tuberculosis (TB) drug resistance is often restricted by the difficulties of transporting and storing sputum samples from remote health centers to the reference laboratories where molecular tests are available. The aim of this study was to evaluate the performance of four transport and storage systems for molecular detection of rifampicin (RIF) and isoniazid (INH) resistance.

Methods: This was a multicenter study.

Platelets in wound healing and regenerative medicine.

Although platelets are widely recognized as having a critical role in primary hemostasis and thrombosis, increasing experimental and clinical evidence identifies these enucleated cells as relevant modulators of other physiopathological processes including inflammation and tissue regeneration. These phenomena are mediated through the release of growth factors, cytokines, and extracellular matrix modulators that sequentially promote (i) revascularization of damaged tissue through the induction of migration, proliferation, differentiation, and stabilization of endothelial cells in new blood vessels; (ii) restoration of damaged connective tissue through migration, proliferation, and activation of fibroblasts; and (iii) proliferation and differentiation of mesenchymal stem cells into tissue-specific cell types. For these reasons, platelet-rich plasma (PRP) derivatives are used in regenerative medicine for the treatment of several clinical conditions including ulcers, burns, muscle repair, bone diseases, and tissue recovery following surgery.

Nucleosomes and neutrophil extracellular traps in septic and burn patients.

NETosis is a host defense mechanism associated with inflammation and tissue damage. Experimental models show that platelets and von Willebrand factor (VWF) are key elements for intravascular NETosis. We determined NETosis in septic and burn patients at 1 and 4days post-admission (dpa).

Platelet toll-like receptors in thromboinflammation.

Besides their undiscussed role in hemostasis and thrombosis, platelets are also key effector cells capable of assisting and modulating inflammatory reactions and immune responses. Platelets play a sentinel role in immune surveillance by recognizing danger signals from pathogens and cell damage through the expression of toll-like receptors (TLRs) on its surface and internal compartments. Platelets express all 10 TLRs transcripts and its signalosome, including adaptor proteins and transcription factors.

NETosis before and after Hyperglycemic Control in Type 2 Diabetes Mellitus Patients.

Introduction And Objective: Diabetes is characterized by chronic inflammation, endothelial dysfunction, increased risk of infections and early cardiovascular disease. By releasing neutrophil extracellular traps (NETs), neutrophils kill bacteria and exert pro-inflammatory and pro-thrombotic activities. Increased NETosis has been found in cross-sectional studies including treated type 2 diabetes mellitus (T2DM) patients.

Monocyte-derived dendritic cells early exposed to Mycobacterium tuberculosis induce an enhanced T helper 17 response and transfer mycobacterial antigens.

Tuberculosis (TB) is a complex disease, and the success of the bacterium depends on its ability to evade the immune response. Previously, we determined that Mycobacterium tuberculosis (Mtb) impairs the function of dendritic cells (DC), promoting the generation of cells that are poor stimulators of mycobacterial antigen-specific CD4T cells, which are required to control this persistent infection. In this study, we aimed to determine the mechanisms by which monocyte-derived DCs differentiated in the presence of Mtb (MtbDC) may impact on the proliferation of specific anti-mycobacterial T cells.

Platelets: New Bricks in the Building of Neutrophil Extracellular Traps.

In addition to being key elements in hemostasis and thrombosis, platelets have an important role in the inflammatory and innate immune response. This activity is associated with their capability to recognize pathogens through the expression of toll-like receptors, the secretion of various cytokines, chemokines, and growth factors stored within their granules, and the expression of cell adhesion molecules that allows interaction with other immune cells, mainly neutrophils and monocytes. As part of the first line of defense, neutrophils control invading pathogens by phagocytosis, the release of antimicrobial proteins during degranulation, or through the formation of web-like structures named neutrophil extracellular traps (NETs).

Unique challenges and experiences of trainees from Reach-the-World countries.

I am fortunate to have received a Reach-the-World (RTW) fellowship from the International Society on Thrombosis and Haemostasis (ISTH) in 2014 to continue my training in thrombosis and inflammation. I believe that the RTW fellowship is an important educational opportunity for young professionals from developing countries, and I hope to encourage other scientists to apply for this career-changing opportunity by sharing my story.