The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans

Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9–11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis patient antibodies react with the LigB domain, suggesting applications in diagnosis and vaccines that are currently limited by the strain-specific leptospiral lipopolysaccharide coats

The Production and Application of Hydrogels for Wound Management: A Review

Wound treatment has increased in importance in the wound care sector due to the pervasiveness of chronic wounds in the high-risk population including, but not limited to, geriatric population, immunocompromised and obese patients. Furthermore, the number of people diagnosed with diabetes is rapidly growing. According to the World Health Organization (WHO), the global diabetic occurrence has increased from 4.7 in 1980 to 8.5 in 2014. As diabetes becomes a common medical condition, it has also become one of the major causes of chronic wounds which require specialised care to address patients’ unique needs. Wound dressings play a vital role in the wound healing process as they protect the wound site from the external environment. They are also capable of interacting with the wound bed in order to facilitate and accelerate the healing process. Advanced dressings such as hydrogels are designed to maintain a moist environment at the site of application and due to high water content are ideal candidates for wound management. Hydrogels can be used for both exudating or dry necrotic wounds. Additionally, hydrogels also demonstrate other unique features such as softness, malleability and biocompatibility. Nowadays, advanced wound care products make up around 7.1 billion of the global market and their production is growing at an annual rate of 8.3 with the market projected to be worth 12.5 billion by 2022. The presented review focuses on novel hydrogel wound dressings, their main characteristics and their wound management applications. It also describes recent methodologies used for their production and the future potential developments

Effects of cell seeding density on real-time monitoring of anti-proliferative effects of transient gene silencing

WOS: 000390112500001PubMed ID: 27981039Background: Real-time cellular analysis systems enable impedance-based label-free and dynamic monitoring of various cellular events such as proliferation. In this study, we describe the effects of initial cell seeding density on the anti-proliferative effects of transient gene silencing monitored via real-time cellular analysis. We monitored the realtime changes in proliferation of Huh7 hepatocellular carcinoma and A7r5 vascular smooth muscle cells with different initial seeding densities following transient receptor potential canonical 1 (TRPC1) silencing using xCELLigence system. Huh7 and A7r5 cells were seeded on E-plate 96 at 10,000, 5000, 1250 and 5000, 2500 cells well(-1), respectively, following silencing vector transfection. The inhibitory effects of transient silencing on cell proliferation monitored every 30 min for 72 h. Results: TRPC1 silencing did not inhibit the proliferation rates of Huh7 cells at 10,000 cells well(-1) seeding density. However, a significant anti-proliferative effect was observed at 1250 cells well(-1) density at each time point throughout 72 h. Furthermore, significant inhibitory effects on A7r5 proliferation were observed at both 5000 and 2500 cells well(-1) for 72 h. Conclusions: Data suggest that the effects of transient silencing on cell proliferation differ depending on the initial cell seeding density. While high seeding densities mask the significant changes in proliferation, the inhibitory effects of silencing become apparent at lower seeding densities as the entry into log phase is delayed. Using the optimal initial seeding density is crucial when studying the effects of transient gene silencing. In addition, the results suggest that TRPC1 may contribute to proliferation and phenotypic switching of vascular smooth muscle cells.Scientific and Technological Research Council of Turkey (TUBITAK Research Project)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [108S072]; Novartis (Turkey)Novartis; Research Infrastructure Project, The State Planning Organization of Turkey (DPT) [2009K120640]This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK Research Project, 108S072) and Novartis (Turkey) to MT. The xCELLigence system was purchased within the Research Infrastructure Project, The State Planning Organization of Turkey (DPT, 2009K120640)

Spinal Abscess after Epidural Catheter Insertion: A Case Report

Introduction Epidural anesthesia has become a common practice for treatment of acute surgical pain and to relieve chronic pain syndromes. Despite its many qualities, potential risks have been described. Spinal epidural abscess is one of its most perilous complications. Materials and Methods A 72-year-old patient was treated due to lung cancer. After the operation, the pain was worsening progressively for many months. As a pain relieving measure, an epidural catheter was inserted into the upper thoracic spinal canal. In the reconvalescent period, progressive weakness of lower extremities suddenly developed and advanced rapidly into paraplegia. There was no fever observed by the patient. Results At admission, hypoesthesia from the upper thoracic level and anesthesia from the lower thoracic level was observed, accompanied with paraplegia. Muscle tone was appropriate and Babinski sign was present bilaterally. MRI revealed epidural fluid formation at the posterior aspect of the spinal canal with an intense compression of the cord at levels Th1 to Th4. An immediate operation followed during which a wide decompression of the spinal cord with complete evacuation of the abscess was performed. In the epidural fluid collection, the tip of the epidural catheter was found. Appropriate antibiotic therapy was started instantly. From the abscess, Staphylococcus epidermidiswas isolated. Postoperative CT scan revealed sufficient decompression of the spinal cord. Unfortunately, initially promising recovery was complicated with pneumonia and lung cancer progression that led to the death of the patient. Conclusion Although rare, the epidural abscess is a dangerous complication, resulting in high morbidity and mortality despite rapid surgical and postoperative interventions. Clinical signs and symptoms may be confusing and may point to other forms of pathology. The importance of very strict sterile procedures during catheter insertion and removal or close monitoring of patients with inserted catheters cannot be overemphasized. Disclosure of Interest None declared References Stäbler A, Reiser MF. Imaging of spinal infection. Radiol Clin North Am 2001;39(1):115–135 Tompkins M, Panuncialman I, Lucas P, Palumbo M. Spinal epidural abscess. J Emerg Med 2010;39(3):384–390 Ugarriza LF, Porras LF, Lorenzana LM, Rodríguez-Sánchez JA, García-Yagüe LM, Cabezudo JM. Brucellar spinal epidural abscesses. Analysis of eleven cases. Br J Neurosurg 2005;19(3):235–240 von Albert HH. [Lumbalgia, lumboischialgia. 2: Instrumental diagnosis, differential diagnosis]. Fortschr Med 1990;108(18):363–364 </jats:sec

Multiple intracranial cavernomas with focal amyloid deposition – diagnostic pitfalls

We report a case of a patient with multiple, intracranial superficial calcified tumorous lesions with focal amyloid deposition. On the basis of the first neuronavigated needle biopsy, the tumors were originally assessed as amyloidomas. Additional data was obtained from a second biopsy and supplementary neuroimaging information and the tumors were diagnosed as of vascular origin, probably cavernomas. The report exemplifies how only one diagnostic tool may sometimes be misleading in establishing a final diagnosis. The additional imaging may thoroughly enhance, supplement and improve the diagnostic process