The tetanic depression in fast motor units of mammalian skeletal muscle can be evoked by lengthening of one initial interpulse interval

A lower than expected tetanic force (the tetanic depression) is regularly observed in fast motor units (MUs) when a higher stimulation frequency immediately follows a lower one. The aim of the present study was to determine whether prolongation of only the first interpulse interval (IPI) resulted in tetanic depression. The experiments were carried out on fast MUs of the medial gastrocnemius muscle in cats and rats. The tetanic depression was measured in each case as the force decrease of a tetanus with one IPI prolonged in relation to the tetanic force at the respective constant stimulation frequency. Force depression was observed in all cases studied and was considerably greater in cats. For cats, the mean values of force depression amounted to 28.64% for FR and 10.86% for FF MUs whereas for rats 9.30 and 7.21% for FR and FF motor units, respectively. Since the phenomenon of tetanic depression in mammalian muscle is commonly observed even after a change in only the initial interpulse interval within a stimulation pattern, it can effectively influence processes of force regulation during voluntary activity of a muscle, when motoneurones progressively increase the firing rate

The Influence of the AgNPs Ligand on the Antiviral Activity Against HSV-2

Emilia Tomaszewska,1 Katarzyna Bednarczyk,1 Martyna Janicka,2,3 Marcin Chodkowski,2 Malgorzata Krzyzowska,2 Grzegorz Celichowski,1 Jarosław Grobelny,1 Katarzyna Ranoszek-Soliwoda1 1University of Lodz, Faculty of Chemistry, Department of Materials Technology and Chemistry, Lodz, 90-236, Poland; 2Military Institute of Hygiene and Epidemiology, Laboratory of Nanobiology and Biomaterials, Warsaw, 01-063, Poland; 3Division of Microbiology, Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, 02-786, PolandCorrespondence: Katarzyna Ranoszek-Soliwoda, University of Lodz, Faculty of Chemistry, Department of Materials Technology and Chemistry, Pomorska, 163, Lodz, 90-236, Poland, Tel +48 42 6354663, Fax +48 42 6355832, Email [email protected]: In this paper, we discuss the influence of the ligand type present on the surface of silver nanoparticles (AgNPs) on its affinity to the virus surface and its virucidal activity against herpes simplex virus type 2 (HSV-2). We selected four different ligands, which potentially exhibit different affinity to the HSV-2 virus surface and used them for functionalization of AgNPs: i) sodium citrate: ii) tannic acid; iii) 1-mercaptoundecane-1-sulfonate (MUS); iv) and poly(ethylene glycol) (PEG).Methods: The antiviral activity was performed by in vitro Vero cell culture. Anti- inflammatory activity was performed by measurement of NF-κB activity. The antiviral potential of functional NPs in vivo was tested with HSV-2 model of genital infection. Cryo- transmission electron microscopy (cryo-TEM) was used to directly visualize the interactions or lack of interactions of functional NPs with the surface of the HSV-2 virus and to assess their affinity for the virus surface.Results: It was found that the surface chemistry of NPs plays a key role in modulation of its interaction with the HSV-2 virus. Two of the selected ligands (sodium citrate and PEG) were inert and show no affinity to the virus surface. AgNPs functionalized with heparan sulfate-mimic ligand (MUS) showed high affinity to the virus surface, and the appearance of these interactions resulted in virus deactivation in about 50%. In the case of silver nanoparticles functionalized with tannic acid, the assessment of the affinity is difficult to be resolved, mainly because TA-AgNPs exhibit very strong virucidal effect (~100%) and immediately after the contact of the HSV-2 virus with those NPs the virus structure is being destroyed.Discussion: The obtained results indicate that the high affinity of functional nanoparticles to the virus surface does not provide the high virucidal effectiveness. The most effective revealed to be TA-AgNPs which exhibit very strong virucidal effect against HSV-2 virus. Keywords: antiviral functional nanoparticles, interactions of nanoparticles with HSV-2, cryo-TEM, surface chemistry of antiviral nanoparticle

Adjuvanticity of Tannic Acid-Modified Nanoparticles Improves Effectiveness of the Antiviral Response

Martyna Janicka,1,2,* Marcin Chodkowski,1,* Aleksandra Osinska,1 Klaudia Bylinska,3,4 Oliwia Obuch-Woszczatyńska,3,4 Magdalena Patrycy,1 Grzegorz Chodaczek,5 Katarzyna Ranoszek-Soliwoda,6 Emilia Tomaszewska,6 Grzegorz Celichowski,6 Jaroslaw Grobelny,6 Joanna Cymerys,2 Małgorzata Krzyżowska1 1Division of Medical and Environmental Microbiology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland; 2Division of Microbiology, Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland; 3Laboratory of Parasitology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland; 4Division of Pharmacology and Toxicology, Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland; 5Łukasiewicz Research Network – PORT Polish Center for Technology Development, Life Sciences and Biotechnology Center, Wroclaw, Poland; 6University of Lodz, Faculty of Chemistry, Department of Materials Technology and Chemistry, Lodz, Poland*These authors contributed equally to this workCorrespondence: Małgorzata Krzyżowska, Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163, Warsaw, Poland, Email [email protected]: Herpes simplex virus type 1 (HSV-1) causes recurrent infections of skin and mucosal tissues with high global prevalence. HSV-1 also invades the nervous system where it establishes a lifelong latency-making infection poorly treatable We previously showed that both tannic acid-modified silver and gold nanoparticles (TA-Ag/AuNPs) inhibit HSV-1 infection in vitro.Methods: We used an in vitro and in vivo model of HSV-1 infection to study how metal type, size and tannic acid modification of nanoparticles can influence development of the early innate response and the mounting of specific anti-HSV-1 response upon treatment of the nasal mucosa.Results: We found that tannic acid is necessary for binding with HSV-1, with smaller sizes independent of the NPs composition, whereas for larger NPs, only TA-AgNPs can inhibit HSV-1 infection. Intranasal treatment of HSV-1 infection with TA-Ag/AuNPs results in lower viral titers and a better antiviral response, followed by increased IFN-α, CXCL9, and CXCL10 levels as well as infiltration of T cells and NK cells in the infected sites. We also found that the application of TA-NPs to the nasal cavities of infected mice induced infiltration of both monocytes and Langerhans cells (LCs), which lasted longer compared to the application of unmodified NPs. Furthermore, TA-NPs activated monocytes and microglia to produce antiviral cytokines and chemokines better than unmodified NPs, except for the large TA-AuNPs.Discussion: Treatment of the mucosal tissues at the early stage of HSV-1 infection helps to modulate specific and effective antiviral immune response by attracting cytotoxic lymphocytes and inducing the production of antiviral cytokines and chemokines. Furthermore, tannic acid modification is helpful for the removal of nanoparticles from the respiratory tract, which increases the safety of nanoparticle applications to treat infections.Keywords: HSV-1, AgNPs, AuNPs, tannic acid, microgli

Sarcopenia: etiology, clinical consequences, intervention, and assessment

The aging process is associated with loss of muscle mass and strength and decline in physical functioning. The term sarcopenia is primarily defined as low level of muscle mass resulting from age-related muscle loss, but its definition is often broadened to include the underlying cellular processes involved in skeletal muscle loss as well as their clinical manifestations. The underlying cellular changes involve weakening of factors promoting muscle anabolism and increased expression of inflammatory factors and other agents which contribute to skeletal muscle catabolism. At the cellular level, these molecular processes are manifested in a loss of muscle fiber cross-sectional area, loss of innervation, and adaptive changes in the proportions of slow and fast motor units in muscle tissue. Ultimately, these alterations translate to bulk changes in muscle mass, strength, and function which lead to reduced physical performance, disability, increased risk of fall-related injury, and, often, frailty. In this review, we summarize current understanding of the mechanisms underlying sarcopenia and age-related changes in muscle tissue morphology and function. We also discuss the resulting long-term outcomes in terms of loss of function, which causes increased risk of musculoskeletal injuries and other morbidities, leading to frailty and loss of independence

Tannic Acid Modified Silver Nanoparticles Show Antiviral Activity in Herpes Simplex Virus Type 2 Infection

The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections.This work was supported by the Polish National Science Centre grant No. 2011/03/B/NZ6/04878 (for MK) and Centre for Preclinical Research and Technology (CePT) Project No. POIG.02.02.00-14-024/08-0 (for MG and MD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip