Subacute toxicological evaluation of AT-533 and AT-533 gel in Sprague-Dawley rats

Exp Ther Med. 2021 Jun;21(6):632. doi: 10.3892/etm.2021.10064. Epub 2021 Apr 15.ABSTRACTAs a novel heat shock protein 90 inhibitor, AT-533 exhibits various biological activities in vitro, including anti-viral, anti-tumor and anti-inflammatory activities. Moreover, AT-533 gel, a gel dosage form of AT-533, has been suggested to have anti-keratitis and herpes simplex virus type-1 infection-induced effects on the skin lesions of animals. However, the safety evaluation of AT-533 and AT-533 gel has, to the best of our knowledge, not been examined in in vivo toxicological tests. Therefore, these toxicological tests were carried out in the present study. A 30-day subacute toxicity test for AT-533 was conducted at doses of 1, 2 and 4 mg/kg in Sprague-Dawley rats, while that for AT-533 gel was conducted using a single dose of 5 g/kg. The toxicological tests showed that a high-dose of AT-533 caused lethality and side effects in Sprague-Dawley rats. However, no mortality, loss of appetite and body weight, adverse reactions, or toxicologically relevant alterations in hematology, biochemistry and macroscopic findings (except for skin) occurred in rats exposed to low-dose AT-533 and single-dose AT-533 gel (5 g/kg) during a 30-day subacute dermic toxicity study. The aforementioned results suggested that AT-533 gel is non-toxic for Sprague-Dawley rats, as shown by a dermic subacute toxicity test and that except for slight skin irritation, AT-533 gel had almost no side effects when administere...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Authors: Source Type: research

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Anti-NMDA receptor (NMDAR) encephalitis is characterized by mood and behavior changes, seizures, abnormal movements, autonomic instability, and encephalopathy. It occurs most commonly in young adults. A paraneoplastic association has been made with ovarian teratoma, though this is rare in children1. More recently, cases of anti-NMDAR encephalitis following viral infections have been reported, including herpes simplex virus (HSV), Japanese encephalitis virus (JEV), and now the 2019 novel coronavirus (SARS-CoV-2)2-5.
Source: Pediatric Neurology - Category: Neurology Authors: Tags: Clinical Letter Source Type: research
Conclusion: By detecting a significant association of the rs12979860-T risk allele for herpes labialis severity with susceptibility to VN, this study gives further indirect evidence for an involvement of HSV-1 in VN pathology, thereby strengthening the virus hypothesis.
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Publication date: 6 October 2020Source: Cell Reports, Volume 33, Issue 1Author(s): Timothy K. Soh, Colin T.R. Davies, Julia Muenzner, Leah M. Hunter, Henry G. Barrow, Viv Connor, Clément R. Bouton, Cameron Smith, Edward Emmott, Robin Antrobus, Stephen C. Graham, Michael P. Weekes, Colin M. Crump
Source: Cell Reports - Category: Cytology Source Type: research
Discussion Herpes simplex virus (HSV) infections are common with an estimated 50% of the US population being infected by age 30, and with latent infection harboring in the trigeminal nerve in 100% of people by age 60 years. HSV infections can cause a vesicular or pustular skin rash that is painful, burning or pruritic and also flu-like symptoms with fever, chills, headache, and fatigue. HSV can also be asymptomatic. To laymen, herpes simplex viruses cause “cold sores,” but to health care personnel, herpes causes many systemic infections including eczema herpeticum, folliculitis, herpes gladiatorum, whitlow, e...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Conclusion: Our results revealed that restraint stress/CORT increased HSV-1 susceptibility by delivering PML into autolysosomes for degradation. The results obtained from in vitro and in vivo models not only demonstrated the adverse effects of stress on HSV-1 infection, but also systematically investigated the underlying molecular mechanisms. These discoveries broaden our understanding of the interplay between host and viruses, and a comprehensive understanding of the role of autophagy in viral infection will provide information for future development of innovative drugs against viral infection.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
Human immunodeficiency virus (HIV) supresses immune system, primarily cell-mediated immunity. Cluster of differentiation 4 (CD4) cell count, viral load, and oral lesions are the most important laboratory parameters to evaluate the evolution of acquired immunodeficiency syndrome. The present study aims to determine the incidence of HIV-related oral lesions with CD4 cell count and viral load in Yunnan, China. A cross-sectional study was conducted from December 2007 to December 2009, in 1812 HIV positive patients from Department of Infectious Diseases in Kunming Third People's Hospital. CD4, CD8, and viral load data were col...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research
An association between herpes simplex virus (HSV) encephalitis and NDMA receptor (NMDAR) encephalitis has been well described. Here, we report a rare case of HSV encephalitis occurring alongside autoimmune encephalitis with leucine-rich glioma inactivated 1 (LGI-1) and NMDAR antibodies.
Source: Neurology Neuroimmunology and Neuroinflammation - Category: Neurology Authors: Tags: Autoimmune diseases, Encephalitis, Viral infections Clinical/Scientific Notes Source Type: research
ABSTRACTBased on research presented during the 10th Amino Acid Assessment Workshop, no observed adverse effect levels (NOAELs) for supplemental methionine at 46  mg/(kg·d) (∼3.2 g/d), for supplemental histidine at 8.0 g/d, and for supplemental lysine at 6.0 g/d have been proposed. These NOAELs are relevant to healthy adults and are applicable only to high-purity amino acids administered in fortified foods or dietary supplements. Because individuals a re exposed to the above supplemental amino acids in the context of complex combinations of essential amino acids or individually in dietary supp...
Source: Journal of Nutrition - Category: Nutrition Source Type: research
PMID: 33004377 [PubMed - in process]
Source: The British Journal of General Practice - Category: Primary Care Authors: Tags: Br J Gen Pract Source Type: research
Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients. The aim of this study was to assess current evidence to determine whether antiviral therapy is as...
Source: Critical Care - Category: Intensive Care Authors: Tags: Research Source Type: research
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