Does the compromised sleep and circadian disruption of night and shiftworkers make them highly vulnerable to 2019 coronavirus disease (COVID-19)?

Rotating and permanent night shiftwork schedules typically result in acute and sometimes chronic sleep deprivation plus acute and sometimes chronic disruption of the circadian time structure. Immune system processes and functionalities are organized as circadian rhythms, and they are also strongly influenced by sleep status. Sleep is a vital behavioral state of living beings and a modulator of immune function and responsiveness. Shiftworkers show increased risk for developing viral infections due to possible compromise of both innate and acquired immunity responses. Short sleep and sleep loss, common consequences of shiftwork, are associated with altered integrity of the immune system. We discuss the possible excess risk for COVID-19 infection in the context of the common conditions among shiftworkers, including nurses, doctors, and first responders, among others of high exposure to the contagion, of sleep imbalance and circadian disruption. ABBREVIATIONS: ACE2: Angiotensin-converting enzyme 2; APC: Antigen.-presenting .cells; CCL: Chemokine (C-C motif) ligand; CD+: .Adhesion molecule expression; COVID-19: 2019 coronavirus disease; DCs: Dendritic cells; GH: Growth hormone; HPA: Hypothalamic-pituitary-adrenal; HSF: Heat shock factor; HSP70: Heat shock protein 70; HSP90: Heat shock protein 90; IL: Interleukin; INFγ: Interferon-gamma; LT/LB: T/B lymphocytes; MHC: Major histocompatibility complex; NK: Natural .killer; RAAS: renin-angiotensin-aldosterone system; SARS: .Severe acute respiratory syndrome; SCN: Suprachiasmatic nucleus;SD: Sleep deprivation; SNS: Sympathetic nervous system; Th1/Th2: T helper lymphocytes 1/2; TLR2/TLR4: Toll-like receptor 2/4; TNF-α: Tumor .necrosis .factor alpha; VEGF: Vascular endothelial growth factor.

Treatment for chemical burning using liquid crystalline nanoparticles as an ophthalmic delivery system for pirfenidone.

Some recent studies have shown that pirfenidone (PFD) has favorable results in the healing process of the cornea. However, PFD in solution exhibits short half-life after topical application, and in this context, a liquid crystal nanoparticle system containing PFD (PFD-LCNPs) was developed. The nanoparticles were characterized by transmission electron microscopy, atomic force microscopy, small angle X-ray diffraction and polarized light microscopy. The PFD-LCNPs had particle size and zeta potential of 247.3 nm and -33.60 mV (stores at 4 °C), respectively, and 257.5 nm and -46.00 mV (stored at 25 °C), respectively. The pH of the formulation was 6.9 and the encapsulation efficiency was 35.9%. The in vitro release profiles indicated that PFD sustained release from PFD-LCNPs for up to 12 h. In vitro study of ocular irritation (HET-CAM test) concluded that components of the formulation are well tolerated for ocular administration. Corneal re-epithelialization time after chemical burning was significantly reduced in rabbits treated with PFD-loaded LCNPs when compared to the group treated with a vehicle. In addition, the anti-inflammatory action of pirfenidone was observed by reducing myeloperoxidase activity (MPO) and inflammatory cells in the histology of the tissues of animals treated with PFD-LCNPs. These findings indicated that the PFD-LCNPs might have the potential for effective ocular drug delivery.

A New Topical Eye Drop Containing LyeTxI-b, A Synthetic Peptide Designed from A Lycosa erithrognata Venom Toxin, Was Effective to Treat Resistant Bacterial Keratitis.

Bacterial keratitis is an ocular infection that can lead to severe visual disability. Staphylococcus aureus is a major pathogen of the eye. We recently demonstrated the strong antimicrobial activity of LyeTxI-b, a synthetic peptide derived from a Lycosa erithrognatha toxin. Herein, we evaluated a topical formulation (eye drops) containing LyeTxI-b to treat resistant bacterial keratitis. Keratitis was induced with intrastromal injection of 4 × 105 cells (4 µL) in New Zealand female white rabbits. Minimum inhibitory concentration (MIC) and biofilm viability were determined. LyeTxI-b ocular toxicity was evaluated through chorioallantoic membrane and Draize tests. One drop of the formulation (LyeTxI-b 28.9 µmol/L +0.5% CMC in 0.9% NaCl) was instilled into each eye four times a day, for a week. Slit-lamp biomicroscopy analysis, corneal histopathological studies and cellular infiltrate quantification through myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) detection were performed. LyeTxI-b was very effective in the treatment of keratitis, with no signs of ocular toxicity. Planktonic bacteria MIC was 3.6 µmol/L and LyeTxI-b treatment reduced biofilm viability in 90%. LyeTxI-b eliminated bacteria and reduced inflammatory cellular activity in the eyes. Healthy and treated animals showed similar NAG and MPO levels. LyeTxI-b is a potent new drug to treat resistant bacterial keratitis, showing effective antimicrobial and anti-inflammatory activity.

Intravitreal injection of the synthetic peptide LyeTx I b, derived from a spider toxin, into the rabbit eye is safe and prevents neovascularization in a chorio-allantoic membrane model.

BACKGROUND: The great diversity of molecules found in spider venoms include amino acids, polyamines, proteins and peptides, among others. Some of these compounds can interact with different neuronal receptors and ion channels including those present in the ocular system. To study potential toxicity and safety of intravitreal injection in rabbits of LyeTx I b, a synthetic peptide derived from the toxin LyeTx I found in venom from the spider Lycosa eritrognatha and to evaluate the angiogenic activity on a CAM model. METHODS: ARPE-19 cells were treated with LyeTx I b (0.36; 0.54; 0.72; 2.89; 4.34 or 9.06 µM). In this study, New Zealand rabbits were used. LyeTx I b (2.89 µM) labeled with FITC dissolved in PBS, or only PBS, were injected into vitreous humor. Electroretinogram (ERG) was recorded 1 day before injection and at 7, 14 and 28 days post-injection. Clinical examination of the retina was conducted through tonometer and eye fundus after ERG. Eyes were enucleated and retinas were prepared for histology in order to assess retinal structure. CAMs were exposed to LyeTx I b (0.54; 0.72; 2.17 or 2.89 µM). RESULTS: ARPE-19 cells exposed to LyeTx I b showed cell viability at the same levels of the control. The fluorescence of LyeTx I b labeled with FITC indicated its retinal localization. Our findings indicate ERG responses from rats injected in the eye with LyeTx I b were very similar to the corresponding responses of those animals injected only with vehicle. Clinical examination found no alterations of intraocular pressure or retinal integrity. No histological damage in retinal layers was observed. CAM presented reduced neovascularization when exposed to LyeTx I b. CONCLUSIONS: Intravitreal injection of LyeTx I b is safe for use in the rabbit eye and prevents neovascularization in the CAM model, at Bevacizumab levels. These findings support intravitreal LyeTx I b as a good candidate to develop future alternative treatment for the retina in neovascularization diseases.

Intravitreal injection of peptides PnPa11 and PnPa13, derivatives of Phoneutria nigriventer spider venom, prevents retinal damage

PnPa11 and PnPa13 are synthetic peptides derived from Phoneutria nigriventer spider venom, which display antinociceptive and neuroprotective properties. In this work, we evaluated the safety of intravitreal use and the neuroprotective effect of these peptides. Methods: The cytotoxicity and the antiangiogenic activity of these peptides were evaluated by the sulforhodamine-B method and chicken chorioallantoic membrane (CAM) assay, respectively. The in vivo safety was analyzed in Wistar rats that were intravitreally injected with different doses (0.50; 1.25; 2.50; 3.75 and 5.00 µg/mL) of these peptides (right eye, n = 6). The retinal function was assessed by electroretinography exams (ERG), intraocular pressure (IOP), and histological analyzes. In order to investigate the neuroprotective effect, Wistar rats received intravitreal injections (right eye, n = 6) of peptides at 1.25 µg/mL and then were exposed to blue LED light. In addition, the visual function and the retinal microstructure were verified. Results: Cytotoxicity analyses demonstrated that the peptides did not present any toxicity over ARPE-19 (adult retinal pigmented epithelial) cell line and the antiangiogenic study highlighted that the peptides promoted the reduction of blood vessels. The intravitreal injection did not cause major changes, neither induced any irreversible damage. In the retinal degeneration assay, the ERG records demonstrated that the prior treatment with PnPa11 and PnPa13 protected the retina from damage. Morphological analyses confirmed the ERG findings. Immunoblotting analyses revealed that PnPa11 increased Erk1/2, NR2A, and NR2B retinal expression after the light stress model, but did not cause Akt1 activation, while PnPa13 prevented Erk1/2 and Akt1 dephosphorylation. Conclusions: The intraocular administration of these peptides was well tolerated and presented protective activity against retinal degeneration, suggesting the potential use of these peptides as neuroprotectors in the ophthalmological field.(AU)

Was postponing the tokyo 2020 olympic and paralympic games a correct decision? / O adiamento dos jogos olímpicos e paralímpicos de tóquio 2020 foi uma decisão correta? / ¿la postergación de los juegos olímpicos y paralímpicos de tokio 2020 fue una decisión correcta?

ABSTRACT In December 2019, Wuhan, in China, attracted international attention due to a pneumonia outbreak caused by the new coronavirus (2019-nCoV). Infection by 2019-nCoV is more likely in elderly people with comorbidities or with associated chronic diseases. Due to the high transmission rate among humans, this disease is rapidly disseminated, which led to several events being canceled, including the Tokyo 2020 Olympic and Paralympic Games. The aim of this article is to discuss the risk factors for Olympic and Paralympic athletes, as well as for spectators, that justify the decision to postpone the Tokyo Games 2020. Regular physical exercise is associated with health and the prevention of chronic diseases. Although athletes generally appear to be healthy and physically fit, this may not be true. The immune system, which protects the organism from invasive microorganisms, can be affected by the duration and quality of sleep, as well as by physical exercise which influences the quality of the immune response. High volumes of high-intensity physical exercise, as well as changes in sleep patterns during the pre-competition period and the impacts of jet lag on athletes traveling for the Tokyo Games in 2020 may lead to immune system suppression, making these groups more vulnerable to infection by 2019-nCoV. Moreover, during the period planned for the games in 2020 the pandemic may be subsiding in some countries and increasing in others, and this was also taken into consideration as a risk factor. Hence, the decision taken to postpone the Tokyo 2020 Olympic and Paralympic Games until 2021 due to the 2019-nCoV was the correct one, and was extremely important to protect the health of Olympic and Paralympic athletes, as well as spectators. Level of evidence V; expert opinion .

RESUMO Em dezembro de 2019, Wuhan, na China, despertou atenção internacional devido a um surto de pneumonia causada pelo novo coronavírus (2019-nCoV). A infecção pelo 2019-nCoV é mais provável em pessoas idosas com comorbidades ou com doenças crônicas associadas. Em virtude da alta taxa de transmissão entre humanos, essa doença tem disseminação rápida, o que fez com que diversos eventos fossem cancelados, dentre eles os Jogos Olímpicos e Paralímpicos de Tóquio 2020. Nesse sentido, o objetivo deste artigo é discutir fatores de risco dos atletas olímpicos e paralímpicos, bem como dos espectadores, que justificam a decisão de adiamento dos Jogos de Tóquio 2020. A prática de exercício físico regular é associada à saúde e à prevenção de doenças crônicas. Embora normalmente pareça que os atletas estão em boa forma e são saudáveis, isso pode não ser verdade. O sistema imunológico, que protege o organismo de microrganismos invasores, pode ser afetado pela quantidade e qualidade do sono, assim como pela prática de exercício físico que influencia a qualidade da resposta imunológica. A prática de exercícios de alta intensidade e grande volume, além das alterações do sono no período pré-competitivo e os impactos do jet lag dos atletas que viajariam para os Jogos de Tóquio no ano de 2020 podem levar à supressão do sistema imunológico, deixando esses grupos mais vulneráveis à contaminação pelo 2019-nCoV. Além disso, no período previsto de ocorrência dos jogos em 2020 a pandemia poderia estar em regressão em alguns países e ascensão em outros, e isso também foi levado em consideração como um fator de risco. Nesse sentido, a tomada de decisão de adiar os Jogos Olímpicos e Paralímpicos de Tóquio 2020 para o ano de 2021 devido ao 2019-nCoV foi correta e de extrema importância para preservar a saúde dos atletas olímpicos e paralímpicos, bem como dos expectadores. Nível de evidência V; opinião do especialista .

RESUMEN En diciembre de 2019, Wuhan, en China, despertó la atención internacional debido a un brote de neumonía causada por el nuevo coronavirus (2019-nCoV). La infección por el 2019-nCoV es más probable en personas de la tercera edad con comorbidades o con enfermedades crónicas asociadas. En virtud de la alta tasa de transmisión entre humanos, esta enfermedad tiene diseminación rápida, lo que hizo con que diversos eventos fuesen cancelados, entre ellos los Juegos Olímpicos y Paralímpicos de Tokio 2020. En ese sentido, el objetivo de este artículo es discutir factores de riesgo de los atletas olímpicos y paralímpicos, bien como de los espectadores, que justifican la decisión de postergación de los Juegos de Tokio 2020. La práctica de ejercicios físicos de forma regular está asociada a la salud y a la prevención de enfermedades crónicas. Aunque normalmente parezca que los atletas están en buena forma y son saludables, eso puede no ser verdad. El sistema inmunológico, que protege el organismo de microorganismos invasores, puede ser afectado por la cantidad y calidad del sueño, así como por la práctica de ejercicios físicos que influencia la calidad de la respuesta inmunológica. La práctica de ejercicios de alta intensidad y gran volumen, además de las alteraciones del sueño en el período precompetitivo y los impactos del jet lag de los atletas que viajarían para los Juegos de Tokio en el año 2020 pueden llevar a la supresión del sistema inmunológico, dejando a esos grupos más vulnerables a la contaminación por el 2019-nCoV. Además, en el período previsto de ocurrencia de los juegos en 2020 la pandemia podría estar en regresión en algunos países y ascensión en otros, y eso también fue llevado en consideración como un factor de riesgo. En ese sentido, la toma de decisión de postergar los Juegos Olímpicos y Paralímpicos de Tokio 2020 para el año 2021 debido al 2019-nCoV fue correcta y de extrema importancia para preservar la salud de los atletas olímpicos y paralímpicos, bien como de los espectadores. Nivel de evidencia V; opinión del especialista .

Intravitreal injection of the synthetic peptide LyeTx I b, derived from a spider toxin, into the rabbit eye is safe and prevents neovascularization in a chorioallantoic membrane model

The great diversity of molecules found in spider venoms include amino acids, polyamines, proteins and peptides, among others. Some of these compounds can interact with different neuronal receptors and ion channels including those present in the ocular system. To study potential toxicity and safety of intravitreal injection in rabbits of LyeTx I b, a synthetic peptide derived from the toxin LyeTx I found in venom from the spider Lycosa eritrognatha and to evaluate the angiogenic activity on a CAM model. Methods: ARPE-19 cells were treated with LyeTx I b (0.36; 0.54; 0.72; 2.89; 4.34 or 9.06 µM). In this study, New Zealand rabbits were used. LyeTx I b (2.89 µM) labeled with FITC dissolved in PBS, or only PBS, were injected into vitreous humor. Electroretinogram (ERG) was recorded 1 day before injection and at 7,14 and 28 days post-injection. Clinical examination of the retina was conducted through tonometer and eye fundus after ERG. Eyes were enucleated and retinas were prepared for histology in order to assess retinal structure. CAMs were exposed to LyeTx I b (0.54; 0.72; 2.17 or 2.89 µM). Results: ARPE-19 cells exposed to LyeTx I b showed cell viability at the same levels of the control. The fluorescence of LyeTx I b labeled with FITC indicated its retinal localization. Our findings indicate ERG responses from rats injected in the eye with LyeTx I b were very similar to the corresponding responses of those animals injected only with vehicle. Clinical examination found no alterations of intraocular pressure or retinal integrity. No histological damage in retinal layers was observed. CAM presented reduced neovascularization when exposed to LyeTx I b. Conclusions: Intravitreal injection of LyeTx I b is safe for use in the rabbit eye and prevents neovascularization in the CAM model, at Bevacizumab levels. These findings support intravitreal LyeTx l b as a good candidate to develop future alternative treatment for the retina in neovascularization diseases.(AU)