Alexandre dos Santos da Silva

Fundação Oswaldo Cruz

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Marcelo Alves Pinto

Fundação Oswaldo Cruz

Vanessa Salete de Paula

Fundação Oswaldo Cruz

Gentil Arthur Lins Bentes Mendonça de Vasconcelos

Fundação Oswaldo Cruz

Arthur Daniel Rocha Alves

Fundação Oswaldo Cruz

Jéssica Vasques Raposo

Fundação Oswaldo Cruz

Juliana Gil Melgaço

Fundação Oswaldo Cruz

Damião Carlos Dos Santos

Estácio (Brazil)

Otacílio C. Moreira

Fundação Oswaldo Cruz

Natália Maria Lanzarini

Fundação Oswaldo Cruz

Juliana Rodrigues Guimarães

Fundação Oswaldo Cruz

Cooperative Institutions

Fundação Oswaldo Cruz

Universidade Federal do Rio de Janeiro

Faculdades Oswaldo Cruz

Universidade de São Paulo

International Olive Council

Universidade Federal de Mato Grosso do Sul

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Universidade do Estado do Rio de Janeiro

National Council for Scientific and Technological Development

National Institute of Science and Technology for Structural Biology and Bioimaging

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Animal models and SARS-CoV-2-induced pulmonary and neurological injuries

Memórias do Instituto Oswaldo Cruz (2022)

Marcelo Alves Pinto Alexandre dos Santos da Silva Daniela del Rosário Flores Rodrigues Rodrigo Müller Gentil Arthur Lins Bentes Mendonça de Vasconcelos

Laboratory animals are essential mainly for experiments aiming to study pathogenesis and evaluate antivirals and vaccines against emerging human infectious diseases. Preclinical studies of coronavirus disease 19 (COVID-19) pathogenesis have used several animal species as models: transgenic human ACE2 mice (K18 mice), inbred BALB/c or C57BL/6N mice, ferrets, minks, domestic cats and dogs, hamsters, and macaques. However, the choice of an animal model relies on several limitations. Besides the host susceptibility, the researcher's experience with animal model management and the correct interpretation of clinical and laboratory records are crucial to succeed in preclinical translational research. Here, we summarise pathological and clinical findings correlated with virological data and immunological changes observed from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experimental infections using different well-established SARS-CoV-2 animal model species. This essay aims to critically evaluate the current state of animal model translation to clinical data, as described in the human SARS-CoV-2 infection.

2019-20 coronavirus outbreak

Betacoronavirus

Pandemic

10.1590/0074-02760220239

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CLEC5A expression can be triggered by spike glycoprotein and may be a potential target for COVID‐19 therapy

Journal of Medical Virology (2022)

Thiago Lazari Machado Alanna Calheiros Santos Tamiris Azamor Andrea M. V. da Silva Vanessa R. Pimenta

Abstract The immune response is crucial for coronavirus disease 19 (COVID‐19) progression, with the participation of proinflammatory cells and cytokines, inducing lung injury and loss of respiratory function. CLEC5A expression on monocytes can be triggered by viral and bacterial infections, leading to poor outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is able to induce neutrophil activation by CLEC5A and Toll‐like receptor 2, leading to an aggressive inflammatory cascade, but little is known about the molecular interactions between CLEC5A and SARS‐CoV‐2 proteins. Here, we aimed to explore how CLEC5A expression could be affected by SARS‐CoV‐2 infection using immunological tools with in vitro, in vivo, and in silico assays. The findings revealed that high levels of CLEC5A expression were found in monocytes from severe COVID‐19 patients in comparison with mild COVID‐19 and unexposed subjects, but not in vaccinated subjects who developed mild COVID‐19. In hamsters, we detected CLEC5A gene expression during 3–15 days of Omicron strain viral challenge. Our results also showed that CLEC5A can interact with SARS‐CoV‐2, promoting inflammatory cytokine production, probably through an interaction with the receptor‐binding domain in the N‐acetylglucosamine binding site (NAG‐601). The high expression of CLEC5A and high levels of proinflammatory cytokine production were reduced in vitro by a human CLEC5A monoclonal antibody. Finally, CLEC5A was triggered by spike glycoprotein, suggesting its involvement in COVID‐19 progression; therapy with a monoclonal antibody could be a good strategy for COVID‐19 treatment, but vaccines are still the best option to avoid hospitalization/deaths.

Proinflammatory cytokine

Cytokine Storm

10.1002/jmv.28427

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Perfil epidemiológico do Herpes simplex no grupo de homens que fazem sexo com homens e avaliação do RNA de interferência como agente antiviral na encefalite herpética em camundongos BALB/c

Alexandre dos Santos da Silva

Herpes simplex virus 1 (HSV-1) is a neurotropic virus responsible for clinical manifestations as herpes labialis, keratoconjunctivitis and herpetic encephalitis (HSE). Herpetic encephalitis (HSE) presents an annual incidence of 1-4 cases/million of inhabitants and causes reduced level of consciousness, convulsive crisis and motor deficit. Besides that, HSE can cause sequels as aphasia, amnesia and motor, cognitive or sensory difficulties. HSE can be more severe and exacerbate in individuals co-infected with HIV/HSV-1, especially in risk behavior group. Nowadays, HSE treatment with antiherpetic antivirals presents elevated toxicity, metabolic side effects and antiviral resistance. An alternative to current treatments is the use of of small interference RNA (siRNA) as inhibitors of viral replication. The aim of this study was (1) to evaluate the prevalence of HSV infection in 283 men who has sex with men (MSM) from Campo Grande, Mato Grosso do Sul and (2) to utilize siRNA anti-HSV-1 conjugated with RVG-9R (siRNA:RVG-9R anti-HSV-1) to evaluate HSE treatment in vivo. At first was evaluated the epidemiological profile by serological testing and risk factors of HSV infection in MSM. After that, was evaluated the HSE infection of BALB/c mice inoculated with different dilutions of HSV-1 EK strain by assessment of HSE clinical signs, IFN-\03B3 and HSV-1 replication. At last, siRNA:RVG-9R anti-HSV-1 treatment was evaluated by kinetics of viral replication inhibition, number of administered doses and treatment with siRNA:RVG-9R anti-HSV-1 combined with acyclovir in HSE experimental model. Besides that, was performed the analysis of HSE clinical signs, mortality and viral replication inhibition The seroprevalence of MSM group was of 85.2% and risk factors as age, education level, low income, frequently sexual practices, drug use and HIV infection were associated with HSV. Animals infected with HSV-1 EK in HSE experimental model presented HSE clinical signs, high mortality, high mortality, increase of IFN-\03B3 concentration and HSV-1 replication in brain and trigeminal ganglia (TG). When evaluating siRNA treatment, animals treated with two doses of siRNA:RVG-9R anti-HSV-1 showed prolonged survival time, reduction of HSE clinical signs and viral replication inhibition in brain (67.7%) and TG (85.7%). Also, animals treated with siRNA:RVG-9R anti-HSV-1 combined with acyclovir demonstrated reduction of HSE clinical signs and survival of 100%, as well as viral replication inhibition in brain (83.2%) and in TG (74.5%). In conclusion, occurred high prevalence of HSV and HIV/HSV co-infection, which can increase the possibility of HSE severity infections on HSH group and facilitate the clinical manifestation. Besides that, the molecule siRNA:RVG-9R anti-HSV-1 demonstrated to be quite effective on HSE treatment, enabling HSE clinical signs reduction, increase of survival and HSV-1 replication inhibition in mice. These results demonstrate that siRNA can be utilized as alternative antiviral therapy on HSE treatment

Herpes Labialis

Neurotropic virus

Tick-borne encephalitis

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Viroses emergentes e reemergentes: considerações gerais, vírus da imunodeficiência humana e as zoonoses virais de importância no Brasil

Editora FIOCRUZ eBooks (2023)

Alexandre dos Santos da Silva Elba Regina Sampaio de Lemos Edson Delatorre Jorlan Fernandes de Jesus Monick Lindenmeyer Guimarães

10.7476/9786557082119.0005

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Equipamentos automatizados na criação e crescimento do zebrafish

Revista da Sociedade Brasileira de Ciência em Animais de Laboratório (2020)

Alexandre dos Santos da Silva

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Craniocervical Descompression in the Hunter Syndrome

Arquivos Brasileiros de Neurocirurgia Brazilian Neurosurgery (2018)

Alexandre dos Santos da Silva Daniel Paz Juliete Melo Diniz Thiago Bortholin Franz Jooji Onishi

Apresentação de caso: Os autores apresentam um relato de caso de um paciente masculino de 27 anos, com diagnóstico de síndrome de Hunter (ou mucopolissacaridose tipo II), que apresentava sintomas de compressão de bulbo há oito meses. Exame de ressonância magnética de crânio e coluna cervical confirmou compressão de bulbo ao nível do forame magno, devido à herniação de tonsilas cerebelares por este forame e pela malformação da porção suboccipital da escama do osso temporal. O paciente foi submetido à cirurgia de craniectomia suboccipital mediana com retirada de arco posterior de C1, com importante melhora dos sintomas no pós-operatório e sem sinais de instabilidade atlantooccipital, com melhora na escal de Bindal de 50 pontos, no pré-operatório, para 15 pontos, no pós-operatório.

10.1055/s-0038-1672505

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Ensaio imunoenzimático para o diagnóstico da hepatite A utilizando IgY anti-HAV

Alexandre dos Santos da Silva

Hepatitis A is an endemic disease in Brazil and Latin America. Prevalence of this infection is related to the low degree of hygiene and sanitation. In developing countries, inadequate sanitation results in larger transmission of the disease mostly in children and young people. Nowadays, due to better sanitation conditions, the epidemiological profile of disease is changing to older ages resulting in the occurrence of outbreaks. Diagnostic kits for detection of total anti-HAV generally use mammals immunoglobulin G (IgG) in the convalescent period of disease for production of capture and conjugated antibodies. One alternative to the application of mammals antibodies in the diagnosis is the use of immunoglobulin Y (IgY), encountered in birds and reptiles. These proteins have several advantages when compared to IgG: high response against mammals antigens, reduction of the background in imunoenzymatic assays and it is obtained by a non-invasive method (harvest of the egg yolks). The objective of this work was the acquisition of anti-HAV IgY antibodies produced in immunized chickens against Hepatitis A virus and the development of an immunoenzymatic assay for total anti-HAV detection using IgY anti-HAV as capture and conjugated immunoglobulins. Five groups of chickens were immunized with different inocula containing: vaccine with and without CpG-ODN adjuvant, HAV with incomplete Freund adjuvant (IFA) with and without CpG-ODN and one control group with IFA. The eggs were harvested and the yolk was purified by precipitation with polyethylene glycol. The purified solution containing anti-HAV IgY was evaluated by espectrofotometry and their specificity and title were determined by an immunoenzymatic assay. These antibodies were conjugated with peroxidase and was estabilized the ideal dilution for capture and conjugated antibodies. For evaluation of the immunoenzymatic “in-house” assay with IgY anti-HAV, a panel composed of 100 positive samples and 100 negative samples for total anti-HAV was assessed. The presence of IgY anti-HAV in egg yolks was established by SDS-PAGE and Western Blotting, and after the purification, the average of the proteins concentrations in the egg yolks was of 8,7406 mg/mL. The group immunized with HAV, IFA and CpG-ODN demonstrate the higher titer of antibodies. The “in-house” assay showed sensibility of 84%, specificity of 79% and efficiency of 81,5%. The methods used for anti-HAV IgY production and conjugation with peroxidase were efficient and the “in-house” immunoenzymatic assay IgY anti-HAV demonstrated a good sensitivity and specificity. The production of IgY anti-HAV showed advantages when compared to the acquisition of IgG anti-HAV. The immunoenzymatic “in-house” assay IgY anti- HAV can be an alternative to the utilization of IgG in immunoenzymatic assays.

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Passive Immunotherapy of Cynomolgus Monkeys with Anti-Rotavirus IgY

Pharmaceutics (2024)

Gentil Arthur Lins Bentes Mendonça de Vasconcelos Juliana Rodrigues Guimarães Eduardo de Mello Volotão Natália Maria Lanzarini Alexandre dos Santos da Silva

Immunoglobulins Y (IgY) purified from egg yolks of hens represents an attractive, cost-effective alternative for the development of new diagnostic and therapeutic platforms. In this study, we evaluated the therapeutic efficacy of rotavirus-specific IgY in a cynomolgus monkey (

10.3390/pharmaceutics16091149

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Knowledge about viral hepatitis among participants of Gay Pride Event in Brazil

The Brazilian Journal of Infectious Diseases (2013)

Nathália Delvaux Vanessa Salete de Paula Márcia Paschoal do Espírito-Santo Elisangela F. da Silva Juliana Custódio Miguel

Knowledge about viral hepatitis among participants of Gay Pride Event in BrazilDear Editor, Male or female homosexual, bisexual and transgender individuals (HBT) can be more exposed to viral hepatitis, but few studies worldwide have been conducted about viral hepatitis knowledge among HBT. 1-5The aim of this study was to evaluate viral hepatitis knowledge and potential risk of HBT and heterosexual individuals attending a Gay Pride Event.A cross-sectional survey was carried out among a randomized sample of 121 Brazilian individuals attending to Gay Pride Event at Copacabana (Rio de Janeiro City) on November 2010.A questionnaire consisting of 23 items regarding demographic data, knowledge about viral hepatitis, sexual and risk factors behaviour was distributed to participants.

Pride

Viral Hepatitis

Hepatitis C

10.1016/j.bjid.2012.09.015

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Epidemiological evaluation of herpes simplex virus in men who have sex with men in Mato Grosso do Sul, Brazil

Sexually Transmitted Infections (2014)

Alexandre dos Santos da Silva Lyana Rodrigues Pinto Lima Amanda Perse da Silva Lisie Souza Castro Grazielli Rocha de Rezende

Background

Harsh disciplinary practices are considered common in developing countries. However, scientific evidence lacks to support this. Primary aim of this study was to determine the prevalence of different forms (physical, emotional maltreatment and neglect) of child abuse in Karachi, Pakistan.

Methods

A cross sectional survey of 800 dyads (children ranging from 11–17 years old and their parent) were selected from 32 clusters of Karachi, using multistage cluster sampling between December 2014 to March 2015. A structured questionnaire adopted from International society of child abuse and neglect (International child abuse screening tool for parent and child). Prevalence of child maltreatment was estimated by mean child abuse score.

Results

Mean score were 51.7 + 11.9 (child), 77.9 + 20.2 (mother) and 63.6 + 17.3 (father). Both parent and child responses revealed similar prevalence (43%) of child maltreatment. The mother’s responses showed a prevalence of physical (42%), emotional (50%) maltreatment and neglect (5.4%) whereas, father’s responses showed a prevalence of physical (39%), emotional (46%) maltreatment and neglect (9.7%). The child’s experiences showed a prevalence of physical (49%), emotional (50%) maltreatment and neglect (57%). A substantial proportion of participants were exposed to at-least one form of maltreatment on mother (58%), father (54%) and child (74%) responses, of which all three maltreatment forms experienced by children were 4%, 9% and 31% on mother, father and child responses respectively.

Conclusions

This study reflects hidden extent of child maltreatment and poly-victimisation in Karachi. Our findings provide evidence to raise public awareness about malpractices and highlight the need to develop positive parenting program.

Psychological abuse

Physical abuse

Victimisation

Child neglect

10.1136/sextrans-2014-051739

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