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1.
Artigo em Inglês | MEDLINE | ID: mdl-39074658

RESUMO

Acute fulminant cerebral edema is a type of rapidly progressive encephalitis that occurs in children and is associated with significant morbidity and mortality. We present a clinical case with seizures, rapid neurological deterioration and the early appearance of cerebral herniation signs. Although the radiological tests were initially normal and there are no established parameters that predict the evolution of encephalitis to a rapidly progressive subtype, the clinical evolution forced to consider the decompressive craniectomy due to the lack of response to the medical management of the cerebral edema. It may be necessary take a brain biopsy to confirm the etiology of the encephalitis origin of acute fulminant cerebral edema. The objective of surgery should be not only to increase survival, but also to reduce subsequent neurological sequelae.

2.
Microorganisms ; 12(4)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38674777

RESUMO

Currently, there is a wide application in the literature of the use of the Fourier Transform Infrared Spectroscopy (FTIR) technique. This basic tool has also proven to be efficient for detecting molecules associated with hosts and pathogens in infections, as well as other molecules present in humans and animals' biological samples. However, there is a crisis in science data reproducibility. This crisis can also be observed in data from experimental animal models (EAMs). When it comes to rodents, a major challenge is to carry out sanitary monitoring, which is currently expensive and requires a large volume of biological samples, generating ethical, legal, and psychological conflicts for professionals and researchers. We carried out a survey of data from the relevant literature on the use of this technique in different diagnostic protocols and combined the data with the aim of presenting the technique as a promising tool for use in EAM. Since FTIR can detect molecules associated with different diseases and has advantages such as the low volume of samples required, low cost, sustainability, and provides diagnostic tests with high specificity and sensitivity, we believe that the technique is highly promising for the sanitary and stress and the detection of molecules of interest of infectious or non-infectious origin.

3.
Clin Oral Investig ; 28(4): 238, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568249

RESUMO

OBJECTIVES: This narrative review addresses relevant points about Chapare virus (CHAV) entry in oral cells, CHAV transmission, and preventive strategies in dental clinical settings. It is critical in dentistry due to the frequent presence of gingival hemorrhage occurred in CHAV-infected patients. MATERIALS AND METHODS: Studies related to CHAV were searched in MEDLINE/PubMed, Scopus, EMBASE, and Web-of-Science databases without language restriction or year of publication. RESULTS: Recently, the PAHO/WHO and CDC indicate a presence of human-to-human transmission of CHAV associated with direct contact with saliva, blood, or urine, and also through droplets or aerosols created in healthcare procedures. CHAV was detected in human oropharyngeal saliva and gingival bleeding was confirmed in all cases of CHAV hemorrhagic fever, including evidence of nosocomial CHAV transmission in healthcare workers. We revisited the human transferrin receptor 1 (TfR1) expression in oral, nasal, and salivary glands tissues, as well as, we firstly identified the critical residues in the pre-glycoprotein (GP) complex of CHAV that interacts with human TfR1 using cutting-edge in silico bioinformatics platforms associated with molecular dynamic analysis. CONCLUSIONS: In this multidisciplinary view, we also point out critical elements to provide perspectives on the preventive strategies for dentists and frontline healthcare workers against CHAV, and in the implementation of salivary diagnostic platforms for virus detection, which can be critical to an urgent plan to prevent human-to-human transmission based on current evidence. CLINICAL RELEVANCE: The preventive strategies in dental clinical settings are pivotal due to the aerosol-generating procedures in dentistry with infected patients or suspected cases of CHAV infection.


Assuntos
Biologia Computacional , Febre Hemorrágica Americana , Humanos , Pessoal de Saúde , Odontologia
4.
Braz Oral Res ; 38: e002, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38198302

RESUMO

This study aimed to estimate the prevalence and extent of bleeding on probing and calculus in 12-year-old schoolchildren of Quito, Ecuador, and evaluate the associated factors. We conducted an epidemiological survey with a representative sample of 1,100 12-year-old schoolchildren from public schools in the urban area of Quito, Ecuador. We assessed the periodontal health using the Community Periodontal Index (CPI). The prevalence and extent of the periodontal condition was based on the presence of at least one site with bleeding on probing (BOP), and the presence of dental calculus was also evaluated. We used univariate and multiple multilevel Poisson regression analyses to verify the association between the independent variables and the number of sextants with BOP and calculus. The prevalence of BOP and calculus was 92% and 69.9%, respectively. The adjusted mean of the affected sextants was 4.3 and 2.2 for BOP and calculus, respectively. The mother's schooling and malocclusion were associated with the number of sextants with bleeding. The mother's schooling and dental caries experience were associated with calculus. Gingival bleeding and the presence of dental calculus are highly prevalent in 12-year-old schoolchildren from Quito. Gingival bleeding is associated with maternal education and malocclusion, and dental calculus is associated with maternal education and dental caries.


Assuntos
Cárie Dentária , Má Oclusão , Humanos , Criança , Equador/epidemiologia , Estudos Transversais , Cálculos Dentários/epidemiologia , Cárie Dentária/epidemiologia , Hemorragia Gengival/epidemiologia
5.
Radiographics ; 44(2): e230138, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38236750

RESUMO

Genitourinary tract soft-tissue sarcomas are rare neoplasms with varied pathologic and clinical features. While some of these tumors may be aggressive high-grade malignancies, others are low grade with a relatively better prognosis. Given that the grade and extent of the disease are important prognostic factors in these tumors, timely diagnosis is crucial. Unfortunately, most imaging features of these malignancies are not pathognomonic, and various histologic subtypes do not manifest with typical classic imaging features. Therefore, reliable differentiation of the various histologic tumor types is not always possible based solely on the radiologic manifestations. Imaging findings need to be considered in the context of clinical history in corroboration with radiologic-pathologic correlation. The authors discuss the specific imaging and pathologic characteristics of various genitourinary tract soft-tissue sarcomas, emphasizing diagnostic difficulties and differential diagnoses. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Sarcoma/diagnóstico por imagem , Sarcoma/patologia , Prognóstico , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologia
6.
Genesis ; 62(1): e23561, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37830148

RESUMO

Hox genes encode transcription factors that play an important role in establishing the basic body plan of animals. In Drosophila, Antennapedia is one of the five genes that make up the Antennapedia complex (ANT-C). Antennapedia determines the identity of the second thoracic segment, known as the mesothorax. Misexpression of Antennapedia at different developmental stages changes the identity of the mesothorax, including the muscles, nervous system, and cuticle. In Drosophila, Antennapedia has two distinct promoters highly regulated throughout development by several transcription factors. Antennapedia proteins are found with other transcription factors in different ANTENNAPEDIA transcriptional complexes to regulate multiple subsets of target genes. In this review, we describe the different mechanisms that regulate the expression and function of Antennapedia and the role of this Hox gene in the development of Drosophila.


Assuntos
Proteínas de Drosophila , Fatores de Transcrição , Animais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Drosophila/genética , Drosophila/metabolismo , Drosophila melanogaster/genética
7.
J Periodontal Res ; 59(2): 237-248, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38135675

RESUMO

BACKGROUND AND OBJECTIVE: As elsewhere in the world, the prevalence of periodontitis in stages I-II is high in the Latin American population, this scenario emphasizes the need for identification of urgent needs for allocating adequate resources to provide diagnosis, prevention, and treatment of these diseases. The aim of this Delphi study was to predict the trends in periodontology/periodontics in the Latin American region by the year 2030. METHODS: A steering committee and an advisory group of experts in periodontology/periodontics were selected from 16 countries. An open questionnaire of 60 questions was validated and used following the Delphi methodology. RESULTS: Two hundred and twenty-five experts from Latin America answered the two rounds of the questionnaire. Moderate to strong consensus was reached on 45 questions (75%). The prediction was that the prevalence of gingivitis and periodontitis in stages I and II will be maintained, the importance of the link with systemic diseases will increase, and the impact of prevention and periodontal treatment will also increase, mainly in the private sector. There was a strong consensus that plastic and regenerative surgical procedures will increase, as well as the demand for training in the specialty of periodontology. CONCLUSIONS: The present study has provided relevant and useful information on predictions in periodontology/periodontics in Latin America, with important level of consensus among experts. It has been predicted that periodontitis will still be a highly prevalent disease, and its links with other medical conditions should demand more attention by health authorities to develop adequate prevention and management policies and strategies.


Assuntos
Doenças Periodontais , Periodontite , Humanos , Periodontia , Doenças Periodontais/epidemiologia , Doenças Periodontais/terapia , América Latina/epidemiologia , Consenso , Técnica Delphi , Periodontite/epidemiologia , Periodontite/terapia
8.
Braz. oral res. (Online) ; 38: e002, 2024. tab
Artigo em Inglês | LILACS-Express | LILACS, BBO - Odontologia | ID: biblio-1528149

RESUMO

Abstract This study aimed to estimate the prevalence and extent of bleeding on probing and calculus in 12-year-old schoolchildren of Quito, Ecuador, and evaluate the associated factors. We conducted an epidemiological survey with a representative sample of 1,100 12-year-old schoolchildren from public schools in the urban area of Quito, Ecuador. We assessed the periodontal health using the Community Periodontal Index (CPI). The prevalence and extent of the periodontal condition was based on the presence of at least one site with bleeding on probing (BOP), and the presence of dental calculus was also evaluated. We used univariate and multiple multilevel Poisson regression analyses to verify the association between the independent variables and the number of sextants with BOP and calculus. The prevalence of BOP and calculus was 92% and 69.9%, respectively. The adjusted mean of the affected sextants was 4.3 and 2.2 for BOP and calculus, respectively. The mother's schooling and malocclusion were associated with the number of sextants with bleeding. The mother's schooling and dental caries experience were associated with calculus. Gingival bleeding and the presence of dental calculus are highly prevalent in 12-year-old schoolchildren from Quito. Gingival bleeding is associated with maternal education and malocclusion, and dental calculus is associated with maternal education and dental caries.

9.
Int J Mol Sci ; 24(18)2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37762664

RESUMO

In this narrative review, we aim to point out the close relationship between mpox virus (MPXV) infection and the role of saliva as a diagnostic tool for mpox, considering the current molecular approach and in the perspective of OMICs application. The MPXV uses the host cell's rough endoplasmic reticulum, ribosomes, and cytoplasmic proteins to replicate its genome and synthesize virions for cellular exit. The presence of oral mucosa lesions associated with mpox infection is one of the first signs of infection; however, current diagnostic tools find it difficult to detect the virus before the rashes begin. MPXV transmission occurs through direct contact with an infected lesion and infected body fluids, including saliva, presenting a potential use of this fluid for diagnostic purposes. Currently available diagnostic tests for MPXV detection are performed either by real-time quantitative PCR (RT-qPCR) or ELISA, which presents several limitations since they are invasive tests. Despite current clinical trials with restricted sample size, MPXV DNA was detected in saliva with a sensitivity of 85%-100%. In this context, the application of transcriptomics, metabolomics, lipidomics, or proteomics analyses coupled with saliva can identify novel disease biomarkers. Thus, it is important to note that the identification and quantification of salivary DNA, RNA, lipid, protein, and metabolite can provide novel non-invasive biomarkers through the use of OMICs platforms aiding in the early detection and diagnosis of MPXV infection. Untargeted mass spectrometry (MS)-based proteomics reveals that some proteins also expressed in saliva were detected with greater expression differences in blood plasma when comparing mpox patients and healthy subjects, suggesting a promising alternative to be applied in screening or diagnostic platforms for mpox salivary diagnostics coupled to OMICs.


Assuntos
Líquidos Corporais , Doenças Transmissíveis , Mpox , Humanos , Patologia Bucal , Saliva
10.
Viruses ; 15(9)2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37766292

RESUMO

The SARS-CoV-2 entry into host cells is mainly mediated by the interactions between the viral spike protein (S) and the ACE-2 cell receptor, which are highly glycosylated. Therefore, carbohydrate binding agents may represent potential candidates to abrogate virus infection. Here, we evaluated the in vitro anti-SARS-CoV-2 activity of two mannose-binding lectins isolated from the Brazilian plants Canavalia brasiliensis and Dioclea violacea (ConBR and DVL). These lectins inhibited SARS-CoV-2 Wuhan-Hu-1 strain and variants Gamma and Omicron infections, with selectivity indexes (SI) of 7, 1.7, and 6.5, respectively for ConBR; and 25, 16.8, and 22.3, for DVL. ConBR and DVL inhibited over 95% of the early stages of the viral infection, with strong virucidal effect, and also protected cells from infection and presented post-entry inhibition. The presence of mannose resulted in the complete lack of anti-SARS-CoV-2 activity by ConBR and DVL, recovering virus titers. ATR-FTIR, molecular docking, and dynamic simulation between SARS-CoV-2 S and either lectins indicated molecular interactions with predicted binding energies of -85.4 and -72.0 Kcal/Mol, respectively. Our findings show that ConBR and DVL lectins possess strong activities against SARS-CoV-2, potentially by interacting with glycans and blocking virus entry into cells, representing potential candidates for the development of novel antiviral drugs.


Assuntos
Antivirais , COVID-19 , Humanos , Antivirais/farmacologia , Lectinas de Ligação a Manose , SARS-CoV-2 , Simulação de Acoplamento Molecular , Lectinas/farmacologia
11.
Sci Rep ; 13(1): 15162, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37704704

RESUMO

wingless expression is exquisitely regulated by different factors and enhancers in the imaginal wing discs of Drosophila melanogaster in four domains: the dorsal band, the dorso-ventral boundary, and the inner and outer ring domains. tonalli is a trithorax group gene that encodes a putative SUMO E3 ligase that binds to chromatin to regulate the expression of its targets, including the Hox genes. However, its role in modulating gene expression is barely known. Here, we show that TnaA modulates the wingless expression at two domains of the wing disc, the dorso-ventral boundary and the inner ring. At first, tonalli interacts genetically with Notch to form the wing margin. In the inner ring domain, TnaA modulates wingless transcription. When the dosage of TnaA increases in or near the inner ring since early larval stages, this domain expands with a rapid increase in wingless expression. TnaA occupies the wingless Inner Ring Enhancer at the wing disc, meanwhile it does not affect wingless expression directed by the Ventral Disc Enhancer in leg discs, suggesting that TnaA acts as a wingless enhancer-specific factor. We describe for the first time the presence of TnaA at the Inner Ring Enhancer as a specific regulator of wingless in the development of wing boundaries.


Assuntos
Drosophila melanogaster , Drosophila , Animais , Drosophila melanogaster/genética , Discos Imaginais , Larva , Ubiquitina-Proteína Ligases
12.
Animals (Basel) ; 13(16)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37627418

RESUMO

Stereotaxic surgeries enable precise access to specific brain regions, being of particular interest for chronic intracerebroventricular drug delivery. However, the challenge of long-term studies at this level is to allow the implantation of drug storage devices and their correct intrathecal connection while guaranteeing animal welfare during the entire study period. In this study, we propose an optimized method for safe intrathecal device implantation, focusing on preoperative, intraoperative, and postoperative procedures, following the 3Rs principle and animal welfare regulations. Our optimized protocol introduces three main refinements. Firstly, we modify the dimensions of the implantable devices, notably diminishing the device-to-mouse weight ratio. Secondly, we use a combination of cyanoacrylate tissue adhesive and UV light-curing resin, which decreases surgery time, improves healing, and notably minimizes cannula detachment or adverse effects. Thirdly, we develop a customized welfare assessment scoresheet to accurately monitor animal well-being during long-term implantations. Taken together, these refinements positively impacted animal welfare by minimizing the negative effects on body weight, surgery-related complications, and anxiety-like behaviors. Overall, the proposed refinements have the potential to reduce animal use, enhance experimental data quality, and improve reproducibility. Additionally, these improvements can be extended to other neurosurgical techniques, thereby advancing neuroscience research, and benefiting the scientific community.

13.
Jpn Dent Sci Rev ; 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37360001

RESUMO

Accurate, self-collected, and non-invasive diagnostics are critical to perform mass-screening diagnostic tests for COVID-19. This systematic review with meta-analysis evaluated the accuracy, sensitivity, and specificity of salivary diagnostics for COVID-19 based on SARS-CoV-2 RNA compared with the current reference tests using a nasopharyngeal swab (NPS) and/or oropharyngeal swab (OPS). An electronic search was performed in seven databases to find COVID-19 diagnostic studies simultaneously using saliva and NPS/OPS tests to detect SARS-CoV-2 by RT-PCR. The search resulted in 10,902 records, of which 44 studies were considered eligible. The total sample consisted of 14,043 participants from 21 countries. The accuracy, specificity, and sensitivity for saliva compared with the NPS/OPS was 94.3% (95%CI= 92.1;95.9), 96.4% (95%CI= 96.1;96.7), and 89.2% (95%CI= 85.5;92.0), respectively. Besides, the sensitivity of NPS/OPS was 90.3% (95%CI= 86.4;93.2) and saliva was 86.4% (95%CI= 82.1;89.8) compared to the combination of saliva and NPS/OPS as the gold standard. These findings suggest a similarity in SARS-CoV-2 RNA detection between NPS/OPS swabs and saliva, and the association of both testing approaches as a reference standard can increase by 3.6% the SARS-CoV-2 detection compared with NPS/OPS alone. This study supports saliva as an attractive alternative for diagnostic platforms to provide a non-invasive detection of SARS-CoV-2.

14.
Diagnostics (Basel) ; 13(8)2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37189545

RESUMO

Zika virus (ZIKV) diagnosis is currently performed through an invasive, painful, and costly procedure using molecular biology. Consequently, the search for a non-invasive, more cost-effective, reagent-free, and sustainable method for ZIKV diagnosis is of great relevance. It is critical to prepare a global strategy for the next ZIKV outbreak given its devastating consequences, particularly in pregnant women. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy has been used to discriminate systemic diseases using saliva; however, the salivary diagnostic application in viral diseases is unknown. To test this hypothesis, we intradermally challenged interferon-gamma gene knockout C57/BL6 mice with ZIKV (50 µL,105 FFU, n = 7) or vehicle (50 µL, n = 8). Saliva samples were collected on day three (due to the peak of viremia) and the spleen was also harvested. Changes in the salivary spectral profile were analyzed by Student's t test (p < 0.05), multivariate analysis, and the diagnostic capacity by ROC curve. ZIKV infection was confirmed by real-time PCR of the spleen sample. The infrared spectroscopy coupled with univariate analysis suggested the vibrational mode at 1547 cm-1 as a potential candidate to discriminate ZIKV and control salivary samples. Three PCs explained 93.2% of the cumulative variance in PCA analysis and the spectrochemical analysis with LDA achieved an accuracy of 93.3%, with a specificity of 87.5% and sensitivity of 100%. The LDA-SVM analysis showed 100% discrimination between both classes. Our results suggest that ATR-FTIR applied to saliva might have high accuracy in ZIKV diagnosis with potential as a non-invasive and cost-effective diagnostic tool.

15.
Int J Biol Macromol ; 227: 630-640, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36529220

RESUMO

Zika virus is the etiologic agent of Zika fever, and has been previously associated with cases of microcephaly, drawing the attention of the health authorities worldwide. However, no vaccine or antiviral are currently available. Phospholipases A2 (PLA2) isolated from snake venoms have demonstrated antiviral activity against several viruses. Here we demonstrated the anti-ZIKV activity of bothropstoxins-I and II (BthTX-I and II) isolated from Bothrops jararacussu venom. Vero E6 cells were infected with ZIKVPE243 in the presence of compounds for 72 h, when virus titers were evaluated. BthTX-I and II presented strong dose-dependent inhibition of ZIKV, with a SI of 149.1 and 1.44 × 105, respectively. These toxins mainly inhibited the early stages of the replicative cycle, such as during the entry of ZIKV into host cells, as shown by the potent virucidal effect, suggesting the action of these toxins on the virus particles. Moreover, BthTX-I and II presented significant activity towards post-entry stages of the ZIKV replicative cycle. Molecular docking analyses showed that BthTX-I and II potentially interact with DII and DIII domains from ZIKV Envelope protein. Our findings show that these PLA2s could be used as useful templates for the development of future antiviral candidate drugs against Zika fever.


Assuntos
Bothrops , Venenos de Crotalídeos , Infecção por Zika virus , Zika virus , Animais , Humanos , Antivirais/farmacologia , Bothrops/metabolismo , Infecção por Zika virus/tratamento farmacológico , Simulação de Acoplamento Molecular , Venenos de Crotalídeos/metabolismo , Anticorpos
16.
Spectrochim Acta A Mol Biomol Spectrosc ; 290: 122259, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-36584643

RESUMO

The development of novel platforms for non-invasive continuous glucose monitoring applied in the screening and monitoring of diabetes is crucial to improve diabetes surveillance systems. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy of urine can be an alternative as a sustainable, label-free, fast, non-invasive, and highly sensitive analysis to detect changes in urine promoted by diabetes and insulin treatment. In this study, we used ATR-FTIR to evaluate the urinary components of non-diabetic (ND), diabetic (D), and diabetic insulin-treated (D + I) rats. As expected, insulin treatment was capable to revert changes in glycemia, 24-h urine collection volume, urine creatinine, urea, and glucose excretion promoted by diabetes. Several differences in the urine spectra of ND, D, and D + I were observed, with urea, creatinine, and glucose analytes being related to these changes. Principal components analysis (PCA) scores plots allowed for the discrimination of ND and D + I from D with an accuracy of âˆ¼ 99 %. The PCA loadings associated with PC1 confirmed the importance of urea and glucose vibrational modes for this discrimination. Univariate analysis of second derivative spectra showed a high correlation (r: 0.865, p < 0.0001) between the height of 1074 cm-1 vibrational mode with urinary glucose concentration. In order to estimate the amount of glucose present in the infrared spectra from urine, multivariate curve resolution-alternating least square (MCR-ALS) was applied and a higher predicted concentration of glucose in the urine was observed with a correlation of 78.9 % compared to urinary glucose concentration assessed using enzyme assays. In summary, ATR-FTIR combined with univariate and multivariate chemometric analyses provides an innovative, non-invasive, and sustainable approach to diabetes surveillance.


Assuntos
Automonitorização da Glicemia , Insulinas , Ratos , Animais , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Creatinina , Glicemia , Glucose/análise , Ureia
17.
Virus Res ; 324: 199029, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36565816

RESUMO

The Chikungunya virus (CHIKV) causes Chikungunya fever, a disease characterized by symptoms such as arthralgia/polyarthralgia. Currently, there are no antivirals approved against CHIKV, emphasizing the need to develop novel therapies. The imidazonaphthyridine compound (RO8191), an interferon-α (IFN-α) agonist, was reported as a potent inhibitor of HCV. Here RO8191 was investigated for its potential to inhibit CHIKV replication in vitro. RO8191 inhibited CHIKV infection in BHK-21 and Vero-E6 cells with a selectivity index (SI) of 12.3 and 37.3, respectively. Additionally, RO8191 was capable to protect cells against CHIKV infection, inhibit entry by virucidal activity, and strongly impair post-entry steps of viral replication. An effect of RO8191 on CHIKV replication was demonstrated in BHK-21 through type-1 IFN production mechanism and in Vero-E6 cells which has a defective type-1 IFN production, also suggesting a type-1 IFN independent mode of action. Molecular docking calculations demonstrated interactions of RO8191 with the CHIKV E proteins, corroborated by the ATR-FTIR assay, and with non-structural proteins, supported by the CHIKV-subgenomic replicon cells assay.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Interferon Tipo I , Animais , Chlorocebus aethiops , Humanos , Febre de Chikungunya/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêutico , Simulação de Acoplamento Molecular , Replicação Viral , Células Vero , Interferon Tipo I/farmacologia
18.
Neurol India ; 70(Supplement): S318-S321, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36412389

RESUMO

Meningeal melanomatosis is an infrequent tumor originating from the melanocytes in the leptomeninges and one of the recognized primary melanocytic tumors of the central nervous system. The average survival has known to be about 5 months. It can be associated with solid tumors, such as meningeal melanocytomas. The patient we present was diagnosed of a meningeal melanomatosis that developed two solid tumors related to an in vitro fertilization. The clinical course was rapidly fatal. Although the use of comprehensive diagnostic procedures, usually the final diagnosis of primary diffuse meningeal melanomatosis is postmortem, it would be advisable for the appropriate management of the patient to make a differential diagnosis and to be aware of the behavior of the tumor.


Assuntos
Fertilização in vitro , Melanoma , Neoplasias Meníngeas , Neoplasias da Medula Espinal , Adulto , Humanos , Evolução Fatal , Fertilização in vitro/efeitos adversos , Melanoma/diagnóstico , Melanoma/etiologia , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/etiologia , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/etiologia
19.
Int J Mol Sci ; 23(16)2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36012525

RESUMO

We have previously proposed a radical change in the current strategy to clear pathogenic proteins from the central nervous system (CNS) based on the cerebrospinal fluid (CSF)-sink therapeutic strategy, whereby pathogenic proteins can be removed directly from the CNS via CSF. To this aim, we designed and manufactured an implantable device for selective and continuous apheresis of CSF enabling, in combination with anti-amyloid-beta (Aß) monoclonal antibodies (mAb), the clearance of Aß from the CSF. Here, we provide the first proof of concept in the APP/PS1 mouse model of Alzheimer's disease (AD). Devices were implanted in twenty-four mice (seventeen APP/PS1 and seven Wt) with low rates of complications. We confirmed that the apheresis module is permeable to the Aß peptide and impermeable to mAb. Moreover, our results showed that continuous clearance of soluble Aß from the CSF for a few weeks decreases cortical Aß plaques. Thus, we conclude that this intervention is feasible and may provide important advantages in terms of safety and efficacy.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Placa Amiloide/metabolismo
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