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1.
J Med Life ; 13(2): 235-240, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742520

RESUMO

Oral fluids provide a readily available and non-invasive medium for the diagnosis of a wide range of diseases and clinical situations. Diabetes mellitus is a common chronic metabolic disorder that affects millions of people. Our objective was to compare the salivary and serum glucose levels in patients with diabetes mellitus and healthy individuals. Two ml of unstimulated whole saliva was collected by the spitting method. Also, 2 ml of the patient's intravenous blood was obtained from the forearm's median cephalic vein. Both the samples were centrifuged at 2000 rpm for 2-3 minutes. Ten µl of both saliva and serum were taken out and added to glucose reagent. These were kept in a temperature-controlled water bath at 37°C for 10 minutes. The color change was noted, and the optical density was measured in a semi-auto analyzer. The presence of glucose was detected in both groups; however, the levels were raised in people with diabetes compared to healthy individuals. The present study indicated a substantial increase in salivary and serum glucose levels in diabetic patients compared to healthy controls. The concentration of glucose in saliva increases with the increase in serum glucose concentration.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus/sangue , Saliva/metabolismo , Adulto , Distribuição por Idade , Estudos de Casos e Controles , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade
2.
PLoS One ; 15(8): e0236566, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785281

RESUMO

INTRODUCTION: Many sleep and circadian studies require participants to adhere to structured sleep-wake schedules designed to stabilize sleep outcomes and circadian phase prior to in-laboratory testing. The effectiveness of this approach has not been rigorously evaluated, however. We therefore investigated the differences between participants' unstructured and structured sleep over a three-week interval. METHODS: Twenty-three healthy young adults completed three weeks of sleep monitoring, including one week of unstructured sleep and two weeks of structured sleep with consistent bed and wake times. Circadian phase was assessed via salivary dim light melatonin onset (DLMO) during both the unstructured and structured sleep episodes. RESULTS: Compared to their unstructured sleep schedule, participants' bed- and wake times were significantly earlier in their structured sleep, by 34 ± 44 mins (M ± SD) and 44 ± 41 mins, respectively. During structured sleep, circadian phase was earlier in 65% of participants (40 ± 32 mins) and was later in 35% (41 ± 25 mins) compared to unstructured sleep but did not change at the group level. While structured sleep reduced night-to-night variability in sleep timing and sleep duration, and improved the alignment (phase angle) between sleep onset and circadian phase in the most poorly aligned individuals (DLMO < 1h or > 3h before sleep onset time; 25% of our sample), sleep duration and quality were unchanged. CONCLUSION: Our results show adherence to a structured sleep schedule results in more regular sleep timing, and improved alignment between sleep and circadian timing for those individuals who previously had poorer alignment. Our findings support the use of structured sleep schedules prior to in-laboratory sleep and circadian studies to stabilize sleep and circadian timing in healthy volunteers.


Assuntos
Ritmo Circadiano/fisiologia , Melatonina/metabolismo , Privação do Sono/fisiopatologia , Sono/fisiologia , Adulto , Ritmo Circadiano/genética , Feminino , Humanos , Individualidade , Luz , Masculino , Pessoa de Meia-Idade , Saliva/metabolismo , Sono/genética , Privação do Sono/metabolismo , Transtornos do Sono-Vigília/metabolismo , Transtornos do Sono-Vigília/fisiopatologia , Fatores de Tempo , Adulto Jovem
3.
Int J Mol Sci ; 21(17)2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32825469

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin, which promote entry of the virus into the host cell, have been identified as determinants of SARS-CoV-2 infection. Dorsal tongue and gingiva, saliva, and tongue coating samples were examined to determine the presence of these molecules in the oral cavity. Immunohistochemical analyses showed that ACE2 was expressed in the stratified squamous epithelium of the dorsal tongue and gingiva. TMPRSS2 was strongly expressed in stratified squamous epithelium in the keratinized surface layer and detected in the saliva and tongue coating samples via Western blot. Furin was localized mainly in the lower layer of stratified squamous epithelium and detected in the saliva but not tongue coating. ACE2, TMPRSS2, and furin mRNA expression was observed in taste bud-derived cultured cells, which was similar to the immunofluorescence observations. These data showed that essential molecules for SARS-CoV-2 infection were abundant in the oral cavity. However, the database analysis showed that saliva also contains many protease inhibitors. Therefore, although the oral cavity may be the entry route for SARS-CoV-2, other factors including protease inhibitors in the saliva that inhibit viral entry should be considered.


Assuntos
Betacoronavirus/metabolismo , Furina/metabolismo , Mucosa Bucal/metabolismo , Peptidil Dipeptidase A/metabolismo , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Infecções por Coronavirus/metabolismo , Gengiva/metabolismo , Humanos , Pandemias , Pneumonia Viral/metabolismo , Saliva/metabolismo , Língua/metabolismo , Internalização do Vírus
4.
PLoS One ; 15(8): e0237004, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756589

RESUMO

Dysregulated expression of MicroRNAs (miRNAs) plays substantial role in the initiation and progression of both diabetes and periodontitis. The aim of the present study was to validate four miRNAs in saliva as potential predictive biomarkers of periodontal disease among patients with and without diabetes mellitus (DM). MiRNAs were extracted from the saliva of 24 adult subjects with DM and 29 healthy controls. Each group was subdivided into periodontally healthy or having periodontitis. In silico analysis identified 4 miRNAs (miRNA 155, 146 a/b and 203) as immune modulators. The expression of miRNAs-146a/b, 155, and 203 was tested using quantitative PCR. The expression levels in the study groups were compared to explore the effect of diabetes on periodontal status and vice versa. In our cohort, the four miRNAs expression were higher in patients with periodontitis and/or diabetes. miRNA-155 was the most reliable predictors of periodontitis among non-diabetics with an optimum cut-off value of < 8.97 with accuracy = 82.6%. MiRNA 146a, on the other hand, was the only reliable predictor of periodontitis among subjects with diabetes with optimum cut-off value of ≥11.04 with accuracy = 86.1%. The results of the present study concluded that MiRNA-146a and miRNA155 in saliva provide reliable, non-invasive, diagnostic and prognostic biomarkers that can be used to monitor periodontal health status among diabetic and non-diabetic patients.


Assuntos
Diabetes Mellitus/diagnóstico , MicroRNAs/metabolismo , Periodontite/diagnóstico , Adolescente , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/genética , Complicações do Diabetes/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Análise Discriminante , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Periodontite/genética , Periodontite/metabolismo , Projetos Piloto , Saliva/metabolismo , Regulação para Cima , Adulto Jovem
5.
PLoS One ; 15(8): e0237410, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817706

RESUMO

The minimum infectious dose required to induce CWD infection in cervids remains unknown, as does whether peripherally shed prions and/or multiple low dose exposures are important factors in CWD transmission. With the goal of better understand CWD infection in nature, we studied oral exposures of deer to very low doses of CWD prions and also examined whether the frequency of exposure or prion source may influence infection and pathogenesis. We orally inoculated white-tailed deer with either single or multiple divided doses of prions of brain or saliva origin and monitored infection by serial longitudinal tissue biopsies spanning over two years. We report that oral exposure to as little as 300 nanograms (ng) of CWD-positive brain or to saliva containing seeding activity equivalent to 300 ng of CWD-positive brain, were sufficient to transmit CWD disease. This was true whether the inoculum was administered as a single bolus or divided as three weekly 100 ng exposures. However, when the 300 ng total dose was apportioned as 10, 30 ng doses delivered over 12 weeks, no infection occurred. While low-dose exposures to prions of brain or saliva origin prolonged the time from inoculation to first detection of infection, once infection was established, we observed no differences in disease pathogenesis. These studies suggest that the CWD minimum infectious dose approximates 100 to 300 ng CWD-positive brain (or saliva equivalent), and that CWD infection appears to conform more with a threshold than a cumulative dose dynamic.


Assuntos
Encéfalo/metabolismo , Exposição Ambiental/efeitos adversos , Príons/metabolismo , Saliva/metabolismo , Doença de Emaciação Crônica/transmissão , Animais , Cervos
6.
J Cancer Res Ther ; 16(3): 401-404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719243

RESUMO

To review the relevance of sialic acid as a tumour marker in oral cancer. Tumour marker are useful in the screening for early malignancy. Sialic acids are important in determining the surface properties of cells and has been implicated in cellular invasiveness, adhesiveness, and immunogenicity. Sialic acids are commonly found at the outermost end of glycan chains of all cell types. Increase in the levels of sialic acid in oral cancer indicates its importance as a tumour marker.Both serum and salivary sialic acid levels can be used as a screening tool and a diagnostic aid for oral cancer. Salivary sialic acid can be used as a non-invasive, cost effective and reliable diagnostic methods for screening and monitoring of oral cancer. In patients with oral cancer, glycoprotein metabolism is altered. Increase in the levels of sialic acid in oral cancer indicate its importance as a tumour marker. Changes in the serum is reflected in saliva. Salivary sialic acid can be used as non-invasive, cost effective and reliable diagnostic methods for screening and monitoring of oral cancer. Early the diagnosis, better the prognosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Bucais/diagnóstico , Ácido N-Acetilneuramínico/análise , Lesões Pré-Cancerosas/diagnóstico , Saliva/metabolismo , Carcinoma de Células Escamosas/metabolismo , Humanos , Neoplasias Bucais/metabolismo , Lesões Pré-Cancerosas/metabolismo , Prognóstico , Saliva/química
7.
J Cancer Res Ther ; 16(3): 452-457, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719250

RESUMO

Introduction: Cytokeratin fragment 21-1 (CYFRA21-1), a constituent of the intermediate filament protein is known to be elevated in cancer. In vitro cleavage of cytokeratin 19 (CK19) protein results in the release of it's fragments into the supernatants of premalignant cell lines. This study was designed with the aim to investigate the concentrations of CYFRA21-1 in serum and saliva of oral potentially malignant disorders (OPMD), to evaluate CK19 expression in tissues of the same patients and to correlate the levels of CYFRA21-1 concentration in serum and saliva with CK19 expression in OPMDs, and to compare it with oral squamous cell carcinoma (OSCC), which was taken as positive control. Materials and Methods: Concentration of CYFRA21-1 was measured in saliva and serum of 30 OPMD cases with five patients having OSCC using ELISA technique and analysis of CK19 protein expression in the tissue of same patients using immunohistochemical technique was done. Results: Concentration of CYFRA21-1 in saliva and serum with regard to CK19 protein expression in tissues was significantly higher in control group than in study groups. Conclusion: CYFRA21-1 can be used as a promising diagnostic molecule and as an adjunctive marker for early detection, disease staging, and monitoring.


Assuntos
Antígenos de Neoplasias/análise , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Queratina-19/análise , Queratina-19/metabolismo , Neoplasias Bucais/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Saliva/metabolismo , Adulto , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Lesões Pré-Cancerosas/metabolismo
8.
Proc Natl Acad Sci U S A ; 117(28): 16167-16173, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32601197

RESUMO

Saliva is a noninvasive biofluid that can contain metabolite signatures of oral squamous cell carcinoma (OSCC). Conductive polymer spray ionization mass spectrometry (CPSI-MS) is employed to record a wide range of metabolite species within a few seconds, making this technique appealing as a point-of-care method for the early detection of OSCC. Saliva samples from 373 volunteers, 124 who are healthy, 124 who have premalignant lesions, and 125 who are OSCC patients, were collected for discovering and validating dysregulated metabolites and determining altered metabolic pathways. Metabolite markers were reconfirmed at the primary tissue level by desorption electrospray ionization MS imaging (DESI-MSI), demonstrating the reliability of diagnoses based on saliva metabolomics. With the aid of machine learning (ML), OSCC and premalignant lesions can be distinguished from the normal physical condition in real time with an accuracy of 86.7%, on a person by person basis. These results suggest that the combination of CPSI-MS and ML is a feasible tool for accurate, automated diagnosis of OSCC in clinical practice.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Metabolômica , Neoplasias Bucais/diagnóstico , Saliva/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Testes Imediatos , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray
9.
Medicine (Baltimore) ; 99(22): e20419, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481437

RESUMO

We explored the potential of combining carcinoembryonic antigen (CEA) and salivary mRNAs for gastric cancer (GC) detection.This study included 2 phases of study: a biomarker discovery phase and an independent validation phase. In the discovery phase, we measured CEA levels in blood samples and expression level of messenger RNAs (SPINK7, PPL, SEMA4B, SMAD4) in saliva samples of 140 GC patients and 140 healthy controls. We evaluated the clinical performance of each biomarker and developed a predictive model using machine-learning algorithm to differentiate GC patients and healthy controls.Our biomarker panel successfully discriminated GC patients from healthy controls with both high sensitivity (0.94) and high specificity (0.91). We next applied our biomarker panel in the independent validation phase, in which we recruited a new patient cohort of 60 GC patients and 60 healthy controls. Using our biomarker panel, the GC patients were discriminated from healthy controls in the validation phase, with sensitivity of 0.92 and specificity of 0.87.A combination of blood CEA and salivary messenger RNA could be a promising approach to detect GC.


Assuntos
Antígeno Carcinoembrionário/metabolismo , RNA Mensageiro/metabolismo , Neoplasias Gástricas/diagnóstico , Biomarcadores Tumorais/metabolismo , Estudos de Coortes , Diagnóstico por Computador , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Plaquinas/metabolismo , Estudo de Prova de Conceito , Saliva/metabolismo , Semaforinas/metabolismo , Sensibilidade e Especificidade , Inibidores de Serinopeptidase do Tipo Kazal/metabolismo , Proteína Smad4/metabolismo , Neoplasias Gástricas/metabolismo
10.
J Anal Toxicol ; 44(7): 741-746, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32591773

RESUMO

Neonatal drug exposure is currently assessed using meconium, urine, blood, hair, or umbilical cord tissue/blood. Due to the invasiveness, challenges, and limitations of collection, and/or analytical difficulties of these matrices, oral fluid may be a more desirable matrix in diagnosing opioid exposure and risk for opioid withdrawal in neonatal abstinence syndrome. Traditional oral fluid collection devices are not viable options as they are too large for neonates' mouths and may contain chemicals on the collection pad. Unstimulated and stimulated infant oral fluid samples have been used for therapeutic drug monitoring as an alternative matrix to blood. The objective of this study was to assess the viability of a simple oral fluid collection system using a sterile foam-tipped swab rinsed in phosphate-buffered saline. Two infants were administered fentanyl for post-operative pain relief while hospitalized in the Neonatal Intensive Care Units at the Children's Hospital of Richmond of Virginia Commonwealth University. Oral fluid samples were collected at 16 h, 2 days, and/or 7 days following the start of intravenous infusion of fentanyl. Samples were analyzed by ultra-high-pressure liquid chromatography-tandem mass spectrometry for fentanyl and norfentanyl after solid-phase extraction. In one of the three samples tested, fentanyl and norfentanyl were detected at concentrations of 28 and 78 ng/mL, respectively. Based on the infusion rate, the theoretical oral fluid fentanyl concentration at steady state was calculated to be 33 ng/mL.


Assuntos
Fentanila/metabolismo , Saliva/metabolismo , Toxicologia Forense , Humanos , Lactente , Recém-Nascido , Extração em Fase Sólida
11.
J Anal Toxicol ; 44(7): 661-671, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32591782

RESUMO

Oral cannabis products (a.k.a. "edibles") have increased in popularity in recent years. Most prior controlled pharmacokinetic evaluations of cannabis have focused on smoked cannabis and included males who were frequent cannabis users. In this study, 17 healthy adults (8 females), with no cannabis use in at least the past 2 months, completed 4 double-blind outpatient sessions where they consumed cannabis brownies containing Δ9-tetrahydrocannabinol (THC) doses of 0, 10, 25 or 50 mg. Whole blood and oral fluid specimens were collected at baseline and for 8 h post-brownie ingestion. Enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) were used to measure THC and relevant metabolites. In whole blood, concentrations of THC and 11-hydroxy-THC (11-OH-THC) peaked 1.5-2 h after brownie consumption, decreased steadily thereafter, and typically returned to baseline within 8 h. Blood concentrations for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) and THCCOOH-glucuronide were higher than THC and 11-OH-THC and these metabolites were often still detected 8 h post-brownie consumption. Women displayed higher peak concentrations for THC and all metabolites in whole blood compared to men, at least partially owing to their lower body weight/body mass index. Detection of THC in oral fluid was immediate and appeared to reflect the degree of cannabis deposition in the oral cavity, not levels of THC circulating in the blood. THC concentrations were substantially higher in oral fluid than in blood; the opposite trend was observed for THCCOOH. Agreement between ELISA and LC-MS-MS results was high (i.e., over 90%) for blood THCCOOH and oral fluid THC but comparatively low for oral fluid THCCOOH (i.e., 67%). Following oral consumption of cannabis, THC was detected in blood much later, and at far lower peak concentrations, compared to what has been observed with inhaled cannabis. These results are important given the widespread use of toxicological testing to detect recent use of cannabis and/or to identify cannabis intoxication.


Assuntos
Dronabinol/farmacocinética , Psicotrópicos/farmacocinética , Administração Oral , Adulto , Cannabis , Dronabinol/metabolismo , Feminino , Humanos , Masculino , Psicotrópicos/metabolismo , Saliva/metabolismo , Detecção do Abuso de Substâncias/métodos , Adulto Jovem
12.
PLoS One ; 15(4): e0232351, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353026

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by major social, communication and behavioural challenges. The cause of ASD is still unclear and it is assumed that environmental, genetic and epigenetic factors influence the risk of ASD occurrence. MicroRNAs (miRNAs) are short 21-25 nucleotide long RNA molecules which post-transcriptionally regulate gene expression. MiRNAs play an important role in central nervous system development; therefore, dysregulation of miRNAs is connected to changes in behaviour and cognition observed in many disorders including ASD. Based on previously published work, on diagnosing ASD using miRNAs, we hypothesized that miRNAs can be used as biomarkers in children with suspected developmental disorders (DD) including ASD within Bosnian-Herzegovinian (B&H) population. 14 selected miRNAs were tested on saliva of children with suspected developmental disorders including ASD. The method of choice was qRT-PCR as a relatively cheap method available in most diagnostic laboratories in low to mid-income countries (LMIC). Out of 14 analysed miRNAs, 6 were differentially expressed between typically developing children and children with some type of developmental disorder including autism spectrum disorder. Using the most optimal logistic regression, we were able to distinguish between ASD and typically developing (TD) children. We have found 5 miRNAs as potential biomarkers. From those, 3 were differentially expressed within the ASD cohort. All 5 miRNAs had shown good chi-square statistics within the logistic regression performed on all 14 analysed miRNAs. The accuracy of 5-miRNAs model training set was 90.2%, while the validation set had a 90% accuracy. This study has shown that miRNAs may be considered as biomarkers for ASD detection and may be used to identify children with ASD along with standard developmental screening tests. By combining these methods we may be able to reach a reliable and accessible diagnostic model for children with ASD in LMIC such as B&H.


Assuntos
Transtorno do Espectro Autista/genética , MicroRNAs/genética , Saliva/metabolismo , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/metabolismo , Biomarcadores/análise , Bósnia e Herzegóvina , Criança , Pré-Escolar , Feminino , Humanos , Masculino , MicroRNAs/análise , Saliva/química
13.
Encephale ; 46(3S): S35-S39, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32387014

RESUMO

OBJECTIVES: The ongoing COVID-19 pandemic comprises a total of more than 2,350,000 cases and 160,000 deaths. The interest in anti-coronavirus drug development has been limited so far and effective methods to prevent or treat coronavirus infections in humans are still lacking. Urgent action is needed to fight this fatal coronavirus infection by reducing the number of infected people along with the infection contagiousness and severity. Since the beginning of the COVID-19 outbreak several weeks ago, we observe in GHU PARIS Psychiatrie & Neurosciences (Sainte-Anne hospital, Paris, France) a lower prevalence of symptomatic and severe forms of COVID-19 infections in psychiatric patients (∼4%) compared to health care professionals (∼14%). Similar observations have been noted in other psychiatric units in France and abroad. Our hypothesis is that psychiatric patients could be protected from severe forms of COVID-19 by their psychotropic treatments. Chlorpromazine (CPZ) is a phenothiazine derivative widely used in clinical routine in the treatment of acute and chronic psychoses. This first antipsychotic medication has been discovered in 1952 by Jean Delay and Pierre Deniker at Sainte-Anne hospital. In addition, to its antipsychotic effects, several in vitro studies have also demonstrated a CPZ antiviral activity via the inhibition of clathrin-mediated endocytosis. Recently, independent studies revealed that CPZ is an anti-MERS-CoV and an anti-SARS-CoV-1 drug. In comparison to other antiviral drugs, the main advantages of CPZ lie in its biodistribution: (i) preclinical and clinical studies have reported a high CPZ concentration in the lungs (20-200 times higher than in plasma), which is critical because of the respiratory tropism of SARS-CoV-2; (ii) CPZ is highly concentrated in saliva (30-100 times higher than in plasma) and could therefore reduce the contagiousness of COVID-19; (iii) CPZ can cross the blood-brain barrier and could therefore prevent the neurological forms of COVID-19. METHODS: Our hypothesis is that CPZ could decrease the unfavorable evolution of COVID-19 infection in oxygen-requiring patients without the need for intensive care, but also reduce the contagiousness of SARS-CoV-2. At this end, we designed a pilot, phase III, multicenter, single blind, randomized controlled clinical trial. Efficacy of CPZ will be assessed according to clinical, biological and radiological criteria. The main objective is to demonstrate a shorter time to response (TTR) to treatment in the CPZ+standard-of-care (CPZ+SOC) group, compared to the SOC group. Response to treatment is defined by a reduction of at least one level of severity on the WHO-Ordinal Scale for Clinical Improvement (WHO-OSCI). The secondary objectives are to demonstrate in the CPZ+SOC group, compared to the SOC group: (A) superior clinical improvement; (B) a greater decrease in the biological markers of viral attack by SARS-CoV-2 (PCR, viral load); (C) a greater decrease in inflammatory markers (e.g. CRP and lymphopenia); (D) a greater decrease in parenchymal involvement (chest CT) on the seventh day post-randomization; (E) to define the optimal dosage of CPZ and its tolerance; (F) to evaluate the biological parameters of response to treatment, in particular the involvement of inflammatory cytokines. Patient recruitment along with the main and secondary objectives are in line with WHO 2020 COVID-19 guidelines. CONCLUSION: This repositioning of CPZ as an anti-SARS-CoV-2 drug offers an alternative and rapid strategy to alleviate the virus propagation and the infection severity and lethality. This CPZ repositioning strategy also avoids numerous developmental and experimental steps and can save precious time to rapidly establish an anti-COVID-19 therapy with well-known, limited and easy to manage side effects. Indeed, CPZ is an FDA-approved drug with an excellent tolerance profile, prescribed for around 70 years in psychiatry but also in clinical routine in nausea and vomiting of pregnancy, in advanced cancer and also to treat headaches in various neurological conditions. The broad spectrum of CPZ treatment - including antipsychotic, anxiolytic, antiemetic, antiviral, immunomodulatory effects along with inhibition of clathrin-mediated endocytosis and modulation of blood-brain barrier - is in line with the historical French commercial name for CPZ, i.e. LARGACTIL, chosen as a reference to its "LARGe ACTion" properties. The discovery of those CPZ properties, as for many other molecules in psychiatry, is both the result of serendipity and careful clinical observations. Using this approach, the field of mental illness could provide innovative therapeutic approaches to fight SARS-CoV-2.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Clorpromazina/uso terapêutico , Ensaios Clínicos Fase III como Assunto/métodos , Infecções por Coronavirus/tratamento farmacológico , Estudos Multicêntricos como Assunto/métodos , Pandemias , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Antivirais/farmacocinética , Antivirais/farmacologia , Biomarcadores , Barreira Hematoencefálica , Clorpromazina/farmacocinética , Clorpromazina/farmacologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Citocinas/sangue , Relação Dose-Resposta a Droga , Reposicionamento de Medicamentos , Endocitose/efeitos dos fármacos , França/epidemiologia , Humanos , Pulmão/metabolismo , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Seleção de Pacientes , Projetos Piloto , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Projetos de Pesquisa , Saliva/metabolismo , Índice de Gravidade de Doença , Método Simples-Cego , Distribuição Tecidual
14.
PLoS One ; 15(5): e0230704, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32357152

RESUMO

BACKGROUND: Cortisol has been used to capture psychophysiological stress during childbirth and postpartum wellbeing. We explored the effect of a brief antenatal training course in self-hypnosis on salivary cortisol during childbirth and 6 weeks postpartum. METHODS: In a randomized, controlled trial conducted at Aarhus University Hospital Skejby Denmark during the period January 2010 until October 2010, a total of 349 healthy nulliparous women were included. They were randomly allocated to a hypnosis group (n = 136) receiving three one-hour lessons in self-hypnosis with additional audio-recordings, a relaxation group (n = 134) receiving three one-hour lessons in various relaxation methods with audio-recordings for additional training, and a usual care group (n = 79) receiving ordinary antenatal care only. Salivary cortisol samples were collected during childbirth (at the beginning of the pushing state, 30 minutes, and 2 hours after childbirth), and 6 weeks postpartum (at wake up, 30 minutes after wake up, and evening). Cortisol concentrations were compared using a linear mixed-effects model. Correlations between cortisol concentrations and length of birth, experienced pain and calmness during birth were examined by a Spearman rank correlation test. FINDINGS: During childbirth, week correlations were found between cortisol concentrations 30 minutes after childbirth and length of birth. In the beginning of the pushing state and 2 hours after childbirth, we found a tendency towards higher cortisol concentrations in the hypnosis group compared to the other two groups (hypnosis versus relaxation p = 0.02 and 0.03, hypnosis versus usual care p = 0.08 and 0.05). No differences were observed in cortisol concentrations between the groups 30 minutes after childbirth (hypnosis versus relaxation p = 0.08, hypnosis versus usual care 0.10) or 6 weeks postpartum (hypnosis versus relaxation: p = 0.85, 0.51, and 0.68, hypnosis versus usual care: p = 0.85, 0.93, and 0.96). CONCLUSION: Antenatal hypnosis training may increase the release of cortisol during childbirth with no long-term consequences. Further research is needed to help interpret these findings.


Assuntos
Hipnose/métodos , Dor do Parto/terapia , Parto/metabolismo , Terapia de Relaxamento , Adulto , Analgesia Obstétrica/efeitos adversos , Parto Obstétrico , Feminino , Humanos , Hidrocortisona/metabolismo , Dor do Parto/metabolismo , Dor do Parto/fisiopatologia , Trabalho de Parto/fisiologia , Parto/fisiologia , Satisfação do Paciente , Período Pós-Parto/metabolismo , Período Pós-Parto/fisiologia , Gravidez , Cuidado Pré-Natal , Saliva/metabolismo
15.
Proc Natl Acad Sci U S A ; 117(23): 12657-12664, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32461364

RESUMO

Blood-feeding arthropods produce antiinflammatory salivary proteins called evasins that function through inhibition of chemokine-receptor signaling in the host. Herein, we show that the evasin ACA-01 from the Amblyomma cajennense tick can be posttranslationally sulfated at two tyrosine residues, albeit as a mixture of sulfated variants. Homogenously sulfated variants of the proteins were efficiently assembled via a semisynthetic native chemical ligation strategy. Sulfation significantly improved the binding affinity of ACA-01 for a range of proinflammatory chemokines and enhanced the ability of ACA-01 to inhibit chemokine signaling through cognate receptors. Comparisons of evasin sequences and structural data suggest that tyrosine sulfation serves as a receptor mimetic strategy for recognizing and suppressing the proinflammatory activity of a wide variety of mammalian chemokines. As such, the incorporation of this posttranslational modification (PTM) or mimics thereof into evasins may provide a strategy to optimize tick salivary proteins for antiinflammatory applications.


Assuntos
Ácaros e Carrapatos/metabolismo , Proteínas de Artrópodes/metabolismo , Quimiocinas/antagonistas & inibidores , Processamento de Proteína Pós-Traducional , Saliva/metabolismo , Animais , Proteínas de Artrópodes/química , Quimiocinas/metabolismo , Células HEK293 , Humanos , Ligação Proteica , Sulfatos/metabolismo , Tirosina/metabolismo
16.
Int J Behav Med ; 27(3): 262-266, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32405916

RESUMO

BACKGROUND: Accurate estimation in statistical models depends on sample size but also, critically, reliability of the measure. Physiometrics is the equivalent of psychometrics for measures such as sex hormones, catabolic hormones, and products of the immune system. METHOD: There are multiple ways to measure physiometrics, from simple correlation to complex generalizability theory designs. Depending on the design, these estimates can provide information about equivalency (e.g., the correlation between two measurements taken close together in time) or stability (e.g., the correlation between two measurements taken farther apart in time). RESULTS: The physiometrics of salivary measures including cortisol, α-amylase, testosterone, and cytokines range from highly stable, requiring only a single sample, to highly unstable, requiring multiple samples to achieve generalizability to longer periods of time. However, generalizability is relative to the study design, and only some designs call for stable and generalizable measures. CONCLUSION: Both dedicated physiometric studies and more reporting of physiometrics in psychoneuroendocrinology and psychoneuroimmunology will improve the quality of salivary bioscience study designs in the future.


Assuntos
Hidrocortisona/metabolismo , Saliva/metabolismo , Humanos , Reprodutibilidade dos Testes , Projetos de Pesquisa , Testosterona/metabolismo
17.
Int J Behav Med ; 27(3): 257-261, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32405917

RESUMO

Behavioral medicine research from across the globe has been catalyzed by the quest to understand the interactions between psychological, social, and physiological factors underlying disparities in human health. A more complete biopsychosocial model increasingly integrates advanced clinical and laboratory assessments of relevant environmental chemicals, biological mediators of inflammation, cardiometabolic and endocrine markers, infectious disease exposure, and genetic polymorphisms determined from saliva specimens. The overarching aims are to identify mechanisms, decode moderating processes that translate adversity into risk, and verify the impact of clinical intervention. This special issue of the International Journal of Behavioral Medicine highlights novel contributions of salivary bioscience with emphasis on research utilizing varied research designs (i.e., experimental, longitudinal, dyadic), incorporating a broad array of salivary analytes, and investigating the influence of psychological and social factors on human health.


Assuntos
Medicina do Comportamento/métodos , Biomarcadores/metabolismo , Saliva/metabolismo , Humanos , Inflamação/patologia
18.
PLoS One ; 15(5): e0232585, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32374750

RESUMO

Neurotropic flavivirus Japanese encephalitis virus (JEV) and West Nile virus (WNV) are amongst the leading causes of encephalitis. Using label-free quantitative proteomics, we identified proteins differentially expressed upon JEV (gp-3, RP9) or WNV (IS98) infection of human neuroblastoma cells. Data are available via ProteomeXchange with identifier PXD016805. Both viruses were associated with the up-regulation of immune response (IFIT1/3/5, ISG15, OAS, STAT1, IRF9) and the down-regulation of SSBP2 and PAM, involved in gene expression and in neuropeptide amidation respectively. Proteins associated to membranes, involved in extracellular matrix organization and collagen metabolism represented major clusters down-regulated by JEV and WNV. Moreover, transcription regulation and mRNA processing clusters were also heavily regulated by both viruses. The proteome of neuroblastoma cells infected by JEV or WNV was significantly modulated in the presence of mosquito saliva, but distinct patterns were associated to each virus. Mosquito saliva favored modulation of proteins associated with gene regulation in JEV infected neuroblastoma cells while modulation of proteins associated with protein maturation, signal transduction and ion transporters was found in WNV infected neuroblastoma cells.


Assuntos
Culicidae/metabolismo , Encefalite Japonesa/metabolismo , Neurônios/patologia , Proteoma/metabolismo , Febre do Nilo Ocidental/metabolismo , Animais , Linhagem Celular Tumoral , Culicidae/virologia , Vírus da Encefalite Japonesa (Subgrupo)/isolamento & purificação , Encefalite Japonesa/patologia , Encefalite Japonesa/virologia , Feminino , Humanos , Neurônios/metabolismo , Neurônios/virologia , Proteoma/análise , Saliva/metabolismo , Saliva/virologia , Febre do Nilo Ocidental/patologia , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/isolamento & purificação
19.
Int J Sports Physiol Perform ; 15(6): 808-815, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32365286

RESUMO

The growing prevalence and popularity of interval training necessitate additional guidelines in regard to maximal levels of time and intensity. PURPOSE: To correlate salivary hormones and time in varying heart-rate (HR) zones. The hypothesis was that chronic exercise durations >9% of total exercise time in the >90% maximum HR zone would lead to decreased variation in salivary cortisol concentration after exercise in a 2-bout high-intensity protocol compared with less or more time in this zone. METHODS: A total of 35 healthy adults who regularly exercised for an average of 8 hours per week recorded their HR during every training session for 3 weeks. Later, they completed an experimental day composed of two 30-minute high-intensity interval sessions separated by 4 hours of nonactive recovery. The authors collected saliva samples before, immediately following, and 30 minutes after each exercise session to assess changes in cortisol concentrations. RESULTS: There was a correlation between weekly time training at an intensity >90% maximum HR and the variables associated with overtraining. Salivary cortisol concentration fluctuated less in the participants who exercised in this extreme zone for >40 minutes per week (P < .001). CONCLUSION: Based on the current study data, for individuals who regularly exercise, 4% to 9% total training time above 90% maximum HR is the ideal duration to maximize fitness and minimize symptoms related to overreaching.


Assuntos
Exercício Físico/fisiologia , Frequência Cardíaca/fisiologia , Treinamento Intervalado de Alta Intensidade/métodos , Hidrocortisona/metabolismo , Saliva/metabolismo , Adulto , Afeto/fisiologia , Aptidão Cardiorrespiratória/fisiologia , Aptidão Cardiorrespiratória/psicologia , Metabolismo Energético , Exercício Físico/psicologia , Feminino , Treinamento Intervalado de Alta Intensidade/psicologia , Humanos , Masculino , Sono/fisiologia , Fatores de Tempo
20.
Medicine (Baltimore) ; 99(18): e19595, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358344

RESUMO

To evaluate the effect of chronic malnutrition on the oral health of children aged 1 to 5 years.An observational, analytical, cross-sectional study was conducted and involved 82 children (12-71 months of age). Nutritional status was evaluated using anthropometric indicators and oral health status/caries prevalence was measured. Non-stimulated saliva was collected and flow rate and buffering capacity was measured.The mean dmft index was 1.38 for the adequately nourished children, 3.04 for those with mild malnutrition, 2.5 for those with moderate malnutrition and 2.4 for those with severe malnutrition. 69 of the 82 children had low to very low buffering capacity. No significant differences among the groups were found between malnutrition and age, buffering capacity or the dmft index (P > .05). However, significant differences in salivary flow were found among the different malnutrition categories (P < .05). Spearman correlation coefficient revealed a weak negative correlation between nutrition and salivary flow (r = -0.267).Malnutrition exerts a negative impact on the oral cavity of children and a reduction in salivary flow rate was observed with the increase in malnutrition. Diagnosing the effects of malnutrition in oral environment of children is important because it could improve the quality of life and give them an adequate treatment.


Assuntos
Transtornos da Nutrição Infantil/fisiopatologia , Cárie Dentária/epidemiologia , Saúde Bucal , Transtornos da Nutrição Infantil/complicações , Pré-Escolar , Doença Crônica , Estudos Transversais , Cárie Dentária/etiologia , Feminino , Humanos , Lactente , Masculino , Estado Nutricional , Prevalência , Saliva/metabolismo
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