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1.
Nucleic Acids Res ; 52(2): 738-754, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38059397

RESUMO

Understanding microRNA (miRNA) functions has been hampered by major difficulties in identifying their biological target(s). Currently, the main limitation is the lack of a suitable strategy to identify biologically relevant targets among a high number of putative targets. Here we provide a proof of concept of successful de novo (i.e. without prior knowledge of its identity) miRNA phenotypic target (i.e. target whose de-repression contributes to the phenotypic outcomes) identification from RNA-seq data. Using the medaka mir-202 knock-out (KO) model in which inactivation leads to a major organism-level reproductive phenotype, including reduced egg production, we introduced novel criteria including limited fold-change in KO and low interindividual variability in gene expression to reduce the list of 2853 putative targets to a short list of 5. We selected tead3b, a member of the evolutionarily-conserved Hippo pathway, known to regulate ovarian functions, due to its remarkably strong and evolutionarily conserved binding affinity for miR-202-5p. Deleting the miR-202-5p binding site in the 3' UTR of tead3b, but not of other Hippo pathway members sav1 and vgll4b, triggered a reduced egg production phenotype. This is one of the few successful examples of de novo functional assignment of a miRNA phenotypic target in vivo in vertebrates.


Assuntos
Via de Sinalização Hippo , MicroRNAs , Oryzias , Animais , Sítios de Ligação , MicroRNAs/genética , MicroRNAs/metabolismo , Fenótipo , RNA-Seq , Oryzias/metabolismo
2.
BMC Med Res Methodol ; 24(1): 20, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267888

RESUMO

Systematic reviews are an essential tool in identifying knowledge gaps and synthesizing evidence from in vivo animal research to improve human health. The review process follows an explicit and systematic methodology to minimize bias, but is not immune to biases or methodological flaws. Pre-registering a systematic review protocol has several benefits, including avoiding unplanned duplication of reviews, reducing reporting biases, and providing structure throughout the review process. It also helps to align the opinions of review team members and can shield researchers from post-hoc critique. PROSPERO4animals is the international prospective register of systematic reviews (PROSPERO) for the preregistration of systematic review of animal studies. As administrators, here we provide 10 tips to facilitate pre-registration in PROSPERO4animals. These tips address common difficulties that both beginners and experienced researchers may face when pre-registering their systematic review protocols. This article aims to help authors write and register a detailed systematic review protocol on PROSPERO4animals.


Assuntos
Revisões Sistemáticas como Assunto , Animais , Humanos , Pesquisadores
3.
Artigo em Inglês | MEDLINE | ID: mdl-38710659

RESUMO

BACKGROUND: Tuberculosis (TB) remains a significant public health concern, particularly within prison settings, where the confluence of adverse health factors and high-risk behaviors contribute to a heightened risk of transmission. This study delves into the perspectives of medical doctors, regarding the implementation of the 2014 TB protocol in Portugal. METHODS: The study has a qualitative, descriptive design. Individual semi-structured interviews with medical doctors from TB outpatient centers in Porto and Lisbon were used for data collection. For the analysis thematic analysis method was used. RESULTS: The study population comprised 21 medical doctors with the majority being female (61.9%) and 57.1% specializing in pulmonology. The results indicate varied perceptions of the protocol's usefulness, with positive impacts on coordination reported by some participants. Improved communication and evolving collaboration between TB outpatient centers and prisons were highlighted, although challenges in contact tracing and resource constraints were acknowledged. The study also sheds light on the role of nurses in patient education. CONCLUSION: Despite overall positive perceptions, challenges such as sustaining therapy post-symptomatic improvement and delays in diagnostic methods were identified. The findings underscore the importance of continuous collaboration between prisons and TB control programs to address challenges, improve disease control and prevent TB transmission.

4.
J Water Health ; 22(2): 268-277, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38421621

RESUMO

Vaccines combatting COVID-19 demonstrate the ability to protect against disease and hospitalization, and reduce the likelihood of death caused by SARS-CoV-2. In addition, monitoring viral loads in sewage emerges as another crucial strategy in the epidemiological context, enabling early and collective detection of outbreaks. The study aimed to monitor the viral concentration of SARS-CoV-2 in untreated sewage in a Brazilian municipality. Also, it attempted to correlate these measurements with the number of clinical cases and deaths resulting from COVID-19 between July 2021 and July 2022. SARS-CoV-2 viral RNA was quantified by RT-qPCR. Pearson's correlation was performed to analyze the variables' relationship using the number of cases, deaths, vaccinated individuals, and viral concentration of SARS-CoV-2. The results revealed a significant negative correlation (p < 0.05) between the number of vaccinated individuals and the viral concentration of SARS-CoV-2, suggesting that after vaccination, the RNA viral load concentration was reduced in the sample population by the circulating concentration of wastewater. Consequently, wastewater monitoring, in addition to functioning as an early warning system for the circulation of SARS-CoV-2 and other pathogens, can offer a novel perspective that enhances decision-making, strengthens vaccination campaigns, and contributes to authorities establishing systematic networks for monitoring SARS-CoV-2.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Águas Residuárias , Esgotos , Brasil/epidemiologia , Vacinação
5.
Epilepsia ; 64(9): 2472-2483, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37301976

RESUMO

OBJECTIVE: Epilepsy is a neurological disease that affects ~50 million people worldwide, 30% of which have refractory epilepsy and recurring seizures, which may contribute to higher anxiety levels and poorer quality of life. Seizure detection may contribute to addressing some of the challenges associated with this condition, by providing information to health professionals regarding seizure frequency, type, and/or location in the brain, thereby improving diagnostic accuracy and medication adjustment, and alerting caregivers or emergency services of dangerous seizure episodes. The main focus of this work was the development of an accurate video-based seizure-detection method that ensured unobtrusiveness and privacy preservation, and provided novel approaches to reduce confounds and increase reliability. METHODS: The proposed approach is a video-based seizure-detection method based on optical flow, principal component analysis, independent component analysis, and machine learning classification. This method was tested on a set of 21 tonic-clonic seizure videos (5-30 min each, total of 4 h and 36 min of recordings) from 12 patients using leave-one-subject-out cross-validation. RESULTS: High accuracy levels were observed, namely a sensitivity and specificity of 99.06% ± 1.65% at the equal error rate and an average latency of 37.45 ± 1.31 s. When compared to annotations by health care professionals, the beginning and ending of seizures was detected with an average offset of 9.69 ± 0.97 s. SIGNIFICANCE: The video-based seizure-detection method described herein is highly accurate. Moreover, it is intrinsically privacy preserving, due to the use of optical flow motion quantification. In addition, given our novel independence-based approach, this method is robust to different lighting conditions, partial occlusions of the patient, and other movements in the video frame, thereby setting the base for accurate and unobtrusive seizure detection.


Assuntos
Epilepsia , Qualidade de Vida , Humanos , Reprodutibilidade dos Testes , Convulsões/diagnóstico , Epilepsia/diagnóstico , Eletroencefalografia/métodos , Computadores
6.
Knee Surg Sports Traumatol Arthrosc ; 30(12): 4225-4237, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35941323

RESUMO

PURPOSE: Achilles tendon ruptures (ATR) are career-threatening injuries in elite soccer players due to the decreased sports performance they commonly inflict. This study presents an exploratory data analysis of match participation before and after ATRs and an evaluation of the performance of a machine learning (ML) model based on pre-injury features to predict whether a player will return to a previous level of match participation. METHODS: The website transfermarkt.com was mined, between January and March of 2021, for relevant entries regarding soccer players who suffered an ATR while playing in first or second leagues. The difference between average minutes played per match (MPM) 1 year before injury and between 1 and 2 years after the injury was used to identify patterns in match participation after injury. Clustering analysis was performed using k-means clustering. Predictions of post-injury match participation were made using the XGBoost classification algorithm. The performance of this model was evaluated using the area under the receiver operating characteristic curve (AUROC) and Brier score loss (BSL). RESULTS: Two hundred and nine players were included in the study. Data from 32,853 matches was analysed. Exploratory data analysis revealed that forwards, midfielders and defenders increased match participation during the first year after injury, with goalkeepers still improving at 2 years. Players were grouped into four clusters regarding the difference between MPMs 1 year before injury and between 1 and 2 years after the injury. These groups ranged between a severe decrease (n = 34; - 59 ± 13 MPM), moderate decrease (n = 75; - 25 ± 8 MPM), maintenance (n = 70; 0 ± 8 MPM), or increase (n = 30; 32 ± 13 MPM). Regarding the predictive model, the average AUROC after cross-validation was 0.81 ± 0.10, and the BSL was 0.12, with the most important features relating to pre-injury match participation. CONCLUSION: Most players take 1 year to reach peak match participation after an ATR. Good performance was attained using a ML classifier to predict the level of match participation following an ATR, with features related to pre-injury match participation displaying the highest importance. LEVEL OF EVIDENCE: I.


Assuntos
Tendão do Calcâneo , Traumatismos do Tornozelo , Desempenho Atlético , Futebol , Traumatismos dos Tendões , Humanos , Futebol/lesões , Tendão do Calcâneo/lesões , Aprendizado de Máquina
7.
Mycoses ; 63(6): 610-616, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32301521

RESUMO

BACKGROUND: Trichophyton rubrum is the most common aetiological agent of human dermatophytoses. These infections mainly occur in keratinised layers such as skin, hair and nails because the fungus uses keratin as a nutrient source. Fluconazole and amphotericin are antifungal agents most commonly used to treat dermatophytoses and acts on cell membrane ergosterol. Despite the clinical importance of T rubrum, the mechanisms underlying the fungal-host relationship have not yet been clarified. Tandem repeats (TRs) are short DNA sequences that are involved in a variety of adaptive functions, including the process of fungal infection. It is known that the larger the number of TRs in the genome, the greater the capacity of cell-cell junction and surface adhesion, especially when these repeats are present in regions encoding cell surface proteins. OBJECTIVES: To identify in silico T rubrum genes containing TR patterns and to analyse the modulation of these genes in culture medium containing keratin (a model simulating skin infection) and antifungal drugs. METHODS: The Dermatophyte Tandem Repeats Database (DTRDB) and the FaaPred tool were used to identify four T rubrum genes containing TR patterns. Quantitative real-time (RT) PCR was used to evaluate the gene expression during the growth of T rubrum on keratin and in the presence of fluconazole, amphotericin B and Congo red (acts in the cell wall). RESULTS: The expression of these genes was found to be induced in culture medium containing keratin. In addition, these genes were induced in the presence of antifungal agents, especially fluconazole, indicating an adaptive response to the stress caused by this drug. CONCLUSION: The results suggest an important role of genes containing TRs in the fungal-host interaction and in the susceptibility to inhibitory compounds, indicating these sequences as new potential targets for the development of antifungal agents.


Assuntos
Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/genética , Dermatomicoses/tratamento farmacológico , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/genética , Sequências de Repetição em Tandem , Antifúngicos/farmacologia , Meios de Cultura , Proteínas Fúngicas/genética , Expressão Gênica , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Humanos , Queratinas/farmacologia , Testes de Sensibilidade Microbiana , Esporos Fúngicos/efeitos dos fármacos , Esporos Fúngicos/genética
8.
Mem Inst Oswaldo Cruz ; 115: e200328, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33111750

RESUMO

Scientists have increasingly recognised that low methodological and analytical rigour combined with publish-or-perish incentives can make the published scientific literature unreliable. As a response to this, large-scale systematic replications of the literature have emerged as a way to assess the problem empirically. The Brazilian Reproducibility Initiative is one such effort, aimed at estimating the reproducibility of Brazilian biomedical research. Its goal is to perform multicentre replications of a quasi-random sample of at least 60 experiments from Brazilian articles published over a 20-year period, using a set of common laboratory methods. In this article, we describe the challenges of managing a multicentre project with collaborating teams across the country, as well as its successes and failures over the first two years. We end with a brief discussion of the Initiative's current status and its possible future contributions after the project is concluded in 2021.


Assuntos
Pesquisa Biomédica/tendências , Projetos de Pesquisa , Brasil , Reprodutibilidade dos Testes
9.
Anesth Analg ; 127(3): 784-791, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29933268

RESUMO

BACKGROUND: Recruitment maneuver and positive end-expiratory pressure (PEEP) can be used to counteract intraoperative anesthesia-induced atelectasis. Variable ventilation can stabilize lung mechanics by avoiding the monotonic tidal volume and protect lung parenchyma as tidal recruitment is encompassed within the tidal volume variability. METHODS: Forty-nine (7 per group) male Wistar rats were anesthetized, paralyzed, and mechanically ventilated. A recruitment maneuver followed by stepwise decremental PEEP titration was performed while continuously estimating respiratory system mechanics using recursive least squares. After a new recruitment, animals were ventilated for 2 hours in volume-control with monotonic (VCV) or variable (VV) tidal volumes. PEEP was adjusted at a level corresponding to the minimum elastance or 2 cm H2O above or below this level. Lungs were harvested for histologic analysis (left lung) and cytokines measurement (right lung). Seven animals were euthanized before the first recruitment as controls. RESULTS: A time-dependent increase in respiratory system elastance was observed and significantly minimized by PEEP (P < .001). Variable ventilation attenuated the amount of concentrations of proinflammatory mediators in lung homogenate: neutrophil cytokine-induced neutrophil chemoattractant 1 (VV = 40 ± 5 and VCV = 57 ± 8 pg/mg; P < .0001) and interleukin-1ß (VV = 59 ± 25 and VCV = 261 ± 113 pg/mg; P < .0001). Variable ventilation was also associated with lower structural lung parenchyma damage. Significant reductions in air fraction at dorsal and caudal lung regions were observed in all ventilated animals (P < .001). CONCLUSIONS: Variable ventilation was more protective than conventional ventilation within the applied PEEP levels.


Assuntos
Anestésicos Dissociativos/administração & dosagem , Pneumonia/metabolismo , Pneumonia/patologia , Respiração com Pressão Positiva/métodos , Mecânica Respiratória/fisiologia , Animais , Pulmão/metabolismo , Pulmão/patologia , Masculino , Pneumonia/etiologia , Respiração com Pressão Positiva/efeitos adversos , Respiração com Pressão Positiva/tendências , Ratos , Ratos Wistar , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Respiração Artificial/tendências , Volume de Ventilação Pulmonar/fisiologia
10.
J Toxicol Environ Health A ; 80(13-15): 776-787, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28850007

RESUMO

Colorectal cancer therapy with 5-fluorouracil (5-Fu) frequently become ineffective due to resistance to this drug; and thus other effective compounds are essential for therapy. It is well-known marine brown seaweeds contain antioxidant compounds the carotenoid fucoxanthin (Fx) and polyphenolic compound phloroglucinol (Ph) which exerted diverse biological activities including antioxidant and anticancer. The aim of this study was to determine the anticancer activities of Fx or Ph alone as well as combination of each chemical with 5-Fu on two human colorectal cancer cell lines (HCT116 and HT29), with comparison to responses in a normal colon cell line (CCD-18Co). Effects of these compounds on cell viability, induction of DNA damage, and cell death were evaluated using MTT assay, comet assay, nuclear condensation assay, and Western blot. 5-Fu decreased cell viability in a concentration-dependent manner in HCT116 and HT29 cells but was not cytotoxic in CCD-18Co cells. 5-Fu induced DNA damage in HCT116 cells with induction of cell death, while no marked effects on DNA damage and cell death were observed in HT29 cells. Fx or Ph alone also reduced cell viability in both cancer cell lines but no apparent cytotoxic effect in CCD-18Co cells, except for Fx at 50 and 100 µM. Diminished cell viability was accompanied by induction of DNA damage (by Fx) and induction of cell death (by Ph). In combination with 5-Fu, Fx at 10 µM (in HCT116 and HT29 cells), and Ph at 300 µM (in HT29 cells) enhanced the cytotoxic effect of 5-Fu; however, no marked cytotoxicity was noted in CCD-18Co cells. Since Fx and Ph alone reduced cancer cell line viability without an effect on normal cells and when in combination enhanced the cytotoxic effect of 5-Fu only in colon cancer cells, these compounds seem promising as anticancer agents.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/farmacologia , Floroglucinol/farmacologia , Alga Marinha/química , Xantofilas/farmacologia , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Colo/efeitos dos fármacos , Quimioterapia Combinada , Fluoruracila/administração & dosagem , Células HCT116 , Células HT29 , Humanos , Floroglucinol/administração & dosagem , Xantofilas/administração & dosagem
13.
Eur J Anaesthesiol ; 32(10): 735-41, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26295750

RESUMO

BACKGROUND: Opioid analgesia not only reduces inhalational anaesthetic requirements but may also induce delayed hyperalgesia, with potential effects on the minimum alveolar concentration (MAC) of inhalational anaesthetics. OBJECTIVES: The objective of this study was to evaluate the development of tramadol-induced hyperalgesia and the associated changes in MAC, and whether ketamine prevents both processes. DESIGN: A randomised, experimental study. SETTING: Experimental Surgery Unit, La Paz University Hospital, Madrid, Spain. ANIMALS: Thirty-nine adult male Wistar rats. INTERVENTIONS: Mechanical nociceptive thresholds (MNT) were determined up to 21 days after the intraperitoneal administration of a single dose of tramadol (50 mg kg) with or without ketamine (10 mg kg), or 0.9% saline. The MNT and the MAC of sevoflurane were also assessed in a second experiment before, early (30 min) and 7 days after drug administration with the same treatments. MAIN OUTCOME MEASURES: The MAC and MNT were evaluated. The analysis of variance (ANOVA) test was employed to determine differences between treatments and times on MAC and MNT. RESULTS: Tramadol, alone or combined with ketamine, produced an early increase in MNT. However, tramadol given alone decreased MNT from day 1 up to 3 weeks, which was associated with an increase in the MAC of sevoflurane (P < 0.05; day 7). Ketamine administration prevented both the reduction in MNT and the increase in MAC (P > 0.05). CONCLUSION: Tramadol-induced hyperalgesia in the rat lasted for several weeks and was associated with an increase in the MAC of sevoflurane. Prior administration of ketamine blocked both phenomena.


Assuntos
Analgésicos Opioides/efeitos adversos , Hiperalgesia/prevenção & controle , Ketamina/farmacologia , Tramadol/efeitos adversos , Analgésicos/farmacologia , Anestésicos Inalatórios/farmacocinética , Animais , Hiperalgesia/induzido quimicamente , Masculino , Éteres Metílicos/farmacocinética , Alvéolos Pulmonares/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Sevoflurano , Fatores de Tempo
14.
Eur J Anaesthesiol ; 32(4): 232-41, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25485881

RESUMO

BACKGROUND: Perioperative opioids reduce inhalational anaesthetic requirements. The initial hypoalgesia may, however, be followed by a rebound hyperalgesia. OBJECTIVES: To determine whether prior opioid administration influences inhalational anaesthetic requirements, which might be associated with opioid-induced hyperalgesia. DESIGN: A prospective, randomised, experimental study. SETTING: Experimental Surgery, La Paz University Hospital, Madrid, Spain. ANIMALS: Seventy-nine adult male Wistar rats. INTERVENTIONS: Sevoflurane minimum alveolar concentration (MAC) and mechanical nociceptive thresholds (MNTs) were assessed at baseline and 7 days later following opioid treatment with remifentanil 120 µg  kg-1  h-1, buprenorphine 150 µg kg-1, methadone 8 mg  kg-1 or morphine 10 mg  kg-1 The duration of the effect of remifentanil on MAC and MNT was evaluated in addition to the preventive effect of ketamine 10 mg  kg-1 on remifentanil-induced hyperalgesia. MAIN OUTCOME MEASURES: The effect of different opioid treatments on MAC and MNT was evaluated using analysis of variance (ANOVA). RESULTS: All studied opioids produced an immediate reduction in sevoflurane MAC, followed by an increase (16%) in baseline MAC 7 days later (P < 0.05), although the immediate MAC reduction produced by these opioids at that time was not different. Remifentanil produced a decrease in MNT (P < 0.05), which was associated with an increase in the MAC (P < 0.05) that persisted at 21 days. The effect of remifentanil on MNT and MAC was blocked by ketamine. CONCLUSION: Opioid-induced hyperalgesia was associated with an increase in the MAC in normal rats who had not undergone surgery. Both effects lasted 21 days and were prevented by ketamine.


Assuntos
Analgésicos Opioides/toxicidade , Anestésicos Inalatórios/farmacocinética , Hiperalgesia/induzido quimicamente , Éteres Metílicos/farmacocinética , Alvéolos Pulmonares/metabolismo , Analgésicos Opioides/administração & dosagem , Anestésicos Inalatórios/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Buprenorfina/toxicidade , Hiperalgesia/fisiopatologia , Hiperalgesia/prevenção & controle , Hiperalgesia/psicologia , Ketamina/farmacologia , Masculino , Metadona/toxicidade , Éteres Metílicos/administração & dosagem , Morfina/toxicidade , Nociceptividade/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Piperidinas/toxicidade , Distribuição Aleatória , Ratos Wistar , Remifentanil , Sevoflurano
15.
Eur J Anaesthesiol ; 32(4): 248-54, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24849503

RESUMO

BACKGROUND: The antidepressant amitriptyline, the inhibitor of microglia activation minocycline, and the neurokinin-1 antagonist maropitant have all been used to prevent or treat hyperalgesia and opioid tolerance. OBJECTIVES: To determine the effect of amitriptyline, minocycline, maropitant, independently or with remifentanil, on the sevoflurane minimum alveolar concentration in rats and whether these drugs may block opioid-induced hyperalgesia and acute opioid tolerance under inhalational anaesthesia. DESIGN: A randomised, laboratory study. SETTING: Experimental Unit, La Paz University Hospital, Madrid, Spain. ANIMALS: One hundred and fourteen adult male Wistar rats. INTERVENTIONS: Intraperitoneal administration of amitriptyline (10 and 50  mg  kg-1), minocycline (30 and 100  mg  kg-1), maropitant (10 and 30 mg  kg-1) or isotonic saline, combined with a constant rate intravenous infusion of remifentanil (240 µg  kg-1  h-1) or saline. MAIN OUTCOME MEASURES: Sevoflurane minimum alveolar concentration was determined before and after administration of the drugs; acute opioid tolerance was defined as a decreased ability of remifentanil to reduce the minimum alveolar concentration in the short term. In addition, mechanical nociceptive thresholds were determined before and after these treatments. Opioid-induced hyperalgesia was defined as an increase in mechanical nociceptive thresholds after opioid administration. RESULTS: Amitriptyline, minocycline and maropitant reduced minimum alveolar concentration up to 24 (8)%, 23 (6)% and 15 (5)%, respectively (P <0.001). Remifentanil alone reduced minimum alveolar concentration by 36 (6)% (P <0.001), and in combination with amitriptyline, minocycline and maropitant, the reduction was 76 (9)%, 75 (16)% and 59 (5)%, respectively (P <0.001). An acute tolerance effect (P < 0.01) and a decrease in the mechanical nociceptive thresholds were observed with remifentanil in all groups. CONCLUSION: Amitriptyline, minocycline and maropitant reduced the minimum alveolar concentration and potentiated the remifentanil minimum alveolar concentration reduction but failed to block opioid-induced hyperalgesia and acute opioid tolerance.


Assuntos
Amitriptilina/farmacologia , Analgésicos Opioides/toxicidade , Anestésicos Inalatórios/farmacocinética , Tolerância a Medicamentos , Hiperalgesia/induzido quimicamente , Éteres Metílicos/farmacocinética , Minociclina/farmacologia , Piperidinas/toxicidade , Alvéolos Pulmonares/metabolismo , Quinuclidinas/farmacologia , Anestésicos Inalatórios/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Hiperalgesia/fisiopatologia , Hiperalgesia/psicologia , Masculino , Éteres Metílicos/administração & dosagem , Nociceptividade/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Distribuição Aleatória , Ratos Wistar , Remifentanil , Sevoflurano
16.
Anim Reprod ; 21(2): e20230158, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39021500

RESUMO

This study aimed to investigate the effect of temperature on gonadal differentiation, growth, survival, and sex ratio of Leporinus friderici reared at 25 °C or 29 °C from 50 to 240 days after eclosion (DAE) in a water recirculation system. A total of 110 fish at 50 DAE (6.7 ± 0.1 cm and 6.1 ± 0.3 g) were equally and randomly distributed in 10 boxes (90 L) (11 fish/box, 5 boxes/temperature). One fish from each experimental unit was randomly sampled at 50, 70, 90, 110, 130, 150, 170, 190, 210 and 240 DAE. Female gonadal differentiation started at 150 DAE (11.4 ± 0.0 cm and 16.4 ± 0.0 g) at 25 °C and at 170 DAE (10.7 ± 0.7 cm and 27.7 ± 8.5 g) at 29 ºC, while testes differentiation only occurred at 29 °C from 190 DAE (12.1 ± 0.0 cm and 38.0 ± 0.0 g). Of 50 fishes sampled in each condition, 17 (12 females and five males) and three (three females) displayed gonadal differentiation at 29 °C and 25 °C, respectively. Final biometric values at 29 °C were twice those obtained at 25 °C, reaching 13.9 ± 0.65 cm and 57.3 ± 10.12 g versus 11.2 ± 0.39 cm and 28.5 ± 2.95 g, respectively. While temperature clearly influenced gonadal differentiation and growth, it had inconclusive effects on sex ratio. The higher temperature (29 °C) has direct implications for the production of this species, as it accelerates growth without causing mortality.

17.
Anesthesiology ; 118(5): 1160-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23407105

RESUMO

BACKGROUND: Opioid antagonists at ultra-low doses have been used with opioid agonists to prevent or limit opioid tolerance. The aim of this study was to evaluate whether an ultra-low dose of naloxone combined with remifentanil could block opioid-induced hyperalgesia and tolerance under sevoflurane anesthesia in rats. METHODS: Male adult Wistar rats were allocated into one of four treatment groups (n = 7), receiving remifentanil (4 µg·kg·min) combined with naloxone (0.17 ng·kg·min), remifentanil alone, naloxone alone, or saline. Animals were evaluated for mechanical nociceptive thresholds (von Frey) and subsequently anesthetized with sevoflurane to determine the baseline minimum alveolar concentration (MAC). Next, treatments were administered, and the MAC was redetermined twice during the infusion. The experiment was performed three times on nonconsecutive days (0, 2, and 4). Hyperalgesia was considered to be a decrease in mechanical thresholds, whereas opioid tolerance was considered to be a decrease in sevoflurane MAC reduction by remifentanil. RESULTS: Remifentanil produced a significant decrease in mechanical thresholds compared with baseline values at days 2 and 4 (mean ± SD, 30.7 ± 5.5, 22.1 ± 6.4, and 20.7 ± 3.7g at days 0, 2, and 4, respectively) and an increase in MAC baseline values (2.5 ± 0.3, 3.0 ± 0.3, and 3.1 ± 0.3 vol% at days 0, 2, and 4, respectively). Both effects were blocked by naloxone coadministration. However, both remifentanil-treated groups (with or without naloxone) developed opioid tolerance determined by their decrease in MAC reduction. CONCLUSIONS: An ultra-low dose of naloxone blocked remifentanil-induced hyperalgesia but did not change opioid tolerance under inhalant anesthesia. Moreover, the MAC increase associated with hyperalgesia was also blocked by naloxone.


Assuntos
Analgésicos Opioides/farmacologia , Anestesia por Inalação , Anestésicos Inalatórios , Hiperalgesia/induzido quimicamente , Éteres Metílicos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Piperidinas/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Tolerância a Medicamentos , Masculino , Limiar da Dor/efeitos dos fármacos , Estimulação Física , Alvéolos Pulmonares/metabolismo , Ratos , Ratos Wistar , Remifentanil , Sevoflurano
18.
Clinics (Sao Paulo) ; 78: 100277, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37647843

RESUMO

OBJECTIVE: To evaluate the hospital cost of newborn infants diagnosed with sepsis from the perspective of the Brazilian Public Health System over 11 years. METHOD: Cross-sectional study that analyzed secondary data from the databases of the Hospital Information System of the Brazilian Public Health System. Infants hospitalized between 0‒29 days after birth with a diagnosis of sepsis from 2008 to 2018 were included. The diagnosis used in the study was the one that the hospital considered the main diagnosis at admission. Costs were analyzed in US dollars and reflected the amount paid by the Brazilian Public Health System to the hospitals for the informed diagnosis upon admission. The costs were evaluated as the total per admission, and they were compared among Brazilian geographic regions, among etiologic agents, and between neonates with the diagnosis of sepsis that survived or died. RESULTS: From 2008 to 2018, 47,554 newborns were hospitalized with sepsis (148.04 cases per 100,000 live births), with an average cost of US$ 3345.59 per hospitalization, ranging from US$ 2970.60 in the North region to US$ 4305.03 in the Midwest. Among sepsis with identified agents, the highest mean cost was related to Gram-negative agents, and the lowest to Streptococcus agalactiae sepsis. Patients with sepsis who died had a higher cost than the survivors (t-test; p = 0.046). CONCLUSIONS: The evaluation of costs related to neonatal sepsis in the country during an 11-year period shows the economic impact of morbidity that may be avoided by improving the quality of neonatal care.


Assuntos
Sepse Neonatal , Sepse , Recém-Nascido , Lactente , Humanos , Sepse Neonatal/epidemiologia , Brasil/epidemiologia , Estudos Transversais , Hospitalização
19.
Anim Reprod Sci ; 254: 107262, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37295049

RESUMO

In this study, we aimed to propose changes in the protocol of cultured Astyanax altiparanae hypophysation to increase the maximum ovulation rate of 60% registered previously. To that two consecutive experiments were conducted. In the first experiment, three carp pituitary homogenate (CPH) doses (3, 6, and 9 mg/kg) were administered in a single injection, while in the second experiment, the 6 mg/kg CPH dose was tested either in single or double injections. In the first experiment, a single injection of 3 mg/kg CPH did not induce final oocyte maturation or spawning, while a dose of 6 mg/kg CPH resulted in an increase in the plasma level of prostaglandin (PGF2α) at ovulation. The single higher dose of 9 mg/kg CPH did not improve reproductive performance and even though anticipated the resumption of meiosis it was detrimental to the spawning rate. In the second experiment, the dose of 6 mg/kg CPH fractionated into two injections led to a higher spawning rate, spawning volume per female body mass, frequency of post-ovulatory complexes, and PGF2α concentration at ovulation compared to the single injection. The most effective treatment remained the 6 mg/kg of CPH fractionated into two injections, but still providing very low proportion of ovulated females (∼40 %). Overall, this study indicates that the spawning protocols for this species need to be improved to induce ovulation in a larger number of females and be more potent in those females that respond positively.


Assuntos
Carpas , Dinoprosta , Feminino , Animais , Dinoprosta/farmacologia , Oócitos , Reprodução , Ovulação , Oogênese , Hormônio Liberador de Gonadotropina/farmacologia
20.
Front Physiol ; 14: 1248899, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37881691

RESUMO

The PreEpiSeizures project was created to better understand epilepsy and seizures through wearable technologies. The motivation was to capture physiological information related to epileptic seizures, besides Electroencephalography (EEG) during video-EEG monitorings. If other physiological signals have reliable information of epileptic seizures, unobtrusive wearable technology could be used to monitor epilepsy in daily life. The development of wearable solutions for epilepsy is limited by the nonexistence of datasets which could validate these solutions. Three different form factors were developed and deployed, and the signal quality was assessed for all acquired biosignals. The wearable data acquisition was performed during the video-EEG of patients with epilepsy. The results achieved so far include 59 patients from 2 hospitals totaling 2,721 h of wearable data and 348 seizures. Besides the wearable data, the Electrocardiogram of the hospital is also useable, totalling 5,838 h of hospital data. The quality ECG signals collected with the proposed wearable is equated with the hospital system, and all other biosignals also achieved state-of-the-art quality. During the data acquisition, 18 challenges were identified, and are presented alongside their possible solutions. Though this is an ongoing work, there were many lessons learned which could help to predict possible problems in wearable data collections and also contribute to the epilepsy community with new physiological information. This work contributes with original wearable data and results relevant to epilepsy research, and discusses relevant challenges that impact wearable health monitoring.

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