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1.
Sensors (Basel) ; 24(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38257717

RESUMO

In health monitoring systems for the elderly, a crucial aspect is unobtrusively and continuously monitoring their activities to detect potentially hazardous incidents such as sudden falls as soon as they occur. However, the effectiveness of current non-contact sensor-based activity detection systems is limited by obstacles present in the environment. To overcome this limitation, a straightforward yet highly efficient approach involves utilizing multiple sensors that collaborate seamlessly. This paper proposes a method that leverages 2D Light Detection and Ranging (Lidar) technology for activity detection. Multiple 2D Lidars are positioned in an indoor environment with varying obstacles such as furniture, working cohesively to create a comprehensive representation of ongoing activities. The data from these Lidars is concatenated and transformed into a more interpretable format, resembling images. A convolutional Long Short-Term Memory (LSTM) Neural Network is then used to process these generated images to classify the activities. The proposed approach achieves high accuracy in three tasks: activity detection, fall detection, and unsteady gait detection. Specifically, it attains accuracies of 96.10%, 99.13%, and 93.13% for these tasks, respectively. This demonstrates the efficacy and promise of the method in effectively monitoring and identifying potentially hazardous events for the elderly through 2D Lidars, which are non-intrusive sensing technology.

3.
Redox Biol ; 66: 102869, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37677999

RESUMO

The lens proteome undergoes dramatic composition changes during development and maturation. A defective developmental process leads to congenital cataracts that account for about 30% of cases of childhood blindness. Gene mutations are associated with approximately 50% of early-onset forms of lens opacity, with the remainder being of unknown etiology. To gain a better understanding of cataractogenesis, we utilized a transgenic mouse model expressing a mutant ubiquitin protein in the lens (K6W-Ub) that recapitulates most of the early pathological changes seen in human congenital cataracts. We performed mass spectrometry-based tandem-mass-tag quantitative proteomics in E15, P1, and P30 control or K6W-Ub lenses. Our analysis identified targets that are required for early normal differentiation steps and altered in cataractous lenses, particularly metabolic pathways involving glutathione and amino acids. Computational molecular phenotyping revealed that glutathione and taurine were spatially altered in the K6W-Ub cataractous lens. High-performance liquid chromatography revealed that both taurine and the ratio of reduced glutathione to oxidized glutathione, two indicators of redox status, were differentially compromised in lens biology. In sum, our research documents that dynamic proteome changes in a mouse model of congenital cataracts impact redox biology in lens. Our findings shed light on the molecular mechanisms associated with congenital cataracts and point out that unbalanced redox status due to reduced levels of taurine and glutathione, metabolites already linked to age-related cataract, could be a major underlying mechanism behind lens opacities that appear early in life.


Assuntos
Catarata , Proteoma , Humanos , Animais , Camundongos , Glutationa , Modelos Animais de Doenças , Camundongos Transgênicos , Proteínas Mutantes , Oxirredução , Taurina , Catarata/genética
4.
Adv Exp Med Biol ; 1415: 229-234, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37440038

RESUMO

Connexins (Cx) are a family of transmembrane proteins that form gap junction intercellular channels that connect neighboring cells. These channels allow the passage of ions and other biomolecules smaller than 1 kDa, thereby synchronizing the cells both electrically and metabolically. Cxs are expressed in all retinal cell types and the diversity of Cx isoforms involved in the assembly of the channels provides a functional syncytium required for visual transduction. In this chapter, we summarize the status of current knowledge regarding Cx biology in retinal tissues and discuss how Cx dysfunction is associated with retinal disease pathophysiology. Although the contribution of Cx deficiency to retinal degeneration is not well understood, recent findings present Cx as a potential therapeutic target. Therefore, we will briefly discuss pharmacological approaches and gene therapies that are being explored to modulate Cx function and fight sight-threatening eye diseases.


Assuntos
Conexinas , Doenças Retinianas , Humanos , Conexinas/genética , Junções Comunicantes/fisiologia , Retina/metabolismo , Doenças Retinianas/terapia , Doenças Retinianas/metabolismo , Biologia
5.
Sensors (Basel) ; 23(5)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36904735

RESUMO

Monitoring the activities of elderly people living alone is of great importance since it allows for the detection of when hazardous events such as falling occur. In this context, the use of 2D light detection and ranging (LIDAR) has been explored, among others, as a way to identify such events. Typically, a 2D LIDAR is placed near the ground and collects measurements continuously, and a computational device classifies these measurements. However, in a realistic environment with home furniture, it is hard for such a device to operate as it requires a direct line of sight (LOS) with its target. Furniture will block the infrared (IR) rays from reaching the monitored person thus limiting the effectiveness of such sensors. Nonetheless, due to their fixed location, if a fall is not detected when it happens, it cannot be detected afterwards. In this context, cleaning robots present a much better alternative given their autonomy. In this paper, we propose to use a 2D LIDAR mounted on top of a cleaning robot. Through continuous movement, the robot is able to collect distance information continuously. Despite having the same drawback, by roaming in the room, the robot can identify if a person is laying on the ground after falling, even after a certain period from the fall event. To achieve such a goal, the measurements captured by the moving LIDAR are transformed, interpolated, and compared to a reference state of the surroundings. A convolutional long short-term memory (LSTM) neural network is trained to classify the processed measurements and identify if a fall event occurs or has occurred. Through simulations, we show that such a system can achieve an accuracy equal to 81.2% in fall detection and 99% in the detection of lying bodies. Compared to the conventional method, which uses a static LIDAR, the accuracy reaches for the same tasks 69.4% and 88.6%, respectively.


Assuntos
Robótica , Idoso , Humanos , Acidentes por Quedas , Atividades Humanas , Raios Infravermelhos , Decoração de Interiores e Mobiliário
6.
Plants (Basel) ; 12(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36771738

RESUMO

The island of Grande-Terre is a French overseas region that belongs to the Guadeloupean archipelago, a biodiversity hotspot with unique flora. Herbal medicine is widely used in the island for therapeutical purposes; however, there is a significant knowledge gap in the records relating to medicinal plants and their associated uses. Ethnobotanical survey methodology using quantitative parameters (informant consensus factor, species use value, relative frequency of citation, frequency use of a treatment and plant for an ailment) provided insights into the traditional medicinal use of a given plant. Ninety-six different plant species distributed among 56 families were identified and 523 remedies were documented in the survey. After data filtering, 22 plants species were associated with 182 remedies. The most frequent plant families were Poaceae, Myrtaceae, Cucurbitaceae and Rubiaceae. Aerial parts of these plants were the most common parts of the plant used for the remedies and the most frequent mode of administration was oral ingestion. This study highlights a valuable traditional knowledge of folklore medicine and helps to document and preserve the association of a plant with-and its use frequency for-a given ailment. These findings might be the starting point for the identification of biologically active phytocompounds to fight common health debilities.

7.
Plants (Basel) ; 11(10)2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35631785

RESUMO

Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia, insulin insufficiency or insulin resistance, and many issues, including vascular complications, glycative stress and lipid metabolism dysregulation. Natural products from plants with antihyperglycemic, hypolipidemic, pancreatic protective, antioxidative, and insulin-like properties complement conventional treatments. Throughout this review, we summarize the current status of knowledge of plants from the Caribbean basin traditionally used to manage DM and treat its sequelae. Seven plants were chosen due to their use in Caribbean folk medicine. We summarize the antidiabetic properties of each species, exploring the pharmacological mechanisms related to their antidiabetic effect reported in vitro and in vivo. We propose the Caribbean flora as a source of innovative bioactive phytocompounds to treat and prevent DM and DM-associated complications.

8.
Rev. latinoam. bioét ; 22(1): 83-96, 2022.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1423993

RESUMO

Resumen: Si bien la interrupción terapéutica del embarazo en los casos de fetos anencefálicos ha sido ampliamente discutida, y se han llegado a conclusiones éticas que la justifican (si no existe contraindicación médica y se obtiene el consentimiento informado de la mujer), es importante reevaluar el tema. Por ello, se deben contrastar los principios bioéticos con sentencias judiciales de fenómenos jurídicos que están surgiendo en el mundo, y que pueden provocar cambios en los derechos sexuales y reproductivos. No obstante, esto no debe implicar un cambio en los argumentos bioéticos. Asimismo, debido al resurgimiento a nivel global de un conservadurismo moral, que propone un planteamiento en torno a la objeción de conciencia, se torna imperativo analizar desde la perspectiva bioética si la misma puede ser invocada en casos de interrupción terapéutica del embarazo. Para ello, se deberían ponderar los principios bioéticos y utilizar una bioética laica, pluralista y basada en ética de mínimos, la cual busque la dignidad de las personas que enfrentan una gestación de fetos anencefálicos. En ese sentido, la objeción de conciencia no debería utilizarse como instrumento para negar la atención a estas personas.


Abstract: Although the therapeutic interruption of pregnancy in cases of anencephalic fetuses has been widely discussed, and ethical conclusions have been reached that justify it (if there is no medical contraindication and the informed consent of the woman is obtained), it is important to reassess the issue. Hence, bioethical principles must be contrasted with judicial rulings on legal phenomena that are emerging in the world, and that can cause changes in sexual and reproductive rights. However, this should not imply a change in the bioethical arguments. Likewise, due to the global resurgence of moral conservatism, which proposes an approach regarding conscientious objection, it becomes imperative to analyze, from a bioethical perspective, if it can be invoked in cases of therapeutic interruption of pregnancy. To do this, bioethical principles should be weighed and a secular, pluralistic bioethics based on minimum ethics should be used, which seeks the dignity of persons facing an anencephalic fetus gestation. In this sense, conscientious objection should not be used as an instrument to deny care to these individuals.


Resumo: Embora a interrupção terapêutica da gravidez nos casos de fetos anencéfalos tenha sido amplamente discutida e tenham chegado a conclusões éticas que a justifiquem (se não houver contraindicação médica e for obtido o consentimento informado da mulher), é importante reavaliar a questão . Por isso, os princípios bioéticos devem ser contrastados com as decisões judiciais sobre fenômenos jurídicos que estão surgindo no mundo e que podem causar mudanças nos direitos sexuais e reprodutivos. No entanto, isso não deve implicar uma mudança nos argumentos bioéticos. Da mesma forma, devido ao ressurgimento global do conservadorismo moral, que propõe uma abordagem em torno da objeção de consciência, torna-se imperativo analisar na perspectiva bioética se ela pode ser invocada nos casos de interrupção terapêutica da gravidez. Para tanto, deve-se pesar os princípios bioéticos e utilizar uma bioética laica, pluralista, pautada na ética mínima, que busque a dignidade das pessoas diante da gestação de feto anencéfalo. Nesse sentido, a objeção de consciência não deve ser utilizada como instrumento para negar atenção a essas pessoas.

9.
Pharmaceutics ; 13(12)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34959300

RESUMO

Cattle tick (Rhipicephalus microplus) represents a severe problem causing substantial economic losses, estimated in billions of dollars annually. Currently, chemical acaricides represent the most widely used control method. However, several problems such as resistance have been described. Phage-based vaccines represent a fast and low-cost tool for antigen delivery. In this regard, the objective of the present work was to develop a candidate phage-based vaccine displaying a cattle tick antigen (Bm86-derived Sbm7462 antigen) on the surface of bacteriophage M13. Phage ELISA and dot blotting analysis confirmed the display of the antigen. Vaccine immunogenicity was evaluated using a bovine monocyte-derived dendritic cell-based ex vivo assay and a murine in vivo assay. The ex vivo model showed the maturation of dendritic cells after being pulsed with the phage-based vaccine. The humoral response was confirmed in the in vivo assay. These results demonstrated the capacity of the phage-based vaccine to induce both humoral and cellular immune-specific responses. Importantly, this is the first report describing a control method for cattle ticks using a candidate phage-based vaccine. Further studies to evaluate the immunogenicity in a bovine model are needed. The current approach represents a promising alternative to control cattle tick infestations.

10.
Cureus ; 12(9): e10530, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33101792

RESUMO

Introduction In the last 18 years, on three occasions, coronavirus has represented a challenge for global health. Between 2002 and 2003 with Severe Acute Respiratory Syndrome, in 2012 with Middle East Respiratory Syndrome, and since the end of 2019 with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) pandemic, which has challenged health care models and the way of doing research, placing bioethics at the center of discussion.  Methods On August 19, 2020, a webinar organized by the Research Institute of Medical Science (IICIMED, for its acronym in Spanish), entitled 'Bioethical Implications in Vaccine Development, a COVID-19 Challenge' took place. Three experts spoke about the importance of bioethics in the race to develop a COVID-19 vaccine, the risk involved in shortening the terms of the clinical trial phases, and how the associated risks can be minimized, in order to expedite research results.  Conclusion With the novel SARS-CoV-2 coronavirus, critical challenges have been posed not only for public health but for research and the scientific community. A safe and effective vaccine is urgently needed to prevent COVID-19 transmission, complications, and deaths; the adherence to ethical principles required by clinical research is mandatory and closer supervision is also essential.

11.
Vaccines (Basel) ; 8(3)2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899720

RESUMO

Vaccines are considered one of the most important bioproducts in medicine. Since the development of the smallpox vaccine in 1796, several types of vaccines for many diseases have been created. However, some vaccines have shown limitations as high cost and low immune responses. In that regard, bacteriophages have been proposed as an attractive alternative for the development of more cost-effective vaccines. Phage-displayed vaccines consists in the expression of antigens on the phage surface. This approach takes advantage of inherent properties of these particles such as their adjuvant capacity, economic production and high stability, among others. To date, three types of phage-based vaccines have been developed: phage-displayed, phage DNA and hybrid phage-DNA vaccines. Typically, phage display technology has been used for the identification of new and protective epitopes, mimotopes and antigens. In this context, phage particles represent a versatile, effective and promising alternative for the development of more effective vaccine delivery systems which should be highly exploited in the future. This review describes current advances in the development of bacteriophage-based vaccines, with special attention to vaccine delivery strategies. Moreover, the immunological aspects of phage-based vaccines, as well as the applications of phage display for vaccine development, are explored. Finally, important challenges and the future of phage-bases vaccines are discussed.

12.
J Hepatol ; 73(3): 582-592, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-30654069

RESUMO

BACKGROUND & AIMS: Chronic hyperammonemia induces neuroinflammation which mediates cognitive impairment. How hyperammonemia induces neuroinflammation remains unclear. We aimed to assess whether: chronic hyperammonemia induces peripheral inflammation, and whether this then contributes to neuroinflammation, altered neurotransmission and impaired spatial learning - before assessing whether this neuroinflammation and impairment is reversible following hyperammonemia elimination or treatment of peripheral inflammation with anti-TNF-α. METHODS: Chronic hyperammonemia was induced by feeding rats an ammonia-containing diet. Peripheral inflammation was analyzed by measuring PGE2, TNF-α, IL-6 and IL-10. We tested whether chronic anti-TNF-α treatment improves peripheral inflammation, neuroinflammation, membrane expression of glutamate receptors in the hippocampus and spatial learning. RESULTS: Hyperammonemic rats show a rapid and reversible induction of peripheral inflammation, with increased pro-inflammatory PGE2, TNF-α and IL-6, followed at around 10 days by reduced anti-inflammatory IL-10. Peripheral anti-TNF-α treatment prevents peripheral inflammation induction and the increase in IL-1b and TNF-α and microglia activation in hippocampus of the rats, which remain hyperammonemic. This is associated with prevention of the altered membrane expression of glutamate receptors and of the impairment of spatial memory assessed in the radial and Morris water mazes. CONCLUSIONS: This report unveils a new mechanism by which chronic hyperammonemia induces neurological alterations: induction of peripheral inflammation. This suggests that reducing peripheral inflammation by safe procedures would improve cognitive function in patients with minimal hepatic encephalopathy. LAY SUMMARY: This article unveils a new mechanism by which chronic hyperammonemia induces cognitive impairment in rats: chronic hyperammonemia per se induces peripheral inflammation, which mediates many of its effects on the brain, including induction of neuroinflammation, which alters neurotransmission, leading to cognitive impairment. It is also shown that reducing peripheral inflammation by treating rats with anti-TNF-α, which does not cross the blood-brain barrier, prevents hyperammonemia-induced neuroinflammation, alterations in neurotransmission and cognitive impairment.


Assuntos
Anti-Inflamatórios/administração & dosagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Hiperamonemia/complicações , Infliximab/administração & dosagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Disfunção Cognitiva/sangue , Modelos Animais de Doenças , Encefalopatia Hepática/tratamento farmacológico , Encefalopatia Hepática/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Memória/efeitos dos fármacos , Ratos , Ratos Wistar , Aprendizagem Espacial/efeitos dos fármacos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
13.
Rev. ecuat. neurol ; 27(2): 70-78, may.-ago. 2018. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1004025

RESUMO

Resumen El síndrome de la encefalopatía posterior reversible conocido como (PRES) es un trastorno neurológico caracterizado por cefalea, alteraciones visuales, deterioro del estado de consciencia, crisis convulsivas y déficits neurológicos variados que tienen como causa, el incremento severo de la presión arterial. Los trastornos hipertensivos del embarazo, principalmente la preeclampsia y eclampsia, siguen siendo una de las causas principales de la morbilidad y mortalidad durante el embarazo, causando complicaciones neurológicas que van desde las crisis convulsivas únicas hasta el desarrollo de estatus convulsivos y del advenimiento de eventos cerebrovasculares potencialmente mortales. Describimos la presentación del síndrome de encefalopatía posterior reversible en una adolescente embarazada quien desarrolló un trastorno hipertensivo del embarazo.


Abstract Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder characterized by headaches, visual disturbances, altered level of consciousness, seizures, and a variety of neurological deficits that are caused by a severe increase in blood pressure. Hypertensive disorders of pregnancy, mainly preeclampsia and eclampsia, continue to be one of the main causes of morbidity and mortality during pregnancy worldwide, causing neurological complications ranging from singular seizures to the development of status epilepticus and the advent of potentially fatal cerebrovascular events. We describe the presentation of posterior reversible encephalopathy syndrome in a pregnant adolescent who developed a hypertensive disorder of pregnancy.

14.
Biotechnol Prog ; 34(5): 1177-1184, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29882325

RESUMO

Aqueous two-phase systems (ATPS) have been widely exploited for the recovery and partial purification of biological compounds. Recently our research group characterized the primary recovery and partial purification of bacteriophage M13 using polymer-salt and ionic liquid-salt ATPS. From such study, it was concluded that PEG 400-potassium phosphate ATPS with a volume ratio (VR ) of 1 and 25% w/w TLL were the best suitable for the primary recovery of bacteriophage M13 from a crude extract, achieving a recovery yield of 83.3%. Although such system parameters were proven to be adequate for the recovery of the product of interest, it was concluded that further optimization was desirable and attainable by studying the effect of additional system parameters such as VR , concentration of neutral salt (M) and sample load (% w/w). This research work presents an optimization of a previously reported process for the recovery of bacteriophage M13 directly from a crude extract using ATPS. The increase in VR and sample load showed a positive effect in the recovery of M13 indicating an improved performance of the proposed ATPS. According to the results presented here, a system composed of PEG 400 17.2% (w/w), potassium phosphate 15.5% (w/w) and a sample load of 30% (w/w) allowed the recovery of M13 directly from a crude extract with a top phase recovery of 80.1%, representing an increase of 4.8 times in the final concentration and a reduction of 2.65 times in the processing costs. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018 © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1177-1184, 2018.


Assuntos
Bacteriófago M13 , Fosfatos/química , Compostos de Potássio/química , Polietilenoglicóis/química , Cloreto de Sódio/química , Água/química
16.
MAbs ; 10(5): 778-795, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29733750

RESUMO

Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory disease in infants and young children worldwide. Currently, treatment is supportive and no vaccines are available. The use of newborn lambs to model hRSV infection in human infants may provide a valuable tool to assess safety and efficacy of new antiviral drugs and vaccines. ALX-0171 is a trivalent Nanobody targeting the hRSV fusion (F) protein and its therapeutic potential was evaluated in newborn lambs infected with a human strain of RSV followed by daily ALX-0171 nebulization for 3 or 5 consecutive days. Colostrum-deprived newborn lambs were infected with hRSV-M37 before being treated by daily nebulization with either ALX-0171 or placebo. Two different treatment regimens were examined: day 1-5 or day 3-5 post-infection. Lambs were monitored daily for general well-being and clinical parameters. Respiratory tissues and bronchoalveolar lavage fluid were collected at day 6 post-inoculation for the quantification of viral lesions, lung viral titers, viral antigen and lung histopathology. Administration by inhalation of ALX-0171 was well-tolerated in these hRSV-infected newborn lambs. Robust antiviral effects and positive effects on hRSV-induced lung lesions and reduction in symptoms of illness were noted. These effects were still apparent when treatment start was delayed and coincided with peak viral loads (day 3 post-infection) and at a time point when signs of RSV disease were apparent. The latter design is expected to have high translational value for planned clinical trials. These results are indicative of the therapeutic potential of ALX-0171 in infants.


Assuntos
Modelos Animais de Doenças , Infecções por Vírus Respiratório Sincicial/veterinária , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Doenças dos Ovinos/prevenção & controle , Anticorpos de Domínio Único/administração & dosagem , Administração por Inalação , Animais , Animais Recém-Nascidos , Antivirais/administração & dosagem , Líquido da Lavagem Broncoalveolar/virologia , Humanos , Lactente , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/fisiologia , Ovinos , Doenças dos Ovinos/virologia , Carga Viral/efeitos dos fármacos
17.
Nat Commun ; 8(1): 167, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28761099

RESUMO

Respiratory syncytial virus is a major cause of acute lower respiratory tract infection in young children, immunocompromised adults, and the elderly. Intervention with small-molecule antivirals specific for respiratory syncytial virus presents an important therapeutic opportunity, but no such compounds are approved today. Here we report the structure of JNJ-53718678 bound to respiratory syncytial virus fusion (F) protein in its prefusion conformation, and we show that the potent nanomolar activity of JNJ-53718678, as well as the preliminary structure-activity relationship and the pharmaceutical optimization strategy of the series, are consistent with the binding mode of JNJ-53718678 and other respiratory syncytial virus fusion inhibitors. Oral treatment of neonatal lambs with JNJ-53718678, or with an equally active close analog, efficiently inhibits established acute lower respiratory tract infection in the animals, even when treatment is delayed until external signs of respiratory syncytial virus illness have become visible. Together, these data suggest that JNJ-53718678 is a promising candidate for further development as a potential therapeutic in patients at risk to develop respiratory syncytial virus acute lower respiratory tract infection.Respiratory syncytial virus causes lung infections in children, immunocompromised adults, and in the elderly. Here the authors show that a chemical inhibitor to a viral fusion protein is effective in reducing viral titre and ameliorating infection in rodents and neonatal lambs.


Assuntos
Imidazolidinas/metabolismo , Indóis/metabolismo , Vírus Sincicial Respiratório Humano/metabolismo , Inibidores de Proteínas Virais de Fusão/metabolismo , Proteínas Virais de Fusão/metabolismo , Animais , Animais Recém-Nascidos , Linhagem Celular Tumoral , Chlorocebus aethiops , Células Epiteliais , Humanos , Imidazolidinas/farmacologia , Imidazolidinas/uso terapêutico , Indóis/farmacologia , Indóis/uso terapêutico , Estrutura Molecular , Pneumonia Viral/tratamento farmacológico , Ratos , Mucosa Respiratória/citologia , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Vírus Sinciciais Respiratórios/metabolismo , Ovinos , Relação Estrutura-Atividade , Células Vero , Inibidores de Proteínas Virais de Fusão/farmacologia , Inibidores de Proteínas Virais de Fusão/uso terapêutico
18.
Sci Adv ; 3(5): e1601693, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28508052

RESUMO

There is a considerable controversy about whether western Amazonia was ever covered by marine waters during the Miocene [23 to 5 Ma (million years ago)]. We investigated the possible occurrence of Miocene marine incursions in the Llanos and Amazonas/Solimões basins, using sedimentological and palynological data from two sediment cores taken in eastern Colombia and northwestern Brazil together with seismic information. We observed two distinct marine intervals in the Llanos Basin, an early Miocene that lasted ~0.9 My (million years) (18.1 to 17.2 Ma) and a middle Miocene that lasted ~3.7 My (16.1 to 12.4 Ma). These two marine intervals are also seen in Amazonas/Solimões Basin (northwestern Amazonia) but were much shorter in duration, ~0.2 My (18.0 to 17.8 Ma) and ~0.4 My (14.1 to 13.7 Ma), respectively. Our results indicate that shallow marine waters covered the region at least twice during the Miocene, but the events were short-lived, rather than a continuous full-marine occupancy of Amazonian landscape over millions of years.

19.
Cad. Ibero Am. Direito Sanit. (Impr.) ; 6(1): 167-179, jan.-mar. 2017.
Artigo em Espanhol | LILACS | ID: biblio-878595

RESUMO

Actualmente en Latinoamérica lo referente al Aborto abre el debate ético-jurídico en torno a la legalización del proceso. Si bien el debate sobre el Aborto está aún lejos de agotarse. Se pretende con esa revisión circunscribir la discusión específicamente a la Interrupción Terapéutica del Embarazo, entendiendo esta como un derecho a la salud de las mujeres, que ha sido plasmado en la jurisprudencia constitucional, y ha sido reconocido en la mayoría de las legislaciones tanto en América como en Europa. El bioderecho nos otorga una nueva perspectiva de análisis de la Interrupción Terapéutica del Embarazo al abordar el problema desde tres corrientes, biológica, ética y jurídica. Además, nos permitimos mediante ejercicios de derecho comparado y análisis de los razonamientos jurisprudenciales, aproximarnos a conclusiones con respecto de un problema de salud que afrontan miles de mujeres.


At present, in Latin America, abortion refers to the ethical-legal debate around the legalization of the process. While the debate on abortion is still far from exhausted. The purpose of this review is to circumscribe the discussion specifically to the Therapeutic Interruption of Pregnancy, understanding this as a right to women's health, which has been reflected in constitutional jurisprudence, and has been recognized in most of the legislations both in America As in Europe. The Bioderecho gives us a new perspective of analysis of the Therapeutic Interruption of Pregnancy in addressing the problem from three streams, biological, ethical and legal; We also allow comparative law exercises and analysis of jurisprudential reasoning to approximate conclusions regarding a health problem faced by thousands of women


Atualmente na América Latina abre-se o debate para a relação do aborto com os temas ético e jurídico em torno do processo de sua legalização. Mas o debate sobre o aborto ainda está longe de se esgotar. Pretende-se com esta revisão circunscrever a discussão especificamente ao aborto terapêutico, entendido como o direito à saúde das mulheres, que foi incorporada na jurisprudência constitucional, e tem sido reconhecida na maioria das leis na América e na Europa. O Biodireito nos dá uma nova perspectiva de análise do aborto terapêutico na abordagem do problema a partir de três eixos: biológicos, éticos e legais. Além disso, permite que o direito comparado através de exercícios e análise da abordagem de raciocínio jurisprudencial conclusa sobre problema de saúde enfrentado por milhares de mulheres.


Assuntos
Feminino , Aborto Induzido/legislação & jurisprudência , Aborto Induzido/estatística & dados numéricos , Bioética , Direitos Humanos
20.
PLoS One ; 10(12): e0143580, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26641081

RESUMO

RATIONALE: Respiratory syncytial virus (RSV) infection in preterm and newborn infants can result in severe bronchiolitis and hospitalization. The lamb lung has several key features conducive to modeling RSV infection in human infants, including susceptibility to human strains of RSV such as the A2, Long, and Memphis Strain 37 (M37). In this study, the kinetics of M37 infection was investigated in newborn lambs in order to better define clinical, viral, physiological, and immunological parameters as well as the pathology and lesions. METHODS: Newborn lambs were nebulized with M37 hRSV (6 mL of 1.27 x 10(7) FFU/mL), monitored daily for clinical responses, and respiratory tissues were collected from groups of lambs at days 1, 3, 4, 6, and 8 post-inoculation for the assessment of viral replication parameters, lesions and also cellular, immunologic and inflammatory responses. RESULTS: Lambs had increased expiratory effort (forced expiration) at days 4, 6, and 8 post-inoculation. Nasal wash lacked RSV titers at day 1, but titers were present at low levels at days 3 (peak), 4, and 8. Viral titers in bronchoalveolar lavage fluid (BALF) reached a plateau at day 3 (4.6 Log10 FFU/mL), which was maintained until day 6 (4.83 Log10 FFU/mL), and were markedly reduced or absent at day 8. Viral RNA levels (detected by RT-qPCR) in BALF were indistinguishable at days 3 (6.22 ± 0.08 Log10 M37 RNA copies/mL; mean ± se) and 4 (6.20 ± 0.16 Log10 M37 RNA copies/mL; mean ± se) and increased slightly on day 6 (7.15 ± 0.2 Log10 M37 RNA copies/mL; mean ± se). Viral antigen in lung tissue as detected by immunohistochemistry was not seen at day 1, was present at days 3 and 4 before reaching a peak by day 6, and was markedly reduced by day 8. Viral antigen was mainly present in airways (bronchi, bronchioles) at day 3 and was increasingly present in alveolar cells at days 4 and 6, with reduction at day 8. Histopathologic lesions such as bronchitis/bronchiolitis, epithelial necrosis and hyperplasia, peribronchial lymphocyte infiltration, and syncytial cells, were consistent with those described previously for lambs and infants. CONCLUSION: This work demonstrates that M37 hRSV replication in the lower airways of newborn lambs is robust with peak replication on day 3 and sustained until day 6. These findings, along with the similarities of lamb lung to those of infants in terms of alveolar development, airway branching and epithelium, susceptibility to human RSV strains, lesion characteristics (bronchiolitis), lung size, clinical parameters, and immunity, further establish the neonatal lamb as a model with key features that mimic RSV infection in infants.


Assuntos
Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/fisiologia , Vírus Sincicial Respiratório Humano/patogenicidade , Animais , Animais Recém-Nascidos , Antígenos Virais/metabolismo , Líquido da Lavagem Broncoalveolar/virologia , Quimiocinas/genética , Citocinas/genética , Modelos Animais de Doenças , Genes Virais , Humanos , Recém-Nascido , Cinética , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , RNA Viral/genética , RNA Viral/metabolismo , Infecções por Vírus Respiratório Sincicial/etiologia , Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sincicial Respiratório Humano/genética , Carneiro Doméstico , Replicação Viral
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