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1.
Cells ; 12(3)2023 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-36766724

RESUMEN

Major depressive disorder (MDD) is a multidimensional psychiatric disorder that is estimated to affect around 350 million people worldwide. Generating valid and effective animal models of depression is critical and has been challenging for neuroscience researchers. For preclinical studies, models based on stress exposure, such as unpredictable chronic mild stress (uCMS), are amongst the most reliable and used, despite presenting concerns related to the standardization of protocols and time consumption for operators. To overcome these issues, we developed an automated system to expose rodents to a standard uCMS protocol. Here, we compared manual (uCMS) and automated (auCMS) stress-exposure protocols. The data shows that the impact of the uCMS exposure by both methods was similar in terms of behavioral (cognition, mood, and anxiety) and physiological (cell proliferation and endocrine variations) measurements. Given the advantages of time and standardization, this automated method represents a step forward in this field of preclinical research.


Asunto(s)
Trastorno Depresivo Mayor , Ratas , Animales , Ansiedad , Cognición
2.
Sensors (Basel) ; 22(16)2022 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-36015899

RESUMEN

This work presents a novel Automated Machine Learning (AutoML) approach for Real-Time Fault Detection and Diagnosis (RT-FDD). The approach's particular characteristics are: it uses only data that are commonly available in industrial automation systems; it automates all ML processes without human intervention; a non-ML expert can deploy it; and it considers the behavior of cyclic sequential machines, combining discrete timed events and continuous variables as features. The capacity for fault detection is analyzed in two case studies, using data from a 3D machine simulation system with faulty and non-faulty conditions. The enhancement of the RT-FDD performance when the proposed approach is applied is proved with the Feature Importance, Confusion Matrix, and F1 Score analysis, reaching mean values of 85% and 100% in each case study. Finally, considering that faults are rare events, the sensitivity of the models to the number of faulty samples is analyzed.


Asunto(s)
Algoritmos , Aprendizaje Automático , Simulación por Computador , Humanos
3.
IEEE Trans Neural Netw Learn Syst ; 33(8): 3251-3263, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33513115

RESUMEN

Hybrid systems, which combine statistical and machine learning (ML) techniques using residual (error forecasting) modeling, have been highlighted in the literature due to their accuracy and ability to forecast time series with different characteristics. In these architectures, a crucial task is the proper modeling of the residuals since they may present random fluctuations, complex nonlinear patterns, and heteroscedastic behavior. Hence, the selection, specification, and training of one ML model to forecast the residuals are costly and challenging tasks since issues, such as underfitting, overfitting, and misspecification, can lead to a system with low accuracy or even deteriorate the linear forecast of the time series. This article proposes a hybrid system, named dynamic residual forecasting (DReF), that employs a modified dynamic selection (DS) algorithm to decide: the most suitable ML model to forecast a pattern of the residual series and if it is a promising candidate to increase the accuracy of the time series forecast from the linear combination. Thus, the DReF aims to reduce the uncertainty of the ML model selection and avoid the deterioration of the time series forecast. Furthermore, the proposed system searches for the most suitable parameters of the DS algorithm for each data set. In this article, the proposed method uses a pool of five ML models widely adopted in the literature: multilayer perceptron, support vector regression, radial basis function, long short-term memory, and convolutional neural network. An experimental evaluation was conducted using ten well-known time series. The results show that the DReF obtains superior results for the majority of the data sets compared with single and hybrid models of the literature.

4.
Sensors (Basel) ; 21(23)2021 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-34884100

RESUMEN

The employment of smart meters for energy consumption monitoring is essential for planning and management of power generation systems. In this context, forecasting energy consumption is a valuable asset for decision making, since it can improve the predictability of forthcoming demand to energy providers. In this work, we propose a data-driven ensemble that combines five single well-known models in the forecasting literature: a statistical linear autoregressive model and four artificial neural networks: (radial basis function, multilayer perceptron, extreme learning machines, and echo state networks). The proposed ensemble employs extreme learning machines as the combination model due to its simplicity, learning speed, and greater ability of generalization in comparison to other artificial neural networks. The experiments were conducted on real consumption data collected from a smart meter in a one-step-ahead forecasting scenario. The results using five different performance metrics demonstrate that our solution outperforms other statistical, machine learning, and ensembles models proposed in the literature.


Asunto(s)
Aprendizaje Automático , Redes Neurales de la Computación , Predicción , Modelos Lineales , Modelos Estadísticos
5.
Brain Res ; 1732: 146700, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-32032613

RESUMEN

The central nervous system (CNS) has a limited auto-regeneration capacity, which makes it challenging for the development of new therapies. Previous studies from our lab have demonstrated the applicability of human bone marrow mesenchymal stem cells (hBM-MSCs) secretome as a possible therapeutic tool for CNS. Astrocytes, glial cells present in all brain regions, are important players in brain function through their vast influence in extracellular homeostasis, neuro-vascular regulation, synaptic modulation and neurogenesis. Thus, in the present work, we aimed to evaluate the specific impact of MSCs secretome on hippocampal proliferation and astrocyte morphology, in both WT and dnSNARE mice, a transgenic model that presents impaired astrocytic exocytosis and consequently impaired astrocytic function. Results demonstrated increased levels of proliferation for WT when treated with secretome. Additionally, it was possible to observe that dnSNARE animals injected with hBM-MSCs secretome disclosed increased levels of proliferating GFAP stained cells at the SGZ. Morphometrical evaluation found increased process hypertrophy and branching of dnSNARE astrocytes when treated with secretome. These results are closely related with the trophic factors present in the secretome, namely FGF-2, BDNF, GDNF, IGF-1, VEGF, CADH2, PEDF and miR-16. Moreover, the impaired exocytosis of astrocytes may also have implications for the response to the proliferative stimulus, given the established autocrine signaling through this mechanism.


Asunto(s)
Astrocitos/metabolismo , Hipocampo/metabolismo , Células Madre Mesenquimatosas/metabolismo , Transducción de Señal/fisiología , Astrocitos/citología , Proliferación Celular/fisiología , Forma de la Célula/fisiología , Medios de Cultivo Condicionados , Hipocampo/citología , Humanos
6.
Lupus Sci Med ; 4(1): e000184, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28123769

RESUMEN

OBJECTIVES: To assess the prevalence and severity of ultrasonographic abnormalities of the hand and wrist of asymptomatic patients with systemic lupus erythematosus (SLE) and compare these findings with those from patients with SLE with musculoskeletal signs or symptoms and healthy controls. METHODS: We conducted a prospective cross-sectional study that evaluated bilaterally, with grey-scale and power Doppler (PD) ultrasound (US), the dorsal hand (2nd to 5th metacarpophalangeal and 2nd to 5th proximal interphalangeal joints) and wrist (radiocarpal, ulnocarpal and intercarpal joints) of 30 asymptomatic patients with SLE, 6 symptomatic patients with SLE and 10 controls. Synovial hypertrophy (SH) and intra-articular PD signal were scored using semiquantitative grading scales (0-3). Individual scores were graded as normal (SH≤1 and PD=0) or abnormal (SH≥2 or PD≥1). Global indexes for SH and PD were also calculated. US findings were correlated with clinical and laboratory data and disease activity indexes. RESULTS: US detected SH (score ≥1) in 77% asymptomatic patients with SLE, mostly graded as minimal (score 1: 63%). 23% of the asymptomatic patients with SLE showed abnormal US PD findings (SH≥2 or PD≥1). SH was present in all symptomatic patients with SLE, mostly graded as moderate (grade 2: 67%), and with associated PD signal (83%). SH (score 1) was identified in 50% of controls, however, none presented abnormal US PD findings. SH index in the asymptomatic SLE group was higher than in the control group (2.0 (0-5) vs 0.5 (0-2), median (range), p=0.01) and lower than in the symptomatic SLE group (7.0 (4-23), median (range), p<0.001). No significant correlation was demonstrated between US PD findings and clinical or laboratory variables and disease activity indexes. CONCLUSION: A small subgroup of asymptomatic patients with SLE may present subclinical joint inflammation. Global US scores and PD signal may be important in disease evaluation and therapeutic monitoring.

7.
Front Cell Neurosci ; 11: 427, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29386997

RESUMEN

Astrocytes are fundamental players in the regulation of synaptic transmission and plasticity. They display unique morphological and phenotypical features that allow to monitor and to dynamically respond to changes. One of the hallmarks of the astrocytic response is the generation of calcium elevations, which further affect downstream cellular processes. Technical advances in the field have allowed to spatially and to temporally quantify and qualify these elevations. However, the impact on brain function remains poorly understood. In this review, we discuss evidences of the functional impact of heterogeneous astrocytic calcium events in several brain regions, and their consequences in synapses, circuits, and behavior.

9.
Anim Reprod Sci ; 144(3-4): 72-8, 2014 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-24388700

RESUMEN

Bone morphogenetic proteins are known to be involved in determining ovulation rate in mammals. The mechanisms through which these proteins determine follicle fate are incompletely understood. In the present study, we used cattle as a model to evaluate the regulation of BMP15 and GDF9 receptors in granulosa cells during dominant follicle (DF) selection. Before follicular deviation (day 2 of the follicular wave), BMPR2 mRNA abundance tended to be higher in the second largest follicles (F2; P<0.1) compared to the future dominant follicle (F1). At the expected time of follicular deviation (day 3), BMPR2 and BMPR1B mRNA levels were higher in subordinate follicles (SFs; P<0.05) compared to dominant follicles (DFs). After deviation (on day 4), BMPR1B mRNA and protein were significantly more abundant in atretic SFs (as assessed by cleaved caspase 3) than in DFs. The fact that BMPR1B is more expressed in atretic follicles was further confirmed by using intrafollicular treatment with two agents known to induce atresia, namely an estradiol receptor antagonist (fulvestrant) and FGF10. In conclusion, the fact that BMPR-1B and -2 are more expressed in the second largest follicles before and at the expected time of follicular deviation is indicative of their inhibitory role in follicle differentiation and steroidogenesis. BMPR1B also seems to have a pivotal role during follicle regression since it is upregulated in advanced atretic follicles.


Asunto(s)
Proteína Morfogenética Ósea 15/metabolismo , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/genética , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/genética , Bovinos/genética , Folículo Ovárico/metabolismo , Ovulación/genética , Animales , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/metabolismo , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/metabolismo , Bovinos/metabolismo , Estradiol/análogos & derivados , Estradiol/farmacología , Receptor alfa de Estrógeno/antagonistas & inhibidores , Femenino , Factor 10 de Crecimiento de Fibroblastos/farmacología , Atresia Folicular/efectos de los fármacos , Atresia Folicular/genética , Atresia Folicular/metabolismo , Fulvestrant , Regulación de la Expresión Génica/efectos de los fármacos , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Factor 9 de Diferenciación de Crecimiento/metabolismo , Folículo Ovárico/citología , Folículo Ovárico/efectos de los fármacos , Ovulación/efectos de los fármacos , Ovulación/metabolismo
10.
Biol Reprod ; 88(6): 144, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23616594

RESUMEN

Paracrine release of ovine interferon tau (oIFNT) from the conceptus alters release of endometrial prostaglandin F2 alpha (PGF) and prevents luteolysis. Endocrine release of oIFNT into the uterine vein occurs by Day 15 of pregnancy and may impart resistance of the corpus luteum (CL) to PGF. It was hypothesized that infusion of recombinant oIFNT (roIFNT) into the uterine or jugular veins on Day 10 of the estrous cycle would protect the CL against exogenous PGF-induced luteolysis. Osmotic pumps were surgically installed in 24 ewes to deliver bovine serum albumin (BSA; n = 12) or roIFNT (200 µg/day; n = 12) for 24 h into the uterine vein. Six ewes in each treatment group received a single injection of PGF (4 mg/58 kg body weight) 12 h after pump installation. In a second experiment, BSA or roIFNT was delivered at 20 or 200 µg/day into the uterine vein or 200 µg/day into the jugular vein for 72 h in 30 ewes. One half of these ewes received an injection of PGF 24 h after pump installation. Concentrations of progesterone in serum declined in BSA-treated ewes injected with PGF, but were sustained in all ewes infused with 20 µg/day of roIFNT into the uterine vein and 200 µg of roIFNT into the jugular vein followed 24 h later with injection of PGF. All concentrations of roIFNT and modes of delivery (uterine or jugular vein) increased luteal concentrations of IFN-stimulated gene (i.e., ISG15) mRNA. Infusion of 200 µg of IFNT over 24 h induced greater mRNA concentrations for cell survival genes, such as BCL2-like 1 (BCL2L1 or Bcl-xL), serine/threonine kinase (AKT), and X-linked inhibitor of apoptosis (XIAP) and decreased prostaglandin F receptor (PTGFR) mRNA concentrations, when compared to controls. It is concluded that endocrine delivery of roIFNT, regardless of route (uterine or jugular vein), effectively protects CL from the luteolytic actions of PGF by mechanisms that involve ISGs and stabilization of cell survival genes.


Asunto(s)
Cuerpo Lúteo/efectos de los fármacos , Dinoprost/farmacología , Ciclo Estral/efectos de los fármacos , Interferón Tipo I/farmacología , Luteólisis/efectos de los fármacos , Proteínas Gestacionales/farmacología , Animales , Cuerpo Lúteo/metabolismo , Endometrio/irrigación sanguínea , Endometrio/efectos de los fármacos , Endometrio/metabolismo , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Ciclo Estral/metabolismo , Femenino , Luteólisis/metabolismo , Transportadores de Anión Orgánico/genética , Transportadores de Anión Orgánico/metabolismo , Progesterona/sangre , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Oxitocina/genética , Receptores de Oxitocina/metabolismo , Receptores de Prostaglandina/genética , Receptores de Prostaglandina/metabolismo , Ovinos , Útero/irrigación sanguínea , Útero/efectos de los fármacos , Útero/metabolismo
11.
Reprod Fertil Dev ; 25(3): 539-46, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23464501

RESUMEN

The present study evaluated whether the gonadotrophin surge modulates components of the renin-angiotensin system and whether angiotensin II (Ang II) plays a role in the production of hormones by follicular cells during the ovulatory process. In Experiment 1, cows were ovariectomised at various times (0, 3, 6, 12 and 24 h) after GnRH injection to obtain preovulatory follicles. The concentration of Ang II in follicular fluid increased after GnRH and reached a peak at 24 h, concomitant with the peak of angiotensinogen (AGT) mRNA expression in granulosa cells. AGT mRNA was not expressed in theca cells. Ang II receptor type 2 and angiotensin-converting enzyme mRNA levels were transiently upregulated in theca cells. In Experiment 2, an in vitro culture was used to determine whether Ang II could modulate hormone production by healthy dominant follicles. In the absence of LH, Ang II did not alter hormonal production by either theca or granulosa cells. Ang II plus LH increased progesterone and prostaglandin secretion by granulosa cells. In summary, the renin-angiotensin system is actively controlled during the preovulatory period and Ang II amplifies the stimulatory effects of LH on the secretion of progesterone and prostaglandins by granulosa cells.


Asunto(s)
Angiotensina II/metabolismo , Angiotensinógeno/biosíntesis , Bovinos/fisiología , Folículo Ovárico/metabolismo , Proestro/metabolismo , Receptor de Angiotensina Tipo 2/biosíntesis , Regulación hacia Arriba , Angiotensinógeno/genética , Angiotensinógeno/metabolismo , Animales , Células Cultivadas , Femenino , Fármacos para la Fertilidad Femenina/farmacología , Líquido Folicular/efectos de los fármacos , Líquido Folicular/metabolismo , Hormona Liberadora de Gonadotropina/farmacología , Células de la Granulosa/citología , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Hormona Luteinizante/metabolismo , Folículo Ovárico/citología , Folículo Ovárico/efectos de los fármacos , Peptidil-Dipeptidasa A/biosíntesis , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Progesterona/metabolismo , Prostaglandinas/metabolismo , Receptor de Angiotensina Tipo 2/genética , Receptor de Angiotensina Tipo 2/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , Células Tecales/efectos de los fármacos , Células Tecales/metabolismo , Técnicas de Cultivo de Tejidos , Regulación hacia Arriba/efectos de los fármacos
12.
Biol Reprod ; 85(6): 1167-74, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21849708

RESUMEN

Angiotensin II (AGT-2) induces follicular prostaglandin release in a number of species and ovulation in rabbits. Conversely, AGT-2 antagonists block ovulation in cattle. To determine the mechanism of action of AGT-2, we used a bovine granulosa cell model in which luteinizing hormone (LH) increased the expression of genes essential for ovulation in a time- and dose-dependent manner. The addition of AGT-2 to LH-stimulated cells significantly increased abundance of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA and protein, whereas AGT-2 alone had no effect. Upstream of PTGS2, AGT-2 increased abundance of mRNA encoding the epidermal growth factor-like ligands amphiregulin (AREG) and epiregulin (EREG) at 6 h posttreatment and abundance of a disintegrin and metalloprotease 17 (ADAM17), a sheddase, within 3 h of treatment. Inhibiting sheddase activity abolished the stimulatory effect of AGT-2 on AREG, EREG, and PTGS2 mRNA. The addition of selective AGT-2 antagonists to cells stimulated with LH plus AGT-2 demonstrated that AGT-2 did not act through the type 1 receptor and did not increase mitogen-activated protein kinase 3/1 phosphorylation. Combined with previous data from studies in vitro, we conclude that AGT-2 is an essential cofactor for LH in the early increase of ADAM expression/activity that induces the cascade of events leading to ovulation.


Asunto(s)
Angiotensina II/fisiología , Técnicas de Cultivo de Célula , Células de la Granulosa/metabolismo , Hormona Luteinizante/fisiología , Ovulación , Proteínas ADAM/metabolismo , Proteína ADAM17 , Anfirregulina , Animales , Bovinos , Células Cultivadas , Ciclooxigenasa 2/metabolismo , Factor de Crecimiento Epidérmico/metabolismo , Epirregulina , Femenino , Glicoproteínas/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo
13.
Hum Mol Genet ; 20(15): 2996-3009, 2011 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-21546381

RESUMEN

The risk of developing neurodegenerative diseases increases with age. Although many of the molecular pathways regulating proteotoxic stress and longevity are well characterized, their contribution to disease susceptibility remains unclear. In this study, we describe a new Caenorhabditis elegans model of Machado-Joseph disease pathogenesis. Pan-neuronal expression of mutant ATXN3 leads to a polyQ-length dependent, neuron subtype-specific aggregation and neuronal dysfunction. Analysis of different neurons revealed a pattern of dorsal nerve cord and sensory neuron susceptibility to mutant ataxin-3 that was distinct from the aggregation and toxicity profiles of polyQ-alone proteins. This reveals that the sequences flanking the polyQ-stretch in ATXN3 have a dominant influence on cell-intrinsic neuronal factors that modulate polyQ-mediated pathogenesis. Aging influences the ATXN3 phenotypes which can be suppressed by the downregulation of the insulin/insulin growth factor-1-like signaling pathway and activation of heat shock factor-1.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuronas/citología , Neuronas/metabolismo , Factores de Transcripción/metabolismo , Animales , Ataxina-3 , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Agregación Celular/genética , Agregación Celular/fisiología , Factores de Transcripción Forkhead , Microscopía Confocal , Proteínas del Tejido Nervioso/genética , Neuronas/patología , Péptidos/metabolismo , Factores de Transcripción/genética
14.
Pesqui. vet. bras ; 30(7): 581-585, July 2010. ilus
Artículo en Inglés | LILACS | ID: lil-557304

RESUMEN

The objective of this study was to evaluate the effect of medroxy-progesterone acetate (MAP) with or without estradiol benzoate (EB) on follicular growth during the estrous cycle in cattle. In the first experiment, Hereford cows were synchronized with a synthetic analogue of PGF2 alpha and were treated with two different doses of MAP (250 or 500 mg) with or without EB for 7 days starting on day 8 of the estrous cycle. Follicular growth was inhibited (P<0.05) in all cows except controls and those receiving 250mg MAP without EB. Seventy-five percent of the animals (15/20) showed estrus on days 21 and 22 of the cycle rather than at MAP withdrawal, demonstrating that these treatments did not induce estrus. To determine whether the EB treatment altered endometrial sensitivity to oxytocin and thus the luteolytic cascade, multiparous pre-synchronized cows received 5 mg of EB followed 6 hours later with 50 IU of oxytocin (OT; n=9). Eight hours after EB injection, endometrial fragments were collected from the cows on days 4, 13 and 17 of the estrous cycle and COX-2 gene expression was measured by PCR. EB increased COX-2 mRNA levels only on day 17 of the estrous cycle (P<0.05). In conclusion, MAP alone or associated with EB is able to suppress bovine follicular growth. However, EB in the presence of MAP is not efficient to induce luteolysis in cows when injected on day 8 of the estrous cycle.


Este estudo teve como objetivo avaliar o efeito do acetato de medroxi-progesterona (MAP) com ou sem benzoato de estradiol (BE) sobre o crescimento folicular durante o ciclo estral bovino. No primeiro experimento, vacas da raça Hereford foram sincronizadas com um análogo sintético de PGF2á e tratadas com duas doses diferentes de MAP (250 ou 500mg), com ou sem EB, durante 7 dias, iniciando-se no oitavo dia do ciclo estral. Observou-se uma inibição do crescimento folicular (P<0,05) em todas as vacas, exceto no grupo controle e no grupo que recebeu 250mg de MAP sem BE. Os 75 por cento dos animais não exibiu estro no momento da remoção do MAP, mas sim nos dias 21 e 22 do ciclo, demonstrando que os tratamentos não induziram cio. Para se determinar se o tratamento com BE alterou a sensibilidade endometrial à ocitocina e, assim, a cascata luteolítica, vacas multíparas pré-sincronizadas receberam 5mg de BE, seguidos, após 6 horas, de 50 UI de ocitocina (OT; n=9). Oito horas após a administração de BE, colheram-se fragmentos endometriais das vacas, nos dias 4, 13 e 17 do ciclo estral, mensurando-se a expressão gênica de COX-2 através de PCR. O BE aumentou os níveis de RNAm de COX-2 apenas no dia 17 do ciclo estral (P<0,05). Em conclusão, o MAP isolado ou associado a BE é capaz de suprimir o crescimento folicular bovino. Entretanto, o BE, na presença de MAP é ineficaz na indução da luteólise bovina, quando injetado no oitavo dia do ciclo estral.


Asunto(s)
Animales , Bovinos , Estro , Fase Folicular , Medroxiprogesterona/uso terapéutico , Bovinos , Ciclooxigenasa 2 , Reacción en Cadena de la Polimerasa
15.
Antimicrob Agents Chemother ; 53(7): 2887-91, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19364846

RESUMEN

In order to assess the prevalence of and risk factors for aminoglycoside-associated nephrotoxicity in intensive care units (ICUs), we evaluated 360 consecutive patients starting aminoglycoside therapy in an ICU. The patients had a baseline calculated glomerular filtration rate (cGFR) of > or =30 ml/min/1.73 m(2). Among these patients, 209 (58%) developed aminoglycoside-associated nephrotoxicity (the acute kidney injury [AKI] group, which consisted of individuals with a decrease in cGFR of >20% from the baseline cGFR), while 151 did not (non-AKI group). Both groups had similar baseline cGFRs. The AKI group developed a lower cGFR nadir (45 +/- 27 versus 79 +/- 39 ml/min/1.73 m(2) for the non-AKI group; P < 0.001); was older (56 +/- 18 years versus 52 +/- 19 years for the non-AKI group; P = 0.033); had a higher prevalence of diabetes (19.6% versus 9.3% for the non-AKI group; P = 0.007); was more frequently treated with other nephrotoxic drugs (51% versus 38% for the non-AKI group; P = 0.024); used iodinated contrast more frequently (18% versus 8% for the non-AKI group; P = 0.0054); and showed a higher prevalence of hypotension (63% versus 44% for the non-AKI group; P = 0.0003), shock (56% versus 31% for the non-AKI group; P < 0.0001), and jaundice (19% versus 8% for the non-AKI group; P = 0.0036). The mortality rate was 44.5% for the AKI group and 29.1% for the non-AKI group (P = 0.0031). A logistic regression model identified as significant (P < 0.05) the following independent factors that affected aminoglycoside-associated nephrotoxicity: a baseline cGFR of <60 ml/min/1.73 m(2) (odds ratio [OR], 0.42), diabetes (OR, 2.13), treatment with other nephrotoxins (OR, 1.61) or iodinated contrast (OR, 2.13), and hypotension (OR, 1.83). In conclusion, AKI was frequent among ICU patients receiving an aminoglycoside, and it was associated with a high rate of mortality. The presence of diabetes or hypotension and the use of other nephrotoxic drugs and iodinated contrast were independent risk factors for the development of aminoglycoside-associated nephrotoxicity.


Asunto(s)
Aminoglicósidos/efectos adversos , Aminoglicósidos/farmacología , Unidades de Cuidados Intensivos , Riñón/efectos de los fármacos , Adulto , Anciano , Amicacina/efectos adversos , Amicacina/farmacología , Estudios de Cohortes , Femenino , Gentamicinas/efectos adversos , Gentamicinas/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Riñón/metabolismo , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo
16.
Bioorg Med Chem ; 16(17): 8172-7, 2008 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-18678498

RESUMEN

The antifungal activity of several di(hetero)arylamine derivatives of the benzo[b]thiophene system was evaluated against clinically relevant Candida, Aspergillus, and dermatophyte species by a broth macrodilution test based on CLSI (formerly NCCLS) guidelines. The most active compound showed a broad spectrum of activity (against all tested fungal strains, including fluconazole-resistant fungi), with particularly low MICs for dermatophytes. Results from the inhibition of the dimorphic transition in Candida albicans and flow cytometry studies further confirmed their biological activity. With this study it was possible to establish some structure-activity relationships (SARs). The hydroxy groups proved to be essential for the activity in the aryl derivatives. Furthermore, the spectrum of activity in the pyridine derivatives was broadened by the absence of the ester group on position 2 of the benzo[b]thiophene system.


Asunto(s)
Aminas/síntesis química , Aminas/farmacología , Antifúngicos/síntesis química , Antifúngicos/farmacología , Tiofenos/química , Aminas/química , Antifúngicos/química , Arthrodermataceae/efectos de los fármacos , Aspergillus/efectos de los fármacos , Candida/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Citometría de Flujo/métodos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Estereoisomerismo , Relación Estructura-Actividad
17.
Neuropharmacology ; 55(4): 447-53, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18680754

RESUMEN

Membrane currents of layer V pyramidal cells in slices of the rat prefrontal cortex (PFC) were recorded with the patch-clamp technique. In an Mg2+-free superfusion medium l-trans-pyrrolidine-2,4-dicarboxylic acid (PDC), a preferential blocker of astrocytic glutamate transporters, caused inward current due to the activation of NMDA receptors. The blockade of conducted action potentials by tetrodotoxin did not interfere with this effect. ATP was inactive when given alone and potentiated the NMDA-induced current in an Mg2+-containing but not Mg2+-free superfusion medium. Agonists of group I ((S)-3,5-dihydroxyphenylglycine; DHPG) and II ((1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid; LY 379268) metabotropic glutamate receptors (mGluRs) also potentiated responses to NMDA, whereas the group III mGluR agonist L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) did not affect them. In contrast to ATP, PDC evoked inward current in the absence but not in the presence of external Mg2+, when given alone, and facilitated the NMDA effect Mg2+-independently. The PDC-induced facilitation of NMDA responses was blocked by group II ((2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid; LY 341495), but not group I ((RS)-1-aminoindan-1,5-dicarboxylic acid; AIDA) or III (alpha-methyl-3-methyl-4-phosphonophenylglycine; UBP 1112) mGluR antagonists. In conclusion, the blockade of astrocytic glutamate uptake by PDC may lead to a stimulation of group II mGluRs, while the triggering of exocytotic glutamate release from astrocytes by ATP may cause activation of group I mGluRs, both situated postsynaptically at layer V PFC pyramidal cells. Either group of mGluRs may interact with NMDA receptors in a positive manner.


Asunto(s)
Sistema de Transporte de Aminoácidos X-AG/fisiología , Potenciales de la Membrana/fisiología , Corteza Prefrontal/citología , Células Piramidales/fisiología , Receptores de Glutamato Metabotrópico/fisiología , Receptores de N-Metil-D-Aspartato/fisiología , Adenosina Trifosfato/farmacología , Animales , Ácidos Carboxílicos/farmacología , Interacciones Farmacológicas , Estimulación Eléctrica , Fármacos actuantes sobre Aminoácidos Excitadores/farmacología , Técnicas In Vitro , Magnesio/metabolismo , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/efectos de la radiación , Modelos Biológicos , Técnicas de Placa-Clamp/métodos , Células Piramidales/efectos de los fármacos , Células Piramidales/efectos de la radiación , Piridinas/farmacología , Ratas , Ratas Wistar
18.
Endocrinology ; 149(3): 1252-9, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18063687

RESUMEN

The ruminant conceptus synthesizes and secretes interferon (IFN)-tau, which presumably acts via an intrauterine paracrine mechanism to signal maternal recognition of pregnancy. The aims of this study were to determine whether IFN-stimulated genes (ISG) such as ISG15 and OAS-1 are differentially expressed in blood cells circulating in the uterus of ewes; whether extrauterine components of the reproductive tract such as the corpus luteum (CL) also express mRNA for these ISG, and whether antiviral activity is greater in uterine vein than in uterine artery during early pregnancy. The concentrations of mRNA for both ISG were significantly greater (P < 0.0001) in endometrium and jugular blood of 15-d pregnant ewes than in nonpregnant ewes. ISG15 and OAS-1 mRNA concentrations were also greater (P < 0.05) in CL from 15-d pregnant ewes than in nonpregnant ewes. Immunohistochemistry revealed intense staining for ISG15 in large luteal cells on d 15 of pregnancy. Blood cells from uterine artery and vein of 15-d pregnant ewes had similar ISG15 and OAS-1 mRNA concentrations, suggesting that these cells were not conditioned by IFN-tau within the uterus. By using an antiviral assay, uterine venous blood was found to contain 500- to 1000-fold higher concentrations of bioactive IFN-tau than in uterine arterial blood on d 15 of pregnancy. It is concluded that uterine vein releases IFN-tau, which induces ISG in extrauterine tissues such as the CL during the time of maternal recognition of pregnancy.


Asunto(s)
Factores Reguladores del Interferón/metabolismo , Interferón Tipo I/metabolismo , Proteínas Gestacionales/metabolismo , Preñez/metabolismo , Útero/metabolismo , Animales , Cuerpo Lúteo/metabolismo , Endometrio/metabolismo , Femenino , Regulación del Desarrollo de la Expresión Génica , Embarazo , ARN Mensajero/metabolismo , Ovinos , Útero/irrigación sanguínea
19.
Genet. mol. biol ; 28(1): 54-59, Jan.-Mar. 2005. tab, graf
Artículo en Inglés | LILACS | ID: lil-399616

RESUMEN

The aim of the present study was to verify associations between reproductive efficiency and four microsatellite markers located in synteny with genes involved in the regulation of reproductive mechanisms. A sample of 107 females from a Brangus Ibagé population (5/8 Aberdeen Angus x 3/8 Nelore) was characterized for ETH225 (D9S1) and MM12E6 (D9S20) microsatellites, mapped on chromosome 9, and HEL5 (D21S15) and AFZ1 (D21S37) on chromosome 21. Associations between the genetic markers and reproductive efficiency were determined by one-way analysis of variance using calving interval (CI), live weight at calving (LWC), live weight at first calving (LW1C) and live weight at second calving (LW2C) as dependent variables. The genotypes were classified according to allele size into homozygous for long alleles, homozygous for short alleles and heterozygous. A longer CI was observed for individuals homozygous for long alleles at the HEL5 locus compared with the others (p = 0.022). For the AFZ1 locus, an inverse correlation between allele size and calving interval was observed (p = 0.022), suggesting that homozygosity for long alleles at this microsatellite could be advantageous. Analysis of the combined effect of favorable genotypes at HEL5 and AFZ1 indicated that animals with unfavorable genotypes (homozygous for long alleles at HEL5 and homozygous for short alleles at AFZ1) presented a significantly longer CI (p = 0.003) when compared to the other genotypes. The ETH225 and MM12E6 systems did not present any association with CI. None of the systems studied showed any significant association with LWC, LW1C or LW2C.


Asunto(s)
Animales , Bovinos , Receptor IGF Tipo 1 , Receptores de Estrógenos , Repeticiones de Microsatélite , Técnicas Reproductivas
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