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1.
Respir Res ; 24(1): 80, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36922832

RESUMEN

BACKGROUND: Premature birth, perinatal inflammation, and life-saving therapies such as postnatal oxygen and mechanical ventilation are strongly associated with the development of bronchopulmonary dysplasia (BPD); these risk factors, alone or combined, cause lung inflammation and alter programmed molecular patterns of normal lung development. The current knowledge on the molecular regulation of lung development mainly derives from mechanistic studies conducted in newborn rodents exposed to postnatal hyperoxia, which have been proven useful but have some limitations. METHODS: Here, we used the rabbit model of BPD as a cost-effective alternative model that mirrors human lung development and, in addition, enables investigating the impact of premature birth per se on the pathophysiology of BPD without further perinatal insults (e.g., hyperoxia, LPS-induced inflammation). First, we characterized the rabbit's normal lung development along the distinct stages (i.e., pseudoglandular, canalicular, saccular, and alveolar phases) using histological, transcriptomic and proteomic analyses. Then, the impact of premature birth was investigated, comparing the sequential transcriptomic profiles of preterm rabbits obtained at different time intervals during their first week of postnatal life with those from age-matched term pups. RESULTS: Histological findings showed stage-specific morphological features of the developing rabbit's lung and validated the selected time intervals for the transcriptomic profiling. Cell cycle and embryo development, oxidative phosphorylation, and WNT signaling, among others, showed high gene expression in the pseudoglandular phase. Autophagy, epithelial morphogenesis, response to transforming growth factor ß, angiogenesis, epithelium/endothelial cells development, and epithelium/endothelial cells migration pathways appeared upregulated from the 28th day of gestation (early saccular phase), which represents the starting point of the premature rabbit model. Premature birth caused a significant dysregulation of the inflammatory response. TNF-responsive, NF-κB regulated genes were significantly upregulated at premature delivery and triggered downstream inflammatory pathways such as leukocyte activation and cytokine signaling, which persisted upregulated during the first week of life. Preterm birth also dysregulated relevant pathways for normal lung development, such as blood vessel morphogenesis and epithelial-mesenchymal transition. CONCLUSION: These findings establish the 28-day gestation premature rabbit as a suitable model for mechanistic and pharmacological studies in the context of BPD.


Asunto(s)
Displasia Broncopulmonar , Hiperoxia , Nacimiento Prematuro , Animales , Embarazo , Femenino , Conejos , Recién Nacido , Humanos , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/patología , Nacimiento Prematuro/metabolismo , Hiperoxia/metabolismo , Transcriptoma , Células Endoteliales/metabolismo , Proteómica , Animales Recién Nacidos , Pulmón/metabolismo , Inflamación/metabolismo
2.
Ann Anat ; 246: 152039, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36436720

RESUMEN

Bronchopulmonary dysplasia (BPD) is the most common complication of preterm delivery, with significant morbidity and mortality in a neonatal intensive care setting. Research in this field aims to identify the mechanisms of late lung development with possible therapeutic targets and the improvement of medical management. Rabbits represent a suitable lab preclinical tool for mimicking the clinical BPD phenotype. Rabbits are born at term in the alveolar phase as occurs in large animals and humans and in addition, they can be delivered prematurely in contrast to mice and rats. Continuous exposure to high oxygen concentration (95% O2) for 7 days induces functional and morphological lung changes in preterm rabbits that resemble those observed in BPD-affected babies. The preclinical research pays great attention to optimize the experimental procedures, reduce the number of animals used in experiments and, where possible, replace animal models with alternative assays, following the principle of the 3 Rs (Replace, Reduce and Refine). The use of in vitro assays based on the ex vivo culture of Precision Cut Lung Slices (PCLS) goes in this direction, representing a good compromise between controlled and flexible in vitro models and the more physiologically relevant in vivo ones. This work aims to set up morphological analyses to be applied in preclinical tests using preterm rabbits derived PCLS, cultured up to 7 days in different oxygen conditions, as a model. After a preliminary optimization of both lung preparation and histological processing methods of the lung slices of 300 µm, the morphological analysis was conducted evaluating a series of histomorphometric parameters derived from those widely used to follow the phases of lung development and its alterations in vivo. Our histomorphometric results demonstrated that the greatest differences from pseudo-normoxia and hyperoxia exposed samples at day 0, used as starting points to compare changes due to treatments and time, are detectable after 4 days of in vitro culture, representing the most suitable time point for analysis in preclinical screening. The combination of parameters suitable for evaluating PCLS morphology in vitro resulted to be Tissue Density and Septal Thickness. Shape Factor and Roughness, evaluated to highlight the increasing complexity of the airspaces, due to the formation of septal crests, gave useful information, however, without significant differences up to day 4. Other parameters like Mean Linear Intercept and Septal Density did not allow to highlight significant differences between different oxygen conditions and time points. Instead, Radial Alveolar Count, could not be applied to PCLS, due to the tissue changes following agar infusion and culture conditions.


Asunto(s)
Displasia Broncopulmonar , Hiperoxia , Lesión Pulmonar , Recién Nacido , Humanos , Conejos , Animales , Ratones , Ratas , Displasia Broncopulmonar/etiología , Animales Recién Nacidos , Pulmón/patología , Lesión Pulmonar/etiología , Hiperoxia/complicaciones , Hiperoxia/genética , Oxígeno , Modelos Animales de Enfermedad
3.
Pediatr Pulmonol ; 57(11): 2808-2814, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35938216

RESUMEN

Stable isotope tracers, like 13 C, can be used for the measurement of the partition between the endogenous and exogenous pulmonary disaturated-phosphatidylcholine (DSPC). Deuterium labeling methods are still not fully explored. Our aim was to investigate the feasibility of using deuterium-depleted water (DDW) and deuterium-enriched water (DEW) to measure endogenous and exogenous pulmonary DSPC in a rabbit model of surfactant depletion. Data obtained from the 13 C dilution method were used as a reference. We studied 9 adult rabbits: 4 drank DDW and 5 DEW for 5 days. Lung surfactant depletion was induced at Day 5 by repeated saline bronchoalveolar lavages (BAL), which were stored as a pool (BAL pool). After endogenous surfactant depletion, rabbits received exogenous surfactant followed by a second BAL depletion procedure (End-Experiment Pool). DSPC quantity, and palmitic acid (PA)-DSPC 2 H/1 H (δ2 H) and 13 C/12 C ratios (δ13 C) of exogenous surfactant batches and of BAL pools were measured by High-Resolution Mass Spectrometry. The amount of exogenous surfactant recovered from the lungs ranged from 45% to 81% and, it was highly correlated with those obtained with the use of the 13 C (r = 0.9844, p < 0.0001). We demonstrated that commercially available purified DDW and even low doses of DEW can be used to modify the deuterium background of endogenous surfactants with the purpose of measuring the contribution of exogenous surfactants to the endogenous alveolar surfactant pool.


Asunto(s)
Surfactantes Pulmonares , Tensoactivos , Animales , Deuterio/análisis , Ácido Palmítico , Fosfatidilcolinas , Surfactantes Pulmonares/análisis , Conejos , Agua
4.
Pharmaceutics ; 14(7)2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35890402

RESUMEN

Thiazolidinediones (TZDs) are potent PPARγ agonists that have been shown to attenuate alveolar simplification after prolonged hyperoxia in term rodent models of bronchopulmonary dysplasia. However, the pulmonary outcomes of postnatal TZDs have not been investigated in preterm animal models. Here, we first investigated the PPARγ selectivity, epithelial permeability, and lung tissue binding of three types of TZDs in vitro (rosiglitazone (RGZ), pioglitazone, and DRF-2546), followed by an in vivo study in preterm rabbits exposed to hyperoxia (95% oxygen) to investigate the pharmacokinetics and the pulmonary outcomes of daily RGZ administration. In addition, blood lipids and a comparative lung proteomics analysis were also performed on Day 7. All TZDs showed high epithelial permeability through Caco-2 monolayers and high plasma and lung tissue binding; however, RGZ showed the highest affinity for PPARγ. The pharmacokinetic profiling of RGZ (1 mg/kg) revealed an equivalent biodistribution after either intratracheal or intraperitoneal administration, with detectable levels in lungs and plasma after 24 h. However, daily RGZ doses of 1 mg/kg did not improve lung function in preterm rabbits exposed to hyperoxia, and daily 10 mg/kg doses were even associated with a significant lung function worsening, which could be partially explained by the upregulation of lung inflammation and lipid metabolism pathways revealed by the proteomic analysis. Notably, daily postnatal RGZ produced an aberrant modulation of serum lipids, particularly in rabbit pups treated with the 10 mg/kg dose. In conclusion, daily postnatal RGZ did not improve lung function and caused dyslipidemia in preterm rabbits exposed to hyperoxia.

5.
ERJ Open Res ; 8(2)2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35615416

RESUMEN

In this review, Early Career Members of the European Respiratory Society (ERS) and the Chairs of the ERS Assembly 7: Paediatrics present the highlights in paediatric respiratory medicine from the ERS International Congress 2021. The eight scientific Groups of this Assembly cover respiratory physiology and sleep, asthma and allergy, cystic fibrosis (CF), respiratory infection and immunology, neonatology and intensive care, respiratory epidemiology, bronchology, and lung and airway development. We here describe new developments in lung function testing and sleep-disordered breathing diagnosis, early life exposures affecting pulmonary function in children and effect of COVID-19 on sleep and lung function. In paediatric asthma, we present the important role of the exposome in asthma development, and how biologics can provide better outcomes. We discuss new methods to assess distal airways in children with CF, as some details remain blind when using the lung clearance index. Moreover, we summarise the new ERS guidelines for bronchiectasis management in children and adolescents. We present interventions to reduce morbidity and monitor pulmonary function in newborns at risk of bronchopulmonary dysplasia and long-term chronic respiratory morbidity of this disease. In respiratory epidemiology, we characterise primary ciliary dyskinesia, identify early life determinants of respiratory health and describe the effect of COVID-19 preventive measures on respiratory symptoms. Also, we describe the epidemiology of interstitial lung diseases, possible consequences of tracheomalacia and a classification of diffuse alveolar haemorrhage in children. Finally, we highlight that the characterisation of genes and pathways involved in the development of a disease is essential to identify new biomarkers and therapeutic targets.

6.
Pharmaceutics ; 14(5)2022 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-35631679

RESUMEN

High-flow nasal cannula (HFNC) is a non-invasive respiratory support (NRS) modality to treat premature infants with respiratory distress syndrome (RDS). The delivery of nebulized surfactant during NRS would represent a truly non-invasive method of surfactant administration and could reduce NRS failure rates. However, the delivery efficiency of nebulized surfactant during HFNC has not been evaluated in vitro or in animal models of respiratory distress. We, therefore, performed first a benchmark study to compare the surfactant lung dose delivered by commercially available neonatal nasal cannulas (NCs) and HFNC circuits commonly used in neonatal intensive care units. Then, the pulmonary effect of nebulized surfactant delivered via HFNC was investigated in spontaneously breathing rabbits with induced respiratory distress. The benchmark study revealed the surfactant lung dose to be relatively low for both types of NCs tested (Westmed NCs 0.5 ± 0.45%; Fisher & Paykel NCs 1.8 ± 1.9% of a nominal dose of 200 mg/kg of Poractant alfa). The modest lung doses achieved in the benchmark study are compatible with the lack of the effect of nebulized surfactant in vivo (400 mg/kg), where arterial oxygenation and lung mechanics did not improve and were significantly worse than the intratracheal instillation of surfactant. The results from the present study indicate a relatively low lung surfactant dose and negligible effect on pulmonary function in terms of arterial oxygenation and lung mechanics. This negligible effect can, for the greater part, be explained by the high impaction of aerosol particles in the ventilation circuit and upper airways due to the high air flows used during HFNC.

7.
J Mass Spectrom ; 57(2): e4808, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35060656

RESUMEN

Stable isotope tracing can be safely used for metabolic studies in animals and humans. The endogenous biosynthesis of lipids (lipogenesis) is a key process throughout the entire life but especially during brain and lung growth. Adequate synthesis of pulmonary surfactant lipids is indispensable for life. With this study, we report the use of deuterium-depleted water (DDW), suitable for human consumption, as metabolic precursor for lipogenesis. We studied 13 adult rabbits for 5 days. Four rabbits drank tap water (TW) and served as controls; in four animals, DDW was substituted to drinking water, whereas five drank deuterium-enriched water (DEW). After 5 days, a blood sample and a bronchoalveolar lavage (BAL) sample were collected. The 2 H/1 H (δ2 H) of BAL palmitic acid (PA) desaturated phosphatidylcholine (DSPC), the major phospholipid of pulmonary surfactant, and of plasma water was determined by high-resolution mass spectrometry. We found that the δ2 H values of DDW, DEW and TW were -984 ± 2‰, +757 ± 2‰ and -58 ± 1‰, respectively. After 5 days, plasma water values were -467 ± 87‰, +377 ± 56‰ and -53 ± 6‰, and BAL DSPC-PA was -401 ± 27‰, -96 ± 38‰ and -249 ± 9‰ in the DDW, DEW and TW, respectively. With this preliminary study, we demonstrated the feasibility of using DDW to label pulmonary surfactant lipids. This novel approach can be used in animals and in humans, and we speculate that it could be associated with more favourable study compliance than DEW in human studies.


Asunto(s)
Agua Potable , Surfactantes Pulmonares , Animales , Deuterio/análisis , Agua Potable/análisis , Fosfatidilcolinas/análisis , Fosfolípidos , Conejos
8.
J Appl Physiol (1985) ; 131(3): 895-904, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34292788

RESUMEN

Evolving bronchopulmonary dysplasia (BPD) is characterized by impaired alveolarization leading to lung aeration inhomogeneities. Hyperoxia-exposed preterm rabbits have been proposed to mimic evolving BPD; therefore, we aimed to verify if this model has the same lung ultrasound and mechanical features of evolving BPD in human neonates. Semiquantitative lung ultrasound and lung mechanics measurement was performed in 25 preterm rabbits (28 days of gestation) and 25 neonates (mean gestational age ≈ 26 wk) with evolving BPD. A modified rabbit lung ultrasound score (rLUS) and a validated neonatal lung ultrasound score (LUS) were used. Lung ultrasound images were recorded and evaluated by two independent observers blinded to each other's evaluation. Lung ultrasound findings were equally heterogeneous both in rabbits as in human neonates and encompassed all the classical lung ultrasound semiology. Lung ultrasound and histology examination were also performed in 13 term rabbits kept under normoxia as further control and showed the absence of ultrasound and histology abnormalities compared with hyperoxia-exposed preterm rabbits. The interrater absolute agreement for the evaluation of lung ultrasound images in rabbits was very high [ICC: 0.989 (95%CI: 0.975-0.995); P < 0.0001], and there was no difference between the two observers. Lung mechanics parameters were similarly altered in both rabbits and human neonates. There were moderately significant correlations between airway resistances and lung ultrasound scores in rabbits (ρ = 0.519; P = 0.008) and in neonates (ρ = 0.409; P = 0.042). In conclusion, the preterm rabbit model fairly reproduces the lung ultrasound and mechanical characteristics of preterm neonates with evolving BPD.NEW & NOTEWORTHY We have reported that hyperoxia-exposed preterm rabbits and human preterm neonates with evolving BPD have the same lung ultrasound appearance, and that lung ultrasound can be fruitfully applied on this model with a brief training. The animal model and human neonates also presented the same relationship between semiquantitative ultrasound-assessed lung aeration and airway resistances. In conclusion, this animal model fairly reproduce evolving BPD as it is seen in clinical practice.


Asunto(s)
Displasia Broncopulmonar , Hiperoxia , Animales , Animales Recién Nacidos , Displasia Broncopulmonar/diagnóstico por imagen , Modelos Animales de Enfermedad , Humanos , Hiperoxia/diagnóstico por imagen , Recién Nacido , Pulmón/diagnóstico por imagen , Conejos , Mecánica Respiratoria
9.
Pediatr Res ; 90(3): 576-583, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33452472

RESUMEN

BACKGROUND: In preterm infants, InSurE (Intubation-Surfactant-Extubation) and LISA (less invasive surfactant administration) techniques allow for exogenous surfactant administration while reducing lung injury associated with mechanical ventilation. We compared the acute pulmonary response and lung deposition of surfactant by LISA and InSurE in surfactant-depleted adult rabbits. METHODS: Twenty-six spontaneously breathing surfactant-depleted adult rabbits (6-7 weeks old) with moderate RDS and managed with nasal continuous positive airway pressure were randomized to 3 groups: (1) 200 mg/kg of surfactant by InSurE; (2) 200 mg/kg of surfactant by LISA; (3) no surfactant treatment (Control). Gas exchange and lung mechanics were monitored for 180 min. After that, surfactant lung deposition and distribution were evaluated monitoring disaturated-phosphatidylcholine (DSPC) and surfactant protein C (SP-C), respectively. RESULTS: No signs of recovery were found in the untreated animals. After InSurE, oxygenation improved more rapidly compared to LISA. However, at 180' LISA and InSurE showed comparable outcomes in terms of gas exchange, ventilation parameters, and lung mechanics. Neither DSPC in the alveolar pool nor SP-C signal distributions in a frontal lung section were significantly different between InSurE and LISA groups. CONCLUSIONS: In an acute setting, LISA demonstrated efficacy and surfactant lung delivery similar to that of InSurE in surfactant-depleted adult rabbits. IMPACT: Although LISA technique is gaining popularity, there are still several questions to address. This is the first study comparing LISA and InSurE in terms of gas exchange, ventilation parameters, and lung mechanics as well as surfactant deposition and distribution. In our animal study, three hours post-treatment, LISA method seems to be as effective as InSurE and showed similar surfactant lung delivery. Our findings provide some clarifications on a fair comparison between LISA and InSurE techniques, particularly in terms of surfactant delivery. They should reassure some of the concerns raised by the clinical community on LISA adoption in neonatal units.


Asunto(s)
Surfactantes Pulmonares/administración & dosificación , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico , Animales , Presión de las Vías Aéreas Positiva Contínua , Modelos Animales de Enfermedad , Humanos , Conejos , Respiración Artificial
10.
Recenti Prog Med ; 111(4): 269, 2020 Apr.
Artículo en Italiano | MEDLINE | ID: mdl-32319451
11.
Respir Res ; 20(1): 158, 2019 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-31319861

RESUMEN

BACKGROUND: Respiratory Distress Syndrome (RDS) is a prematurity-related breathing disorder caused by a quantitative deficiency of pulmonary surfactant. Surfactant replacement therapy is effective for RDS newborns, although treatment failure has been reported. The aim of this study is to trace exogenous surfactant by 13C variation and estimate the amount reaching the lungs at different doses of the drug. METHODS: Forty-four surfactant-depleted rabbits were obtained by serial bronchoalveolar lavages (BALs), that were merged into a pool (BAL pool) for each animal. Rabbits were in nasal continuous positive airway pressure and treated with 0, 25, 50, 100 or 200 mg/kg of poractant alfa by InSurE. After 90 min, rabbits were depleted again and a new pool (BAL end experiment) was collected. Disaturated-phosphatidylcholine (DSPC) was measured by gas chromatography. DSPC-Palmitic acid (PA) 13C/12C was analyzed by isotope ratio mass spectrometry. One-way non-parametric ANOVA and post-hoc Dunn's multiple comparison were used to assess differences among experimental groups. RESULTS: Based on DSPC-PA 13C/12C in BAL pool and BAL end experiment, the estimated amount of exogenous surfactant ranged from 61 to 87% in dose-dependent way (p < 0.0001) in animals treated with 25 up to 200 mg/kg. Surfactant administration stimulated endogenous surfactant secretion. The percentage of drug recovered from lungs did not depend on the administered dose and accounted for 31% [24-40] of dose. CONCLUSIONS: We reported a risk-free method to trace exogenous surfactant in vivo. It could be a valuable tool for assessing, alongside the physiological response, the delivery efficiency of surfactant administration techniques.


Asunto(s)
Productos Biológicos/metabolismo , Isótopos de Carbono/metabolismo , Pulmón/metabolismo , Fosfolípidos/metabolismo , Surfactantes Pulmonares/metabolismo , Animales , Productos Biológicos/administración & dosificación , Isótopos de Carbono/administración & dosificación , Relación Dosis-Respuesta a Droga , Pulmón/efectos de los fármacos , Masculino , Fosfolípidos/administración & dosificación , Surfactantes Pulmonares/administración & dosificación , Conejos , Tensoactivos/administración & dosificación , Tensoactivos/metabolismo
12.
Prof Inferm ; 71(3): 173-177, 2018.
Artículo en Italiano | MEDLINE | ID: mdl-30457271

RESUMEN

INTRODUCTION: The nature of nursing has prompted researchers nurses to use a large number of qualitative methodology research. The trend showed a substantial increase in its production between 1997 and 2000 to settle back down in the following years although until recently the qualitative methodology was considered a non-scientific research. The growing number of publications with qualitative design is paid concern to verify the rigor and credibility of studies using this method. The use of the quality assessment tools showed that the methodological precision of studies with a qualitative design has grown over time. AIM: Assessing, using the tool Critical Appraisal Skills Programme, the quality of qualitative studies published in the last five years by international nursing journals with higher impact factor. METHOD: We will search the qualitative articles published on the ten most influential nursing journals that will be submitted by two independent researchers at the Critical Appraisal Skills Programme tool in its original version. EXPECTED RESULTS: The results make it possible to observe whether the qualitative research produced in the field of nursing uses a rigorous methodology in the drafting of the report, assuming that the quality has grown in the past five years than in previous years. CONCLUSION: The study will help researchers assess which level reached nurses in the development of qualitative research.


Asunto(s)
Investigación en Enfermería/normas , Publicaciones Periódicas como Asunto/normas , Investigación Cualitativa , Proyectos de Investigación/tendencias , Estudios Transversales , Humanos , Factor de Impacto de la Revista , Investigación en Enfermería/tendencias
13.
PLoS One ; 13(7): e0200542, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30001410

RESUMEN

Nasal intermittent positive pressure ventilation (NIPPV) holds great potential as a primary ventilation support method for Respiratory Distress Syndrome (RDS). The use of NIPPV may also be of great value combined with minimally invasive surfactant delivery. Our aim was to implement an in vivo model of RDS, which can be managed with different non-invasive ventilation (NIV) strategies, including non-synchronized NIPPV, synchronized NIPPV (SNIPPV), and nasal continuous positive airway pressure (NCPAP). Forty-two surfactant-depleted adult rabbits were allocated in six different groups: three groups of animals were treated with only NIV for three hours (NIPPV, SNIPPV, and NCPAP groups), while three other groups were treated with surfactant (SF) followed by NIV (NIPPV+SF, SNIPPV+SF, and NCPAP+SF groups). Arterial gas exchange, ventilation indices, and dynamic compliance were assessed. Post-mortem the lungs were sampled for histological evaluation. Surfactant depletion was successfully achieved by repeated broncho-alveolar lavages (BALs). After BALs, all animals developed a moderate respiratory distress, which could not be reverted by merely applying NIV. Conversely, surfactant administration followed by NIV induced a rapid improvement of arterial oxygenation in all surfactant-treated groups. Breath synchronization was associated with a significantly better response in terms of gas exchange and dynamic compliance compared to non-synchronized NIPPV, showing also the lowest injury scores after histological assessment. The proposed in vivo model of surfactant deficiency was successfully managed with NCPAP, NIPPV, or SNIPPV; this model resembles a moderate respiratory distress and it is suitable for the preclinical testing of less invasive surfactant administration techniques.


Asunto(s)
Respiración con Presión Positiva , Surfactantes Pulmonares/farmacología , Síndrome de Dificultad Respiratoria/fisiopatología , Síndrome de Dificultad Respiratoria/terapia , Animales , Modelos Animales de Enfermedad , Conejos
14.
J Mass Spectrom ; 53(7): 560-564, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29633450

RESUMEN

Variation of the isotopic abundance of selected nutrients and molecules has been used for pharmacological and kinetics studies under the premise that the administered molecule has a different isotopic enrichment from the isotopic background of the recipient subject. The aim of this study is to test the feasibility of assessing the contribution of exogenous surfactant phospholipids to the endogenous alveolar pool in vivo after exogenous surfactant replacement therapy in rabbits. The study consisted in measuring the consistency of 13 C/12 C ratio of disaturated-phosphatidylcholine palmitate (DSPC-PA) in 7 lots of poractant alfa, produced over a year, and among bronchoalveolar lavages of 20 rabbits fed with a standard chow. A pilot study was performed in a rabbit model of lavage-induced surfactant deficiency: 7 control rabbits and 4 treated with exogenous surfactant. The contribution of exogenous surfactant to the alveolar pool was assessed after intra-tracheal administration of 200 mg/kg of poractant alfa. The 13 C content of DSPC-PA was measured by isotope ratio mass spectrometry. The mean DSPC-PA 13 C/12 C ratio of the 7 lots of poractant alfa was -18.8‰ with a SD of 0.1‰ (range: -18.9‰; -18.6‰). The mean 13 C/12 C ratio of surfactant DSPC recovered from the lung lavage of 20 rabbits was -28.8 ± 1.2‰ (range: -31.7‰; -25.7‰). The contribution of exogenous surfactant to the total alveolar surfactant could be calculated in the treated rabbits, and it ranged from 83.9% to 89.6%. This pilot study describes a novel method to measure the contribution of the exogenous surfactant to the alveolar pool. This method is based on the natural variation of 13 C, and therefore it does not require the use of chemically synthetized tracers. This method could be useful in human research and especially in surfactant replacement studies in preterm infants.


Asunto(s)
Productos Biológicos/farmacología , Fosfolípidos/farmacología , Alveolos Pulmonares/efectos de los fármacos , Surfactantes Pulmonares/farmacología , Animales , Productos Biológicos/uso terapéutico , Isótopos de Carbono , Estudios de Factibilidad , Humanos , Fosfolípidos/uso terapéutico , Proyectos Piloto , Alveolos Pulmonares/metabolismo , Surfactantes Pulmonares/uso terapéutico , Conejos
15.
Prof Inferm ; 70(3): 161-168, 2017.
Artículo en Italiano | MEDLINE | ID: mdl-29186649

RESUMEN

BACKGROUND: The pain in instituzionalized elderly people with cognitive impairment is common. This symptom is severely under-reported and under-treated within this population. Evaluation of pain intensity is an essential component of pain assessment. Self-report approach to pain assessment is generally regarded as the gold standard of pain measurement in people with mild and moderate cognitive decay. The literature demonstrated more different unidimensional self-report scales but the conclusions of the studies suggested often the utilization of different scales. AIM: The goal of this study was to compare three different unidimensional pain assessment scales to be used with 84 instituzionalized elderly people with an average Mini-Mental State Examination score of 18. METHOD: This was a descriptive cross-sectional study. The pain assessment was carried out by administering the three scales Faces Pain Scale (FPS), Numeric Rating Scale (NRS), Verbal Rating Scale (VRS). RESULTS: The results showed that the prevalence of pain was 60-70%. All three pain intensity scales had good reliability and validity (p=0.0001); The compilation time of Faces Pain Scale most above than the other two scales (p=0.0001). CONCLUSION: The findings of this article support the implementation of these scales in operative protocols considering the compilation time and preferences of the patients.


Asunto(s)
Demencia , Dimensión del Dolor/métodos , Anciano , Anciano de 80 o más Años , Estudios Transversales , Demencia/complicaciones , Demencia/diagnóstico , Femenino , Hogares para Ancianos , Humanos , Masculino , Dolor/complicaciones
17.
J Palliat Med ; 17(10): 1143-9, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25188766

RESUMEN

BACKGROUND: Although their benefits are controversial, artificial nutrition and hydration are often administered as a form of basic care to terminally ill patients. An important reason for this may be that these treatments have strong emotional and psychological meanings. AIMS: In the present article we investigated the opinions of Italian physicians and nurses on the administration of artificial nutrition and hydration to terminally ill patients with advanced dementia. We also investigated the antecedents of these opinions, considering feelings and thoughts related to death, ethical issues and training in palliative care. METHOD: A questionnaire was administered to Italian physicians (n=288) and nurses (n=763). We analyzed the percentages of agreement with the administration of artificial nutrition and hydration and, using multivariate logistic regressions, the possible antecedents of these opinions. RESULTS: Agreement with the provision of artificial hydration was higher (73%) than for artificial nutrition (48%), suggesting that artificial hydration may be seen as a form of basic care. Agreement with their administration was generally lower among professionals in northern Italy working in geriatrics wards who had received training in palliative care. We also found that death-related feelings and thoughts and ethical issues played a different part for physicians and nurses. CONCLUSIONS: Our findings suggest that opinions concerning artificial nutrition and hydration not only derive from scientific background, but also relate to cultural, ethical, and psychological issues. Our results also reveal important differences between physicians' and nurses' opinions, providing useful information for interpreting and overcoming obstacles to the effective cooperation between these professionals.


Asunto(s)
Actitud del Personal de Salud , Demencia/terapia , Fluidoterapia , Enfermeras y Enfermeros/psicología , Apoyo Nutricional , Médicos/psicología , Cuidado Terminal , Adulto , Femenino , Humanos , Italia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Cuidado Terminal/ética , Enfermo Terminal
18.
Recenti Prog Med ; 105(4): 166-74, 2014 Apr.
Artículo en Italiano | MEDLINE | ID: mdl-24770543

RESUMEN

Pain is one of the most frequent symptom in elderly people with dementia and despite of this, it is still under-acknowledged and under-treated. The best approach to pain assessment is to evaluate it with the most appropriate scale. While in the elderly suffering mild-moderate cognitive impairment, it's possible to use self-report scales, in the elderly with severe cognitive impairment the use of observational scales is recommended. The objective of this review is to analyze the various types of pain assessment tools used in patients with cognitive impairment. Literature review was carried out through consultation of the most important bio-medical databases: Medline (PubMed), KT+, Trip Database, Cinahl, Cochrane Library, Embase. The keywords used were: "pain measurement", "pain assessment", "dementia", "validation study", "aged". All keywords were linked using AND and OR boolean operators. Altogether 5 self-report scales and 17 observational scales were retrieved, 7 of which available in Italian validated versions. The review analyzes potential and limitations of each assessment tool, in order to assist the clinician to make the most appropriate choice when using it in health care contexts.


Asunto(s)
Demencia/fisiopatología , Dimensión del Dolor/métodos , Dolor/diagnóstico , Anciano , Trastornos del Conocimiento/fisiopatología , Humanos , Dolor/epidemiología , Índice de Severidad de la Enfermedad
19.
Prof Inferm ; 66(1): 5-16, 2013.
Artículo en Italiano | MEDLINE | ID: mdl-23591031

RESUMEN

Focused Assessment with Sonography for Trauma (commonly abbreviated as FAST) is considered for patients with blunt abdominal trauma as the gold standard for accident assessment in site. This method is increasingly used even by not radiologists professionals, as well as by nurses who works in emergency settings. This systematic review is aimed at evaluating the effectiveness of ultrasound FAST performed by nurses in emergencies department. Seven databases of primary and secondary literature as well as three national journals relevant to the field were consulted. The review was conducted between March and August 2011 developing 9 search strings. Articles have been critically reviewed by two authors independently. No restriction on language or time of publication have been used. A total of 4767 documents were displayed, of those only 4 were considered to be reviewed. A total of 1035 FAST ultrasound performed by nurses were included. The results show that the use of ultrasound FAST performed by trained nurses is very effective, with a sensitivity of 84% (95% CI 72.1-92.2) and a specificity of 97.37% (95% CI 92.55-99.10) . Practice execution time was an average of 156 seconds (2.6 minutes), median time of 138 seconds (range = 76 to 357). Just one study specified the training course that nurses were required to attend. To sum up, FAST ultrasound performed by nurses have an important role in emergencies management as well as in triage setting as valid screening tool.


Asunto(s)
Traumatismos Abdominales/diagnóstico por imagen , Diagnóstico de Enfermería , Heridas no Penetrantes/diagnóstico por imagen , Servicio de Urgencia en Hospital , Humanos , Ultrasonografía
20.
Aging Clin Exp Res ; 24(5): 537-47, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22960350

RESUMEN

BACKGROUND AND AIMS: In Italy there is a paucity of empirical data on practices concerning end-of-life decisions (ELDs) in geriatrics. We aimed to investigate the frequency and characteristics of ELDs made by Italian physicians and nurses in the geriatric setting. METHODS: In 2009, an anonymous questionnaire was sent to 54 geriatric units, 21 hospices, and 382 nursing homes in the Veneto and Trentino Alto Adige regions, and to professionals in the area who are members of the Italian Gerontology and Geriatrics Association. RESULTS: This paper reports the results of 552 questionnaires answered by 171 physicians, 368 nurses and 13 professionals who did not state their profession. Death was preceded by decisions to start or continue treatments likely to prolong the patients' life in 51.3% of cases. The proportion of deaths preceded by a decision to end life (DEL) was 20.8%; 18% of DELs concerned non-treatment decisions. There were 9 cases of ending of life without patient's explicit request. No cases of doctor-assisted suicide were reported, while there were 2 cases of euthanasia, one reported by a physician and one by a nurse. CONCLUSION: In geriatrics, DELs often precede the deaths of terminally-ill Italian patients. Nurses report making DELs more often than physicians, especially in incompetent patients. Continuous deep sedation was adopted by 39.5% of the Italian physicians for deaths not occurring suddenly and unexpectedly. Our report on physicians' and nurses' experiences of ELD making in geriatric settings can offer a valuable contribution to the current debate on end-of-life treatment, an issue that goes beyond national borders.


Asunto(s)
Toma de Decisiones , Geriatría/métodos , Enfermeras y Enfermeros , Médicos , Pautas de la Práctica en Medicina , Cuidado Terminal/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Eutanasia , Femenino , Conocimientos, Actitudes y Práctica en Salud , Hospitales para Enfermos Terminales , Humanos , Italia , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Cuidados Paliativos/métodos , Encuestas y Cuestionarios
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