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1.
Ir Med J ; 115(4): 584, 2022 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-35695798

RESUMEN

Aim The fundamental concept of multidisciplinary education is a shared mental model that leads to better interdependent collaboration. The aim of this bootcamp was to create a sustainable induction curriculum for Anaesthesiology and Emergency Medicine trainees and nurses through training in a simulated multidisciplinary environment. Methods The two-day bootcamp consisted of lectures, equipment demonstration, workshops, and high-fidelity simulated scenarios. A pre- and post-course MCQ test was used for assessment of knowledge acquisition. Pre and post confidence scores were used to evaluate procedural skill confidence level. A 5-point Likert scale was used to evaluate qualitative feedback from participants. Results Seven anaesthesiology trainees, two anaesthetic nurses, six emergency medicine trainees and three emergency medicine nurses were enrolled. There was a statistically significant increase (p-value<0.01) in post-MCQ scores, portraying significant knowledge acquisition. The total procedural confidence scores increased from 375 (±9.15) to 550 (±8.43), (p < 0.01). All participants agreed that the stated educational objectives were met and relevant to their clinical practice, and strongly commended team training exercises. Conclusion Multidisciplinary simulation-based training improves team performance as well as transfer of knowledge across two or more disciplines. Overlapped training between Anaesthesiology and Emergency Medicine created an opportunity for sharing of educational resources in the current time-based speciality training system.


Asunto(s)
Anestesiología , Medicina de Emergencia , Entrenamiento Simulado , Competencia Clínica , Curriculum , Humanos
2.
Mol Psychiatry ; 25(7): 1382-1405, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31222184

RESUMEN

A decrease in adult hippocampal neurogenesis has been linked to age-related cognitive impairment. However, the mechanisms involved in this age-related reduction remain elusive. Glucocorticoid hormones (GC) are important regulators of neural stem/precursor cells (NSPC) proliferation. GC are released from the adrenal glands in ultradian secretory pulses that generate characteristic circadian oscillations. Here, we investigated the hypothesis that GC oscillations prevent NSPC activation and preserve a quiescent NSPC pool in the aging hippocampus. We found that hippocampal NSPC populations lacking expression of the glucocorticoid receptor (GR) decayed exponentially with age, while GR-positive populations decayed linearly and predominated in the hippocampus from middle age onwards. Importantly, GC oscillations controlled NSPC activation and GR knockdown reactivated NSPC proliferation in aged mice. When modeled in primary hippocampal NSPC cultures, GC oscillations control cell cycle progression and induce specific genome-wide DNA methylation profiles. GC oscillations induced lasting changes in the methylation state of a group of gene promoters associated with cell cycle regulation and the canonical Wnt signaling pathway. Finally, in a mouse model of accelerated aging, we show that disruption of GC oscillations induces lasting changes in dendritic complexity, spine numbers and morphology of newborn granule neurons. Together, these results indicate that GC oscillations preserve a population of GR-expressing NSPC during aging, preventing their activation possibly by epigenetic programming through methylation of specific gene promoters. Our observations suggest a novel mechanism mediated by GC that controls NSPC proliferation and preserves a dormant NSPC pool, possibly contributing to a neuroplasticity reserve in the aging brain.


Asunto(s)
Envejecimiento/metabolismo , Encéfalo/metabolismo , Ritmo Circadiano , Glucocorticoides/metabolismo , Hipocampo/citología , Células-Madre Neurales/metabolismo , Animales , Encéfalo/citología , Proliferación Celular , Masculino , Ratones , Neurogénesis , Receptores de Glucocorticoides/metabolismo
3.
BMC Public Health ; 19(1): 1099, 2019 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-31409324

RESUMEN

BACKGROUND: Sedentary behaviour is any waking behaviour characterised by an energy expenditure of ≤1.5 metabolic equivalent of task while in a sitting or reclining posture. Prolonged bouts of sedentary behaviour have been associated with negative health outcomes in all age groups. We examined qualitative research investigating perceptions and experiences of sedentary behaviour and of participation in non-workplace interventions designed to reduce sedentary behaviour in adult populations. METHOD: A systematic search of seven databases (MEDLINE, AMED, Cochrane, PsychINFO, SPORTDiscus, CINAHL and Web of Science) was conducted in September 2017. Studies were assessed for methodological quality and a thematic synthesis was conducted. Prospero database ID: CRD42017083436. RESULTS: Thirty individual studies capturing the experiences of 918 individuals were included. Eleven studies examined experiences and/or perceptions of sedentary behaviour in older adults (typically ≥60 years); ten studies focused on sedentary behaviour in people experiencing a clinical condition, four explored influences on sedentary behaviour in adults living in socio-economically disadvantaged communities, two examined university students' experiences of sedentary behaviour, two on those of working-age adults, and one focused on cultural influences on sedentary behaviour. Three analytical themes were identified: 1) the impact of different life stages on sedentary behaviour 2) lifestyle factors influencing sedentary behaviour and 3) barriers and facilitators to changing sedentary behaviour. CONCLUSIONS: Sedentary behaviour is multifaceted and influenced by a complex interaction between individual, environmental and socio-cultural factors. Micro and macro pressures are experienced at different life stages and in the context of illness; these shape individuals' beliefs and behaviour related to sedentariness. Knowledge of sedentary behaviour and the associated health consequences appears limited in adult populations, therefore there is a need for provision of accessible information about ways in which sedentary behaviour reduction can be integrated in people's daily lives. Interventions targeting a reduction in sedentary behaviour need to consider the multiple influences on sedentariness when designing and implementing interventions.


Asunto(s)
Promoción de la Salud/estadística & datos numéricos , Conducta Sedentaria , Adulto , Humanos , Investigación Cualitativa
4.
J Microsc ; 266(2): 166-177, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28257147

RESUMEN

The new high-sensitive and high-resolution technique, Re-scan Confocal Microscopy (RCM), is based on a standard confocal microscope extended with a re-scan detection unit. The re-scan unit includes a pair of re-scanning mirrors that project the emission light onto a camera in a scanning manner. The signal-to-noise ratio of Re-scan Confocal Microscopy is improved by a factor of 4 compared to standard confocal microscopy and the lateral resolution of Re-scan Confocal Microscopy is 170 nm (compared to 240 nm for diffraction limited resolution, 488 nm excitation, 1.49 NA). Apart from improved sensitivity and resolution, the optical setup of Re-scan Confocal Microscopy is flexible in its configuration in terms of control of the mirrors, lasers and filters. Because of this flexibility, the Re-scan Confocal Microscopy can be configured to address specific biological applications. In this paper, we explore a number of possible configurations of Re-scan Confocal Microscopy for specific biomedical applications such as multicolour, FRET, ratio-metric (e.g. pH and intracellular Ca2+ measurements) and FRAP imaging.


Asunto(s)
Técnicas Citológicas/instrumentación , Técnicas Citológicas/métodos , Microscopía Confocal/instrumentación , Microscopía Confocal/métodos , Animales , Línea Celular , Humanos
5.
Mol Psychiatry ; 18(9): 993-1005, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22925833

RESUMEN

Glucocorticoids (GCs) secreted after stress reduce adult hippocampal neurogenesis, a process that has been implicated in cognitive aspects of psychopathology, amongst others. Yet, the exact role of the GC receptor (GR), a key mediator of GC action, in regulating adult neurogenesis is largely unknown. Here, we show that GR knockdown, selectively in newborn cells of the hippocampal neurogenic niche, accelerates their neuronal differentiation and migration. Strikingly, GR knockdown induced ectopic positioning of a subset of the new granule cells, altered their dendritic complexity and increased their number of mature dendritic spines and mossy fiber boutons. Consistent with the increase in synaptic contacts, cells with GR knockdown exhibit increased basal excitability parallel to impaired contextual freezing during fear conditioning. Together, our data demonstrate a key role for the GR in newborn hippocampal cells in mediating their synaptic connectivity and structural as well as functional integration into mature hippocampal circuits involved in fear memory consolidation.


Asunto(s)
Hipocampo/citología , Motivación/genética , Neurogénesis/genética , Neuronas/fisiología , Receptores de Glucocorticoides/deficiencia , Animales , Movimiento Celular/genética , Condicionamiento Clásico/fisiología , Corticosterona/metabolismo , Dendritas/metabolismo , Dendritas/ultraestructura , Espinas Dendríticas/metabolismo , Espinas Dendríticas/ultraestructura , Miedo , Vectores Genéticos/fisiología , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Técnicas In Vitro , Trastornos de la Memoria/genética , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Proteínas del Tejido Nervioso/metabolismo , Neuronas/ultraestructura , Terminales Presinápticos/metabolismo , ARN Interferente Pequeño/metabolismo , Radioinmunoensayo
6.
Transl Psychiatry ; 14(1): 170, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38555299

RESUMEN

Chronic stress is a major risk factor for neuropsychiatric conditions such as depression. Adult hippocampal neurogenesis (AHN) has emerged as a promising target to counteract stress-related disorders given the ability of newborn neurons to facilitate endogenous plasticity. Recent data sheds light on the interaction between cannabinoids and neurotrophic factors underlying the regulation of AHN, with important effects on cognitive plasticity and emotional flexibility. Since physical exercise (PE) is known to enhance neurotrophic factor levels, we hypothesised that PE could engage with cannabinoids to influence AHN and that this would result in beneficial effects under stressful conditions. We therefore investigated the actions of modulating cannabinoid type 2 receptors (CB2R), which are devoid of psychotropic effects, in combination with PE in chronically stressed animals. We found that CB2R inhibition, but not CB2R activation, in combination with PE significantly ameliorated stress-evoked emotional changes and cognitive deficits. Importantly, this combined strategy critically shaped stress-induced changes in AHN dynamics, leading to a significant increase in the rates of cell proliferation and differentiation of newborn neurons, overall reduction in neuroinflammation, and increased hippocampal levels of BDNF. Together, these results show that CB2Rs are crucial regulators of the beneficial effects of PE in countering the effects of chronic stress. Our work emphasises the importance of understanding the mechanisms behind the actions of cannabinoids and PE and provides a framework for future therapeutic strategies to treat stress-related disorders that capitalise on lifestyle interventions complemented with endocannabinoid pharmacomodulation.


Asunto(s)
Cannabinoides , Animales , Cannabinoides/farmacología , Receptores de Cannabinoides , Ejercicio Físico , Hipocampo , Neurogénesis/fisiología , Antidepresivos/farmacología
7.
Nat Commun ; 15(1): 5222, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890340

RESUMEN

Traumatic brain injury (TBI) can result in long-lasting changes in hippocampal function. The changes induced by TBI on the hippocampus contribute to cognitive deficits. The adult hippocampus harbors neural stem cells (NSCs) that generate neurons (neurogenesis), and astrocytes (astrogliogenesis). While deregulation of hippocampal NSCs and neurogenesis have been observed after TBI, it is not known how TBI may affect hippocampal astrogliogenesis. Using a controlled cortical impact model of TBI in male mice, single cell RNA sequencing and spatial transcriptomics, we assessed how TBI affected hippocampal NSCs and the neuronal and astroglial lineages derived from them. We observe an increase in NSC-derived neuronal cells and a concomitant decrease in NSC-derived astrocytic cells, together with changes in gene expression and cell dysplasia within the dentate gyrus. Here, we show that TBI modifies NSC fate to promote neurogenesis at the cost of astrogliogenesis and identify specific cell populations as possible targets to counteract TBI-induced cellular changes in the adult hippocampus.


Asunto(s)
Astrocitos , Lesiones Traumáticas del Encéfalo , Hipocampo , Células-Madre Neurales , Neurogénesis , Animales , Masculino , Lesiones Traumáticas del Encéfalo/patología , Lesiones Traumáticas del Encéfalo/fisiopatología , Hipocampo/patología , Hipocampo/citología , Astrocitos/metabolismo , Ratones , Células-Madre Neurales/metabolismo , Células-Madre Neurales/citología , Neuronas/metabolismo , Ratones Endogámicos C57BL , Giro Dentado/patología , Modelos Animales de Enfermedad , Diferenciación Celular , Transcriptoma
8.
West Afr J Med ; 30(4): 239-44, 2011.
Artículo en Inglés, Francés | MEDLINE | ID: mdl-22669826

RESUMEN

BACKGROUND: Some dermatoses worsen during pregnancy, some improve, yet others have unpredictable course. OBJECTIVE: To conduct evidence-based search, and review of current management of specific dermatoses of pregnancy. METHODS: Comprehensive literature search was conducted, with Medline and Cochrane Database regarding skin diseases in pregnancy from 1990- 2005. International pharmaceutical abstracts science search (1997- 2003) was used for search references found in the articles. All articles selected for inclusion in this review were evaluated critically with regards to their impact factor, source, and evidence based contribution on this topic as measured by their citation index and the journals they were published in. This review was limited to specific dermatoses of pregnancy generally and some of the skin disorders modified by pregnancy. RESULTS: Intrahepatic cholestasis of pregnancy should be managed as high risk pregnancies as several investigations have shown foetal complications. Recent randomised trials have demonstrated beneficial effects of ursodeoxycholic acid (UDCA) in intrahepatic cholestasis of pregnancy (ICP). Pruritice ruption of pregnancy is associated with multiple pregnancies. It has variable clinical features and has to be differentiated from pemphigoid gestationis, which is associated with an increased incidence of both prematurity and small for date's babies. Prurigo of pregnancy is extremely itchy with papules appearing on the extensor surfaces of the limbs and trunk. It has no maternal risk. The eruptions in pruritic folliculitis of pregnancy clear spontaneously in the postpartum period, with no associated morbidity either in the mother or baby. CONCLUSION: Some skin diseases like obstetric cholestasis may have adverse foetal outcome, while other disorders like pruritic folliculitis of pregnancy have no significant effect on either the mother or baby.


Asunto(s)
Complicaciones del Embarazo , Enfermedades de la Piel , Colestasis Intrahepática/complicaciones , Femenino , Humanos , Penfigoide Ampolloso/complicaciones , Embarazo , Prevalencia , Factores de Riesgo , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/epidemiología , Enfermedades de la Piel/etiología
9.
Animal ; : 1-8, 2020 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-32172706

RESUMEN

Cellular mitochondrial function has been suggested to contribute to variation in feed efficiency (FE) among animals. The objective of this study was to determine mitochondrial abundance and activities of various mitochondrial respiratory chain complexes (complex I (CI) to complex IV (CIV)) in liver and muscle tissue from beef cattle phenotypically divergent for residual feed intake (RFI), a measure of FE. Individual DM intake (DMI) and growth were measured in purebred Simmental heifers (n = 24) and bulls (n = 28) with an initial mean BW (SD) of 372 kg (39.6) and 387 kg (50.6), respectively. All animals were offered concentrates ad libitum and 3 kg of grass silage daily, and feed intake was recorded for 70 days. Residuals of the regression of DMI on average daily gain (ADG), mid-test BW0.75 and backfat (BF), using all animals, were used to compute individual RFI coefficients. Animals were ranked within sex, by RFI into high (inefficient; top third of the population), medium (middle third of population) and low (efficient; bottom third of the population) terciles. Statistical analysis was carried out using the MIXED procedure of SAS v 9.3. Overall mean ADG (SD) and daily DMI (SD) for heifers were 1.2 (0.4) and 9.1 (0.5) kg, respectively, and for bulls were 1.8 (0.3) and 9.5 (1.02) kg, respectively. Heifers and bulls ranked as high RFI consumed 10% and 15% more (P < 0.05), respectively, than their low RFI counterparts. There was no effect of RFI on mitochondrial abundance in either liver or muscle (P > 0.05). An RFI × sex interaction was apparent for CI activity in muscle. High RFI animals had an increased activity (P < 0.05) of CIV in liver tissue compared to their low RFI counterparts; however, the relevance of that observation is not clear. Our data provide no clear evidence that cellular mitochondrial function within either skeletal muscle or hepatic tissue has an appreciable contributory role to overall variation in FE among beef cattle.

11.
Behav Brain Res ; 372: 112032, 2019 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-31199935

RESUMEN

Adult hippocampal neurogenesis plays a critical role in a wide spectrum of hippocampus-dependent functions. Brain pathologies that involve the hippocampus like epilepsy, stroke, and traumatic brain injury, are commonly associated with cognitive impairments and mood disorders. These insults can affect neural stem cells and the subsequent neurogenic cascade in the hippocampus, resulting in the induction of aberrant neurogenesis, which is thought to compromise hippocampal network function, thereby hampering hippocampus-dependent behavior. We here summarize recent preclinical literature on hippocampal insult-induced changes in neurogenesis and based on that, we propose that normalizing aberrant neurogenesis post-insult may help to prevent or rescue behavioral deficits which could help develop novel therapeutic strategies.


Asunto(s)
Hipocampo/metabolismo , Neurogénesis/fisiología , Neuronas/metabolismo , Animales , Lesiones Traumáticas del Encéfalo/fisiopatología , Trastornos del Conocimiento/fisiopatología , Modelos Animales de Enfermedad , Epilepsia/fisiopatología , Hipocampo/patología , Humanos , Trastornos del Humor/fisiopatología , Células-Madre Neurales/patología , Neuronas/patología , Accidente Cerebrovascular/fisiopatología
12.
Animal ; 12(9): 1815-1826, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29779496

RESUMEN

Improvements in feed efficiency of beef cattle have the potential to increase producer profitability and simultaneously lower the environmental footprint of beef production. Although there are many different approaches to measuring feed efficiency, residual feed intake (RFI) has increasingly become the measure of choice. Defined as the difference between an animal's actual and predicted feed intake (based on weight and growth), RFI is conceptually independent of growth and body size. In addition, other measurable traits related to energy expenditure such as estimates of body composition can be included in the calculation of RFI to also force independence from these traits. Feed efficiency is a multifactorial and complex trait in beef cattle and inter-animal variation stems from the interaction of many biological processes influenced, in turn, by physiological status and management regimen. Thus, the purpose of this review was to summarise and interpret current published knowledge and provide insight into research areas worthy of further investigation. Indeed, where sufficient suitable reports exist, meta-analyses were conducted in order to mitigate ambiguity between studies in particular. We have identified a paucity of information on the contribution of key biological processes, including appetite regulation, post-ruminal nutrient absorption, and cellular energetics and metabolism to the efficiency of feed utilisation in cattle. In addition, insufficient information exists on the relationship between RFI status and productivity-related traits at pasture, a concept critical to the overall lifecycle of beef production systems. Overall, published data on the effect of RFI status on both terminal and maternal traits, coupled with the moderate repeatability and heritability of the trait, suggest that breeding for improved RFI, as part of a multi-trait selection index, is both possible and cumulative, with benefits evident throughout the production cycle. Although the advent of genomic selection, with associated improved prediction accuracy, will expedite the introgression of elite genetics for feed efficiency within beef cattle populations, there are challenges associated with this approach which may, in the long-term, be overcome by increased international collaborative effort but, in the short term, will not obviate the on-going requirement for accurate measurement of the primary phenotype.


Asunto(s)
Alimentación Animal , Bovinos , Carne Roja , Alimentación Animal/normas , Animales , Peso Corporal , Cruzamiento , Ingestión de Alimentos , Metabolismo Energético , Fenotipo
13.
J Meas Phys Behav ; 1(1): 26-31, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30159548

RESUMEN

The Seniors USP study measured sedentary behaviour (activPAL3, 9 day wear) in older adults. The measurement protocol had three key characteristics: enabling 24-hour wear (monitor location, waterproofing); minimising data loss (reducing monitor failure, staff training, communication); and quality assurance (removal by researcher, confidence about wear). Two monitors were not returned; 91% (n=700) of returned monitors had 7 valid days of data. Sources of data loss included monitor failure (n=11), exclusion after quality assurance (n=5), early removal for skin irritation (n=8) or procedural errors (n=10). Objective measurement of physical activity and sedentary behaviour in large studies requires decisional trade-offs between data quantity (collecting representative data) and utility (derived outcomes that reflect actual behaviour).

14.
BMJ Open ; 7(4): e013844, 2017 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-28391233

RESUMEN

OBJECTIVE: Sedentary behaviour (SB) has distinct deleterious health outcomes, yet there is no consensus on best practice for measurement. This study aimed to identify the optimal self-report tool for population surveillance of SB, using a systematic framework. DESIGN: A framework, TAxonomy of Self-reported Sedentary behaviour Tools (TASST), consisting of four domains (type of assessment, recall period, temporal unit and assessment period), was developed based on a systematic inventory of existing tools. The inventory was achieved through a systematic review of studies reporting SB and tracing back to the original description. A systematic review of the accuracy and sensitivity to change of these tools was then mapped against TASST domains. DATA SOURCES: Systematic searches were conducted via EBSCO, reference lists and expert opinion. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: The inventory included tools measuring SB in adults that could be self-completed at one sitting, and excluded tools measuring SB in specific populations or contexts. The systematic review included studies reporting on the accuracy against an objective measure of SB and/or sensitivity to change of a tool in the inventory. RESULTS: The systematic review initially identified 32 distinct tools (141 questions), which were used to develop the TASST framework. Twenty-two studies evaluated accuracy and/or sensitivity to change representing only eight taxa. Assessing SB as a sum of behaviours and using a previous day recall were the most promising features of existing tools. Accuracy was poor for all existing tools, with underestimation and overestimation of SB. There was a lack of evidence about sensitivity to change. CONCLUSIONS: Despite the limited evidence, mapping existing SB tools onto the TASST framework has enabled informed recommendations to be made about the most promising features for a surveillance tool, identified aspects on which future research and development of SB surveillance tools should focus. TRIAL REGISTRATION NUMBER: International prospective register of systematic reviews (PROPSPERO)/CRD42014009851.


Asunto(s)
Promoción de la Salud/clasificación , Salud Pública , Conducta Sedentaria , Terapia Conductista , Benchmarking , Humanos , Vigilancia de la Población , Autoinforme
15.
FEBS Lett ; 508(2): 245-8, 2001 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-11718724

RESUMEN

Histidine decarboxylase (HDC) is the single enzyme responsible for histamine synthesis. HDC-deficient mice (HDC(-/-)) have no histamine in their tissues when kept on a histamine-free diet. Therefore, the HDC(-/-) mice provide a suitable model to investigate the involvement of histamine in the regulation of histamine receptor expression. Gene expression of H1 and H2 histamine receptors was studied in several organs of HDC(-/-) mice and compared to standard (HDC(+/+)) mice. In many tissues, prolonged absence of histamine induced down-regulation of the H2 receptor subtype. The expression of the H1 receptor was less sensitive to histamine deficiency. Exogenous histamine present in the diet abolished the differences observed in H2 receptor expression. These results suggest that the expression of mouse H2 receptor is under the control of histamine in a tissue-specific manner.


Asunto(s)
Cimetidina/análogos & derivados , Regulación hacia Abajo , Histamina/metabolismo , Histidina Descarboxilasa/deficiencia , Receptores Histamínicos H2/genética , Receptores Histamínicos H2/metabolismo , Animales , Cimetidina/metabolismo , Eliminación de Gen , Perfilación de la Expresión Génica , Histidina Descarboxilasa/genética , Histidina Descarboxilasa/metabolismo , Ratones , Ratones Noqueados , Especificidad de Órganos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
16.
Eur J Cancer ; 34(6): 889-94, 1998 May.
Artículo en Inglés | MEDLINE | ID: mdl-9797703

RESUMEN

The aim of this study was to develop an experimental model for the study of cancer associated with diabetes. For diabetes induction, Sprague-Dawley rats were given streptozotocin (STZ, 90 mg/kg body weight (BW), by intraperitoneal injection on the second day of life. For mammary tumour induction, rats were injected with 50 mg/kg BW of N-nitroso-N-methylurea (NMU) at 50, 80 and 110 days old. The neoplastic process and the effect of tamoxifen treatment was examined in non-diabetic and diabetic rats. The latency period, NMU-induced tumour incidence and the number of tumours per rat in diabetic rats versus controls were 117 +/- 7 days versus 79 +/- 9 days (P < 0.001); 93% versus 95% (NS); and 5.2 +/- 1.6 versus 2.7 +/- 0.5 (P < 0.02). A more benign histological pattern for tumours in diabetic animals was observed. Mammary tumours in diabetic rats grew more slowly than in controls. Tamoxifen (1 mg/kg/day) treated diabetic rats showed tumour regression in 67% of NMU-induced mammary tumours versus 53% in controls (NS). Our results show that tumour progression seems to be affected by diabetes in this experimental model. We suggest this is the result of changes to insulin-like growth factors and their receptors, which occur in diabetics, and our future research will examine this hypothesis.


Asunto(s)
Anticarcinógenos/uso terapéutico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Neoplasias Mamarias Experimentales/etiología , Tamoxifeno/uso terapéutico , Animales , Antibacterianos , Carcinógenos/toxicidad , División Celular , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/patología , Femenino , Insulina/sangre , Neoplasias Mamarias Experimentales/sangre , Neoplasias Mamarias Experimentales/patología , Metilnitrosourea/toxicidad , Ratas , Estreptozocina
17.
Math Biosci ; 154(2): 103-15, 1998 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-9949650

RESUMEN

This paper describes an efficient method for tracing interactions between a radiation track and molecular targets in a cell or nucleus. The method is efficient because it ensures that a minimal subset of interactions in the track needs to be tested for each score. It is most useful for high-energy particles since the number of interactions and range of the tracks increase with particle energy. In this method, the set of interactions, i.e. the track, is considered as a collection of points in three-dimensional space. This set, together with the eight vertices of a bounding box, is discretised as a collection of tetrahedra, each of which satisfies the Delaunay criterion. Because of the geometric properties of these tetrahedra, only those points which are connected to vertices of tetrahedra through which the target passes need be tested for scoring. An efficient algorithm is used to follow the track through the cell or the nucleus. The main benefit of the method is that it eliminates the need to test those interactions which are geometrically distant from the target. In particular, in cases where there are no interactions in the target, very few interactions need to be checked.


Asunto(s)
Algoritmos , ADN/efectos de la radiación , Modelos Biológicos , Radiación Ionizante
18.
Hepatogastroenterology ; 32(4): 163-7, 1985 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-2865199

RESUMEN

Standard biochemical liver function tests and the clearances of antipyrine and indocyanine green have been compared in psoriatic patients taking methotrexate, psoriatic patients on topical treatment, patient controls and patients with hepatic cirrhosis. The methotrexate-treated patients showed significant elevations in alkaline phosphatase (p less than 0.025) and gamma glutamyl transpeptidase activities (p less than 0.05) compared to topically treated psoriatics and patient controls. The clearance of antipyrine was reduced in the methotrexate treated group but not significantly (p less than 0.1 greater than 0.05). In contradistinction, the weight-adjusted clearance of indocyanine green was significantly impaired in the methotrexate group in comparison with the topically treated psoriatics (p less than 0.01). The clearance of both antipyrine and indocyanine green were markedly lowered in the cirrhotics (p less than 0.001 against all other groups). These data suggest that the serial measurement of alkaline phosphatase and indocyanine green clearance may provide a non-invasive indicator of the development and progression of methotrexate-related liver injury.


Asunto(s)
Cirrosis Hepática/metabolismo , Hígado/metabolismo , Metotrexato/uso terapéutico , Psoriasis/tratamiento farmacológico , Anciano , Fosfatasa Alcalina/metabolismo , Antipirina/metabolismo , Femenino , Humanos , Verde de Indocianina/metabolismo , Cinética , Hígado/efectos de los fármacos , Pruebas de Función Hepática , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Factores de Tiempo , gamma-Glutamiltransferasa/metabolismo
19.
Animal ; 8(6): 949-59, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24679649

RESUMEN

This study examined the relationship of residual feed intake (RFI) with digestion, body composition, carcass traits and visceral organ weights in beef bulls offered a high concentrate diet. Individual dry matter (DM) intake (DMI) and growth were measured in a total of 67 Simmental bulls (mean initial BW 431 kg (s.d.=63.7)) over 3 years. Bulls were offered concentrates (860 g/kg rolled barley, 60 g/kg soya bean meal, 60 g/kg molasses and 20 g/kg minerals per vitamins) ad libitum plus 0.8 kg grass silage DM daily for 105 days pre-slaughter. Ultrasonic muscle and fat depth, body condition score (BCS), muscularity score, skeletal measurements, blood metabolites, rumen fermentation and total tract digestibility (indigestible marker) were determined. After slaughter, carcasses and perinephric and retroperitoneal fat were weighed, carcasses were graded for conformation and fat score and weight of non-carcass organs, liver, heart, kidneys, lungs, gall bladder, spleen, reticulo-rumen full and empty and intestines full, were determined. The residuals of the regression of DMI on average daily gain (ADG), mid-test metabolic BW (BW0.75) and the fixed effect of year, using all animals, were used to compute individual RFI coefficients. Animals were ranked on RFI and assigned to high (inefficient), medium or low groupings. Overall mean ADG and daily DMI were 1.6 kg (s.d.=0.36) and 9.4 kg (s.d.=1.16), respectively. High RFI bulls consumed 7 and 14% more DM than medium and low RFI bulls, respectively (P<0.001). No differences between high and low RFI bulls were detected (P>0.05) for ADG, BW, BCS, skeletal measurements, muscularity scores, ultrasonic measurements, carcass weight, perinephric and retroperitoneal fat weight, kill-out proportion and carcass conformation and fat score. However, regression analysis indicated that a 1 kg DM/day increase in RFI was associated with a decrease in kill-out proportion of 20 g/kg (P<0.05) and a decrease in carcass conformation of 0.74 units (P<0.05). Weight of non-carcass organs did not differ (P>0.05) between RFI groups except for the empty weight of reticulo-rumen, which was 8% lighter (P=0.05) in low RFI compared with high RFI bulls. Regression analysis indicated that a 1 kg DM/day increase in RFI was associated with a 1 kg increase in reticulo-rumen empty weight (P<0.05). Of the visceral organs measured, the reticulo-rumen may be a biologically significant contributory factor to variation in RFI in beef bulls finished on a high concentrate diet.


Asunto(s)
Alimentación Animal , Bovinos/fisiología , Rumen/fisiología , Animales , Composición Corporal , Peso Corporal , Bovinos/sangre , Dieta , Digestión , Fermentación , Masculino , Tamaño de los Órganos , Poaceae , Ensilaje
20.
J Anim Sci ; 92(5): 2170-81, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24663212

RESUMEN

This study examined the relationship of residual feed intake (RFI) and performance with feeding behavior and ruminal fermentation variables in pregnant beef cows offered a grass silage diet. Individual grass silage DMI (dry matter digestibility = 666 g/kg) was recorded on 47 gestating (mean gestation d 166, SD = 26 d) Simmental and Simmental × Holstein-Friesian beef cows for a period of 80 d. Cow BW, BCS, skeletal measurements, ultrasonically scanned muscle and fat depth, visual muscular score, ruminal fermentation, blood metabolites, and feeding behavior were measured. Phenotypic RFI was calculated as actual DMI minus expected DMI. Expected DMI was computed for each animal by regressing DMI on conceptus-adjusted mean BW(0.75) and ADG over an 80-d period. Within breed, cows were ranked by RFI into low (efficient), medium, or high groups. Overall mean (SD) values for DMI (kg/d), RFI, initial conceptus-adjusted BW, and conceptus-adjusted ADG were 8.41 (1.09) kg/d, 0.01 (0.13) kg/d, 646 (70) kg, and -0.07 (0.32) kg, respectively. High-RFI cows ate 25% and 8% more than low- and medium-RFI cows, respectively. Live weight and ADG were not correlated (P > 0.05), and DMI was positively correlated (r = 0.80; P < 0.001) with RFI. The low- and high-RFI groups had similar (P > 0.05) BW, ADG, BCS, visual muscular scores, skeletal measurements, blood metabolites, calf birth weight, and calving difficulty scores. All ultrasonic fat and muscle depth measurements were similar (P > 0.05) for low- and high-RFI cows except for back fat thickness change, where low-RFI cows gained less fat (P < 0.05) than high-RFI cows. Low-RFI cows had greater pH and lower ammonia concentrations in ruminal fluid compared to their high-RFI contemporaries. Low-RFI cows had fewer (P < 0.001) daily feeding events, but these were of longer (P < 0.001) duration (min·feed event(-1)·d(-1)). Despite this, total daily duration of feeding was shorter (P < 0.001; min/d) for low- compared to high-RFI cows. High-RFI cows had more and a longer total duration of nonfeeding events (P < 0.001) than low-RFI cows. This study showed that compared to cows with high RFI, those with low RFI consumed less feed for similar levels of productivity, spent less time engaged in feeding-behavior-related activities, and differed in ruminal fermentation parameters. Feeding events are a significant (17%) contributory factor to variation in RFI in pregnant beef cows offered grass silage.


Asunto(s)
Bovinos/fisiología , Ingestión de Alimentos/fisiología , Conducta Alimentaria/fisiología , Rumen/fisiología , Ensilaje , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta/veterinaria , Femenino , Fermentación , Embarazo
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