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1.
Conserv Physiol ; 11(1): coad004, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36937992

RESUMEN

Recreational fishing has the potential to cause evolutionary change in fish populations; a phenomenon referred to as fisheries-induced evolution. However, detecting and quantifying the magnitude of recreational fisheries selection in the wild is inherently difficult, largely owing to the challenges associated with variation in environmental factors and, in most cases, the absence of pre-selection or baseline data against which comparisons can be made. However, exploration of recreational fisheries selection in wild populations may be possible in systems where fisheries exclusion zones exist. Lakes that possess intra-lake freshwater protected areas (FPAs) can provide investigative opportunities to evaluate the evolutionary impact(s) of differing fisheries management strategies within the same waterbody. To address this possibility, we evaluated how two physiological characteristics (metabolic phenotype and stress responsiveness) as well as a proxy for angling vulnerability, catch-per-unit-effort (CPUE), differed between populations of largemouth bass (Micropterus salmoides) inhabiting long-standing (>70 years active) intra-lake FPAs and adjacent, open access, main-lake areas. Fish from FPA populations had significantly higher aerobic scope (AS) capacity (13%) and CPUE rates compared with fish inhabiting the adjacent main-lake areas. These findings are consistent with theory and empirical evidence linking exploitation with reduced metabolic performance, supporting the hypothesis that recreational fishing may be altering the metabolic phenotype of wild fish populations. Reductions in AS are concerning because they suggest a reduced scope for carrying out essential life-history activities, which may result in fitness level implications. Furthermore, these results highlight the potential for unexploited FPA populations to serve as benchmarks to further investigate the evolutionary consequences of recreational fishing on wild fish and to preserve high-performance phenotypes.

2.
Mol Cell Endocrinol ; 559: 111798, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36243201

RESUMEN

Juvenile rainbow trout (Oncorhynchus mykiss) form dominance hierarchies in which subordinates experience chronic social stress and suppression of food intake. Here we tested the hypothesis that inhibition of food intake reflects increased expression of anorexigenic (appetite inhibiting) signals and decreased expression of orexigenic (appetite stimulating) signals. Trout were confined in pairs for 1 or 4 days, or were confined in pairs for 4 days and then allowed to recover from social interactions for 2 or 4 days; sham fish were handled identically but held alone. Subordinates did not feed during social interaction and had lower food intake than dominants or shams during recovery. In parallel, plasma cortisol (∼18-26x) and liver leptin (lep-a1) transcript abundance (∼10-14x) were elevated in subordinates during social interaction but not recovery, suggesting that these factors contributed to the suppression of food intake. Fish deemed likely to become subordinate based on inhibition of food intake in response to a mild stressor also showed elevated liver lep-a1 transcript abundance (∼5x). The moderate response in these fish coupled with a correlation between liver lep-a1 and cortisol suggest that stress-induced elevation of cortisol increased liver lep-a1 transcript abundance in subordinate trout, contributing to stress-induced suppression of food intake.


Asunto(s)
Oncorhynchus mykiss , Animales , Oncorhynchus mykiss/metabolismo , Hidrocortisona/metabolismo , Apetito , Estrés Psicológico/metabolismo , Hígado/metabolismo
3.
Am J Physiol Regul Integr Comp Physiol ; 323(4): R532-R546, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-35993559

RESUMEN

The sensing of environmental fluctuations and initiation of appropriate physiological responses is crucial to homeostasis. Neuroepithelial cells (NECs) in fishes are putative chemoreceptors, resembling mammalian Type I (glomus) cells, that respond in vitro to changes in O2, CO2, NH3, and pH. Cytosolic carbonic anhydrase (Ca17a) is thought to be involved in CO2 sensing owing to its presence in NECs. Zebrafish (Danio rerio) lacking functional Ca17a were generated via CRISPR/Cas9 technology and used to assess the role of Ca17a in initiating the cardiorespiratory responses to elevated CO2 (hypercapnia). Unfortunately, the homozygous knockout mutants (ca17a-/-) did not survive more than ∼12-14 days postfertilization (dpf), restricting experiments to early developmental stages (4-8 dpf). Changes in ventilation (fV) and cardiac (fH) frequency in response to hypercapnia (1% CO2) in wild-type (ca17a+/+), heterozygous (ca17a+/-) and ca17a-/- fish were used to investigate Ca17a-dependent CO2 sensing and downstream signaling. Wild-type fish exhibited hyperventilation during hypercapnia as indicated by an increase in fV. In the ca17a-/- fish, the hyperventilatory response was attenuated markedly but only at 8 dpf. Hypercapnic tachycardia was observed for all genotypes and did not appear to be influenced by the absence of Ca17a. Interestingly, ca17a-/- fish exhibited a significantly lower resting fH that became more pronounced as the fish aged. The decrease in resting fH was prevented ("rescued") when ca17a-/- embryos were injected with ca17a mRNA. Collectively, the results of this study support a role for Ca17a in promoting hyperventilation during hypercapnia in larval zebrafish and suggest a previously unrecognized role for Ca17a in determining resting heart rate.


Asunto(s)
Anhidrasas Carbónicas , Pez Cebra , Animales , Dióxido de Carbono , Anhidrasas Carbónicas/genética , Branquias/fisiología , Hipercapnia , Hiperventilación , Mamíferos , ARN Mensajero , Pez Cebra/fisiología
4.
Respir Physiol Neurobiol ; 295: 103781, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34481078

RESUMEN

Tracing the evolution of the central rhythm generators associated with ventilation in vertebrates is hindered by a lack of information surrounding key transitions. To begin with, central rhythm generation has been studied in detail in only a few species from four vertebrate groups, lamprey, anuran amphibians, turtles, and mammals (primarily rodents). Secondly, there is a lack of information regarding the transition from water breathing fish to air breathing amniotes (reptiles, birds, and mammals). Specifically, the respiratory rhythm generators of fish appear to be single oscillators capable of generating both phases of the respiratory cycle (expansion and compression) and projecting to motoneurons in cranial nerves innervating bucco-pharyngeal muscles. In the amniotes we find oscillators capable of independently generating separate phases of the respiratory cycle (expiration and inspiration) and projecting to pre-motoneurons in the ventrolateral medulla that in turn project to spinal motoneurons innervating thoracic and abdominal muscles (reptiles, birds, and mammals). Studies of the one group of amphibians that lie at this transition (the anurans), raise intriguing possibilities but, for a variety of reasons that we explore, also raise unanswered questions. In this review we summarize what is known about the rhythm generating circuits associated with breathing that arise from the different rhombomeric segments in each of the different vertebrate classes. Assuming oscillating circuits form in every pair of rhombomeres in every vertebrate during development, we trace what appears to be the evolutionary fate of each and highlight the questions that remain to be answered to properly understand the evolutionary transitions in vertebrate central respiratory rhythm generation.


Asunto(s)
Evolución Biológica , Generadores de Patrones Centrales/fisiología , Respiración , Animales , Vertebrados
5.
AJNR Am J Neuroradiol ; 42(11): 2077-2085, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34620587

RESUMEN

BACKGROUND AND PURPOSE: Neuroimaging has an important role in detecting CNS involvement in children with systemic or CNS isolated hemophagocytic lymphohistiocytosis. We characterized a cohort of pediatric patients with CNS hemophagocytic lymphohistiocytosis focusing on neuroradiologic features and assessed whether distinct MR imaging patterns and genotype correlations can be recognized. MATERIALS AND METHODS: We retrospectively enrolled consecutive pediatric patients diagnosed with hemophagocytic lymphohistiocytosis with CNS involvement treated at 2 pediatric neurology centers between 2010 and 2018. Clinical and MR imaging data were analyzed. RESULTS: Fifty-seven children (40 primary, 70%) with a median age of 36 months (interquartile range, 5.5-80.8 months) were included. One hundred twenty-three MR imaging studies were assessed, and 2 broad imaging patterns were identified. Pattern 1 (significant parenchymal disease, 32/57, 56%) was seen in older children (P = .004) with worse clinical profiles. It had 3 onset subpatterns: multifocal white matter lesions (21/32, 66%), brainstem predominant disease (5, 15%), and cerebellitis (6, 19%). All patients with the brainstem pattern failed to meet the radiologic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. An attenuated imaging phenotype (pattern 2) was seen in 25 patients (44%, 30 studies) and was associated with younger age. CONCLUSIONS: Distinct MR imaging patterns correlating with clinical phenotypes and possible genetic underpinnings were recognized in this cohort of pediatric CNS hemophagocytic lymphohistiocytosis. Disruptive mutations and missense mutations with absent protein expression correlate with a younger onset age. Children with brainstem and cerebellitis patterns and a negative etiologic work-up require directed assessment for CNS hemophagocytic lymphohistiocytosis.


Asunto(s)
Encefalopatías , Linfohistiocitosis Hemofagocítica , Niño , Preescolar , Humanos , Lactante , Linfohistiocitosis Hemofagocítica/diagnóstico por imagen , Linfohistiocitosis Hemofagocítica/genética , Imagen por Resonancia Magnética , Neuroimagen , Estudios Retrospectivos
6.
J Comp Physiol B ; 191(1): 69-84, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33064210

RESUMEN

As a key endocrine axis involved in responding to stress, the hypothalamic-pituitary-interrenal axis plays dual roles in mobilizing energy and maintaining ionic/osmotic balance in fishes. Although these roles have been examined independently in detail in adult fishes, less attention has been paid to the effects of an endogenous stress response during early life, particularly with respect to its potential effects on ionic/osmotic balance. The present study tested the hypothesis that exposure of zebrafish to stress during early development would alter ion balance later in life. Zebrafish at three developmental stages (4, 7, or 15 days post-fertilization, dpf) were subjected to an air-exposure stressor twice a day for 2 days, causing elevation of whole-body cortisol levels. Individuals stressed early in life exhibited decreased survival and growth, altered cortisol responses to a subsequent air-exposure stressor, and increased whole-body Na+ and Ca2+ concentrations. Changes in whole-body Ca2+ concentrations were accompanied by increased ionocyte abundance at 7 dpf and increased rates of Ca2+ uptake from the environment. Differences in whole-body ion concentrations at 15 and 35 dpf were not accompanied by altered ion uptake rates. Across all ages examined, air-exposure stress experienced at 7 dpf was particularly effective at eliciting phenotypic changes, suggesting a critical window at this age for a stress response to influence development. These findings demonstrate that early-life stress in zebrafish triggers developmental plasticity, with age-dependent effects on both the cortisol stress axis and ion balance.


Asunto(s)
Experiencias Adversas de la Infancia , Pez Cebra , Animales , Sistema Endocrino , Humanos , Hidrocortisona , Sodio
7.
Am J Physiol Regul Integr Comp Physiol ; 319(3): R329-R342, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32697653

RESUMEN

Peripheral chemosensitivity in fishes is thought to be mediated by serotonin-enriched neuroepithelial cells (NECs) that are localized to the gills of adults and the integument of larvae. In adult zebrafish (Danio rerio), branchial NECs are presumed to mediate the cardiorespiratory reflexes associated with hypoxia or hypercapnia, whereas in larvae, there is indirect evidence linking cutaneous NECs to hypoxic hyperventilation and hypercapnic tachycardia. No study yet has examined the ventilatory response of larval zebrafish to hypercapnia, and regardless of developmental stage, the signaling pathways involved in CO2 sensing remain unclear. In the mouse, a background potassium channel (TASK-2) contributes to the sensitivity of chemoreceptor cells to CO2. Zebrafish possess two TASK-2 channel paralogs, TASK-2 and TASK-2b, encoded by kcnk5a and kcnk5b, respectively. The present study aimed to determine whether TASK-2 channels are expressed in NECs of larval zebrafish and whether they are involved in CO2 sensing. Using immunohistochemical approaches, TASK-2 protein was observed on the surface of NECs in larvae. Exposure of larvae to hypercapnia caused cardiac and breathing frequencies to increase, and these responses were blunted in fish experiencing TASK-2 and/or TASK-2b knockdown. The results of these experiments suggest that TASK-2 channels are involved in CO2 sensing by NECs and contribute to the initiation of reflex cardiorespiratory responses during exposure of larvae to hypercapnia.


Asunto(s)
Dióxido de Carbono/metabolismo , Hipercapnia/metabolismo , Hipoxia/metabolismo , Células Neuroepiteliales/metabolismo , Canales de Potasio de Dominio Poro en Tándem/metabolismo , Proteínas de Pez Cebra/metabolismo , Animales , Células Quimiorreceptoras/metabolismo , Branquias/metabolismo , Hiperventilación/metabolismo , Células Neuroepiteliales/citología , Oxígeno/metabolismo , Pez Cebra/fisiología
8.
Rheumatology (Oxford) ; 58(7): 1227-1238, 2019 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-30715505

RESUMEN

OBJECTIVES: Monogenic autoinflammatory disorders (AID) and primary immunodeficiencies can present early in life with features that may be mistaken for Behçet's disease (BD). We aimed to retrospectively describe the clinical and laboratory features of 11 paediatric cases referred for suspected BD who turned out to have an alternative, monogenic disease mimicking BD. METHODS: Retrospective, paediatric BD specialist multicentre case series. Next generation sequencing (NGS) or conventional candidate gene screening approaches were utilized, facilitated in some cases by functional assays. RESULTS: Eleven children referred with suspected BD underwent genetic screening because of atypical BD features, and/or presentation before age 5 years. Eight patients (73%) were Caucasian, two were Pakistani and one was Turkish; 55% were female. A positive family history of BD was reported in 54% cases. The median age of disease onset was 0.6 (range 0.2-2.3) years. All had systemic inflammation and oral ulceration; 5/11 had genital ulceration; 3/11 had ocular involvement; and 9/11 had cutaneous manifestations. Nine/11 had known disease-causing genetic mutations in: TNFAIP3 (n = 2), WDR1 (n = 2), NCF1, AP1S3, LYN, MEFV and GLA. The remaining two cases each had novel variants in STAT1 and TNFRSF1A. CONCLUSION: Rare monogenic diseases can mimic BD, particularly when presenting early in life. These observations are now informing a strategy to explore screening for genetic mimics of BD in a UK cohort of children and adults to better understand the proportion of UK BD patients who may in fact have an underlying monogenetic diagnosis.


Asunto(s)
Síndrome de Behçet/diagnóstico , Edad de Inicio , Síndrome de Behçet/genética , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas/métodos , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Mutación , Estudios Retrospectivos
10.
J Fish Biol ; 92(1): 229-236, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29194613

RESUMEN

This study demonstrates that vegetable shortening and cocoa butter are two effective vehicles for intraperitoneal cortisol implants in juvenile teleosts, specifically brown trout Salmo trutta, residing in north temperate freshwater environments. Each vehicle showed a different pattern of cortisol elevation. Vegetable shortening was found to be a more suitable vehicle for long-term cortisol elevation [elevated at 3, 6 and 9 days post treatment (dpt)], while cocoa butter may be better suited for short-term cortisol elevation (only elevated at 3 dpt). Additionally, plasma cortisol levels were higher with cortisol-vegetable shortening than with cortisol-cocoa butter implants. Plasma glucose levels were elevated 6 and 9 dpt for fishes injected with cortisol-vegetable shortening, but did not change relative to controls and shams in cortisol-cocoa butter fishes. In conclusion, vegetable shortening and cocoa butter are both viable techniques for cortisol manipulation in fishes in temperate climates, providing researchers with different options depending on study objectives.


Asunto(s)
Grasas de la Dieta , Hidrocortisona/farmacología , Bombas de Infusión Implantables , Animales , Glucemia , Trucha/sangre , Trucha/metabolismo
11.
Clin Exp Immunol ; 191(2): 198-202, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28976005

RESUMEN

Assessment of thymic output by measurement of naive T cells is carried out routinely in clinical diagnostic laboratories, predominantly using flow cytometry with a suitable panel of antibodies. Naive T cell measurements can also be made using molecular analyses to quantify T cell receptor excision circle (TRECs) levels in sorted cells from peripheral blood. In this study we have compared TRECs levels retrospectively with CD45RA+ CD27+ T cells and also with CD45RA+ CD31+ T cells in 134 patient samples at diagnosis or during follow-up. Both panels provide naive T cell measurements that have a strongly positive correlation with TRECs numbers and are suitable for use with enumerating naive T cell levels in a clinical laboratory.


Asunto(s)
Células Sanguíneas/inmunología , Citometría de Flujo/métodos , Técnicas de Diagnóstico Molecular/métodos , Receptores de Antígenos de Linfocitos T/genética , Subgrupos de Linfocitos T/inmunología , Linfocitos T/inmunología , Estudios de Seguimiento , Humanos , Memoria Inmunológica , Antígenos Comunes de Leucocito/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Estudios Retrospectivos , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismo
12.
Am J Physiol Regul Integr Comp Physiol ; 313(5): R549-R559, 2017 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-28768660

RESUMEN

Rainbow trout (Oncorhynchus mykiss) confined in pairs form social hierarchies in which subordinate fish typically experience fasting and high circulating cortisol levels, resulting in low growth rates. The present study investigated the role of AMP-activated protein kinase (AMPK) in mediating metabolic adjustments associated with social status in rainbow trout. After 3 days of social interaction, liver AMPK activity was significantly higher in subordinate than dominant or sham (fish handled in the same fashion as paired fish but held individually) trout. Elevated liver AMPK activity in subordinate fish likely reflected a significantly higher ratio of phosphorylated AMPK (phospho-AMPK) to total AMPK protein, which was accompanied by significantly higher AMPKα1 relative mRNA abundance. Liver ATP and creatine phosphate concentrations in subordinate fish also were elevated, perhaps as a result of AMPK activity. Sham fish that were fasted for 3 days exhibited effects parallel to those of subordinate fish, suggesting that low food intake was an important trigger of elevated AMPK activity in subordinate fish. Effects on white muscle appeared to be influenced by the physical activity associated with social interaction. Overall, muscle AMPK activity was significantly higher in dominant and subordinate than sham fish. The ratio of phospho-AMPK to total AMPK protein in muscle was highest in subordinate fish, while muscle AMPKα1 relative mRNA abundance was elevated by social dominance. Muscle ATP and creatine phosphate concentrations were high in dominant and subordinate fish at 6 h of interaction and decreased significantly thereafter. Collectively, the findings of the present study support a role for AMPK in mediating liver and white muscle metabolic adjustments associated with social hierarchy formation in rainbow trout.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Metabolismo Energético/fisiología , Hidrocortisona/metabolismo , Relaciones Interpersonales , Oncorhynchus mykiss , Animales , Hígado/metabolismo , Medio Social , Estrés Psicológico/metabolismo
13.
Am J Physiol Regul Integr Comp Physiol ; 313(2): R65-R66, 2017 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-28592460
14.
Gen Comp Endocrinol ; 242: 30-37, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-26718080

RESUMEN

In fishes, maternal exposure to a stressor can influence offspring size and behavior. However, less is known about how maternal stress influences physiological processes in offspring, such as function of the hypothalamic-pituitary-interrenal (HPI) axis. We examined the impact of chronic maternal exposure to an acute chase stressor on the stress response/HPI activity of progeny in wild sockeye salmon (Oncorhynchus nerka). Resting plasma cortisol and brain preoptic area (POA) corticotropin-releasing factor (CRF) mRNA levels did not vary between offspring reared from undisturbed, control females and offspring reared from females exposed to the stressor. However, resting levels of POA glucocorticoid receptors (GR1 and GR2), and head kidney melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR), and cytochrome P450 side chain cleavage enzyme (P450scc) were elevated in offspring reared from stressor-exposed females. Offspring reared from stressor-exposed females had lower plasma cortisol levels 1-h after an acute chase stressor compared to cortisol levels in offspring reared from control females. In offspring reared from chased females, mRNA levels of genes associated with cortisol biosynthesis were reduced in the head kidney post-chase. In offspring reared from control females, mRNA levels in the head kidney did not vary pre- to post-chase. Together, the results of the present study suggest maternal programming of progeny with respect to baseline and stressor-induced mediators of HPI axis activity.


Asunto(s)
Riñón Cefálico/fisiología , Sistema Hipotálamo-Hipofisario/fisiología , Exposición Materna , Salmón/fisiología , Estrés Fisiológico , Animales , Hormona Liberadora de Corticotropina/metabolismo , Sistema Enzimático del Citocromo P-450/clasificación , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Femenino , Regulación de la Expresión Génica/fisiología , Hidrocortisona/sangre , Fosfoproteínas , Receptor de Melanocortina Tipo 2 , Receptores de Glucocorticoides/sangre , Receptores de Glucocorticoides/metabolismo
15.
J Exp Biol ; 219(Pt 8): 1237-48, 2016 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-26896551

RESUMEN

Parental care is an essential life-history component of reproduction for many animal species, and it entails a suite of behavioural and physiological investments to enhance offspring survival. These investments can incur costs to the parent, reducing their energetic and physiological condition, future reproductive capabilities and survival. In fishes, relatively few studies have focused on how these physiological costs are mediated. Male smallmouth bass provide parental care for developing offspring until the brood reaches independence. During this energetically demanding life stage, males cease active foraging as they vigorously defend their offspring. Experimental manipulation of cortisol levels (via implantation) and food (via supplemental feeding) in parental males was used to investigate the fitness consequences of parental care. Improving the nutritional condition of nest-guarding males increased their reproductive success by reducing premature nest abandonment. However, supplemental feeding and cortisol treatment had no effect on parental care behaviours. Cortisol treatment reduced plasma lymphocyte numbers, but increased neutrophil and monocyte concentrations, indicating a shift in immune function. Supplemental feeding improved the physiological condition of parental fish by reducing the accumulation of oxidative injury. Specifically, supplemental feeding reduced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) on DNA nucleotides. Increasing the nutritional condition of parental fish can reduce the physiological cost associated with intensive parental activity and improve overall reproductive success, illustrating the importance of nutritional condition as a key modulator of parental fitness.


Asunto(s)
Lubina/sangre , Lubina/fisiología , Conducta Animal , Conducta Alimentaria , Hidrocortisona/sangre , Estado Nutricional , Estrés Psicológico/fisiopatología , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Lubina/inmunología , Glucemia/metabolismo , Cloruros/sangre , Colesterol/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Lagos , Leucocitos/metabolismo , Magnesio/sangre , Masculino , Ontario , Estrés Oxidativo , Estrés Psicológico/sangre
16.
Br J Cancer ; 114(3): 281-9, 2016 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-26794276

RESUMEN

BACKGROUND: Preclinical studies in endometrial cancer (EC) show that metformin reduces cellular proliferation by PI3K-AKT-mTOR inhibition. We tested the hypothesis that short-term presurgical metformin reduces cellular proliferation in atypical endometrial hyperplasia (AEH) and endometrioid EC, and assessed the feasibility of using phosphorylated PI3K-AKT-mTOR proteins as tissue end points. METHODS: Women with AEH or EC received metformin 850 mg twice a day or no drug in the presurgical window between diagnosis and hysterectomy. Before and after the window, tissue samples were obtained; serum markers of insulin resistance (e.g. homeostasis model of assessment of insulin resistance index) were determined; and anthropometrics measured (e.g. BMI). Cell proliferation (Ki-67) and PI3K-AKT-mTOR phosphostatus were assessed by immunohistochemistry and scored blinded to treatment. RESULTS: Twenty-eight metformin-treated and 12 untreated patients, well matched for age and BMI, completed the study. Metformin treatment (median 20 days, range 7-34) was associated with a 17.2% reduction in tumour Ki-67 (95% CI -27.4, -7.0, P=0.002), in a dose-dependent manner. Tumour PI3K-AKT-mTOR protein phosphostatus varied but the effects were not significant after adjusting for changes in controls. CONCLUSIONS: Short-term metformin was associated with reduced Ki-67 expression in EC. Changes in tumour PI3K-AKT-mTOR protein phosphostatus were seen in both groups. Future studies should address the variability attributed to different sampling techniques including devascularisation of the uterus at hysterectomy.


Asunto(s)
Carcinoma Endometrioide/tratamiento farmacológico , Hiperplasia Endometrial/tratamiento farmacológico , Neoplasias Endometriales/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Histerectomía , Metformina/uso terapéutico , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Péptido C/metabolismo , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/patología , Hiperplasia Endometrial/metabolismo , Hiperplasia Endometrial/patología , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Insulina/metabolismo , Resistencia a la Insulina , Antígeno Ki-67 , Persona de Mediana Edad , Miometrio/patología , Terapia Neoadyuvante , Clasificación del Tumor , Invasividad Neoplásica , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Cuidados Preoperatorios , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Resultado del Tratamiento
17.
Gen Comp Endocrinol ; 204: 195-202, 2014 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-24879931

RESUMEN

Male smallmouth bass (Micropterus dolomieu) provide sole parental care until offspring reach independence, a period of several weeks. During the early parental care period when males are guarding fresh eggs (MG-FE), cortisol responsiveness is attenuated; the response is re-established when males reach the end of the parental care period and are guarding free-swimming fry (MG-FSF). It was hypothesized that attenuation of the cortisol response in male smallmouth bass during early parental care reflected modulation of hypothalamic-pituitary-interrenal (HPI) axis function. Male smallmouth bass were sampled at the beginning (MG-FE) and end of the parental care period (MG-FSF), before and/or 25 min after exposure to a standardized stressor consisting of 3 min of air exposure. Repeated sampling of stressed fish for analysis of plasma cortisol and adrenocorticotropic hormone (ACTH) levels was carried out. Males significantly elevated both plasma cortisol and ACTH levels when guarding free-swimming fry but not during early parental care. Control and stressed fish were terminally sampled for tissue mRNA abundance of preoptic area (POA) and hypothalamic corticotropin-releasing factor (CRF) as well as head kidney melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc). No significant differences in either hypothalamus CRF or head kidney P450scc mRNA abundance were found across parental care stages or in response to stress. However, POA CRF mRNA abundance and interrenal cell MC2R and StAR mRNA abundances failed to increase in response to stress in MG-FE. Thus, the attenuated cortisol response in males guarding fresh eggs may be explained by hypoactive HPI axis function in response to stress. The present is one of few studies, and the first teleost study, to address the mechanisms underlying resistance to stress during the reproductive/parental care period.


Asunto(s)
Lubina/metabolismo , Hormona Liberadora de Corticotropina/sangre , Hidrocortisona/sangre , Sistema Hipotálamo-Hipofisario/metabolismo , Animales , Lubina/crecimiento & desarrollo , Riñón Cefálico/metabolismo , Masculino , Área Preóptica/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor de Melanocortina Tipo 2/genética , Receptor de Melanocortina Tipo 2/metabolismo , Reproducción/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
18.
J Sports Med Phys Fitness ; 54(1): 34-42, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24445543

RESUMEN

A case study into the preparation and physiological responses of competing in the Marathon des Sables (MDS) was conducted by preparing a male competitor for, and monitoring him during, his first attempt at the race. The aims of this case report were to (a) prepare and monitor an ex-Olympic, male rower (S1) during the 2010 race and; (b) compare his physiological responses and race performance to that of the current MDS record holder (S2). S1 (age 37 y; body mass 94.0 kg; height 1.92 m; VO(2peak) 66.0 ml·kg⁻¹·min⁻¹) and S2 (age 37 y; body mass 60.8 kg; height 1.68 m; VO(2peak) 65.9 ml·kg⁻¹·min⁻¹) completed a heat test and S1 subsequently underwent 7 d of heat acclimation prior to the MDS. Gastro-intestinal temperature (Tgi) and heart rate (HR) were measured for S1 during Stages 2, 4, and 5 of the MDS and pre- and post-stage body mass, and urine specific gravity were measured for all stages. Race time and average speeds were collected for S1 and S2. Total race times for S1 and S2 were 25:29:35 and 19:45:08 h:min:s. S1's mean (± 1 SD) percentage HR range (%HRR=[HR-HRmin]/[HRmax-HRmin]x100) was 66.1 ± 13.4% and Tgi ranged between 36.63-39.65°C. The results provide a case report on the physiological responses of a highly aerobically-trained, but novice ultra-endurance runner competing in the MDS, and allow for a comparison with an elite performer.


Asunto(s)
Acondicionamiento Físico Humano , Carrera/fisiología , Adulto , Rendimiento Atlético/fisiología , Temperatura Corporal/fisiología , Frecuencia Cardíaca/fisiología , Calor , Humanos , Masculino , Resistencia Física/fisiología , Aptitud Física/fisiología
19.
Gen Comp Endocrinol ; 196: 8-16, 2014 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-24269985

RESUMEN

In rainbow trout (Oncorhynchus mykiss) of subordinate social status, circulating cortisol concentrations were elevated under resting conditions but the plasma cortisol and glucose responses to an acute stressor (confinement in a net) were attenuated relative to those of dominant trout. An in vitro head kidney preparation, and analysis of the expression of key genes in the stress axis prior to and following confinement in a net were then used to examine the mechanisms underlying suppression of the acute cortisol stress response in trout experiencing chronic social stress. With porcine adrenocorticotropic hormone (ACTH) as the secretagogue, ACTH-stimulated cortisol production was significantly lower for head kidney preparations from subordinate trout than for those from dominant trout. Dominant and subordinate fish did not, however, differ in the relative mRNA abundance of melanocortin-2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) or cytochrome P450 side chain cleavage enzyme (P450scc) within the head kidney, although the relative mRNA abundance of these genes was significantly higher in both dominant and subordinate fish than in sham trout (trout that did not experience social interactions but were otherwise treated identically to the dominant and subordinate fish). The relative mRNA abundance of all three genes was significantly higher in trout exposed to an acute net stressor than under control conditions. Upstream of cortisol production in the stress axis, plasma ACTH concentrations were not affected by social stress, nor was the relative mRNA abundance of the binding protein for corticotropin releasing factor (CRF-BP). The relative mRNA abundance of CRF in the pre-optic area of subordinate fish was significantly higher than that of dominant or sham fish 1h after exposure to the stressor. Collectively, the results indicate that chronic social stress modulates cortisol production at the level of the interrenal cells, resulting in an attenuated cortisol response to an acute stressor.


Asunto(s)
Hormona Adrenocorticotrópica/farmacología , Riñón Cefálico/metabolismo , Hidrocortisona/sangre , Oncorhynchus mykiss/fisiología , Medio Social , Estrés Psicológico/sangre , Animales , Proteínas de Peces/genética , Riñón Cefálico/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Porcinos
20.
Artículo en Inglés | MEDLINE | ID: mdl-23507569

RESUMEN

Rainbow trout (Oncorhynchus mykiss) exposed to an acute heat shock (1 h at 25 °C after raising water temperature from 13 °C to 25 °C over 4 h) mount a significant catecholamine response. The present study investigated the proximate mechanisms underlying catecholamine mobilization. Trout exposed to heat shock in vivo exhibited a significant reduction in arterial O(2) tension, but arterial O(2) concentration was not affected by heat shock, nor was catecholamine release during heat shock prevented by prior and concomitant exposure to hyperoxia (to prevent the fall in arterial O(2) tension). Thus, catecholamine mobilization probably was not triggered by impaired blood O(2) transport. Heat-shocked trout also exhibited an elevation of arterial CO(2) tension coupled with a fall in arterial pH, but these factors are not expected to trigger catecholamine release. The changes in blood O(2) and CO(2) tension occurred despite a significant hyperventilatory response to heat shock. Future studies should investigate whether catecholamine mobilization during heat shock in rainbow trout is triggered by a specific effect of high temperature activating the sympathetic nervous system via a thermosensitive transient receptor potential channel.


Asunto(s)
Catecolaminas/metabolismo , Respuesta al Choque Térmico/fisiología , Calor , Oncorhynchus mykiss/fisiología , Análisis de Varianza , Animales , Arterias/fisiología , Análisis de los Gases de la Sangre , Dióxido de Carbono/sangre , Dióxido de Carbono/metabolismo , Dióxido de Carbono/fisiología , Catecolaminas/sangre , Frío , Concentración de Iones de Hidrógeno , Oncorhynchus mykiss/sangre , Oxígeno/sangre , Oxígeno/metabolismo , Oxígeno/fisiología , Agua
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