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1.
J Therm Biol ; 90: 102592, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32479387

RESUMEN

Kisspeptin, a neuropeptide that activates gonadotropin-releasing hormone (GnRH) neurons, has also been implicated as a regulator of energy balance. Kisspeptin receptor (Kiss1r) knockout (KO) mice display an obese phenotype in adulthood compared to wild-type (WT) controls due to reduced energy expenditure. Additionally, experimental evidence shows that the temperature of typical rodent housing conditions (22 °C) increases the metabolism of mice above basal levels. Female Kiss1r KO mice show reduced core temperature and impaired temperature adaptation to an acute cold challenge, suggesting their temperature homeostasis processes are altered. The present study examined the phenotype of gonadectomised Kiss1r KO mice at both sub-thermoneutral and thermoneutral temperature (22 °C and 30 °C). Our results confirmed the obese phenotype in Kiss1r KO mice at 22 °C, and revealed a sexually dimorphic effect of thermal neutrality on the phenotype. In female KO mice, the obesity observed at 22 °C was attenuated at 30 °C. Plasma leptin levels were higher in KO than WT female mice at 22 °C (P < 0.001) but not at 30 °C. Importantly, the expression of Ucp1 mRNA in brown adipose tissue was lower in KO mice compared to WT mice at 22 °C (P < 0.05), but not different from WT at 30 °C. In male KO mice, a metabolic phenotype was observed at 22 °C and 30 °C. These results provide further evidence for kisspeptin-mediated regulation of adiposity via altered energy expenditure. Moreover, thermoneutral housing alleviated the obese phenotype in female Kiss1r KO mice, compared to WT, indicating the impairment in these mice may relate to an inability to adapt to the chronic cold stress that is experienced at 22 °C.


Asunto(s)
Obesidad/metabolismo , Receptores de Kisspeptina-1/genética , Temperatura , Adiponectina/genética , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Temperatura Corporal , Ingestión de Alimentos , Femenino , Hormonas/sangre , Vivienda para Animales , Hipotálamo/metabolismo , Leptina/sangre , Leptina/genética , Masculino , Ratones Noqueados , Obesidad/sangre , Obesidad/genética , Fenotipo , Caracteres Sexuales , Proteína Desacopladora 1/genética
2.
Reprod Fertil Dev ; 31(11): 1682-1691, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31511141

RESUMEN

Rams respond to acute nutritional supplementation by increasing the frequency of gonadotrophin-releasing hormone (GnRH) pulses. Kisspeptin neurons may mediate the effect of environmental cues on GnRH secretion, so we tested whether the ram response to nutrition involves activation of kisspeptin neurons in the arcuate nucleus (ARC), namely kisspeptin, neurokin B, dynorphin (KNDy) neurons. Rams were given extra lupin grain with their normal ration. Blood was sampled before feeding, and continued until animals were killed for collection of brain tissue at 2 or 11h after supplementation. In supplemented rams, LH pulse frequency increased after feeding, whereas control animals showed no change. Within the caudal ARC, there were more kisspeptin neurons in supplemented rams than in controls and a higher proportion of kisspeptin cells coexpressed Fos, regardless of the time the rams were killed. There were more Fos cells in the mid-ARC and mid-dorsomedial hypothalamus of the supplemented compared with control rams. No effect of nutrition was found on kisspeptin expression in the rostral or mid-ARC, or on GnRH expression in the preoptic area. Kisspeptin neurons in the caudal ARC appear to mediate the increase in GnRH and LH production due to acute nutritional supplementation, supporting the hypothesised role of the KNDy neurons as the pulse generator for GnRH.


Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales , Núcleo Arqueado del Hipotálamo/metabolismo , Kisspeptinas/metabolismo , Hipernutrición/metabolismo , Oveja Doméstica/fisiología , Animales , Metabolismo Energético/fisiología , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Luteinizante/metabolismo , Masculino , Neuronas/metabolismo , Hipernutrición/veterinaria
3.
Biol Lett ; 8(4): 594-7, 2012 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-22496076

RESUMEN

It has been hypothesized that radiation-induced oxidative stress is the mechanism for a wide range of negative impacts on biota living in radioactively contaminated areas around Chernobyl. The present study tests this hypothesis mechanistically, for the first time, by modelling the impacts of radiolysis products within the cell resulting from radiations (low linear energy transfer ß and γ), and dose rates appropriate to current contamination types and densities in the Chernobyl exclusion zone and at Fukushima. At 417 µGy h(-1) (illustrative of the most contaminated areas at Chernobyl), generation of radiolysis products did not significantly impact cellular concentrations of reactive oxygen species, or cellular redox potential. This study does not support the hypothesis that direct oxidizing stress is a mechanism for damage to organisms exposed to chronic radiation at dose rates typical of contaminated environments.


Asunto(s)
Antioxidantes/metabolismo , Hígado/patología , Hígado/efectos de la radiación , Radiación Ionizante , Especies Reactivas de Oxígeno/metabolismo , Animales , Aves/metabolismo , Carotenoides/metabolismo , Accidente Nuclear de Chernóbil , Monitoreo del Ambiente/métodos , Transferencia Lineal de Energía , Hígado/metabolismo , Oxidación-Reducción , Estrés Oxidativo , alfa-Tocoferol/metabolismo
4.
Artículo en Inglés | MEDLINE | ID: mdl-35992190

RESUMEN

The performance of SwissSPAD2 (SS2), a large scale, widefield time-gated CMOS SPAD imager developed for fluorescence lifetime imaging, has recently been described in the context of visible range and fluorescence lifetime imaging microscopy (FLIM) of dyes with lifetimes in the 2.5 - 4 ns range. Here, we explore its capabilities in the NIR regime relevant for small animal imaging, where its sensitivity is lower and typical NIR fluorescent dye lifetimes are much shorter (1 ns or less). We carry out this study in a simple macroscopic imaging setup based on a compact NIR picosecond pulsed laser, an engineered diffuser-based illumination optics, and NIR optimized imaging lens suitable for well-plate or small animal imaging. Because laser repetition rates can vary between models, but the synchronization signal frequency accepted by SS2 is fixed to 20 MHz, we first checked that a simple frequency-division scheme enables data recording for different laser repetition rates. Next, we acquired data using different time gate widths, including gates with duration longer than the laser period, and analyzed the resulting data using both standard nonlinear least-square fit (NLSF) and phasor analysis. We show that the fixed synchronization rate and large gate widths characterizing SS2 (10 ns and over) are not an obstacle to accurately extracting lifetime in the 1 ns range and to distinguishing between close lifetimes. In summary, SS2 and similar very large gated SPAD imagers appear as a versatile alternative to other widefield time-resolved detectors for NIR fluorescence lifetime imaging, including preclinical molecular applications.

5.
J Radiol Prot ; 30(2): 341-73, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20530868

RESUMEN

There is now general acknowledgement that there is a requirement to demonstrate that species other than humans are protected from anthropogenic releases of radioactivity. A number of approaches have been developed for estimating the exposure of wildlife and some of these are being used to conduct regulatory assessments. There is a requirement to compare the outputs of such approaches against available data sets to ensure that they are robust and fit for purpose. In this paper we describe the application of seven approaches for predicting the whole-body ((90)Sr, (137)Cs, (241)Am and Pu isotope) activity concentrations and absorbed dose rates for a range of terrestrial species within the Chernobyl exclusion zone. Predictions are compared against available measurement data, including estimates of external dose rate recorded by thermoluminescent dosimeters attached to rodent species. Potential reasons for differences between predictions between the various approaches and the available data are explored.


Asunto(s)
Accidente Nuclear de Chernóbil , Exposición a Riesgos Ambientales/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Modelos Biológicos , Radiometría/estadística & datos numéricos , Radiometría/veterinaria , Animales , Simulación por Computador , Internacionalidad , Dosis de Radiación , Ucrania/epidemiología
6.
J Radiol Prot ; 30(2): 299-340, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20530860

RESUMEN

Under the International Atomic Energy Agency (IAEA)'s EMRAS (Environmental Modelling for Radiation Safety) programme, activity concentrations of (60)Co, (90)Sr, (137)Cs and (3)H in Perch Lake at Atomic Energy of Canada Limited's Chalk River Laboratories site were predicted, in freshwater primary producers, invertebrates, fishes, herpetofauna and mammals using eleven modelling approaches. Comparison of predicted radionuclide concentrations in the different species types with measured values highlighted a number of areas where additional work and understanding is required to improve the predictions of radionuclide transfer. For some species, the differences could be explained by ecological factors such as trophic level or the influence of stable analogues. Model predictions were relatively poor for mammalian species and herpetofauna compared with measured values, partly due to a lack of relevant data. In addition, concentration ratios are sometimes under-predicted when derived from experiments performed under controlled laboratory conditions representative of conditions in other water bodies.


Asunto(s)
Agua Dulce/análisis , Modelos Biológicos , Plantas , Monitoreo de Radiación/métodos , Radioisótopos/análisis , Radioisótopos/farmacocinética , Animales , Canadá , Simulación por Computador , Internacionalidad , Especificidad de la Especie
7.
Domest Anim Endocrinol ; 73: 106467, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32278499

RESUMEN

Kisspeptin, encoded by Kiss1 gene expressing neurons in the hypothalamus, is a requisite for fertility and now appears critical in the regulation of energy balance. Kisspeptin neurons, particularly those in the arcuate nucleus (ARC), receive information directly and indirectly from a diverse array of brain regions including the bed nucleus of the stria terminalis, amygdala, interpeduncular nucleus, hippocampus, and cortex. On the other hand, kisspeptin neuron projections clearly extend to GnRH neuron cell bodies in rodents, sheep, and primates and beyond to other-non-GnRH-brain areas. Kiss1r, the kisspeptin receptor, is expressed on GnRH neurons and also in additional brain areas and peripheral tissues, indicating a nonreproductive role. Kisspeptin neurons clearly receive signals pertinent to deviations in energy balance but are now recognized as a novel neuroendocrine player in the fine balance of energy intake and expenditure. Mice that have a dysfunctional gene for Kiss1r develop an obese and diabetic phenotype. The mechanism behind this altered metabolic state is still mostly unknown; however, Kiss1r expression in the pancreas and brown adipose tissue is clearly functional and required for normal glucose tolerance and energy expenditure, respectively. Kisspeptin neurons in the ARC also participate in the generation of circadian rhythms, specifically those concerning food intake and metabolism, offering a potential explanation for the obesity in Kiss1r knockout mice. Overall, the discoveries of new mechanistic roles for kisspeptin in both normal and pathophysiologic states of energy balance may lead to further understating of obesity prevalence and novel therapeutic targets and interventions.


Asunto(s)
Hormona Liberadora de Gonadotropina/metabolismo , Kisspeptinas/metabolismo , Receptores de Kisspeptina-1/metabolismo , Animales , Fertilidad , Regulación de la Expresión Génica/fisiología , Kisspeptinas/genética , Mutación , Receptores de Kisspeptina-1/genética
8.
Clin Radiol ; 64(10): 988-93, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19748004

RESUMEN

AIM: To question practising radiologists and radiology trainees at a large international meeting in an attempt to survey individuals about error reporting. MATERIALS AND METHODS: Radiologists attending the 2007 Radiological Society of North America (RSNA) annual meeting were approached to fill in a written questionnaire. Participants were questioned as to their grade, country in which they practised, and subspecialty interest. They were asked whether they kept a personal log of their errors (with an error defined as "a mistake that has management implications for the patient"), how many errors they had made in the preceding 12 months, and the types of errors that had occurred. They were also asked whether their local department held regular discrepancy/errors meetings, how many they had attended in the preceding 12 months, and the perceived atmosphere at these meetings (on a qualitative scale). RESULTS: A total of 301 radiologists with a wide range of specialty interests from 32 countries agreed to take part. One hundred and sixty-six of 301 (55%) of responders were consultant/attending grade. One hundred and thirty-five of 301 (45%) were residents/fellows. Fifty-nine of 301 (20%) of responders kept a personal record of their errors. The number of errors made per person per year ranged from none (2%) to 16 or more (7%). The majority (91%) reported making between one and 15 errors/year. Overcalls (40%), under-calls (25%), and interpretation error (15%) were the predominant error types. One hundred and seventy-eight of 301 (59%) of participants stated that their department held regular errors meeting. One hundred and twenty-seven of 301 (42%) had attended three or more meetings in the preceding year. The majority (55%) who had attended errors meetings described the atmosphere as "educational." Only a small minority (2%) described the atmosphere as "poor" meaning non-educational and/or blameful. CONCLUSION: Despite the undeniable importance of learning from errors, many radiologists and institutions do not engage in such practice. Radiologists and radiology departments must continue to improve the process of recording and addressing errors.


Asunto(s)
Competencia Clínica/estadística & datos numéricos , Errores Diagnósticos/estadística & datos numéricos , Radiología/estadística & datos numéricos , Actitud del Personal de Salud , Educación de Postgrado en Medicina , Humanos , Internado y Residencia , Cuerpo Médico de Hospitales/estadística & datos numéricos , Radiología/educación , Autorrevelación , Encuestas y Cuestionarios
9.
Ecotoxicology ; 18(7): 906-17, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19533343

RESUMEN

The impact of potentially toxic chemicals on wildlife is commonly assessed by comparing the intake of the contaminant with the "no observable effects level" (NOAEL) of intake. It is known, however, that there are considerable uncertainties inherent in this method. This study presents a Monte-Carlo based model to assess the degree of risk posed to birds (dunlin, Calidris alpina) from important estuarine habitats, and to show the limitations of such risk assessments, particularly with regard to data availability. The model was applied to predict the uptake of metals (Hg, Pb) in this shorebird species in Poole Harbour and the Severn Estuary/Bristol Channel, UK, two internationally important shorebird habitats. The results show that in both areas, Pb and Hg concentrations may pose an ecologically relevant toxic risk to wading birds. For Pb, uncertainty in NOAEL values dominates the overall uncertainty. Use of lethal toxicity data (LD50/100) was investigated as a method for assessing sub-lethal impacts from Hg. It was found that this method led to a significant under-estimate of the potential impact of Hg contamination, compared with direct estimation of NOAEL.


Asunto(s)
Charadriiformes/fisiología , Exposición a Riesgos Ambientales/efectos adversos , Monitoreo del Ambiente/métodos , Metales Pesados/toxicidad , Ríos/química , Contaminantes Químicos del Agua/toxicidad , Animales , Cadena Alimentaria , Intoxicación por Plomo/etiología , Intoxicación por Plomo/metabolismo , Metales Pesados/análisis , Metales Pesados/metabolismo , Compuestos de Metilmercurio/análisis , Compuestos de Metilmercurio/metabolismo , Compuestos de Metilmercurio/toxicidad , Modelos Estadísticos , Método de Montecarlo , Nivel sin Efectos Adversos Observados , Reproducción/efectos de los fármacos , Reproducción/fisiología , Medición de Riesgo , Reino Unido , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/metabolismo
10.
Pharm Pharmacol Int J ; 7(3): 133-145, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-34368440

RESUMEN

Medical treatment becomes challenging when complicated injuries arise from secondary reactive metabolic and inflammatory products induced by initial acute ionizing radiation injury (RI) or when combined with subsequent trauma insult(s) (CI). With such detrimental effects on many organs, CI exacerbates the severity of primary injuries and decreases survival. Previously, in a novel study, we reported that ghrelin therapy significantly improved survival after CI. This study aimed to investigate whether brain hemorrhage induced by RI and CI could be inhibited by ghrelin therapy with pegylated G-CSF (i.e., Neulasta®, an FDA-approved drug). B6D2F1 female mice were exposed to 9.5 Gy 60Co-γ-radiation followed by 15% total-skin surface wound. Several endpoints were measured at several days. Brain hemorrhage and platelet depletion were observed in RI and CI mice. Brain hemorrhage severity was significantly higher in CI mice than in RI mice. Ghrelin therapy with pegylated G-CSF reduced the severity in brains of both RI and CI mice. RI and CI did not alter PARP and NF-κB but did significantly reduce PGC-1α and ghrelin receptors; the therapy, however, was able to partially recover ghrelin receptors. RI and CI significantly increased IL-6, KC, Eotaxin, G-CSF, MIP-2, MCP-1, MIP-1α, but significantly decreased IL-2, IL-9, IL-10, MIG, IFN-γ, and PDGF-bb; the therapy inhibited these changes. RI and CI significantly reduced platelet numbers, cellular ATP levels, NRF1/2, and AKT phosphorylation. The therapy significantly mitigated these CI-induced changes and reduced p53-mdm2 mediated caspase-3 activation. Our data are the first to support the view that Ghrelin therapy with pegylated G-CSF is potentially a novel therapy for treating brain hemorrhage after RI and CI.

11.
Endocrinology ; 149(4): 1951-9, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18162520

RESUMEN

There is strong evidence that kisspeptin acts to regulate GnRH secretion, but whether there is also a component of action on the gonadotropes is not clear. Using quantitative RT-PCR, we found that G protein-coupled receptor-54 mRNA is expressed in ovine pituitary cell fractions enriched for gonadotropes as well as in somatotropes and lactotropes. To test whether kisspeptin acts directly on the pituitary gonadotropes, we first examined LH release from primary ovine pituitary cell cultures treated with kisspeptin. We found that kisspeptin treatment increased the concentration of LH in culture media by 80%, compared with control, but only in pituitary cultures from ewes during the follicular phase of the estrous cycle. After this, we determined whether kisspeptin acts on the pituitary gland in vivo. Using GnRH-replaced ovariectomized hypothalamo-pituitary-disconnected ewes, we were not able to achieve any effect of kisspeptin on LH under steady-state conditions or during the period of an estrogen-induced LH surge. Finally, we collected hypophysial portal blood samples from ovariectomized ewes and measured kisspeptin levels. Low but detectable amounts of kisspeptin were found in portal plasma, but levels were similar in ovariectomized ewes that were untreated or given estrogen to elicit an LH surge. Thus, although we observed an effect of kisspeptin on LH release in vitro in some situations, similar findings were not obtained in vivo. Moreover, the low concentrations of kisspeptin in hypophysial portal blood and the lack of any change during the period of an estrogen-induced GnRH/LH surge suggest that action on the pituitary gland is not of major consequence in terms of LH release.


Asunto(s)
Gonadotrofos/efectos de los fármacos , Hormona Luteinizante/metabolismo , Proteínas Supresoras de Tumor/farmacología , Animales , Femenino , Kisspeptinas , Ovulación , Sistema Porta , ARN Mensajero/análisis , Receptores Acoplados a Proteínas G/genética , Ovinos
12.
J Endocrinol ; 237(2): 165-173, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29549187

RESUMEN

Kisspeptin signalling is indispensable for fertility, stimulating gonadotropin-releasing hormone (GnRH) secretion and mediating gonadal steroid feedback on GnRH neurons. Moreover, kisspeptin neurons have been implicated in other non-reproductive neuroendocrine roles. Kisspeptin appears to also regulate growth hormone secretion but much of the data appear contradictory. We sought to clarify a potential role of kisspeptin in growth hormone (GH) regulation by examining the effect of kisspeptin antagonists on GH secretion in ewes under various physiological conditions. Our data show clear and robust increases in GH secretion following lateral ventricle or third ventricle infusion of kisspeptin antagonists p-234 and p-271 in either ovariectomized or anestrous ewes. Central infusion of kisspeptin-10 had no effect on GH secretion. To determine the level at which kisspeptin may influence GH secretion, we examined expression of the cognate kisspeptin receptor, GPR54, in pituitary cells and showed by immunocytochemistry that the majority of somatotropes express GPR54 while expression was largely negative in other pituitary cells. Overall, we have demonstrated that blocking kisspeptin signalling by antagonists stimulates GH secretion in ewes and that this is likely mediated by inhibiting endogenous kisspeptin activation of GPR54 expressed on somatotropes. The findings suggest that endogenous kisspeptin inhibits GH secretion through GPR54 expressed on somatotropes.


Asunto(s)
Hormona del Crecimiento/metabolismo , Antagonistas de Hormonas/farmacología , Kisspeptinas/antagonistas & inhibidores , Animales , Femenino , Hormona del Crecimiento/sangre , Hidrocortisona/metabolismo , Infusiones Intraventriculares , Kisspeptinas/administración & dosificación , Kisspeptinas/farmacología , Hormona Luteinizante/metabolismo , Ovariectomía , Ovario/fisiología , Prolactina/metabolismo , Vías Secretoras/efectos de los fármacos , Ovinos
13.
Endocrinology ; 148(11): 5258-67, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17702853

RESUMEN

We determined whether kisspeptin could be used to manipulate the gonadotropin axis and ovulation in sheep. First, a series of experiments was performed to determine the gonadotropic responses to different modes and doses of kisspeptin administration during the anestrous season using estradiol-treated ovariectomized ewes. We found that: 1) injections (iv) of doses as low as 6 nmol human C-terminal Kiss1 decapeptide elevate plasma LH and FSH levels, 2) murine C-terminal Kiss1 decapeptide was equipotent to human C-terminal Kiss1 decapeptide in terms of the release of LH or FSH, and 3) constant iv infusion of kisspeptin induced a sustained release of LH and FSH over a number of hours. During the breeding season and in progesterone-synchronized cyclical ewes, constant iv infusion of murine C-terminal Kiss1 decapeptide-10 (0.48 mumol/h over 8 h) was administered 30 h after withdrawal of a progesterone priming period, and surge responses in LH occurred within 2 h. Thus, the treatment synchronized preovulatory LH surges, whereas the surges in vehicle-infused controls were later and more widely dispersed. During the anestrous season, we conducted experiments to determine whether kisspeptin treatment could cause ovulation. Infusion (iv) of 12.4 nmol/h kisspeptin for either 30 or 48 h caused ovulation in more than 80% of kisspeptin-treated animals, whereas less than 20% of control animals ovulated. Our results indicate that systemic delivery of kisspeptin provides new strategies for the manipulation of the gonadotropin secretion and can cause ovulation in noncyclical females.


Asunto(s)
Ciclo Estral/efectos de los fármacos , Fase Folicular/efectos de los fármacos , Gonadotropinas/sangre , Oligopéptidos/farmacología , Ovulación/efectos de los fármacos , Ovinos , Animales , Relación Dosis-Respuesta a Droga , Ciclo Estral/sangre , Femenino , Fase Folicular/sangre , Hormona Liberadora de Gonadotropina/líquido cefalorraquídeo , Humanos , Kisspeptinas , Ratones , Ovulación/sangre , Inducción de la Ovulación/métodos , Inducción de la Ovulación/veterinaria , Reproducción/efectos de los fármacos , Estaciones del Año
14.
J Environ Radioact ; 92(2): 63-71, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17126964

RESUMEN

Two different models for predicting the time-dependent mobility of (90)Sr in river systems have been evaluated using post-Chernobyl monitoring data for five large Belarusian rivers (Dnieper, Pripyat, Sozh, Besed and Iput) in the period between 1990 and 2004. The results of model predictions are shown to be in good agreement (within a factor of 5) with the measurements of (90)Sr activity concentration in river waters over a long period of time after the accident. This verifies the relatively good accuracy of the generalised input parameters of these models which were derived primarily from measurements of (90)Sr deposited after atmospheric nuclear weapons testing (NWT). For the cases studied here, the simpler AQUASCOPE model performed just as well as the more complex "Global" model which used GIS-based catchment data as an input. The reasons for this are discussed. Exponential decay equations were also curve-fitted to the data for each river to help assess the uncertainties in the predictive models.


Asunto(s)
Accidente Nuclear de Chernóbil , Modelos Teóricos , Ríos/química , Estroncio/análisis , Valor Predictivo de las Pruebas , República de Belarús , Estroncio/química , Radioisótopos de Estroncio/análisis
15.
J Child Orthop ; 11(6): 414-418, 2017 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-29263752

RESUMEN

PURPOSE: Spine surgeons have increasingly used intraoperative application of topical vancomycin powder (TVP) to prevent surgical site infections (SSIs). The goals of this study were to define the rate of pharmacological adverse reaction to TVP in young patients undergoing posterior spinal surgery and to summarise institutional variation in TVP dosing. METHODS: This retrospective observational study included ten spine centres in the United States and one in Europe. Patients with early onset scoliosis who underwent posterior spine surgery were eligible for inclusion. Age, weight, TVP dose and surgery type were recorded. Surgeries where patient age was > 12 years were excluded. Pharmacological adverse reactions were defined as clinical instances of Red Man Syndrome, rash, nephrotoxicity, proteinuria, hepatotoxicity or ototoxicity. The rate of pharmacological adverse reaction to TVP was calculated. Dosing practices were summarised. RESULTS: Patient age was in the range of seven months to 12 years (median ten years). Of 1398 observations, there was one possible pharmacological adverse reaction. This was in a ten-year-old, 20.4-kg female patient with neuromuscular sco-liosis undergoing growing rod implantation. She was dosed with 1500 mg of TVP and immediately developed a transient rash without systemic symptoms. This abated over minutes without any medical intervention. There were no other adverse reactions in the sample. The population rate of pharmacological adverse reaction was 0.072% (95% confidence interval 0 to 0.4). Significant variability in dosing practices existed between centres. CONCLUSION: Pharmacological adverse reactions to TVP are rare. Future work may establish evidence-based guidelines for TVP dosing based on patient weight and other variables.

16.
Placenta ; 27(2-3): 208-14, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16338466

RESUMEN

This study investigated placental expression of the two main isoforms of the progesterone receptor and the regulation of placental and fetal growth by progesterone over the final third of rat pregnancy, the period of maximal fetal growth. Expression patterns of mRNAs encoding the two major progesterone receptor isoforms (PR-A and PR-B) were measured by real-time RT-PCR in the two morphologically- and functionally-distinct regions of the placenta, the basal and labyrinth zones, at days 16 and 22 of pregnancy (term=day 23). PR-A and PR-B mRNA expression was extremely low in labyrinth zone on days 16 and 22, close to the limits of detection. In contrast, the basal zone exhibited much higher levels of mRNA expression for both PR-A (>10-fold higher than in labyrinth zone) and PR-B (3-fold higher at day 16). To assess the role of progesterone in placental growth, maternal progesterone was reduced from day 16 by ovariectomy with full estradiol replacement and partial progesterone replacement until day 22. Progesterone reduction lowered fetal (10%), whole placental (24%), basal zone (37%) and labyrinth zone (14%) weights at day 22 compared with sham-controls, whereas fetal and placental weights (both zones) were maintained in ovariectomised rats given full estradiol/progesterone replacement. The effects of progesterone withdrawal were not associated with changes in placental expression of either IGF-II or IGFBP-2, both important players in growth factor regulation of placental growth. Importantly, however, IGF-II expression remained elevated in the labyrinth zone but fell markedly in basal zone ( approximately 7-fold) between days 16 and 22 of normal pregnancy, consistent with the growth patterns of these two placental regions over this period.


Asunto(s)
Retardo del Crecimiento Fetal/metabolismo , Placentación , Progesterona/deficiencia , Receptores de Progesterona/metabolismo , Animales , Estradiol/sangre , Femenino , Retardo del Crecimiento Fetal/genética , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , Tamaño de los Órganos , Ovariectomía , Placenta/metabolismo , Placentación/genética , Embarazo , Progesterona/sangre , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Ratas , Receptores de Progesterona/genética , Transcripción Genética
17.
J Neuroendocrinol ; 18(4): 298-303, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16503925

RESUMEN

Leptin is an adipocyte-derived hormone that acts on the hypothalamus to influence feeding, metabolism and reproduction, but the cellular and molecular targets for the action of leptin in the brain have yet to be fully elucidated. Kisspeptins are encoded by the Kiss1 gene, which is expressed in the hypothalamus and has been implicated in the neuroendocrine regulation of gonadotrophin-releasing hormone secretion. We tested the hypothesis that kisspeptin-expressing neurones are targets for leptin. First, we examined whether leptin regulates the expression of Kiss1 by comparing levels of KiSS-1 mRNA in the arcuate nucleus among groups of mice having different circulating levels of leptin: (i) wild-type (WT); (ii) leptin-deficient ob/ob; and (iii) ob/ob mice treated with leptin. All mice were castrated to control for endogenous concentrations of gonadal steroids. KiSS-1 mRNA was significantly reduced in ob/ob compared to WT mice and levels of KiSS-1 mRNA in ob/ob mice treated with leptin were increased, but not fully restored to that found in WT animals. Second, we performed double-label in situ hybridisation for KiSS-1 mRNA and the leptin receptor (Ob-Rb) mRNA and found that almost one-half (approximately 40%) of KiSS-1 mRNA-expressing cells in the arcuate nucleus expressed Ob-Rb mRNA. These results demonstrate that KiSS-1 neurones are direct targets for regulation by leptin and suggest that the reproductive deficits associated with leptin-deficient states may be attributable, in part, to diminished expression of Kiss1.


Asunto(s)
Núcleo Arqueado del Hipotálamo/metabolismo , Hipotálamo/metabolismo , Leptina/fisiología , Neuronas/metabolismo , Proteínas/metabolismo , Animales , Núcleo Arqueado del Hipotálamo/citología , Corticosterona/sangre , Hipotálamo/citología , Kisspeptinas , Leptina/deficiencia , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Proteínas/genética , ARN Mensajero/análisis , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Receptores de Leptina , Distribución Tisular , Triyodotironina/metabolismo
18.
J Neuroendocrinol ; 18(10): 806-9, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16965299

RESUMEN

Kisspeptins are encoded by the gene KiSS-1 and regulate gonadotrophin-releasing hormone (GnRH) and gonadotrophin secretion in various species, including humans. Here, we quantify gene expression of KiSS-1 in the arcuate nucleus (ARC) across the ovine oestrous cycle and demonstrate an increase in the caudal division of the ARC during the preovulatory period. These data strongly suggest that kisspeptins are involved in the generation of the preovulatory GnRH and luteinising hormone surge.


Asunto(s)
Núcleo Arqueado del Hipotálamo/metabolismo , Ciclo Estral/fisiología , Hormona Liberadora de Gonadotropina/fisiología , Hormona Luteinizante/fisiología , Ovulación/fisiología , Animales , Ciclo Estral/metabolismo , Retroalimentación Fisiológica , Femenino , Regulación de la Expresión Génica , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Luteinizante/metabolismo , Ovulación/metabolismo , Progesterona/sangre , Ovinos
19.
Sci Total Environ ; 368(2-3): 502-18, 2006 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-16647745

RESUMEN

This paper evaluates and generalizes state-of-the-art approaches for dynamic modelling of bioaccumulation in fish resulting from short duration liquid discharges of radionuclides ((3)H, (14)C, (60)Co, (134)Cs, (137)Cs, (65)Zn, (89)Sr, (90)Sr, (125)I, (131)I, (241)Am, isotopes of Pu and U) to rivers. Based on a review of model parameter values, predictions are made of maximum and time-integrated activity concentrations in fish. A simplified version of the model was developed and presented as "look-up" graphs. The influence of various environmental parameters on model output was evaluated by sensitivity analysis. Maximum and time-integrated concentrations in fish may be predicted for rivers based on the river volumetric flow rate and water temperature. It is demonstrated that the dynamic model gives lower and more realistic predictions of maximum concentrations in fish than the simpler "Concentration Factor" approach. However, for time-integrated concentration in fish, and estimation of radiation dose to humans from consumption of the fish, the Concentration Factor approach gives similar predictions to the dynamic model.


Asunto(s)
Peces/metabolismo , Modelos Biológicos , Radioisótopos/metabolismo , Contaminantes Radiactivos del Agua/metabolismo , Animales , Cadena Alimentaria
20.
Sci Total Environ ; 368(2-3): 485-501, 2006 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-16678242

RESUMEN

This paper evaluates and generalises state-of-the-art approaches for modelling short duration liquid discharges of radionuclides ((3)H, (14)C, (60)Co, (134)Cs, (137)Cs, (65)Zn, (89)Sr, (90)Sr, (125)I, (131)I, (241)Am, isotopes of Pu and U) to rivers. An advection-dispersion model was parameterised and used to predict the concentrations of radionuclides in the river environment, i.e. in river water, river bed sediment and fish (Part II of this paper covers uptake to fish). The coupled transport and bio-uptake model was used to predict the concentrations of radionuclides in the River Thames, UK, and one of its tributaries as a result of hypothetical short duration discharges. A simplified version of this model was developed and presented as "look-up" graphs. The influence of various environmental parameters on model output was evaluated by sensitivity analysis. Time-integrated water and sediment concentrations and maximum sediment concentrations may be predicted for all rivers on the basis of the river volumetric flow rate only. Maximum concentration in water is, however, also dependent on other river characteristics. For this latter case, generalised modelling approaches are tested for use in situations where detailed hydrological and dispersion data are not available.


Asunto(s)
Modelos Teóricos , Radioisótopos/análisis , Ríos , Contaminantes Radiactivos del Agua/análisis , Sedimentos Geológicos/análisis , Movimientos del Agua
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