65 research outputs found

    Role of glucocorticoids in development and growth of the cardiovascular system in the zebrafish

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    INTRODUCTION: Glucocorticoids (GCs) are synthesised endogenously in mammals by the hypothalamic pituitary adrenal (HPA) axis in response to stress. These hormones can elicit a number of physiological roles by binding to and activating specific receptors (glucocorticoid or mineralocorticoid receptors- GR or MR). GCs are important in tissue development and maturation and commonly used therapeutically. Mammalian animal studies have suggested that over-exposure to GCs, whether pharmacologically or through induction of maternal stress, is associated with increased cardiovascular disease risk in adult life. The underlying mechanisms underpinning this early life programming are poorly understood, however GC exposure during development may have direct and indirect effects on the structure and function of developing tissues and organs which may predispose to disease in later life. Current mammalian models of programming do not lend themselves well to studying organ development during embryogenesis. The zebrafish provides an ideal model to study this phenomenon due to the transparent nature of developing larvae and the availability of transgenic lines expressing fluorescent markers. METHODS: GC pathways were comprehensively characterised during zebrafish embryo development using qRT-PCR and steroid ELISAs. The physiological roles of GCs were assessed during early zebrafish development (first 120 hours post fertilisation (hpf)) assessing stress response, swim activity and global development following various genetic and pharmacological manipulations of the GC system. The impact that GC manipulation had on the cardiovascular system was also investigated. Embryos which had been exposed to GC manipulation during early development were then allowed to develop to adulthood in order to assess the long term impact. The same parameters were investigated in the adult as in the embryo. RESULTS: The key components of the GC system are present and functional in the developing embryo with de novo cortisol biosynthesis evident from 48hpf. A functioning hypothalamic pituitary inter-renal (HPI) axis is demonstrable from 72hpf. Manipulation of specific components of the GC pathway during early embryonic development influences growth-rate, head-trunk angle, chorion hatch-rate and swim behaviour. Manipulation of GCs during embryogenesis resulted in altered body weight, length and girth in adulthood, with altered stress response and swim behaviour also detected. Embryonic heart development was also affected with a reduction in ventricle cardiomyocyte number, cardiac gene abundance (vhmc) and cardiac function during embryogenesis resulting in structural abnormalities such as fewer trabeculae and increased intra-ventricular space. Embryonic GC manipulation also alters the formation and patterning of intersegmental blood vessels by 120hpf. In adulthood this manifests as a reduced angiogenic capacity. CONCLUSION: The zebrafish embryo represents a valid and physiologically relevant model for GC research. Manipulation of GCs during early development results in altered growth, gene abundance and cardiovascular structure. These findings have significant implications for on-going research addressing GC mediated programming and suggest that the zebrafish is a highly suitable model for GC researc

    Can Carbon Sinks be Operational? An RFF Workshop Summary

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    An RFF Workshop brought together experts from around the world to assess the feasibility of using biological sinks to sequester carbon as part of a global atmospheric mitigation effort. The chapters of this proceeding are a result of that effort. Although the intent of the workshop was not to generate a consensus, a number of studies suggest that sinks could be a relatively inexpensive and effective carbon management tool. The chapters cover a variety of aspects and topics related to the monitoring and measurement of carbon in biological systems. They tend to support the view the carbon sequestration using biological systems is technically feasible with relatively good precision and at relatively low cost. Thus carbon sinks can be operational.carbon, sinks, global warming, sequestration, forests

    Prognostic use of a qrs scoring system after hospital discharge for initial acute myocardial infarction in the framingham cohort

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    Myocardial infarct size is an important risk factor for survival after acute myocardial infarction (AMI). The purpose of this study was to determine the prognostic value of myocardial infarct size, as estimated by the Selvester 54-criteria/32-point QRS scoring system, in the Framingham cohort. During the first 30 years of the Framingham Heart Study, a total of 384 participants developed an AMI requiring hospitalization; from this group, 243 patients met the following inclusion criteria: (1) no electrocardiographic changes due to a previous infarction, (2) survival >3 days after discharge from the AMI hospitalization and (3) no electrocardiographic evidence of conduction disturbances or ventricular hypertrophy at the time of their final inhospital electrocardiogram. Univariate and multivariate analyses were performed to test the association of the QRS score, and other associated risk factors, with time until coronary heart diseaserelated death. QRS score was found to be significantly associated with outcome (p = 0.03), as was the systolic blood pressure before infarction (p >0.001). Both univariate and multivariate analysis showed that a history of systolic hypertension was the variable most strongly associated with coronary heart disease-related death. Thus, identification of AMI survivors at high risk for subsequent mortality can be improved by routine blood pressure measurement before AMI, and QRS scoring of the electrocardiogram taken at hospital discharge

    Gluten-Free Products Are Insufficient Source of Folate and Vitamin B12 for Coeliac Patients

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    Bezglutenska prehrana, jedini lijek za oboljele od celijakije, može biti neuravnotežena zbog nedostataka nekih hranjivih tvari. Bezglutenski proizvodi sadrže manju količinu vitamina B, osobito folata, nego slični proizvodi koji sadrže gluten. U zdravih osoba koncentracija homocisteina u plazmi uglavnom ovisi o prehrambenom unosu folata. Povećana vrijednost homocisteina u posljednje se vrijeme povezuje s osteoporozom koja je učestala u osoba s celijakijom. Svrha je ovoga rada utvrditi unos folata i status homocisteina kao metaboličkoga biljega suboptimalnog unosa folata i vitamina B12 u osoba s celijakijom na području Republike Hrvatske. U istraživanju su sudjelovale 52 osobe s celijakijom koje su na bezglutenskoj prehrani (83 % žena, dobi 35±13 godina). Analizom krvi utvrđena je koncentracija homocisteina, folata u serumu i eritrocitima te vitamina B12 u serumu. Kvantitativni je upitnik za procjenu unosa hrane i pića upotrijebljen radi utvrđivanja prehrambenog unosa folata. Prosječni je unos folata bio 206 µg ekvivalenata folata (eng. dietary folate equivalents-DFE), što je kudikamo manje od nacionalne preporuke koja navodi 400 µg DFE odnosno 200 µg folne kiseline. Prosječna vrijednost homocisteina iznosila je 9±2 µmol/L (raspon 5,42-13,90 µmol/L). Povećana vrijednost homocisteina (>10 µmol/L) utvrđena je u 34 % ispitanika. Može se zaključiti da osobe s celijakijom koje se pridržavaju bezglutenske prehrane, a sudjelovale su u ovom istraživanju, imaju mali unos folata i suboptimalan status folata i vitamina B12, vjerojatno zbog unosa folatom siromašnih bezglutenskih proizvoda. Stoga bi obogaćivanje ili dodatak folata u bezglutenske proizvode mogao povoljno utjecati na osobe s celijakijom, te predstavljati izazov prehrambenoj industriji.The gluten-free diet, the only treatment in coeliac disease, can be nutritionally unbalanced and deficient in several nutrients. Gluten-free products contain much lower levels of B vitamins, especially lower folate concentrations than their gluten-containing counterparts. Folate intake is considered as a major dietary determinant of plasma homocysteine concentration in healthy population. Elevated homocysteine is an independent risk factor for cardiovascular disease and has been associated with osteoporotic fractures, which are an increased risk factor in coeliac disease. The aim of this study is to determine dietary folate intake and plasma homocysteine concentration as metabolic markers of suboptimal intake of folate and B12 in Croatian coeliac patients living on a gluten-free diet. Subjects were 52 coeliac patients (83 % female, age 35±13) adhering to a gluten-free diet. Blood samples were analyzed for plasma homocysteine, serum and red blood cell folate and serum B12. Quantitative food frequency questionnaire was used to measure dietary folate intake. Mean dietary folate intake was 206 mg of dietary folate equivalents (DFE), which was far below the national recommendation of 400 µg of DFE (or 200 μg of folic acid). Mean homocysteine was (9±2) μmol/L (range from 5.42 to 13.90 μmol/L), while elevated homocysteine concentrations (>10 μmol/L) were found in 34 % of subjects. In conclusion, coeliac patients adhering to gluten-free diet included in this study showed low folate intake and suboptimal folate and vitamin B12 status, possibly due to low folate content in gluten-free products. Therefore, folate fortification or enrichment of gluten-free products could be beneficial for coeliac patients and it would be of great interest for the food industry
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