WorldWideScience

Sample records for human hypothalamus heart

  1. Sexual differentiation of the human hypothalamus

    NARCIS (Netherlands)

    Swaab, Dick F.; Chung, Wilson C. J.; Kruijver, Frank P. M.; Hofman, Michael A.; Ishunina, Tatjana A.

    2002-01-01

    Functional sex differences in reproduction, gender and sexual orientation and in the incidence of neurological and psychiatric diseases are presumed to be based on structural and functional differences in the hypothalamus and other limbic structures. Factors influencing gender, i.e., the feeling to

  2. Imaging of serotonin transporters with [123I]FP-CIT SPECT in the human hypothalamus

    NARCIS (Netherlands)

    Borgers, A.J.; Alkemade, A.; Van de Giessen, E.M.; Drent, M.L.; Booij, J.; Bisschop, P.H.; Fliers, E.

    2013-01-01

    Background: Serotonergic neurons in the rodent hypothalamus are implicated in key neuroendocrine and metabolic functions, including circadian rhythmicity. However, the assessment of the serotonergic system in the human hypothalamus in vivo is difficult as delineation of the hypothalamus is

  3. Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus

    NARCIS (Netherlands)

    Alkemade, Anneke; Friesema, Edith C.; Unmehopa, Unga A.; Fabriek, Babs O.; Kuiper, George G.; Leonard, Jack L.; Wiersinga, Wilmar M.; Swaab, Dick F.; Visser, Theo J.; Fliers, Eric

    2005-01-01

    Context: Recent findings point to an increasing number of hypothalamic proteins involved in the central regulation of thyroid hormone feedback. The functional neuroanatomy of these proteins in the human hypothalamus is largely unknown at present. Objective: The aim of this study was to report the

  4. The accessory magnocellular neurosecretory system of the rostral human hypothalamus

    DEFF Research Database (Denmark)

    Møller, Morten; Busch, Johannes R.; Jacobsen, Christina

    2018-01-01

    magnocellular neurons were often located along the blood vessels and projections of some of these neurons penetrated the vascular endothelium. The accessory magnocellular cell bodies expressed either neurophysin I or neurophysin II immunoreactivity. Summarizing, the accessory magnocellular system in the human......The morphology and neurophysin expression of the magnocellular accessory neuroendocrine system located in the rostral human hypothalamus is investigated in a series of brains obtained at autopsy. The hypothalami were fixed in formalin and embedded in paraffin, or after cryoprotection, frozen...

  5. Anatomy of the human hypothalamus (chiasmatic and tuberal region).

    Science.gov (United States)

    Braak, H; Braak, E

    1992-01-01

    The hypothalamus sensu stricto consists of the chiasmatic, the tuberal and the mamillary region. The present study is confined to the poorly myelinated chiasmatic and tuberal region. Both regions harbor many nuclear grays with relatively clear-cut boundaries embedded in an ill-defined nerve cell assembly referred to as the hypothalamic gray. Prominent components of the chiasmatic region are the magnocellular neurosecretory complex (supraoptic nucleus, paraventricular nucleus, accessory neurosecretory nucleus), the sexually dimorphic intermediate nucleus, the suprachiasmatic and retrochiasmatic nuclei. The dominating structure of the tuberal region is the complex of the ventromedial, posteromedial and dorsomedial nuclei supplemented by the periventricular and infundibular nuclei. Lateral portions of the tuber cinereum harbor the lateral tuberal nucleus and the tuberomamillary nucleus. The lateral tuberal nucleus exhibits pronounced cell loss in Huntington's chorea and is also severely involved in cases of dementia with argyrophilic grains. The large nerve cells of the tuberomamillary nucleus show particularly severe affection in both Alzheimer's (intraneuronal neurofibrillary changes) and Parkinson's disease (Lewy bodies).

  6. Sex differences in the hypothalamus in the different stages of human life

    NARCIS (Netherlands)

    Swaab, Dick F.; Chung, Wilson C. J.; Kruijver, Frank P. M.; Hofman, Michel A.; Hestiantoro, Andon

    2003-01-01

    Quite a number of structural and functional sex differences have been reported in the human hypothalamus and adjacent structures that may be related to not only reproduction, sexual orientation and gender identity, but also to the often pronounced sex differences in prevalence of psychiatric and

  7. Activation and degeneration during aging: a morphometric study of the human hypothalamus

    NARCIS (Netherlands)

    Zhou, J. N.; Swaab, D. F.

    1999-01-01

    During the course of aging both activation and degenerative changes are found in the human hypothalamus. Degeneration may start around middle-age in some neurotransmitter- or neuromodulator-containing neurons. For instance, a decreased number of vasoactive intestinal polypeptide (VIP) neurons was

  8. Estrogen receptor-alpha distribution in the human hypothalamus in relation to sex and endocrine status

    NARCIS (Netherlands)

    Kruijver, Frank P. M.; Balesar, Rawien; Espila, Ana M.; Unmehopa, Unga A.; Swaab, Dick F.

    2002-01-01

    The present study reports the first systematic rostrocaudal distribution of estrogen receptor-a immunoreactivity (ERalpha-ir) in the human hypothalamus and its adjacent areas in young adults. Postmortem material taken from 10 subjects (five male and five female), between 20 and 39 years of age, was

  9. Human heart by art.

    Science.gov (United States)

    Tamir, Abraham

    2012-11-01

    Heart is of great importance in maintaining the life of the body. Enough to stop working for a few minutes to cause death, and hence the great importance in physiology, medicine, and research. This fact was already emphasized in the Bible in the Book of Proverbs, chapter 4 verse 23: "Keep your heart with all diligence, for out of it is the wellspring of life." Art was able to demonstrate the heart from various aspects; realistically, as done by Leonardo de Vinci who demonstrated the halves of the heart and its blood vessels. Symbolically, as a source of life, the heart was demonstrated by the artist Mrs. Erlondeiel, as a caricature by Salvador Dali, as an open heart by Sawaya, etc. Finally, it should be emphasized that different demonstrations of the human heart by many artworks make this most important organ of our body (that cannot be seen from outside) more familiar and clearer to us. And this is the purpose of this article-to demonstrate the heart through a large number of artworks of different kinds.

  10. Exposure to chronic isolation modulates receptors mRNAs for oxytocin and vasopressin in the hypothalamus and heart.

    Science.gov (United States)

    Pournajafi-Nazarloo, Hossein; Kenkel, William; Mohsenpour, Seyed Ramezan; Sanzenbacher, Lisa; Saadat, Habibollah; Partoo, Leila; Yee, Jason; Azizi, Fereidoun; Carter, C Sue

    2013-05-01

    The goal of our study was to explore the effect of social isolation stress of varying durations on the plasma oxytocin (OT), messenger ribonucleic acid (mRNA) for oxytocin receptor (OTR), plasma arginine vasopressin (AVP) and mRNA for V1a receptor of AVP (V1aR) expression in the hypothalamus and heart of socially monogamous female and male prairie voles (Microtus ochrogaster). Continuous isolation for 4 weeks (chronic isolation) increased plasma OT level in females, but not in males. One hour of isolation every day for 4 weeks (repeated isolation) was followed by a significant increase in plasma AVP level. Chronic isolation, but not repeated isolation, significantly decreased OTR mRNA in the hypothalamus and heart in both sexes. Chronic isolation significantly decreased cardiac V1aR mRNA, but no effect on hypothalamic V1aR mRNA expression. We did not find a gender difference within repeated social isolation groups. The results of the present study reveal that although chronic social isolation can down-regulate gene expression for the OTR in both sexes, the release of the OT peptide was increased after chronic isolation only in females, possibly somewhat protecting females from the negative consequences of isolation. In both sexes repeated, but not chronic, isolation increased plasma AVP, which could be permissive for mobilization and thus adaptive in response to a repeated stressor. The differential effects of isolation on OT and AVP systems may help in understanding mechanisms through social interactions can be protective against emotional and cardiovascular disorders. Published by Elsevier Inc.

  11. Colloid cyst of the third ventricle, hypothalamus, and heart: a dangerous link for sudden death

    Directory of Open Access Journals (Sweden)

    Turillazzi Emanuela

    2012-10-01

    Full Text Available Abstract Colloid cysts are rare congenital, intracranial neoplasms, commonly located in the third ventricle. Colloid cysts are endodermal congenital malformations. The cysts commonly range in size from 1–2 cm in diameter, although large cysts >3 cm in size have been reported. The components of the cyst include an outer fibrous capsule over an inner epithelium. The epithelium is usually a single layer of mucin-producing or ciliated cells. Such cysts contain mucoid and gelatinous material, which is positive for both Periodic acid Schiff (PAS and mucicarmen staining. Although colloid cysts usually represent histopathologically benign neoplasms, they can result in sudden, unexpected and potentially lethal complications. The mechanism(s of death is still a controversial subject and several mechanisms have been postulated to explain the sudden onset of severe symptoms and of fatal rapid deterioration in patients with colloid cysts. In this case, macroscopic and histological findings addressed the diagnosis of colloid cyst of the third ventricle with diffuse myocardial injury (coagulative myocytolysis or contraction band necrosis, CBN and led us to conclude that acute cardiac arrest due to hypothalamus stimulation in the context of colloid cyst of the third ventricle was the cause of death. As the hypothalamic structures which are involved in neuroendocrine and autonomic regulation playing a key role in cardiovascular control are located close to the walls of the third ventricle which is the most frequent anatomical site of colloid cyst, this may suggest that reflex cardiac effects due to the compression of the hypothalamic cardiovascular regulatory centers by the cyst explain the sudden death in patients harboring a colloid cyst when signs of hydrocephalus or brain herniation are lacking. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4915842848034158

  12. Decreased number of oxytocin neurons in the paraventricular nucleus of the human hypothalamus in AIDS

    NARCIS (Netherlands)

    Purba, J. S.; Hofman, M. A.; Portegies, P.; Troost, D.; Swaab, D. F.

    1993-01-01

    The number of immunocytochemically identified vasopressin (AVP) and oxytocin (OXT) neurons was determined morphometrically in the paraventricular nucleus of the hypothalamus of 20 acquired immunodeficiency syndrome (AIDS) patients and 10 controls. The AIDS group consisted of 14 homosexual males (age

  13. Volumetric parcellation methodology of the human hypothalamus in neuroimaging: normative data and sex differences

    NARCIS (Netherlands)

    Makris, Nikos; Swaab, Dick F.; van der Kouwe, Andre; Abbs, Brandon; Boriel, Denise; Handa, Robert J.; Tobet, Stuart; Goldstein, Jill M.

    2013-01-01

    There is increasing evidence regarding the importance of the hypothalamus for understanding sex differences in relation to neurological, psychiatric, endocrine and sleep disorders. Although different in histology, physiology, connections and function, multiple hypothalamic nuclei subserve

  14. Participation of the hypothalamus-hypophysis axis in the sympathetic activation of human obesity.

    Science.gov (United States)

    Grassi, G; Seravalle, G; Dell'Oro, R; Turri, C; Pasqualinotto, L; Colombo, M; Mancia, G

    2001-12-01

    Previous studies have shown that hypothalamic and hypophyseal factors are involved in the acute sympathoexcitation induced by a variety of laboratory stimuli. Whether a chronic condition of sympathetic activation, such as that characterizing human obesity, is also dependent on these factors has never been investigated. In 40 normotensive obese subjects ([mean+/-SEM] age, 39.1+/-0.8 years) we measured blood pressure (Finapres), heart rate (ECG), and postganglionic muscle sympathetic nerve activity (MSNA) (microneurography). In 20 subjects measurements were repeated, according to a double-blind randomized sequence, after a midnight oral dose of dexamethasone (1 mg) (n=10) or placebo (n=10), while in the remaining subjects they were performed again after 1 week of a daily evening oral administration of 1 mg of dexamethasone (n=10) or placebo (n=10). The same protocol was performed in 16 age-matched lean normotensives. In both groups acute dexamethasone administration markedly reduced plasma cortisol (radioimmunoassay), without affecting hemodynamic and neural variables. In contrast to the acute administration, in obese subjects prolonged dexamethasone administration, although not affecting blood pressure and heart rate, significantly reduced both plasma cortisol (from 16.0+/-1.3 to 0.7+/-0.1 microg/dL; P<0.01) and MSNA (from 59.5+/-2.8 to 39.6+/-2.9 bursts per 100 heartbeats; P<0.02; -33.1+/-4.1%). This was not the case in lean subjects, in which the dexamethasone-induced reduction in plasma cortisol was associated with a slight and nonsignificant MSNA decrease. In both lean and obese subjects, placebo administration caused no change in any variable. Thus, prolonged dexamethasone administration exerts in obese subjects marked sympathoinhibitory effects that are not detectable in lean individuals. This suggests that hypothalamic and hypophyseal factors substantially contribute to the sympathoexcitation of obesity.

  15. Galanin neurons in the intermediate nucleus (InM) of the human hypothalamus in relation to sex, age, and gender identity

    NARCIS (Netherlands)

    Garcia-Falgueras, Alicia; Ligtenberg, Lisette; Kruijver, Frank P. M.; Swaab, Dick F.

    2011-01-01

    The intermediate nucleus (InM) in the preoptic area of the human brain, also known as the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the interstitial nucleus of the anterior hypothalamus-1 (INAH-1) is explored here. We investigated its population of galanin-immunoreactive (Gal-Ir)

  16. TUB gene expression in hypothalamus and adipose tissue and its association with obesity in humans

    NARCIS (Netherlands)

    Nies, V J M; Struik, D; Wolfs, M G M; Rensen, S S; Szalowska, E; Unmehopa, U A; Fluiter, K.; van der Meer, T P; Hajmousa, G; Buurman, W A; Greve, J W; Rezaee, F; Shiri-Sverdlov, R; Vonk, R.J.; Swaab, D F; Wolffenbuttel, B H R; Jonker, J W; van Vliet-Ostaptchouk, J V

    2018-01-01

    BACKGROUND/OBJECTIVES: Mutations in the Tubby gene (TUB) cause late-onset obesity and insulin resistance in mice and syndromic obesity in humans. Although TUB gene function has not yet been fully elucidated, studies in rodents indicate that TUB is involved in the hypothalamic pathways regulating

  17. TUB gene expression in hypothalamus and adipose tissue and its association with obesity in humans

    NARCIS (Netherlands)

    Nies, V. J. M.; Struik, D.; Wolfs, M. G. M.; Rensen, S. S.; Szalowska, E.; Unmehopa, U. A.; Fluiter, K.; van der Meer, T. P.; Hajmousa, G.; Buurman, W. A.; Greve, J. W.; Rezaee, F.; Shiri-Sverdlov, R.; Vonk, R. J.; Swaab, D. F.; Wolffenbuttel, B. H. R.; Jonker, J. W.; van Vliet-Ostaptchouk, J. V.

    2017-01-01

    Mutations in the Tubby gene (TUB) cause late-onset obesity and insulin resistance in mice and syndromic obesity in humans. Although TUB gene function has not yet been fully elucidated, studies in rodents indicate that TUB is involved in the hypothalamic pathways regulating food intake and adiposity.

  18. TUB gene expression in hypothalamus and adipose tissue and its association with obesity in humans

    NARCIS (Netherlands)

    Nies, V J M; Struik, D; Wolfs, M G M; Rensen, S S; Szalowska, E; Unmehopa, U A; Fluiter, K; van der Meer, T P; Hajmousa, G; Buurman, W A; Greve, J W; Rezaee, F; Shiri-Sverdlov, R; Vonk, R J; Swaab, D F; Wolffenbuttel, B H R; Jonker, J W; van Vliet-Ostaptchouk, J V

    BACKGROUND/OBJECTIVES: Mutations in the Tubby gene (TUB) cause late-onset obesity and insulin resistance in mice and syndromic obesity in humans. Although TUB gene function has not yet been fully elucidated, studies in rodents indicate that TUB is involved in the hypothalamic pathways regulating

  19. Total excitation of the isolated human heart

    NARCIS (Netherlands)

    Durrer, D.; Dam, R.Th. van; Freud, G.E.; Janse, M.J.; Meijler, F.L.; Arzbaecher, R.C.

    To obtain information conceming the time course and instantaneous distribution of the excitatory process of the normal human healt, studies were made on isolated human hearts from seven individuals who died from various cerebral conditions, but who had no history of cardiac disease. Measurements

  20. Insulin-regulated aminopeptidase immunoreactivity is abundantly present in human hypothalamus and posterior pituitary gland, with reduced expression in paraventricular and suprachiasmatic neurons in chronic schizophrenia.

    Science.gov (United States)

    Bernstein, Hans-Gert; Müller, Susan; Dobrowolny, Hendrik; Wolke, Carmen; Lendeckel, Uwe; Bukowska, Alicja; Keilhoff, Gerburg; Becker, Axel; Trübner, Kurt; Steiner, Johann; Bogerts, Bernhard

    2017-08-01

    The vasopressin- and oxytocin-degrading enzyme insulin-regulated aminopeptidase (IRAP) is expressed in various organs including the brain. However, knowledge about its presence in human hypothalamus is fragmentary. Functionally, for a number of reasons (genetic linkage, hydrolysis of oxytocin and vasopressin, its role as angiotensin IV receptor in learning and memory and others) IRAP might play a role in schizophrenia. We studied the regional and cellular localization of IRAP in normal human brain with special emphasis on the hypothalamus and determined numerical densities of IRAP-expressing cells in the paraventricular, supraoptic and suprachiasmatic nuclei in schizophrenia patients and controls. By using immunohistochemistry and Western blot analysis, IRAP was immunolocalized in postmortem human brains. Cell countings were performed to estimate numbers and numerical densities of IRAP immunoreactive hypothalamic neurons in schizophrenia patients and control cases. Shape, size and regional distribution of IRAP-expressing cells, as well the lack of co-localization with the glia marker glutamine synthetase, show that IRAP is expressed in neurons. IRAP immunoreactive cells were observed in the hippocampal formation, cerebral cortex, thalamus, amygdala and, abundantly, hypothalamus. Double labeling experiments (IRAP and oxytocin/neurophysin 1, IRAP with vasopressin/neurophysin 2) revealed that IRAP is present in oxytocinergic and in vasopressinergic neurons. In schizophrenia patients, the numerical density of IRAP-expressing neurons in the paraventricular and the suprachiasmatic nuclei is significantly reduced, which might be associated with the reduction in neurophysin-containing neurons in these nuclei in schizophrenia. The pathophysiological role of lowered hypothalamic IRAP expression in schizophrenia remains to be established.

  1. Distinct modulatory effects of satiety and sibutramine on brain responses to food images in humans: a double dissociation across hypothalamus, amygdala and ventral striatum

    Science.gov (United States)

    Fletcher, PC; Napolitano, A; Skeggs, A; Miller, SR; Delafont, B; Cambridge, VC; de Wit, S; Nathan, PJ; Brooke, A; O’Rahilly, S; Farooqi, IS; Bullmore, ET

    2012-01-01

    We used fMRI to explore brain responses to food images in overweight humans, examining independently the impact of a pre-scan meal (“satiety”) and the anti-obesity drug sibutramine, a serotonin and noradrenaline reuptake inhibitor. We identified significantly different responses to these manipulations in amygdala, hypothalamus and ventral striatum. Each region was specifically responsive to high calorie compared to low calorie food images. However, the ventral striatal response was attenuated by satiety (but unaffected by sibutramine) while the hypothalamic and amygdala responses were attenuated by drug but unaffected by satiety. Direct assessment of regional interactions confirmed the significance of this double dissociation. We explored the regional responses in greater detail by determining whether they were predictive of eating behaviour and weight change. We observed that across the different regions, the individual-specific magnitude of drug- and satiety-induced modulation was associated with both variables: the sibutramine-induced modulation of the hypothalamic response was correlated with the drug’s impact on both weight and subsequently-measured ad libitum eating. The satiety-induced modulation of striatal response also correlated with subsequent ad lib eating. These results suggest that hypothalamus and amygdala have roles in the control of food intake that are distinct from those of ventral striatum. Furthermore, they support a regionally-specific effect on brain function through which sibutramine exerts its clinical effect. PMID:20980590

  2. Vision and the hypothalamus.

    Science.gov (United States)

    Trachtman, Joseph N

    2010-02-01

    For nearly 2 millennia, signs of hypothalamic-related vision disorders have been noticed as illustrated by paintings and drawings of that time of undiagnosed Horner's syndrome. It was not until the 1800s, however, that specific connections between the hypothalamus and the vision system were discovered. With a fuller elaboration of the autonomic nervous system in the early to mid 1900s, many more pathways were discovered. The more recently discovered retinohypothalamic tracts show the extent and influence of light stimulation on hypothalamic function and bodily processes. The hypothalamus maintains its myriad connections via neural pathways, such as with the pituitary and pineal glands; the chemical messengers of the peptides, cytokines, and neurotransmitters; and the nitric oxide mechanism. As a result of these connections, the hypothalamus has involvement in many degenerative diseases. A complete feedback mechanism between the eye and hypothalamus is established by the retinohypothalamic tracts and the ciliary nerves innervating the anterior pole of the eye and the retina. A discussion of hypothalamic-related vision disorders includes neurologic syndromes, the lacrimal system, the retina, and ocular inflammation. Tables and figures have been used to aid in the explanation of the many connections and chemicals controlled by the hypothalamus. The understanding of the functions of the hypothalamus will allow the clinician to gain better insight into the many pathologies associated between the vision system and the hypothalamus. In the future, it may be possible that some ocular disease treatments will be via direct action on hypothalamic function. Copyright 2010 American Optometric Association. Published by Elsevier Inc. All rights reserved.

  3. Pig models for the human heart failure syndrome

    DEFF Research Database (Denmark)

    Hunter, Ingrid; Terzic, Dijana; Zois, Nora Elisabeth

    2014-01-01

    Human heart failure remains a challenging illness despite advances in the diagnosis and treatment of heart failure patients. There is a need for further improvement of our understanding of the failing myocardium and its molecular deterioration. Porcine models provide an important research tool...... in this respect as molecular changes can be examined in detail, which is simply not feasible in human patients. However, the human heart failure syndrome is based on symptoms and signs, where pig models mostly mimic the myocardial damage, but without decisive data on clinical presentation and, therefore, a heart...... to elucidate the human heart failure syndrome....

  4. ILK induces cardiomyogenesis in the human heart.

    Directory of Open Access Journals (Sweden)

    Alexandra Traister

    Full Text Available Integrin-linked kinase (ILK is a widely conserved serine/threonine kinase that regulates diverse signal transduction pathways implicated in cardiac hypertrophy and contractility. In this study we explored whether experimental overexpression of ILK would up-regulate morphogenesis in the human fetal heart.Primary cultures of human fetal myocardial cells (19-22 weeks gestation yielded scattered aggregates of cardioblasts positive for the early cardiac lineage marker nk × 2.5 and containing nascent sarcomeres. Cardiac cells in colonies uniformly expressed the gap junction protein connexin 43 (C × 43 and displayed a spectrum of differentiation with only a subset of cells exhibiting the late cardiomyogenic marker troponin T (cTnT and evidence of electrical excitability. Adenovirus-mediated overexpression of ILK potently increased the number of new aggregates of primitive cardioblasts (p<0.001. The number of cardioblast colonies was significantly decreased (p<0.05 when ILK expression was knocked down with ILK targeted siRNA. Interestingly, overexpression of the activation resistant ILK mutant (ILK(R211A resulted in much greater increase in the number of new cell aggregates as compared to overexpression of wild-type ILK (ILK(WT. The cardiomyogenic effects of ILK(R211A and ILK(WT were accompanied by concurrent activation of β-catenin (p<0.001 and increase expression of progenitor cell marker islet-1, which was also observed in lysates of transgenic mice with cardiac-specific over-expression of ILK(R211A and ILK(WT. Finally, endogenous ILK expression was shown to increase in concert with those of cardiomyogenic markers during directed cardiomyogenic differentiation in human embryonic stem cells (hESCs.In the human fetal heart ILK activation is instructive to the specification of mesodermal precursor cells towards a cardiomyogenic lineage. Induction of cardiomyogenesis by ILK overexpression bypasses the requirement of proximal PI3K activation for

  5. Distribution of MT1 melatonin receptor immunoreactivity in the human hypothalamus and pituitary gland: colocalization of MT1 with vasopressin, oxytocin, and corticotropin-releasing hormone.

    NARCIS (Netherlands)

    Wu, Y.-H.; Zhou, J.-N.; Balesar, R.; Unmehopa, U.; Bao, A.; Jockers, R.; Heerikhuize, J.; Swaab, D.F.

    2006-01-01

    Melatonin is implicated in numerous physiological processes, including circadian rhythms, stress, and reproduction, many of which are mediated by the hypothalamus and pituitary. The physiological actions of melatonin are mainly mediated by melatonin receptors. We here describe the distribution of

  6. Restoration of heart functions using human embryonic stem cells derived heart muscle cells.

    Science.gov (United States)

    Gepstein, Lior; Kehat, Izhak

    2005-02-01

    Extract: Recent advances in molecular and cellular biology and specifically in the areas of stem cell biology and tissue engineering have paved the way for the development of a new field in biomedicine, regenerative medicine. This exciting approach seeks to develop new biological solutions, using the mobilization of endogenous stem cells or delivery of exogenous cells to replace or modify the function of diseased, absent, or malfunctioning tissue. The adult heart represents an attractive candidate for these emerging technologies, since adult cardiomyocytes have limited regenerative capacity. Thus, any significant heart cell loss or dysfunction, such as occurs during heart attack, is mostly irreversible and may lead to the development of progressive heart failure, one of the leading causes of world-wide morbidity and mortality. Similarly, dysfunction of the specialized electrical conduction system within the heart may result in inefficient rhythm initiation or impulse conduction, leading to significant slowing of the heart rate, usually requiring the implantation of a permanent electronic pacemaker. Replacement of the dysfunctional myocardium (heart muscle) by implantation of external heart muscle cells is emerging as a novel paradigm for restoration of the myocardial electromechanical properties, but has been significantly hampered by the paucity of cell sources for human heart cells and by the relatively limited evidence for functional integration between grafted and host cells. The recently described human embryonic stem cell (hESC) lines may provide a possible solution for the aforementioned cell sourcing problem.

  7. Galanin neurons in the intermediate nucleus (InM) of the human hypothalamus in relation to sex, age, and gender identity.

    Science.gov (United States)

    Garcia-Falgueras, Alicia; Ligtenberg, Lisette; Kruijver, Frank P M; Swaab, Dick F

    2011-10-15

    The intermediate nucleus (InM) in the preoptic area of the human brain, also known as the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the interstitial nucleus of the anterior hypothalamus-1 (INAH-1) is explored here. We investigated its population of galanin-immunoreactive (Gal-Ir) neurons in relation to sex, age, and gender identity in the postmortem brain of 77 subjects. First we compared the InM volume and number of Gal-Ir neurons of 22 males and 22 females in the course of aging. In a second experiment, we compared for the first time the InM volume and the total and Gal-Ir neuron number in 43 subjects with different gender identities: 14 control males (M), 11 control females (F), 10 male-to-female (MtF) transsexual people, and 5 men who were castrated because of prostate cancer (CAS). In the first experiment we found a sex difference in the younger age group ( 45 years. In the second experiment the MtF transsexual group presented an intermediate value for the total InM neuron number and volume that did not seem different in males and females. Because the CAS group did not have total neuron numbers that were different from the intact males, the change in adult circulating testosterone levels does not seem to explain the intermediate values in the MtF group. Organizational and activational hormone effects on the InM are discussed. Copyright © 2011 Wiley-Liss, Inc.

  8. Impaired mitochondrial function in chronically ischemic human heart

    DEFF Research Database (Denmark)

    Stride, Nis Ottesen; Larsen, Steen; Hey-Mogensen, Martin

    2013-01-01

    , and finally to assess myocardial antioxidant levels. Mitochondrial respiration in biopsies from ischemic and nonischemic regions from the left ventricle of the same heart was compared in nine human subjects. Maximal oxidative phosphorylation capacity in fresh muscle fibers was lower in ischemic compared.......05), and the levels of antioxidant protein expression was lower. Diminished mitochondrial respiration capacity and excessive ROS production demonstrate an impaired mitochondrial function in ischemic human heart muscle. No chronic ischemic preconditioning effect was found....

  9. Changes in estrogen receptor-alpha and -beta in the infundibular nucleus of the human hypothalamus are related to the occurrence of Alzheimer's disease neuropathology

    NARCIS (Netherlands)

    Hestiantoro, Andon; Swaab, Dick F.

    2004-01-01

    The expression of estrogen receptor (ER)alpha and -beta in the infundibular nucleus of the hypothalamus was studied immunocytochemically in 28 control subjects and 14 patients with Alzheimer's disease (AD). A shift was found from more nuclear staining of ERalpha in young female controls to more

  10. Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances.

    NARCIS (Netherlands)

    Wang, S.S.; Kamphuis, W.; Huitinga, I.; Zhou, J.N.; Swaab, D.F.

    2008-01-01

    Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors

  11. How Live Performance Moves the Human Heart.

    Directory of Open Access Journals (Sweden)

    Haruka Shoda

    Full Text Available We investigated how the audience member's physiological reactions differ as a function of listening context (i.e., live versus recorded music contexts. Thirty-seven audience members were assigned to one of seven pianists' performances and listened to his/her live performances of six pieces (fast and slow pieces by Bach, Schumann, and Debussy. Approximately 10 weeks after the live performance, each of the audience members returned to the same room and listened to the recorded performances of the same pianists' via speakers. We recorded the audience members' electrocardiograms in listening to the performances in both conditions, and analyzed their heart rates and the spectral features of the heart-rate variability (i.e., HF/TF, LF/HF. Results showed that the audience's heart rate was higher for the faster than the slower piece only in the live condition. As compared with the recorded condition, the audience's sympathovagal balance (LF/HF was less while their vagal nervous system (HF/TF was activated more in the live condition, which appears to suggest that sharing the ongoing musical moments with the pianist reduces the audience's physiological stress. The results are discussed in terms of the audience's superior attention and temporal entrainment to live performance.

  12. Plasma urocortin in human systolic heart failure.

    Science.gov (United States)

    Ng, Leong L; Loke, Ian W; O'Brien, Russell J; Squire, Iain B; Davies, Joan E

    2004-04-01

    Urocortin (UCN), a member of the corticotrophin-releasing factor family, is expressed in heart, brain and gut. UCN has potent cardiostimulatory, cardioprotective, vasodilator and diuretic/natriuretic effects, and cardiac UCN expression is increased in heart failure (HF). In the present study, we investigated plasma levels of UCN in 119 patients with HF and 212 age- and gender-matched controls to clarify its relationship with gender and disease severity. UCN was elevated in HF [normal males, 19.5 (3.9-68.8) pmol/l and HF males, 50.2 (6.9-108.2) pmol/l, P fall in UCN levels with increasing NYHA class was reinforced by a significant correlation between UCN and ejection fraction ( r(s) = 0.45, P < 0.0005) in HF patients. Although receiver operating characteristic (ROC) curves for diagnosis of all HF cases yielded an area under the curve (AUC) of 0.76, ROC AUCs for patients with early HF (NYHA class I and II) were better (0.91). ROC AUCs for logistic models incorporating N-terminal probrain natriuretic peptide (N-BNP) and UCN were better than either peptide alone. In conclusion, plasma UCN is elevated in HF, especially in its early stages. Its decline with increasing HF severity may expedite disease progression due to diminished cardioprotective/anti-inflammatory effects. UCN measurement may also complement N-BNP in the diagnosis of early HF.

  13. FISH CONSUMPTION, METHYLMERCURY, AND HUMAN HEART DISEASE.

    Energy Technology Data Exchange (ETDEWEB)

    LIPFERT, F.W.; SULLIVAN, T.M.

    2005-09-21

    Environmental mercury continues to be of concern to public health advocates, both in the U.S. and abroad, and new research continues to be published. A recent analysis of potential health benefits of reduced mercury emissions has opened a new area of public health concern: adverse effects on the cardiovascular system, which could account for the bulk of the potential economic benefits. The authors were careful to include caveats about the uncertainties of such impacts, but they cited only a fraction of the applicable health effects literature. That literature includes studies of the potentially harmful ingredient (methylmercury, MeHg) in fish, as well as of a beneficial ingredient, omega-3 fatty acids or ''fish oils''. The U.S. Food and Drug Administration (FDA) recently certified that some of these fat compounds that are primarily found in fish ''may be beneficial in reducing coronary heart disease''. This paper briefly summarizes and categorizes the extensive literature on both adverse and beneficial links between fish consumption and cardiovascular health, which are typically based on studies of selected groups of individuals (cohorts). Such studies tend to comprise the ''gold standard'' of epidemiology, but cohorts tend to exhibit a great deal of variability, in part because of the limited numbers of individuals involved and in part because of interactions with other dietary and lifestyle considerations. Note that eating fish will involve exposure to both the beneficial effects of fatty acids and the potentially harmful effects of contaminants like Hg or PCBs, all of which depend on the type of fish but tend to be correlated within a population. As a group, the cohort studies show that eating fish tends to reduce mortality, especially due to heart disease, for consumption rates up to about twice weekly, above which the benefits tend to level off. A Finnish cohort study showed increased mortality risks

  14. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

    International Nuclear Information System (INIS)

    Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L.; Vickers, Alison E.M.

    2014-01-01

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol

  15. Influence of heart failure on nucleolar organization and protein expression in human hearts

    International Nuclear Information System (INIS)

    Roselló-Lletí, Esther; Rivera, Miguel; Cortés, Raquel; Azorín, Inmaculada; Sirera, Rafael; Martínez-Dolz, Luis; Hove, Leif; Cinca, Juan; Lago, Francisca; González-Juanatey, José R.; Salvador, Antonio; Portolés, Manuel

    2012-01-01

    Highlights: ► Heart failure alters nucleolar morphology and organization. ► Nucleolin expression is significant increased in ischemic and dilated cardiomyopathy. ► Ventricular function of heart failure patients was related with nucleolin levels. -- Abstract: We investigate for the first time the influence of heart failure (HF) on nucleolar organization and proteins in patients with ischemic (ICM) or dilated cardiomyopathy (DCM). A total of 71 human hearts from ICM (n = 38) and DCM (n = 27) patients, undergoing heart transplantation and control donors (n = 6), were analysed by western-blotting, RT-PCR and cell biology methods. When we compared protein levels according to HF etiology, nucleolin was increased in both ICM (117%, p < 0.05) and DCM (141%, p < 0.01). Moreover, mRNA expression were also upregulated in ICM (1.46-fold, p < 0.05) and DCM (1.70-fold, p < 0.05. Immunofluorescence studies showed that the highest intensity of nucleolin was into nucleolus (p < 0.0001), and it was increased in pathological hearts (p < 0.0001). Ultrastructure analysis by electron microscopy showed an increase in the nucleus and nucleolus size in ICM (17%, p < 0.05 and 131%, p < 0.001) and DCM (56%, p < 0.01 and 69%, p < 0.01). Nucleolar organization was influenced by HF irrespective of etiology, increasing fibrillar centers (p < 0.001), perinucleolar chromatin (p < 0.01) and dense fibrillar components (p < 0.01). Finally, left ventricular function parameters were related with nucleolin levels in ischemic hearts (p < 0.0001). The present study demonstrates that HF influences on morphology and organization of nucleolar components, revealing changes in the expression and in the levels of nucleolin protein.

  16. Influence of heart failure on nucleolar organization and protein expression in human hearts

    Energy Technology Data Exchange (ETDEWEB)

    Rosello-Lleti, Esther; Rivera, Miguel; Cortes, Raquel [Cardiocirculatory Unit, Research Center, Hospital Universitario La Fe, Valencia (Spain); Azorin, Inmaculada [Experimental Neurology, Research Center, Hospital Universitario La Fe, Valencia (Spain); Sirera, Rafael [Biotechnology Department, Universidad Politecnica, Valencia (Spain); Martinez-Dolz, Luis [Cardiology Unit, Hospital Universitario La Fe, Valencia (Spain); Hove, Leif; Cinca, Juan [Cardiology Unit, Hospital San Pau, Barcelona (Spain); Lago, Francisca; Gonzalez-Juanatey, Jose R. [Cardiology Unit, Institute of Biomedical Research, Hospital Clinicode Santiagode Compostela (Spain); Salvador, Antonio [Experimental Neurology, Research Center, Hospital Universitario La Fe, Valencia (Spain); Portoles, Manuel, E-mail: portoles_man@gva.es [Cell Biology and Pathology Unit, Research Center, Hospital Universitario La Fe, Valencia (Spain)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Heart failure alters nucleolar morphology and organization. Black-Right-Pointing-Pointer Nucleolin expression is significant increased in ischemic and dilated cardiomyopathy. Black-Right-Pointing-Pointer Ventricular function of heart failure patients was related with nucleolin levels. -- Abstract: We investigate for the first time the influence of heart failure (HF) on nucleolar organization and proteins in patients with ischemic (ICM) or dilated cardiomyopathy (DCM). A total of 71 human hearts from ICM (n = 38) and DCM (n = 27) patients, undergoing heart transplantation and control donors (n = 6), were analysed by western-blotting, RT-PCR and cell biology methods. When we compared protein levels according to HF etiology, nucleolin was increased in both ICM (117%, p < 0.05) and DCM (141%, p < 0.01). Moreover, mRNA expression were also upregulated in ICM (1.46-fold, p < 0.05) and DCM (1.70-fold, p < 0.05. Immunofluorescence studies showed that the highest intensity of nucleolin was into nucleolus (p < 0.0001), and it was increased in pathological hearts (p < 0.0001). Ultrastructure analysis by electron microscopy showed an increase in the nucleus and nucleolus size in ICM (17%, p < 0.05 and 131%, p < 0.001) and DCM (56%, p < 0.01 and 69%, p < 0.01). Nucleolar organization was influenced by HF irrespective of etiology, increasing fibrillar centers (p < 0.001), perinucleolar chromatin (p < 0.01) and dense fibrillar components (p < 0.01). Finally, left ventricular function parameters were related with nucleolin levels in ischemic hearts (p < 0.0001). The present study demonstrates that HF influences on morphology and organization of nucleolar components, revealing changes in the expression and in the levels of nucleolin protein.

  17. Heart research advances using database search engines, Human Protein Atlas and the Sydney Heart Bank.

    Science.gov (United States)

    Li, Amy; Estigoy, Colleen; Raftery, Mark; Cameron, Darryl; Odeberg, Jacob; Pontén, Fredrik; Lal, Sean; Dos Remedios, Cristobal G

    2013-10-01

    This Methodological Review is intended as a guide for research students who may have just discovered a human "novel" cardiac protein, but it may also help hard-pressed reviewers of journal submissions on a "novel" protein reported in an animal model of human heart failure. Whether you are an expert or not, you may know little or nothing about this particular protein of interest. In this review we provide a strategic guide on how to proceed. We ask: How do you discover what has been published (even in an abstract or research report) about this protein? Everyone knows how to undertake literature searches using PubMed and Medline but these are usually encyclopaedic, often producing long lists of papers, most of which are either irrelevant or only vaguely relevant to your query. Relatively few will be aware of more advanced search engines such as Google Scholar and even fewer will know about Quertle. Next, we provide a strategy for discovering if your "novel" protein is expressed in the normal, healthy human heart, and if it is, we show you how to investigate its subcellular location. This can usually be achieved by visiting the website "Human Protein Atlas" without doing a single experiment. Finally, we provide a pathway to discovering if your protein of interest changes its expression level with heart failure/disease or with ageing. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  18. Stem cell markers in the heart of the human newborn

    Directory of Open Access Journals (Sweden)

    Armando Faa

    2016-07-01

    Full Text Available The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. Several recent studies now show that the different cell types that characterize the adult human heart arise from a common ancestor. Human cardiac stem cells differentiate into cardiomyocytes, and, in lesser extent, into smooth muscle and endothelial cells. The characterization of human cardiac stem cells (CSCs has important clinical implications. In recent years, CD117 (c-kit has been reported to mark a subtype of stem/progenitor cells in the human heart, with stem cell-like properties, including the ability to self-renewal and clonogenicity multipotentiality. Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  19. Fractionated magnetic-resonance elastography on the human heart

    International Nuclear Information System (INIS)

    Rump, Jens

    2008-01-01

    Imaging techniques, including magnetic resonance imaging, belong to the most important tools in modern medical diagnostics. Another diagnostic aid is palpation, which is suitable for the qualitative characterization of pathological changes in organs near the surface. Magnetic resonance elastography (MRE) is a combination of these techniques. In principle, MRE uses motionsensitive MR-imaging to depict tissue deformation caused by externally induced shear waves. The type of deformation supply useful information about the elasticity of the tissue. Cardiac disorders are among the most common diseases. The goal of this study was to develop a method of applying in-vivo MRE to the human heart. The development of the mechanical stimulus, ultimately resulting in the introduction of an audio speaker as the source of vibration, provided the necessary means to introduce vibrations into inner organs. A crucial factor in applying MRE to the heart is the speed of the recording, which led to the development of ''fractional MRE''. The currently conventional fast heart imaging techniques were used as a starting point. The use of an unbalanced phase preparation gradient in the balanced steady-state imaging technique resulted in an improved phase-to-noise ratio. Along with the spoiled steady-state MRE imaging technique, initial MRE-studies on the human heart were performed. For the first time, externally induced mechanical vibrations were successfully introduced into the heart and were detected using fractional MRE with a high temporal resolution. The modulation of the shear wave amplitudes observed in the myocard of 6 healthy subjects correlated with the phases of the cardiac cycle. The techniques and methods developed here are a step toward routine clinical application of MRE of the heart and indicate high potential in the area of early diagnosis of cardiac disease. (orig.)

  20. General anesthesia suppresses normal heart rate variability in humans

    Science.gov (United States)

    Matchett, Gerald; Wood, Philip

    2014-06-01

    The human heart normally exhibits robust beat-to-beat heart rate variability (HRV). The loss of this variability is associated with pathology, including disease states such as congestive heart failure (CHF). The effect of general anesthesia on intrinsic HRV is unknown. In this prospective, observational study we enrolled 100 human subjects having elective major surgical procedures under general anesthesia. We recorded continuous heart rate data via continuous electrocardiogram before, during, and after anesthesia, and we assessed HRV of the R-R intervals. We assessed HRV using several common metrics including Detrended Fluctuation Analysis (DFA), Multifractal Analysis, and Multiscale Entropy Analysis. Each of these analyses was done in each of the four clinical phases for each study subject over the course of 24 h: Before anesthesia, during anesthesia, early recovery, and late recovery. On average, we observed a loss of variability on the aforementioned metrics that appeared to correspond to the state of general anesthesia. Following the conclusion of anesthesia, most study subjects appeared to regain their normal HRV, although this did not occur immediately. The resumption of normal HRV was especially delayed on DFA. Qualitatively, the reduction in HRV under anesthesia appears similar to the reduction in HRV observed in CHF. These observations will need to be validated in future studies, and the broader clinical implications of these observations, if any, are unknown.

  1. The human heart: application of the golden ratio and angle.

    Science.gov (United States)

    Henein, Michael Y; Zhao, Ying; Nicoll, Rachel; Sun, Lin; Khir, Ashraf W; Franklin, Karl; Lindqvist, Per

    2011-08-04

    The golden ratio, or golden mean, of 1.618 is a proportion known since antiquity to be the most aesthetically pleasing and has been used repeatedly in art and architecture. Both the golden ratio and the allied golden angle of 137.5° have been found within the proportions and angles of the human body and plants. In the human heart we found many applications of the golden ratio and angle, in addition to those previously described. In healthy hearts, vertical and transverse dimensions accord with the golden ratio, irrespective of different absolute dimensions due to ethnicity. In mild heart failure, the ratio of 1.618 was maintained but in end-stage heart failure the ratio significantly reduced. Similarly, in healthy ventricles mitral annulus dimensions accorded with the golden ratio, while in dilated cardiomyopathy and mitral regurgitation patients the ratio had significantly reduced. In healthy patients, both the angles between the mid-luminal axes of the pulmonary trunk and the ascending aorta continuation and between the outflow tract axis and continuation of the inflow tract axis of the right ventricle approximate to the golden angle, although in severe pulmonary hypertension, the angle is significantly increased. Hence the overall cardiac and ventricular dimensions in a normal heart are consistent with the golden ratio and angle, representing optimum pump structure and function efficiency, whereas there is significant deviation in the disease state. These findings could have anatomical, functional and prognostic value as markers of early deviation from normality. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  2. Angiotensinergic and noradrenergic neurons in the rat and human heart.

    Science.gov (United States)

    Patil, Jaspal; Stucki, Silvan; Nussberger, Juerg; Schaffner, Thomas; Gygax, Susanne; Bohlender, Juergen; Imboden, Hans

    2011-02-25

    Although the physiological and pharmacological evidences suggest a role for angiotensin II (Ang II) with the mammalian heart, the source and precise location of Ang II are unknown. To visualize and quantitate Ang II in atria, ventricular walls and interventricular septum of the rat and human heart and to explore the feasibility of local Ang II production and function, we investigated by different methods the expression of proteins involved in the generation and function of Ang II. We found mRNA of angiotensinogen (Ang-N), of angiotensin converting enzyme, of the angiotensin type receptors AT(1A) and AT₂ (AT(1B) not detected) as well as of cathepsin D in any part of the hearts. No renin mRNA was traceable. Ang-N mRNA was visualized by in situ hybridization in atrial ganglial neurons. Ang II and dopamine-β-hydroxylase (DβH) were either colocalized inside the same neuronal cell or the neurons were specialized for Ang II or DβH. Within these neurons, the vesicular acetylcholine transporter (VAChT) was neither colocalized with Ang II nor DβH, but VAChT-staining was found with synapses en passant encircle these neuronal cells. The fibers containing Ang II exhibited with blood vessels and with cardiomyocytes supposedly angiotensinergic synapses en passant. In rat heart, right atrial median Ang II concentration appeared higher than septal and ventricular Ang II. The distinct colocalization of neuronal Ang II with DβH in the heart may indicate that Ang II participates together with norepinephrine in the regulation of cardiac functions: produced as a cardiac neurotransmitter Ang II may have inotropic, chronotropic or dromotropic effects in atria and ventricles and contributes to blood pressure regulation. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Human heart disease : lessons from human pluripotent stem cell-derived cardiomyocytes

    NARCIS (Netherlands)

    Giacomelli, E.; Mummery, C.L.; Bellin, M.

    2017-01-01

    Technical advances in generating and phenotyping cardiomyocytes from human pluripotent stem cells (hPSC-CMs) are now driving their wider acceptance as in vitro models to understand human heart disease and discover therapeutic targets that may lead to new compounds for clinical use. Current

  4. The world's first human-to-human heart transplant at Groote Schuur ...

    African Journals Online (AJOL)

    The world's first human-to-human heart transplant at Groote Schuur Hospital: 50 years later. Johan Brink, Tim Pennel, Karen Seele, Peter Zilla. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO ...

  5. THERP and HEART integrated methodology for human error assessment

    Science.gov (United States)

    Castiglia, Francesco; Giardina, Mariarosa; Tomarchio, Elio

    2015-11-01

    THERP and HEART integrated methodology is proposed to investigate accident scenarios that involve operator errors during high-dose-rate (HDR) treatments. The new approach has been modified on the basis of fuzzy set concept with the aim of prioritizing an exhaustive list of erroneous tasks that can lead to patient radiological overexposures. The results allow for the identification of human errors that are necessary to achieve a better understanding of health hazards in the radiotherapy treatment process, so that it can be properly monitored and appropriately managed.

  6. Defining the molecular signatures of human right heart failure.

    Science.gov (United States)

    Williams, Jordan L; Cavus, Omer; Loccoh, Emefah C; Adelman, Sara; Daugherty, John C; Smith, Sakima A; Canan, Benjamin; Janssen, Paul M L; Koenig, Sara; Kline, Crystal F; Mohler, Peter J; Bradley, Elisa A

    2018-03-01

    Right ventricular failure (RVF) varies significantly from the more common left ventricular failure (LVF). This study was undertaken to determine potential molecular pathways that are important in human right ventricular (RV) function and may mediate RVF. We analyzed mRNA of human non-failing LV and RV samples and RVF samples from patients with pulmonary arterial hypertension (PAH), and post-LVAD implantation. We then performed transcript analysis to determine differential expression of genes in the human heart samples. Immunoblot quantification was performed followed by analysis of non-failing and failing phenotypes. Inflammatory pathways were more commonly dysregulated in RV tissue (both non-failing and failing phenotypes). In non-failing human RV tissue we found important differences in expression of FIGF, TRAPPAC, and CTGF suggesting that regulation of normal RV and LV function are not the same. In failing RV tissue, FBN2, CTGF, SMOC2, and TRAPP6AC were differentially expressed, and are potential targets for further study. This work provides some of the first analyses of the molecular heterogeneity between human RV and LV tissue, as well as key differences in human disease (RVF secondary to pulmonary hypertension and LVAD mediated RVF). Our transcriptional data indicated that inflammatory pathways may be more important in RV tissue, and changes in FIGF and CTGF supported this hypothesis. In PAH RV failure samples, upregulation of FBN2 and CTGF further reinforced the potential significance that altered remodeling and inflammation play in normal RV function and failure. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Magnetic resonance (MR) cine imaging of the human heart

    International Nuclear Information System (INIS)

    Waterton, J.C.

    1985-01-01

    A novel approach has been developed for MR cine imaging of the human heart by a modified ECG-gated 2DFT method. A pulse sequence has been devised to minimise the effects of saturation which can be anticipated in sequences that require rapid pulsing. Five frames are produced at the same anatomical level at predetermined intervals during the cardiac cycle. The total time taken to achieve this data is 8 minutes. Additional frames can be interleaved by repeating the sequence with an ECG-gated delay. The anatomical sections, which can be in any orthogonal plane, are then displayed as a cine loop. Cine display in the coronal plane has been used to examine 10 volunteers and 12 patients. In addition to the morphological feature displayed in single slice ECG-gated imaging, areas of dyskinesia can be detected and subjective estimates have been made of left ventricular function. (author)

  8. Distinct modulatory effects of satiety and sibutramine on brain responses to food images in humans: a double dissociation across hypothalamus, amygdala, and ventral striatum

    NARCIS (Netherlands)

    Fletcher, P.C.; Napolitano, A.; Skeggs, A.; Miller, S.R.; Delafont, B.; Cambridge, V.C.; de Wit, S.; Nathan, P.J.; Brooke, A.; O'Rahilly, S.; Farooqi, I.S.; Bullmore, E.T.

    2010-01-01

    We used functional magnetic resonance imaging to explore brain responses to food images in overweight humans, examining independently the impact of a prescan meal ("satiety") and the anti-obesity drug sibutramine, a serotonin and noradrenaline reuptake inhibitor. We identified significantly

  9. Epicardial excitation pattern as observed in the isolated revived and perfused fetal human heart

    NARCIS (Netherlands)

    Durrer, D.; Büller, J.; Graaff, P.; Lo, G.I.; Meijler, F.L.

    1961-01-01

    The resuscitated fetal human heart can be used as an experimental tooI for the investigation of the excitatory process in the human heart. During perfusion the configuration of the epicardial electrocardiograms does not change appreciably. For accurate recording permitting a detailed analysis, the

  10. Characteristic parameters of electromagnetic signals from a human heart system

    International Nuclear Information System (INIS)

    Liu Xin-Yuan; Wang Yin; Zhang Su-Ming; Gao Hong-Lei; Pei Liu-Qing; Dai Yuan-Dong

    2011-01-01

    The electromagnetic field of a human heart system is a bioelectromagnetic field. Electrocardiography (ECG) and magnetocardiography (MCG) are both carriers of electromagnetic information about the cardiac system, and they are nonstationary signals. In this study, ECG and MCG data from healthy subjects are acquired; the MCG data are captured using a high-T c radio frequency superconducting quantum interference device (HTc rf SQUIDs) and the QRS complexes in these data are analysed by the evolutionary spectrum analysis method. The results show that the quality factor Q and the central frequency f z of the QRS complex evolutionary spectrum are the characteristic parameters (CHPs) of ECG and MCG in the time—frequency domain. The confidence intervals of the mean values of the CHPs are estimated by the Student t distribution method in mathematical statistics. We believe that there are threshold ranges of the mean values of Q and f z for healthy subjects. We have postulated the following criterion: if the mean values of CHPs are in the proper ranges, the cardiac system is in a normal condition and it possesses the capability of homeostasis. In contrast, if the mean values of the CHPs do not lie in the proper ranges, the homeostasis of the cardiac system is lacking and some cardiac disease may follow. The results and procedure of MCG CHPs in the study afford a technological route for the application of HTc rf SQUIDs in cardiology. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  11. Resonance of about-weekly human heart rate rhythm with solar activity change.

    Science.gov (United States)

    Cornelissen, G; Halberg, F; Wendt, H W; Bingham, C; Sothern, R B; Haus, E; Kleitman, E; Kleitman, N; Revilla, M A; Revilla, M; Breus, T K; Pimenov, K; Grigoriev, A E; Mitish, M D; Yatsyk, G V; Syutkina, E V

    1996-12-01

    In several human adults, certain solar activity rhythms may influence an about 7-day rhythm in heart rate. When no about-weekly feature was found in the rate of change in sunspot area, a measure of solar activity, the double amplitude of a circadian heart rate rhythm, approximated by the fit of a 7-day cosine curve, was lower, as was heart rate corresponds to about-weekly features in solar activity and/or relates to a sunspot cycle.

  12. High expression of arachidonate 15-lipoxygenase and proinflammatory markers in human ischemic heart tissue

    International Nuclear Information System (INIS)

    Magnusson, Lisa U.; Lundqvist, Annika; Asp, Julia; Synnergren, Jane; Johansson, Cecilia Thalén; Palmqvist, Lars; Jeppsson, Anders; Hultén, Lillemor Mattsson

    2012-01-01

    Highlights: ► We found a 17-fold upregulation of ALOX15 in the ischemic heart. ► Incubation of human muscle cells in hypoxia showed a 22-fold upregulation of ALOX15. ► We observed increased levels of proinflammatory markers in ischemic heart tissue. ► Suggesting a link between ischemia and inflammation in ischemic heart biopsies. -- Abstract: A common feature of the ischemic heart and atherosclerotic plaques is the presence of hypoxia (insufficient levels of oxygen in the tissue). Hypoxia has pronounced effects on almost every aspect of cell physiology, and the nuclear transcription factor hypoxia inducible factor-1α (HIF-1α) regulates adaptive responses to low concentrations of oxygen in mammalian cells. In our recent work, we observed that hypoxia increases the proinflammatory enzyme arachidonate 15-lipoxygenase (ALOX15B) in human carotid plaques. ALOX15 has recently been shown to be present in the human myocardium, but the effect of ischemia on its expression has not been investigated. Here we test the hypothesis that ischemia of the heart leads to increased expression of ALOX15, and found an almost 2-fold increase in HIF-1α mRNA expression and a 17-fold upregulation of ALOX15 mRNA expression in the ischemic heart biopsies from patients undergoing coronary bypass surgery compared with non ischemic heart tissue. To investigate the effect of low oxygen concentration on ALOX15 we incubated human vascular muscle cells in hypoxia and showed that expression of ALOX15 increased 22-fold compared with cells incubated in normoxic conditions. We also observed increased mRNA levels of proinflammatory markers in ischemic heart tissue compared with non-ischemic controls. In summary, we demonstrate increased ALOX15 in human ischemic heart biopsies. Furthermore we demonstrate that hypoxia increases ALOX15 in human muscle cells. Our results yield important insights into the underlying association between hypoxia and inflammation in the human ischemic heart disease.

  13. Reconstructed image of human heart for total artificial heart implantation, based on MR image and cast silicone model of heart

    International Nuclear Information System (INIS)

    Komoda, Takashi; Maeta, Hajime; Uyama, Chikao.

    1991-01-01

    Based on transverse (TRN) and LV long axis (LAX) MR images of two cadaver hearts, three-dimensional (3-D) computer models of the connecting interface between remaining heart and total artificial heart, i.e., mitral and tricuspid valvular annuli (MVA and TVA), ascending aorta (Ao) and pulmonary artery (PA), were reconstructed to compare the shape and the size of MVA and those of TVA, the distance between the center of MVA and TVA (D G ), the angle between the plane of MVA and that of TVA (R T ), and the angles of Ao and PA, respectively, to the plane of MVA (R A , R P ), with those obtained in cast silicone models. It was found that based on LAX rather than TRN MR image, MVA and TVA might be more precisely reconstructed. The data obtained in 3-D images of MVA, TVA, Ao and PA based on silicone models of 32 hearts were as follows: D G (cm): 4.17±0.43, R T (degrees): 22.1±11.3, R A (degrees): 54.9±15.3, R P (degrees): 30.8±17.1. (author)

  14. The Visible Heart® project and free-access website 'Atlas of Human Cardiac Anatomy'.

    Science.gov (United States)

    Iaizzo, Paul A

    2016-12-01

    Pre- and post-evaluations of implantable cardiac devices require innovative and critical testing in all phases of the design process. The Visible Heart ® Project was successfully launched in 1997 and 3 years later the Atlas of Human Cardiac Anatomy website was online. The Visible Heart ® methodologies and Atlas website can be used to better understand human cardiac anatomy, disease states and/or to improve cardiac device design throughout the development process. To date, Visible ® Heart methodologies have been used to reanimate 75 human hearts, all considered non-viable for transplantation. The Atlas is a unique free-access website featuring novel images of functional and fixed human cardiac anatomies from >400 human heart specimens. Furthermore, this website includes education tutorials on anatomy, physiology, congenital heart disease and various imaging modalities. For instance, the Device Tutorial provides examples of commonly deployed devices that were present at the time of in vitro reanimation or were subsequently delivered, including: leads, catheters, valves, annuloplasty rings, leadless pacemakers and stents. Another section of the website displays 3D models of vasculature, blood volumes, and/or tissue volumes reconstructed from computed tomography (CT) and magnetic resonance images (MRI) of various heart specimens. A new section allows the user to interact with various heart models. Visible Heart ® methodologies have enabled our laboratory to reanimate 75 human hearts and visualize functional cardiac anatomies and device/tissue interfaces. The website freely shares all images, video clips and CT/MRI DICOM files in honour of the generous gifts received from donors and their families. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

  15. Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts

    NARCIS (Netherlands)

    Vermeulen, J. T.; McGuire, M. A.; Opthof, T.; Coronel, R.; de Bakker, J. M.; Klöpping, C.; Janse, M. J.

    1994-01-01

    The aim of the study was to assess the occurrence of triggered activity and automaticity in ventricular trabeculae from failing human hearts and normal and failing rabbit hearts during exposure to a normal and altered extracellular environment. Ventricular trabeculae were harvested from failing

  16. Myocardial bridges of the coronary arteries in the human fetal heart.

    Science.gov (United States)

    Cakmak, Yusuf Ozgür; Cavdar, Safiye; Yalin, Aymelek; Yener, Nuran; Ozdogmus, Omer

    2010-09-01

    During the last century, many investigators reported on myocardial bridges in the adult human heart. In the present study, 39 human fetal hearts (the mean gestastional age was 30 weeks) were studied for myocardial bridging, and the results were correlated with adult data. Among the 39 (27 male and 12 female) fetal hearts studied, 26 bridges were observed on 18 fetal hearts (46.2%). Ten of the bridges had one myocardial bridge, whereas double myocardial bridges were observed in eight fetal hearts. The most frequent myocardial bridges were observed on the left anterior descending artery (LAD), which had 13 bridges (50%). Eight (30.7%) myocardial bridges were on the diagonal artery, and on the posterior descending artery there were five (19.3%). Myocardial bridges were not observed on the circumflex artery. The data presented in this study may provide potentially useful information for the preoperative evaluation of the newborn and may have a clinical implication for sudden fetal death.

  17. Electrical admittance for filling of the heart during lower body negative pressure in humans

    DEFF Research Database (Denmark)

    Cai, Yujia; Holm, S; Jenstrup, M

    2000-01-01

    To evaluate whether electrical admittance of intracellular water is applicable for monitoring filling of the heart, we determined the difference in intracellular water in the thorax (Thorax(ICW)), measured as the reciprocal value of the electrical impedance for the thorax at 1.5 and 100 kHz during...... lower body negative pressure (LBNP) in humans. Changes in Thorax(ICW) were compared with positron emission tomography-determined C(15)O-labeled erythrocytes over the heart. During -40 mmHg LBNP, the blood volume of the heart decreased by 21 +/- 3% as the erythrocyte volume was reduced by 20 +/- 2.......6 to 40.9 +/- 5.0 S. 10(-4); P = 0.08). The correlation between Thorax(ICW) and heart erythrocyte volume was 0.84 (P electrical admittance of intracellular water can be applied to evaluate changes in blood volume of the heart during LBNP in humans....

  18. Visualization of Fiber Structure in the Left and Right Ventricle of a Human Heart

    International Nuclear Information System (INIS)

    Rohmer, Damien; Sitek, Arkadiusz; Gullberg, Grant T.

    2006-01-01

    The human heart is composed of a helical network of muscle fibers. Anisotropic least squares filtering followed by fiber tracking techniques were applied to Diffusion Tensor Magnetic Resonance Imaging(DTMRI) data of the excised human heart. The fiber configuration was visualized by using thin tubes to increase 3-dimensional visual perception of the complex structure. All visualizations were performed using the high-quality ray-tracing software POV-Ray. The fibers are shown within the left and right ventricles. Both ventricles exhibit similar fiber architecture and some bundles of fibers are shown linking right and left ventricles on the posterior region of the heart

  19. Region and cell-type resolved quantitative proteomic map of the human heart

    DEFF Research Database (Denmark)

    Doll, Sophia; Dreßen, Martina; Geyer, Philipp E

    2017-01-01

    The heart is a central human organ and its diseases are the leading cause of death worldwide, but an in-depth knowledge of the identity and quantity of its constituent proteins is still lacking. Here, we determine the healthy human heart proteome by measuring 16 anatomical regions and three major...... cardiac cell types by high-resolution mass spectrometry-based proteomics. From low microgram sample amounts, we quantify over 10,700 proteins in this high dynamic range tissue. We combine copy numbers per cell with protein organellar assignments to build a model of the heart proteome at the subcellular...

  20. Total lymphatic irradiation and bone marrow in human heart transplantation

    International Nuclear Information System (INIS)

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-01-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem

  1. Human technology after cardiac epigenesis. Artificial heart versus cardiac transplantation.

    Science.gov (United States)

    Losman, J G

    1977-09-24

    Cardiovascular disease is the chief cause of death in technologically advanced countries and accounts for more than 50% of all deaths in the USA. For a patient with end-stage cardiac failure the only treatment presently available is organ replacement, either by transplantation or by the use of a mechanical heart. Transplantation has demonstrated its value: survival of more than 8 years and restoration of a normal quality of life to patients who were in end-stage cardiac decompensation. However, the prospect of routine clinical application of an artificial heart remains distant. The development of a totally implantable artificial heart still presents a series of challenging engineering problems with regard to strict constraints of size, weight, blood-material compatibility, adaptability of output to demand, efficiency and reliability of the power supply, and safety if nuclear fuel is used. The totally artificial heart is presently not an alternative to the cardiac allograft, but could provide short-term support for patients awaiting cardiac transplantation.

  2. Adrenergic innervation of the rat hypothalamus

    NARCIS (Netherlands)

    Palkovits, M.; Mezey, E.; Záborszky, L.; Feminger, A.; Versteeg, D.H.G.; Wijnen, H.J.L.M.; Jong, Wybren de; Fekete, M.I.K.; Herman, J.P.; Kanyicska, B.

    The adrenergic innervation of the hypothalamus was studied by measuring hypothalamic adrenaline levels following surgical transection of the lower brain stem or electrolytic lesion of the medullary adrenaline-containing cell groups. The adrenaline levels in some hypothalamic nuclei and in the median

  3. The hypothalamus at the crossroads of psychopathology and neurosurgery.

    Science.gov (United States)

    Barbosa, Daniel A N; de Oliveira-Souza, Ricardo; Monte Santo, Felipe; de Oliveira Faria, Ana Carolina; Gorgulho, Alessandra A; De Salles, Antonio A F

    2017-09-01

    The neurosurgical endeavor to treat psychiatric patients may have been part of human history since its beginning. The modern era of psychosurgery can be traced to the heroic attempts of Gottlieb Burckhardt and Egas Moniz to alleviate mental symptoms through the ablation of restricted areas of the frontal lobes in patients with disabling psychiatric illnesses. Thanks to the adaptation of the stereotactic frame to human patients, the ablation of large volumes of brain tissue has been practically abandoned in favor of controlled interventions with discrete targets. Consonant with the role of the hypothalamus in the mediation of the most fundamental approach-avoidance behaviors, some hypothalamic nuclei and regions, in particular, have been selected as targets for the treatment of aggressiveness (posterior hypothalamus), pathological obesity (lateral or ventromedial nuclei), sexual deviations (ventromedial nucleus), and drug dependence (ventromedial nucleus). Some recent improvements in outcomes may have been due to the use of stereotactically guided deep brain stimulation and the change of therapeutic focus from categorical diagnoses (such as schizophrenia) to dimensional symptoms (such as aggressiveness), which are nonspecific in terms of formal diagnosis. However, agreement has never been reached on 2 related issues: 1) the choice of target, based on individual diagnoses; and 2) reliable prediction of outcomes related to individual targets. Despite the lingering controversies on such critical aspects, the experience of the past decades should pave the way for advances in the field. The current failure of pharmacological treatments in a considerable proportion of patients with chronic disabling mental disorders is reminiscent of the state of affairs that prevailed in the years before the early psychosurgical attempts. This article reviews the functional organization of the hypothalamus, the effects of ablation and stimulation of discrete hypothalamic regions, and the

  4. Cardiac spheroids as promising in vitro models to study the human heart microenvironment

    DEFF Research Database (Denmark)

    Polonchuk, Liudmila; Chabria, Mamta; Badi, Laura

    2017-01-01

    Three-dimensional in vitro cell systems are a promising alternative to animals to study cardiac biology and disease. We have generated three-dimensional in vitro models of the human heart ("cardiac spheroids", CSs) by co-culturing human primary or iPSC-derived cardiomyocytes, endothelial cells an...

  5. Imaging of the human heart after administration of l-(N-13)glutamate

    International Nuclear Information System (INIS)

    Gelbard, A.S.; Benua, R.S.; Reiman, R.E.; McDonald, J.M.; Vomero, J.J.; Laughlin, J.S.

    1980-01-01

    In normal volunteers and cancer patients, studies using L-(N-13)glutamate as an imaging agent showed localization of N-13 activity in the heart. Other organs that were well visualized include the liver, pancreas, and salivary glands. The concentration of N-13 activity in the human heart could not be predicted from previous studies involving myocardial uptake in dogs and rodents after administration of L-(N-13)glutamate

  6. Triboelectric Nanogenerator Enabled Body Sensor Network for Self-Powered Human Heart-Rate Monitoring.

    Science.gov (United States)

    Lin, Zhiming; Chen, Jun; Li, Xiaoshi; Zhou, Zhihao; Meng, Keyu; Wei, Wei; Yang, Jin; Wang, Zhong Lin

    2017-09-26

    Heart-rate monitoring plays a critical role in personal healthcare management. A low-cost, noninvasive, and user-friendly heart-rate monitoring system is highly desirable. Here, a self-powered wireless body sensor network (BSN) system is developed for heart-rate monitoring via integration of a downy-structure-based triboelectric nanogenerator (D-TENG), a power management circuit, a heart-rate sensor, a signal processing unit, and Bluetooth module for wireless data transmission. By converting the inertia energy of human walking into electric power, a maximum power of 2.28 mW with total conversion efficiency of 57.9% was delivered at low operation frequency, which is capable of immediately and sustainably driving the highly integrated BSN system. The acquired heart-rate signal by the sensor would be processed in the signal process circuit, sent to an external device via the Bluetooth module, and displayed on a personal cell phone in a real-time manner. Moreover, by combining a TENG-based generator and a TENG-based sensor, an all-TENG-based wireless BSN system was developed, realizing continuous and self-powered heart-rate monitoring. This work presents a potential method for personal heart-rate monitoring, featured as being self-powered, cost-effective, noninvasive, and user-friendly.

  7. Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor

    OpenAIRE

    Singh, Sanjay; Sayers, Scott; Walter, James S.; Thomas, Donald; Dieter, Robert S.; Nee, Lisa M.; Wurster, Robert D.

    2013-01-01

    Background Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hyper...

  8. MicroRNAs in the Hypothalamus

    DEFF Research Database (Denmark)

    Meister, Björn; Herzer, Silke; Silahtaroglu, Asli

    2013-01-01

    MicroRNAs (miRNAs) are short (∼22 nucleotides) non-coding ribonucleic acid (RNA) molecules that negatively regulate the expression of protein-coding genes. Posttranscriptional silencing of target genes by miRNA is initiated by binding to the 3'-untranslated regions of target mRNAs, resulting...... of the hypothalamus and miRNAs have recently been shown to be important regulators of hypothalamic control functions. The aim of this review is to summarize some of the current knowledge regarding the expression and role of miRNAs in the hypothalamus.......RNA molecules are abundantly expressed in tissue-specific and regional patterns and have been suggested as potential biomarkers, disease modulators and drug targets. The central nervous system is a prominent site of miRNA expression. Within the brain, several miRNAs are expressed and/or enriched in the region...

  9. Muscle metaboreflex and autonomic regulation of heart rate in humans

    DEFF Research Database (Denmark)

    Fisher, James P; Adlan, Ahmed M; Shantsila, Alena

    2013-01-01

    ) conditions, but attenuated with β-adrenergic blockade (0.2 ± 1 beats min(-1); P > 0.05 vs. rest). Thus muscle metaboreflex activation-mediated increases in HR are principally attributable to increased cardiac sympathetic activity, and only following exercise with a large muscle mass (PEI following leg......We elucidated the autonomic mechanisms whereby heart rate (HR) is regulated by the muscle metaboreflex. Eight male participants (22 ± 3 years) performed three exercise protocols: (1) enhanced metaboreflex activation with partial flow restriction (bi-lateral thigh cuff inflation) during leg cycling...... exercise, (2) isolated muscle metaboreflex activation (post-exercise ischaemia; PEI) following leg cycling exercise, (3) isometric handgrip followed by PEI. Trials were undertaken under control (no drug), β1-adrenergic blockade (metoprolol) and parasympathetic blockade (glycopyrrolate) conditions. HR...

  10. The anterior hypothalamus in cluster headache.

    Science.gov (United States)

    Arkink, Enrico B; Schmitz, Nicole; Schoonman, Guus G; van Vliet, Jorine A; Haan, Joost; van Buchem, Mark A; Ferrari, Michel D; Kruit, Mark C

    2017-10-01

    Objective To evaluate the presence, localization, and specificity of structural hypothalamic and whole brain changes in cluster headache and chronic paroxysmal hemicrania (CPH). Methods We compared T1-weighted magnetic resonance images of subjects with cluster headache (episodic n = 24; chronic n = 23; probable n = 14), CPH ( n = 9), migraine (with aura n = 14; without aura n = 19), and no headache ( n = 48). We applied whole brain voxel-based morphometry (VBM) using two complementary methods to analyze structural changes in the hypothalamus: region-of-interest analyses in whole brain VBM, and manual segmentation of the hypothalamus to calculate volumes. We used both conservative VBM thresholds, correcting for multiple comparisons, and less conservative thresholds for exploratory purposes. Results Using region-of-interest VBM analyses mirrored to the headache side, we found enlargement ( p cluster headache compared to controls, and in all participants with episodic or chronic cluster headache taken together compared to migraineurs. After manual segmentation, hypothalamic volume (mean±SD) was larger ( p cluster headache compared to controls (1.72 ± 0.15 ml) and migraineurs (1.68 ± 0.19 ml). Similar but non-significant trends were observed for participants with probable cluster headache (1.82 ± 0.19 ml; p = 0.07) and CPH (1.79 ± 0.20 ml; p = 0.15). Increased hypothalamic volume was primarily explained by bilateral enlargement of the anterior hypothalamus. Exploratory whole brain VBM analyses showed widespread changes in pain-modulating areas in all subjects with headache. Interpretation The anterior hypothalamus is enlarged in episodic and chronic cluster headache and possibly also in probable cluster headache or CPH, but not in migraine.

  11. Proteomic profiling of the rat hypothalamus

    Directory of Open Access Journals (Sweden)

    Pedroso Amanda P

    2012-04-01

    Full Text Available Abstract Background The hypothalamus plays a pivotal role in numerous mechanisms highly relevant to the maintenance of body homeostasis, such as the control of food intake and energy expenditure. Impairment of these mechanisms has been associated with the metabolic disturbances involved in the pathogenesis of obesity. Since rodent species constitute important models for metabolism studies and the rat hypothalamus is poorly characterized by proteomic strategies, we performed experiments aimed at constructing a two-dimensional gel electrophoresis (2-DE profile of rat hypothalamus proteins. Results As a first step, we established the best conditions for tissue collection and protein extraction, quantification and separation. The extraction buffer composition selected for proteome characterization of rat hypothalamus was urea 7 M, thiourea 2 M, CHAPS 4%, Triton X-100 0.5%, followed by a precipitation step with chloroform/methanol. Two-dimensional (2-D gels of hypothalamic extracts from four-month-old rats were analyzed; the protein spots were digested and identified by using tandem mass spectrometry and database query using the protein search engine MASCOT. Eighty-six hypothalamic proteins were identified, the majority of which were classified as participating in metabolic processes, consistent with the finding of a large number of proteins with catalytic activity. Genes encoding proteins identified in this study have been related to obesity development. Conclusion The present results indicate that the 2-DE technique will be useful for nutritional studies focusing on hypothalamic proteins. The data presented herein will serve as a reference database for studies testing the effects of dietary manipulations on hypothalamic proteome. We trust that these experiments will lead to important knowledge on protein targets of nutritional variables potentially able to affect the complex central nervous system control of energy homeostasis.

  12. The Development of Marine Accidents Human Reliability Assessment Approach: HEART Methodology and MOP Model

    Directory of Open Access Journals (Sweden)

    Ludfi Pratiwi Bowo

    2017-06-01

    Full Text Available Humans are one of the important factors in the assessment of accidents, particularly marine accidents. Hence, studies are conducted to assess the contribution of human factors in accidents. There are two generations of Human Reliability Assessment (HRA that have been developed. Those methodologies are classified by the differences of viewpoints of problem-solving, as the first generation and second generation. The accident analysis can be determined using three techniques of analysis; sequential techniques, epidemiological techniques and systemic techniques, where the marine accidents are included in the epidemiological technique. This study compares the Human Error Assessment and Reduction Technique (HEART methodology and the 4M Overturned Pyramid (MOP model, which are applied to assess marine accidents. Furthermore, the MOP model can effectively describe the relationships of other factors which affect the accidents; whereas, the HEART methodology is only focused on human factors.

  13. Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds.

    Science.gov (United States)

    Ellenberg, Ursula; Mattern, Thomas; Seddon, Philip J

    2013-01-01

    Intuition is a poor guide for evaluating the effects of human disturbance on wildlife. Using the endangered Yellow-eyed penguin, Megadyptes antipodes, as an example, we show that heart rate responses provide an objective tool to evaluate human disturbance stimuli and encourage the wider use of this simple and low-impact approach. Yellow-eyed penguins are a flagship species for New Zealand's wildlife tourism; however, unregulated visitor access has recently been associated with reduced breeding success and lower first year survival. We measured heart rate responses of Yellow-eyed penguins via artificial eggs to evaluate a range of human stimuli regularly occurring at their breeding sites. We found the duration of a stimulus to be the most important factor, with elevated heart rate being sustained while a person remained within sight. Human activity was the next important component; a simulated wildlife photographer, crawling slowly around during his stay, elicited a significantly higher heart rate response than an entirely motionless human spending the same time at the same distance. Stimuli we subjectively might perceive as low impact, such as the careful approach of a 'wildlife photographer', resulted in a stronger response than a routine nest-check that involved lifting a bird up to view nest contents. A single, slow-moving human spending 20 min within 2 m from the nest may provoke a response comparable to that of 10 min handling a bird for logger deployment. To reduce cumulative impact of disturbance, any human presence in the proximity of Yellow-eyed penguins needs to be kept at a minimum. Our results highlight the need for objective quantification of the effects of human disturbance in order to provide a sound basis for guidelines to manage human activity around breeding birds.

  14. Estimation of human core temperature from sequential heart rate observations

    International Nuclear Information System (INIS)

    Buller, Mark J; Tharion, William J; Cheuvront, Samuel N; Montain, Scott J; Kenefick, Robert W; Castellani, John; Latzka, William A; Hoyt, Reed W; Roberts, Warren S; Richter, Mark; Jenkins, Odest Chadwicke

    2013-01-01

    Core temperature (CT) in combination with heart rate (HR) can be a good indicator of impending heat exhaustion for occupations involving exposure to heat, heavy workloads, and wearing protective clothing. However, continuously measuring CT in an ambulatory environment is difficult. To address this problem we developed a model to estimate the time course of CT using a series of HR measurements as a leading indicator using a Kalman filter. The model was trained using data from 17 volunteers engaged in a 24 h military field exercise (air temperatures 24–36 °C, and 42%–97% relative humidity and CTs ranging from 36.0–40.0 °C). Validation data from laboratory and field studies (N = 83) encompassing various combinations of temperature, hydration, clothing, and acclimation state were examined using the Bland–Altman limits of agreement (LoA) method. We found our model had an overall bias of −0.03 ± 0.32 °C and that 95% of all CT estimates fall within ±0.63 °C (>52 000 total observations). While the model for estimating CT is not a replacement for direct measurement of CT (literature comparisons of esophageal and rectal methods average LoAs of ±0.58 °C) our results suggest it is accurate enough to provide practical indication of thermal work strain for use in the work place. (paper)

  15. Estimation of human core temperature from sequential heart rate observations.

    Science.gov (United States)

    Buller, Mark J; Tharion, William J; Cheuvront, Samuel N; Montain, Scott J; Kenefick, Robert W; Castellani, John; Latzka, William A; Roberts, Warren S; Richter, Mark; Jenkins, Odest Chadwicke; Hoyt, Reed W

    2013-07-01

    Core temperature (CT) in combination with heart rate (HR) can be a good indicator of impending heat exhaustion for occupations involving exposure to heat, heavy workloads, and wearing protective clothing. However, continuously measuring CT in an ambulatory environment is difficult. To address this problem we developed a model to estimate the time course of CT using a series of HR measurements as a leading indicator using a Kalman filter. The model was trained using data from 17 volunteers engaged in a 24 h military field exercise (air temperatures 24-36 °C, and 42%-97% relative humidity and CTs ranging from 36.0-40.0 °C). Validation data from laboratory and field studies (N = 83) encompassing various combinations of temperature, hydration, clothing, and acclimation state were examined using the Bland-Altman limits of agreement (LoA) method. We found our model had an overall bias of -0.03 ± 0.32 °C and that 95% of all CT estimates fall within ±0.63 °C (>52 000 total observations). While the model for estimating CT is not a replacement for direct measurement of CT (literature comparisons of esophageal and rectal methods average LoAs of ±0.58 °C) our results suggest it is accurate enough to provide practical indication of thermal work strain for use in the work place.

  16. Do anabolic nutritional supplements stimulate human growth hormone secretion in elderly women with heart failure?

    NARCIS (Netherlands)

    Smeets, Ellen T.H.C.; Schutzler, Scott E.; Wei, Jeanne Y.; Azhar, Gohar; Wolfe, Robert R.

    2017-01-01

    Growth hormone treatment has gained attention over the past decade as a treatment for heart failure. Human growth hormone (HGH) must be administered by injections (usually daily), so there is considerable advantage to stimulation of endogenous secretion by amino acid-based nutritional

  17. Visualization of human heart conduction system by means of fluorescence spectroscopy

    Science.gov (United States)

    Venius, Jonas; Bagdonas, Saulius; Žurauskas, Edvardas; Rotomskis, Ricardas

    2011-10-01

    The conduction system of the heart is a specific muscular tissue, where a heartbeat signal originates and initiates the depolarization of the ventricles. The muscular origin makes it complicated to distinguish the conduction system from the surrounding tissues. A surgical intervention can lead to the accidental harm of the conduction system, which may eventually result in a dangerous obstruction of the heart functionality. Therefore, there is an immense necessity for developing a helpful method to visualize the conduction system during the operation time. The specimens for the spectroscopic studies were taken from nine diverse human hearts. The localization of distinct types of the tissue was preliminary marked by the pathologist and approved histologically after the spectral measurements. Variations in intensity, as well as in shape, were detected in autofluorescence spectra of different heart tissues. The most distinct differences were observed between the heart conduction system and the surrounding tissues under 330 and 380 nm excitation. The spectral region around 460 nm appeared to be the most suitable for an unambiguous differentiation of the human conduction system avoiding the absorption peak of blood. The visualization method, based on the intensity ratios calculated for two excitation wavelengths, was also demonstrated.

  18. A new look at the comparative physiology of insect and human hearts.

    Science.gov (United States)

    Sláma, Karel

    2012-08-01

    Recent electrocardiographic (ECG) studies of insect hearts revealed the presence of human-like, involuntary and purely myogenic hearts. Certain insects, like a small light-weight species of hoverfly (Episyrphus balteatus), have evolved a very efficient cardiac system comprised of a compact heart ventricle and a narrow tube of aorta, which evolved as an adaptation to sustained hovering flights. Application of thermocardiographic and optocardiographic ECG methods revealed that adult flies of this species use the compact muscular heart chamber (heart ventricle) for intensive pumping of insect "blood" (haemolymph) into the head and thorax which is ringed all over with indirect flight musculature. The recordings of these hearts revealed extremely high, record rates of forward-directed, anterograde heartbeat (up to 10Hz), associated with extremely enhanced synchronic (not peristaltic) propagation of systolic myocardial contractions (32.2mm/s at room temperature). The relatively slow, backward-directed or retrograde cardiac contractions occurred only sporadically in the form of individual or twinned pulses replacing occasionally the resting periods. The compact heart ventricle contained bi-directional lateral apertures, whose opening and closure diverted the intracardiac anterograde "blood" streams between the abdominal haemocoelic cavity and the aortan artery, respectively. The visceral organs of this flying machine (crop, midgut) exhibited myogenic, extracardiac peristaltic pulsations similar to heartbeat, including the periodically reversed forward and backward direction of the peristaltic waves. The tubular crop contracted with a periodicity of 1Hz, both forwards and backwards, with propagation of the peristaltic waves at 4.4mm/s. The air-inflated and blindly ended midgut contracted at 0.2Hz, with a 0.9mm/s propagation of the peristaltic contraction waves. The neurogenic system of extracardiac haemocoelic pulsations, widely engaged in the regulation of circulatory and

  19. Haploinsufficiency of TAB2 causes congenital heart defects in humans

    DEFF Research Database (Denmark)

    Thienpont, Bernard; Zhang, Litu; Postma, Alex V

    2010-01-01

    . To definitively confirm the role of this candidate gene in CHDs, we performed mutation analysis of TAB2 in 402 patients with a CHD, which revealed two evolutionarily conserved missense mutations. Finally, a balanced translocation was identified, cosegregating with familial CHD. Mapping of the breakpoints...... demonstrated that this translocation disrupts TAB2. Taken together, these data clearly demonstrate a role for TAB2 in human cardiac development....

  20. Na+,K+-ATPase concentration in rodent and human heart and skeletal muscle

    DEFF Research Database (Denmark)

    Kjeldsen, K; Bjerregaard, P; Richter, Erik

    1988-01-01

    rats, cardiomyopathic hamsters, and human subjects. These methods have earlier been shown to quantify the Na+,K+-ATPase concentration in muscle tissue with high accuracy. When rats were swim trained for six weeks the heart ventricular muscle Na+,K+-ATPase concentration was increased by 20% (p less than...... was increased by up to 46% (p less than 0.001) and decreased by up to 30% (p less than 0.005) after training and immobilisation respectively. Cardiomyopathic hamsters showed a reduction of 33% (p less than 0.005) in the heart ventricular Na+,K+-ATPase concentration compared with normal hamsters. This decrease...

  1. Plasma vs heart tissue concentration in humans - literature data analysis of drugs distribution.

    Science.gov (United States)

    Tylutki, Zofia; Polak, Sebastian

    2015-03-12

    Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Changes in hypothalamus in continuously irradiated sheep

    International Nuclear Information System (INIS)

    Arendarcik, J.; Stanikova, A.; Rajtova, V.; Molnarova, M.

    1983-01-01

    Neurosecretion, PAS-positive mucopolysaccharides and the Nissl substance were studied in the neurons of the rostral, medial and caudal hypothalamus of continuously irradiated ewes. The study was performed on 21 ewes of the Slovak Merino breed of a live weight of 34 kg. The animals were in the period of physiological anoestrus and their age was two to three years. The first group of six ewes was the control. The second group included 15 sheep irradiated with a total dose of 6.7 Gy (700 R) for seven days. Co 60 was used as the source of irradiation. The animals of this group were killed seven days following treatment. The ewes in the third group were left for the study of mortality. The brains were perfused with 2% buffered paraformaldehyde immediately after the bleeding of the sheep; then the brains were removed from the skulls and fixed in buffered picroformol. Paraffin slices were stained with haematoxylin-eosine, aldehyde-fuchsine and alcian blue for neurosecretion, by the PAS reaction for mucopolysaccharides and with cresyl violet for the Nissl substance. It was found that irradiation of the whole body inhibited the activity of neurosecretory cells in the rostral and medial hypothalamus, thus reducing neurosecretion. These regions also showed a reduced activity of the PAS reaction used for the demonstration of mucopolysaccharides. The observed changes also included damage of the endothelium of blood vessels with the occurrence of erythrocyte extravasates and with haemorrhages. In this way, the trophism of neurosecretory cells was affected, which is ascribed to the decrease in the amount of neurosecretory material. In the caudal hypothalamus, neurosecretion and PAS-positivity were slightly stimulated by irradiation. The Nissl substance disappeared as a result of irradiation. (author)

  3. Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart.

    Science.gov (United States)

    Nagy, Norbert; Szél, Tamás; Jost, Norbert; Tóth, András; Gy Papp, Julius; Varró, András

    2015-09-01

    Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

  4. The quantitative assessment of epicardial fat distribution on human hearts: Implications for epicardial electrophysiology.

    Science.gov (United States)

    Mattson, Alexander R; Soto, Mario J; Iaizzo, Paul A

    2018-07-01

    Epicardial electrophysiological procedures rely on dependable interfacing with the myocardial tissue. For example, epicardial pacing systems must generate sustainable chronic pacing capture, while epicardial ablations must effectively deliver energy to the target hyper-excitable myocytes. The human heart has a significant adipose layer which may impede epicardial procedures. The objective of this study was to quantitatively assess the relative location of epicardial adipose on the human heart, to define locations where epicardial therapies might be performed successfully. We studied perfusion-fixed human hearts (n = 105) in multiple isolated planes including: left ventricular margin, diaphragmatic surface, and anterior right ventricle. Relative adipose distribution was quantitatively assessed via planar images, using a custom-generated image analysis algorithm. In these specimens, 76.7 ± 13.8% of the left ventricular margin, 72.7 ± 11.3% of the diaphragmatic surface, and 92.1 ± 8.7% of the anterior right margin were covered with superficial epicardial adipose layers. Percent adipose coverage significantly increased with age (P history of coronary artery disease (P history of hypertension, and/or history of congestive heart failure. Additionally, we describe two-dimensional probability distributions of epicardial adipose coverage for each of the three analysis planes. In this study, we detail the quantitative assessment and probabilistic mapping of the distribution of superficial epicardial adipose on the adult human heart. These findings have implications relative to performing epicardial procedures and/or designing procedures or tools to successfully perform such treatments. Clin. Anat. 31:661-666, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  5. Fractionated magnetic-resonance elastography on the human heart; Fraktionierte Magnetresonanzelastographie am menschlichen Herzen

    Energy Technology Data Exchange (ETDEWEB)

    Rump, Jens

    2008-07-28

    Imaging techniques, including magnetic resonance imaging, belong to the most important tools in modern medical diagnostics. Another diagnostic aid is palpation, which is suitable for the qualitative characterization of pathological changes in organs near the surface. Magnetic resonance elastography (MRE) is a combination of these techniques. In principle, MRE uses motionsensitive MR-imaging to depict tissue deformation caused by externally induced shear waves. The type of deformation supply useful information about the elasticity of the tissue. Cardiac disorders are among the most common diseases. The goal of this study was to develop a method of applying in-vivo MRE to the human heart. The development of the mechanical stimulus, ultimately resulting in the introduction of an audio speaker as the source of vibration, provided the necessary means to introduce vibrations into inner organs. A crucial factor in applying MRE to the heart is the speed of the recording, which led to the development of 'fractional MRE'. The currently conventional fast heart imaging techniques were used as a starting point. The use of an unbalanced phase preparation gradient in the balanced steady-state imaging technique resulted in an improved phase-to-noise ratio. Along with the spoiled steady-state MRE imaging technique, initial MRE-studies on the human heart were performed. For the first time, externally induced mechanical vibrations were successfully introduced into the heart and were detected using fractional MRE with a high temporal resolution. The modulation of the shear wave amplitudes observed in the myocard of 6 healthy subjects correlated with the phases of the cardiac cycle. The techniques and methods developed here are a step toward routine clinical application of MRE of the heart and indicate high potential in the area of early diagnosis of cardiac disease. (orig.)

  6. Can stem cells really regenerate the human heart? Use your noggin, dickkopf! Lessons from developmental biology.

    Science.gov (United States)

    Sommer, Paula

    2013-06-01

    The human heart is the first organ to develop and its development is fairly well characterised. In theory, the heart has the capacity to regenerate, as its cardiomyocytes may be capable of cell division and the adult heart contains a cardiac stem cell niche, presumably capable of differentiating into cardiomyocytes and other cardiac-associated cell types. However, as with most other organs, these mechanisms are not activated upon serious injury. Several experimental options to induce regeneration of the damaged heart tissue are available: activate the endogenous cardiomyocytes to divide, coax the endogenous population of stem cells to divide and differentiate, or add exogenous cell-based therapy to replace the lost cardiac tissue. This review is a summary of the recent research into all these avenues, discussing the reasons for the limited successes of clinical trials using stem cells after cardiac injury and explaining new advances in basic science. It concludes with a reiteration that chances of successful regeneration would be improved by understanding and implementing the basics of heart development and stem cell biology.

  7. Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts.

    Directory of Open Access Journals (Sweden)

    Kaytlyn A Gerbin

    Full Text Available Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300-390 beats per minute (5-6.5 Hz. Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart's pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they

  8. Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair.

    Science.gov (United States)

    Tiburcy, Malte; Hudson, James E; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Chang Liao, Mei-Ling; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A; Unger, Andreas; Linke, Wolfgang A; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C; Zimmermann, Wolfram-Hubertus

    2017-05-09

    Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions. We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We used morphological, functional, and transcriptome analyses to benchmark maturation of EHM. EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β 1 - and β 2 -adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and N-terminal pro B-type natriuretic peptide release; all are classical hallmarks of heart failure. In addition, we demonstrate the scalability of EHM according to anticipated clinical demands for cardiac repair. We provide proof-of-concept for a universally applicable technology for the engineering of macroscale human myocardium for disease modeling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. © 2017 American Heart Association, Inc.

  9. Tracking fusion of human mesenchymal stem cells after transplantation to the heart.

    Science.gov (United States)

    Freeman, Brian T; Kouris, Nicholas A; Ogle, Brenda M

    2015-06-01

    Evidence suggests that transplanted mesenchymal stem cells (MSCs) can aid recovery of damaged myocardium caused by myocardial infarction. One possible mechanism for MSC-mediated recovery is reprogramming after cell fusion between transplanted MSCs and recipient cardiac cells. We used a Cre/LoxP-based luciferase reporter system coupled to biophotonic imaging to detect fusion of transplanted human pluripotent stem cell-derived MSCs to cells of organs of living mice. Human MSCs, with transient expression of a viral fusogen, were delivered to the murine heart via a collagen patch. At 2 days and 1 week later, living mice were probed for bioluminescence indicative of cell fusion. Cell fusion was detected at the site of delivery (heart) and in distal tissues (i.e., stomach, small intestine, liver). Fusion was confirmed at the cellular scale via fluorescence in situ hybridization for human-specific and mouse-specific centromeres. Human cells in organs distal to the heart were typically located near the vasculature, suggesting MSCs and perhaps MSC fusion products have the ability to migrate via the circulatory system to distal organs and engraft with local cells. The present study reveals previously unknown migratory patterns of delivered human MSCs and associated fusion products in the healthy murine heart. The study also sets the stage for follow-on studies to determine the functional effects of cell fusion in a model of myocardial damage or disease. Mesenchymal stem cells (MSCs) are transplanted to the heart, cartilage, and other tissues to recover lost function or at least limit overactive immune responses. Analysis of tissues after MSC transplantation shows evidence of fusion between MSCs and the cells of the recipient. To date, the biologic implications of cell fusion remain unclear. A newly developed in vivo tracking system was used to identify MSC fusion products in living mice. The migratory patterns of fusion products were determined both in the target organ (i

  10. Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor.

    Science.gov (United States)

    Singh, Sanjay; Sayers, Scott; Walter, James S; Thomas, Donald; Dieter, Robert S; Nee, Lisa M; Wurster, Robert D

    2013-08-19

    Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy. Somal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm(2); Phearts (767.80±18.37 versus 650.23±9.84 μm(2); Pneurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm(2); Pneurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures. Hypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia.

  11. Nocturnal variations in peripheral blood flow, systemic blood pressure, and heart rate in humans

    DEFF Research Database (Denmark)

    Sindrup, J H; Kastrup, J; Christensen, H

    1991-01-01

    Subcutaneous adipose tissue blood flow rate, together with systemic arterial blood pressure and heart rate under ambulatory conditions, was measured in the lower legs of 15 normal human subjects for 12-20 h. The 133Xe-washout technique, portable CdTe(Cl) detectors, and a portable data storage uni.......0001). The synchronism of the nocturnal subcutaneous hyperemia and the decrease in systemic mean arterial blood pressure point to a common, possibly central nervous or humoral, eliciting mechanism.......Subcutaneous adipose tissue blood flow rate, together with systemic arterial blood pressure and heart rate under ambulatory conditions, was measured in the lower legs of 15 normal human subjects for 12-20 h. The 133Xe-washout technique, portable CdTe(Cl) detectors, and a portable data storage unit...

  12. [Healthcare and Christianity, the human person at the heart of God's concerns].

    Science.gov (United States)

    Onfray, Jean-Marie

    2015-10-01

    French society is still influenced by its Christian traditions and many patients are attached to this aspect. It is therefore important to clarify the reference framework put forward by the Christian religion when dealing with the notions of health, illness and care in this context. The human person, with his/her strengths and weaknesses, is at the heart of Christian reflections. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. Improvement of Heart Failure by Human Amniotic Mesenchymal Stromal Cell Transplantation in Rats.

    Science.gov (United States)

    Razavi Tousi, Seyed Mohammad Taghi; Faghihi, Mahdieh; Nobakht, Maliheh; Molazem, Mohammad; Kalantari, Elham; Darbandi Azar, Amir; Aboutaleb, Nahid

    2016-07-06

    Background: Recently, stem cells have been considered for the treatment of heart diseases, but no marked improvement has been recorded. This is the first study to examine the functional and histological effects of the transplantation of human amniotic mesenchymal stromal cells (hAMSCs) in rats with heart failure (HF). Methods: This study was conducted in the years 2014 and 2015. 35 male Wistar rats were randomly assigned into 5 equal experimental groups (7 rats each) as 1- Control 2- Heart Failure (HF) 3- Sham 4- Culture media 5- Stem Cell Transplantation (SCT). Heart failure was induced using 170 mg/kg/d of isoproterenol subcutaneously injection in 4 consecutive days. The failure confirmed by the rat cardiac echocardiography on day 28. In SCT group, 3×10 6 cells in 150 µl of culture media were transplanted to the myocardium. At the end, echocardiographic and hemodynamic parameters together with histological evaluation were done. Results: Echocardiography results showed that cardiac ejection fraction in HF group increased from 58/73 ± 9% to 81/25 ± 6/05% in SCT group (p value < 0.001). Fraction shortening in HF group was increased from 27/53 ± 8/58% into 45/55 ± 6/91% in SCT group (p value < 0.001). Furthermore, hAMSCs therapy significantly improved mean diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, rate pressure product, and left ventricular end-diastolic pressure compared to those in the HF group, with the values reaching the normal levels in the control group. A marked reduction in fibrosis tissue was also found in the SCT group (p value < 0.001) compared with the animals in the HF group. Conclusion: The transplantation of hAMSCs in rats with heart failure not only decreased the level of fibrosis but also conferred significant improvement in heart performance in terms of echocardiographic and hemodynamic parameters.

  14. Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial.

    Science.gov (United States)

    Ardehali, Abbas; Esmailian, Fardad; Deng, Mario; Soltesz, Edward; Hsich, Eileen; Naka, Yoshifumi; Mancini, Donna; Camacho, Margarita; Zucker, Mark; Leprince, Pascal; Padera, Robert; Kobashigawa, Jon

    2015-06-27

    The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts. The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital. We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation. We did this prospective, open-label, multicentre, randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe. Eligible heart-transplant candidates (aged >18 years) were randomly assigned (1:1) to receive donor hearts preserved with either the Organ Care System or standard cold storage. Participants, investigators, and medical staff were not masked to group assignment. The primary endpoint was 30 day patient and graft survival, with a 10% non-inferiority margin. We did analyses in the intention-to-treat, as-treated, and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT00855712. Between June 29, 2010, and Sept 16, 2013, we randomly assigned 130 patients to the Organ Care System group (n=67) or the standard cold storage group (n=63). 30 day patient and graft survival rates were 94% (n=63) in the Organ Care System group and 97% (n=61) in the standard cold storage group (difference 2·8%, one-sided 95% upper confidence bound 8·8; p=0·45). Eight (13%) patients in the Organ Care System group and nine (14%) patients in the standard cold storage group had cardiac-related serious adverse events. Heart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes. The metabolic assessment capability of the Organ Care System needs further study. TransMedics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. A human pericardium biopolymeric scaffold for autologous heart valve tissue engineering: cellular and extracellular matrix structure and biomechanical properties in comparison with a normal aortic heart valve.

    Science.gov (United States)

    Straka, Frantisek; Schornik, David; Masin, Jaroslav; Filova, Elena; Mirejovsky, Tomas; Burdikova, Zuzana; Svindrych, Zdenek; Chlup, Hynek; Horny, Lukas; Daniel, Matej; Machac, Jiri; Skibová, Jelena; Pirk, Jan; Bacakova, Lucie

    2018-04-01

    The objective of our study was to compare the cellular and extracellular matrix (ECM) structure and the biomechanical properties of human pericardium (HP) with the normal human aortic heart valve (NAV). HP tissues (from 12 patients) and NAV samples (from 5 patients) were harvested during heart surgery. The main cells in HP were pericardial interstitial cells, which are fibroblast-like cells of mesenchymal origin similar to the valvular interstitial cells in NAV tissue. The ECM of HP had a statistically significantly (p structures of the two tissues, the dense part of fibrous HP (49 ± 2%) and the lamina fibrosa of NAV (47 ± 4%), was similar. In both tissues, the secant elastic modulus (Es) was significantly lower in the transversal direction (p structure and has the biomechanical properties required for a tissue from which an autologous heart valve replacement may be constructed.

  16. Maximal heart rate does not limit cardiovascular capacity in healthy humans

    DEFF Research Database (Denmark)

    Munch, G D W; Svendsen, J H; Damsgaard, R

    2014-01-01

    In humans, maximal aerobic power (VO2 max ) is associated with a plateau in cardiac output (Q), but the mechanisms regulating the interplay between maximal heart rate (HRmax) and stroke volume (SV) are unclear. To evaluate the effect of tachycardia and elevations in HRmax on cardiovascular function...... and capacity during maximal exercise in healthy humans, 12 young male cyclists performed incremental cycling and one-legged knee-extensor exercise (KEE) to exhaustion with and without right atrial pacing to increase HR. During control cycling, Q and leg blood flow increased up to 85% of maximal workload (WLmax...... and RAP (P healthy...

  17. Transmural expression of ion channels and transporters in human nondiseased and end-stage failing hearts

    DEFF Research Database (Denmark)

    Soltysinska, Ewa; Olesen, Søren-Peter; Christ, Torsten

    2009-01-01

    The cardiac action potential is primarily shaped by the orchestrated function of several different types of ion channels and transporters. One of the regional differences believed to play a major role in the progression and stability of the action potential is the transmural gradient of electrica...... cardiac ion channels and transporters which may in part explain the increased susceptibility to arrhythmia in end-state failing hearts....... activity across the ventricular wall. An altered balance in the ionic currents across the free wall is assumed to be a substrate for arrhythmia. A large fraction of patients with heart failure experience ventricular arrhythmia. However, the underlying substrate of these functional changes is not well......-established as expression analyses of human heart failure (HF) are sparse. We have investigated steady-state RNA levels by quantitative polymerase chain reaction of ion channels, transporters, connexin 43, and miR-1 in 11 end-stage HF and seven nonfailing (NF) hearts. The quantifications were performed on endo-, mid...

  18. Impact of space weather on human heart rate during the years 2011-2013

    Science.gov (United States)

    Galata, E.; Ioannidou, S.; Papailiou, M.; Mavromichalaki, H.; Paravolidakis, K.; Kouremeti, M.; Rentifis, L.; Simantirakis, E.; Trachanas, K.

    2017-08-01

    During the last years a possible link between different levels of solar and geomagnetic disturbances and human physiological parameters is suggested by several published studies. In this work the examination of the potential association between heart rate variations and specific space weather activities was performed. A total of 482 individuals treated at Hippocratio General Hospital in Athens, the Cardiology clinics of Nikaia General Hospital in Piraeus and the Heraklion University Hospital in Crete, Greece, were assessed from July 2011 to April 2013. The heart rate of the individuals was recorded by a Holter monitor on a n hourly basis, while the hourly variations of the cosmic ray intensity measured by the Neutron Monitor Station of the Athens University and of the geomagnetic index Dst provided by the Kyoto Observatory were used. The ANalysis Of VAriance (ANOVA) and the Multiple Linear Regression analysis were used for analysis of these data. A statistically significant effect of both cosmic rays and geomagnetic activity on heart rate was observed, which may indicate that changes in space weather could be linked to heart rate variations.

  19. Hypothalamus-Related Resting Brain Network Underlying Short-Term Acupuncture Treatment in Primary Hypertension

    Directory of Open Access Journals (Sweden)

    Hongyan Chen

    2013-01-01

    Full Text Available The present study attempted to explore modulated hypothalamus-seeded resting brain network underlying the cardiovascular system in primary hypertensive patients after short-term acupuncture treatment. Thirty right-handed patients (14 male were divided randomly into acupuncture and control groups. The acupuncture group received a continuous five-day acupuncture treatment and undertook three resting-state fMRI scans and 24-hour ambulatory blood pressure monitoring (ABPM as well as SF-36 questionnaires before, after, and one month after acupuncture treatment. The control group undertook fMRI scans and 24-hour ABPM. For verum acupuncture, average blood pressure (BP and heart rate (HR decreased after treatment but showed no statistical differences. There were no significant differences in BP and HR between the acupuncture and control groups. Notably, SF-36 indicated that bodily pain (P = 0.005 decreased and vitality (P = 0.036 increased after acupuncture compared to the baseline. The hypothalamus-related brain network showed increased functional connectivity with the medulla, brainstem, cerebellum, limbic system, thalamus, and frontal lobes. In conclusion, short-term acupuncture did not decrease BP significantly but appeared to improve body pain and vitality. Acupuncture may regulate the cardiovascular system through a complicated brain network from the cortical level, the hypothalamus, and the brainstem.

  20. Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types.

    Science.gov (United States)

    Loh, Kyle M; Chen, Angela; Koh, Pang Wei; Deng, Tianda Z; Sinha, Rahul; Tsai, Jonathan M; Barkal, Amira A; Shen, Kimberle Y; Jain, Rajan; Morganti, Rachel M; Shyh-Chang, Ng; Fernhoff, Nathaniel B; George, Benson M; Wernig, Gerlinde; Salomon, Rachel E A; Chen, Zhenghao; Vogel, Hannes; Epstein, Jonathan A; Kundaje, Anshul; Talbot, William S; Beachy, Philip A; Ang, Lay Teng; Weissman, Irving L

    2016-07-14

    Stem-cell differentiation to desired lineages requires navigating alternating developmental paths that often lead to unwanted cell types. Hence, comprehensive developmental roadmaps are crucial to channel stem-cell differentiation toward desired fates. To this end, here, we map bifurcating lineage choices leading from pluripotency to 12 human mesodermal lineages, including bone, muscle, and heart. We defined the extrinsic signals controlling each binary lineage decision, enabling us to logically block differentiation toward unwanted fates and rapidly steer pluripotent stem cells toward 80%-99% pure human mesodermal lineages at most branchpoints. This strategy enabled the generation of human bone and heart progenitors that could engraft in respective in vivo models. Mapping stepwise chromatin and single-cell gene expression changes in mesoderm development uncovered somite segmentation, a previously unobservable human embryonic event transiently marked by HOPX expression. Collectively, this roadmap enables navigation of mesodermal development to produce transplantable human tissue progenitors and uncover developmental processes. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Inspiration from heart development: Biomimetic development of functional human cardiac organoids.

    Science.gov (United States)

    Richards, Dylan J; Coyle, Robert C; Tan, Yu; Jia, Jia; Wong, Kerri; Toomer, Katelynn; Menick, Donald R; Mei, Ying

    2017-10-01

    Recent progress in human organoids has provided 3D tissue systems to model human development, diseases, as well as develop cell delivery systems for regenerative therapies. While direct differentiation of human embryoid bodies holds great promise for cardiac organoid production, intramyocardial cell organization during heart development provides biological foundation to fabricate human cardiac organoids with defined cell types. Inspired by the intramyocardial organization events in coronary vasculogenesis, where a diverse, yet defined, mixture of cardiac cell types self-organizes into functional myocardium in the absence of blood flow, we have developed a defined method to produce scaffold-free human cardiac organoids that structurally and functionally resembled the lumenized vascular network in the developing myocardium, supported hiPSC-CM development and possessed fundamental cardiac tissue-level functions. In particular, this development-driven strategy offers a robust, tunable system to examine the contributions of individual cell types, matrix materials and additional factors for developmental insight, biomimetic matrix composition to advance biomaterial design, tissue/organ-level drug screening, and cell therapy for heart repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Human engineered heart tissue as a versatile tool in basic research and preclinical toxicology.

    Directory of Open Access Journals (Sweden)

    Sebastian Schaaf

    Full Text Available Human embryonic stem cell (hESC progenies hold great promise as surrogates for human primary cells, particularly if the latter are not available as in the case of cardiomyocytes. However, high content experimental platforms are lacking that allow the function of hESC-derived cardiomyocytes to be studied under relatively physiological and standardized conditions. Here we describe a simple and robust protocol for the generation of fibrin-based human engineered heart tissue (hEHT in a 24-well format using an unselected population of differentiated human embryonic stem cells containing 30-40% α-actinin-positive cardiac myocytes. Human EHTs started to show coherent contractions 5-10 days after casting, reached regular (mean 0.5 Hz and strong (mean 100 µN contractions for up to 8 weeks. They displayed a dense network of longitudinally oriented, interconnected and cross-striated cardiomyocytes. Spontaneous hEHT contractions were analyzed by automated video-optical recording and showed chronotropic responses to calcium and the β-adrenergic agonist isoprenaline. The proarrhythmic compounds E-4031, quinidine, procainamide, cisapride, and sertindole exerted robust, concentration-dependent and reversible decreases in relaxation velocity and irregular beating at concentrations that recapitulate findings in hERG channel assays. In conclusion this study establishes hEHT as a simple in vitro model for heart research.

  3. Defined Engineered Human Myocardium with Advanced Maturation for Applications in Heart Failure Modelling and Repair

    Science.gov (United States)

    Tiburcy, Malte; Hudson, James E.; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Liao, Mei-Ling Chang; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D.; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W.; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A.; Unger, Andreas; Linke, Wolfgang A.; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C.; Zimmermann, Wolfram-Hubertus

    2017-01-01

    Background Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modelling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) towards an adult phenotype under defined conditions. Methods We systematically investigated cell composition, matrix and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We employed morphological, functional, and transcriptome analyses to benchmark maturation of EHM. Results EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M-bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency-response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β1- and β2-adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and NT-proBNP release; all are classical hallmarks of heart failure. Additionally, we demonstrate scalability of EHM according to anticipated clinical demands for cardiac repair. Conclusions We provide proof-of-concept for a universally applicable technology for the engineering of macro-scale human myocardium for disease modelling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. PMID:28167635

  4. Analysis of Ion Currents Contribution to Repolarization in Human Heart Failure Using Computer Models

    Energy Technology Data Exchange (ETDEWEB)

    Marotta, F.; Paci, M.A.; Severi, S.; Trenor, B.

    2016-07-01

    The mechanisms underlying repolarization of the ventricular action potential (AP) are subject of research for anti-arrhythmic drugs. In fact, the prolongation of the AP occurs in several conditions of heart disease, such as heart failure, a major problem precursor for serious arrhythmias. In this study, we investigated the phenomena of repolarization reserve, defined as the capacity of the cell to repolarize in case of a functional loss, and the all-or-none repolarization, which depends on the delicate balance of inward and outward currents in the different phases of the AP, under conditions of human heart failure (HF). To simulate HF conditions, the O'Hara et al. human AP model was modified and specific protocols for all-or-none repolarization were applied. Our results show that in the early repolarization the threshold for all-or-none repolarization is not altered in HF even if a decrease in potassium currents can be observed. To quantify the contribution of the individual ion currents to HF induced AP prolongation, we used a novel piecewise-linear approximation approach proposed by Paci et al. In particular, INaL and ICaL are the main responsible for APD prolongation due to HF (85 and 35 ms respectively). Our results highlight this novel algorithm as a powerful tool to have a more complete picture of the complex ionic mechanisms underlying this disease and confirm the important role of the late sodium current in HF repolarization. (Author)

  5. Concentration of 24 Trace Elements in Human Heart Tissue Determined by Neutron Activation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wester, P O

    1964-06-15

    By means of neutron-activation analysis, human heart tissue from autopsy of 20 victims of traumatic accidents has been investigated with respect to the concentration of 24 different trace elements. A recently developed ion-exchange technique combined with gamma spectrometry has been used, which permits simultaneous determination of a large number of trace elements. The following trace elements have been determined quantitatively: Ag, As, Au, Ba, Br; Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mo, Pt, Rb, Sb, Se, Se, Sm, Zn, W. In some heart samples, Hf and Os were determined qualitatively. The mean and standard deviation are given for the elements Cu, Fe, Se and Zn, Since none of the other quantitatively determined trace elements were normally distributed, the median is given as the central value. When possible, comparisons with values from other investigations have been made. No marked differences in the trace-element concentrations with age or sex could be detected.

  6. Combined use of autogenic therapy and biofeedback in training effective control of heart rate by humans

    Science.gov (United States)

    Cowings, P. S.

    1977-01-01

    Experiments were performed on 24 men and women (aged 20-27 yr) in three equal groups who were taught to control their own heart rates by autogenic training and biofeedback under dark and sound-isolated conditions. Group I was parasympathetic dominant, group II was sympathetic dominant, and group III consisted of parasympathetic-dominant subjects and controls who received only biofeedback of their own heart rates. The results corroborate three hypotheses: (1) subjects with para-sympathetic-dominant autonomic profiles perform in a way that is both qualitatively and quantitatively different from subjects with sympathetic-dominant autonomic profiles; (2) tests of interindividual variability yield data relevant to individual performance in visceral learning tasks; and (3) the combined use of autogenic training, biofeedback, and verbal feedback is suitable for conditioning large stable autonomic responses in humans.

  7. Concentration of 24 Trace Elements in Human Heart Tissue Determined by Neutron Activation Analysis

    International Nuclear Information System (INIS)

    Wester, P.O.

    1964-06-01

    By means of neutron-activation analysis, human heart tissue from autopsy of 20 victims of traumatic accidents has been investigated with respect to the concentration of 24 different trace elements. A recently developed ion-exchange technique combined with gamma spectrometry has been used, which permits simultaneous determination of a large number of trace elements. The following trace elements have been determined quantitatively: Ag, As, Au, Ba, Br; Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mo, Pt, Rb, Sb, Se, Se, Sm, Zn, W. In some heart samples, Hf and Os were determined qualitatively. The mean and standard deviation are given for the elements Cu, Fe, Se and Zn, Since none of the other quantitatively determined trace elements were normally distributed, the median is given as the central value. When possible, comparisons with values from other investigations have been made. No marked differences in the trace-element concentrations with age or sex could be detected

  8. Pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes of rats with mammary gland cancer induced by N-methyl nitrosourea.

    Science.gov (United States)

    Carrera, M P; Ramírez-Expósito, M J; Valenzuela, M T; García, M J; Mayas, M D; Arias de Saavedra, J M; Sánchez, R; Pérez, M C; Martínez-Martos, J M

    2005-02-01

    Pyrrolidon carboxypeptidase is an omega-peptidase that hydrolyses N-terminal pyroglutamyl residues from biologically active peptides such as gonadotropin-releasing and thyrotrophin-releasing hormones. We previously described a decrease in both rat and human pyrrolidon carboxypeptidase activity with breast cancer, suggesting that gonadotropin-releasing hormone may be an important local intracrine, autocrine and/or paracrine hormonal factor in the pathogenesis of breast cancer while playing a role in the tumoral process. However, the other susceptible substrate of pyrrolidon carboxypeptidase, thyrotrophin-releasing hormone, may also be modified with breast cancer, supporting an association between breast cancer and thyroid disorders. The present work analyses soluble and membrane-bound pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes in N-methyl nitrosourea-induced breast cancer in rats. Our aim was to determine the possible relationship between gonadotropin-releasing hormone and thyrotrophin-releasing hormone regulation through pyrrolidon carboxypeptidase activity. We propose that pyrrolidon carboxypeptidase activity dysregulation at various local and systemic levels may participate in the initiation, promotion and progression of breast cancer induced in rat by N-methyl nitrosourea through the increase in gonadotropin-releasing hormone. Since pyrrolidon carboxypeptidase activity also acts on thyrotrophin-releasing hormone, the dysregulation of this enzyme's activity could indirectly affect hypothalamus-pituitary-thyroid axis function, and thus potentially represent a link between the diseases of thyroid and breast cancer.

  9. Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography

    International Nuclear Information System (INIS)

    Schwaiger, M.; Kalff, V.; Rosenspire, K.; Haka, M.S.; Molina, E.; Hutchins, G.D.; Deeb, M.; Wolfe, E. Jr.; Wieland, D.M.

    1990-01-01

    The noninvasive functional characterization of the cardiac sympathetic nervous system by imaging techniques may provide important pathophysiological information in various cardiac disease states. Hydroxyephedrine labeled with carbon 11 has been developed as a new catecholamine analogue to be used in the in vivo evaluation of presynaptic adrenergic nerve terminals by positron emission tomography (PET). To determine the feasibility of this imaging approach in the human heart, six normal volunteers and five patients with recent cardiac transplants underwent dynamic PET imaging after intravenous injection of 20 mCi [11C]hydroxyephedrine. Blood and myocardial tracer kinetics were assessed using a regions-of-interest approach. In normal volunteers, blood 11C activity cleared rapidly, whereas myocardium retained 11C activity with a long tissue half-life. Relative tracer retention in the myocardium averaged 79 +/- 31% of peak activity at 60 minutes after tracer injection. The heart-to-blood 11C activity ratio exceeded 6:1 as soon as 30 minutes after tracer injection, yielding excellent image quality. Little regional variation of tracer retention was observed, indicating homogeneous sympathetic innervation throughout the left ventricle. In the transplant recipients, myocardial [11C]hydroxyephedrine retention at 60 minutes was significantly less (-82%) than that of normal volunteers, indicating only little non-neuronal binding of the tracer in the denervated human heart. Thus, [11C]hydroxyephedrine, in combination with dynamic PET imaging, allows the noninvasive delineation of myocardial adrenergic nerve terminals. Tracer kinetic modeling may permit quantitative assessment of myocardial catecholamine uptake, which will in turn provide insights into the effects of various disease processes on the neuronal integrity of the heart

  10. CARDIOVASCULAR EFFECTS AND CHANGES IN MIDBRAIN PERIAQUEDUCTAL GRAY NEURONAL-ACTIVITY INDUCED BY ELECTRICAL-STIMULATION OF THE HYPOTHALAMUS IN THE RAT

    NARCIS (Netherlands)

    VANDERPLAS, J; WIERSINGAPOST, JEC; MAES, FW; BOHUS, B

    1995-01-01

    The effects of low-intensity electrical stimulation of sites in the hypothalamus and zona incerta (ZI) on mean blood pressure (MBP), heart rate (HR), and neuronal activity in the midbrain periaqueductal gray (FAG) were investigated in rats. Longlasting depressor responses were elicited from 67 sites

  11. CD133 antibody conjugation to decellularized human heart valves intended for circulating cell capture.

    Science.gov (United States)

    Vossler, John D; Min Ju, Young; Williams, J Koudy; Goldstein, Steven; Hamlin, James; Lee, Sang Jin; Yoo, James J; Atala, Anthony

    2015-09-03

    The long term efficacy of tissue based heart valve grafts may be limited by progressive degeneration characterized by immune mediated inflammation and calcification. To avoid this degeneration, decellularized heart valves with functionalized surfaces capable of rapid in vivo endothelialization have been developed. The aim of this study is to examine the capacity of CD133 antibody-conjugated valve tissue to capture circulating endothelial progenitor cells (EPCs). Decellularized human pulmonary valve tissue was conjugated with CD133 antibody at varying concentrations and exposed to CD133 expressing NTERA-2 cl.D1 (NT2) cells in a microflow chamber. The amount of CD133 antibody conjugated on the valve tissue surface and the number of NT2 cells captured in the presence of shear stress was measured. Both the amount of CD133 antibody conjugated to the valve leaflet surface and the number of adherent NT2 cells increased as the concentration of CD133 antibody present in the surface immobilization procedure increased. The data presented in this study support the hypothesis that the rate of CD133(+) cell adhesion in the presence of shear stress to decellularized heart valve tissue functionalized by CD133 antibody conjugation increases as the quantity of CD133 antibody conjugated to the tissue surface increases.

  12. Polonium 210Po activities in human blood of patients with ischaemic heart disease from Gda?sk in Poland

    OpenAIRE

    Bory?o, Alicja; Skwarzec, Bogdan; Roma?czyk, Grzegorz; Siebert, Janusz

    2013-01-01

    The determination of polonium 210Po in human blood samples is presented and discussed in this paper. The human blood samples were collected from patients of Medical University of Gda?sk with ischaemic heart disease (morbus ischaemicus cordis, MIC). The polonium concentrations in analyzed human blood samples are very differentiated. 210Po is of particular interest in public health and although is present in the environment in extremely low amounts, it is easily bioaccumulated to the human body...

  13. Hypothalamus-pituitary-thyroid axis activity and function of cardiac muscle in energy deficit

    Directory of Open Access Journals (Sweden)

    Katarzyna Lachowicz

    2017-12-01

    Full Text Available Frequently repeated statement that energy restriction is a factor that improves cardiovascular system function seems to be not fully truth. Low energy intake modifies the hypothalamus-pituitary-thyroid axis activity and thyroid hormone peripheral metabolism. Thyroid hormones, as modulators of the expression and activity of many cardiomyocyte proteins, control heart function. Decreased thyroid hormone levels and their disturbanced conversion and action result in alternation of cardiac remodeling, disorder of calcium homeostasis and diminish myocardial contractility. This review provides a summary of the current state of knowledge about the mechanisms of energy restriction effects on thyroidal axis activity, thyroid hormone peripheral metabolism and action in target tissues, especially in cardiac myocytes. We also showed the existence of energy restriction-thyroid-heart pathway.

  14. Heart regeneration.

    Science.gov (United States)

    Breckwoldt, Kaja; Weinberger, Florian; Eschenhagen, Thomas

    2016-07-01

    Regenerating an injured heart holds great promise for millions of patients suffering from heart diseases. Since the human heart has very limited regenerative capacity, this is a challenging task. Numerous strategies aiming to improve heart function have been developed. In this review we focus on approaches intending to replace damaged heart muscle by new cardiomyocytes. Different strategies for the production of cardiomyocytes from human embryonic stem cells or human induced pluripotent stem cells, by direct reprogramming and induction of cardiomyocyte proliferation are discussed regarding their therapeutic potential and respective advantages and disadvantages. Furthermore, different methods for the transplantation of pluripotent stem cell-derived cardiomyocytes are described and their clinical perspectives are discussed. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Analysis of cardiac myosin binding protein-C phosphorylation in human heart muscle.

    Science.gov (United States)

    Copeland, O'Neal; Sadayappan, Sakthivel; Messer, Andrew E; Steinen, Ger J M; van der Velden, Jolanda; Marston, Steven B

    2010-12-01

    A unique feature of MyBP-C in cardiac muscle is that it has multiple phosphorylation sites. MyBP-C phosphorylation, predominantly by PKA, plays an essential role in modulating contractility as part of the cellular response to β-adrenergic stimulation. In vitro studies indicate MyBP-C can be phosphorylated at Serine 273, 282, 302 and 307 (mouse sequence) but little is known about the level of MyBP-C phosphorylation or the sites phosphorylated in heart muscle. Since current methodologies are limited in specificity and are not quantitative we have investigated the use of phosphate affinity SDS-PAGE together with a total anti MyBP-C antibody and a range of phosphorylation site-specific antibodies for the main sites (Ser-273, -282 and -302). With these newly developed methods we have been able to make a detailed quantitative analysis of MyBP-C phosphorylation in heart tissue in situ. We have found that MyBP-C is highly phosphorylated in non-failing human (donor) heart or mouse heart; tris and tetra-phosphorylated species predominate and less than 10% of MyBP-C is unphosphorylated (0, 9.3 ± 1%: 1P, 13.4 ± 2.7%: 2P, 10.5 ± 3.3%: 3P, 28.7 ± 3.7%: 4P, 36.4 ± 2.7%, n=21). Total phosphorylation was 2.7 ± 0.07 mol Pi/mol MyBP-C. In contrast in failing heart and in myectomy samples from HCM patients the majority of MyBP-C was unphosphorylated. Total phosphorylation levels were 23% of normal in failing heart myofibrils (0, 60.1 ± 2.8%: 1P, 27.8 ± 2.8%: 2P, 4.8 ± 2.0%: 3P, 3.7 ± 1.2%: 4P, 2.8 ± 1.3%, n=19) and 39% of normal in myectomy samples. The site-specific antibodies showed a distinctive distribution pattern of phosphorylation sites in the multiple phosphorylation level species. We found that phosphorylated Ser-273, Ser-282 and Ser-302 were all present in the 4P band of MyBP-C but none of them were significant in the 1P band, indicating that there must be at least one other site of MyBP-C phosphorylation in human heart. The pattern of phosphorylation at the

  16. Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation.

    Science.gov (United States)

    Meyer-Roxlau, Stefanie; Lämmle, Simon; Opitz, Annett; Künzel, Stephan; Joos, Julius P; Neef, Stefan; Sekeres, Karolina; Sossalla, Samuel; Schöndube, Friedrich; Alexiou, Konstantin; Maier, Lars S; Dobrev, Dobromir; Guan, Kaomei; Weber, Silvio; El-Armouche, Ali

    2017-07-01

    Protein phosphatase 1 (PP1) is a key regulator of important cardiac signaling pathways. Dysregulation of PP1 has been heavily implicated in cardiac dysfunctions. Accordingly, pharmacological targeting of PP1 activity is considered for therapeutic intervention in human cardiomyopathies. Recent evidence from animal models implicated previously unrecognized, isoform-specific activities of PP1 in the healthy and diseased heart. Therefore, this study examined the expression of the distinct PP1 isoforms PP1α, β, and γ in human heart failure (HF) and atrial fibrillation (AF) and addressed the consequences of β-adrenoceptor blocker (beta-blocker) therapy for HF patients with reduced ejection fraction on PP1 isoform expression. Using western blot analysis, we found greater abundance of PP1 isoforms α and γ but unaltered PP1β levels in left ventricular myocardial tissues from HF patients as compared to non-failing controls. However, expression of all three PP1 isoforms was higher in atrial appendages from patients with AF compared to patients with sinus rhythm. Moreover, we found that in human failing ventricles, beta-blocker therapy was associated with lower PP1α abundance and activity, as indicated by higher phosphorylation of the PP1α-specific substrate eIF2α. Greater eIF2α phosphorylation is a known repressor of protein translation, and accordingly, we found lower levels of the endoplasmic reticulum (ER) stress marker Grp78 in the very same samples. We propose that isoform-specific targeting of PP1α activity may be a novel and innovative therapeutic strategy for the treatment of human cardiac diseases by reducing ER stress conditions.

  17. In vitro cultured progenitors and precursors of cardiac cell lineages from human normal and post-ischemic hearts

    Directory of Open Access Journals (Sweden)

    F Di Meglio

    2009-08-01

    Full Text Available The demonstration of the presence of dividing primitive cells in damaged hearts has sparked increased interest about myocardium regenerative processes. We examined the rate and the differentiation of in vitro cultured resident cardiac primitive cells obtained from pathological and normal human hearts in order to evaluate the activation of progenitors and precursors of cardiac cell lineages in post-ischemic human hearts. The precursors and progenitors of cardiomyocyte, smooth muscle and endothelial lineage were identified by immunocytochemistry and the expression of characteristic markers was studied by western blot and RT-PCR. The amount of proteins characteristic for cardiac cells (a-SA and MHC, VEGFR-2 and FVIII, SMA for the precursors of cardiomyocytes, endothelial and smooth muscle cells, respectively inclines toward an increase in both a-SA and MHC. The increased levels of FVIII and VEGFR2 are statistically significant, suggesting an important re-activation of neoangiogenesis. At the same time, the augmented expression of mRNA for Nkx 2.5, the trascriptional factor for cardiomyocyte differentiation, confirms the persistence of differentiative processes in terminally injured hearts. Our study would appear to confirm the activation of human heart regeneration potential in pathological conditions and the ability of its primitive cells to maintain their proliferative capability in vitro. The cardiac cell isolation method we used could be useful in the future for studying modifications to the microenvironment that positively influence cardiac primitive cell differentiation or inhibit, or retard, the pathological remodeling and functional degradation of the heart.

  18. Correlation between endogenous polyamines in human cardiac tissues and clinical parameters in patients with heart failure.

    Science.gov (United States)

    Meana, Clara; Rubín, José Manuel; Bordallo, Carmen; Suárez, Lorena; Bordallo, Javier; Sánchez, Manuel

    2016-02-01

    Polyamines contribute to several physiological and pathological processes, including cardiac hypertrophy in experimental animals. This involves an increase in ornithine decarboxylase (ODC) activity and intracellular polyamines associated with cyclic adenosine monophosphate (cAMP) increases. The aim of the study was to establish the role of these in the human heart in living patients. For this, polyamines (by high performance liquid chromatography) and the activity of ODC and N(1)-acetylpolyamine oxidases (APAO) were determined in the right atrial appendage of 17 patients undergoing extracorporeal circulation to correlate with clinical parameters. There existed enzymatic activity associated with the homeostasis of polyamines. Left atria size was positively associated with ODC (r = 0.661, P = 0.027) and negatively with APAO-N(1) -acetylspermine (r = -0.769, P = 0.026), suggesting that increased levels of polyamines are associated with left atrial hemodynamic overload. Left ventricular ejection fraction (LVEF) and heart rate were positively associated with spermidine (r = 0.690, P = 0.003; r = 0.590, P = 0.021) and negatively with N(1)-acetylspermidine (r = -0.554, P = 0.032; r = -0.644, P = 0.018). LVEF was negatively correlated with cAMP levels (r = -0.835, P = 0.001) and with cAMP/ODC (r = -0.794, P = 0.011), cAMP/spermidine (r = -0.813, P = 0.001) and cAMP/spermine (r = -0.747, P = 0.003) ratios. Abnormal LVEF patients showed decreased ODC activity and spermidine, and increased N(1) -acetylspermidine, and cAMP. Spermine decreased in congestive heart failure patients. The trace amine isoamylamine negatively correlated with septal wall thickness (r = -0.634, P = 0.008) and was increased in cardiac heart failure. The results indicated that modifications in polyamine homeostasis might be associated with cardiac function and remodelling. Increased cAMP might have a deleterious effect on function. Further studies should confirm these findings and the involvement of

  19. Human care system for heart-rate and human-movement trajectory in home and its application to detect mental disease

    Science.gov (United States)

    Hata, Yutaka; Kanazawa, Seigo; Endo, Maki; Tsuchiya, Naoki; Nakajima, Hiroshi

    2012-06-01

    This paper proposes a heart rate monitoring system for detecting autonomic nervous system by the heart rate variability using an air pressure sensor to diagnose mental disease. Moreover, we propose a human behavior monitoring system for detecting the human trajectory in home by an infrared camera. In day and night times, the human behavior monitoring system detects the human movement in home. The heart rate monitoring system detects the heart rate in bed in night time. The air pressure sensor consists of a rubber tube, cushion cover and pressure sensor, and it detects the heart rate by setting it to bed. It unconstraintly detects the RR-intervals; thereby the autonomic nervous system can be assessed. The autonomic nervous system analysis can examine the mental disease. While, the human behavior monitoring system obtains distance distribution image by an infrared camera. It classifies adult, child and the other object from distance distribution obtained by the camera, and records their trajectories. This behavior, i.e., trajectory in home, strongly corresponds to cognitive disorders. Thus, the total system can detect mental disease and cognitive disorders by uncontacted sensors to human body.

  20. Cardiac re-entry dynamics and self-termination in DT-MRI based model of Human Foetal Heart

    Science.gov (United States)

    Biktasheva, Irina V.; Anderson, Richard A.; Holden, Arun V.; Pervolaraki, Eleftheria; Wen, Fen Cai

    2018-02-01

    The effect of human foetal heart geometry and anisotropy on anatomy induced drift and self-termination of cardiac re-entry is studied here in MRI based 2D slice and 3D whole heart computer simulations. Isotropic and anisotropic models of 20 weeks of gestational age human foetal heart obtained from 100μm voxel diffusion tensor MRI data sets were used in the computer simulations. The fiber orientation angles of the heart were obtained from the orientation of the DT-MRI primary eigenvectors. In a spatially homogeneous electrophysiological monodomain model with the DT-MRI based heart geometries, cardiac re-entry was initiated at a prescribed location in a 2D slice, and in the 3D whole heart anatomy models. Excitation was described by simplified FitzHugh-Nagumo kinetics. In a slice of the heart, with propagation velocity twice as fast along the fibres than across the fibers, DT-MRI based fiber anisotropy changes the re-entry dynamics from pinned to an anatomical re-entry. In the 3D whole heart models, the fiber anisotropy changes cardiac re-entry dynamics from a persistent re-entry to the re-entry self-termination. The self-termination time depends on the re-entry’s initial position. In all the simulations with the DT-MRI based cardiac geometry, the anisotropy of the myocardial tissue shortens the time to re-entry self-termination several folds. The numerical simulations depend on the validity of the DT-MRI data set used. The ventricular wall showed the characteristic transmural rotation of the helix angle of the developed mammalian heart, while the fiber orientation in the atria was irregular.

  1. Congenital heart block maternal sera autoantibodies target an extracellular epitope on the α1G T-type calcium channel in human fetal hearts.

    Directory of Open Access Journals (Sweden)

    Linn S Strandberg

    Full Text Available Congenital heart block (CHB is a transplacentally acquired autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal autoantibodies and is characterized primarily by atrioventricular (AV block of the fetal heart. This study aims to investigate whether the T-type calcium channel subunit α1G may be a fetal target of maternal sera autoantibodies in CHB.We demonstrate differential mRNA expression of the T-type calcium channel CACNA1G (α1G gene in the AV junction of human fetal hearts compared to the apex (18-22.6 weeks gestation. Using human fetal hearts (20-22 wks gestation, our immunoprecipitation (IP, Western blot analysis and immunofluorescence (IF staining results, taken together, demonstrate accessibility of the α1G epitope on the surfaces of cardiomyocytes as well as reactivity of maternal serum from CHB affected pregnancies to the α1G protein. By ELISA we demonstrated maternal sera reactivity to α1G was significantly higher in CHB maternal sera compared to controls, and reactivity was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of the extracellular loop linking transmembrane segments S5-S6 in α1G repeat I. Maternal sera from CHB affected pregnancies also reacted more weakly to the homologous region (7/15 amino acids conserved of the α1H channel. Electrophysiology experiments with single-cell patch-clamp also demonstrated effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN cells.Taken together, these results indicate that CHB maternal sera antibodies readily target an extracellular epitope of α1G T-type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show reactivity for α1H suggesting that autoantibodies can target multiple fetal targets.

  2. Protective effects of recombinant human brain natriuretic peptide in perioperative period during open heart surgery.

    Science.gov (United States)

    Xu, Yunbin; Li, Yong; Bao, Weiguo; Qiu, Shi

    2018-03-01

    The aim of the present study was to evaluate the protective effects and safety aspects of recombinant human brain natriuretic peptide (rhBNP) on cardiac functions of patients undergoing open-heart surgery during perioperative period. In total, 150 patients undergoing open heart surgery in the Second Hospital of Shandong Universty from August 2015 to July 2016 were randomly divided into control group and observation group each with 75 cases. Patients in control group were treated by routine rehabilitation while patients in the observation group were treated by both the routine rehabilitation and rhBNP. All the observations were made before operation, after operation and 7 days after operation. The changes of N-terminal pro-brain natriuretic peptide (NT-proBNP) of patients, the left ventricular ejection fraction (LVEF), cardiac function [Cardiac output (CO), pulmonary capillary wedge pressure (PAWP) and central venous pressure (CVP)] of patients were measured. Further, respirator support time, ICU stay time, incidence of complications and vital signs (BP, HR, SaO2) of patients in the two groups were also compared. NT-proBNP levels of all patients improved after operation but it decreased in both groups after 7 days of operation. The decrease of NT-proBNP levels in observation group was significantly higher than that of control group. Whereas, LVEF, CO, PAWP and CVP of patients in both the groups increased after operation but effects were significantly higher in the observation group after 7 days of medication. Respirator support time and ICU stay time of patients in observation group were significantly shorter than those in control group, and the incidence of postoperative complications of patients in the observation group were significantly lower than the control group. Moreover, BP, HR and SaO2 of patients in observation group were significantly elevated in comparison to control group (Popen heart surgery, and is safe as well as reliable.

  3. Human atrial natriuretic peptide treatment for acute heart failure: a systematic review of efficacy and mortality.

    Science.gov (United States)

    Kobayashi, Daiki; Yamaguchi, Norihiro; Takahashi, Osamu; Deshpande, Gautam A; Fukui, Tsuguya

    2012-01-01

    The objectives of this study were to assess the effect of human atrial natriuretic peptide (hANP) treatment on physiological parameters and mortality in acute heart failure. The MEDLINE (1966-2009), EMBASE (1980-2009), Cochrane Central Register of Controlled Trials (1991-2009), American College of Physicians Journal Club (1991), Ichushi (Japana Centra Revuo Medicina) (1983-2009), Cinni (NII Scholarly and Academic Information Navigator) (1959-2009), National Diet Library Online Public Access Catalog (1969-2009), Webcat Plus (Japanese National Institute of Informatics) (1986-2009), Medical Online (1947-2009), and JST China (1981-2009) databases were searched for studies that compared the efficacy of hANP and the mortality in patients with acute heart failure with placebo controls. Only randomized controlled trials (RCTs) were included in the study. Out of 347 articles, a total of 4 studies involving 220 patients with acute heart failure fulfilled the predefined inclusion criteria. There were significant differences in the hemodynamic parameters between the hANP and placebo groups, especially in the pulmonary capillary wedge pressure (PCWP) reduction (standard mean difference [SMD] 2.07; 95% confidence interval [CI], 0.34-3.81) and the cardiac index (SMD 1.79; 95% CI, 0.12-3.47). No statistically significant differences in mortality rates were found (relative risk 1.03; 95% CI, 0.27-3.92). In a limited number of studies, hANP appears to improve several hemodynamic parameters, including pulmonary capillary wedge pressure and cardiac index, but not mortality. Further high-quality studies are needed to corroborate these results. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  4. Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart

    International Nuclear Information System (INIS)

    Mongillo, Marco; Leccisotti, Lucia; John, Anna S.; Pennell, Dudley J.; Camici, Paolo G.

    2007-01-01

    We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic β-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF. Eight patients (aged 67 ± 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 ± 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [ 11 C]meta-hydroxy-ephedrine (HED) volume of distribution (V d ) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 ± 4 years, p -1 .g -1 ) and dysfunctional (0.49 ± 0.14 μmol.min -1 .g -1 ) segments compared with controls (0.61 ± 0.7 μmol.min -1 .g -1 ; p d was reduced in dysfunctional segments of patients (38.9 ± 21.2 ml.g -1 ) compared with normal segments (52.2 ± 19.6 ml.g -1 ) and compared with controls (62.7 ± 11.3 ml.g -1 ). In patients, regional MGU was correlated with HED V d . The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts. (orig.)

  5. Deep RNA sequencing reveals dynamic regulation of myocardial noncoding RNAs in failing human heart and remodeling with mechanical circulatory support.

    Science.gov (United States)

    Yang, Kai-Chien; Yamada, Kathryn A; Patel, Akshar Y; Topkara, Veli K; George, Isaac; Cheema, Faisal H; Ewald, Gregory A; Mann, Douglas L; Nerbonne, Jeanne M

    2014-03-04

    Microarrays have been used extensively to profile transcriptome remodeling in failing human heart, although the genomic coverage provided is limited and fails to provide a detailed picture of the myocardial transcriptome landscape. Here, we describe sequencing-based transcriptome profiling, providing comprehensive analysis of myocardial mRNA, microRNA (miRNA), and long noncoding RNA (lncRNA) expression in failing human heart before and after mechanical support with a left ventricular (LV) assist device (LVAD). Deep sequencing of RNA isolated from paired nonischemic (NICM; n=8) and ischemic (ICM; n=8) human failing LV samples collected before and after LVAD and from nonfailing human LV (n=8) was conducted. These analyses revealed high abundance of mRNA (37%) and lncRNA (71%) of mitochondrial origin. miRNASeq revealed 160 and 147 differentially expressed miRNAs in ICM and NICM, respectively, compared with nonfailing LV. Among these, only 2 (ICM) and 5 (NICM) miRNAs are normalized with LVAD. RNASeq detected 18 480, including 113 novel, lncRNAs in human LV. Among the 679 (ICM) and 570 (NICM) lncRNAs differentially expressed with heart failure, ≈10% are improved or normalized with LVAD. In addition, the expression signature of lncRNAs, but not miRNAs or mRNAs, distinguishes ICM from NICM. Further analysis suggests that cis-gene regulation represents a major mechanism of action of human cardiac lncRNAs. The myocardial transcriptome is dynamically regulated in advanced heart failure and after LVAD support. The expression profiles of lncRNAs, but not mRNAs or miRNAs, can discriminate failing hearts of different pathologies and are markedly altered in response to LVAD support. These results suggest an important role for lncRNAs in the pathogenesis of heart failure and in reverse remodeling observed with mechanical support.

  6. Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy

    Directory of Open Access Journals (Sweden)

    Olla Carlo

    2007-08-01

    Full Text Available Abstract Background The Down syndrome phenotype has been attributed to overexpression of chromosome 21 (Hsa21 genes. However, the expression profile of Hsa21 genes in trisomic human subjects as well as their effects on genes located on different chromosomes are largely unknown. Using oligonucleotide microarrays we compared the gene expression profiles of hearts of human fetuses with and without Hsa21 trisomy. Results Approximately half of the 15,000 genes examined (87 of the 168 genes on Hsa21 were expressed in the heart at 18–22 weeks of gestation. Hsa21 gene expression was globally upregulated 1.5 fold in trisomic samples. However, not all genes were equally dysregulated and 25 genes were not upregulated at all. Genes located on other chromosomes were also significantly dysregulated. Functional class scoring and gene set enrichment analyses of 473 genes, differentially expressed between trisomic and non-trisomic hearts, revealed downregulation of genes encoding mitochondrial enzymes and upregulation of genes encoding extracellular matrix proteins. There were no significant differences between trisomic fetuses with and without heart defects. Conclusion We conclude that dosage-dependent upregulation of Hsa21 genes causes dysregulation of the genes responsible for mitochondrial function and for the extracellular matrix organization in the fetal heart of trisomic subjects. These alterations might be harbingers of the heart defects associated with Hsa21 trisomy, which could be based on elusive mechanisms involving genetic variability, environmental factors and/or stochastic events.

  7. Regenerating the human heart: direct reprogramming strategies and their current limitations.

    Science.gov (United States)

    Ghiroldi, Andrea; Piccoli, Marco; Ciconte, Giuseppe; Pappone, Carlo; Anastasia, Luigi

    2017-10-27

    Cardiovascular diseases are the leading cause of death in the Western world. Unfortunately, current therapies are often only palliative, consequently essentially making heart transplantation necessary for many patients. However, several novel therapeutic approaches in the past two decades have yielded quite encouraging results. The generation of induced pluripotent stem cells, through the forced expression of stem cell-specific transcription factors, has inspired the most promising strategies for heart regeneration by direct reprogramming of cardiac fibroblasts into functional cardiomyocytes. Initial attempts at this reprogramming were conducted using a similar approach to the one used with transcription factors, but during years, novel strategies have been tested, e.g., miRNAs, recombinant proteins and chemical molecules. Although preliminary results on animal models are promising, the low reprogramming efficiency, as well as the incomplete maturation of the cardiomyocytes, still represents important obstacles. This review covers direct transdifferentiation strategies that have been proposed and developed and illustrates the pros and cons of each approach. Indeed, as described in the manuscript, there are still many unanswered questions and drawbacks that require a better understanding of the basic signaling pathways and transcription factor networks before functional cells, suitable for cardiac regeneration and safe for the patients, can be generated and used for human therapies.

  8. Consciousness, mind and body : investigating Sartre's view on human being : "what lies at the heart of man?"

    OpenAIRE

    Karlsen, Lise Storm

    2008-01-01

    “What lies at the heart of human being?” That is the central theme of this paper. An investigation into human being can be approached in many ways. Mine is different than for instance psychology, anthropology, social science and biology. It is more in the direction of the metaphorically use of the expression “at the heart”: Having “her heart in it” (being committed, motivated, truly interested): Being a leader “with heart” (being generous, emphatic, accepting): A “heartfelt truth” (an intuiti...

  9. Artificial heart

    Energy Technology Data Exchange (ETDEWEB)

    1984-10-18

    Super-pure plutonium-238 could use heat produced during fission to power an implanted artificial heart. Three model hearts have worked for some time. Concern that excess heat would make the procedure unsafe for humans has broadened the search for another energy source, such as electrohydraulic drive or an external power battery. A back pack approach may provide an interim solution until materials are developed which can withstand heart activity and be small enough for implantation.

  10. Thallium-201 myocardial scintigraphy and cardiac pool scintigraphy with technetium-99m labelled human serum albumin of complicated anomalous heart

    International Nuclear Information System (INIS)

    Tanaka, Minoru; Watanabe, Takashi; Murase, Mitsuya; Shimizu, Ken; Abe, Toshio

    1979-01-01

    Nuclear cardiology has been used in the diagnosis of congenital heart disease, but these studies have not shown the dramatic increase that has occurred in their use in coronary heart disease. In this report, thallium-201 myocardial scintigraphy and cardiac pool scintigraphy with technetium-99m labelled human serum albumin of 13 patients with complicated congenital heart disease were compared with contrast angiography. The application of these scanning methods to visualization of the size and shape of ventricle and interventricular septum was very useful. At times these methods give us the more accurate information about cardiac shape, especially of complicated anomalous heart, than contrast angiography. Of course these methods will never replace cardiac catheterization and contrast angiography. But these studies are non-invasive. So it was concluded that these scanning methods had better be applied in patients with complicated cardiac anomaly before invasive contrast angiography. (author)

  11. Effect of human leukocyte antigen-C and -DQ matching on pediatric heart transplant graft survival.

    Science.gov (United States)

    Butts, Ryan J; Savage, Andrew J; Nietert, Paul J; Kavarana, Minoo; Moussa, Omar; Burnette, Ali L; Atz, Andrew M

    2014-12-01

    A higher degree of human leukocyte antigen (HLA) matching at the A, B, and DR loci has been associated with improved long-term survival after pediatric heart transplantation in multiple International Society for Heart and Lung Transplantation registry reports. The aim of this study was to investigate the association of HLA matching at the C and DQ loci with pediatric graft survival. The United Network of Organ Sharing database was queried for isolated heart transplants that occurred from 1988 to 2012 with a recipient age of 17 or younger and at least 1 postoperative follow-up encounter. When HLA matching at the C or DQ loci were analyzed, only transplants with complete typing of donor and recipient at the respective loci were included. Transplants were divided into patients with at least 1 match at the C locus (C-match) vs no match (C-no), and at least 1 match at the DQ (DQ-match) locus vs no match (DQ-no). Primary outcome was graft loss. Univariate analysis was performed with the log-rank test. Cox regression analysis was performed with the following patient factors included in the model: recipient age, ischemic time; recipient on ventilator, extracorporeal membrane oxygenation, ventricular assist device, or inotropes at transplant; recipient serum bilirubin and creatinine closest to transplant, ratio of donor weight to recipient weight, underlying cardiac diagnosis, crossmatch results, transplant year, and HLA matching at the A, B, and DR loci. Complete typing at the C locus occurred in 2,429 of 4,731 transplants (51%), and complete typing at the DQ locus occurred in 3,498 of 4,731 transplants (74%). Patient factors were similar in C-match and C-no, except for year of transplant (median year, 2007 [interquartile range, 1997-2010] vs year 2005 [interquartile range, 1996-2009], respectively; p = 0.03) and the degree of HLA matching at the A, B, and DR loci (high level of HLA matching in 11.9% vs 3%, respectively; p HLA matching at the C locus or the DQ locus

  12. Relationship between the level of essential metal elements in human hair and coronary heart disease

    International Nuclear Information System (INIS)

    Bor-Tsung Hsieh; Kai-Yuan Cheng; Ying-Chen Chang

    2011-01-01

    Studies on epidemics have demonstrated the relationship between coronary heart disease (CHD) and mineral substances, such as selenium, calcium, magnesium, sodium, potassium, copper, zinc, iron, manganese, and vanadium, in human bodies. In this study, instrumental neutron activation analysis (INAA) and flame atomic absorption spectrophotometry (FAAS) were applied to evaluate the levels of selenium, calcium, magnesium, sodium, potassium, copper, zinc, and iron in healthy individuals and CHD patients. Hair samples were collected from 42 healthy participants and 28 diagnosed CHD patients. Calcium, magnesium, copper, and zinc levels in healthy individuals are significantly higher than the levels found in the patients (p < 0.01). Calcium/selenium ratio is also significantly higher in healthy individuals (p < 0.05). Based on the possible synergies and/or antagonisms of elements and their absorption and metabolism, magnesium/calcium, zinc/copper, and sodium/potassium ratios showed positive relevance (p < 0.01). (author)

  13. To be, or not to be obese - that's the challenge: a hypothesis on the cortical inhibition of the hypothalamus and its therapeutical consequences.

    Science.gov (United States)

    Kreier, Felix

    2010-08-01

    Today, obesity is the most urgent unsolved medical problem, with the threat of a decreased life expectancy rate for the first time in medical history. Many obese subjects try to lose weight by dieting and exercising, without success on a long term basis. The only therapy with some effect is bariatric surgery with the impact of sustainable adverse effects only suitable in morbid obesity. Why are the therapies to treat obesity not working? Within the last years, we have become more aware of the role of the brain in energy homeostasis. The three main players within the brain controlling our weight are the cortex for cognition, hypothalamus for vital body functions and limbic-reward system for emotions. One hypothesizes that the failure of the cortex to inhibit the hypothalamus is the main cause of obesity. The evolutionary old hypothalamus constantly seeks for a positive energy balance, always in endeavor to avoid any energy shortage in the future. The hypothalamus is executing its tasks in a parallel mode. It can coordinate a set of vital routines independently, yet simultaneously. For e.g., energy balance, salt balance, body temperature and sleep are executed even in a coma. The hypothalamus is primitive but stable. The cortex in humans is, compared to rodents, much bigger and more complex, while the hypothalamus bears more similarities between these two species. The cortex in humans is evolutionary younger and represents higher cognition, an unique human feature. In contrast to the hypothalamus, the cortex focuses on one problem at a time, thus functioning on an attention-based manner. Due to this serial mode, the cortex uses a large part of its capacity for one problem at a time. Therefore, it can solve more complex calculations than the hypothalamus by thinking about one problem after another. It is even strong enough to veto the hypothalamus, if necessary. If the concentration on weight loss is distorted, the hypothalamus is free of inhibition by the cortex, and

  14. Adopting a music-to-heart rate alignment strategy to measure the impact of music and its tempo on human heart rate

    OpenAIRE

    Van Dyck, Edith; Six, Joren; Soyer, Esin Nisa; Denys, Marlies; Bardijn, Ilka; Leman, Marc

    2017-01-01

    Music is frequently used as a means of relaxation. Conversely, it is used as a means of arousal in sports and exercise contexts. Previous research suggests that tempo is one of the most significant determinants of music-related arousal and relaxation effects. Here we investigate the specific effect of music tempo, but also more generally, the influence of music on human heart rate. We took the pulses of 32 participants in silence, and then we played them non-vocal, ambient music at a tempo co...

  15. Profile of Heart Donors from the Human Valve Bank of the Santa Casa de Misericórdia de Curitiba.

    Science.gov (United States)

    Ferreira, Renata Maria; da Costa, Marise Teresinha Brenner Affonso; Canciglieri Junior, Osiris; Sant'Anna, Ângelo Márcio Oliveira

    2016-04-01

    Human heart valves are used as replacement valves and have satisfactory functional results compared with conventional prostheses. Characterize the profile of effective heart donors from the human valve bank of the santa casa de misericórdia de curitiba and analyze the association between the profile variables. It consists of a retrospective and quantitative study of electronic medical records from heart donors for heart valves. every heart donation made to the bank between january 2004 and december 2014 was studied. 2,149 donations were analyzed, from donors aged 0 to 71 years old, with an average of 34.9 ± 15.03 years old. most donors were male 65.7% (n=1,411) and 34.3% (n=738) were female. among the most frequent causes of the donors' death are trauma at 53% (n=1,139) and cerebral vascular accident at 34.2% (n=735). there was significant statistical association between the analyzed variables. There has been an improvement in brazil's donation rate, being essential that the tissue banks work together with the state and federal district centers for notification, procurement and distribution of organs in order to increase the number of donors.

  16. Simulation and mechanistic investigation of the arrhythmogenic role of the late sodium current in human heart failure.

    Directory of Open Access Journals (Sweden)

    Beatriz Trenor

    Full Text Available Heart failure constitutes a major public health problem worldwide. The electrophysiological remodeling of failing hearts sets the stage for malignant arrhythmias, in which the role of the late Na(+ current (I(NaL is relevant and is currently under investigation. In this study we examined the role of I(NaL in the electrophysiological phenotype of ventricular myocytes, and its proarrhythmic effects in the failing heart. A model for cellular heart failure was proposed using a modified version of Grandi et al. model for human ventricular action potential that incorporates the formulation of I(NaL. A sensitivity analysis of the model was performed and simulations of the pathological electrical activity of the cell were conducted. The proposed model for the human I(NaL and the electrophysiological remodeling of myocytes from failing hearts accurately reproduce experimental observations. The sensitivity analysis of the modulation of electrophysiological parameters of myocytes from failing hearts due to ion channels remodeling, revealed a role for I(NaL in the prolongation of action potential duration (APD, triangulation of the shape of the AP, and changes in Ca(2+ transient. A mechanistic investigation of intracellular Na(+ accumulation and APD shortening with increasing frequency of stimulation of failing myocytes revealed a role for the Na(+/K(+ pump, the Na(+/Ca(2+ exchanger and I(NaL. The results of the simulations also showed that in failing myocytes, the enhancement of I(NaL increased the reverse rate-dependent APD prolongation and the probability of initiating early afterdepolarizations. The electrophysiological remodeling of failing hearts and especially the enhancement of the I(NaL prolong APD and alter Ca(2+ transient facilitating the development of early afterdepolarizations. An enhanced I(NaL appears to be an important contributor to the electrophysiological phenotype and to the dysregulation of [Ca(2+](i homeostasis of failing myocytes.

  17. CONSUMPTION OF SATURATED ANIMAL FATS IN THE DIET OF HUMANS MAY DECREASE THE RATE OF HEART DISEASE IN THE FUTURE

    OpenAIRE

    Somayeh Zaminpira; Sorush Niknamian

    2017-01-01

    Fats, as part of the human dietary regime are a concentrated source of energy. Animals contain saturated and plants contain unsaturated type of fatty acids. In this prospective research, the role of animal saturated fatty acids is highlighted and is proven to be a rational dietary source for the human diet. Saturated fats consumption is a wise choice in order to reduce the coronary heart disease risk, although it is believed in an opposite way. Researching through the healthiest tribes and kn...

  18. Human engineered heart tissue as a model system for drug testing.

    Science.gov (United States)

    Eder, Alexandra; Vollert, Ingra; Hansen, Arne; Eschenhagen, Thomas

    2016-01-15

    Drug development is time- and cost-intensive and, despite extensive efforts, still hampered by the limited value of current preclinical test systems to predict side effects, including proarrhythmic and cardiotoxic effects in clinical practice. Part of the problem may be related to species-dependent differences in cardiomyocyte biology. Therefore, the event of readily available human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) has raised hopes that this human test bed could improve preclinical safety pharmacology as well as drug discovery approaches. However, hiPSC-CM are immature and exhibit peculiarities in terms of ion channel function, gene expression, structural organization and functional responses to drugs that limit their present usefulness. Current efforts are thus directed towards improving hiPSC-CM maturity and high-content readouts. Culturing hiPSC-CM as 3-dimensional engineered heart tissue (EHT) improves CM maturity and anisotropy and, in a 24-well format using silicone racks, enables automated, multiplexed high content readout of contractile function. This review summarizes the principal technology and focuses on advantages and disadvantages of this technology and its potential for preclinical drug screening. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart

    Energy Technology Data Exchange (ETDEWEB)

    Mongillo, Marco; Leccisotti, Lucia [Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, London (United Kingdom); John, Anna S. [Hammersmith Hospital, National Heart and Lung Institute, Imperial College, London (United Kingdom); Pennell, Dudley J. [Royal Brompton Hospital, National Heart and Lung Institute, Imperial College, London (United Kingdom); Camici, Paolo G. [Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, London (United Kingdom); Hammersmith Hospital, National Heart and Lung Institute, Imperial College, London (United Kingdom)

    2007-08-15

    We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic {beta}-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF. Eight patients (aged 67 {+-} 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 {+-} 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with {sup 18}F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [{sup 11}C]meta-hydroxy-ephedrine (HED) volume of distribution (V{sub d}) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 {+-} 4 years, p < 0.01 vs patients) and HED (n = 8, aged 40 {+-} 6 years, p < 0.01 vs patients) data. MGU in patients was reduced in both normal remote (0.44 {+-} 0.14 {mu}mol.min{sup -1}.g{sup -1}) and dysfunctional (0.49 {+-} 0.14 {mu}mol.min{sup -1}.g{sup -1}) segments compared with controls (0.61 {+-} 0.7 {mu}mol.min{sup -1}.g{sup -1}; p < 0.001 vs both). HED V{sub d} was reduced in dysfunctional segments of patients (38.9 {+-} 21.2 ml.g{sup -1}) compared with normal segments (52.2 {+-} 19.6 ml.g{sup -1}) and compared with controls (62.7 {+-} 11.3 ml.g{sup -1}). In patients, regional MGU was correlated with HED V{sub d}. The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts. (orig.)

  20. 31P MR spectroscopic measurement of intracellular pH in normal human hearts

    International Nuclear Information System (INIS)

    Kwon, Jae Hyun; Lee, Hui Joong; Jang, Yong Min

    2002-01-01

    To assess the usefulness of intracellular pH (pHi), calculated by determining the shift of a high-energy metabolite such as inorganic phosphate (Pi) of γ-ATP after performing MRS with ECG-gated two-dimensional 31 P CSI (chemical shift imaging), as a parameter for the overall state of the intracellular milieu. Proto decoupled 31 P CSI was performed on a 1.5-T scanner using a 1 H 31 P dual-tuned surface coil. Cardiac MRS data were obtained from eight normal volunteers aged 24-32 years with no history of heart disease. From the spectra obtained from several regions of the heart, peack position and peak area were estimated. The metabolic ratios of α-, β-, γ-ATP, PCr, Pi, phosphodiester and diphosphoglycerate were calculated, and pHi was estimated from the chemical shift of Pi and γ-ATP resonance. We then compared the data for the anterior myocardium with those previously published. The major phosphorous metabolites identified in these human hearts were as follows: PCr, at -0.1 to +0.1 ppm; three phosphate peaks from ATP, with a chemical shift centered at about -2.7 ppm (γ-ATP), -7.8 ppm (α-ATP), and -16.3 ppm (β-ATP); and phosphodiester (PDE) at 2-3 ppm, inorganic phosphate (Pi) at 4.5-5.4 ppm, and diphosphoglycerate (DPG) at 5.4-6.3 ppm. The PCr/β-ATP ratio was 2.20±0.17 and the PDE/β-ATP ratio, 1.04±0.09 pHi readings were 7.31±0.23 (calculated by the shift of Pi) and 6.81±0.20 (calculated by the shift of γ-ATP). Pi/PCR was 0.539, a ratio higher than that mentioned in previously published reports. The measurement of intracellular metabolism was affected by various kinds of factors. We believe, however, that pHi readings indicate the overall state of the cardiac intracellular milieu. An unexpected pHi readings, seen at MRS, may reflect errors in the MR procedure itself and, or in the analytical method

  1. {sup 31}P MR spectroscopic measurement of intracellular pH in normal human hearts

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jae Hyun; Lee, Hui Joong; Jang, Yong Min [Kyungpook National Univ., Taegu (Korea, Republic of)] [and others

    2002-05-01

    To assess the usefulness of intracellular pH (pHi), calculated by determining the shift of a high-energy metabolite such as inorganic phosphate (Pi) of {gamma}-ATP after performing MRS with ECG-gated two-dimensional {sup 31}P CSI (chemical shift imaging), as a parameter for the overall state of the intracellular milieu. Proto decoupled {sup 31}P CSI was performed on a 1.5-T scanner using a {sup 1}H{sup 31}P dual-tuned surface coil. Cardiac MRS data were obtained from eight normal volunteers aged 24-32 years with no history of heart disease. From the spectra obtained from several regions of the heart, peack position and peak area were estimated. The metabolic ratios of {alpha}-, {beta}-, {gamma}-ATP, PCr, Pi, phosphodiester and diphosphoglycerate were calculated, and pHi was estimated from the chemical shift of Pi and {gamma}-ATP resonance. We then compared the data for the anterior myocardium with those previously published. The major phosphorous metabolites identified in these human hearts were as follows: PCr, at -0.1 to +0.1 ppm; three phosphate peaks from ATP, with a chemical shift centered at about -2.7 ppm ({gamma}-ATP), -7.8 ppm ({alpha}-ATP), and -16.3 ppm ({beta}-ATP); and phosphodiester (PDE) at 2-3 ppm, inorganic phosphate (Pi) at 4.5-5.4 ppm, and diphosphoglycerate (DPG) at 5.4-6.3 ppm. The PCr/{beta}-ATP ratio was 2.20{+-}0.17 and the PDE/{beta}-ATP ratio, 1.04{+-}0.09 pHi readings were 7.31{+-}0.23 (calculated by the shift of Pi) and 6.81{+-}0.20 (calculated by the shift of {gamma}-ATP). Pi/PCR was 0.539, a ratio higher than that mentioned in previously published reports. The measurement of intracellular metabolism was affected by various kinds of factors. We believe, however, that pHi readings indicate the overall state of the cardiac intracellular milieu. An unexpected pHi readings, seen at MRS, may reflect errors in the MR procedure itself and, or in the analytical method.

  2. Elasticity-based determination of isovolumetric phases in the human heart

    Directory of Open Access Journals (Sweden)

    Braun Jürgen

    2010-10-01

    Full Text Available Abstract Background/Motivation To directly determine isovolumetric cardiac time intervals by magnetic resonance elastography (MRE using the magnitude of the complex signal for deducing morphological information combined with the phase of the complex signal for tension-relaxation measurements. Methods Thirty-five healthy volunteers and 11 patients with relaxation abnormalities were subjected to transthoracic wave stimulation using vibrations of approximately 25 Hz. A k-space-segmented, ECG-gated gradient-recalled echo steady-state sequence with a 500-Hz bipolar motion-encoding gradient was used for acquiring a series of 360 complex images of a short-axis view of the heart at a frame rate of less than 5.2 ms. Magnitude images were employed for measuring the cross-sectional area of the left ventricle, while phase images were used for analyzing the amplitudes of the externally induced waves. The delay between the decrease in amplitude and onset of ventricular contraction was determined in all subjects and assigned to the time of isovolumetric tension. Conversely, the delay between the increase in wave amplitude and ventricular dilatation was used for measuring the time of isovolumetric elasticity relaxation. Results Wave amplitudes decreased during systole and increased during diastole. The variation in wave amplitude occurred ahead of morphological changes. In healthy volunteers the time of isovolumetric elasticity relaxation was 75 ± 31 ms, which is significantly shorter than the time of isovolumetric tension of 136 ± 36 ms (P n = 11 isovolumetric elasticity relaxation was significantly prolonged, with 133 ± 57 ms (P P = 0.053. Conclusion The complex MRE signal conveys complementary information on cardiac morphology and elasticity, which can be combined for directly measuring isovolumetric tension and elasticity relaxation in the human heart.

  3. Using the Human Activity Profile to Assess Functional Performance in Heart Failure.

    Science.gov (United States)

    Ribeiro-Samora, Giane Amorim; Pereira, Danielle Aparecida Gomes; Vieira, Otávia Alves; de Alencar, Maria Clara Noman; Rodrigues, Roseane Santo; Carvalho, Maria Luiza Vieira; Montemezzo, Dayane; Britto, Raquel Rodrigues

    2016-01-01

    To investigate (1) the validity of using the Human Activity Profile (HAP) in patients with heart failure (HF) to estimate functional capacity; (2) the association between the HAP and 6-Minute Walk Test (6MWT) distance; and (3) the ability of the HAP to differentiate between New York Heart Association (NYHA) functional classes. In a cross-sectional study, we evaluated 62 clinically stable patients with HF (mean age, 47.98 years; NYHA class I-III). Variables included maximal functional capacity as measured by peak oxygen uptake ((Equation is included in full-text article.)O2) using a cardiopulmonary exercise test (CPET), peak (Equation is included in full-text article.)O2 as estimated by the HAP, and exercise capacity as measured by the 6MWT. The difference between the measured (CPET) and estimated (HAP) peak (Equation is included in full-text article.)O2 against the average values showed a bias of 2.18 mL/kg/min (P = .007). No agreement was seen between these measures when applying the Bland-Altman method. Peak (Equation is included in full-text article.)O2 in the HAP showed a moderate association with the 6MWT distance (r = 0.62; P < .0001). Peak (Equation is included in full-text article.)O2 in the HAP was able to statistically differentiate NYHA functional classes I, II, and III (P < .05). The estimated peak (Equation is included in full-text article.)O2 using the HAP was not concordant with the gold standard CPET measure. On the contrary, the HAP was able to differentiate NYHA functional class associated with the 6MWT distance; therefore, the HAP is a useful tool for assessing functional performance in patients with HF.

  4. Morphologic expression of the left coronary artery in pigs. An approach in relation to human heart

    Directory of Open Access Journals (Sweden)

    Fabian Alejandro Gómez

    2014-04-01

    Full Text Available Introduction: In spite of its importance as an experimental model, the information on the left coronary artery in pigs is sparse. Objective: To determine the morphologic features of the left coronary artery in pigs. Methods: We evaluated 158 pig hearts. The left coronary artery was perfused with synthetic resin after their ostia had been catheterized. Diameters and courses of the vascular beds were measured with an electronic caliper (Mitutoyo(r. Results: The diameter of left coronary artery was 6.98 ± 1.56 mm and its length was 3.51±0.99 mm. It was found to end up by bifurcating itself into the anterior interventricular artery and the circumflex artery in 79% of the cases, and by trifurcating in 21% of the cases, with the presence of the diagonal artery. The anterior interventricular artery ended up at the apex in 79.7% of the cases, and the circumflex artery at the posterior aspect of the left ventricle in 64% of the case, this artery never reached the posterior interventricular sulcus. An anastomosis between the terminal branches of the anterior interventricular artery and the posterior interventricular artery was found in 7.6% of the specimens. The antero-superior branch of the anterior interventricular artery occurred in 89.9% of the hearts. A left marginal branch was observed in 87.9% of the cases with a diameter of 2.25±0.55 mm. Conclusion: Compared with humans, pigs have shorter left coronary artery trunks and branches; even the circumflex artery never reaches the posterior interventricular sulcus. Our findings are useful for the design of experimental hemodynamic and procedural models.

  5. Effects of acute dieldrin exposure on neurotransmitters and global gene transcription in largemouth bass (Micropterus salmoides) hypothalamus

    Science.gov (United States)

    Martyniuk, Christopher J.; Feswick, April; Spade, Daniel J.; Kroll, Kevin J.; Barber, David S.; Denslow, Nancy D.

    2010-01-01

    Exposure to dieldrin induces neurotoxic effects in the vertebrate CNS and disrupts reproductive processes in teleost fish. Reproductive impairment observed in fish by dieldrin is likely the result of multiple effects along the hypothalamic-pituitary-gonadal axis but the molecular signaling cascades are not well characterized. To better elucidate the mode of action of dieldrin in the hypothalamus, this study measured neurotransmitter levels and examined the transcriptomic response in female largemouth bass (LMB) to an acute treatment of dieldrin. Male and female LMB were injected with either vehicle or 10 mg dieldrin/kg and sacrificed after seven days. There were no significant changes in dopamine or DOPAC concentrations in the neuroendocrine brain of males and females after treatment but GABA levels in females were moderately increased 20–30% in the hypothalamus and cerebellum. In the female hypothalamus, there were 227 transcripts (p<0.001) identified as being differentially regulated by dieldrin. Functional enrichment analysis revealed transcription, DNA repair, ubiquitin-proteasome pathway, and cell communication, as biological processes over-represented in the microarray analysis. Pathway analysis identified DNA damage, inflammation, regeneration, and Alzheimer’s disease as major cell processes and diseases affected by dieldrin. Using multiple bioinformatics approaches, this study demonstrates that the teleostean hypothalamus is a target for dieldrin-induced neurotoxicity and provides mechanistic evidence that dieldrin activates similar cell pathways and biological processes that are also associated with the etiology of human neurological disorders. PMID:20438755

  6. A simulation study of the reaction of human heart to biphasic electrical shocks

    Directory of Open Access Journals (Sweden)

    Seemann Gunnar

    2004-06-01

    Full Text Available Abstract Background This article presents a study, which examines the effects of biphasic electrical shocks on human ventricular tissue. The effects of this type of shock are not yet fully understood. Animal experiments showed the superiority of biphasic shocks over monophasic ones in defibrillation. A mathematical computer simulation can increase the knowledge of human heart behavior. Methods The research presented in this article was done with different models representing a three-dimensional wedge of ventricular myocardium. The electrophysiology was described with Priebe-Beuckelmann model. The realistic fiber twist, which is specific to human myocardium was included. Planar electrodes were placed at the ends of the longest side of the virtual cardiac wedge, in a bath medium. They were sources of electrical shocks, which varied in magnitude from 0.1 to 5 V. In a second arrangement ring electrodes were placed directly on myocardium for getting a better view on secondary electrical sources. The electrical reaction of the tissue was generated with a bidomain model. Results The reaction of the tissue to the electrical shock was specific to the initial imposed characteristics. Depolarization appeared in the first 5 ms in different locations. A further study of the cardiac tissue behavior revealed, which features influence the response of the considered muscle. It was shown that the time needed by the tissue to be totally depolarized is much shorter when a biphasic shock is applied. Each simulation ended only after complete repolarization was achieved. This created the possibility of gathering information from all states corresponding to one cycle of the cardiac rhythm. Conclusions The differences between the reaction of the homogeneous tissue and a tissue, which contains cleavage planes, reveals important aspects of superiority of biphasic pulses. ...

  7. Effects of Moxa (Folium Artemisiae argyi Smoke Exposure on Heart Rate and Heart Rate Variability in Healthy Young Adults: A Randomized, Controlled Human Study

    Directory of Open Access Journals (Sweden)

    Yingxue Cui

    2013-01-01

    Full Text Available Objective. To determine the effects of the moxa smoke on human heart rate (HR and heart rate variability (HRV. Methods. Fifty-five healthy young adults were randomly divided into experimental (n=28 and control (n=27 groups. Experimental subjects were exposed to moxa smoke (2.5 ± 0.5 mg/m3 twice for 25 minutes in one week. ECG monitoring was performed before, during, and after exposure. Control subjects were exposed to normal indoor air in a similar environment and similarly monitored. Followup was performed the following week. Short-term (5 min HRV parameters were analyzed with HRV analysis software. SPSS software was used for statistical analysis. Results. During and after the first exposure, comparison of percentage changes or changes in all parameters between groups showed no significant differences. During the second exposure, percentage decrease in HR, percentage increases in lnTP, lnHF, lnLF, and RMSSD, and increase in PNN50 were significantly greater in the experimental group than in control. Conclusion. No significant adverse HRV effects were associated with this clinically routine 25-minute exposure to moxa smoke, and the data suggests that short-term exposure to moxa smoke might have positive regulating effects on human autonomic function. Further studies are warranted to confirm these findings.

  8. Activity changes of the cat paraventricular hypothalamus during stressor exposure

    DEFF Research Database (Denmark)

    Kristensen, Morten Pilgaard; Rector, David M; Poe, Gina R

    2004-01-01

    Dorso-medial paraventricular hypothalamus (PVH) activity was assessed by light scattering procedures in freely behaving cats during auditory stressor exposure. Acoustic noise (> 95dB) raised plasma ACTH concentrations, somatic muscle tonus, respiratory frequency and cardiac rates; PVH activity...

  9. Combined effect of whole-body vibration and ambient lighting on human discomfort, heart rate, and reaction time.

    Science.gov (United States)

    Monazzam, Mohammad Reza; Shoja, Esmaeil; Zakerian, Seyed Abolfazl; Foroushani, Abbas Rahimi; Shoja, Mohsen; Gharaee, Masoumeh; Asgari, Amin

    2018-03-12

    This study aimed to investigate the effect of whole-body vibration and ambient lighting, as well as their combined effect on human discomfort, heart rate, and reaction time in laboratory conditions. 44 men were recruited with an average age of 25.4 ± 1.9 years. Each participant was subjected to 12 experimental steps, each step lasting five minutes for four different vibration accelerations in X, Y, and Z axes at a fixed frequency; three different lighting intensities of 50, 500, and 1000 lx were also considered. At each step, a visual computerized reaction test was taken from subjects and their heart rate recorded by pulse oximeter. In addition, the discomfort rate of subjects was measured using Borg scale. Increasing vibration acceleration significantly increased the discomfort rate and heart beat but not the reaction time. Lack of lighting caused more discomfort in the subjects, but there was no significant correlation between lighting intensity with heart rate and reaction time. The results also showed that the combined effect of vibration and lighting had no significant effect on any of the discomfort, heart rate, and reaction time variables. Whole-body vibration is an important factor in the development of human subjective and physiological reactions compared to lighting. Therefore, consideration of the level of vibration to which an individual is exposed in workplaces subject to vibration plays an important role in reducing the level of human discomfort, but its interaction with ambient lighting does not have a significant effect on human subjective and physiological responses.

  10. Noradrenergic and GABAergic systems in the medial hypothalamus are activated during hypoglycemia

    NARCIS (Netherlands)

    Beverly, JL; De Vries, MG; Bouman, SD; Arseneau, LM

    Noradrenergic and GABAergic systems in the medial hypothalamus influence plasma glucose and may be activated during glucoprivation. Microdialysis probes were placed into the ventromedial nucleus (VMH), lateral hypothalamus (LHA), and paraventricular nucleus (PVH) of male Sprague-Dawley rats to

  11. Contribution of the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic to de novo presentations of heart disease in the Heart of Soweto Study cohort.

    Science.gov (United States)

    Sliwa, Karen; Carrington, Melinda J; Becker, Anthony; Thienemann, Friedrich; Ntsekhe, Mpiko; Stewart, Simon

    2012-04-01

    The contemporary impact of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic on heart disease in South Africa (>5 million people affected) is unknown. The Heart of Soweto Study provides a unique opportunity to identify the contribution of cardiac manifestations of this epidemic to de novo presentations of heart disease in an urban African community in epidemiological transition. Chris Hani Baragwanath Hospital services the >1 million people living in Soweto, South Africa. A prospective, clinical registry captured data from all de novo cases of heart disease presenting to the Cardiology Unit during 2006-08. We describe all cases where HIV/AIDS was concurrently diagnosed. Overall, 518 of 5328 de novo cases of heart disease were identified as HIV-positive (9.7%) with 54% of these prescribed highly active anti-retroviral therapies on presentation. Women (62%) and Africans (97%) predominated with women being significantly younger than men 38 ± 13 vs. 42 ± 13 years (P = 0.002). The most common primary diagnosis attributable to HIV/AIDS was HIV-related cardiomyopathy (196 cases, 38%); being prescribed more anti-retroviral therapy (127/196 vs. 147/322; odds ratio 2.85, 95% confidence interval 1.81-3.88) with higher viral loads [median 110 000 (inter-quartile range 26 000-510 000) vs. 19 000 (3200-87 000); P = 0.018] and a lower CD4 count [median 180 (71-315) vs. 211 (96-391); P = 0.019] than the rest. An additional 128 cases (25%) were diagnosed with pericarditis/pericardial effusion with a range of other concurrent diagnoses evident, including 42 cases (8.1%) of HIV-related pulmonary arterial hypertension. Only 14 of all 581 cases of coronary artery disease (CAD) (2.4%, mean age 41 ± 13 years) were confirmed HIV-positive. Cardiac manifestations of HIV/AIDS identified within this cohort were relatively infrequent. While HIV-related cardiomyopathy and pericardial disease remain important targets for early detection and treatment in

  12. Flat panel computed tomography of human ex vivo heart and bone specimens: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Nikolaou, Konstantin; Becker, Christoph R.; Reiser, Maximilian F. [Ludwig-Maximilians-University, Department of Clinical Radiology, Munich (Germany); Flohr, Thomas; Stierstorfer, Karl [CT Division, Siemens Medical Solutions, Forchheim (Germany)

    2005-02-01

    The aim of this technical investigation was the detailed description of a prototype flat panel detector computed tomography system (FPCT) and its initial evaluation in an ex vivo setting. The prototype FPCT scanner consists of a conventional radiographic flat panel detector, mounted on a multi-slice CT scanner gantry. Explanted human ex vivo heart and foot specimens were examined. Images were reformatted with various reconstruction algorithms and were evaluated for high-resolution anatomic information. For comparison purposes, the ex vivo specimens were also scanned with a conventional 16-detector-row CT scanner (Sensation 16, Siemens Medical Solutions, Forchheim, Germany). With the FPCT prototype used, a 1,024 x 768 resolution matrix can be obtained, resulting in an isotropic voxel size of 0.25 x 0.25 x 0.25 mm at the iso-center. Due to the high spatial resolution, very small structures such as trabecular bone or third-degree, distal branches of coronary arteries could be visualized. This first evaluation showed that flat panel detector systems can be used in a cone-beam computed tomography scanner and that very high spatial resolutions can be achieved. However, there are limitations for in vivo use due to constraints in low contrast resolution and slow scan speed. (orig.)

  13. Oxygen-saving effect of a new cardiotonic agent, MCI-154, in diseased human hearts.

    Science.gov (United States)

    Mori, M; Takeuchi, M; Takaoka, H; Hata, K; Hayashi, Y; Yamakawa, H; Yokoyama, M

    1997-03-01

    The aim of this study was to examine the left ventricular mechanoenergetic effects of a novel Ca2+ sensitizing agent, MCI-154, on diseased human hearts compared with dobutamine. Unlike conventional cardiotonic agents, a Ca2+ sensitizer that could produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+ could generate force with smaller amounts of Ca2+; thus, it may potentially save energy expenditure. The left ventricular pressure-volume relation and myocardial oxygen consumption per beat (Vo2) were measured by a conductance (volume) catheter and a Webster catheter. Left ventricular contractility (Emax), systolic pressure-volume area (PVA [index of left ventricular total mechanical energy]) and Vo2 were assessed before and after infusion of MCI-154 or dobut-amine. The PVA-independent Vo2 (Vo2 mainly for excitation-contraction coupling) was assessed as the Vo2 at zero PVA. Both agents increased Emax comparably (dobutamine: from 3.55 +/- 1.10 [mean +/- SD] to 5.04 +/- 1.16 mm Hg/ml per m2, p delta PVA-independent Vo2/delta Emax) was less with MCI-154 than with dobutamine (0.14 +/- 0.18 vs. 1.10 +/- 0.80 J/mm Hg per ml per m2, p action mediated by MCI-154 could provide an energetic advantage over the conventional cardiotonic action with currently used inotropic agents.

  14. Structural and functional sex differences in the human hypothalamus

    NARCIS (Netherlands)

    Swaab, D. F.; Chung, W. C.; Kruijver, F. P.; Hofman, M. A.; Ishunina, T. A.

    2001-01-01

    Sex differences in the brain may be the basis not only for sex differences in reproduction, gender identity (the feeling of being male or female), and sexual orientation (heterosexuality vs homosexuality), but also for the sex difference in prevalence of psychiatric and neurological diseases ( Swaab

  15. Effect of propionyl-L-carnitine on L-type calcium channels in human heart sarcolemma

    International Nuclear Information System (INIS)

    Bevilacqua, M.; Vago, T.; Norbiato, G.

    1991-01-01

    Propionyl-L-carnitine (PC) protects perfused rat hearts against damage by ischemia-reperfusion. Activation of L-type calcium channel play a role on ischemia-reperfusion damage. Therefore, we studied the effect of PC on some properties of L-type calcium channels in an in vitro preparation from human myocardium sarcolemma (from patients with idiopathic dilated cardiomyopathy). Binding of the L-type calcium channel blockers isradipine [ 3 H]-PN 200-110 (PN) to plasma membrane preparations revealed a single population of binding sites (total number: Bmax = 213 +/- 34 fM/mg protein and affinity: Kd = 152 +/- 19 nM; n = 6). The characteristics of these binding sites were evaluated in the presence and in the absence of Ca 2+ and of calcium blockers (D-888, a verapamillike drug, and diltiazem). Incubation in a Ca 2+ -containing buffer increased the affinity of PN binding sites. Binding sites for PN were modulated by organic calcium channel blockers; in competition isotherms at 37 degree C, D-888 (desmethoxyverapamil) decreased the PN binding, whereas diltiazem increased it. These results strongly suggest that the site labelled by PN is the voltage-operated calcium channel of the human myocardium. The addition of PC (1 mM) to plasma membranes labelled with PN at 37 degree C decreased the affinity of the binding; this effect was counteracted by the addition of Ca 2+ to the medium. This result was consistent with a competition between Ca 2+ and PC. The effect of PC incubation at 4 degree C was the opposite; at this temperature PC increased the affinity of the binding sites and the effect was obscured by Ca 2+

  16. File list: Unc.Neu.10.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.10.AllAg.Hypothalamus mm9 Unclassified Neural Hypothalamus SRX956253,SRX956...254 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.10.AllAg.Hypothalamus.bed ...

  17. File list: ALL.Neu.10.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.10.AllAg.Hypothalamus mm9 All antigens Neural Hypothalamus SRX956253,SRX956...254 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.10.AllAg.Hypothalamus.bed ...

  18. File list: ALL.Neu.05.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.05.AllAg.Hypothalamus mm9 All antigens Neural Hypothalamus SRX956254,SRX956...253 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.05.AllAg.Hypothalamus.bed ...

  19. File list: ALL.Neu.50.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.50.AllAg.Hypothalamus mm9 All antigens Neural Hypothalamus SRX956253,SRX956...254 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.50.AllAg.Hypothalamus.bed ...

  20. File list: ALL.Neu.20.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.20.AllAg.Hypothalamus mm9 All antigens Neural Hypothalamus SRX956253,SRX956...254 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.20.AllAg.Hypothalamus.bed ...

  1. File list: Unc.Neu.20.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.20.AllAg.Hypothalamus mm9 Unclassified Neural Hypothalamus SRX956253,SRX956...254 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.20.AllAg.Hypothalamus.bed ...

  2. File list: Unc.Neu.05.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.05.AllAg.Hypothalamus mm9 Unclassified Neural Hypothalamus SRX956254,SRX956...253 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.05.AllAg.Hypothalamus.bed ...

  3. File list: Unc.Neu.50.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.50.AllAg.Hypothalamus mm9 Unclassified Neural Hypothalamus SRX956253,SRX956...254 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.50.AllAg.Hypothalamus.bed ...

  4. NPY intraperitoneal injections produce antidepressant-like effects and downregulate BDNF in the rat hypothalamus.

    Science.gov (United States)

    Gelfo, Francesca; Tirassa, Paola; De Bartolo, Paola; Croce, Nicoletta; Bernardini, Sergio; Caltagirone, Carlo; Petrosini, Laura; Angelucci, Francesco

    2012-06-01

    Several studies have documented an involvement of Neuropeptide Y (NPY) in stress-related disorders. Stress-related disorders are also characterized by changes in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), neurotrophins implicated in the survival and function of neurons. Thus the aim of this study was to investigate whether an NPY intraperitoneal treatment has antidepressant-like effects in rats subjected to a classical stress paradigm, the Forced Swim Test (FST), in association with changes in local brain neurotrophin production. Rats were intraperitoneally injected with either NPY (60 μg/kg) or a vehicle for three consecutive days between two FST sessions and then tested for time spent (or delay onset) in immobile posture. Moreover, we measured by enzyme-linked immunosorbent assay (ELISA) neurotrophin levels in the hypothalamus and corticosterone levels in plasma. The data showed that NPY induced a significant delay in the onset and a significant reduction in the duration of the immobility posture in FST. We also found that NPY decreased BDNF levels in the hypothalamus and corticosterone levels in plasma. Immobility posture in FST can be reduced by antidepressant drugs. Thus, our data show an antidepressant-like effect of NPY associated with changes in BDNF levels in the hypothalamus and reduced activity of hypothalamic-pituitary-adrenal (HPA) axis. These findings, while confirming the involvement of the NPY system in stress-related disorders, suggest that a less invasive route of administration, such as an intraperitoneal injection, may be instrumental in coping with stressful events in animal models and perhaps in humans. © 2012 Blackwell Publishing Ltd.

  5. A New Approach to Heart Valve Tissue Engineering Based on Modifying Autologous Human Pericardium by 3D Cellular Mechanotransduction

    Czech Academy of Sciences Publication Activity Database

    Straka, František; Schorník, David; Mašín, J.; Filová, Elena; Miřejovský, T.; Burdíková, Z.; Švindrych, Z.; Chlup, H.; Horný, L.; Veselý, J.; Pirk, J.; Bačáková, Lucie

    2017-01-01

    Roč. 7, č. 7 (2017), s. 527-543 ISSN 2157-9083 R&D Projects: GA MZd(CZ) NV15-29153A; GA MZd(CZ) NT11270 Institutional support: RVO:67985823 Keywords : autologous human pericardium * pericardial interstitial cells * heart valve * 3D mechanotranduction * bioreactor Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Cardiac and Cardiovascular systems Impact factor: 1.383, year: 2016

  6. Effects of Adenovirus-Mediated Delivery of the Human Hepatocyte Growth Factor Gene in Experimental Radiation-Induced Heart Disease

    International Nuclear Information System (INIS)

    Hu Shunying; Chen Yundai; Li Libing; Chen Jinlong; Wu Bin; Zhou, Xiao; Zhi Guang; Li Qingfang; Wang Rongliang; Duan Haifeng; Guo Zikuan; Yang Yuefeng; Xiao Fengjun; Wang Hua; Wang Lisheng

    2009-01-01

    Purpose: Irradiation to the heart may lead to late cardiovascular complications. The purpose of this study was to investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor gene could reduce post-irradiation damage of the rat heart and improve heart function. Methods and Materials: Twenty rats received single-dose irradiation of 20 Gy gamma ray locally to the heart and were randomized into two groups. Two weeks after irradiation, these two groups of rats received Ad-HGF or mock adenovirus vector intramyocardial injection, respectively. Another 10 rats served as sham-irradiated controls. At post-irradiation Day 120, myocardial perfusion was tested by myocardial contrast echocardiography with contrast agent injected intravenously. At post-irradiation Day 180, cardiac function was assessed using the Langendorff technique with an isolated working heart model, after which heart samples were collected for histological evaluation. Results: Myocardial blood flow was significantly improved in HGF-treated animals as measured by myocardial contrast echocardiography at post-irradiation Day 120 . At post-irradiation Day 180, cardiac function was significantly improved in the HGF group compared with mock vector group, as measured by left ventricular peak systolic pressure (58.80 ± 9.01 vs. 41.94 ± 6.65 mm Hg, p < 0.05), the maximum dP/dt (5634 ± 1303 vs. 1667 ± 304 mm Hg/s, p < 0.01), and the minimum dP/dt (3477 ± 1084 vs. 1566 ± 499 mm Hg/s, p < 0.05). Picrosirius red staining analysis also revealed a significant reduction of fibrosis in the HGF group. Conclusion: Based on the study findings, hepatocyte growth factor gene transfer can attenuate radiation-induced cardiac injury and can preserve cardiac function.

  7. Polonium 210Po activities in human blood of patients with ischaemic heart disease from Gdansk in Poland

    International Nuclear Information System (INIS)

    Alicja Borylo; Bogdan Skwarzec; Grzegorz Romanczyk; Janusz Siebert

    2013-01-01

    The determination of polonium 210 Po in human blood samples is presented and discussed in this paper. The human blood samples were collected from patients of Medical University of Gdansk with ischaemic heart disease (morbus ischaemicus cordis, MIC). The polonium concentrations in analyzed human blood samples are very differentiated. 210 Po is of particular interest in public health and although is present in the environment in extremely low amounts, it is easily bioaccumulated to the human body. The study shows that the amount of 210 Po that is incorporated into the human body depends on the food habits and some difference in its levels could be observed between smokers and non-smokers. (author)

  8. Polonium 210Po activities in human blood of patients with ischaemic heart disease from Gdańsk in Poland.

    Science.gov (United States)

    Boryło, Alicja; Skwarzec, Bogdan; Romańczyk, Grzegorz; Siebert, Janusz

    The determination of polonium 210 Po in human blood samples is presented and discussed in this paper. The human blood samples were collected from patients of Medical University of Gdańsk with ischaemic heart disease ( morbus ischaemicus cordis , MIC ). The polonium concentrations in analyzed human blood samples are very differentiated. 210 Po is of particular interest in public health and although is present in the environment in extremely low amounts, it is easily bioaccumulated to the human body. The study shows that the amount of 210 Po that is incorporated into the human body depends on the food habits and some difference in its levels could be observed between smokers and non-smokers.

  9. Human Heart Pulse Wave Responses Measured Simultaneously at Several Sensor Placements by Two MR-Compatible Fibre Optic Methods

    Directory of Open Access Journals (Sweden)

    Teemu Myllylä

    2012-01-01

    Full Text Available This paper presents experimental measurements conducted using two noninvasive fibre optic methods for detecting heart pulse waves in the human body. Both methods can be used in conjunction with magnetic resonance imaging (MRI. For comparison, the paper also performs an MRI-compatible electrocardiogram (ECG measurement. By the simultaneous use of different measurement methods, the propagation of pressure waves generated by each heart pulse can be sensed extensively in different areas of the human body and at different depths, for example, on the chest and forehead and at the fingertip. An accurate determination of a pulse wave allows calculating the pulse transit time (PTT of a particular heart pulse in different parts of the human body. This result can then be used to estimate the pulse wave velocity of blood flow in different places. Both measurement methods are realized using magnetic resonance-compatible fibres, which makes the methods applicable to the MRI environment. One of the developed sensors is an extraordinary accelerometer sensor, while the other one is a more common sensor based on photoplethysmography. All measurements, involving several test patients, were performed both inside and outside an MRI room. Measurements inside the MRI room were conducted using a 3-Tesla strength closed MRI scanner in the Department of Diagnostic Radiology at the Oulu University Hospital.

  10. Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts

    NARCIS (Netherlands)

    van der Velden, J.; Klein, L. J.; Zaremba, R.; Boontje, N. M.; Huybregts, M. A.; Stooker, W.; Eijsman, L.; de Jong, J. W.; Visser, C. A.; Visser, F. C.; Stienen, G. J.

    2001-01-01

    During ischemia, the intracellular calcium and inorganic phosphate (P(i)) concentrations rise and pH falls. We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the

  11. Social Control of Hypothalamus-Mediated Male Aggression.

    Science.gov (United States)

    Yang, Taehong; Yang, Cindy F; Chizari, M Delara; Maheswaranathan, Niru; Burke, Kenneth J; Borius, Maxim; Inoue, Sayaka; Chiang, Michael C; Bender, Kevin J; Ganguli, Surya; Shah, Nirao M

    2017-08-16

    How environmental and physiological signals interact to influence neural circuits underlying developmentally programmed social interactions such as male territorial aggression is poorly understood. We have tested the influence of sensory cues, social context, and sex hormones on progesterone receptor (PR)-expressing neurons in the ventromedial hypothalamus (VMH) that are critical for male territorial aggression. We find that these neurons can drive aggressive displays in solitary males independent of pheromonal input, gonadal hormones, opponents, or social context. By contrast, these neurons cannot elicit aggression in socially housed males that intrude in another male's territory unless their pheromone-sensing is disabled. This modulation of aggression cannot be accounted for by linear integration of environmental and physiological signals. Together, our studies suggest that fundamentally non-linear computations enable social context to exert a dominant influence on developmentally hard-wired hypothalamus-mediated male territorial aggression. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Effects of train noise and vibration on human heart rate during sleep: an experimental study.

    Science.gov (United States)

    Croy, Ilona; Smith, Michael G; Waye, Kerstin Persson

    2013-05-28

    Transportation of goods on railways is increasing and the majority of the increased numbers of freight trains run during the night. Transportation noise has adverse effects on sleep structure, affects the heart rate (HR) during sleep and may be linked to cardiovascular disease. Freight trains also generate vibration and little is known regarding the impact of vibration on human sleep. A laboratory study was conducted to examine how a realistic nocturnal railway traffic scenario influences HR during sleep. Case-control. Healthy participants. 24 healthy volunteers (11 men, 13 women, 19-28 years) spent six consecutive nights in the sleep laboratory. All participants slept during one habituation night, one control and four experimental nights in which train noise and vibration were reproduced. In the experimental nights, 20 or 36 trains with low-vibration or high-vibration characteristics were presented. Polysomnographical data and ECG were recorded. The train exposure led to a significant change of HR within 1 min of exposure onset (p=0.002), characterised by an initial and a delayed increase of HR. The high-vibration condition provoked an average increase of at least 3 bpm per train in 79% of the participants. Cardiac responses were in general higher in the high-vibration condition than in the low-vibration condition (p=0.006). No significant effect of noise sensitivity and gender was revealed, although there was a tendency for men to exhibit stronger HR acceleration than women. Freight trains provoke HR accelerations during sleep, and the vibration characteristics of the trains are of special importance. In the long term, this may affect cardiovascular functioning of persons living close to railways.

  13. Metabolic mystery: Aging, obesity, diabetes and ventromedial hypothalamus

    OpenAIRE

    Mobbs, Charles V.; Moreno, Cesar L.; Poplawski, Michael

    2013-01-01

    We propose that energy balance, glucose homeostasis, and aging are all regulated largely by the same nutrient-sensing neurons in the ventromedial hypothalamus (VMH)., Although the central role of these neurons in regulating energy balance is clear, their role in regulating glucose homeostasis has only become more clear recently. It is the latter function that may be most relevant to aging and lifespan, by controlling the rate of glucose metabolism. Specifically, glucose-sensing neurons in VMH...

  14. Increased heart rate variability but normal resting metabolic rate in hypocretin/orexin-deficient human narcolepsy.

    NARCIS (Netherlands)

    Fronczek, R.; Overeem, S.; Reijntjes, R.; Lammers, G.J.; Dijk, J.G.M.; Pijl, H.

    2008-01-01

    STUDY OBJECTIVES: We investigated autonomic balance and resting metabolic rate to explore their possible involvement in obesity in hypocretin/orexin-deficient narcoleptic subjects. METHODS: Resting metabolic rate (using indirect calorimetry) and variability in heart rate and blood pressure were

  15. Short-term fasting promotes insulin expression in rat hypothalamus.

    Science.gov (United States)

    Dakic, Tamara B; Jevdjovic, Tanja V; Peric, Mina I; Bjelobaba, Ivana M; Markelic, Milica B; Milutinovic, Bojana S; Lakic, Iva V; Jasnic, Nebojsa I; Djordjevic, Jelena D; Vujovic, Predrag Z

    2017-07-01

    In the hypothalamus, insulin takes on many roles involved in energy homoeostasis. Therefore, the aim of this study was to examine hypothalamic insulin expression during the initial phase of the metabolic response to fasting. Hypothalamic insulin content was assessed by both radioimmunoassay and Western blot. The relative expression of insulin mRNA was examined by qPCR. Immunofluorescence and immunohistochemistry were used to determine the distribution of insulin immunopositivity in the hypothalamus. After 6-h fasting, both glucose and insulin levels were decreased in serum but not in the cerebrospinal fluid. Our study showed for the first time that, while the concentration of circulating glucose and insulin decreased, both insulin mRNA expression and insulin content in the hypothalamic parenchyma were increased after short-term fasting. Increased insulin immunopositivity was detected specifically in the neurons of the hypothalamic periventricular nucleus and in the ependymal cells of fasting animals. These novel findings point to the complexity of mechanisms regulating insulin expression in the CNS in general and in the hypothalamus in particular. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  16. Sonic hedgehog signaling in the development of the mouse hypothalamus

    Directory of Open Access Journals (Sweden)

    Sandra eBlaess

    2015-01-01

    Full Text Available The expression pattern of Sonic Hedgehog (Shh in the developing hypothalamus changes over time. Shh is initially expressed in the prechordal mesoderm and later in the hypothalamic neuroepithelium-- first medially, and then in two off-medial domains. This dynamic expression suggests that Shh might regulate several aspects of hypothalamic development. To gain insight into them, lineage tracing, (conditional gene inactivation in mouse, in ovo loss- and gain-of-function approaches in chick and analysis of Shh expression regulation have been employed. We will focus on mouse studies and refer to chick and fish when appropriate to clarify. These studies show that Shh-expressing neuroepithelial cells serve as a signaling center for neighboring precursors, and give rise to most of the basal hypothalamus (tuberal and mammillary regions. Shh signaling is initially essential for hypothalamic induction. Later, Shh signaling from the neuroepithelium controls specification of the lateral hypothalamic area and growth-patterning coordination in the basal hypothalamus. To further elucidate the role of Shh in hypothalamic development, it will be essential to understand how Shh regulates the downstream Gli transcription factors.

  17. The characterisation of blood rotation in a human heart chamber based on statistical analysis of vorticity maps

    Science.gov (United States)

    Wong, Kelvin K. L.; Kelso, Richard M.; Worthley, Stephen G.; Sanders, Prashanthan; Mazumdar, Jagannath; Abbott, Derek

    2008-12-01

    Modelling of non-stationary cardiac structures is complicated by the complexity of their intrinsic and extrinsic motion. The first known study of haemodynamics due to the beating of heart was made by Leonardo Da Vinci, giving the idea of fluid-solid interaction by describing how vortices develop during cardiac structural interaction with the blood. Heart morphology affects in changes of cardio dynamics during the systolic and diastolic phrases. In a chamber of the heart, vortices are discovered to exist as the result of the unique morphological changes of the cardiac chamber wall by using flow-imaging techniques such as phase contrast magnetic resonance imaging. The first part of this paper attempts to quantify vortex characteristics by means of calculating vorticity numerically and devising two dimensional vortical flow maps. The technique relies on determining the properties of vorticity using a statistical quantification of the flow maps and comparison of these quantities based on different scenarios. As the characteristics of our vorticity maps vary depending on the phase of a cardiac cycle, there is a need for robust quantification method to analyse vorticity. In the second part of the paper, the approach is then utilised for examining vortices within the human right atrium. Our study has shown that a proper quantification of vorticity for the flow field can indicate the strength and number of vortices within a heart chamber.

  18. ALDH1A2 (RALDH2 genetic variation in human congenital heart disease

    Directory of Open Access Journals (Sweden)

    Mesquita Sonia MF

    2009-11-01

    Full Text Available Abstract Background Signaling by the vitamin A-derived morphogen retinoic acid (RA is required at multiple steps of cardiac development. Since conversion of retinaldehyde to RA by retinaldehyde dehydrogenase type II (ALDH1A2, a.k.a RALDH2 is critical for cardiac development, we screened patients with congenital heart disease (CHDs for genetic variation at the ALDH1A2 locus. Methods One-hundred and thirty-three CHD patients were screened for genetic variation at the ALDH1A2 locus through bi-directional sequencing. In addition, six SNPs (rs2704188, rs1441815, rs3784259, rs1530293, rs1899430 at the same locus were studied using a TDT-based association approach in 101 CHD trios. Observed mutations were modeled through molecular mechanics (MM simulations using the AMBER 9 package, Sander and Pmemd programs. Sequence conservation of observed mutations was evaluated through phylogenetic tree construction from ungapped alignments containing ALDH8 s, ALDH1Ls, ALDH1 s and ALDH2 s. Trees were generated by the Neighbor Joining method. Variations potentially affecting splicing mechanisms were cloned and functional assays were designed to test splicing alterations using the pSPL3 splicing assay. Results We describe in Tetralogy of Fallot (TOF the mutations Ala151Ser and Ile157Thr that change non-polar to polar residues at exon 4. Exon 4 encodes part of the highly-conserved tetramerization domain, a structural motif required for ALDH oligomerization. Molecular mechanics simulation studies of the two mutations indicate that they hinder tetramerization. We determined that the SNP rs16939660, previously associated with spina bifida and observed in patients with TOF, does not affect splicing. Moreover, association studies performed with classical models and with the transmission disequilibrium test (TDT design using single marker genotype, or haplotype information do not show differences between cases and controls. Conclusion In summary, our screen indicates that

  19. Heart Health - Brave Heart

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Cover Story Heart Health Brave Heart Past Issues / Winter 2009 Table of Contents For ... you can have a good life after a heart attack." Lifestyle Changes Surviving—and thriving—after such ...

  20. Pharmacological and physiological assessment of serotonin formation and degradation in isolated preparations from mouse and human hearts.

    Science.gov (United States)

    Gergs, Ulrich; Jung, Franziska; Buchwalow, Igor B; Hofmann, Britt; Simm, Andreas; Treede, Hendrik; Neumann, Joachim

    2017-12-01

    Using transgenic (TG) mice that overexpress the human serotonin (5-HT) 4a receptor specifically in cardiomyocytes, we wanted to know whether 5-HT can be formed and degraded in the mammalian heart and whether this can likewise lead to inotropic and chronotropic effects in this TG model. We noted that the 5-HT precursor 5-hydroxy-tryptophan (5-HTP) can exert inotropic and chronotropic effects in cardiac preparations from TG mice but not from wild-type (WT) mice; similar results were found in human atrial preparations as well as in intact TG animals using echocardiography. Moreover, by immunohistochemistry we could detect 5-HT metabolizing enzymes and 5-HT transporters in mouse hearts as well as in human atria. Hence, in the presence of an inhibitor of aromatic l-amino acid decarboxylase, the positive inotropic effects of 5-HTP were absent in TG and isolated human atrial preparations, and, moreover, inhibitors of enzymes involved in 5-HT degradation enhanced the efficacy of 5-HT in TG atria. A releaser of neurotransmitters increased inotropy in the isolated TG atrium, and this effect could be blocked by a 5-HT 4a receptor antagonist. Fluoxetine, an inhibitor of 5-HT uptake, elevated the potency of 5-HT to increase contractility in the TG atrium. In addition, inhibitors of organic cation and monoamine transporters apparently reduced the positive inotropic potency of 5-HT in the TG atrium. Hence, we tentatively conclude that a local production and degradation of 5-HT in the mammalian heart and more specifically in mammalian myocytes probably occurs. Conceivably, this formation of 5-HT and possibly impaired degradation may be clinically relevant in cases of unexplained tachycardia and other arrhythmias. NEW & NOTEWORTHY The present work suggests that inotropically active serotonin (5-HT) can be formed in the mouse and human heart and probably by cardiomyocytes themselves. Moreover, active degradation of 5-HT seems to occur in the mammalian heart. These findings may again

  1. Neuromyelitis optica spectrum disorder presenting with repeated hypersomnia due to involvement of the hypothalamus and hypothalamus-amygdala linkage.

    Science.gov (United States)

    Kume, Kodai; Deguchi, Kazushi; Ikeda, Kazuyo; Takata, Tadayuki; Kokudo, Yohei; Kamada, Masaki; Touge, Tetsuo; Takahashi, Toshiyuki; Kanbayashi, Takashi; Masaki, Tsutomu

    2015-06-01

    We report the case of a 46-year-old Japanese woman with neuromyelitis optica spectrum disorder presenting with repeated hypersomnia accompanied by decreased CSF orexin level. First episode associated with hypothalamic-pituitary dysfunction showed bilateral hypothalamic lesions that can cause secondary damage to the orexin neurons. The second episode associated with impaired memory showed a left temporal lesion involving the amygdala. The mechanism remains unknown, but the reduced blood flow in the hypothalamus ipsilateral to the amygdala lesion suggested trans-synaptic hypothalamic dysfunction secondary to the impaired amygdala. A temporal lesion involving the amygdala and hypothalamus could be responsible for hypersomnia due to neuromyelitis optica spectrum disorder. © The Author(s), 2015.

  2. Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.

    Directory of Open Access Journals (Sweden)

    Matthew A Schechter

    Full Text Available The molecular differences between ischemic (IF and non-ischemic (NIF heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins and 823 phosphopeptides (corresponding to 400 proteins from the unenriched and phospho-enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins exhibited a ≥ 2-fold alteration in phosphorylation state (p<0.05 when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure.

  3. The human heart and the circulatory system as an interesting interdisciplinary topic in lessons of physics and biology

    International Nuclear Information System (INIS)

    Volná, M; Látal, F; Kubínek, R; Richterek, L

    2014-01-01

    Many topics which are closely related can be found in the national curriculum of the Czech Republic for physics and biology. One of them is the heart and the circulatory system in the human body. This topic was examined cross curriculum, a teaching module was created and the topic was chosen for our research. The task was to determine if the students of bachelor study are aware of connections between physics and biology within this topic and whether we can help them effectively to describe the corresponding physics phenomena in the human body connected, for example, with a heart attack or with the measurement of blood pressure. In this paper, the heart and the circulatory system are presented as suitable topics for an interdisciplinary teaching module which includes both theoretical and experimental parts. The module was evaluated by a group of first-year undergraduate students of physics at the Faculty of Science, Palacký University. The acquired knowledge was compared with another control group through a test. The highest efficiency of the module was evaluated on the basis of questions that covered the calculation problems. (paper)

  4. Heart Attack Payment - National

    Data.gov (United States)

    U.S. Department of Health & Human Services — Payment for heart attack patients measure – national data. This data set includes national-level data for payments associated with a 30-day episode of care for heart...

  5. Heart Attack Payment - Hospital

    Data.gov (United States)

    U.S. Department of Health & Human Services — Payment for heart attack patients measure – provider data. This data set includes provider data for payments associated with a 30-day episode of care for heart...

  6. Heart Attack Payment - State

    Data.gov (United States)

    U.S. Department of Health & Human Services — Payment for heart attack patients measure – state data. This data set includes state-level data for payments associated with a 30-day episode of care for heart...

  7. A pilot investigation of the effect of extremely low frequency pulsed electromagnetic fields on humans' heart rate variability.

    Science.gov (United States)

    Baldi, Emilio; Baldi, Claudio; Lithgow, Brian J

    2007-01-01

    The question whether pulsed electromagnetic field (PEMF) can affect the heart rhythm is still controversial. This study investigates the effects on the cardiocirculatory system of ELF-PEMFs. It is a follow-up to an investigation made of the possible therapeutic effect ELF-PEMFs, using a commercially available magneto therapeutic unit, had on soft tissue injury repair in humans. Modulation of heart rate (HR) or heart rate variability (HRV) can be detected from changes in periodicity of the R-R interval and/or from changes in the numbers of heart-beat/min (bpm), however, R-R interval analysis gives only a quantitative insight into HRV. A qualitative understanding of HRV can be obtained considering the power spectral density (PSD) of the R-R intervals Fourier transform. In this study PSD is the investigative tool used, more specifically the low frequency (LF) PSD and high frequency (HF) PSD ratio (LF/HF) which is an indicator of sympatho-vagal balance. To obtain the PSD value, variations of the R-R time intervals were evaluated from a continuously recorded ECG. The results show a HR variation in all the subjects when they are exposed to the same ELF-PEMF. This variation can be detected by observing the change in the sympatho-vagal equilibrium, which is an indicator of modulation of heart activity. Variation of the LF/HF PSD ratio mainly occurs at transition times from exposure to nonexposure, or vice versa. Also of interest are the results obtained during the exposure of one subject to a range of different ELF-PEMFs. This pilot study suggests that a full investigation into the effect of ELF-PEMFs on the cardiovascular system is justified.

  8. Common variation in ISL1 confers genetic susceptibility for human congenital heart disease.

    Directory of Open Access Journals (Sweden)

    Kristen N Stevens

    Full Text Available Congenital heart disease (CHD is the most common birth abnormality and the etiology is unknown in the overwhelming majority of cases. ISLET1 (ISL1 is a transcription factor that marks cardiac progenitor cells and generates diverse multipotent cardiovascular cell lineages. The fundamental role of ISL1 in cardiac morphogenesis makes this an exceptional candidate gene to consider as a cause of complex congenital heart disease. We evaluated whether genetic variation in ISL1 fits the common variant-common disease hypothesis. A 2-stage case-control study examined 27 polymorphisms mapping to the ISL1 locus in 300 patients with complex congenital heart disease and 2,201 healthy pediatric controls. Eight genic and flanking ISL1 SNPs were significantly associated with complex congenital heart disease. A replication study analyzed these candidate SNPs in 1,044 new cases and 3,934 independent controls and confirmed that genetic variation in ISL1 is associated with risk of non-syndromic congenital heart disease. Our results demonstrate that two different ISL1 haplotypes contribute to risk of CHD in white and black/African American populations.

  9. Reconstruction and Visualization of Fiber and Laminar Structure in the Normal Human Heart from Ex Vivo DTMRI Data

    International Nuclear Information System (INIS)

    Rohmer, Damien; Sitek, Arkadiusz; Gullberg, Grant T.

    2006-01-01

    Background--The human heart is composed of a helical network of muscle fibers. These fibers are organized to form sheets that are separated by cleavage surfaces. This complex structure of fibers and sheets is responsible for the orthotropic mechanical properties of cardiac muscle. The understanding of the configuration of the 3D fiber and sheet structure is important for modeling the mechanical and electrical properties of the heart and changes in this configuration maybe of significant importance to understand the remodeling after myocardial infarction. Methods--Anisotropic least square filtering followed by fiber and sheet tracking techniques were applied to Diffusion Tensor Magnetic Resonance Imaging (DTMRI) data of the excised human heart. The fiber configuration was visualized by using thin tubes to increase 3-dimensional visual perception of the complex structure. The sheet structures were reconstructed from the DTMRI data, obtaining surfaces that span the wall from the endo- to the epicardium. All visualizations were performed using the high-quality ray-tracing software POV-Ray. Results--The fibers are shown to lie in sheets that have concave or convex transmural structure which correspond to histological studies published in the literature. The fiber angles varied depending on the position between the epi- and endocardium. The sheets had a complex structure that depended on the location within the myocardium. In the apex region the sheets had more curvature. Conclusions--A high-quality visualization algorithm applied to demonstrated high quality DTMRI data is able to elicit the comprehension of the complex 3 dimensional structure of the fibers and sheets in the heart

  10. Myocardial blood flow and its transit time, oxygen utilization, and efficiency of highly endurance-trained human heart.

    Science.gov (United States)

    Heinonen, Ilkka; Kudomi, Nobuyuki; Kemppainen, Jukka; Kiviniemi, Antti; Noponen, Tommi; Luotolahti, Matti; Luoto, Pauliina; Oikonen, Vesa; Sipilä, Hannu T; Kopra, Jaakko; Mononen, Ilkka; Duncker, Dirk J; Knuuti, Juhani; Kalliokoski, Kari K

    2014-07-01

    Highly endurance-trained athlete's heart represents the most extreme form of cardiac adaptation to physical stress, but its circulatory alterations remain obscure. In the present study, myocardial blood flow (MBF), blood mean transit time (MTT), oxygen extraction fraction (OEF) and consumption (MVO2), and efficiency of cardiac work were quantified in highly trained male endurance athletes and control subjects at rest and during supine cycling exercise using [(15)O]-labeled radiotracers and positron emission tomography. Heart rate and MBF were lower in athletes both at rest and during exercise. OEF increased in response to exercise in both groups, but was higher in athletes (70 ± 21 vs. 63 ± 11 % at rest and 86 ± 13 vs. 73 ± 10 % during exercise). MTT was longer and vascular resistance higher in athletes both at rest and during exercise, but arterial content of 2,3-diphosphoglycerate (oxygen affinity) was unchanged. MVO2 per gram of myocardium trended (p = 0.08) lower in athletes both at rest and during exercise, while myocardial efficiency of work and MVO2 per beat were not different between groups. Arterial levels of free fatty acids were ~twofold higher in athletes likely leading to higher myocardial fatty acid oxidation and hence oxygen cost, which may have blunted the bradycardia-induced decrease in MVO2. Finally, the observed group differences in MBF, OEF, MTT and vascular resistance remained significant also after they were controlled for differences in MVO2. In conclusion, in highly endurance-trained human heart, increased myocardial blood transition time enables higher oxygen extraction levels with a lower myocardial blood flow and higher vascular resistance. These physiological adaptations to exercise training occur independently of the level of oxygen consumption and together with training-induced bradycardia may serve as mechanisms to increase functional reserve of the human heart.

  11. Bleeding-Heart Liberals and Hard-Hearted Conservatives: Subtle Political Dehumanization Through Differential Attributions of Human Nature and Human Uniqueness Traits

    Directory of Open Access Journals (Sweden)

    Jarret T. Crawford

    2013-10-01

    Full Text Available This research demonstrated that human nature (HN and human uniqueness (HU traits capture the content of Americans’ stereotypes about liberals and conservatives, respectively. Consistent with expectations derived from dehumanization theory, people more strongly associated HN traits with liberals than with conservatives, and more strongly associated HU traits with conservatives than with liberals. A trait × target ideology × perceiver ideology × trait valence interaction suggested that both liberals and conservatives more strongly associated their ingroup with stereotype-consistent positive traits, and their outgroup with stereotype-consistent negative traits. Mediation analyses revealed that outgroup antipathy, but not ingroup liking, explained the relationship between ideology and political outgroup dehumanization. Finally, humanness traits captured subtle differences in political stereotype content not captured with the warmth and competence dimensions derived from the stereotype content model. Together, these results indicate that differential attributions of HN and HU traits capture political stereotype content and function to subtly dehumanize one’s political opponents.

  12. Growth and remodeling play opposing roles during postnatal human heart valve development.

    Science.gov (United States)

    Oomen, Pim J A; Holland, Maria A; Bouten, Carlijn V C; Kuhl, Ellen; Loerakker, Sandra

    2018-01-19

    Tissue growth and remodeling are known to govern mechanical homeostasis in biological tissue, but their relative contributions to homeostasis remain unclear. Here, we use mechanical models, fueled by experimental findings, to demonstrate that growth and remodeling have different effects on heart valve stretch homeostasis during physiological postnatal development. Two developmental stages were considered: early-stage (from infant to adolescent) and late-stage (from adolescent to adult) development. Our models indicated that growth and remodeling play opposing roles in preserving tissue stretch and with time. During early-stage development, excessive tissue stretch was decreased by tissue growth and increased by remodeling. In contrast, during late-stage development tissue stretch was decreased by remodeling and increased by growth. Our findings contribute to an improved understanding of native heart valve adaptation throughout life, and are highly relevant for the development of tissue-engineered heart valves.

  13. Interactions between Activation and Repolarization Restitution Properties in the Intact Human Heart: In-Vivo Whole-Heart Data and Mathematical Description.

    Directory of Open Access Journals (Sweden)

    Michele Orini

    Full Text Available The restitution of the action potential duration (APDR and conduction velocity (CVR are mechanisms whereby cardiac excitation and repolarization adapt to changes in heart rate. They modulate the vulnerability to dangerous arrhythmia, but the mechanistic link between restitution and arrhythmogenesis remains only partially understood.This paper provides an experimental and theoretical study of repolarization and excitation restitution properties and their interactions in the intact human epicardium. The interdependence between excitation and repolarization dynamic is studied in 8 patients (14 restitution protocols, 1722 restitution curves undergoing global epicardial mapping with multi-electrode socks before open heart surgery. A mathematical description of the contribution of both repolarization and conduction dynamics to the steepness of the APDR slope is proposed.This study demonstrates that the APDR slope is a function of both activation and repolarization dynamics. At short cycle length, conduction delay significantly increases the APDR slope by interacting with the diastolic interval. As predicted by the proposed mathematical formulation, the APDR slope was more sensitive to activation time prolongation than to the simultaneous shortening of repolarization time. A steep APDR slope was frequently identified, with 61% of all cardiac sites exhibiting an APDR slope > 1, suggesting that a slope > 1 may not necessarily promote electrical instability in the human epicardium. APDR slope did not change for different activation or repolarization times, and it was not a function of local baseline APD. However, it was affected by the spatial organization of electrical excitation, suggesting that in tissue APDR is not a unique function of local electrophysiological properties. Spatial heterogeneity in both activation and repolarization restitution contributed to the increase in the modulated dispersion of repolarization, which for short cycle length was

  14. Heart MRI

    Science.gov (United States)

    Magnetic resonance imaging - cardiac; Magnetic resonance imaging - heart; Nuclear magnetic resonance - cardiac; NMR - cardiac; MRI of the heart; Cardiomyopathy - MRI; Heart failure - MRI; Congenital heart disease - MRI

  15. Vortex ring behavior provides the epigenetic blueprint for the human heart.

    Science.gov (United States)

    Arvidsson, Per M; Kovács, Sándor J; Töger, Johannes; Borgquist, Rasmus; Heiberg, Einar; Carlsson, Marcus; Arheden, Håkan

    2016-02-26

    The laws of fluid dynamics govern vortex ring formation and precede cardiac development by billions of years, suggesting that diastolic vortex ring formation is instrumental in defining the shape of the heart. Using novel and validated magnetic resonance imaging measurements, we show that the healthy left ventricle moves in tandem with the expanding vortex ring, indicating that cardiac form and function is epigenetically optimized to accommodate vortex ring formation for volume pumping. Healthy hearts demonstrate a strong coupling between vortex and cardiac volumes (R(2) = 0.83), but this optimized phenotype is lost in heart failure, suggesting restoration of normal vortex ring dynamics as a new, and possibly important consideration for individualized heart failure treatment. Vortex ring volume was unrelated to early rapid filling (E-wave) velocity in patients and controls. Characteristics of vortex-wall interaction provide unique physiologic and mechanistic information about cardiac diastolic function that may be applied to guide the design and implantation of prosthetic valves, and have potential clinical utility as therapeutic targets for tailored medicine or measures of cardiac health.

  16. Modeling the Human Scarred Heart In Vitro: Toward New Tissue Engineered Models.

    Science.gov (United States)

    Deddens, Janine C; Sadeghi, Amir Hossein; Hjortnaes, Jesper; van Laake, Linda W; Buijsrogge, Marc; Doevendans, Pieter A; Khademhosseini, Ali; Sluijter, Joost P G

    2017-02-01

    Cardiac remodeling is critical for effective tissue healing, however, excessive production and deposition of extracellular matrix components contribute to scarring and failing of the heart. Despite the fact that novel therapies have emerged, there are still no lifelong solutions for this problem. An urgent need exists to improve the understanding of adverse cardiac remodeling in order to develop new therapeutic interventions that will prevent, reverse, or regenerate the fibrotic changes in the failing heart. With recent advances in both disease biology and cardiac tissue engineering, the translation of fundamental laboratory research toward the treatment of chronic heart failure patients becomes a more realistic option. Here, the current understanding of cardiac fibrosis and the great potential of tissue engineering are presented. Approaches using hydrogel-based tissue engineered heart constructs are discussed to contemplate key challenges for modeling tissue engineered cardiac fibrosis and to provide a future outlook for preclinical and clinical applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Modeling the Human Scarred Heart In Vitro : Toward New Tissue Engineered Models

    NARCIS (Netherlands)

    Deddens, Janine C.; Sadeghi, Amir Hossein; Hjortnaes, Jesper; van Laake, Linda W.; Buijsrogge, Marc; Doevendans, Pieter A.; Khademhosseini, Ali; Sluijter, Joost P G

    2017-01-01

    Cardiac remodeling is critical for effective tissue healing, however, excessive production and deposition of extracellular matrix components contribute to scarring and failing of the heart. Despite the fact that novel therapies have emerged, there are still no lifelong solutions for this problem. An

  18. Decreased mitochondrial oxidative phosphorylation capacity in the human heart with left ventricular systolic dysfunction

    DEFF Research Database (Denmark)

    Stride, Nis; Larsen, Steen; Hey-Mogensen, Martin

    2013-01-01

    Heart failure (HF) with left ventricular systolic dysfunction (LVSD) is associated with a shift in substrate utilization and a compromised energetic state. Whether these changes are connected with mitochondrial dysfunction is not known. We hypothesized that the cardiac phenotype in LVSD could...

  19. Variation in tissue outcome of ovine and human engineered heart valve constructs : relevance for tissue engineering

    NARCIS (Netherlands)

    Geemen, van D.; Driessen - Mol, A.; Grootzwagers, L.G.M.; Soekhradj - Soechit, R.S.; Riem Vis, P.W.; Baaijens, F.P.T.; Bouten, C.V.C.

    AIM: Clinical application of tissue engineered heart valves requires precise control of the tissue culture process to predict tissue composition and mechanical properties prior to implantation, and to understand the variation in tissue outcome. To this end we investigated cellular phenotype and

  20. Hydrocortisone at stress-associated concentrations helps maintain human heart rate variability during subsequent endotoxin challenge.

    Science.gov (United States)

    Rassias, Athos J; Guyre, Paul M; Yeager, Mark P

    2011-12-01

    We evaluated the differential impact of stress-associated vs high pharmacologic concentrations of hydrocortisone pretreatment on heart rate variability (HRV) during a subsequent systemic inflammatory stimulus. Healthy volunteers were randomized to receive placebo (Control) and hydrocortisone at 1.5 μg/kg per minute (STRESS) or at 3.0 μg/kg per minute (PHARM) as a 6-hour infusion. The STRESS dose was chosen to replicate the condition of physiologic adrenal cortical output during acute systemic stress. The PHARM dose was chosen to induce a supraphysiologic concentration of cortisol. The next day, all subjects received 2 ng/kg Escherichia coli endotoxin (lipopolysaccharide). Heart rate variability was analyzed with the statistic approximate entropy (ApEn). A lower ApEn correlates with decreased HRV. At the 3-hour nadir, the decrease in ApEn in the STRESS group was significantly less compared to placebo (P statistically different. We also found that the maximal decrease in ApEn preceded maximal increase in heart rate in all groups. The decrease in R-R interval was maximal at 4 hours, whereas the ApEn nadir was 1 hour earlier at 3 hours. Pretreatment with a stress dose of hydrocortisone but not a higher pharmacologic dose maintained a significantly higher ApEn after endotoxin exposure when compared to a placebo. In addition, decreases in ApEn preceded increases in heart rate. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Transcriptome analyses identify five transcription factors differentially expressed in the hypothalamus of post- versus prepubertal Brahman heifers.

    Science.gov (United States)

    Fortes, M R S; Nguyen, L T; Weller, M M D C A; Cánovas, A; Islas-Trejo, A; Porto-Neto, L R; Reverter, A; Lehnert, S A; Boe-Hansen, G B; Thomas, M G; Medrano, J F; Moore, S S

    2016-09-01

    Puberty onset is a developmental process influenced by genetic determinants, environment, and nutrition. Mutations and regulatory gene networks constitute the molecular basis for the genetic determinants of puberty onset. The emerging knowledge of these genetic determinants presents opportunities for innovation in the breeding of early pubertal cattle. This paper presents new data on hypothalamic gene expression related to puberty in (Brahman) in age- and weight-matched heifers. Six postpubertal heifers were compared with 6 prepubertal heifers using whole-genome RNA sequencing methodology for quantification of global gene expression in the hypothalamus. Five transcription factors (TF) with potential regulatory roles in the hypothalamus were identified in this experiment: , , , , and . These TF genes were significantly differentially expressed in the hypothalamus of postpubertal versus prepubertal heifers and were also identified as significant according to the applied regulatory impact factor metric ( cancer and developmental processes. Mutations in were associated with puberty in humans. Mutations in these TF, together with other genetic determinants previously discovered, could be used in genomic selection to predict the genetic merit of cattle (i.e., the likelihood of the offspring presenting earlier than average puberty for Brahman). Knowledge of key mutations involved in genetic traits is an advantage for genomic prediction because it can increase its accuracy.

  2. Developmental exposure to fluoxetine modulates the serotonin system in hypothalamus.

    Directory of Open Access Journals (Sweden)

    Cecilia Berg

    Full Text Available The selective serotonin reuptake inhibitor (SSRI fluoxetine (FLU, Prozac® is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of serotonin in brain development and its cross-talk with sex hormone function, we investigated effects of developmental exposure to pharmacologically relevant concentrations of FLU (3 and 30 nM (measured on brain neurotransmitter levels, gonadal differentiation, aromatase activity in brain and gonads, and the thyroid system, using the Xenopus tropicalis model. Tadpoles were chronically exposed (8 weeks until metamorphosis. At metamorphosis brains were cryosectioned and levels of serotonin, dopamine, norepinephrine, and their metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in discrete regions (telencephalon, hypothalamus and the reticular formation of the cryosections using high-performance liquid chromatography. Exposure to 30 nM FLU increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus compared with controls. FLU exposure did not affect survival, time to metamorphosis, thyroid histology, gonadal sex differentiation, or aromatase activity implying that the effect on the serotonergic neurotransmitter system in the hypothalamus region was specific. The FLU concentration that impacted the serotonin system is lower than the concentration measured in umbilical cord serum, suggesting that the serotonin system of the developing brain is highly sensitive to in utero exposure to FLU. To our knowledge this is the first study showing effects of developmental FLU exposure on brain neurochemistry. Given that SSRIs are present in the aquatic environment the current results warrant further investigation into the neurobehavioral effects of SSRIs in aquatic wildlife.

  3. Seasonal superoxide overproduction and endothelial activation in guinea-pig heart; seasonal oxidative stress in rats and humans.

    Science.gov (United States)

    Konior, Anna; Klemenska, Emilia; Brudek, Magdalena; Podolecka, Ewa; Czarnowska, Elżbieta; Beręsewicz, Andrzej

    2011-04-01

    Seasonality in endothelial dysfunction and oxidative stress was noted in humans and rats, suggesting it is a common phenomenon of a potential clinical relevance. We aimed at studying (i) seasonal variations in cardiac superoxide (O(2)(-)) production in rodents and in 8-isoprostane urinary excretion in humans, (ii) the mechanism of cardiac O(2)(-) overproduction occurring in late spring/summer months in rodents, (iii) whether this seasonal O(2)(-)-overproduction is associated with a pro-inflammatory endothelial activation, and (iv) how the summer-associated changes compare to those caused by diabetes, a classical cardiovascular risk factor. Langendorff-perfused guinea-pig and rat hearts generated ~100% more O(2)(-), and human subjects excreted 65% more 8-isoprostane in the summer vs. other seasons. Inhibitors of NADPH oxidase, xanthine oxidase, and NO synthase inhibited the seasonal O(2)(-)-overproduction. In the summer vs. other seasons, cardiac NADPH oxidase and xanthine oxidase activity, and protein expression were increased, the endothelial NO synthase and superoxide dismutases were downregulated, and, in guinea-pig hearts, adhesion molecules upregulation and the endothelial glycocalyx destruction associated these changes. In guinea-pig hearts, the summer and a streptozotocin-induced diabetes mediated similar changes, yet, more severe endothelial activation associated the diabetes. These findings suggest that the seasonal oxidative stress is a common phenomenon, associated, at least in guinea-pigs, with the endothelial activation. Nonetheless, its biological meaning (regulatory vs. deleterious) remains unclear. Upregulated NADPH oxidase and xanthine oxidase and uncoupled NO synthase are the sources of the seasonal O(2)(-)-overproduction. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Substance P release from rat hypothalamus and spinal cord

    International Nuclear Information System (INIS)

    Kronheim, S.; Sheppard, M.C.; Pimstone, B.L.

    1980-01-01

    A specific and sensitive radioimmunoassay for substance P has been developed to study the release of immunoreactive substance P from incubated rat hypothalamus and rat spinal cord in vitro. Release was significantly increased in the presence of two depolarizing stimuli (56 mM KCl and 75 μM veratrine) and was calcium-dependent. The released immunoreactive material diluted in parallel with synthetic substance P and showed close identity on Sephadex chromatography. A neuromodulator role for the peptide in the central nervous system is suggested

  5. Reconstruction and Visualization of Fiber and Laminar Structure inthe Normal Human Heart from Ex Vivo DTMRI Data

    Energy Technology Data Exchange (ETDEWEB)

    Rohmer, Damien; Sitek, Arkadiusz; Gullberg, Grant T.

    2006-12-18

    Background - The human heart is composed of a helicalnetwork of muscle fibers. These fibers are organized to form sheets thatare separated by cleavage surfaces. This complex structure of fibers andsheets is responsible for the orthotropic mechanical properties ofcardiac muscle. The understanding of the configuration of the 3D fiberand sheet structure is important for modeling the mechanical andelectrical properties of the heart and changes in this configuration maybe of significant importance to understand the remodeling aftermyocardial infarction.Methods - Anisotropic least square filteringfollowed by fiber and sheet tracking techniques were applied to DiffusionTensor Magnetic Resonance Imaging (DTMRI) data of the excised humanheart. The fiber configuration was visualized by using thin tubes toincrease 3-dimensional visual perception of the complex structure. Thesheet structures were reconstructed from the DTMRI data, obtainingsurfaces that span the wall from the endo- to the epicardium. Allvisualizations were performed using the high-quality ray-tracing softwarePOV-Ray. Results - The fibers are shown to lie in sheets that haveconcave or convex transmural structure which correspond to histologicalstudies published in the literature. The fiber angles varied depending onthe position between the epi- and endocardium. The sheets had a complexstructure that depended on the location within the myocardium. In theapex region the sheets had more curvature. Conclusions - A high-qualityvisualization algorithm applied to demonstrated high quality DTMRI datais able to elicit the comprehension of the complex 3 dimensionalstructure of the fibers and sheets in the heart.

  6. Anizotropy characteristics of the left ventricle false chordae tendineae as one of varieties of myoendocardial formations of the human heart

    Science.gov (United States)

    Gavrylyak, M. S.; Malyk, Yu. Yu.; Tsyhykalo, O. V.; Semeniuk, T. O.; Penteleichuk, N. P.; Burkovets, D. N.; Yermolenko, S. B.

    2018-01-01

    The morphological and anizotropy characteristics of the left ventricle false chordae tendineae of human heart in the aspect of their anisotropic properties using spectroscopic-polarization methods was studied. There are given the results of statistical correlation structure of the spectral dependence of the two-dimensional Mueller matrix elements and phase shifts of histological sections of different morphological structure and physiological state. The relationship between the distribution of orientations of the optical axes birefringent miozyn fibrils with a set of statistical moments that characterize the distributions of Mueller matrix elements in different spectral ranges and half-width corresponding autocorrelation functions are established.

  7. Hypoxia changes the expression of the epidermal growth factor (EGF) system in human hearts and cultured cardiomyocytes

    DEFF Research Database (Denmark)

    Munk, Mathias; Memon, Ashfaque Ahmed; Goetze, Jens Peter

    2012-01-01

    by treatment with trastuzumab (20 nM). This resulted in inhibition of cardiomyocyte proliferation, but interestingly only in hypoxic cells. Co-treatment of HL-1 cells with HB-EGF (10 nM) but not with NRG-1 (5 ng/ml) rescued the cardiomyocytes from HER2 inhibition. HL-1 cardiomyocytes exposed to hypoxia...... revealed nuclear translocation of activated MAPK and the activity of this downstream signaling molecule was decreased by HER2 inhibition (20 nM trastuzumab), and re-established by HB-EGF (10 nM). CONCLUSIONS/SIGNIFICANCE: Hypoxia in the human heart alters the expression of the EGF system. Mimicking the HER...

  8. Evaluation of methods for MR imaging of human right ventricular heart volumes and mass

    International Nuclear Information System (INIS)

    Jauhiainen, T.; Jaervinen, V.M.; Hekali, P.E.

    2002-01-01

    Purpose: To assess the utility of two different imaging directions in the evaluation of human right ventricular (RV) heart volumes and mass with MR imaging; to compare breath-hold vs. non-breath-hold imaging in volume analysis; and to compare turbo inversion recovery imaging (TIR) with gradient echo imaging in RV mass measurement. Material and Methods: We examined 12 healthy volunteers (age 27-59 years). Breath-hold gradient echo MR imaging was performed in two imaging planes: 1) perpendicular to the RV inflow tract (RVIT view), and 2) in the transaxial view (TA view). The imaging was repeated in the TA view while the subjects were breathing freely. To analyze RV mass using TIR images, the RV was again imaged at end-diastole using the two views. The RV end-diastolic cavity (RVEDV) and muscle volume as well as end-systolic cavity volume (RVESV) were determined with the method of discs. All measurements were done blindly twice to assess repeatability of image analysis. To assess reproducibility of the measurements, 6 of the subjects were imaged twice at an interval of 5-9 weeks. Results: RVEDV averaged 133.2 ml, RVESV 61.5 ml and the RVmass 46.2 g in the RVIT view and 119.9 ml, 56.9 ml and 38.3 g in the TA view, respectively. The volumes obtained with breath-holding were slightly but not significantly smaller than the volumes obtained during normal breathing. There were no marked differences in the RV muscle mass obtained with gradient echo imaging compared to TIR imaging in either views. Repeatability of volume analysis was better in TA than RVIT view: the mean differences were 0.7±4.0 ml and 5.4±14.0 ml in end-diastole and 1.6±3.1 ml and 1.5±13.9 ml in end-systole, respectively. Repeatability of mass analysis was good in both TIR and cine images in the RVIT view but slightly better in TIR images: 0.5±2.4 g compared to 0.8±2.9 g in cine images. Reproducibility of imaging was good, mean differences for RVEDV and RVESV were 1.0±4.8 ml and 0.8±2.8 ml

  9. Distinct types of feeding related neurons in mouse hypothalamus

    Directory of Open Access Journals (Sweden)

    Yan eTang

    2016-05-01

    Full Text Available The last two decades of research provided evidence for a substantial heterogeneity among feeding-related neurons (FRNs in the hypothalamus. However, it remains unclear how FRNs differ in their firing patterns during food intake. Here, we investigated the relationship between the activity of neurons in mouse hypothalamus and their feeding behavior. Using tetrode-based in vivo recording technique, we identified various firing patterns of hypothalamic FRNs, which, after the initiation of food intake, can be sorted into four types: sharp increase (type I, slow increase (type II, sharp decrease (type III and sustained decrease (type IV of firing rates. The feeding-related firing response of FRNs was rigidly related to the duration of food intake and, to a less extent, associated with the type of food. The majority of these FRNs responded to glucose and leptin and exhibited electrophysiological characteristics of putative GABAergic neurons. In conclusion, our study demonstrated the diversity of neurons in the complex hypothalamic network coordinating food intake.

  10. Gallium-67 imaging in human heart transplantation: correlation with endomyocardial biopsy

    International Nuclear Information System (INIS)

    Meneguetti, J.C.; Camargo, E.E.; Soares, J. Jr.

    1987-01-01

    Endomyocardial biopsy seems to be the most accurate method to use for diagnosis and follow-up of acute rejection of the transplanted heart. This investigation compared a noninvasive procedure, gallium-67 imaging, with endomyocardial biopsy in the detection of acute rejection in heart transplantation. Seven male patients (aged 41 to 54 years) sequentially had 46 gallium-67 scintigrams and 46 endomyocardial biopsies between 1 week and 8 months after transplantation. Both studies were obtained in the same day, 48 hours after the administration of an intravenous injection of gallium-67 citrate. Cardiac uptake was graded as negative, mild, moderate, and marked according to an increasing count ratio with rib and sternal uptakes. Histologic findings were graded as negative, mild acute rejection, moderate acute rejection, severe acute rejection, resolving rejection, and nonspecific reaction. Negative biopsies were not found with moderate uptake, and neither moderate nor severe acute rejection were found with negative scintigrams. Imaging sensitivity was 83% with 17% false negatives and 9% false positives. Of seven studies with moderate uptake, five showed moderate acute rejection, and the patients had specific therapy with a decline in uptake, which correlated with resolving rejection. It is conceivable that in the future this technique may be used as a screening procedure for sequential endomyocardial biopsies in the follow-up of heart transplant patients

  11. The Heart of Coaching

    Science.gov (United States)

    Docheff, Dennis M.; Gerdes, Dan

    2015-01-01

    This article challenges coaches to address the more personal, human elements of coaching--the HEART of coaching. While there is much research on numerous aspects of coaching, this article provides ideas that make a lasting impact on the hearts of athletes. Using HEART as an acronym, five elements of effective coaching are presented: Humility,…

  12. Coping with continuous human disturbance in the wild: insights from penguin heart rate response to various stressors.

    Science.gov (United States)

    Viblanc, Vincent A; Smith, Andrew D; Gineste, Benoit; Groscolas, René

    2012-07-11

    A central question for ecologists is the extent to which anthropogenic disturbances (e.g. tourism) might impact wildlife and affect the systems under study. From a research perspective, identifying the effects of human disturbance caused by research-related activities is crucial in order to understand and account for potential biases and derive appropriate conclusions from the data. Here, we document a case of biological adjustment to chronic human disturbance in a colonial seabird, the king penguin (Aptenodytes patagonicus), breeding on remote and protected islands of the Southern ocean. Using heart rate (HR) as a measure of the stress response, we show that, in a colony with areas exposed to the continuous presence of humans (including scientists) for over 50 years, penguins have adjusted to human disturbance and habituated to certain, but not all, types of stressors. When compared to birds breeding in relatively undisturbed areas, birds in areas of high chronic human disturbance were found to exhibit attenuated HR responses to acute anthropogenic stressors of low-intensity (i.e. sounds or human approaches) to which they had been subjected intensely over the years. However, such attenuation was not apparent for high-intensity stressors (i.e. captures for scientific research) which only a few individuals experience each year. Habituation to anthropogenic sounds/approaches could be an adaptation to deal with chronic innocuous stressors, and beneficial from a research perspective. Alternately, whether penguins have actually habituated to anthropogenic disturbances over time or whether human presence has driven the directional selection of human-tolerant phenotypes, remains an open question with profound ecological and conservation implications, and emphasizes the need for more knowledge on the effects of human disturbance on long-term studied populations.

  13. Coping with continuous human disturbance in the wild: insights from penguin heart rate response to various stressors

    Directory of Open Access Journals (Sweden)

    Viblanc Vincent A

    2012-07-01

    Full Text Available Abstract Background A central question for ecologists is the extent to which anthropogenic disturbances (e.g. tourism might impact wildlife and affect the systems under study. From a research perspective, identifying the effects of human disturbance caused by research-related activities is crucial in order to understand and account for potential biases and derive appropriate conclusions from the data. Results Here, we document a case of biological adjustment to chronic human disturbance in a colonial seabird, the king penguin (Aptenodytes patagonicus, breeding on remote and protected islands of the Southern ocean. Using heart rate (HR as a measure of the stress response, we show that, in a colony with areas exposed to the continuous presence of humans (including scientists for over 50 years, penguins have adjusted to human disturbance and habituated to certain, but not all, types of stressors. When compared to birds breeding in relatively undisturbed areas, birds in areas of high chronic human disturbance were found to exhibit attenuated HR responses to acute anthropogenic stressors of low-intensity (i.e. sounds or human approaches to which they had been subjected intensely over the years. However, such attenuation was not apparent for high-intensity stressors (i.e. captures for scientific research which only a few individuals experience each year. Conclusions Habituation to anthropogenic sounds/approaches could be an adaptation to deal with chronic innocuous stressors, and beneficial from a research perspective. Alternately, whether penguins have actually habituated to anthropogenic disturbances over time or whether human presence has driven the directional selection of human-tolerant phenotypes, remains an open question with profound ecological and conservation implications, and emphasizes the need for more knowledge on the effects of human disturbance on long-term studied populations.

  14. Heart murmurs

    Science.gov (United States)

    Chest sounds - murmurs; Heart sounds - abnormal; Murmur - innocent; Innocent murmur; Systolic heart murmur; Diastolic heart murmur ... The heart has 4 chambers: Two upper chambers (atria) Two lower chambers (ventricles) The heart has valves that close ...

  15. Human torso phantom for imaging of heart with realistic modes of cardiac and respiratory motion

    Science.gov (United States)

    Boutchko, Rostyslav; Balakrishnan, Karthikayan; Gullberg, Grant T; O& #x27; Neil, James P

    2013-09-17

    A human torso phantom and its construction, wherein the phantom mimics respiratory and cardiac cycles in a human allowing acquisition of medical imaging data under conditions simulating patient cardiac and respiratory motion.

  16. Androstenol--a steroid derived odor activates the hypothalamus in women.

    Directory of Open Access Journals (Sweden)

    Ivanka Savic

    Full Text Available BACKGROUND: Whether pheromone signaling exists in humans is still a matter of intense discussion. In the present study we tested if smelling of Androstenol, a steroid produced by the human body and reported to affect human behavior, may elicit cerebral activation. A further issue was to evaluate whether the pattern of activation resembles the pattern of common odors. METHODOLOGY: PET measurements of regional cerebral blood flow (rCBF were conducted in 16 healthy heterosexual women during passive smelling of Androstenol, four ordinary odors (OO, and odorless air (the base line condition. PRINCIPAL FINDINGS: Smelling Androstenol caused activation of a portion of the hypothalamus, which according to animal data mediates the pheromone triggered mating behavior. Smelling of OO, on the other hand, engaged only the classical olfactory regions (the piriform cortex, lateral amygdala, anterior insular and anterior cingulate cortex. CONCLUSIONS: The observed pattern of activation is very similar to the pattern previously detected with 4,16-androstadien-3-one in heterosexual females. It suggests that several compounds released by human body may activate cerebral networks involved in human reproduction.

  17. Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis

    Czech Academy of Sciences Publication Activity Database

    Melenovský, V.; Petrák, J.; Mráček, Tomáš; Beneš, J.; Borlaug, B. A.; Nůsková, Hana; Pluháček, T.; Špatenka, J.; Kovalčíková, Jana; Drahota, Zdeněk; Kautzner, J.; Pirk, J.; Houštěk, Josef

    2017-01-01

    Roč. 19, č. 4 (2017), s. 522-530 ISSN 1388-9842 R&D Projects: GA ČR(CZ) GB14-36804G; GA MZd(CZ) NT14050; GA MŠk(CZ) LQ1604; GA MZd NT14250; GA MŠk(CZ) ED1.1.00/02.0109; GA MZd(CZ) NV16-27496A Institutional support: RVO:67985823 Keywords : heart failure * mitochondria * iron deficiency * bioenergetics * metabolism * reactive oxygen species Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 6.968, year: 2016

  18. Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure.

    Science.gov (United States)

    Marques, Francine Z; Prestes, Priscilla R; Byars, Sean G; Ritchie, Scott C; Würtz, Peter; Patel, Sheila K; Booth, Scott A; Rana, Indrajeetsinh; Minoda, Yosuke; Berzins, Stuart P; Curl, Claire L; Bell, James R; Wai, Bryan; Srivastava, Piyush M; Kangas, Antti J; Soininen, Pasi; Ruohonen, Saku; Kähönen, Mika; Lehtimäki, Terho; Raitoharju, Emma; Havulinna, Aki; Perola, Markus; Raitakari, Olli; Salomaa, Veikko; Ala-Korpela, Mika; Kettunen, Johannes; McGlynn, Maree; Kelly, Jason; Wlodek, Mary E; Lewandowski, Paul A; Delbridge, Lea M; Burrell, Louise M; Inouye, Michael; Harrap, Stephen B; Charchar, Fadi J

    2017-06-14

    Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants. We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2 -knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2 -knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis -eQTL for LCN2 expression. Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  19. Comprehensive metabolomics identified lipid peroxidation as a prominent feature in human plasma of patients with coronary heart diseases

    Directory of Open Access Journals (Sweden)

    Jianhong Lu

    2017-08-01

    Full Text Available Coronary heart disease (CHD is a complex human disease associated with inflammation and oxidative stress. The underlying mechanisms and diagnostic biomarkers for the different types of CHD remain poorly defined. Metabolomics has been increasingly recognized as an enabling technique with the potential to identify key metabolomic features in an attempt to understand the pathophysiology and differentiate different stages of CHD. We performed comprehensive metabolomic analysis in human plasma from 28 human subjects with stable angina (SA, myocardial infarction (MI, and healthy control (HC. Subsequent analysis demonstrated a uniquely altered metabolic profile in these CHD: a total of 18, 37 and 36 differential metabolites were identified to distinguish SA from HC, MI from SA, and MI from HC groups respectively. Among these metabolites, glycerophospholipid (GPL metabolism emerged as the most significantly disturbed pathway. Next, we used a targeted metabolomic approach to systematically analyze GPL, oxidized phospholipid (oxPL, and downstream metabolites derived from polyunsaturated fatty acids (PUFAs, such as arachidonic acid and linoleic acid. Surprisingly, lipids associated with lipid peroxidation (LPO pathways including oxidized PL and isoprostanes, isomers of prostaglandins, were significantly elevated in plasma of MI patients comparing to HC and SA, consistent with the notion that oxidative stress-induced LPO is a prominent feature in CHD. Our studies using the state-of-the-art metabolomics help to understand the underlying biological mechanisms involved in the pathogenesis of CHD; LPO metabolites may serve as potential biomarkers to differentiation MI from SA and HC. Keywords: Metabolomics, Lipid peroxidation, Lipidomics, Myocardial infarction, Isoprostanes, Coronary heart disease (CHD

  20. Effect of mental challenge induced by movie clips on action potential duration in normal human subjects independent of heart rate.

    Science.gov (United States)

    Child, Nicholas; Hanson, Ben; Bishop, Martin; Rinaldi, Christopher A; Bostock, Julian; Western, David; Cooklin, Michael; O'Neil, Mark; Wright, Matthew; Razavi, Reza; Gill, Jaswinder; Taggart, Peter

    2014-06-01

    Mental stress and emotion have long been associated with ventricular arrhythmias and sudden death in animal models and humans. The effect of mental challenge on ventricular action potential duration (APD) in conscious healthy humans has not been reported. Activation recovery intervals measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady-state pacing, whilst subjects watched an emotionally charged film clip. To assess the possible modulating role of altered respiration on APD, the subjects then repeated the same breathing pattern they had during the stress, but without the movie clip. Hemodynamic parameters (mean, systolic, and diastolic blood pressure, and rate of pressure increase) and respiration rate increased during the stressful part of the film clip (P=0.001). APD decreased during the stressful parts of the film clip, for example, for global right ventricular activation recovery interval at end of film clip 193.8 ms (SD, 14) versus 198.0 ms (SD, 13) during the matched breathing control (end film left ventricle 199.8 ms [SD, 16] versus control 201.6 ms [SD, 15]; P=0.004). Respiration rate increased during the stressful part of the film clip (by 2 breaths per minute) and was well matched in the respective control period without any hemodynamic or activation recovery interval changes. Our results document for the first time direct recordings of the effect of a mental challenge protocol on ventricular APD in conscious humans. The effect of mental challenge on APD was not secondary to emotionally induced altered respiration or heart rate. © 2014 American Heart Association, Inc.

  1. Human Fitting Studies of Cleveland Clinic Continuous-Flow Total Artificial Heart

    Science.gov (United States)

    Karimov, Jamshid H.; Steffen, Robert J.; Byram, Nicole; Sunagawa, Gengo; Horvath, David; Cruz, Vincent; Golding, Leonard A.R.; Fukamachi, Kiyotaka; Moazami, Nader

    2015-01-01

    Implantation of mechanical circulatory support devices is challenging, especially in patients with a small chest cavity. We evaluated how well the Cleveland Clinic continuous-flow total artificial heart (CFTAH) fit the anatomy of patients about to receive a heart transplant. A mock pump model of the CFTAH was rapid-prototyped using biocompatible materials. The model was brought to the operative table, and the direction, length, and angulation of the inflow/outflow ports and outflow conduits were evaluated after the recipient's ventricles had been resected. Thoracic cavity measurements were based on preoperative computed tomographic data. The CFTAH fit well in all five patients (height, 170 ± 9 cm; weight, 75 ± 24 kg). Body surface area was 1.9 ± 0.3 m2 (range, 1.6-2.1 m2). The required inflow and outflow port orientation of both the left and right housings appeared consistent with the current version of the CFTAH implanted in calves. The left outflow conduit remained straight, but the right outflow direction necessitated a 73 ± 22 degree angulation to prevent potential kinking when crossing over the connected left outflow. These data support the fact that our design achieves the proper anatomical relationship of the CFTAH to a patient's native vessels. PMID:25806613

  2. The lateral hypothalamus : A site for integration of nutrient and fluid balance

    NARCIS (Netherlands)

    van Dijk, Gertjan; Evers, Simon S.; Guidotti, Stefano; Thornton, Simon N.; Scheurink, Anton J. W.; Nyakas, Csaba

    2011-01-01

    This paper reviews seemingly obligatory relations between nutrient and fluid balance. A relatively novel neuronal pathway involving interplay between acetylcholine and the melanocortins, alpha MSH and AGRP in the arcuate nucleus (Arc) of the hypothalamus projecting to the lateral hypothalamus (LH)

  3. Angiotensin II Reduces Food Intake by Altering Orexigenic Neuropeptide Expression in the Mouse Hypothalamus

    Science.gov (United States)

    Yoshida, Tadashi; Semprun-Prieto, Laura; Wainford, Richard D.; Sukhanov, Sergiy; Kapusta, Daniel R.

    2012-01-01

    Angiotensin II (Ang II), which is elevated in many chronic disease states such as end-stage renal disease and congestive heart failure, induces cachexia and skeletal muscle wasting by increasing muscle protein breakdown and reducing food intake. Neurohormonal mechanisms that mediate Ang II-induced appetite suppression are unknown. Consequently, we examined the effect of Ang II on expression of genes regulating appetite. Systemic Ang II (1 μg/kg · min) infusion in FVB mice rapidly reduced hypothalamic expression of neuropeptide Y (Npy) and orexin and decreased food intake at 6 h compared with sham-infused controls but did not change peripheral leptin, ghrelin, adiponectin, glucagon-like peptide, peptide YY, or cholecystokinin levels. These effects were completely blocked by the Ang II type I receptor antagonist candesartan or deletion of Ang II type 1a receptor. Ang II markedly reduced phosphorylation of AMP-activated protein kinase (AMPK), an enzyme that is known to regulate Npy expression. Intracerebroventricular Ang II infusion (50 ng/kg · min) caused a reduction of food intake, and Ang II dose dependently reduced Npy and orexin expression in the hypothalamus cultured ex vivo. The reduction of Npy and orexin in hypothalamic cultures was completely prevented by candesartan or the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside. Thus, Ang II type 1a receptor-dependent Ang II signaling reduces food intake by suppressing the hypothalamic expression of Npy and orexin, likely via AMPK dephosphorylation. These findings have major implications for understanding mechanisms of cachexia in chronic disease states such as congestive heart failure and end-stage renal disease, in which the renin-angiotensin system is activated. PMID:22234465

  4. Human heart-type fatty acid-binding protein as an early diagnostic marker of doxorubicin cardiac toxicity

    Directory of Open Access Journals (Sweden)

    Ashraf H. ElGhandour

    2009-04-01

    Full Text Available Progressive cardiotoxicity following treatment with doxorubicin-based chemotherapy in patients with non-Hodgkin’s lymphoma (NHL may lead to late onset cardiomyopathy. So, early prediction of toxicity can lead to prevention of heart failure in these patients. The aim of this work was to investigate the role of H-FABP as an early diagnostic marker of anthracycline-induced cardiac toxicity together with brain natriuretic peptide (BNP as an indication of ventricular dysfunction in such patients. Our study was conducted on 40 NHL patients who received 6 cycles of a doxorubicin containing chemotherapy protocol (CHOP, not exceeding the total allowed dose of doxorubicin (500 mg/m2. Ten healthy controls were included in our study. Human heart-type fatty acid binding protein (H-FABP was assessed 24 hours after the first cycle of CHOP. Plasma levels of BNP were estimated both before starting chemotherapy and after the last cycle of CHOP. Resting echocardiography was also performed before and at the end of chemotherapy cycles. The ejection fraction (EF of 8 of our patients decreased below 50% at the end of the sixth cycle. Elevated levels of both H-FABP and BNP were found in all patients wth EF below 50% and both markers showed a positive correlation with each other. We concluded that H-FABP may serve as a reliable early marker for prediction of cardiomyopathy induced by doxorubicin. Thus, in patients with elevated H-FABP, alternative treatment modalities with no cardiac toxicity may be considered in order to prevent subsequent heart failure in these patients.

  5. Acute cardiovascular toxicity of sterilizers, PHMG, and PGH: severe inflammation in human cells and heart failure in zebrafish.

    Science.gov (United States)

    Kim, Jae-Yong; Kim, Hak Hyeon; Cho, Kyung-Hyun

    2013-06-01

    In 2011, dozens of children and pregnant women in Korea died by exposure to sterilizer for household humidifier, such as Oxy(®) and Cefu(®). Until now, however, it remains unknown how the sterilizer affect the human health to cause the acute deaths. To find its toxicity for organ, we investigated the putative toxicity of the sterilizer in the cardiovascular system. The sterilizers, polyhexamethylene guanidine phosphate (PHMG, Cefu(®)), and oligo-[2-(2-ethoxy)-ethoxyethyl)-guanidinium-chloride (PGH, Oxy(®)) were treated to human lipoproteins, macrophages, and dermal fibroblast cells. The PGH and PHMG at normal dosages caused severe atherogenic process in human macrophages, cytotoxic effect, and aging in human dermal cell. Zebrafish embryos, which were exposed to the sterilizer, showed early death with acute inflammation and attenuated developmental speed. All zebrafish exposed to the working concentration of PHMG (final 0.3 %) and PGH (final 10 mM) died within 70 min and displayed acute increases in serum triacylglycerol level and fatty liver induction. The dead zebrafish showed severe accumulation of fibrous collagen in the bulbous artery of the heart with elevation of reactive oxygen species. In conclusion, the sterilizers showed acute toxic effect in blood circulation system, causing by severe inflammation, atherogenesis, and aging, with embryo toxicity.

  6. The Development of Marine Accidents Human Reliability Assessment Approach: HEART Methodology and MOP Model

    OpenAIRE

    Ludfi Pratiwi Bowo; Wanginingastuti Mutmainnah; Masao Furusho

    2017-01-01

    Humans are one of the important factors in the assessment of accidents, particularly marine accidents. Hence, studies are conducted to assess the contribution of human factors in accidents. There are two generations of Human Reliability Assessment (HRA) that have been developed. Those methodologies are classified by the differences of viewpoints of problem-solving, as the first generation and second generation. The accident analysis can be determined using three techniques of analysis; sequen...

  7. The Ku Protein Complex Interacts with YY1, Is Up-Regulated in Human Heart Failure, and Represses α Myosin Heavy-Chain Gene Expression

    Science.gov (United States)

    Sucharov, Carmen C.; Helmke, Steve M.; Langer, Stephen J.; Perryman, M. Benjamin; Bristow, Michael; Leinwand, Leslie

    2004-01-01

    Human heart failure is accompanied by repression of genes such as α myosin heavy chain (αMyHC) and SERCA2A and the induction of fetal genes such as βMyHC and atrial natriuretic factor. It seems likely that changes in MyHC isoforms contribute to the poor contractility seen in heart failure, because small changes in isoform composition can have a major effect on the contractility of cardiac myocytes and the heart. Our laboratory has recently shown that YY1 protein levels are increased in human heart failure and that YY1 represses the activity of the human αMyHC promoter. We have now identified a region of the αMyHC promoter that binds a factor whose expression is increased sixfold in failing human hearts. Through peptide mass spectrometry, we identified this binding activity to be a heterodimer of Ku70 and Ku80. Expression of Ku represses the human αMyHC promoter in neonatal rat ventricular myocytes. Moreover, overexpression of Ku70/80 decreases αMyHC mRNA expression and increases skeletal α-actin. Interestingly, YY1 interacts with Ku70 and Ku80 in HeLa cells. Together, YY1, Ku70, and Ku80 repress the αMyHC promoter to an extent that is greater than that with YY1 or Ku70/80 alone. Our results suggest that Ku is an important factor in the repression of the human αMyHC promoter during heart failure. PMID:15367688

  8. The neuroanatomical function of leptin in the hypothalamus.

    Science.gov (United States)

    van Swieten, M M H; Pandit, R; Adan, R A H; van der Plasse, G

    2014-11-01

    The anorexigenic hormone leptin plays an important role in the control of food intake and feeding-related behavior, for an important part through its action in the hypothalamus. The adipose-derived hormone modulates a complex network of several intercommunicating orexigenic and anorexigenic neuropeptides in the hypothalamus to reduce food intake and increase energy expenditure. In this review we present an updated overview of the functional role of leptin in respect to feeding and feeding-related behavior per distinct hypothalamic nuclei. In addition to the arcuate nucleus, which is a major leptin sensitive hub, leptin-responsive neurons in other hypothalamic nuclei, including the, dorsomedial-, ventromedial- and paraventricular nucleus and the lateral hypothalamic area, are direct targets of leptin. However, leptin also modulates hypothalamic neurons in an indirect manner, such as via the melanocortin system. The dissection of the complexity of leptin's action on the networks involved in energy balance is subject of recent and future studies. A full understanding of the role of hypothalamic leptin in the regulation of energy balance requires cell-specific manipulation using of conditional deletion and expression of leptin receptors. In addition, optogenetic and pharmacogenetic tools in combination with other pharmacological (such as the recent discovery of a leptin receptor antagonist) and neuronal tracing techniques to map the circuit, will be helpful to understand the role of leptin receptor expressing neurons. Better understanding of these circuits and the involvement of leptin could provide potential sites for therapeutic interventions in obesity and metabolic diseases characterized by dysregulation of energy balance. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. M(o)TOR of aging: MTOR as a universal molecular hypothalamus.

    Science.gov (United States)

    Blagosklonny, Mikhail V

    2013-07-01

    A recent ground-breaking publication described hypothalamus-driven programmatic aging. As a Russian proverb goes "everything new is well-forgotten old". In 1958, Dilman proposed that aging and its related diseases are programmed by the hypothalamus. This theory, supported by beautiful experiments, remained unnoticed just to be re-discovered recently. Yet, it does not explain all manifestations of aging. And would organism age without hypothalamus? Do sensing pathways such as MTOR (mechanistic Target of Rapamycin) and IKK-beta play a role of a "molecular hypothalamus" in every cell? Are hypothalamus-driven alterations simply a part of quasi-programmed aging manifested by hyperfunction and secondary signal-resistance? Here are some answers.

  10. Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Dehai Yu

    2017-01-01

    Full Text Available Background. Fetal heart can regenerate to restore its normal anatomy and function in response to injury, but this regenerative capacity is lost within the first week of postnatal life. Although the specific molecular mechanisms remain to be defined, it is presumed that aging of cardiac stem or progenitor cells may contribute to the loss of regenerative potential. Methods. To study this aging-related dysfunction, we cultured mesenchymal stem cells (MSCs from human fetal heart tissues. Senescence was induced by exposing cells to chronic oxidative stress/low serum. Mitochondrial DNA methylation was examined during the period of senescence. Results. Senescent MSCs exhibited flattened and enlarged morphology and were positive for the senescence-associated beta-galactosidase (SA-β-Gal. By scanning the entire mitochondrial genome, we found that four CpG islands were hypomethylated in close association with senescence in MSCs. The mitochondrial COX1 gene, which encodes the main subunit of the cytochrome c oxidase complex and contains the differentially methylated CpG island 4, was upregulated in MSCs in parallel with the onset of senescence. Knockdown of DNA methyltransferases (DNMT1, DNMT3a, and DNMT3B also upregulated COX1 expression and induced cellular senescence in MSCs. Conclusions. This study demonstrates that mitochondrial CpG hypomethylation may serve as a critical biomarker associated with cellular senescence induced by chronic oxidative stress.

  11. Development of the Human Placenta and Fetal Heart: Synergic or Independent?

    Directory of Open Access Journals (Sweden)

    Graham J. Burton

    2018-04-01

    Full Text Available The placenta is the largest fetal organ, and toward the end of pregnancy the umbilical circulation receives at least 40% of the biventricular cardiac output. It is not surprising, therefore, that there are likely to be close haemodynamic links between the development of the placenta and the fetal heart. Development of the placenta is precocious, and in advance of that of the fetus. The placenta undergoes considerable remodeling at the end of the first trimester of pregnancy, and its vasculature is capable of adapting to environmental conditions and to variations in the blood supply received from the mother. There are two components to the placental membranes to consider, the secondary yolk sac and the chorioallantoic placenta. The yolk sac is the first of the extraembryonic membranes to be vascularized, and condensations in the mesenchyme at ~17 days post-conception (p.c. give rise to endothelial and erythroid precursors. A network of blood vessels is established ~24 days p.c., with the vitelline vein draining through the region of the developing liver into the sinus venosus. Gestational sacs of early pregnancy failures often display aberrant development of the yolk sac, which is likely to be secondary to abnormal fetal development. Vasculogenesis occurs in the villous mesenchyme of the chorioallantoic placenta at a similarly early stage. Nucleated erythrocytes occupy the lumens of the placental capillaries and end-diastolic flow is absent in the umbilical arterial circulation throughout most of the first trimester, indicating a high resistance to blood flow. Resistance begins to fall in the umbilico-placental circulation around 12–14 weeks. During normal early pregnancy the placental capillary network is plastic, and considerable remodeling occurs in response to the local oxygen concentration, and in particular to oxidative stress. In pregnancies complicated by preeclampsia and/or fetal growth restriction, utero-placental malperfusion induces

  12. Enlarged Heart

    Science.gov (United States)

    ... rheumatic fever, a heart defect, infections (infectious endocarditis), connective tissue disorders, certain medications or radiation treatments for cancer, your heart may enlarge. Disease of the heart ...

  13. Blood pressure and heart rate variability analysis of orthostatic challenge in normal human pregnancies.

    Science.gov (United States)

    Heiskanen, Nonna; Saarelainen, Heli; Valtonen, Pirjo; Lyyra-Laitinen, Tiina; Laitinen, Tomi; Vanninen, Esko; Heinonen, Seppo

    2008-11-01

    The aim of the present study was to evaluate pregnancy-related changes in autonomic regulatory functions in healthy subjects. We studied cardiovascular autonomic responses to head-up tilt (HUT) in 28 pregnant women during the third trimester of pregnancy and 3 months after parturition. The maternal ECG and non-invasive beat-to-beat blood pressure were recorded in the horizontal position (left-lateral position) and during HUT in the upright position. Stroke volume was assessed from blood pressure signal by using the arterial pulse contour method. Heart rate variability (HRV) was analysed in frequency domain, and baroreflex sensitivity by the cross-spectral and the sequence methods. In the horizontal position, all frequency components of HRV were lower during pregnancy than 3 months after parturition (P pregnancy had no influence on normalized low frequency and high frequency powers. During pregnancy haemodynamics was well balanced with only minor changes in response to postural change while haemodynamic responses to HUT were more remarkable after parturition. In pregnant women HRV and especially its very low frequency component increased in response to HUT, whereas at 3 months after parturition the direction of these changes was opposite. Parasympathetic deactivation towards term is likely to contribute to increased heart rate and cardiac output at rest, whereas restored sympathetic modulation with modest responses may contribute stable peripheral resistance and sufficient placental blood supply under stimulated conditions. It is important to understand cardiovascular autonomic nervous system and haemodynamic control in normal pregnancy before being able to judge whether they are dysregulated in complicated pregnancies.

  14. An integrative analysis of DNA methylation and RNA-Seq data for human heart, kidney and liver

    Directory of Open Access Journals (Sweden)

    Xie Linglin

    2011-12-01

    Full Text Available Abstract Background Many groups, including our own, have proposed the use of DNA methylation profiles as biomarkers for various disease states. While much research has been done identifying DNA methylation signatures in cancer vs. normal etc., we still lack sufficient knowledge of the role that differential methylation plays during normal cellular differentiation and tissue specification. We also need thorough, genome level studies to determine the meaning of methylation of individual CpG dinucleotides in terms of gene expression. Results In this study, we have used (insert statistical method here to compile unique DNA methylation signatures from normal human heart, lung, and kidney using the Illumina Infinium 27 K methylation arraysand compared those to gene expression by RNA sequencing. We have identified unique signatures of global DNA methylation for human heart, kidney and liver, and showed that DNA methylation data can be used to correctly classify various tissues. It indicates that DNA methylation reflects tissue specificity and may play an important role in tissue differentiation. The integrative analysis of methylation and RNA-Seq data showed that gene methylation and its transcriptional levels were comprehensively correlated. The location of methylation markers in terms of distance to transcription start site and CpG island showed no effects on the regulation of gene expression by DNA methylation in normal tissues. Conclusions This study showed that an integrative analysis of methylation array and RNA-Seq data can be utilized to discover the global regulation of gene expression by DNA methylation and suggests that DNA methylation plays an important role in normal tissue differentiation via modulation of gene expression.

  15. A new dynamic 3D virtual methodology for teaching the mechanics of atrial septation as seen in the human heart.

    Science.gov (United States)

    Schleich, Jean-Marc; Dillenseger, Jean-Louis; Houyel, Lucile; Almange, Claude; Anderson, Robert H

    2009-01-01

    Learning embryology remains difficult, since it requires understanding of many complex phenomena. The temporal evolution of developmental events has classically been illustrated using cartoons, which create difficulty in linking spatial and temporal aspects, such correlation being the keystone of descriptive embryology. We synthesized the bibliographic data from recent studies of atrial septal development. On the basis of this synthesis, consensus on the stages of atrial septation as seen in the human heart has been reached by a group of experts in cardiac embryology and pediatric cardiology. This has permitted the preparation of three-dimensional (3D) computer graphic objects for the anatomical components involved in the different stages of normal human atrial septation. We have provided a virtual guide to the process of normal atrial septation, the animation providing an appreciation of the temporal and morphologic events necessary to separate the systemic and pulmonary venous returns. We have shown that our animations of normal human atrial septation increase significantly the teaching of the complex developmental processes involved, and provide a new dynamic for the process of learning.

  16. Acellular therapeutic approach for heart failure: in vitro production of extracellular vesicles from human cardiovascular progenitors.

    Science.gov (United States)

    El Harane, Nadia; Kervadec, Anaïs; Bellamy, Valérie; Pidial, Laetitia; Neametalla, Hany J; Perier, Marie-Cécile; Lima Correa, Bruna; Thiébault, Léa; Cagnard, Nicolas; Duché, Angéline; Brunaud, Camille; Lemitre, Mathilde; Gauthier, Jeanne; Bourdillon, Alexandra T; Renault, Marc P; Hovhannisyan, Yeranuhi; Paiva, Solenne; Colas, Alexandre R; Agbulut, Onnik; Hagège, Albert; Silvestre, Jean-Sébastien; Menasché, Philippe; Renault, Nisa K E

    2018-05-21

    We have shown that extracellular vesicles (EVs) secreted by embryonic stem cell-derived cardiovascular progenitor cells (Pg) recapitulate the therapeutic effects of their parent cells in a mouse model of chronic heart failure (CHF). Our objectives are to investigate whether EV released by more readily available cell sources are therapeutic, whether their effectiveness is influenced by the differentiation state of the secreting cell, and through which mechanisms they act. The total EV secreted by human induced pluripotent stem cell-derived cardiovascular progenitors (iPSC-Pg) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) were isolated by ultracentrifugation and characterized by Nanoparticle Tracking Analysis, western blot, and cryo-electron microscopy. In vitro bioactivity assays were used to evaluate their cellular effects. Cell and EV microRNA (miRNA) content were assessed by miRNA array. Myocardial infarction was induced in 199 nude mice. Three weeks later, mice with left ventricular ejection fraction (LVEF) ≤ 45% received transcutaneous echo-guided injections of iPSC-CM (1.4 × 106, n = 19), iPSC-Pg (1.4 × 106, n = 17), total EV secreted by 1.4 × 106 iPSC-Pg (n = 19), or phosphate-buffered saline (control, n = 17) into the peri-infarct myocardium. Seven weeks later, hearts were evaluated by echocardiography, histology, and gene expression profiling, blinded to treatment group. In vitro, EV were internalized by target cells, increased cell survival, cell proliferation, and endothelial cell migration in a dose-dependent manner and stimulated tube formation. Extracellular vesicles were rich in miRNAs and most of the 16 highly abundant, evolutionarily conserved miRNAs are associated with tissue-repair pathways. In vivo, EV outperformed cell injections, significantly improving cardiac function through decreased left ventricular volumes (left ventricular end systolic volume: -11%, P < 0.001; left

  17. Effect of global cardiac ischemia on human ventricular fibrillation: insights from a multi-scale mechanistic model of the human heart.

    Directory of Open Access Journals (Sweden)

    Ivan V Kazbanov

    2014-11-01

    Full Text Available Acute regional ischemia in the heart can lead to cardiac arrhythmias such as ventricular fibrillation (VF, which in turn compromise cardiac output and result in secondary global cardiac ischemia. The secondary ischemia may influence the underlying arrhythmia mechanism. A recent clinical study documents the effect of global cardiac ischaemia on the mechanisms of VF. During 150 seconds of global ischemia the dominant frequency of activation decreased, while after reperfusion it increased rapidly. At the same time the complexity of epicardial excitation, measured as the number of epicardical phase singularity points, remained approximately constant during ischemia. Here we perform numerical studies based on these clinical data and propose explanations for the observed dynamics of the period and complexity of activation patterns. In particular, we study the effects on ischemia in pseudo-1D and 2D cardiac tissue models as well as in an anatomically accurate model of human heart ventricles. We demonstrate that the fall of dominant frequency in VF during secondary ischemia can be explained by an increase in extracellular potassium, while the increase during reperfusion is consistent with washout of potassium and continued activation of the ATP-dependent potassium channels. We also suggest that memory effects are responsible for the observed complexity dynamics. In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels from these measurements.

  18. Effects of heavy-ion exposure to rat's hypothalamus on the copulatory behavior

    International Nuclear Information System (INIS)

    Saito, Masayoshi; Uno, Takashi; Kawata, Tetsuya; Liu, C.; Kan'o, Momoe; Okamura, Junko; Ito, Hisao; Takai, Nobuhiko; Ando, Koichi

    2006-01-01

    The present study was designed to determine whether irradiation (carbon particles 290 MeV/nucleon, Mono Peak 30-60 Gy, irradiation field 5 mm cube in hypothalamus) to hypothalamus modifies the copulatory behavior of male rats. By the second year, we studied the chronic effects for heavy ions on the copulatory behavior. In addition, the influence of heavy ions to cortex (irradiation field width and depth 5 mm, respectively) was studied. The copulatory items were recorded: frequency number of mounting, intromission and ejaculation during 30 min after 1, 3 and 6-7 months following irradiation. Results are as follows. At 60 Gy to hypothalamus, the frequency number of intromission and ejaculation was decreased from one month to 7 months following irradiation. Particularly, suppression for the copulatory behavior was recognized in 3 and 4 months after irradiation. At 3 and 4 months after 60 Gy irradiation, the frequency number of ejaculation was decreased in comparison with non-irradiated (control) male rats. At 45 Gy to hypothalamus or cortex, the frequency number of ejaculation was decreased after one month (Both sides of hypothalamus and cortex) and 3 months (Only as for hypothalamus) following irradiation. At 30 Gy to cortex, the frequency number of ejaculation was similar but irradiation to hypothalamus decreased it 3 months following irradiation. (author)

  19. Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart

    NARCIS (Netherlands)

    Schultz, D; Mikala, G; Yatani, A; Engle, D B; Iles, D E; Segers, B; Sinke, R J; Weghuis, D O; Klöckner, U; Wakamori, M

    1993-01-01

    A unique structural variant of the cardiac L-type voltage-dependent calcium channel alpha 1 subunit cDNA was isolated from libraries derived from normal human heart mRNA. The deduced amino acid sequence shows significant homology to other calcium channel alpha 1 subunits. However, differences from

  20. Effects of halothane on the conduction system of the heart in humans

    NARCIS (Netherlands)

    Scheffer, G. J.; Jonges, R.; Holley, H. S.; Grimbergen, C. A.; Ros, H. H.; Peper, A.; Booij, L. H.

    1989-01-01

    The effects of 2.0 MAC halothane on atrioventricular conduction times in humans were studied. A real-time recording system for the detection of surface His-Purkinje potentials based on signal averaging techniques was used. Recordings were made in 23 patients before and after the administration of

  1. Characterization of Common Measures of Heart Period Variability in Healthy Human Subjects: Implications for Patient Monitoring

    Science.gov (United States)

    2010-01-01

    sports medicine and science. Sports Med 2000; 30: 1–15. 41. Eckberg DL. The human respiratory gate. J Physiol 2003; 548: 339–352. 42. Kamen PW, Krum H...in short-term HRV analysis. Biomed Tech 2006; 51: 190–193. 45. Hayano J, Taylor JA, Yamada A, et al. Continuous assessment of hemodynamic control by

  2. Letting Our Hearts Break: On Facing the "Hidden Wound" of Human Supremacy

    Science.gov (United States)

    Martusewicz, Rebecca

    2014-01-01

    In this paper I argue that education must be defined by our willingness to experience compassion in the face of others' suffering and thus by an ethical imperative, and seek to expose psycho-social processes of shame as dark matters that inferiorize and subjugate those expressing such compassion for the more-than-human world. Beginning with…

  3. Radial Pressure Pulse and Heart Rate Variability in Heat- and Cold-Stressed Humans

    Directory of Open Access Journals (Sweden)

    Chin-Ming Huang

    2011-01-01

    Full Text Available This study aims to explore the effects of heat and cold stress on the radial pressure pulse (RPP and heart rate variability (HRV. The subjects immersed their left hand into 45°C and 7°C water for 2 minutes. Sixty healthy subjects (age 25±4 yr; 29 men and 31 women were enrolled in this study. All subjects underwent the supine temperature measurements of the bilateral forearms, brachial arterial blood pressure, HRV and RPP with a pulse analyzer in normothermic conditions, and thermal stresses. The power spectral low-frequency (LF and high-frequency (HF components of HRV decreased in the heat test and increased in the cold test. The heat stress significantly reduced radial augmentation index (AIr (P<.05, but the cold stress significantly increased AIr (P<.01. The spectral energy of RPP did not show any statistical difference in 0∼10 Hz region under both conditions, but in the region of 10∼50 Hz, there was a significant increase (P<.01 in the heat test and a significant decrease in the cold test (P<.01. The changes in AIr induced by heat and cold stress were significantly negatively correlated with the spectral energy in the region of 10∼50 Hz (SE10−50 Hz but not in the region of 0∼10 Hz (SE0−10 Hz. The results demonstrated that the SE10−50 Hz, which only possessed a small percentage in total pulse energy, presented more physiological characteristics than the SE0−10 Hz under the thermal stresses.

  4. Radial Pressure Pulse and Heart Rate Variability in Heat- and Cold-Stressed Humans

    Science.gov (United States)

    Huang, Chin-Ming; Chang, Hsien-Cheh; Kao, Shung-Te; Li, Tsai-Chung; Wei, Ching-Chuan; Chen, Chiachung; Liao, Yin-Tzu; Chen, Fun-Jou

    2011-01-01

    This study aims to explore the effects of heat and cold stress on the radial pressure pulse (RPP) and heart rate variability (HRV). The subjects immersed their left hand into 45°C and 7°C water for 2 minutes. Sixty healthy subjects (age 25 ± 4 yr; 29 men and 31 women) were enrolled in this study. All subjects underwent the supine temperature measurements of the bilateral forearms, brachial arterial blood pressure, HRV and RPP with a pulse analyzer in normothermic conditions, and thermal stresses. The power spectral low-frequency (LF) and high-frequency (HF) components of HRV decreased in the heat test and increased in the cold test. The heat stress significantly reduced radial augmentation index (AIr) (P < .05), but the cold stress significantly increased AIr (P < .01). The spectral energy of RPP did not show any statistical difference in 0 ~ 10 Hz region under both conditions, but in the region of 10 ~ 50 Hz, there was a significant increase (P < .01) in the heat test and a significant decrease in the cold test (P < .01). The changes in AIr induced by heat and cold stress were significantly negatively correlated with the spectral energy in the region of 10 ~ 50 Hz (SE10−50 Hz) but not in the region of 0 ~ 10 Hz (SE0−10 Hz). The results demonstrated that the SE10−50 Hz, which only possessed a small percentage in total pulse energy, presented more physiological characteristics than the SE0−10 Hz under the thermal stresses. PMID:21113292

  5. Efficient computation of electrograms and ECGs in human whole heart simulations using a reaction-eikonal model.

    Science.gov (United States)

    Neic, Aurel; Campos, Fernando O; Prassl, Anton J; Niederer, Steven A; Bishop, Martin J; Vigmond, Edward J; Plank, Gernot

    2017-10-01

    Anatomically accurate and biophysically detailed bidomain models of the human heart have proven a powerful tool for gaining quantitative insight into the links between electrical sources in the myocardium and the concomitant current flow in the surrounding medium as they represent their relationship mechanistically based on first principles. Such models are increasingly considered as a clinical research tool with the perspective of being used, ultimately, as a complementary diagnostic modality. An important prerequisite in many clinical modeling applications is the ability of models to faithfully replicate potential maps and electrograms recorded from a given patient. However, while the personalization of electrophysiology models based on the gold standard bidomain formulation is in principle feasible, the associated computational expenses are significant, rendering their use incompatible with clinical time frames. In this study we report on the development of a novel computationally efficient reaction-eikonal (R-E) model for modeling extracellular potential maps and electrograms. Using a biventricular human electrophysiology model, which incorporates a topologically realistic His-Purkinje system (HPS), we demonstrate by comparing against a high-resolution reaction-diffusion (R-D) bidomain model that the R-E model predicts extracellular potential fields, electrograms as well as ECGs at the body surface with high fidelity and offers vast computational savings greater than three orders of magnitude. Due to their efficiency R-E models are ideally suitable for forward simulations in clinical modeling studies which attempt to personalize electrophysiological model features.

  6. Significance of myoglobin as an oxygen store and oxygen transporter in the intermittently perfused human heart: a model study.

    Science.gov (United States)

    Endeward, Volker; Gros, Gerolf; Jürgens, Klaus D

    2010-07-01

    The mechanisms by which the left ventricular wall escapes anoxia during the systolic phase of low blood perfusion are investigated, especially the role of myoglobin (Mb), which can (i) store oxygen and (ii) facilitate intracellular oxygen transport. The quantitative role of these two Mb functions is studied in the maximally working human heart. Because discrimination between Mb functions has not been achieved experimentally, we use a Krogh cylinder model here. At a heart rate of 200 beats/min and a 1:1 ratio of diastole/systole, the systole lasts for 150 ms. The basic model assumption is that, with mobile Mb, the oxygen stored in the end-diastolic left ventricle wall exactly meets the demand during the 150 ms of systolic cessation of blood flow. The coronary blood flow necessary to achieve this agrees with literature data. By considering Mb immobile or setting its concentration to zero, respectively, we find that, depending on Mb concentration, Mb-facilitated O(2) transport maintains O(2) supply to the left ventricle wall during 22-34 of the 150 ms, while Mb storage function accounts for a further 12-17 ms. When Mb is completely absent, anoxia begins to develop after 116-99 ms. While Mb plays no significant role during diastole, it supplies O(2) to the left ventricular wall for < or = 50 ms of the 150 ms systole, whereas capillary haemoglobin is responsible for approximately 80 ms. Slight increases in haemoglobin concentration, blood flow, or capillary density can compensate the absence of Mb, a finding which agrees well with the observations using Mb knockout mice.

  7. Magnetic resonance imaging of hypothalamus hypophysis axis lesions

    International Nuclear Information System (INIS)

    Shiina, Takeki; Uno, Kimiichi; Arimizu, Noboru; Yoshida, Sho; Yamada, Kenichi.

    1990-01-01

    Magnetic resonance imaging (MRI) using a 0.5T superconductive machine was performed to the thirty three cases with a variety of the sellar and parasellar tumors and with dysfunction of the hypothalamus-hypophysis axis. Posterior pituitary bright spot (PBS) on T1 weighted image was evaluated with the pituitary hormonal function. These cases were 12 cases of post-treated tumors including pituitary adenoma (9 patients), suprasellar germinoma (2 patients) and craniopharyngioma (one patient), and non-tumorous conditions including 15 cases of central diabetes insipidus (DI), Syndrome of inappropriate secretion of ADH (SIADH) (one patient), Sheehan's syndrome (3 patients) and anorexia nervosa (2 patients). Pituitary bright spot was not seen in all 19 cases with overt DI. On the other hand, PBS was not seen in 9 cases without overt DI. Three cases of these 9 cases showing Sheehan's syndrome with insufficient antidiuretic hormone (ADH) secretion was considered as the state of subclinical DI. Posterior bright spot was not seen in all 13 cases of empty sella including partial empty sella. The results suggested that disappearance of PBS represents abnormality or loss of posterior pituitary function and also it was considered to be closely related to the empty sella. (author)

  8. The Humans in Space Art Program - Engaging the Mind, and the Heart, in Science

    Science.gov (United States)

    McPhee, J. C.

    2017-12-01

    How can we do a better job communicating about space, science and technology, getting more people engaged, understanding the impact that future space exploration will have on their lives, and thinking about how they can contribute? Humans naturally express their visions and interests through various forms of artistic expression because art is inherently capable of expressing not only the "what and how" but also the "why" of ideas. Offering opportunities that integrate space, science and technology with art allows more people to learn about space, relay their visions of the future, and discuss why exploration and research are important. The Humans in Space Art Program, managed by the nonprofit SciArt Exchange, offers a science-integrated-with-art opportunity. Through international online competitions, we invite participants to share their visions of the future using visual, literary, musical and video art. We then use their artwork in multi-media displays and live performances online, locally worldwide, and in space to engage listeners and viewers. The Program has three projects, targeting different types of participants: the Youth Competition (ages 10-18), the Challenge (college and early career) and Celebrity Artist-Fed Engagement (CAFÉ: professional artists). To date, the Program has received 3400 artworks from over 52 countries and displayed the artwork in 110 multi-media events worldwide, on the International Space Station and bounced off the Moon. 100,000's have thus viewed artwork considering topics such as: why we explore; where and how we will go and when; and what we will do when we arrive. The Humans in Space Art Program is a flexible public engagement model applicable to multiple settings, including classrooms, art and entertainment events, and scientific conferences. It provides a system to accessibly inspire all ages about space, science and technology, making them hungry to learn more and to take a personal role.

  9. Characterizing potential heart agents with an isolated perfused heart system

    International Nuclear Information System (INIS)

    Pendleton, D.B.; Sands, H.; Gallagher, B.M.; Camin, L.L.

    1984-01-01

    The authors have used an isolated perfused heart system for characterizing potential myocardial perfusion radiopharamaceuticals. Rabbit or guinea pig (GP) hearts are removed and perfused through the aorta with a blood-free buffer. Heart rate and ventricular pressure are monitored as indices of viability. Tc-99m-MAA is 96-100% retained in these hearts, and Tc-99m human serum albumin shows less than 5% extraction. Tl-201 is 30-40% extracted. It is known that in-vivo, Tc-99m(dmpe)/sub 2/Cl/sub 2//sup +/ is taken up by rabbit heart but not by GP or human heart. Analogous results are obtained with the isolated perfused heart model, where the complex is extracted well by the isolated rabbit heart (24%) but not by the GP heart (<5%). Values are unchanged if human, rabbit or GP blood is mixed and co-injected with the complex. Tc-99m)dmpe)/sub 3//sup +/ is also taken up by rabbit but not by GP hearts in-vivo. However, isolated perfused hearts of both species extract this complex well (45-52%). Heart uptake is diminished to <7% if the complex is pre-equilibrated with human blood. GP blood produces a moderate inhibition (in GP hearts only) and rabbit blood has no effect. This suggests that a human or GP blood factor may have a significant effect on heart uptake of this complex. Tc-99m(CN-t-butyl)/sub 6//sup +/ is taken up well by both rabbit and GP hearts in-vivo, and is extracted 100% by both isolated perfused hearts. Heart retention remains high (73-75%) in the presence of human blood

  10. Activity changes of the cat paraventricular hypothalamus during phasic respiratory events

    DEFF Research Database (Denmark)

    Kristensen, Morten Pilgaard; Poe, G R; Rector, D M

    1997-01-01

    We monitored the spatiotemporal organization of cellular activity in the medial paraventricular hypothalamus during spontaneously-occurring periods of increased inspiratory effort followed by prolonged respiratory pauses (sigh/apnea) in the freely-behaving cat. Paraventricular hypothalamic activity...

  11. Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography

    International Nuclear Information System (INIS)

    Corp, E.S.; Woods, S.C.; Figlewicz, D.P.; Porte, D. Jr.; Baskin, D.G.; Dorsa, D.M.

    1986-01-01

    In vitro autoradiography and computer video densitometry were used to localize and quantify binding of 125 I-insulin in the hypothalamus of the rat brain. Highest specific binding was found in the arculate, dorsomedial, suprachiasmatic, paraventricular and periventricular regions. Significantly lower binding was present in the ventromedial nucleus and median eminence. The results are consistent with the hypothesis that insulin modulates the neural regulation of feeding by acting at sites in the hypothalamus. (author)

  12. Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia

    OpenAIRE

    Ihnatko, Robert; Post, Claes; Blomqvist, Anders

    2013-01-01

    Background: Anorexia-cachexia is a common and severe cancer-related complication but the underlying mechanisms are largely unknown. Here, using a mouse model for tumour-induced anorexia-cachexia, we screened for proteins that are differentially expressed in the hypothalamus, the brain’s metabolic control centre. Methods: The hypothalamus of tumour-bearing mice with implanted methylcholanthrene-induced sarcoma (MCG 101) displaying anorexia and their sham-implanted pair-fed or free-fed litterma...

  13. Slits Are Chemorepellents Endogenous to Hypothalamus and Steer Thalamocortical Axons into Ventral Telencephalon

    OpenAIRE

    Braisted, Janet E.; Ringstedt, Thomas; O'Leary, Dennis D. M.

    2009-01-01

    Thalamocortical axons (TCAs) originate in dorsal thalamus, extend ventrally along the lateral thalamic surface, and as they approach hypothalamus make a lateral turn into ventral telencephalon. In vitro studies show that hypothalamus releases a chemorepellent for TCAs, and analyses of knockout mice indicate that Slit chemorepellents and their receptor Robo2 influence TCA pathfinding. We show that Slit chemorepellents are the hypothalamic chemorepellent and act through Robos to steer TCAs into...

  14. Heart Failure

    Science.gov (United States)

    Heart failure is a condition in which the heart can't pump enough blood to meet the body's needs. Heart failure does not mean that your heart has stopped ... and shortness of breath Common causes of heart failure are coronary artery disease, high blood pressure and ...

  15. Regulating Hypothalamus Gene Expression in Food Intake: Dietary Composition or Calorie Density?

    Directory of Open Access Journals (Sweden)

    Mi Jang

    2017-01-01

    Full Text Available BackgroundThe proportion of saturated fatty acids/unsaturated fatty acids in the diet seems to act as a physiological regulation on obesity, cardiovascular diseases, and diabetes. Differently composed fatty acid diets may induce satiety of the hypothalamus in different ways. However, the direct effect of the different fatty acid diets on satiety in the hypothalamus is not clear.MethodsThree experiments in mice were conducted to determine whether: different compositions of fatty acids affects gene mRNA expression of the hypothalamus over time; different types of fatty acids administered into the stomach directly affect gene mRNA expression of the hypothalamus; and fat composition changes in the diet affects gene mRNA expression of the hypothalamus.ResultsThe type of fat in cases of purified fatty acid administration directly into the stomach may cause changes of gene expressions in the hypothalamus. Gene expression by dietary fat may be regulated by calorie amount ingested rather than weight amount or type of fat.ConclusionTherefore, the calorie density factor of the diet in regulating hypothalamic gene in food intake may be detrimental, although the possibility of type of fat cannot be ruled out.

  16. Chromium VI administration induces oxidative stress in hypothalamus and anterior pituitary gland from male rats.

    Science.gov (United States)

    Nudler, Silvana I; Quinteros, Fernanda A; Miler, Eliana A; Cabilla, Jimena P; Ronchetti, Sonia A; Duvilanski, Beatriz H

    2009-03-28

    Hexavalent chromium (Cr VI)-containing compounds are known carcinogens which are present in industrial settings and in the environment. The major route of chromium exposure for the general population is oral intake. Previously we have observed that Cr VI affects anterior pituitary secretion and causes oxidative stress in vitro. The aim of the present work was to investigate if in vivo Cr VI treatment (100 ppm of Cr VI in drinking water for up 30 days) causes oxidative stress in hypothalamus and anterior pituitary gland from male rats. This treatment produced a 4-fold increase of chromium content in hypothalamus and 10-fold increase in anterior pituitary gland. Lipid peroxidation showed a significant increase in hypothalamus and anterior pituitary. Cr VI augmented superoxide dismutase activity in anterior pituitary gland and glutathione reductase activity in hypothalamus, but glutathione peroxidase and catalase activities remained unchanged in both tissues. Heme oxygenase-1 mRNA expression significantly rose in both tissues. Metallothionein 1 mRNA content increased in anterior pituitary and metallothionein 3 mRNA increased in hypothalamus. These results show, for the first time, that oral chronic administration of Cr VI produces oxidative stress on the hypothalamus and anterior pituitary gland which may affect normal endocrine function.

  17. Effect of low dose radiation on POMC transcription level in mouse hypothalamus and immune organs

    International Nuclear Information System (INIS)

    Wan Hong; Liu Shuzheng

    1998-01-01

    Objective: To disclose the changes in mRNA transcription level of POMC in the hypothalamus and immune organs after low dose radiation. Method: In situ hybridization was used to examine the changes of POMC mRNA transcription level in mouse hypothalamus and immune organs following whole body irradiation (WBI) with 75 mGy X-rays. Results: There was a basal expression of POMC mRNA in both the hypothalamus and immune organs. POMC mRNA-positive neutron were located in the arcuate nucleus of hypothalamus. WBI with 75 mGy X-rays could significantly down-regulate the POMC transcription level that was remarkable within 1h and remained low in the observation period of 12h. POMC transcription level in mouse immune organs increased with time within 8h after irradiation and then began to decrease but still remained at a higher than normal level. The changes of POMC transcription level were more marked in the spleen than in other immune organs. Conclusion: These findings suggest that the immediate decrease of POMC transcription level in the hypothalamus might be the direct cause of the down-regulation of the hypothalamus-pituitary-adrenocortical axis after WBI with 75 mGy X-rays, accompanied with an increase in POMC transcription in immune organs

  18. The ventromedial hypothalamus oxytocin induces locomotor behavior regulated by estrogen.

    Science.gov (United States)

    Narita, Kazumi; Murata, Takuya; Matsuoka, Satoshi

    2016-10-01

    Our previous studies demonstrated that excitation of neurons in the rat ventromedial hypothalamus (VMH) induced locomotor activity. An oxytocin receptor (Oxtr) exists in the VMH and plays a role in regulating sexual behavior. However, the role of Oxtr in the VMH in locomotor activity is not clear. In this study we examined the roles of oxytocin in the VMH in running behavior, and also investigated the involvement of estrogen in this behavioral change. Microinjection of oxytocin into the VMH induced a dose-dependent increase in the running behavior in male rats. The oxytocin-induced running activity was inhibited by simultaneous injection of Oxtr-antagonist, (d(CH2)5(1), Try(Me)(2), Orn(8))-oxytocin. Oxytocin injection also induced running behavior in ovariectomized (OVX) female rats. Pretreatment of the OVX rats with estrogen augmented the oxytocin-induced running activity twofold, and increased the Oxtr mRNA in the VMH threefold. During the estrus cycle locomotor activity spontaneously increased in the dark period of proestrus. The Oxtr mRNA was up-regulated in the proestrus afternoon. Blockade of oxytocin neurotransmission by its antagonist before the onset of the dark period of proestrus decreased the following nocturnal locomotor activity. These findings demonstrate that Oxtr in the VMH is involved in the induction of running behavior and that estrogen facilitates this effect by means of Oxtr up-regulation, suggesting the involvement of oxytocin in the locomotor activity of proestrus female rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease

    Science.gov (United States)

    Singh, Swati; Kumar, Ashok; Khare, Shashi; Mulchandani, Ashok; Rajesh

    2014-11-01

    A specific and ultrasensitive, label free single-walled carbon nanotubes (SWNTs) based chemiresistive genosensor was fabricated for the early detection of Streptococcus pyogenes infection in human causing rheumatic heart disease. The mga gene of S. pyogenes specific 24 mer ssDNA probe was covalently immobilized on SWNT through a molecular bilinker, 1-pyrenemethylamine, using carbodiimide coupling reaction. The sensor was characterized by the current-voltage (I-V) characteristic curve and scanning electron microscopy. The sensing performance of the sensor was studied with respect to changes in conductance in SWNT channel based on hybridization of the target S. pyogenes single stranded genomic DNA (ssG-DNA) to its complementary 24 mer ssDNA probe. The sensor shows negligible response to non-complementary Staphylococcus aureus ssG-DNA, confirming the specificity of the sensor only with S. pyogenes. The genosensor exhibited a linear response to S. pyogenes G-DNA from 1 to1000 ng ml-1 with a limit of detection of 0.16 ng ml-1.

  20. Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease

    International Nuclear Information System (INIS)

    Singh, Swati; Kumar, Ashok; Khare, Shashi; Mulchandani, Ashok; Rajesh

    2014-01-01

    A specific and ultrasensitive, label free single-walled carbon nanotubes (SWNTs) based chemiresistive genosensor was fabricated for the early detection of Streptococcus pyogenes infection in human causing rheumatic heart disease. The mga gene of S. pyogenes specific 24 mer ssDNA probe was covalently immobilized on SWNT through a molecular bilinker, 1-pyrenemethylamine, using carbodiimide coupling reaction. The sensor was characterized by the current-voltage (I-V) characteristic curve and scanning electron microscopy. The sensing performance of the sensor was studied with respect to changes in conductance in SWNT channel based on hybridization of the target S. pyogenes single stranded genomic DNA (ssG-DNA) to its complementary 24 mer ssDNA probe. The sensor shows negligible response to non-complementary Staphylococcus aureus ssG-DNA, confirming the specificity of the sensor only with S. pyogenes. The genosensor exhibited a linear response to S. pyogenes G-DNA from 1 to1000 ng ml −1 with a limit of detection of 0.16 ng ml −1

  1. Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Swati; Kumar, Ashok, E-mail: rajesh-csir@yahoo.com, E-mail: ashokigib@rediffmail.com [CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007 (India); Academy of Scientific and Innovative Research (AcSIR), New Delhi (India); Khare, Shashi [National Centre for Disease Control, Sham Nath Marg, Delhi 110054 (India); Mulchandani, Ashok [Department of Chemical and Environmental Engineering, University of California, Riverside, California 92521 (United States); Rajesh, E-mail: rajesh-csir@yahoo.com, E-mail: ashokigib@rediffmail.com [CSIR-National Physical Laboratory, Dr. K. S. Krishnan Road, New Delhi 110012 (India)

    2014-11-24

    A specific and ultrasensitive, label free single-walled carbon nanotubes (SWNTs) based chemiresistive genosensor was fabricated for the early detection of Streptococcus pyogenes infection in human causing rheumatic heart disease. The mga gene of S. pyogenes specific 24 mer ssDNA probe was covalently immobilized on SWNT through a molecular bilinker, 1-pyrenemethylamine, using carbodiimide coupling reaction. The sensor was characterized by the current-voltage (I-V) characteristic curve and scanning electron microscopy. The sensing performance of the sensor was studied with respect to changes in conductance in SWNT channel based on hybridization of the target S. pyogenes single stranded genomic DNA (ssG-DNA) to its complementary 24 mer ssDNA probe. The sensor shows negligible response to non-complementary Staphylococcus aureus ssG-DNA, confirming the specificity of the sensor only with S. pyogenes. The genosensor exhibited a linear response to S. pyogenes G-DNA from 1 to1000 ng ml{sup −1} with a limit of detection of 0.16 ng ml{sup −1}.

  2. EPR analysis of cyanide complexes of wild-type human neuroglobin and mutants in comparison to horse heart myoglobin.

    Science.gov (United States)

    Van Doorslaer, Sabine; Trandafir, Florin; Harmer, Jeffrey R; Moens, Luc; Dewilde, Sylvia

    2014-06-01

    Electron paramagnetic resonance (EPR) data reveal large differences between the ferric ((13)C-)cyanide complexes of wild-type human neuroglobin (NGB) and its H64Q and F28L point mutants and the cyanide complexes of mammalian myo- and haemoglobin. The point mutations, which involve residues comprising the distal haem pocket in NGB, induce smaller, but still significant changes, related to changes in the stabilization of the cyanide ligand. Furthermore, for the first time, the full (13)C hyperfine tensor of the cyanide carbon of cyanide-ligated horse heart myoglobin (hhMb) was determined using Davies ENDOR (electron nuclear double resonance). Disagreement of these experimental data with earlier predictions based on (13)C NMR data and a theoretical model reveal significant flaws in the model assumptions. The same ENDOR procedure allowed also partial determination of the corresponding (13)C hyperfine tensor of cyanide-ligated NGB and H64QNGB. These (13)C parameters differ significantly from those of cyanide-ligated hhMb and challenge our current theoretical understanding of how the haem environment influences the magnetic parameters obtained by EPR and NMR in cyanide-ligated haem proteins. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Practical training on porcine hearts enhances students' knowledge of human cardiac anatomy.

    Science.gov (United States)

    Musumeci, Giuseppe; Loreto, Carla; Mazzone, Venera; Szychlinska, Marta Anna; Castrogiovanni, Paola; Castorina, Sergio

    2014-05-01

    Historically, cadavers have been used for the study of anatomy. Nowadays, the territorial and legal limitations of this approach have led to the introduction of alternative teaching methods such as the use of practical exercise consisting of dissection and observation of animal organs. The aim of this study was to evaluate the use of practical training on animal organs compared with the traditional method of anatomy teaching, based on the dissection of human cadavers. In this study, we seek to demonstrate the usefulness of practical exercise on animal organs. This practical training was held a week after the series of lectures, thus leaving time for the students to learn and understand the topics discussed. Immediately after the lecture, all of the students completed a preliminary test to assess the immediate effect of the lecture. Immediately before the practical exercise, both control and experimental groups completed a second test to assess the effectiveness of personal study. Immediately after practical training, a third test was completed by the experimental group and the control group (no practical activity on animal organs) to highlight the added value of hands-on practice in addition to the lecture. Data obtained from statistical analysis showed a panatomy learning between control and experimental groups. Thus, the results of this study emphasize the utility of practical training on animal organs in learning and understanding anatomy, considering the limitations of the use of cadavers. Copyright © 2014 Elsevier GmbH. All rights reserved.

  4. Healthcare performance and the effects of the binaural beats on human blood pressure and heart rate.

    Science.gov (United States)

    Carter, Calvin

    2008-01-01

    Binaural beats are the differences in two different frequencies (in the range of 30-1000 Hz). Binaural beats are played through headphones and are perceived by the superior olivary nucleus of each hemisphere of the brain. The brain perceives the binaural beat and resonates to its frequency (frequency following response). Once the brain is in tune with the binaural beat it produces brainwaves of that frequency altering the listener's state of mind. In this experiment, the effects of the beta and theta binaural beat on human blood pressure and pulse were studied. Using headphones, three sounds were played for 7 minutes each to 12 participants: the control,- the sound of a babbling brook (the background sound to the two binaural beats), the beta binaural beat (20 Hz), and the theta binaural beat (7 Hz). Blood pressure and pulse were recorded before and after each sound was played. Each participant was given 2 minutes in-between each sound. The results showed that the control and the two binaural beats did not affect the 12 participant's blood pressure or pulse (p > 0.05). One reason for this may be that the sounds were not played long enough for the brain to either perceive and/or resonate to the frequency. Another reason why the sounds did not affect blood pressure and pulse may be due to the participant's age since older brains may not perceive the binaural beats as well as younger brains.

  5. The testosterone-dependent and independent transcriptional networks in the hypothalamus of Gpr54 and Kiss1 knockout male mice are not fully equivalent

    Directory of Open Access Journals (Sweden)

    Sutcliffe Margaret

    2011-04-01

    Full Text Available Abstract Background Humans and mice with loss of function mutations in GPR54 (KISS1R or kisspeptin do not progress through puberty, caused by a failure to release GnRH. The transcriptional networks regulated by these proteins in the hypothalamus have yet to be explored by genome-wide methods. Results We show here, using 1 million exon mouse arrays (Exon 1.0 Affymetrix and quantitative polymerase chain reaction (QPCR validation to analyse microdissected hypothalamic tissue from Gpr54 and Kiss1 knockout mice, the extent of transcriptional regulation in the hypothalamus. The sensitivity to detect important transcript differences in microdissected RNA was confirmed by the observation of counter-regulation of Kiss1 expression in Gpr54 knockouts and confirmed by immunohistochemistry (IHC. Since Gpr54 and Kiss1 knockout animals are effectively pre-pubertal with low testosterone (T levels, we also determined which of the validated transcripts were T-responsive and which varied according to genotype alone. We observed four types of transcriptional regulation (i genotype only dependent regulation, (ii T only dependent regulation, (iii genotype and T-dependent regulation with interaction between these variables, (iv genotype and T-dependent regulation with no interaction between these variables. The results implicate for the first time several transcription factors (e.g. Npas4, Esr2, proteases (Klk1b22, and the orphan 10-transmembrane transporter TMEM144 in the biology of GPR54/kisspeptin function in the hypothalamus. We show for the neuronal activity regulated transcription factor NPAS4, that distinct protein over-expression is seen in the hypothalamus and hippocampus in Gpr54 knockout mice. This links for the first time the hypothalamic-gonadal axis with this important regulator of inhibitory synapse formation. Similarly we confirm TMEM144 up-regulation in the hypothalamus by RNA in situ hybridization and western blot. Conclusions Taken together, global

  6. Creatine kinase rate constant in the human heart measured with 3D‐localization at 7 tesla

    Science.gov (United States)

    Robson, Matthew D.; Neubauer, Stefan; Rodgers, Christopher T.

    2016-01-01

    Purpose We present a new Bloch‐Siegert four Angle Saturation Transfer (BOAST) method for measuring the creatine kinase (CK) first‐order effective rate constant kf in human myocardium at 7 tesla (T). BOAST combines a variant of the four‐angle saturation transfer (FAST) method using amplitude‐modulated radiofrequency pulses, phosphorus Bloch‐Siegert B1+‐mapping to determine the per‐voxel flip angles, and nonlinear fitting to Bloch simulations for postprocessing. Methods Optimal flip angles and repetition time parameters were determined from Monte Carlo simulations. BOAST was validated in the calf muscle of two volunteers at 3T and 7T. The myocardial CK forward rate constant was then measured in 10 volunteers at 7T in 82 min (after 1H localization). Results BOAST kfCK values were 0.281 ± 0.002 s−1 in the calf and 0.35 ± 0.05 s−1 in myocardium. These are consistent with literature values from lower fields. Using a literature values for adenosine triphosphate concentration, we computed CK flux values of 4.55 ± 1.52 mmol kg−1 s−1. The sensitive volume for BOAST depends on the B1 inhomogeneity of the transmit coil. Conclusion BOAST enables measurement of the CK rate constant in the human heart at 7T, with spatial localization in three dimensions to 5.6 mL voxels, using a 10‐cm loop coil. Magn Reson Med 78:20–32, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:27579566

  7. Vortex-ring mixing as a measure of diastolic function of the human heart: Phantom validation and initial observations in healthy volunteers and patients with heart failure.

    Science.gov (United States)

    Töger, Johannes; Kanski, Mikael; Arvidsson, Per M; Carlsson, Marcus; Kovács, Sándor J; Borgquist, Rasmus; Revstedt, Johan; Söderlind, Gustaf; Arheden, Håkan; Heiberg, Einar

    2016-06-01

    To present and validate a new method for 4D flow quantification of vortex-ring mixing during early, rapid filling of the left ventricle (LV) as a potential index of diastolic dysfunction and heart failure. 4D flow mixing measurements were validated using planar laser-induced fluorescence (PLIF) in a phantom setup. Controls (n = 23) and heart failure patients (n = 23) were studied using 4D flow at 1.5T (26 subjects) or 3T (20 subjects) to determine vortex volume (VV) and inflowing volume (VVinflow ). The volume mixed into the vortex-ring was quantified as VVmix-in = VV-VVinflow . The mixing ratio was defined as MXR = VVmix-in /VV. Furthermore, we quantified the fraction of the end-systolic volume (ESV) mixed into the vortex-ring (VVmix-in /ESV) and the fraction of the LV volume at diastasis (DV) occupied by the vortex-ring (VV/DV). PLIF validation of MXR showed fair agreement (R(2) = 0.45, mean ± SD 1 ± 6%). MXR was higher in patients compared to controls (28 ± 11% vs. 16 ± 10%, P Vortex-ring mixing can be quantified using 4D flow. The differences in mixing parameters observed between controls and patients motivate further investigation as indices of diastolic dysfunction. J. Magn. Reson. Imaging 2016;43:1386-1397. © 2015 Wiley Periodicals, Inc.

  8. Hypothalamus transcriptome profile suggests an anorexia-cachexia syndrome in the anx/anx mouse model.

    Science.gov (United States)

    Mercader, Josep Maria; Lozano, Juan José; Sumoy, Lauro; Dierssen, Mara; Visa, Joana; Gratacòs, Mònica; Estivill, Xavier

    2008-11-12

    The anx/anx mouse displays poor appetite and lean appearance and is considered a good model for the study of anorexia nervosa. To identify new genes involved in feeding behavior and body weight regulation we performed an expression profiling in the hypothalamus of the anx/anx mice. Using commercial microarrays we detected 156 differentially expressed genes and validated 92 of those using TaqMan low-density arrays. The expression of a set of 87 candidate genes selected based on literature evidences was also quantified by TaqMan low-density arrays. Our results showed enrichment in deregulated genes involved in cell death, cell morphology, and cancer, as well as an alteration of several signaling circuits involved in energy balance including neuropeptide Y and melanocortin signaling. The expression profile along with the phenotype led us to conclude that anx/anx mice resemble the anorexia-cachexia syndrome typically observed in cancer, infection with human immunodeficiency virus or chronic diseases, rather than starvation, and that anx/anx mice could be considered a good model for the treatment and investigation of this condition.

  9. Leptin-dependent neuronal NO signaling in the preoptic hypothalamus facilitates reproduction.

    Science.gov (United States)

    Bellefontaine, Nicole; Chachlaki, Konstantina; Parkash, Jyoti; Vanacker, Charlotte; Colledge, William; d'Anglemont de Tassigny, Xavier; Garthwaite, John; Bouret, Sebastien G; Prevot, Vincent

    2014-06-01

    The transition to puberty and adult fertility both require a minimum level of energy availability. The adipocyte-derived hormone leptin signals the long-term status of peripheral energy stores and serves as a key metabolic messenger to the neuroendocrine reproductive axis. Humans and mice lacking leptin or its receptor fail to complete puberty and are infertile. Restoration of leptin levels in these individuals promotes sexual maturation, which requires the pulsatile, coordinated delivery of gonadotropin-releasing hormone to the pituitary and the resulting surge of luteinizing hormone (LH); however, the neural circuits that control the leptin-mediated induction of the reproductive axis are not fully understood. Here, we found that leptin coordinated fertility by acting on neurons in the preoptic region of the hypothalamus and inducing the synthesis of the freely diffusible volume-based transmitter NO, through the activation of neuronal NO synthase (nNOS) in these neurons. The deletion of the gene encoding nNOS or its pharmacological inhibition in the preoptic region blunted the stimulatory action of exogenous leptin on LH secretion and prevented the restoration of fertility in leptin-deficient female mice by leptin treatment. Together, these data indicate that leptin plays a central role in regulating the hypothalamo-pituitary-gonadal axis in vivo through the activation of nNOS in neurons of the preoptic region.

  10. Effects of n-3 fatty acids from fish on premature ventricular complexes and heart rate in humans

    NARCIS (Netherlands)

    Geelen, A.; Brouwer, I.A.; Katan, M.B.; Schouten, E.G.; Maan, A.C.; Zock, P.L.

    2005-01-01

    Background: A large body of evidence suggests that n-3 fatty acids from fish prevent fatal heart disease. They may be an effective and safe alternative to drug treatment for reducing the risk of arrhythmia and sudden cardiac death. Objective: We investigated the effect of n-3 fatty acids on heart

  11. The influence of age on N-isopropyl-p-[123I]iodoamphetamine accumulation in the human heart

    International Nuclear Information System (INIS)

    Nakajo, Masayuki; Nakabeppu, Yoshiaki; Iwashita, Shinji; Shinohara, Shinji

    1990-01-01

    Variations in heart intensity in the 30 min and 4 hr chest images of the radiolabelled lipophilic amine, N-isopropyl-p-[ 123 I]iodoamphetamine ( 123 I-IMP) were observed in 130 patients with lung diseases, aged 23 to 85 yrs. The heart intensity had a significant positive linear correlation with age (r=0.43 at 30 min, 0.66 at 4 hr). The ratio of 4 hr heart intensity to 30 min heart intensity also had a positive linear correlation (r=0.59), suggesting slower clearance of the radioactivity from the heart in older than in younger patients during this interval. Other parameters including sex, EKG findings, liver function, blood pressure, the presence of diabetes mellitus and smoking history had no relationship to heart intensity. A significant difference between heart intensities in bronchogenic carcinoma and pneumonia patient groups might be probably due to the age difference between the two groups. Therefore heart intensity in the 4 hr 123 I-IMP image may reflect certain metabolic and/or myocardial changes with aging. (author)

  12. The protective effect of ursodeoxycholic acid in an in vitro model of the human fetal heart occurs via targeting cardiac fibroblasts.

    Science.gov (United States)

    Schultz, Francisca; Hasan, Alveera; Alvarez-Laviada, Anita; Miragoli, Michele; Bhogal, Navneet; Wells, Sarah; Poulet, Claire; Chambers, Jenny; Williamson, Catherine; Gorelik, Julia

    2016-01-01

    Bile acids are elevated in the blood of women with intrahepatic cholestasis of pregnancy (ICP) and this may lead to fetal arrhythmia, fetal hypoxia and potentially fetal death in utero. The bile acid taurocholic acid (TC) causes abnormal calcium dynamics and contraction in neonatal rat cardiomyocytes. Ursodeoxycholic acid (UDCA), a drug clinically used to treat ICP, prevents adverse effects of TC. During development, the fetus is in a state of relative hypoxia. Although this is essential for the development of the heart and vasculature, resident fibroblasts can transiently differentiate into myofibroblasts and form gap junctions with cardiomyocytes in vitro, resulting in cardiomyocyte depolarization. We expanded on previously published work using an in vitro hypoxia model to investigate the differentiation of human fetal fibroblasts into myofibroblasts. Recent evidence shows that potassium channels are involved in maintaining the membrane potential of ventricular fibroblasts and that ATP-dependent potassium (KATP) channel subunits are expressed in cultured fibroblasts. KATP channels are a valuable target as they are thought to have a cardioprotective role during ischaemic and hypoxic conditions. We investigated whether UDCA could modulate fibroblast membrane potential. We established the isolation and culture of human fetal cardiomyocytes and fibroblasts to investigate the effect of hypoxia, TC and UDCA on human fetal cardiac cells. UDCA hyperpolarized myofibroblasts and prevented TC-induced depolarisation, possibly through the activation of KATP channels that are expressed in cultured fibroblasts. Also, similar to the rat model, UDCA can counteract TC-induced calcium abnormalities in human fetal cultures of cardiomyocytes and myofibroblasts. Under normoxic conditions, we found a higher number of myofibroblasts in cultures derived from human fetal hearts compared to cells isolated from neonatal rat hearts, indicating a possible increased number of myofibroblasts

  13. E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells

    OpenAIRE

    Lee, Hyun-Wook; Park, Sung-Hyun; Weng, Mao-wen; Wang, Hsiang-Tsui; Huang, William C.; Lepor, Herbert; Wu, Xue-Ru; Chen, Lung-Chi; Tang, Moon-shong

    2018-01-01

    Significance E-cigarette smoke (ECS) delivers nicotine through aerosols without burning tobacco. ECS is promoted as noncarcinogenic. We found that ECS induces DNA damage in mouse lung, bladder, and heart and reduces DNA-repair functions and proteins in lung. Nicotine and its nitrosation product 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone can cause the same effects as ECS and enhance mutations and tumorigenic cell transformation in cultured human lung and bladder cells. These results indica...

  14. Embryonic and foetal Islet-1 positive cells in human hearts are also positive to c-Kit

    Directory of Open Access Journals (Sweden)

    C. Serradifalco

    2011-12-01

    Full Text Available During embryogenesis, the mammalian heart develops from a primitive heart tube originating from two bilateral primary heart fields located in the lateral plate mesoderm. Cells belongings to the pre-cardiac mesoderm will differentiate into early cardiac progenitors, which express early transcription factors which are also common to the Isl-1 positive cardiac progenitor cells isolated from the developing pharyngeal mesoderm and the foetal and post-natal mice hearts. A second population of cardiac progenitor cells positive to c-Kit has been abundantly isolated from adult hearts. Until now, these two populations have been considered two different sets of progenitor cells present in the heart in different stages of an individual life. In the present study we collected embryonic, foetal and infant hearts, and we tested the hypotheses that c-Kit positive cells, usually isolated from the adult heart, are also present in the intra-uterine life and persist in the adult heart after birth, and that foetal Isl-1 positive cells are also positive to c-Kit. Using immunohistochemistry we studied the temporal distribution of Isl-1 positive and c-Kit/CD105 double positive cells, and by immunofluorescence and confocal analysis we studied the co-localization of c-Kit and Isl-1 positive cells. The results indicated that cardiomyocytes and interstitial cells were positive for c-Kit from the 9th to the 19th gestational week, that cells positive for both c-Kit and CD105 appeared in the interstitium at the 17th gestational week and persisted in the postnatal age, and that the Isl-1 positive cells were a subset of the c-Kit positive population.

  15. Heart Diseases

    Science.gov (United States)

    ... you're like most people, you think that heart disease is a problem for others. But heart disease is the number one killer in the ... of disability. There are many different forms of heart disease. The most common cause of heart disease ...

  16. Heart Transplantation

    Science.gov (United States)

    A heart transplant removes a damaged or diseased heart and replaces it with a healthy one. The healthy heart comes from a donor who has died. It is the last resort for people with heart failure when all other treatments have failed. The ...

  17. Physiological Mechanisms Mediating the Coupling between Heart Period and Arterial Pressure in Response to Postural Changes in Humans

    NARCIS (Netherlands)

    Silvani, A.; Calandra-Buonaura, G.; Johnson, B.D.; Helmond, N. van; Barletta, G.; Cecere, A.G.; Joyner, M.J.; Cortelli, P.

    2017-01-01

    The upright posture strengthens the coupling between heart period (HP) and systolic arterial pressure (SAP) consistently with a greater contribution of the arterial baroreflex to cardiac control, while paradoxically decreasing cardiac baroreflex sensitivity (cBRS). To investigate the physiological

  18. Transcriptome-wide identification of preferentially expressed genes in the hypothalamus and pituitary gland.

    Science.gov (United States)

    St-Amand, Jonny; Yoshioka, Mayumi; Tanaka, Keitaro; Nishida, Yuichiro

    2011-01-01

    To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the hypothalamus, pituitary gland, and parietal cortex in male mice (12-15 weeks old) using serial analysis of gene expression (SAGE). Total counts of SAGE tags for the hypothalamus, pituitary gland, and parietal cortex were 165824, 126688, and 161045 tags, respectively. This represented 59244, 45151, and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix, and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis, and turnover, cell differentiation, the cell cycle, and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland.

  19. Transcriptome-wide identification of preferentially expressed genes in the hypothalamus and pituitary gland

    Directory of Open Access Journals (Sweden)

    Jonny eSt-Amand

    2012-01-01

    Full Text Available To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the mouse hypothalamus, pituitary gland and parietal cortex using serial analysis of gene expression (SAGE. Total counts of SAGE tags for the hypothalamus, pituitary gland and parietal cortex were 165824, 126688 and 161045 tags, respectively. This represented 59244, 45151 and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis and turnover, cell differentiation, the cell cycle and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland.

  20. Hypothalamus-Anchored Resting Brain Network Changes before and after Sertraline Treatment in Major Depression

    Directory of Open Access Journals (Sweden)

    Rui Yang

    2014-01-01

    Full Text Available Sertraline, one of the oldest antidepressants, remains to be the most efficacious treatment for depression. However, major depression disorder (MDD is characterized by altered emotion processing and deficits in cognitive control. In cognitive interference tasks, patients with MDD have shown excessive hypothalamus activity. The purpose of this study was to examine the effects of antidepressant treatment (sertraline on hypothalamus-anchored resting brain circuitry. Functional magnetic resonance imaging was conducted on depressed patients (n=12 both before and after antidepressant treatment. After eight weeks of antidepressant treatment, patients with depression showed significantly increased connectivity between the hypothalamus and dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, insula, putamen, caudate, and claustrum. By contrast, decreased connectivity of the hypothalamus-related areas was primarily located in the inferior frontal gyrus, medial frontal gyrus, cingulated gyrus, precuneus, thalamus, and cerebellum. After eight weeks of antidepressant therapy, 8 out of the 12 depressed subjects achieved 70% reduction or better in depressive symptoms, as measured on the Hamilton depression rating scale. Our findings may infer that antidepressant treatment can alter the functional connectivity of the hypothalamus resting brain to achieve its therapeutic effect.

  1. Creatine kinase rate constant in the human heart measured with 3D-localization at 7 tesla.

    Science.gov (United States)

    Clarke, William T; Robson, Matthew D; Neubauer, Stefan; Rodgers, Christopher T

    2017-07-01

    We present a new Bloch-Siegert four Angle Saturation Transfer (BOAST) method for measuring the creatine kinase (CK) first-order effective rate constant k f in human myocardium at 7 tesla (T). BOAST combines a variant of the four-angle saturation transfer (FAST) method using amplitude-modulated radiofrequency pulses, phosphorus Bloch-Siegert B1+-mapping to determine the per-voxel flip angles, and nonlinear fitting to Bloch simulations for postprocessing. Optimal flip angles and repetition time parameters were determined from Monte Carlo simulations. BOAST was validated in the calf muscle of two volunteers at 3T and 7T. The myocardial CK forward rate constant was then measured in 10 volunteers at 7T in 82 min (after 1 H localization). BOAST kfCK values were 0.281 ± 0.002 s -1 in the calf and 0.35 ± 0.05 s -1 in myocardium. These are consistent with literature values from lower fields. Using a literature values for adenosine triphosphate concentration, we computed CK flux values of 4.55 ± 1.52 mmol kg -1 s -1 . The sensitive volume for BOAST depends on the B 1 inhomogeneity of the transmit coil. BOAST enables measurement of the CK rate constant in the human heart at 7T, with spatial localization in three dimensions to 5.6 mL voxels, using a 10-cm loop coil. Magn Reson Med 78:20-32, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  2. A crucial role of activin A-mediated growth hormone suppression in mouse and human heart failure.

    Directory of Open Access Journals (Sweden)

    Noritoshi Fukushima

    Full Text Available Infusion of bone marrow-derived mononuclear cells (BMMNC has been reported to ameliorate cardiac dysfunction after acute myocardial infarction. In this study, we investigated whether infusion of BMMNC is also effective for non-ischemic heart failure model mice and the underlying mechanisms. Intravenous infusion of BMMNC showed transient cardioprotective effects on animal models with dilated cardiomyopathy (DCM without their engraftment in heart, suggesting that BMMNC infusion improves cardiac function via humoral factors rather than their differentiation into cardiomyocytes. Using conditioned media from sorted BMMNC, we found that the cardioprotective effects were mediated by growth hormone (GH secreted from myeloid (Gr-1(+ cells and the effects was partially mediated by signal transducer and activator of transcription 3 in cardiomyocytes. On the other hand, the GH expression in Gr-1(+ cells was significantly downregulated in DCM mice compared with that in healthy control, suggesting that the environmental cue in heart failure might suppress the Gr-1(+ cells function. Activin A was upregulated in the serum of DCM models and induced downregulation of GH levels in Gr-1(+ cells and serum. Furthermore, humoral factors upregulated in heart failure including angiotensin II upregulated activin A in peripheral blood mononuclear cells (PBMNC via activation of NFκB. Similarly, serum activin A levels were also significantly higher in DCM patients with heart failure than in healthy subjects and the GH levels in conditioned medium from PBMNC of DCM patients were lower than that in healthy subjects. Inhibition of activin A increased serum GH levels and improved cardiac function of DCM model mice. These results suggest that activin A causes heart failure by suppressing GH activity and that inhibition of activin A might become a novel strategy for the treatment of heart failure.

  3. From Shuttle Main Engine to the Human Heart: A Presentation to the Federal Lab Consortium for Technology Transfer

    Science.gov (United States)

    Fogarty, Jennifer A.

    2010-01-01

    A NASA engineer received a heart transplant performed by Drs. DeBakey and Noon after suffering a serious heart attack. 6 months later that engineer returned to work at NASA determined to use space technology to help people with heart disease. A relationship between NASA and Drs. DeBakey and Noon was formed and the group worked to develop a low cost, low power implantable ventricular assist device (VAD). NASA patented the method to reduce pumping damage to red blood cells and the design of a continuous flow heart pump (#5,678,306 and #5,947,892). The technology and methodology were licensed exclusively to MicroMed Technology, Inc.. In late 1998 MicroMed received international quality and electronic certifications and began clinical trials in Europe. Ventricular assist devices were developed to bridge the gap between heart failure and transplant. Early devices were cumbersome, damaged red blood cells, and increased the risk of developing dangerous blood clots. Application emerged from NASA turbopump technology and computational fluid dynamics analysis capabilities. To develop the high performance required of the Space Shuttle main engines, NASA pushed the state of the art in the technology of turbopump design. NASA supercomputers and computational fluid dynamics software developed for use in the modeling analysis of fuel and oxidizer flow through rocket engines was used in the miniaturization and optimization of a very small heart pump. Approximately 5 million people worldwide suffer from chronic heart failure at a cost of 40 billion dollars In the US, more than 5000 people are on the transplant list and less than 3000 transplants are performed each year due to the lack of donors. The success of ventricular assist devices has led to an application as a therapeutic destination as well as a bridge to transplant. This success has been attributed to smaller size, improved efficiency, and reduced complications such as the formation of blood clots and infection.

  4. Effect of gamma irradiation on the activity of monoamine oxidase in the hypothalamus of ewes

    International Nuclear Information System (INIS)

    Pastorova, B.; Stanikova, A.

    2008-01-01

    The study investigated changes in monoamine oxidase (MAO) activity in the hypothalamus of ewes in the anoestrous period exposed to a whole body Co-60 irradiation with a total dose of 6.7 Gy for the period of 7 days. The activity of MAO was determined by means of a radiochemical method using C-14 tryptamine as a substrate. Whole body exposure to gamma radiation of total dose of 6.7 Gy increased significantly (P < 0.001) the activity of MAO in the caudal, medial and rostral hypothalamus of the investigated ewes. It may by assumed that an increased degradation of catecholamines caused by MAO is one of the mechanisms responsible for pronounced changes in the level of catecholamines in the hypothalamus of ewes after irradiation. (authors)

  5. Study on the interaction between leucine-enkephalin and hypothalamus-pituitary-thyroid axis

    International Nuclear Information System (INIS)

    Li Fengying; Chen Jialun; Chen Mingdao; Tang Jinfeng; Li Jiping

    2001-01-01

    Objective: To study the possible interaction between leucine enkephalin and hypothalamus-pituitary-thyroid axis. Methods: Mice models of hyperthyroidism and hypothyroidism were produced. Serum thyroid hormonal levels (T 3 , T 4 , TSH, TRH), the leucine enkephalin content of the whole brain and 5-HT of the hypothalamus were determined in the animals sacrificed on different days after the animal models were established. Results: In hyperthyroid rats, the levels of T 3 , T 4 increased progressively (P 3 , T 4 levels were persistent lower (P < 0.001) along with gradually increasing of serum TSH and TRH levels while pituitary TSh hypothalamus TRH content decreased gradually (P < 0.01), but rose back when reaching the nadir, Besides, LEK elevated and 5-HT decreased (P<0.01). Conclusion: The thyroid functional hormonal changes are not necessarily accompanied by a corresponding increase or decrease of brain LEK

  6. Catecholamine levels in sheep hypothalamus, hypophysis and adrenals following whole-body gamma irradiation

    International Nuclear Information System (INIS)

    Pastorova, B.; Arendarcik, J.; Molnarova, M.

    1985-01-01

    Changes were studied in the levels of catecholamines and L-DOPA in the control system of the reproduction cycle (hypothalamus, hypophysis) and in the adrenal glands of sheep after whole-body irradiation with 60 Co at a total dose of 6.7 Gy for seven days. The output of the radiation source was 0.039 Gy/h. The catecholamines (noradrenaline, dopamine and adrenaline) and L-DOPA were determined after separation from the tissues by the method of spectral fluorometry. After whole-body exposure to gamma radiation, noradrenaline dropped in the hypothalamus in comparison with the control group, most significantly in the rostral (by 74.2%) and caudal (by 40%) parts. A similar drop was also observed in dopamine, the concentrations of which decreased in the rostral hypothalamus by 60%. Adrenaline showed a drop in the hypothalamus, most significant in the caudal region (by 62%). Consequently, the level of the precursor of the synthesis of catecholamines and L-DOPA changed and showed in the studied regions of the hypothalamus significantly lower levels than in the control group. As regards the hypophysis, after irradiation no significant changes in the levels of noradrenaline and adrenaline were recorded, however, dopamine and L-DOPA dropped significantly (P<0.01). The exposure to gamma radiation also causes a decrease in the concentrations of catecholamines and L-DOPA in the adrenal glands of sheep, most significantly in noradrenaline (by 61%). It was thus found that whole-body irradiation of sheep with a dose of 6.7 Gy results in a significant decrease in the level of catecholamines in the hypothalamus, hypophysis and adrenal glands, which is probably in relation to the failure of synthesis and degradation of catecholamines and to the total organism injury

  7. A Newly Defined Area of the Mouse Anterior Hypothalamus Involved in Septohypothalamic Circuit: Perifornical Area of the Anterior Hypothalamus, PeFAH.

    Science.gov (United States)

    Horii-Hayashi, Noriko; Nishi, Mayumi

    2018-02-27

    Although the hypothalamus is classified into more than 10 compartments, it still contains uncharacterized areas. In this study, we identified a new triangular-shaped area between the paraventricular hypothalamic nucleus (PVN) and the fornix area in the mouse anterior hypothalamus, which is enriched in chondroitin sulfate proteoglycans (CSPGs). We designated this region as the perifornical area of the anterior hypothalamus (PeFAH) based on its anatomical location. As evidenced by Nissl staining, the PeFAH was distinguishable as an area of relatively low density. Immunohistochemical and DNA microarray analyses indicated that PeFAH contains sparsely distributed calretinin-positive neurons and densely clustered enkephalin-positive neurons. Furthermore, the PeFAH was shown to have bidirectional neural connections with the lateral septum. Indeed, we confirmed enkephalinergic projections from PeFAH neurons to the lateral septum, and inversely, calbindin-positive lateral septum neurons as afferents to the PeFAH. Finally, c-Fos expression analysis revealed that the activity of certain PeFAH neuronal populations tended to be increased by psychological stressors, but not that of enkephalinergic neurons. We proposed PeFAH as a new region in the AH.

  8. Optogenetic activation of leptin- and glucose-regulated GABAergic neurons in dorsomedial hypothalamus promotes food intake via inhibitory synaptic transmission to paraventricular nucleus of hypothalamus

    Directory of Open Access Journals (Sweden)

    Zesemdorj Otgon-Uul

    2016-08-01

    Full Text Available Objective: The dorsomedial hypothalamus (DMH has been considered an orexigenic nucleus, since the DMH lesion reduced food intake and body weight and induced resistance to diet-induced obesity. The DMH expresses feeding regulatory neuropeptides and receptors including neuropeptide Y (NPY, cocaine- and amphetamine-regulated transcript (CART, cholecystokinin (CCK, leptin receptor, and melanocortin 3/4 receptors. However, the principal neurons generating the orexigenic function in the DMH remain to be defined. This study aimed to clarify the role of the DMH GABAergic neurons in feeding regulation by using optogenetics and electrophysiological techniques. Methods: We generated the mice expressing ChRFR-C167A, a bistable chimeric channelrhodopsin, selectively in GABAergic neurons of DMH via locally injected adeno-associated virus 2. Food intake after optogenetic activation of DMH GABAergic neurons was measured. Electrophysiological properties of DMH GABAergic neurons were measured using slice patch clamp. Results: Optogenetic activation of DMH GABAergic neurons promoted food intake. Leptin hyperpolarized and lowering glucose depolarized half of DMH GABAergic neurons, suggesting their orexigenic property. Optical activation of axonal terminals of DMH GABAergic neurons at the paraventricular nucleus of hypothalamus (PVN, where anorexigenic neurons are localized, increased inhibitory postsynaptic currents on PVN neurons and promoted food intake. Conclusion: DMH GABAergic neurons are regulated by metabolic signals leptin and glucose and, once activated, promote food intake via inhibitory synaptic transmission to PVN. Keywords: Dorsomedial hypothalamus, GABAergic neuron, Feeding, Leptin, Glucose, Optogenetics

  9. Revealing Hearts

    DEFF Research Database (Denmark)

    Saghaug, Kristin Falck; Pattison, George; Lindgren, Peter

    2014-01-01

    with reference to Tillich’s account of the meaning of revelation through culture and art, summed up in the statement that “(...) revelation is the manifestation of the ground of being for human knowledge” (Tillich, 1951, p.94), which, we argue, can be extended to everyday experiences, for example, in business......Some small business owners want to balance personal values as well as economic values. “I have to follow my heart” or “it must be meaningful” some of them say. But how might they be able to know what gives meaning to the heart? The philosophical theologian Paul Tillich finds that the problem...... life. In Tillich’s own terms, even preliminary concerns may point at an ultimate concern (Tillich, 1964), which can also be understood as ‘knowledge of the heart’. Our account is also connected to wider discussions concerning the nature of intuition....

  10. Evolution of hypothalamus-pituitary growth axis among fish, amphibian, birds and mammals

    Directory of Open Access Journals (Sweden)

    Moaeen-Ud-Din M.

    2015-01-01

    Full Text Available Hypothalamus-pituitary growth axis (HP growth axis regulates animal growth and development in pre-natal and post natal life governed by many factors. However, until recently, the evolutionary history of this axis among lineages is not understood. Aim of the present study was to understand the major events in evolution and evolutionary history and trend of HP growth axis. The diversity among Homo sapience, Mus musculus, Rattus norvegicus, Gallus gallus, Danio rerio and Xenopus laevis was determined for genes involved in HP growth axis in current study. Sequences of HP growth axis genes were retrieved from NCBI (http://www.ncbi.nlm.nih.gov/. Nucleotide diversity using Kimura’s two-parameter method; codon-based test of positive selection using the Nei-Gojobori; equality of evolutionary rate with Tajima's relative rate test and phylogenetic history using the RelTime method were estimated in MEGA6. Estimates of the coefficients of evolutionary differentiation based on nucleotides and amino acids substitution patterns of HP growth axis genes showed contrasting evolutionary patterns among the lineages. The results demonstrated that although these genes might have crucial functional roles in each of the species, however, their sequence divergence did not necessarily reflect similar molecular evolution among the species. Codon-based test of positive selection revealed that Human vs Mouse, Chicken vs Rat, Human vs Rat and Mouse vs Rat had similar and higher non synonymous substitutions (P > 0.05. Higher rate of non-synonymous substitutions at similar orthologs level among species indicated a similar positive selection pressure in these species. Results for relative rate test assessed with the chi-squared test showed difference on unique mutations among lineages at synonymous and non synonymous sites except Chicken vs Mouse, Human vs Mouse, Chicken vs Rat, Human vs Rat and Mouse vs Rat. This indicated that the mutagenic process that generates

  11. Activation of SF1 Neurons in the Ventromedial Hypothalamus by DREADD Technology Increases Insulin Sensitivity in Peripheral Tissues.

    Science.gov (United States)

    Coutinho, Eulalia A; Okamoto, Shiki; Ishikawa, Ayako Wendy; Yokota, Shigefumi; Wada, Nobuhiro; Hirabayashi, Takahiro; Saito, Kumiko; Sato, Tatsuya; Takagi, Kazuyo; Wang, Chen-Chi; Kobayashi, Kenta; Ogawa, Yoshihiro; Shioda, Seiji; Yoshimura, Yumiko; Minokoshi, Yasuhiko

    2017-09-01

    The ventromedial hypothalamus (VMH) regulates glucose and energy metabolism in mammals. Optogenetic stimulation of VMH neurons that express steroidogenic factor 1 (SF1) induces hyperglycemia. However, leptin acting via the VMH stimulates whole-body glucose utilization and insulin sensitivity in some peripheral tissues, and this effect of leptin appears to be mediated by SF1 neurons. We examined the effects of activation of SF1 neurons with DREADD (designer receptors exclusively activated by designer drugs) technology. Activation of SF1 neurons by an intraperitoneal injection of clozapine- N -oxide (CNO), a specific hM3Dq ligand, reduced food intake and increased energy expenditure in mice expressing hM3Dq in SF1 neurons. It also increased whole-body glucose utilization and glucose uptake in red-type skeletal muscle, heart, and interscapular brown adipose tissue, as well as glucose production and glycogen phosphorylase a activity in the liver, thereby maintaining blood glucose levels. During hyperinsulinemic-euglycemic clamp, such activation of SF1 neurons increased insulin-induced glucose uptake in the same peripheral tissues and tended to enhance insulin-induced suppression of glucose production by suppressing gluconeogenic gene expression and glycogen phosphorylase a activity in the liver. DREADD technology is thus an important tool for studies of the role of the brain in the regulation of insulin sensitivity in peripheral tissues. © 2017 by the American Diabetes Association.

  12. Heart Truth

    Science.gov (United States)

    ... health! Get a free badge or banner to post to your website or blog. Are you at risk for heart disease? Here's how to find out . Planning to use The Heart Truth logo? Check out our logo guidelines and downloads. ...

  13. Heart Disease

    Science.gov (United States)

    ... it may be caused by diseases, such as connective tissue disorders, excessive iron buildup in your body (hemochromatosis), the buildup of abnormal proteins (amyloidosis) or by some cancer treatments. Causes of heart infection A heart infection, ...

  14. Heart Attack

    Science.gov (United States)

    ... family history of heart attack race – African Americans, Mexican Americans, Native Americans, and native Hawaiians are at ... Your doctor will prescribe the medicines that are right for you. If you have had a heart ...

  15. Persistent expression of activated notch in the developing hypothalamus affects survival of pituitary progenitors and alters pituitary structure.

    Science.gov (United States)

    Aujla, Paven K; Bogdanovic, Vedran; Naratadam, George T; Raetzman, Lori T

    2015-08-01

    As the pituitary gland develops, signals from the hypothalamus are necessary for pituitary induction and expansion. Little is known about the control of cues that regulate early signaling between the two structures. Ligands and receptors of the Notch signaling pathway are found in both the hypothalamus and Rathke's pouch. The downstream Notch effector gene Hes1 is required for proper pituitary formation; however, these effects could be due to the action of Hes1 in the hypothalamus, Rathke's pouch, or both. To determine the contribution of hypothalamic Notch signaling to pituitary organogenesis, we used mice with loss and gain of Notch function within the developing hypothalamus. We demonstrate that loss of Notch signaling by conditional deletion of Rbpj in the hypothalamus does not affect expression of Hes1 within the posterior hypothalamus or expression of Hes5. In contrast, expression of activated Notch within the hypothalamus results in ectopic Hes5 expression and increased Hes1 expression, which is sufficient to disrupt pituitary development and postnatal expansion. Taken together, our results indicate that Rbpj-dependent Notch signaling within the developing hypothalamus is not necessary for pituitary development, but persistent Notch signaling and ectopic Hes5 expression in hypothalamic progenitors affects pituitary induction and expansion. © 2015 Wiley Periodicals, Inc.

  16. Heart pacemaker

    Science.gov (United States)

    Cardiac pacemaker implantation; Artificial pacemaker; Permanent pacemaker; Internal pacemaker; Cardiac resynchronization therapy; CRT; Biventricular pacemaker; Arrhythmia - pacemaker; Abnormal heart ...

  17. The role of indium-111 antimyosin (Fab) imaging as a noninvasive surveillance method of human heart transplant rejection

    International Nuclear Information System (INIS)

    De Nardo, D.; Scibilia, G.; Macchiarelli, A.G.

    1989-01-01

    The identification of rejection after heart transplantation in patients receiving cyclosporine immunosuppressive therapy requires the endomyocardial biopsy, an invasive method associated with a finite morbidity. To evaluate the role of indium-111 antimyosin (Fab) scintigraphy as a noninvasive surveillance method of heart transplant rejection, the Fab fragment of murine monoclonal antimyosin antibodies labeled with indium-111 was administered intravenously in 30 scintigraphic studies to 10 consecutive heart transplant recipients. Endomyocardial biopsy specimens were obtained 72 hours after each scintigraphic study. Nineteen scintigraphic studies had negative findings; no false negative finding was obtained. Eleven antimyosin scintigraphic studies had positive findings, and in these studies endomyocardial biopsy revealed mild rejection in two cases, moderate acute rejection with myocyte necrosis in two cases, myocyte necrosis as a consequence of ischemic injury in six cases, and possibly cytotoxic damage in one case. Antimyosin scintigraphy may represent a reliable screening method for the surveillance of heart transplant patients. In the presence of a negative finding from antimyosin scintigraphy, it may be possible to avoid endomyocardial biopsy. Conversely, in patients who have a positive finding from antimyosin scintigraphy, the endomyocardial biopsy is mandatory to establish the definitive diagnosis by histologic examination of the myocardium

  18. Effect of a single oral dose of milrinone on left ventricular diastolic performance in the failing human heart

    NARCIS (Netherlands)

    F. Piscione; B.E. Jaski; G.J. Wenting (Gert); P.W.J.C. Serruys (Patrick)

    1987-01-01

    textabstractIn 14 patients with severe congestive heart failure, left ventricular pressure (measured by tip manometer) and derived variables were measured before and every 10 minutes after administration of oral milrinone (10 mg) for 50 minutes along with measurements of coronary sinus blood flow

  19. Alloreactive lymphoid infiltrates in human heart transplants: Loss of class II-directed cytotoxicity more than 3 months after transplantation

    NARCIS (Netherlands)

    A.J. Ouwehand; L.M.B. Vaessen (Leonard); C.C. Baan (Carla); N.H.P.M. Jutte (Nicolet); A.H.M.M. Balk (Aggie); C.E. Essed; E. Bos (Egbert); F.H.J. Claas (Frans); W. Weimar (Willem)

    1991-01-01

    markdownabstractAbstract From 535 endomyocardial biopsies (87 heart transplant recipients) 283 cell cultures could be generated. All cultures tested contained T lymphocytes and in most cases CD4 was the predominant phenotype at any time posttransplant. A significantly higher proportion of

  20. Are adipose-derived stem cells cultivated in human platelet lysate suitable for heart valve tissue engineering?

    NARCIS (Netherlands)

    Frese, L.; Sasse, T.; Sanders, B.; Baaijens, F.P.T.; Beer, G.M.; Hoerstrup, S.P.

    2017-01-01

    Tissue-engineered heart valves represent a promising strategy for the growing need for valve replacements in cardiovascular medicine. Recent studies have shown that adipose-derived stem cells (ADSC) are a viable cell source, as they are readily available in both the young and the elderly, show

  1. Perioperative and postoperative course of cytokines and the metabolic activity of neutrophils in human cardiac operations and heart transplantation

    Czech Academy of Sciences Publication Activity Database

    Kubala, Lukáš; Číž, Milan; Vondráček, Jan; Černý, J.; Němec, P.; Studeník, P.; Čížová, Hana; Lojek, Antonín

    2002-01-01

    Roč. 124, č. 12 (2002), s. 1122-1129 ISSN 0022-5223 R&D Projects: GA ČR GA524/01/1219; GA ČR GA524/00/1223 Institutional research plan: CEZ:AV0Z5004920 Keywords : heart transplantation * cardiopulmonary bypass * inflammation Subject RIV: BO - Biophysics Impact factor: 2.842, year: 2002

  2. Plasma Amino Acid Abnormalities in Chronic Heart Failure. Mechanisms, Potential Risks and Targets in Human Myocardium Metabolism

    Directory of Open Access Journals (Sweden)

    Roberto Aquilani

    2017-11-01

    Full Text Available The goal of this study was to measure arterial amino acid levels in patients with chronic heart failure (CHF, and relate them to left ventricular function and disease severity. Amino acids (AAs play a crucial role for heart protein-energy metabolism. In heart failure, arterial AAs, which are the major determinant of AA uptake by the myocardium, are rarely measured. Forty-one subjects with clinically stable CHF (New York Heart Association (NYHA class II to IV were analyzed. After overnight fasting, blood samples from the radial artery were taken to measure AA concentrations. Calorie (KcalI, protein-, fat-, carbohydrate-intake, resting energy expenditure (REE, total daily energy expenditure (REE × 1.3, and cardiac right catheterization variables were all measured. Eight matched controls were compared for all measurements, with the exception of cardiac catheterization. Compared with controls, CHF patients had reduced arterial AA levels, of which both their number and reduced rates are related to Heart Failure (HF severity. Arterial aspartic acid correlated with stroke volume index (r = 0.6263; p < 0.0001 and cardiac index (r = 0.4243; p = 0.0028. The value of arterial aspartic acid (µmol/L multiplied by the cardiac index was associated with left ventricular ejection fraction (r = 0.3765; p = 0.0076. All NYHA groups had adequate protein intake (≥1.1 g/kg/day and inadequate calorie intake (KcalI < REE × 1.3 was found only in class IV patients. This study showed that CHF patients had reduced arterial AA levels directly related to clinical disease severity and left ventricular dysfunction.

  3. Preoperative assessment of congestive liver dysfunction using technetium-99m galactosyl human Serum albumin liver scintigraphy in patients with severe valvular heart disease

    International Nuclear Information System (INIS)

    Nishi, Hiroyuki; Matsumiya, Goro; Takano, Hiroshi; Ichikawa, Hajime; Miyagawa, Shigeru; Sawa, Yoshiki; Takahashi, Toshiki

    2007-01-01

    Severe valvular heart disease is often complicated by congestive liver dysfunction, which greatly compromises the operative results. We evaluated congestive liver dysfunction by a novel approach using technetium-99m galactosyl human serum albumin ( 99m Tc-GSA) with liver scintigraphy. Between 1998 and 2004, we performed scintigraphy accompanied by 99m Tc-GSA in 28 patients who had valvular heart disease with moderate-to-severe tricuspid regurgitation and who showed symptoms of right heart failure. Based on the results, we calculated a receptor index (LHL15) and an index of blood clearance (HH15) and assessed the correlation between these factors and postoperative liver dysfunction, defined as the maximum serum total bilirubin level (max T-bil) as >2.0 mg/dl. Nineteen patients, including four who died in hospital, had postoperative liver dysfunction. The level of HH15 was significantly higher and the level of cholinesterase was significantly lower (P 99m Tc-GSA is a clinically useful predictor of postoperative liver dysfunction in patients with severe valvular disease. (author)

  4. Effects of HPM irradiation on expression of GR in hypothalamus and pituitary gland of rats

    International Nuclear Information System (INIS)

    Meng Li; Peng Ruiyun; Gao Yabing; Ma Junjie; Wang Shuiming; Hu Wenhua; Wang Dewen; Su Zhentao

    2005-01-01

    Objective: To explore the expression and significance of glucocorticoid receptor (GR) in hypothalamus and pituitary gland of rats after high power microwave (HPM) exposure. Methods: A total of 130 male Wistar rats were sacrificed at 6 h, 1 d, 3 d, 7 d, 14 d, 28 d and 3 m after whole body irradiation by 2-90 mW/cm 2 HPM and their hypothalamus and pituitary gland were collected. The changes of GR in the two tissues after HPM exposure were investigated by means of immunohistochemical staining and image analysis. Results: The expression of GR in hypothalamus was decreased after HPM exposure. The level of GR in the group of 10 mW/cm 2 was significantly lower (P 2 group was significantly lower (P 2 group was significantly higher (P 2 group was significantly higher (P<0.01) on 1 d and 3 d after HPM exposure. Conclusion: The expression of GR in hypothalamus was decreased while that in the anterior pituitary was increased after HPM exposure. The refore, the negative feedback of hypothalamic-pituitary-adrenal (HPA) axis was upset and the changes of GR is involved in the pathophysiological course of HPA. (authors)

  5. GABAergic projections from lateral hypothalamus to paraventricular hypothalamic nucleus promote feeding

    Science.gov (United States)

    Lesions of the lateral hypothalamus (LH) cause hypophagia. However, activation of glutamatergic neurons in LH inhibits feeding. These results suggest a potential importance for other LH neurons in stimulating feeding. Our current study in mice showed that disruption of GABA release from adult LH GAB...

  6. Influence of internal exposure on the morphofunctional characteristics of hypothalamus, pituitary and adrenal gland

    International Nuclear Information System (INIS)

    Derev'yanko, L.P.; Nosov, A.T.

    2004-01-01

    The phase changes in morphofunctional states of hypothalamus, pituitary, cortex and medulla of adrenal gland of rats, which for a long time (9 month) were fed a 137 Cs diary, were determined. At early stages of experiment (7 - 30 days) the enhancing of morphofunctional and secretory activity of cells of hypothalamus, pituitary, cortex and medulla of adrenal gland cells, were observed (total absorbed doses of 0,3 sGy). After 9 months (total absorbed doses of 3,0 sGy) in cells of hypothalamus, pituitary, cortex and medulla of adrenal gland the progressions of dystrophic-destructive changes of intracellular structures with the sings of decreasing of morphofunctional and secretory activities were determined. It is necessary to underline, that the sings of intracellular reparative regeneration, were observed in a small part of cells against the background of presence of dystrophic-destructive changes. In spite of the processes of intracellular reparative regeneration which were observed 9 months later after exposure, the completely renewing of morphofunctional and secretory activities in cells of hypothalamus, pituitary, cortex and medulla of adrenal gland cells were absent

  7. The role of gut hormones and the hypothalamus in appetite regulation.

    Science.gov (United States)

    Suzuki, Keisuke; Simpson, Katherine A; Minnion, James S; Shillito, Joyceline C; Bloom, Stephen R

    2010-01-01

    The World Health Organisation has estimated that by 2015 approximately 2.3 billion adults will be overweight and more than 700 million obese. Obesity is associated with an increased risk of diabetes, cardiovascular events, stroke and cancer. The hypothalamus is a crucial region for integrating signals from central and peripheral pathways and plays a major role in appetite regulation. In addition, there are reciprocal connections with the brainstem and higher cortical centres. In the arcuate nucleus of the hypothalamus, there are two major neuronal populations which stimulate or inhibit food intake and influence energy homeostasis. Within the brainstem, the dorsal vagal complex plays a role in the interpretation and relaying of peripheral signals. Gut hormones act peripherally to modulate digestion and absorption of nutrients. However, they also act as neurotransmitters within the central nervous system to control food intake. Peptide YY, pancreatic polypeptide, glucagon-like peptide-1 and oxyntomodulin suppress appetite, whilst ghrelin increases appetite through afferent vagal fibres to the caudal brainstem or directly to the hypothalamus. A better understanding of the role of these gut hormones may offer the opportunity to develop successful treatments for obesity. Here we review the current understanding of the role of gut hormones and the hypothalamus on food intake and body weight control.

  8. Optimization of viral vector technology to study gene function in the hypothalamus

    NARCIS (Netherlands)

    de Backer, M.W.A.

    2010-01-01

    The neural circuits involved in energy homeostasis are complex and include multiple brain regions and neuropeptides. The many functions of the different neuropeptide systems in the hypothalamus have been described; however, the specific roles of the different neuropeptides in specific hypothalamic

  9. Insulin in the arcuate nucleus of the hypothalamus reduces fat consumption in rats

    NARCIS (Netherlands)

    van Dijk, G; de Groote, C; Chavez, M; van der Werf, Y; Steffens, AB; Strubbe, JH

    1997-01-01

    Data are accumulating that insulin acting in the central nervous system is a physiological regulator of food intake and body weight, presumably via its effect in the hypothalamus. The present study investigated whether infusion of a small dose of insulin into two major hypothalamic insulin-binding

  10. 60 YEARS OF NEUROENDOCRINOLOGY: The structure of the neuroendocrine hypothalamus: the neuroanatomical legacy of Geoffrey Harris.

    Science.gov (United States)

    Watts, Alan G

    2015-08-01

    In November 1955, Geoffrey Harris published a paper based on the Christian A Herter Lecture he had given earlier that year at Johns Hopkins University in Baltimore, MD, USA. The paper reviewed the contemporary research that was starting to explain how the hypothalamus controlled the pituitary gland. In the process of doing so, Harris introduced a set of properties that helped define the neuroendocrine hypothalamus. They included: i) three criteria that putative releasing factors for adenohypophysial hormones would have to fulfill; ii) an analogy between the representation of body parts in the sensory and motor cortices and the spatial localization of neuroendocrine function in the hypothalamus; and iii) the idea that neuroendocrine neurons are motor neurons and the pituitary stalk functions as a Sherringtonian final common pathway through which the impact of sensory and emotional events on neuroendocrine neurons must pass in order to control pituitary hormone release. Were these properties a sign that the major neuroscientific discoveries that were being made in the early 1950s were beginning to influence neuroendocrinology? This Thematic Review discusses two main points: the context and significance of Harris's Herter Lecture for how our understanding of neuroendocrine anatomy (particularly as it relates to the control of the adenohypophysis) has developed since 1955; and, within this framework, how novel and powerful techniques are currently taking our understanding of the structure of the neuroendocrine hypothalamus to new levels. © 2015 Society for Endocrinology.

  11. In vivo somatostatin, vasopressin, and oxytocin synthesis in diabetic rat hypothalamus

    International Nuclear Information System (INIS)

    Fernstrom, J.D.; Fernstrom, M.H.; Kwok, R.P.

    1990-01-01

    The in vivo labeling of somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin was studied in rat hypothalamus after third ventricular administration of [35S]cysteine to streptozotocin-diabetic and normal rats. Immunoreactive somatostatin levels in hypothalamus were unaffected by diabetes, as was the incorporation of [35S]cysteine into hypothalamic somatostatin-14 and somatostatin-28. In contrast, immunoreactive vasopressin levels in hypothalamus and posterior pituitary (and oxytocin levels in posterior pituitary) were below normal in diabetic rats. Moreover, [35S]cysteine incorporation into hypothalamic vasopressin and oxytocin (probably mainly in the paraventricular nucleus because of its proximity to the third ventricular site of label injection) was significantly above normal. The increments in vasopressin and oxytocin labeling were reversed by insulin administration. In vivo cysteine specific activity and the labeling of acid-precipitable protein did not differ between normal and diabetic animals; effects of diabetes on vasopressin and oxytocin labeling were therefore not caused by simple differences in cysteine specific activity. These results suggest that diabetes (1) does not influence the production of somatostatin peptides in hypothalamus but (2) stimulates the synthesis of vasopressin and oxytocin. For vasopressin at least, the increase in synthesis may be a compensatory response to the known increase in its secretion that occurs in uncontrolled diabetes

  12. Neuroregulatory and neuroendocrine GnRH pathways in the hypothalamus and forebrain of the baboon.

    Science.gov (United States)

    Marshall, P E; Goldsmith, P C

    1980-07-14

    The distribution of neurons containing gonadotropin-releasing hormone (GnRH) in the baboon hypothalamus and forebrain was studied immunocytochemically by light and electron microscopy. GnRH was present in the perikarya, axonal and dendritic processes of immunoreactive neurons. Three populations of GnRH neurons could be distinguished. Most of the GnRH neurons which are assumed to directly influence the anterior pituitary were in the medial basal hypothalamus. Other cells that projected to the median eminence were found scattered throughout the hypothalamus. A second, larger population of neurons apparently was not involved with control of the anterior pituitary. These neurons were generally found within afferent and efferent pathways of the hypothalamus and forebrain, and may receive external information affecting reproduction. A few neurons projecting to the median eminence were also observed sending collaterals to other brain areas. Thus, in addition to their neuroendocrine role, these cells possibly have neuroregulatory functions. The inference is made that these bifunctional neurons, together with the widely observed GnRH-GnRH cellular interactions may help to synchronize ovulation and sexual behavior.

  13. Energy expenditure and bone formation share a common sensitivity to AP-1 transcription in the hypothalamus

    DEFF Research Database (Denmark)

    Rowe, Glenn C; Vialou, Vincent; Sato, Kazusa

    2012-01-01

    ) whether these effects were due to antagonism to AP1. Our results show that stereotactic injection of an adeno-associated virus vector to restrict overexpression of ¿FosB to the ventral hypothalamus of wildtype mice induced a profound increase in both energy expenditure and bone formation and bone mass...

  14. Genome-wide DNA methylation analysis of the porcine hypothalamus-pituitary-ovary axis

    DEFF Research Database (Denmark)

    Yuan, Xiao Long; Zhang, Zhe; Li, Bin

    2017-01-01

    Previous studies have suggested that DNA methylation in both CpG and CpH (where H = C, T or A) contexts plays a critical role in biological functions of different tissues. However, the genome-wide DNA methylation patterns of porcine hypothalamus-pituitary-ovary (HPO) tissues remain virtually unex...

  15. A semi-automated algorithm for hypothalamus volumetry in 3 Tesla magnetic resonance images.

    Science.gov (United States)

    Wolff, Julia; Schindler, Stephanie; Lucas, Christian; Binninger, Anne-Sophie; Weinrich, Luise; Schreiber, Jan; Hegerl, Ulrich; Möller, Harald E; Leitzke, Marco; Geyer, Stefan; Schönknecht, Peter

    2018-07-30

    The hypothalamus, a small diencephalic gray matter structure, is part of the limbic system. Volumetric changes of this structure occur in psychiatric diseases, therefore there is increasing interest in precise volumetry. Based on our detailed volumetry algorithm for 7 Tesla magnetic resonance imaging (MRI), we developed a method for 3 Tesla MRI, adopting anatomical landmarks and work in triplanar view. We overlaid T1-weighted MR images with gray matter-tissue probability maps to combine anatomical information with tissue class segmentation. Then, we outlined regions of interest (ROIs) that covered potential hypothalamus voxels. Within these ROIs, seed growing technique helped define the hypothalamic volume using gray matter probabilities from the tissue probability maps. This yielded a semi-automated method with short processing times of 20-40 min per hypothalamus. In the MRIs of ten subjects, reliabilities were determined as intraclass correlations (ICC) and volume overlaps in percent. Three raters achieved very good intra-rater reliabilities (ICC 0.82-0.97) and good inter-rater reliabilities (ICC 0.78 and 0.82). Overlaps of intra- and inter-rater runs were very good (≥ 89.7%). We present a fast, semi-automated method for in vivo hypothalamus volumetry in 3 Tesla MRI. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Localisation of SCN10A gene product Na(v)1.8 and novel pain-related ion channels in human heart.

    Science.gov (United States)

    Facer, Paul; Punjabi, Prakash P; Abrari, Andleeb; Kaba, Riyaz A; Severs, Nicholas J; Chambers, John; Kooner, Jaspal S; Anand, Praveen

    2011-01-01

    We have shown that the gene SCN10A encoding the sodium channel Na(v)1.8 is a susceptibility factor for heart block and serious ventricular arrhythmia. Since Na(v)1.8 is known to be present in nerve fibres that mediate pain, it may be related to both cardiac pain and dysrhythmia. The localisation of Na(v)1.8 and other key nociceptive ion channels, including Na(v)1.7, Na(v)1.9, capsaicin receptor TRPV1, and purinergic receptor P2X(3), have not been reported in human heart. The aim of this study was to determine the distribution of Na(v)1.8, related sodium and other sensory channels in human cardiac tissue, and correlate their density with sympathetic nerves, regenerating nerves (GAP-43), and vascularity. Human heart atrial appendage tissues (n = 13) were collected during surgery for valve disease. Tissues were investigated by immunohistology using specific antibodies to Na(v)1.8 and other markers. Na(v)1.8 immunoreactivity was detected in nerve fibres and fascicles in the myocardium, often closely associated with small capillaries. Na(v)1.8 nerve fibres per mm(2) correlated significantly with vascular markers. Na(v)1.8-immunoreactivity was present also in cardiomyocytes with a similar distribution pattern to that seen with connexins, the specialised gap junction proteins of myocardial intercalated discs. Na(v)1.5-immunoreactivity was detected in cardiomyocytes but not in nerve fibres. Na(v)1.7, Na(v)1.9, TRPV1, P2X(3)/P2X(2), and GAP43 positive nerve fibres were relatively sparse, whereas sympathetic innervation and connexin43 were abundant. We conclude that sodium channel Na(v)1.8 is present in sensory nerves and cardiomyocytes of human heart. Na(v)1.8 and other pain channels provide new targets for the understanding and treatment of cardiac pain and dysrhythmia.

  17. Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions

    Directory of Open Access Journals (Sweden)

    Alvarez-Bolado Gonzalo

    2012-01-01

    Full Text Available Abstract Background The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM to map the lineages derived from Shh-expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary. Results Shh-expressing progenitors labeled at an early stage (before embryonic day (E9.5 contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia. Progenitors labeled at later stages (after E9.5 give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh-expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes. Conclusions We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh-expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly

  18. [Oxidative metabolism of main and accessory olfactory bulbs, limpic system and hypothalamus during the estral cycle of the rat (author's transl)].

    Science.gov (United States)

    Sánchez-Criado, J E

    1979-06-01

    The in vitro oxidative metabolism of hypothalamus, olfactory and limbic systems from female rats in the estrous cycle have been measured. The accessory olfactory bulb becomes most active during diestrous when the hypothalamus reaches its lowest values.

  19. Xiaoyaosan Improves Depressive-Like Behaviors in Mice through Regulating Apelin-APJ System in Hypothalamus.

    Science.gov (United States)

    Yan, Zhiyi; Jiao, Haiyan; Ding, Xiufang; Ma, Qingyu; Li, Xiaojuan; Pan, Qiuxia; Wang, Tingye; Hou, Yajing; Jiang, Youming; Liu, Yueyun; Chen, Jiaxu

    2018-05-03

    Background: The apelin-APJ system has been considered to play a crucial role in HPA axis function, and how the traditional Chinese compound prescription Xiaoyaosan regulates the apelin-APJ system as a supplement to treat depressive disorders. Objective: To investigate the depression-like behaviors and expression of apelin and APJ in hypothalamus of chronic unpredictable mild stress (CUMS) mice and study whether these changes related to the regulation of Xiaoyaosan. Methods: 60 adult C57BL/6J mice were randomly divided into four groups, including control group, CUMS group, Xiaoyaosan treatment group and fluoxetine treatment group. Mice in the control group and CUMS group received 0.5 mL physiological saline once a day by intragastric administration. Mice in two treatment groups received Xiaoyaosan (0.25 g/kg/d) and fluoxetine (2.6 mg/kg/d), respectively. After 21 days of modeling with CUMS, the expression of apelin and APJ in hypothalamus were measured by real-time fluorescence quantitative PCR, western blot and immunohistochemical staining. The physical condition, body weight, food intake and behavior tests such as open field test, sucrose preference test and force swimming test were measured to evaluate depressive-like behaviors. Results: In this study, significant behavioral changes were found in CUMS-induced mice, meanwhile the expressions of apelin and APJ in the hypothalamus were changed after modeling. The body weight, food-intake and depressive-like behaviors in CUMS-induced mice could be improved by Xiaoyaosan treatment which is similar with the efficacy of fluoxetine, while the expressions of apelin and APJ in hypothalamus were modified by Xiaoyaosan. Conclusions: The data suggest that apelin-APJ system changes in the hypothalamus may be a target of depressive disorders, and the beneficial effects of Chinese compound prescription Xiaoyaosan on depressive-like behaviors may be mediated by the apelin-APJ system.

  20. Phenotyping of nNOS neurons in the postnatal and adult female mouse hypothalamus.

    Science.gov (United States)

    Chachlaki, Konstantina; Malone, Samuel A; Qualls-Creekmore, Emily; Hrabovszky, Erik; Münzberg, Heike; Giacobini, Paolo; Ango, Fabrice; Prevot, Vincent

    2017-10-15

    Neurons expressing nitric oxide (NO) synthase (nNOS) and thus capable of synthesizing NO play major roles in many aspects of brain function. While the heterogeneity of nNOS-expressing neurons has been studied in various brain regions, their phenotype in the hypothalamus remains largely unknown. Here we examined the distribution of cells expressing nNOS in the postnatal and adult female mouse hypothalamus using immunohistochemistry. In both adults and neonates, nNOS was largely restricted to regions of the hypothalamus involved in the control of bodily functions, such as energy balance and reproduction. Labeled cells were found in the paraventricular, ventromedial, and dorsomedial nuclei as well as in the lateral area of the hypothalamus. Intriguingly, nNOS was seen only after the second week of life in the arcuate nucleus of the hypothalamus (ARH). The most dense and heavily labeled population of cells was found in the organum vasculosum laminae terminalis (OV) and the median preoptic nucleus (MEPO), where most of the somata of the neuroendocrine neurons releasing GnRH and controlling reproduction are located. A great proportion of nNOS-immunoreactive neurons in the OV/MEPO and ARH were seen to express estrogen receptor (ER) α. Notably, almost all ERα-immunoreactive cells of the OV/MEPO also expressed nNOS. Moreover, the use of EYFP Vglut2 , EYFP Vgat , and GFP Gad67 transgenic mouse lines revealed that, like GnRH neurons, most hypothalamic nNOS neurons have a glutamatergic phenotype, except for nNOS neurons of the ARH, which are GABAergic. Altogether, these observations are consistent with the proposed role of nNOS neurons in physiological processes. © 2017 Wiley Periodicals, Inc.

  1. Physiological Mechanisms Mediating the Coupling between Heart Period and Arterial Pressure in Response to Postural Changes in Humans

    OpenAIRE

    Silvani, Alessandro; Calandra-Buonaura, Giovanna; Johnson, Blair D.; van Helmond, Noud; Barletta, Giorgio; Cecere, Anna G.; Joyner, Michael J.; Cortelli, Pietro

    2017-01-01

    The upright posture strengthens the coupling between heart period (HP) and systolic arterial pressure (SAP) consistently with a greater contribution of the arterial baroreflex to cardiac control, while paradoxically decreasing cardiac baroreflex sensitivity (cBRS). To investigate the physiological mechanisms that mediate the coupling between HP and SAP in response to different postures, we analyzed the cross-correlation functions between low-frequency HP and SAP fluctuations and estimated cBR...

  2. Generation of human iPSC line from a patient with laterality defects and associated congenital heart anomalies carrying a DAND5 missense alteration

    Directory of Open Access Journals (Sweden)

    Fernando Cristo

    2017-12-01

    Full Text Available A human iPSC line was generated from exfoliated renal epithelial (ERE cells of a patient affected with Congenital Heart Disease (CHD and Laterality Defects carrying tshe variant p.R152H in the DAND5 gene. The transgene-free iPSCs were generated with the human OSKM transcription factor using the Sendai-virus reprogramming system. The established iPSC line had the specific heterozygous alteration, a stable karyotype, expressed pluripotency markers and generated embryoid bodies that can differentiate towards the three germ layers in vitro. This iPSC line offers a useful resource to study the molecular mechanisms of cardiomyocyte proliferation, as well as for drug testing.

  3. Conscious and unconscious sensory inflows allow effective control of the functions of the human brain and heart at the initial ageing stage.

    Science.gov (United States)

    Bykov, Anatolij T; Malyarenko, Tatyana N; Malyarenko, Yurij E; Terentjev, Vladimir P; Dyuzhikov, Alexandr A

    2006-11-01

    The authors of the present article based their assumption on the concept that the sensory systems are the "windows to the brain" through which various functions of the human organism can be controlled. Comprehension of the fundamental mechanisms of the optimization of the sensory systems, brain, and cardiac functions has increased based on the prolonged sensory flows using conscious and unconscious aromatherapy and multimodal sensory activation. Sensory flow evoked stable systemic responses, including adaptive alteration of psycho-emotional state, attention, memory, sensorimotor reactions, intersensory interaction, visual information processing, statokinetic stability, and autonomic heart rhythm control. The efficacy and expediency of the use of sensory flow for non-medicinal correction of vital functions of the human organism at the initial stages of ageing was revealed.

  4. One-day high-fat diet induces inflammation in the nodose ganglion and hypothalamus of mice.

    Science.gov (United States)

    Waise, T M Zaved; Toshinai, Koji; Naznin, Farhana; NamKoong, Cherl; Md Moin, Abu Saleh; Sakoda, Hideyuki; Nakazato, Masamitsu

    2015-09-04

    A high-fat diet (HFD) induces inflammation in systemic organs including the hypothalamus, resulting in obesity and diabetes. The vagus nerve connects the visceral organs and central nervous system, and the gastric-derived orexigenic peptide ghrelin transmits its starvation signals to the hypothalamus via the vagal afferent nerve. Here we investigated the inflammatory response in vagal afferent neurons and the hypothalamus in mice following one day of HFD feeding. This treatment increased the number of macrophages/microglia in the nodose ganglion and hypothalamus. Furthermore, one-day HFD induced expression of Toll-like receptor 4 in the goblet cells of the colon and upregulated mRNA expressions of the proinflammatory biomarkers Emr1, Iba1, Il6, and Tnfα in the nodose ganglion and hypothalamus. Both subcutaneous administration of ghrelin and celiac vagotomy reduced HFD-induced inflammation in these tissues. HFD intake triggered inflammatory responses in the gut, nodose ganglion, and subsequently in the hypothalamus within 24 h. These findings suggest that the vagal afferent nerve may transfer gut-derived inflammatory signals to the hypothalamus via the nodose ganglion, and that ghrelin may protect against HFD-induced inflammation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Three Experiments Examining the Use of Electroencephalogram,Event-Related Potentials, and Heart-Rate Variability for Real-Time Human-Centered Adaptive Automation Design

    Science.gov (United States)

    Prinzel, Lawrence J., III; Parasuraman, Raja; Freeman, Frederick G.; Scerbo, Mark W.; Mikulka, Peter J.; Pope, Alan T.

    2003-01-01

    Adaptive automation represents an advanced form of human-centered automation design. The approach to automation provides for real-time and model-based assessments of human-automation interaction, determines whether the human has entered into a hazardous state of awareness and then modulates the task environment to keep the operator in-the-loop , while maintaining an optimal state of task engagement and mental alertness. Because adaptive automation has not matured, numerous challenges remain, including what the criteria are, for determining when adaptive aiding and adaptive function allocation should take place. Human factors experts in the area have suggested a number of measures including the use of psychophysiology. This NASA Technical Paper reports on three experiments that examined the psychophysiological measures of event-related potentials, electroencephalogram, and heart-rate variability for real-time adaptive automation. The results of the experiments confirm the efficacy of these measures for use in both a developmental and operational role for adaptive automation design. The implications of these results and future directions for psychophysiology and human-centered automation design are discussed.

  6. Heart Failure

    OpenAIRE

    McMurray, John; Ponikowski, Piotr

    2011-01-01

    Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort intolerance, fluid retention, and increased mortality. The 5-year mortality in people with systolic heart failure ranges from 25% to 75%, often owing to sudden death following ventricular arrhythmia. Risks of cardiovascular events are increased in people with left ventricular systolic dysfunction (LVSD) or heart failure.

  7. Types of Heart Failure

    Science.gov (United States)

    ... Introduction Types of Heart Failure Classes of Heart Failure Heart Failure in Children Advanced Heart Failure • Causes and ... and procedures related to heart disease and stroke. Heart Failure Questions to Ask Your Doctor Use these questions ...

  8. Lhx6 delineates a pathway mediating innate reproductive behaviors from the amygdala to the hypothalamus.

    Science.gov (United States)

    Choi, Gloria B; Dong, Hong-Wei; Murphy, Andrew J; Valenzuela, David M; Yancopoulos, George D; Swanson, Larry W; Anderson, David J

    2005-05-19

    In mammals, innate reproductive and defensive behaviors are mediated by anatomically segregated connections between the amygdala and hypothalamus. This anatomic segregation poses the problem of how the brain integrates activity in these circuits when faced with conflicting stimuli eliciting such mutually exclusive behaviors. Using genetically encoded and conventional axonal tracers, we have found that the transcription factor Lhx6 delineates the reproductive branch of this pathway. Other Lhx proteins mark neurons in amygdalar nuclei implicated in defense. We have traced parallel projections from the posterior medial amygdala, activated by reproductive or defensive olfactory stimuli, respectively, to a point of convergence in the ventromedial hypothalamus. The opposite neurotransmitter phenotypes of these convergent projections suggest a "gate control" mechanism for the inhibition of reproductive behaviors by threatening stimuli. Our data therefore identify a potential neural substrate for integrating the influences of conflicting behavioral cues and a transcription factor family that may contribute to the development of this substrate.

  9. Picomolar-affinity binding and inhibition of adenylate cyclase activity by melatonin in Syrian hamster hypothalamus

    International Nuclear Information System (INIS)

    Niles, L.P.; Hashemi, F.

    1990-01-01

    1. The effect of melatonin on forskolin-stimulated adenylate cyclase activity was measured in homogenates of Syrian hamster hypothalamus. In addition, the saturation binding characteristics of the melatonin receptor ligand, [ 125 I]iodomelatonin, was examined using an incubation temperature (30 degree C) similar to that used in enzyme assays. 2. At concentrations ranging from 10 pM to 1 nM, melatonin caused a significant decrease in stimulated adenylate cyclase activity with a maximum inhibition of approximately 22%. 3. Binding experiments utilizing [ 125 I]iodomelatonin in a range of approximately 5-80 pM indicated a single class of high-affinity sites: Kd = 55 +/- 9 pM, Bmax = 1.1 +/- 0.3 fmol/mg protein. 4. The ability of picomolar concentrations of melatonin to inhibit forskolin-stimulated adenylate cyclase activity suggests that this affect is mediated by picomolar-affinity receptor binding sites for this hormone in the hypothalamus

  10. Replacement of C305 in heart/muscle-type isozyme of human carnitine palmitoyltransferase I with aspartic acid and other amino acids.

    Science.gov (United States)

    Matsuo, Taisuke; Yamamoto, Atsushi; Yamamoto, Takenori; Otsuki, Kaoru; Yamazaki, Naoshi; Kataoka, Masatoshi; Terada, Hiroshi; Shinohara, Yasuo

    2010-04-01

    Liver- and heart/muscle-type isozymes of human carnitine palmitoyltransferase I (L- and M-CPTI, respectively) show a certain similarity in their amino acid sequences, and mutation studies on the conserved amino acids between these two isozymes often show essentially the same effects on their enzymatic properties. Earlier mutation studies on C305 in human M-CPTI and its counterpart residue, C304, in human L-CPTI showed distinct effects of the mutations, especially in the aspect of enzyme stability; however, simple comparison of these effects on the conserved Cys residue between L- and M-CPTI was difficult, because these studies were carried out using different expression systems and distinct amino acids as replacements. In the present study, we carried out mutation studies on the C305 in human M-CPTI using COS cells for the expression system. Our results showed that C305 was replaceable with aspartic acid but that substitution with other amino acids caused both loss of function and reduced expression.

  11. Stability Analysis for an Extended Model of the Hypothalamus-Pituitary-Thyroid Axis

    OpenAIRE

    Beata Jackowska-Zduniak

    2016-01-01

    We formulate and analyze a mathematical model describing dynamics of the hypothalamus-pituitary-thyroid homoeostatic mechanism in endocrine system. We introduce to this system two types of couplings and delay. In our model, feedback controls the secretion of thyroid hormones and delay reflects time lags required for transportation of the hormones. The influence of delayed feedback on the stability behaviour of the system is discussed. Analytical results are illustrated by...

  12. Galanin-Expressing GABA Neurons in the Lateral Hypothalamus Modulate Food Reward and Noncompulsive Locomotion

    OpenAIRE

    Qualls-Creekmore, Emily; Yu, Sangho; Francois, Marie; Hoang, John; Huesing, Clara; Bruce-Keller, Annadora; Burk, David; Berthoud, Hans-Rudolf; Morrison, Christopher D.; Münzberg, Heike

    2017-01-01

    The lateral hypothalamus (LHA) integrates reward and appetitive behavior and is composed of many overlapping neuronal populations. Recent studies associated LHA GABAergic neurons (LHAGABA), which densely innervate the ventral tegmental area (VTA), with modulation of food reward and consumption; yet, LHAGABA projections to the VTA exclusively modulated food consumption, not reward. We identified a subpopulation of LHAGABA neurons that coexpress the neuropeptide galanin (LHAGal). These LHAGal n...

  13. Progesterone metabolism by the hypothalamus, pituitary, and uterus of the rat during pregnancy

    International Nuclear Information System (INIS)

    Marrone, B.L.; Karavolas, H.J.

    1981-01-01

    Metabolites of [ 3 H]progesterone were quantitated from incubations of hypothalamus, pituitary, and uterus of rats during different stages of pregnancy. The hypothalamus, anterior pituitary, and a section of uterus from five rats on Days 1, 8, 15, and 21 of pregnancy were incubated individually with [3H]progesterone and analyzed for metabolite formation by reverse isotopic dilution analysis. The radioactive metabolites present were 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 alpha-hydroxy-5 alpha-pregnan-20-one, 20 alpha-hydroxy-4-pregnen-3-one, 20 alpha-hydroxy-5 alpha-pregnan-3-one, and 5 alpha-pregnane-3 alpha, 20 alpha-diol. The major metabolite formed by the hypothalamus and pituitary was 5 alpha-DHP. In the pituitary samples, formation of 5 alpha-DHP was decreased on Days 15 and 21 of pregnancy compared to Day 1, and formation of 20 alpha-hydroxy-5 alpha-pregnan-3-one was decreased on Day 21 compared to Day 1. In the uterine samples, 3 alpha-hydroxy-5 alpha-pregnan-20-one was the major metabolite formed at all stages of pregnancy. The formation of all metabolic products of progesterone by the uterus was increased on Day 21 compared to Days 1, 8, and 15 of pregnancy. No changes in the formation of progesterone metabolites were observed in the hypothalamic samples during pregnancy. It is concluded that there are different profiles in the in vitro metabolism of [3H]progesterone by the hypothalamus, pituitary, and uterus of the rat during the course of pregnancy

  14. A route for direct retinal input to the preoptic hypothalamus: dendritic projections into the optic chiasm.

    Science.gov (United States)

    Silver, J; Brand, S

    1979-07-01

    With the use of Golgi, horseradish peroxidase, and electron microscopic techniques, neurons within a broad region of the preoptic hypothalamus of the mouse were shown to have dendrites that projected well into the depths of the optic chiasm. Further experimental and ultrastructural investigation demonstrated synapses between these dendrites and retinal axonal boutons within the chiasm. All synapses located in the chiasm were classified as Gray's type I. The possible function of these dendritic projections is discussed.

  15. A Role for Glucocorticoids in Stress-Impaired Reproduction: Beyond the Hypothalamus and Pituitary

    OpenAIRE

    Whirledge, Shannon; Cidlowski, John A.

    2013-01-01

    In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that oth...

  16. Large central lesions compressing the hypothalamus and brainstem. Operative approaches and combination treatment with radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Hiroshi K.; Negishi, Masatoshi; Kohga, Hideaki; Hirato, Masafumi; Ohye, Chihiro [Gunma Univ., Maebashi (Japan). School of Medicine; Shibazaki, Tohru

    1998-09-01

    A major aim of minimally invasive neurosurgery is to preserve function in the brain and cranial nerves. Based on previous results of radiosurgery for central lesions (19 craniopharyngiomas, 46 pituitary adenomas, 9 meningeal tumors), combined micro- and/or radiosurgery was applied for large lesions compressing the hypothalamus and/or brainstem. A basal interhemispheric approach via superomedial orbitotomy or a transcallosal-transforaminal approach was used for these large tumors. Tumors left behind in the hypothalamus or cavernous sinus were treated with radiosurgery using a gamma unit. Preoperative hypothalamo-pituitary functions were preserved in most of these patients. Radiosurgical results were evaluated in patients followed for more than 2 years after treatment. All 9 craniopharyngiomas decreased in size after radiosurgery, although a second treatment was required in 4 patients. All 20 pituitary adenomas were stable or decreased in size and 5 of 7 functioning adenomas showed normalized values of hormones in the serum. All 3 meningeal tumors were stable or decreased in size after treatment. No cavernous sinus symptoms developed after radiosurgery. We conclude that combined micro- and radio-neurosurgery is an effective and less invasive treatment for large central lesions compressing the hypothalamus and brainstem. (author)

  17. Prosomeric organization of the hypothalamus in an elasmobranch, the catshark Scyliorhinus canicula.

    Directory of Open Access Journals (Sweden)

    Gabriel-Nicolás eSantos-Durán

    2015-04-01

    Full Text Available The hypothalamus has been a central topic in neuroanatomy because of its important physiological functions, but its mature organization remains elusive. Deciphering its embryonic and adult organization is crucial in an evolutionary approach of the organization of the vertebrate forebrain. Here we studied the molecular organization of the hypothalamus and neighboring telencephalic domains in a cartilaginous fish, the catshark, Scyliorhinus canicula, focusing on ScFoxg1a, ScShh, ScNkx2.1, ScDlx2/5, ScOtp and ScTbr1 expression profiles and on the identification α-acetylated-tubulin-immunoreactive (ir, TH-ir, 5-HT-ir and GFAP-ir structures by means of immunohistochemistry. Analysis of the results within the updated prosomeric model framework support the existence of alar and basal histogenetic compartments in the hypothalamus similar to those described in the mouse, suggesting the ancestrality of these subdivisions in jawed vertebrates. These data provide new insights into hypothalamic organization in cartilaginous fishes and highlight the generality of key features of the prosomeric model in jawed vertebrates.

  18. Prosomeric organization of the hypothalamus in an elasmobranch, the catshark Scyliorhinus canicula.

    Science.gov (United States)

    Santos-Durán, Gabriel N; Menuet, Arnaud; Lagadec, Ronan; Mayeur, Hélène; Ferreiro-Galve, Susana; Mazan, Sylvie; Rodríguez-Moldes, Isabel; Candal, Eva

    2015-01-01

    The hypothalamus has been a central topic in neuroanatomy because of its important physiological functions, but its mature organization remains elusive. Deciphering its embryonic and adult organization is crucial in an evolutionary approach of the organization of the vertebrate forebrain. Here we studied the molecular organization of the hypothalamus and neighboring telencephalic domains in a cartilaginous fish, the catshark, Scyliorhinus canicula, focusing on ScFoxg1a, ScShh, ScNkx2.1, ScDlx2/5, ScOtp, and ScTbr1 expression profiles and on the identification α-acetylated-tubulin-immunoreactive (ir), TH-ir, 5-HT-ir, and GFAP-ir structures by means of immunohistochemistry. Analysis of the results within the updated prosomeric model framework support the existence of alar and basal histogenetic compartments in the hypothalamus similar to those described in the mouse, suggesting the ancestrality of these subdivisions in jawed vertebrates. These data provide new insights into hypothalamic organization in cartilaginous fishes and highlight the generality of key features of the prosomeric model in jawed vertebrates.

  19. Morphometry of the pituitary gland and hypothalamus in long-term survivors of childhood trauma.

    Science.gov (United States)

    Porto, L; Margerkurth, J; Althaus, J; You, S-J; Zanella, F E; Kieslich, M

    2011-11-01

    Chronic pituitary dysfunction is increasingly recognized as a sequela of traumatic brain injury (TBI). Our aim was to rule out any late morphometric changes of the pituitary gland and hypothalamus in survivors of TBI during childhood requiring intensive care. We assessed morphometric abnormalities of the sella region and hypothalamus in patients who sustained TBI during childhood. The patients showed no clinical hormonal dysfunction at the acute phase and pituitary hormone levels at the time of our study were within normal limits. From the 18 enrolled patients in the magnetic resonance study, five were removed due to morphological changes or anatomical variations. We studied the MRI of 13 male survivors (mean age 27 years, mean time after trauma 20 years) and compared them to 13 male control subjects who were matched in terms of age (mean age, 26 years), education and ethnicity. Analyses of the pituitary gland and sella on a midsagittal T2- and T1-weighted image were performed. We used voxel-based morphometry (VBM), an unbiased MRI morphometric method to investigate hypothalamic region in this group of patients. There was only a trend towards a reduced pituitary gland width in the patient group compared to controls. However, no significant morphological and morphometric abnormality was seen and VBM showed no hypothalamic grey matter loss. In the absence of hormonal dysfunction, no persisting morphometric changes of the pituitary gland and hypothalamus were seen in survivors of childhood TBI requiring intensive care.

  20. Active coping with stress suppresses glucose metabolism in the rat hypothalamus.

    Science.gov (United States)

    Ono, Yumie; Lin, Hsiao-Chun; Tzen, Kai-Yuan; Chen, Hui-Hsing; Yang, Pai-Feng; Lai, Wen-Sung; Chen, Jyh-Horng; Onozuka, Minoru; Yen, Chen-Tung

    2012-03-01

    We used 18F-fluorodeoxyglucose small-animal positron-emission tomography to determine whether different styles of coping with stress are associated with different patterns of neuronal activity in the hypothalamus. Adult rats were subjected to immobilization (IMO)-stress or to a non-immobilized condition for 30 min, in random order on separate days, each of which was followed by brain-scanning. Some rats in the immobilized condition were allowed to actively cope with the stress by chewing a wooden stick during IMO, while the other immobilized rats were given nothing to chew on. Voxel-based statistical analysis of the brain imaging data shows that chewing counteracted the stress-induced increased glucose uptake in the hypothalamus to the level of the non-immobilized condition. Region-of-interest analysis of the glucose uptake values further showed that chewing significantly suppressed stress-induced increased glucose uptake in the paraventricular hypothalamic nucleus and the anterior hypothalamic area but not in the lateral hypothalamus. Together with the finding that the mean plasma corticosterone concentration at the termination of the IMO was also significantly suppressed when rats had an opportunity to chew a wooden stick, our results showed that active coping by chewing inhibited the activation of the hypothalamic-pituitary-adrenal axis to reduce the endocrine stress response.

  1. Large central lesions compressing the hypothalamus and brainstem. Operative approaches and combination treatment with radiosurgery

    International Nuclear Information System (INIS)

    Inoue, Hiroshi K.; Negishi, Masatoshi; Kohga, Hideaki; Hirato, Masafumi; Ohye, Chihiro; Shibazaki, Tohru

    1998-01-01

    A major aim of minimally invasive neurosurgery is to preserve function in the brain and cranial nerves. Based on previous results of radiosurgery for central lesions (19 craniopharyngiomas, 46 pituitary adenomas, 9 meningeal tumors), combined micro- and/or radiosurgery was applied for large lesions compressing the hypothalamus and/or brainstem. A basal interhemispheric approach via superomedial orbitotomy or a transcallosal-transforaminal approach was used for these large tumors. Tumors left behind in the hypothalamus or cavernous sinus were treated with radiosurgery using a gamma unit. Preoperative hypothalamo-pituitary functions were preserved in most of these patients. Radiosurgical results were evaluated in patients followed for more than 2 years after treatment. All 9 craniopharyngiomas decreased in size after radiosurgery, although a second treatment was required in 4 patients. All 20 pituitary adenomas were stable or decreased in size and 5 of 7 functioning adenomas showed normalized values of hormones in the serum. All 3 meningeal tumors were stable or decreased in size after treatment. No cavernous sinus symptoms developed after radiosurgery. We conclude that combined micro- and radio-neurosurgery is an effective and less invasive treatment for large central lesions compressing the hypothalamus and brainstem. (author)

  2. Effects of heavy-ion exposure to rat's hypothalamus on the copulatory behavior

    International Nuclear Information System (INIS)

    Saito, Masayoshi; Kawata, Tetsuya; Liu, C.; Kan'o, Momoe; Ito, Hisao; Takai, Nobuhiko; Ando, Koichi

    2005-01-01

    The effect of heavy-ion irradiation to brain on sexual behavior is not yet known. The present study was designed to determine whether irradiation (carbon particles 290 MeV/nucleon, Mono peak 15∼120 Gy, irradiation field 5-millimeter cube in hypothalamus) to rat's hypothalamus modifies the copulatory behavior of male rats. For the first year, we planned to estimate the short-term effects of carbon-irradiation on the copulatory behavior using a relatively high doses, and observation of sexual behavior was conducted for 30 min after 1, 2 or 3 months following irradiation. Results obtained in the first year are as follows. At dosages of 15 Gy, 30 Gy, 45 Gy and 60 Gy these were no changes in copulatory behavior after one month following irradiation; however, the intromission and ejaculation was found to decrease after 3-month follow-up in rats exposed to 60 Gy. At higher doses such as 90 Gy, 120 Gy, the number of mounting, intromission (120 Gy alone) and ejaculation (90 Gy, 120 Gy) were decreased. It may be possible to describe that carbon irradiation to hypothalamus does not inhibit the activity of copulatory behavior after short-term. Further experiments after long-term follow-up after irradiation are necessary to determine the chronic effects of heavy ions on the copulatory behavior. (author)

  3. [Biogenic amines in the epiphysis and hypothalamus under normal conditions and following ovariectomy].

    Science.gov (United States)

    Grishchenko, V I; Koliada, L D; Demidenko, D I

    1977-01-01

    Melatonin content in the epiphysis, serotonin, noradrenaline, dopamine-in the hypothalamus, gonadotropins--in the hypophysis of rats was studied under normal conditions and following ovariectomy; regularly of the estral cycle phases was studied as well. Two series of experiments were conducted on 120 rats with regular estral cycles. The animals were divided into groups according to the estral cycle phase. Melatonin concentration in the epiphysis, serotonin, noradrenaline, dopamine--in the hypothalamus was subject to variations coinciding with the estral cycle phases. Serotonin, noradrenaline, and dopamine content decreased in the hypophysis of ovariectomized rats in comparison with control; melatonin content rose in the epiphysis. There was no complete extinction of the estral cycle in the course of investigation (20 days). The action of castration on the sexual cycle depended on the phase at which the rats were subjected to ovariectomy. A reverse relationship existed between the melatonin content in the epiphysis and serotonin content in the hypothalamus, this serving as one of the important factors in the regulation of the sexual function.

  4. Heat stress-induced neuroinflammation and aberration in monoamine levels in hypothalamus are associated with temperature dysregulation.

    Science.gov (United States)

    Chauhan, Nishant Ranjan; Kapoor, Medha; Prabha Singh, Laxmi; Gupta, Rajinder Kumar; Chand Meena, Ramesh; Tulsawani, Rajkumar; Nanda, Sarita; Bala Singh, Shashi

    2017-09-01

    Heat Stress (HS) induces diverse pathophysiological changes, which include brain ischemia, oxidative stress and neuronal damage. The present study was undertaken with the objective to ascertain whether neuroinflammation in Hypothalamus (HTH) caused under HS affects monoamine levels and hence, its physiological role in thermoregulation. Rats were exposed to HS in a heat simulation environmental chamber (Ambient temperature, Ta=45±0.5°C and Relative Humidity, RH=30±10%) with real-time measurement of core temperature (Tc) and skin temperature (Ts). Animals were divided into two subgroups: Moderate HS (MHS) (Tc=40°C) and Severe HS (SHS)/Heat stroke (Tc=42°C). Rats with MHS showed an increase in Mean Arterial Pressure (MAP) and Heart Rate (HR) while fall in MAP and rise in HR was observed in rats with SHS. In addition, oxidative stress and an increase in pyknotic neurons were observed in HTH. High levels of Adrenocorticotropic-hormone (ACTH), Epinephrine (EPI), Norepinephrine (NE) and Dopamine (DA) in the systemic circulation and progressive increase in EPI and DA levels in HTH were recorded after the thermal insult. Moreover, a substantial increase in Glutamate (Glu) level was observed in HTH as well as in systemic circulation of heat stroke rats. We found a rise in NE whereas a fall in Serotonin (5-HT) level in HTH at MHS, without perturbing inflammatory mediators. However, rats with SHS exhibited significant elevations in NF-kB, IL-1β, COX2, GFAP and Iba1 protein expression in HTH. In conclusion, the data suggest that SHS induces neuroinflammation in HTH, which is associated with monoamines and Glu imbalances, leading to thermoregulatory disruption. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. The Influence of New Colored Light Stimulation Methods on Heart Rate Variability, Temperature, and Well-Being: Results of a Pilot Study in Humans

    Directory of Open Access Journals (Sweden)

    Daniela Litscher

    2013-01-01

    Full Text Available Changes of light intensity of different colors can shift many physiological parameters and conditions like melatonin, alertness, body temperature, heart rate (HR, and heart rate variability (HRV. The aim of this pilot study was to investigate acute temperature, HR, HRV, and state of mind reactivities after illumination with red (631 nm and blue (456 nm light (illuminance 140 lux for both. Seven healthy volunteers (5 females, 2 males; mean age ± SD 34.1 ± 11.9 years were investigated at the Medical University of Graz, using new color light panels. Significant decreases were found only after 10 min blue light stimulation in nose temperature (P=0.046, HR (P<0.05, and total HRV (P=0.029, in association with a significant alteration of the emotional state (stress level score, P=0.006. However, red light stimulation of the same persons did not induce the same effects in these parameters. The effect of blue light as environmental stimulation on human health is not clarified in detail and needs further investigations.

  6. Heart-type fatty-acid-binding protein (FABP3 is a lysophosphatidic acid-binding protein in human coronary artery endothelial cells

    Directory of Open Access Journals (Sweden)

    Ryoko Tsukahara

    2014-01-01

    Full Text Available Fatty-acid-binding protein 3, muscle and heart (FABP3, also known as heart-type FABP, is a member of the family of intracellular lipid-binding proteins. It is a small cytoplasmic protein with a molecular mass of about 15 kDa. FABPs are known to be carrier proteins for transporting fatty acids and other lipophilic substances from the cytoplasm to the nucleus, where these lipids are released to a group of nuclear receptors such as peroxisome proliferator-activated receptors (PPARs. In this study, using lysophosphatidic acid (LPA-coated agarose beads, we have identified FABP3 as an LPA carrier protein in human coronary artery endothelial cells (HCAECs. Administration of LPA to HCAECs resulted in a dose-dependent increase in PPARγ activation. Furthermore, the LPA-induced PPARγ activation was abolished when the FABP3 expression was reduced using small interfering RNA (siRNA. We further show that the nuclear fraction of control HCAECs contained a significant amount of exogenously added LPA, whereas FABP3 siRNA-transfected HCAECs had a decreased level of LPA in the nucleus. Taken together, these results suggest that FABP3 governs the transcriptional activities of LPA by targeting them to cognate PPARγ in the nucleus.

  7. Extracellular pH modulates GABAergic neurotransmission in rat hypothalamus.

    Science.gov (United States)

    Chen, Z L; Huang, R Q

    2014-06-20

    Changes in extracellular pH have a modulatory effect on GABAA receptor function. It has been reported that pH sensitivity of the GABA receptor is dependent on subunit composition and GABA concentration. Most of previous investigations focused on GABA-evoked currents, which only reflect the postsynaptic receptors. The physiological relevance of pH modulation of GABAergic neurotransmission is not fully elucidated. In the present studies, we examined the influence of extracellular pH on the GABAA receptor-mediated inhibitory neurotransmission in rat hypothalamic neurons. The inhibitory postsynaptic currents (IPSCs), tonic currents, and the GABA-evoked currents were recorded with whole-cell patch techniques on the hypothalamic slices from Sprague-Dawley rats at 15-26 postnatal days. The amplitude and frequency of spontaneous GABA IPSCs were significantly increased while the external pH was changed from 7.3 to 8.4. In the acidic pH (6.4), the spontaneous GABA IPSCs were reduced in amplitude and frequency. The pH induced changes in miniature GABA IPSCs (mIPSCs) similar to that in spontaneous IPSCs. The pH effect on the postsynaptic GABA receptors was assessed with exogenously applied varying concentrations of GABA. The tonic currents and the currents evoked by sub-saturating concentration of GABA ([GABA]) (10 μM) were inhibited by acidic pH and potentiated by alkaline pH. In contrast, the currents evoked by saturating [GABA] (1mM) were not affected by pH changes. We also investigated the influence of pH buffers and buffering capacity on pH sensitivity of GABAA receptors on human recombinant α1β2γ2 GABAA receptors stably expressed in HEK 293 cells. The pH influence on GABAA receptors was similar in HEPES- and MES-buffered media, and not dependent on protonated buffers, suggesting that the observed pH effect on GABA response is a specific consequence of changes in extracellular protons. Our data suggest that the hydrogen ions suppress the GABAergic neurotransmission

  8. Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus

    International Nuclear Information System (INIS)

    Dickerson, Sarah M.; Cunningham, Stephanie L.; Gore, Andrea C.

    2011-01-01

    Neonatal exposure to endocrine disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs) can interfere with hormone-sensitive developmental processes, including brain sexual differentiation. We hypothesized that disruption of these processes by gestational PCB exposure would be detectable as early as the day after birth (postnatal day (P) 1) through alterations in hypothalamic gene and protein expression. Pregnant Sprague-Dawley rats were injected twice, once each on gestational days 16 and 18, with one of the following: DMSO vehicle; the industrial PCB mixture Aroclor 1221 (A1221); a reconstituted mixture of the three most prevalent congeners found in humans, PCB138, PCB153, and PCB180; or estradiol benzoate (EB). On P1, litter composition, anogenital distance (AGD), and body weight were assessed. Pups were euthanized for immunohistochemistry of estrogen receptor α (ERα) or TUNEL labeling of apoptotic cells or quantitative PCR of 48 selected genes in the preoptic area (POA). We found that treatment with EB or A1221 had a sex-specific effect on developmental apoptosis in the neonatal anteroventral periventricular nucleus (AVPV), a sexually dimorphic hypothalamic region involved in the regulation of reproductive neuroendocrine function. In this region, exposed females had increased numbers of apoptotic nuclei, whereas there was no effect of treatment in males. For ERα, EB treatment increased immunoreactive cell numbers and density in the medial preoptic nucleus (MPN) of both males and females, while A1221 and the PCB mixture had no effect. PCR analysis of gene expression in the POA identified nine genes that were significantly altered by prenatal EDC exposure, in a manner that varied by sex and treatment. These genes included brain-derived neurotrophic factor, GABA B receptors-1 and -2, IGF-1, kisspeptin receptor, NMDA receptor subunits NR2b and NR2c, prodynorphin, and TGFα. Collectively, these results suggest that the disrupted sexual differentiation

  9. Periodontal bacteria DNA findings in human cardiac tissue - Is there a link of periodontitis to heart valve disease?

    Science.gov (United States)

    Ziebolz, D; Jahn, C; Pegel, J; Semper-Pinnecke, E; Mausberg, R F; Waldmann-Beushausen, R; Schöndube, F A; Danner, B C

    2018-01-15

    The aim of the study was to detect periodontal pathogens DNA in atrial and myocardial tissue, and to investigate periodontal status and their connection to cardiac tissue inflammation. In 30 patients, biopsy samples were taken from the atrium (A) and the ventricle myocardium (M) during aortic valve surgery. The dental examination included the dental and periodontal status (PS) and a collection of a microbiological sample. The detection of 11 periodontal pathogens DNA in oral and heart samples was carried out using PCR. The heart samples were prepared for detecting the LPS-binding protein (LBP), and for inflammation scoring on immunohistochemistry (IHC), comprising macrophages (CD68), LPS-binding protein receptor (CD14), and LBP (big42). 28 (93%) patients showed moderate to severe periodontitis. The periodontal pathogens in the oral samples of all patients revealed a similar distribution (3-93%). To a lesser extent and with a different distribution, these bacteria DNA were also detected in atrium and myocardium (3-27%). The LBP was detected in higher amount in atrium (0.22±0.16) versus myocardium (0.13±0.13, p=0.001). IHC showed a higher inflammation score in atrial than myocardial tissue as well as for CD14, CD68 and for LBP. Additional, periodontal findings showed a significant correlation to CD14 and CD68. The results provide evidence of the occurrence of oral bacteria DNA at the cardiac tissue, with a different impact on atrial and myocardial tissue inflammation. Influence of periodontal findings was identified, but their relevance is not yet distinct. Therefore further clinical investigations with long term implication are warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Left ventricular mechanics in humans with high aerobic fitness: adaptation independent of structural remodelling, arterial haemodynamics and heart rate

    Science.gov (United States)

    Stöhr, Eric J; McDonnell, Barry; Thompson, Jane; Stone, Keeron; Bull, Tom; Houston, Rory; Cockcroft, John; Shave, Rob

    2012-01-01

    Individuals with high aerobic fitness have lower systolic left ventricular strain, rotation and twist (‘left ventricular (LV) mechanics’) at rest, suggesting a beneficial reduction in LV myofibre stress and more efficient systolic function. However, the mechanisms responsible for this functional adaptation are not known and the influence of aerobic fitness on LV mechanics during dynamic exercise has never been studied. We assessed LV mechanics, LV wall thickness and dimensions, central augmentation index (AIx), aortic pulse wave velocity (aPWV), blood pressure and heart rate in 28 males (age: 21 ± 2 years SD) with a consistent physical activity level (no change >6 months). Individuals were examined at rest and during exercise (40% peak exercise capacity) and separated post hoc into a moderate and high aerobic fitness group (: 49 ± 5 and 63 ± 7 ml kg−1 min−1, respectively, P 0.05). However, for the same AIx, the high group had significantly lower LV apical rotation (P = 0.002) and LV twist (P = 0.003) while basal rotation and strain indices did not differ between groups (P > 0.05). We conclude that young males with high aerobic fitness have lower LV apical rotation at rest and during submaximal exercise that can occur without changes in gross LV structure, arterial haemodynamics or heart rate. The findings suggest a previously unknown type of physiological adaptation of the left ventricle that may have important implications for exercise training in older individuals and patient populations in which exercise training has previously failed to show clear benefits for LV function. PMID:22431336

  11. Dynamic of bioelectric activity back hypothalamus changes in conditions of pyroxan application on the background of stress-reaction developmen

    Directory of Open Access Journals (Sweden)

    T. G. Chaus

    2005-04-01

    Full Text Available The dynamic of changes of capacity of electroencephalogram’s rhythms back hypothalamus at animals of control group and group in stress conditions in parallel with rats who on a background of stress development accepted pyroxan is analyzed. The submitted results have shown influence of a pharmacological preparation pyroxan on bioelectric activity of back hypothalamus in stress conditions that restoration of electric activity under action of this preparation was more shown at 3 weeks of its application.

  12. [The catecholamine content of the hypothalamus during the modelling of the ulcer process in the gastroduodenal area].

    Science.gov (United States)

    Iemel'ianenko, I V; Sultanova, I D; Voronych, N M

    1995-01-01

    The content of catecholamines in rat hypothalamus in experimental ulcer process in gastroduodenal region has been studied in experiments on rats. It was determined that under these conditions the content of hypothalamus adrenalin increases and the content of noradrenalin decreases. The level of dofamin and DOFA in this brain structure changes in phases. The mentioned shifts depended on the duration and character of the pathological process in the gastroduodenal region.

  13. Simple, heart-smart substitutions

    Science.gov (United States)

    Coronary artery disease - heart smart substitutions; Atherosclerosis - heart smart substitutions; Cholesterol - heart smart substitutions; Coronary heart disease - heart smart substitutions; Healthy diet - heart ...

  14. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

    Directory of Open Access Journals (Sweden)

    Li-Juan Zhu

    Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  15. Effect of prolonged gamma irradiation (6.7 Gy) on monoamine oxidase activity in ewe hypothalamus in anestral period

    International Nuclear Information System (INIS)

    Pastorova, B.; Arendarcik, J.

    1988-01-01

    Changes were studied of monoamine oxidase (MAO) activity in the hypothalamus and hypophysis of ewes in the anestral period following whole-body 60 Co irradiation for 7 days with a dose of 6.7 Gy. The gamma radiation exposure rate was 0.039 Gy/h. The activity of MAO was determined using the radiochemical method. 14 C-tryptamine was used as the substrate. The highest activity was determined in the rostral hypothalamus (1100 pmol.mg -1 .min -1 ). MAO activity was at its lowest in the caudal region of the hypothalamus (550 pmol). The results show that whole-body exposure to gamma radiation with a total dose of 6.7 Gy makes a statistically significant increase (P<0.001) in MAO activity in the caudal hypothalamus of ewes while remaining at the level of the control group or increasing insignificantly in the rostral and medial hypothalamus. A significant decrease (P<0.05) was recorded in the hypophysis. It may be assumed that the increased degradation of catecholamines caused by MAO is one of the mechanisms responsible for the decreased concentration of catecholamines in the hypothalamus of ewes after irradiation. (author). 1 fig., 22 refs

  16. 31P-MR spectroscopy of all regions of the human heart at 1.5 T with acquisition-weighted chemical shift imaging

    International Nuclear Information System (INIS)

    Koestler, H.; Beer, M.; Buchner, S.; Sandstede, J.; Pabst, T.; Kenn, W.; Hahn, D.

    2001-01-01

    Aim: Aim of this study was to show whether or not acquisition-weighted chemical shift imaging (AW-CSI) allows the determination of PCr and ATP in the lateral and posterior wall of the human heart at 1.5 T. Methods: 12 healthy volunteers were examined using a conventional chemical shift imaging (CSI) and an AW-CSI. The sequences differed only in the number of repetitions for each point in k space. A hanning function was used as filter function leading to 7 repetitions in the center of the k space and 0 in the corners. Thus, AW-CSI had the same resolution as the CSI sequence. The results for both sequences were analyzed using identically positioned voxels in the septal, anterior, lateral and posterior wall. Results: The determined averaged AW-CSI signal to noise ratios were higher for PCr by a factor of 1.3 and for ATP by 1.4 than those of CSI. The PCr/ATP ratios were higher by a factor of 1.2 - 1.3 and showed a smaller standard deviation in all locations for AW-CSI. The mean PCr/ATP ratios determined by AW-CSI of septal, lateral and posterior wall were almost identical (1.72 - 1.76), while it was higher in the anterior wall (1.9). Conclusions: The reduced contamination in AW-CSI improves the signal to noise ratio and the determination of the PCr/ATP ratio in cardiac 31 P spectroscopy compared to CSI with the same resolution. The results in volunteers indicate that AW-CSI renders 31 P spectroscopy of the lateral and posterior wall of the human heart feasible for patient studies at 1.5 T. (orig.) [de

  17. Coping with continuous human disturbance in the wild: insights from penguin heart rate response to various stressors.

    OpenAIRE

    Viblanc, V.A.; Smith, A.D.; Gineste, B.; Groscolas, R.

    2012-01-01

    Abstract Background A central question for ecologists is the extent to which anthropogenic disturbances (e.g. tourism) might impact wildlife and affect the systems under study. From a research perspective, identifying the effects of human disturbance caused by research-related activities is crucial in order to understand and account for potential biases and derive appropriate conclusions from the data. Results Here, we document a case of biological adjustment to chronic human disturbance in a...

  18. What Is Coronary Heart Disease?

    Science.gov (United States)

    ... is: 12 ounces of beer 5 ounces of wine 1½ ounces of liquor Maintaining a Healthy Weight ... Your Heart U.S. Department of Health and Human Services’ 2008 Physical Activity Guidelines for Americans Talk with ...

  19. Spatial distribution of "tissue-specific" antigens in the developing human heart and skeletal muscle. III. An immunohistochemical analysis of the distribution of the neural tissue antigen G1N2 in the embryonic heart; implications for the development of the atrioventricular conduction system

    NARCIS (Netherlands)

    Wessels, A.; Vermeulen, J. L.; Verbeek, F. J.; Virágh, S.; Kálmán, F.; Lamers, W. H.; Moorman, A. F.

    1992-01-01

    A monoclonal antibody raised against an extract from the Ganglion Nodosum of the chick and designated G1N2 proves to bind specifically to a subpopulation of cardiomyocytes in the embryonic human heart. In the youngest stage examined (Carnegie stage 14, i.e., 4 1/2 weeks of development) these

  20. Genome-wide analysis of DHEA- and DHT-induced gene expression in mouse hypothalamus and hippocampus.

    Science.gov (United States)

    Mo, Qianxing; Lu, Shifang; Garippa, Carrie; Brownstein, Michael J; Simon, Neal G

    2009-04-01

    Dehydroepiandrosterone (DHEA) is the most abundant steroid in humans and a multi-functional neuroactive steroid that has been implicated in a variety of biological effects in both the periphery and central nervous system. Mechanistic studies of DHEA in the periphery have emphasized its role as a prohormone and those in the brain have focused on effects exerted at cell surface receptors. Recent results demonstrated that DHEA is intrinsically androgenic. It competes with DHT for binding to androgen receptor (AR), induces AR-regulated reporter gene expression in vitro, and exogenous DHEA administration regulates gene expression in peripheral androgen-dependent tissues and LnCAP prostate cancer cells, indicating genomic effects and adding a level of complexity to functional models. The absence of information about the effect of DHEA on gene expression in the CNS is a significant gap in light of continuing clinical interest in the compound as a hormone replacement therapy in older individuals, patients with adrenal insufficiency, and as a treatment that improves sense of well-being, increases libido, relieves depressive symptoms, and serves as a neuroprotective agent. In the present study, ovariectomized CF-1 female mice, an established model for assessing CNS effects of androgens, were treated with DHEA (1mg/day), dihydrotestosterone (DHT, a potent androgen used as a positive control; 0.1mg/day) or vehicle (negative control) for 7 days. The effects of DHEA on gene expression were assessed in two regions of the CNS that are enriched in AR, hypothalamus and hippocampus, using DNA microarray, real-time RT-PCR, and immunohistochemistry. RIA of serum samples assessed treatment effects on circulating levels of major steroids. In hypothalamus, DHEA and DHT significantly up-regulated the gene expression of hypocretin (Hcrt; also called orexin), pro-melanin-concentrating hormone (Pmch), and protein kinase C delta (Prkcd), and down-regulated the expression of deleted in bladder

  1. Artificial heart for humanoid robot

    Science.gov (United States)

    Potnuru, Akshay; Wu, Lianjun; Tadesse, Yonas

    2014-03-01

    A soft robotic device inspired by the pumping action of a biological heart is presented in this study. Developing artificial heart to a humanoid robot enables us to make a better biomedical device for ultimate use in humans. As technology continues to become more advanced, the methods in which we implement high performance and biomimetic artificial organs is getting nearer each day. In this paper, we present the design and development of a soft artificial heart that can be used in a humanoid robot and simulate the functions of a human heart using shape memory alloy technology. The robotic heart is designed to pump a blood-like fluid to parts of the robot such as the face to simulate someone blushing or when someone is angry by the use of elastomeric substrates and certain features for the transport of fluids.

  2. Heart Failure

    Science.gov (United States)

    ... Other diseases. Chronic diseases — such as diabetes, HIV, hyperthyroidism, hypothyroidism, or a buildup of iron (hemochromatosis) or ... transplantation or support with a ventricular assist device. Prevention The key to preventing heart failure is to ...

  3. Heart Attack

    Science.gov (United States)

    ... properly causes your body's blood sugar levels to rise, increasing your risk of heart attack. Metabolic syndrome. This occurs when you have obesity, high blood pressure and high blood sugar. Having metabolic ...

  4. Classes of Heart Failure

    Science.gov (United States)

    ... Introduction Types of Heart Failure Classes of Heart Failure Heart Failure in Children Advanced Heart Failure • Causes and ... and Advanced HF • Tools and Resources • Personal Stories Heart Failure Questions to Ask Your Doctor Use these questions ...

  5. Men and Heart Disease

    Science.gov (United States)

    ... Pressure Salt Cholesterol Million Hearts® WISEWOMAN Men and Heart Disease Fact Sheet Recommend on Facebook Tweet Share Compartir Source: Interactive Atlas of Heart Disease and Stroke Heart Disease Facts in Men Heart disease is the leading ...

  6. Wine and heart health

    Science.gov (United States)

    Health and wine; Wine and heart disease; Preventing heart disease - wine; Preventing heart disease - alcohol ... more often just to lower your risk of heart disease. Heavier drinking can harm the heart and ...

  7. Serial in vivo imaging of the porcine heart after percutaneous, intramyocardially injected 111In-labeled human mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Lyngbaek, Stig; Ripa, Rasmus S; Haack-Sørensen, Mandana

    2010-01-01

    This pilot trial aimed to investigate the utilization of (111)In-labeling of mesenchymal stromal cells (MSC) for in vivo tracking after intramyocardial transplantation in a xenotransplantation model with gender mismatched cells. Human male MSC were expanded ex vivo and labeled with (111)In...

  8. Serial in vivo imaging of the porcine heart after percutaneous, intramyocardially injected (111)In-labeled human mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Lyngbæk, Stig; Ripa, Rasmus Sejersten; Haack-Sørensen, Mandana

    2009-01-01

    This pilot trial aimed to investigate the utilization of (111)In-labeling of mesenchymal stromal cells (MSC) for in vivo tracking after intramyocardial transplantation in a xenotransplantation model with gender mismatched cells. Human male MSC were expanded ex vivo and labeled with (111)In...

  9. Octylphenol (OP) alters the expression of members of the amyloid protein family in the hypothalamus of the snapping turtle, Chelydra serpentina serpentina.

    Science.gov (United States)

    Trudeau, Vance L; Chiu, Suzanne; Kennedy, Sean W; Brooks, Ronald J

    2002-03-01

    The gonadal estrogen estradiol-17beta (E(2)) is important for developing and regulating hypothalamic function and many aspects of reproduction in vertebrates. Pollutants such as octylphenol (OP) that mimic the actions of estrogens are therefore candidate endocrine-disrupting chemicals. We used a differential display strategy (RNA-arbitrarily primed polymerase chain reaction) to isolate partial cDNA sequences of neurotransmitter, developmental, and disease-related genes that may be regulated by OP or E(2) in the snapping turtle Chelydra serpentina serpentina hypothalamus. Hatchling and year-old male snapping turtles were exposed to a 10 ng/mL nominal concentration of waterborne OP or E(2) for 17 days. One transcript [421 base pairs (bp)] regulated by OP and E(2) was 93% identical to human APLP-2. APLP-2 and the amyloid precursor protein (APP) regulate neuronal differentiation and are also implicated in the genesis of Alzheimer disease in humans. Northern blot analysis determined that the turtle hypothalamus contains a single APLP-2 transcript of 3.75 kb in length. Exposure to OP upregulated hypothalamic APLP-2 mRNA levels 2-fold (p < 0.05) in month-old and yearling turtles. E(2) did not affect APLP-2 mRNA levels in hatchlings but stimulated a 2-fold increase (p < 0.05) in APLP-2 mRNA levels in yearling males. The protein beta-amyloid, a selectively processed peptide derived from APP, is also involved in neuronal differentiation, and accumulation of this neurotoxic peptide causes neuronal degeneration in the brains of patients with Alzheimer disease. Therefore, we also sought to determine the effects of estrogens on the expression of beta-amyloid. Using homology cloning based on known sequences, we isolated a cDNA fragment (474 bp) from turtle brain with 88% identity to human APP. Northern blot analysis determined that a single 3.5-kb transcript was expressed in the turtle hypothalamus. Waterborne OP also increased the expression of hypothalamic APP after 35 days of

  10. Comparison of 11-C-Palmitic Acid (CPA), and 123-I-heptadecanoic acid (IHA) turnover in human heart

    International Nuclear Information System (INIS)

    Notohamiprodjo, G.; Schmid, A.; Spohr, G.; Vyska, K.; Feinendegen, L.E.

    1985-01-01

    This study was designed to compare the results obtained with IHA in the investigation of myocardial fatty acid metabolism (MFAM) with those obtained by the use of CPA.- 8 patients (pts) without clinical signs of heart or metabolic disease were investigated under rest and fasting condition by dynamic PET following i.v. injection of 3 mCi CPA and by conventional scintigraphy following i.v. injection of 3 mCi IHA. Data were collected over a period of 90 min (frame rate was 1/min) and corrected for blood activity and catabolically released 123-I.-In 6 pts a good agreement between CPA and IHA data was observed. The activity release from the myocardium in these cases was biexponential. The ratio Q ranged between 0.7 and 6.7. -In the remaining 2 pts significant discrepancies between CPA and IHA data were observed. Since these pts were known to have cardiac neurosis and the first measurement was carried out with CPA, the authors assumed that the anxiety of the pt during CPA examination is responsible for the changing of the MFAM. This was confirmed by examination of these pts with IHA under mental stress. In both vases the data obtained by the use of CPA agree closely with those obtained by the use of IHA under mental stress. These data indicate that both CPA and IHa are applicable for studying MFAM and that in external assessment of MFAM, not only the dietary status, but also the mental state of the pts should be considered

  11. Comparison of 11-C-Palmitic Acid (CPA), and 123-I-heptadecanoic acid (IHA) turnover in human heart

    Energy Technology Data Exchange (ETDEWEB)

    Notohamiprodjo, G.; Schmid, A.; Spohr, G.; Vyska, K.; Feinendegen, L.E.

    1985-05-01

    This study was designed to compare the results obtained with IHA in the investigation of myocardial fatty acid metabolism (MFAM) with those obtained by the use of CPA.- 8 patients (pts) without clinical signs of heart or metabolic disease were investigated under rest and fasting condition by dynamic PET following i.v. injection of 3 mCi CPA and by conventional scintigraphy following i.v. injection of 3 mCi IHA. Data were collected over a period of 90 min (frame rate was 1/min) and corrected for blood activity and catabolically released 123-I.-In 6 pts a good agreement between CPA and IHA data was observed. The activity release from the myocardium in these cases was biexponential. The ratio Q ranged between 0.7 and 6.7. -In the remaining 2 pts significant discrepancies between CPA and IHA data were observed. Since these pts were known to have cardiac neurosis and the first measurement was carried out with CPA, the authors assumed that the anxiety of the pt during CPA examination is responsible for the changing of the MFAM. This was confirmed by examination of these pts with IHA under mental stress. In both vases the data obtained by the use of CPA agree closely with those obtained by the use of IHA under mental stress. These data indicate that both CPA and IHa are applicable for studying MFAM and that in external assessment of MFAM, not only the dietary status, but also the mental state of the pts should be considered.

  12. Physiological Mechanisms Mediating the Coupling between Heart Period and Arterial Pressure in Response to Postural Changes in Humans.

    Science.gov (United States)

    Silvani, Alessandro; Calandra-Buonaura, Giovanna; Johnson, Blair D; van Helmond, Noud; Barletta, Giorgio; Cecere, Anna G; Joyner, Michael J; Cortelli, Pietro

    2017-01-01

    The upright posture strengthens the coupling between heart period (HP) and systolic arterial pressure (SAP) consistently with a greater contribution of the arterial baroreflex to cardiac control, while paradoxically decreasing cardiac baroreflex sensitivity (cBRS). To investigate the physiological mechanisms that mediate the coupling between HP and SAP in response to different postures, we analyzed the cross-correlation functions between low-frequency HP and SAP fluctuations and estimated cBRS with the sequence technique in healthy male subjects during passive head-up tilt test (HUTT, n = 58), during supine wakefulness, supine slow-wave sleep (SWS), and in the seated and active standing positions ( n = 8), and during progressive loss of 1 L blood ( n = 8) to decrease central venous pressure in the supine position. HUTT, SWS, the seated, and the standing positions, but not blood loss, entailed significant increases in the positive correlation between HP and the previous SAP values, which is the expected result of arterial baroreflex control, compared with baseline recordings in the supine position during wakefulness. These increases were mirrored by increases in the low-frequency variability of SAP in each condition but SWS. cBRS decreased significantly during HUTT, in the seated and standing positions, and after blood loss compared with baseline during wakefulness. These decreases were mirrored by decreases in the RMSSD index, which reflects cardiac vagal modulation. These results support the view that the cBRS decrease associated with the upright posture is a byproduct of decreased cardiac vagal modulation, triggered by the arterial baroreflex in response to central hypovolemia. Conversely, the greater baroreflex contribution to cardiac control associated with upright posture may be explained, at least in part, by enhanced fluctuations of SAP, which elicit a more effective entrainment of HP fluctuations by the arterial baroreflex. These SAP fluctuations may result

  13. No upregulation of digitalis glycoside receptor (Na,K-ATPase) concentration in human heart left ventricle samples obtained at necropsy after long term digitalisation.

    Science.gov (United States)

    Schmidt, T A; Holm-Nielsen, P; Kjeldsen, K

    1991-08-01

    life is associated with a 34% occupancy of digitalis glycoside receptors with digoxin. In the human heart there was no evidence for upregulation of digitalis glycoside receptor concentration due to long term digitalisation. Thus at receptor level there was no evidence for development of tolerance to digoxin therapy. The lower digitalis glycoside receptor concentration in the left ventricle observed in the heart failure patients may support the report of a relationship between Na,K-ATPase concentration as evaluated by 3H-ouabain binding and left ventricular function.

  14. Paraventricular nucleus of the human hypothalamus in primary hypertension: Activation of corticotropin-releasing hormone neurons

    NARCIS (Netherlands)

    Goncharuk, Valeri D.; van Heerikhuize, Joop; Swaab, Dick F.; Buijs, Ruud M.

    2002-01-01

    By using quantitative immunohistochemical and in situ hybridization techniques, we studied corticotropin-releasing hormone (CRH)-producing neurons of the hypothalamic paraventricular nucleus (PVN) in patients who suffered from primary hypertension and died due to acute cardiac failure. The control

  15. The stress system in depression and neurodegeneration: focus on the human hypothalamus.

    Science.gov (United States)

    Bao, A-M; Meynen, G; Swaab, D F

    2008-03-01

    The stress response is mediated by the hypothalamo-pituitary-adrenal (HPA) system. Activity of the corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) forms the basis of the activity of the HPA-axis. The CRH neurons induce adrenocorticotropin (ACTH) release from the pituitary, which subsequently causes cortisol release from the adrenal cortex. The CRH neurons co-express vasopressin (AVP) which potentiates the CRH effects. CRH neurons project not only to the median eminence but also into brain areas where they, e.g., regulate the adrenal innervation of the autonomic system and affect mood. The hypothalamo-neurohypophysial system is also involved in stress response. It releases AVP from the PVN and the supraoptic nucleus (SON) and oxytocin (OXT) from the PVN via the neurohypophysis into the bloodstream. The suprachiasmatic nucleus (SCN), the hypothalamic clock, is responsible for the rhythmic changes of the stress system. Both centrally released CRH and increased levels of cortisol contribute to the signs and symptoms of depression. Symptoms of depression can be induced in experimental animals by intracerebroventricular injection of CRH. Depression is also a frequent side effect of glucocorticoid treatment and of the symptoms of Cushing's syndrome. The AVP neurons in the hypothalamic PVN and SON are also activated in depression, which contributes to the increased release of ACTH from the pituitary. Increased levels of circulating AVP are also associated with the risk for suicide. The prevalence, incidence and morbidity risk for depression are higher in females than in males and fluctuations in sex hormone levels are considered to be involved in the etiology. About 40% of the activated CRH neurons in mood disorders co-express nuclear estrogen receptor (ER)-alpha in the PVN, while estrogen-responsive elements have been found in the CRH gene promoter region, and estrogens stimulate CRH production. An androgen-responsive element in the CRH gene promoter region initiates a suppressing effect on CRH expression. The decreased activity of the SCN is the basis for the disturbances of circadian and circannual fluctuations in mood, sleep and hormonal rhythms found in depression. Neuronal loss was also reported in the hippocampus of stressed or corticosteroid-treated rodents and primates. Because of the inhibitory control of the hippocampus on the HPA-axis, damage to this structure was expected to disinhibit the HPA-axis, and to cause a positive feedforward cascade of increasing glucocorticoid levels over time. This 'glucocorticoid cascade hypothesis' of stress and hippocampal damage was proposed to be causally involved in age-related accumulation of hippocampal damage in disorders like Alzheimer's disease and depression. However, in postmortem studies we could not find the presumed hippocampal damage of steroid overexposure in either depressed patients or in patients treated with synthetic steroids.

  16. Functional neuroanatomy of thyroid hormone feedback in the human hypothalamus and pituitary gland

    NARCIS (Netherlands)

    Fliers, Eric; Unmehopa, Unga A.; Alkemade, Anneke

    2006-01-01

    A major change in thyroid setpoint regulation occurs in various clinical conditions such as critical illness and psychiatric disorders. As a first step towards identifying determinants of these setpoint changes, we have studied the distribution and expression of thyroid hormone receptor (TR)

  17. The stress system in depression and neurodegeneration: Focus on the human hypothalamus

    NARCIS (Netherlands)

    Bao, A.-M.; Meynen, G.; Swaab, D.F.

    2008-01-01

    The stress response is mediated by the hypothalamo-pituitary-adrenal (HPA) system. Activity of the corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) forms the basis of the activity of the HPA-axis. The CRH neurons induce adrenocorticotropin (ACTH)

  18. Structure of the human-heart fatty-acid-binding protein 3 in complex with the fluorescent probe 1-anilinonaphthalene-8-sulphonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, Mika; Sugiyama, Shigeru, E-mail: sugiyama@chem.eng.osaka-u.ac.jp [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Ishida, Hanako; Niiyama, Mayumi [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Matsuoka, Daisuke; Hara, Toshiaki [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Mizohata, Eiichi [Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Murakami, Satoshi [Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama, Kanagaw 226-8501 (Japan); Inoue, Tsuyoshi [Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Matsuoka, Shigeru; Murata, Michio [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan)

    2013-11-01

    The crystal structure of human-heart-type fatty-acid-binding protein in complex with anilinonaphthalene-8-sulfonate was solved at 2.15 Å resolution revealing the detailed binding mechanism of the fluorescent probe 1-anilinonaphthalene-8-sulfonate. Heart-type fatty-acid-binding protein (FABP3), which is a cytosolic protein abundantly found in cardiomyocytes, plays a role in trafficking fatty acids throughout cellular compartments by reversibly binding intracellular fatty acids with relatively high affinity. The fluorescent probe 1-anilinonaphthalene-8-sulfonate (ANS) is extensively utilized for examining the interaction of ligands with fatty-acid-binding proteins. The X-ray structure of FABP3 was determined in the presence of ANS and revealed the detailed ANS-binding mechanism. Furthermore, four water molecules were clearly identified in the binding cavity. Through these water molecules, the bound ANS molecule forms indirect hydrogen-bond interactions with FABP3. The adipocyte-type fatty-acid-binding protein (FABP4) exhibits 67% sequence identity with FABP3 and its crystal structure is almost the same as that of FABP3. However, FABP4 can bind with a higher affinity to ANS than FABP3. To understand the difference in their ligand specificities, a structural comparison was performed between FABP3–ANS and FABP4–ANS complexes. The result revealed that the orientation of ANS binding to FABP3 is completely opposite to that of ANS binding to FABP4, and the substitution of valine in FABP4 to leucine in FABP3 may result in greater steric hindrance between the side-chain of Leu115 and the aniline ring of ANS.

  19. Structure of the human-heart fatty-acid-binding protein 3 in complex with the fluorescent probe 1-anilinonaphthalene-8-sulphonic acid

    International Nuclear Information System (INIS)

    Hirose, Mika; Sugiyama, Shigeru; Ishida, Hanako; Niiyama, Mayumi; Matsuoka, Daisuke; Hara, Toshiaki; Mizohata, Eiichi; Murakami, Satoshi; Inoue, Tsuyoshi; Matsuoka, Shigeru; Murata, Michio

    2013-01-01

    The crystal structure of human-heart-type fatty-acid-binding protein in complex with anilinonaphthalene-8-sulfonate was solved at 2.15 Å resolution revealing the detailed binding mechanism of the fluorescent probe 1-anilinonaphthalene-8-sulfonate. Heart-type fatty-acid-binding protein (FABP3), which is a cytosolic protein abundantly found in cardiomyocytes, plays a role in trafficking fatty acids throughout cellular compartments by reversibly binding intracellular fatty acids with relatively high affinity. The fluorescent probe 1-anilinonaphthalene-8-sulfonate (ANS) is extensively utilized for examining the interaction of ligands with fatty-acid-binding proteins. The X-ray structure of FABP3 was determined in the presence of ANS and revealed the detailed ANS-binding mechanism. Furthermore, four water molecules were clearly identified in the binding cavity. Through these water molecules, the bound ANS molecule forms indirect hydrogen-bond interactions with FABP3. The adipocyte-type fatty-acid-binding protein (FABP4) exhibits 67% sequence identity with FABP3 and its crystal structure is almost the same as that of FABP3. However, FABP4 can bind with a higher affinity to ANS than FABP3. To understand the difference in their ligand specificities, a structural comparison was performed between FABP3–ANS and FABP4–ANS complexes. The result revealed that the orientation of ANS binding to FABP3 is completely opposite to that of ANS binding to FABP4, and the substitution of valine in FABP4 to leucine in FABP3 may result in greater steric hindrance between the side-chain of Leu115 and the aniline ring of ANS

  20. Hyperactive hypothalamus, motivated and non-distractible chronic overeating in ADAR2 transgenic mice.

    Science.gov (United States)

    Akubuiro, A; Bridget Zimmerman, M; Boles Ponto, L L; Walsh, S A; Sunderland, J; McCormick, L; Singh, M

    2013-04-01

    ADAR2 transgenic mice misexpressing the RNA editing enzyme ADAR2 (Adenosine Deaminase that act on RNA) show characteristics of overeating and experience adult onset obesity. Behavioral patterns and brain changes related to a possible addictive overeating in these transgenic mice were explored as transgenic mice display chronic hyperphagia. ADAR2 transgenic mice were assessed in their food preference and motivation to overeat in a competing reward environment with ad lib access to a running wheel and food. Metabolic activity of brain and peripheral tissue were assessed with [(18) F] fluorodeoxyglucose positron emission tomography (FDG-PET) and RNA expression of feeding related genes, ADAR2, dopamine and opiate receptors from the hypothalamus and striatum were examined. The results indicate that ADAR2 transgenic mice exhibit, (1) a food preference for diets with higher fat content, (2) significantly increased food intake that is non-distractible in a competing reward environment, (3) significantly increased messenger RNA (mRNA) expressions of ADAR2, serotonin 2C receptor (5HT2C R), D1, D2 and mu opioid receptors and no change in corticotropin-releasing hormone mRNAs and significantly reduced ADAR2 protein expression in the hypothalamus, (4) significantly increased D1 receptor and altered bioamines with no change in ADAR2, mu opioid and D2 receptor mRNA expression in the striatum and (5) significantly greater glucose metabolism in the hypothalamus, brain stem, right hippocampus, left and right mid brain regions and suprascapular peripheral tissue than controls. These results suggest that highly motivated and goal-oriented overeating behaviors of ADAR2 transgenic mice are associated with altered feeding, reward-related mRNAs and hyperactive brain mesolimbic region. Genes, Brain and Behavior © 2013 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

  1. Effect of monochromatic light on circadian rhythmic expression of clock genes in the hypothalamus of chick.

    Science.gov (United States)

    Jiang, Nan; Wang, Zixu; Cao, Jing; Dong, Yulan; Chen, Yaoxing

    2017-08-01

    To clarify the effect of monochromatic light on circadian clock gene expression in chick hypothalamus, a total 240 newly hatched chickens were reared under blue light (BL), green light (GL), red light (RL) and white light (WL), respectively. On the post-hatched day 14, 24-h profiles of seven core clock genes (cClock, cBmal1, cBmal2, cCry1, cCry2, cPer2 and cPer3) were measured at six time points (CT 0, CT 4, CT 8, CT 12, CT 16, CT 20, circadian time). We found all these clock genes expressed with a significant rhythmicity in different light wavelength groups. Meanwhile, cClock and cBmal1 showed a high level under GL, and followed a corresponding high expression of cCry1. However, RL decreased the expression levels of these genes. Be consistent with the mRNA level, CLOCK and BMAL1 proteins also showed a high level under GL. The CLOCK-like immunoreactive neurons were observed not only in the SCN, but also in the non-SCN brain region such as the nucleus anterior medialis hypothalami, the periventricularis nucleus, the paraventricular nucleus and the median eminence. All these results are consistent with the auto-regulatory circadian feedback loop, and indicate that GL may play an important role on the circadian time generation and development in the chick hypothalamus. Our results also suggest that the circadian clock in the chick hypothalamus such as non-SCN brain region were involved in the regulation of photo information. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Melatonin modulates monochromatic light-induced melatonin receptor expression in the hypothalamus of chicks.

    Science.gov (United States)

    Zhang, Liwei; Chen, Funing; Cao, Jing; Dong, Yulan; Wang, Zixu; Chen, Yaoxing

    2017-09-01

    To study the mechanism of the effect of monochromatic light on physiological function in chicken, a total of 192 newly hatched chicks were randomly divided into intact, sham-operated and pinealectomy groups then exposed to white light (WL), red light (RL), green light (GL) and blue light (BL) using a light-emitting diode (LED) system for two weeks. At P14, the hypothalami were immediately collected for immunohistochemical staining of melatonin receptor subtypes (Mel1a and Mel1b) and detection of Mel1a and Mel1b expressions using RT-PCR and western blot. Immunohistochemical staining of the hypothalamus showed that the Mel1a-ir cells were distributed in the preoptic area (POA), nucleus preopticus periventricularis (POP) and suprachiasmatic nuclei (SCN), and the Mel1b-ir cells were presented in the POA and SCN. Analysis of RT-PCR and western blot showed that the mRNA and protein levels of Mel1a and Mel1b in the hypothalamus of chick exposed to GL were increased by 10.7-29.3%, 9.18-35.9% and 8.97-27.3% compared to those in the chicks exposed to WL (P=0.029-0.002), RL (P=0.027-0.001) and BL (P=0.038-0.007) in the intact group, respectively. After pinealectomy, however, these parameters decreased and there were no significant differences among the WL, RL, GL and BL groups. These findings suggested that melatonin plays a critical role in GL illumination-enhanced Mel1a and Mel1b expressions in the hypothalamus of chicks. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. The role of hypothalamus tuberomammillary nucleus on the regulation of respiratory movement of rats with asthma

    Directory of Open Access Journals (Sweden)

    Chen CHEN

    2016-01-01

    Full Text Available Objective  To explore the role of central histaminergic neurons in the tuberomammillary nucleus (TMN of posterior hypothalamus on asthma. Methods  Seventy-two healthy male SD rats were served as study objects. Sixty-four rats were sensitized with ovalbumin (OA solution intraperitoneally and challenged with OA aerosol inhalation to prepare asthma model. Asthma attack was evoked in asthmatic rats by OA solution injected intravenously, the electrical activities of TMN in posterior hypothalamus were recorded with biological signal collecting system and the power spectra were analyzed. TMN was lesioned or stimulated electrically by central stereo positioning technology. Histamine H3 receptor agonist R-(α-methylhistamine (RMHA or antagonist thioperamide (THIO was microinjected into TMN by central nuclear group microinjection technology, and the pulmonary function indexes were detected including diaphragm electromyography (EMGdi frequency, EMGdi integral, minute ventilation volume (MVV, expiratory time/inspiratory time (TE/TI, airway resistance (Raw and dynamic pulmonary compliance (Cdyn. Results  Compared with control group, the percentage of α, β1 and β2 wave in the electrical activities of TMN of asthmatic rats increased significantly, while the percentage of δ and θ wave decreased and the total discharge power increased. Compared with the corresponding control group, electric lesion of TMN or TMN microinjected with histamine H3 receptor antagonist increased EMGdi frequency, TE/TI, Raw, and decreased EMGdi integral, MVV and Cdyn. Compared with the corresponding control group, electric stimulation of TMN or TMN microinjected with histamine H3 receptor agonist decreased EMGdi frequency, TE/TI, Raw, and increased EMGdi integral, MVV and Cdyn. Conclusion  Central histaminergic neurons in tuberomammillary nucleus of posterior hypothalamus are activated in asthmatic rats. DOI: 10.11855/j.issn.0577-7402.2015.12.09

  4. Energy metabolism of rat cerebral cortex, hypothalamus and hypophysis during ageing.

    Science.gov (United States)

    Villa, R F; Ferrari, F; Gorini, A

    2012-12-27

    Ageing is one of the main risk factors for brain disorders. According to the neuroendocrine theory, ageing modifies the sensitivity of hypothalamus-pituitary-adrenal axis to homoeostatic signals coming from the cerebral cortex. The relationships between the energy metabolism of these areas have not been considered yet, in particular with respect to ageing. For these reasons, this study was undertaken to systematically investigate in female Sprague-Dawley rats aged 4, 6, 12, 18, 24, 28 months and in 4-month-old male ones, the catalytic properties of energy-linked enzymes of the Krebs' cycle, electron transport chain, glutamate and related amino acids on different mitochondrial subpopulations, i.e. non-synaptic perikaryal and intra-synaptic (two types) mitochondria. The biochemical enzymatic pattern of these mitochondria shows different expression of the above-mentioned enzymatic activities in the investigated brain areas, including frontal cerebral cortex, hippocampus, striatum, hypothalamus and hypophysis. The study shows that: (i) the energy metabolism of the frontal cerebral cortex is poorly affected by physiological ageing; (ii) the biochemical machinery of non-synaptic perikaryal mitochondria is differently expressed in the considered brain areas; (iii) at 4-6 months, hypothalamus and hypophysis possess lower oxidative metabolism with respect to the frontal cerebral cortex while (iv), during ageing, the opposite situation occurs. We hypothesised that these metabolic modifications likely try to grant HPA functionality in response to the incoming external stress stimuli increased during ageing. It is particularly notable that age-related changes in brain bioenergetics and in mitochondrial functionality may be considered as remarkable factors during physiological ageing and should play important roles in predisposing the brain to physiopathological events, tightly related to molecular mechanisms evoked for pharmacological treatments. Copyright © 2012 IBRO

  5. Neonatal maternal separation up-regulates protein signalling for cell survival in rat hypothalamus.

    Science.gov (United States)

    Irles, Claudine; Nava-Kopp, Alicia T; Morán, Julio; Zhang, Limei

    2014-05-01

    We have previously reported that in response to early life stress, such as maternal hyperthyroidism and maternal separation (MS), the rat hypothalamic vasopressinergic system becomes up-regulated, showing enlarged nuclear volume and cell number, with stress hyperresponsivity and high anxiety during adulthood. The detailed signaling pathways involving cell death/survival, modified by adverse experiences in this developmental window remains unknown. Here, we report the effects of MS on cellular density and time-dependent fluctuations of the expression of pro- and anti-apoptotic factors during the development of the hypothalamus. Neonatal male rats were exposed to 3 h-daily MS from postnatal days 2 to 15 (PND 2-15). Cellular density was assessed in the hypothalamus at PND 21 using methylene blue staining, and neuronal nuclear specific protein and glial fibrillary acidic protein immunostaining at PND 36. Expression of factors related to apoptosis and cell survival in the hypothalamus was examined at PND 1, 3, 6, 9, 12, 15, 20 and 43 by Western blot. Rats subjected to MS exhibited greater cell-density and increased neuronal density in all hypothalamic regions assessed. The time course of protein expression in the postnatal brain showed: (1) decreased expression of active caspase 3; (2) increased Bcl-2/Bax ratio; (3) increased activation of ERK1/2, Akt and inactivation of Bad; PND 15 and PND 20 were the most prominent time-points. These data indicate that MS can induce hypothalamic structural reorganization by promoting survival, suppressing cell death pathways, increasing cellular density which may alter the contribution of these modified regions to homeostasis.

  6. Engineering a 3D-Bioprinted Model of Human Heart Valve Disease Using Nanoindentation-Based Biomechanics

    Directory of Open Access Journals (Sweden)

    Dewy C. van der Valk

    2018-05-01

    Full Text Available In calcific aortic valve disease (CAVD, microcalcifications originating from nanoscale calcifying vesicles disrupt the aortic valve (AV leaflets, which consist of three (biomechanically distinct layers: the fibrosa, spongiosa, and ventricularis. CAVD has no pharmacotherapy and lacks in vitro models as a result of complex valvular biomechanical features surrounding resident mechanosensitive valvular interstitial cells (VICs. We measured layer-specific mechanical properties of the human AV and engineered a three-dimensional (3D-bioprinted CAVD model that recapitulates leaflet layer biomechanics for the first time. Human AV leaflet layers were separated by microdissection, and nanoindentation determined layer-specific Young’s moduli. Methacrylated gelatin (GelMA/methacrylated hyaluronic acid (HAMA hydrogels were tuned to duplicate layer-specific mechanical characteristics, followed by 3D-printing with encapsulated human VICs. Hydrogels were exposed to osteogenic media (OM to induce microcalcification, and VIC pathogenesis was assessed by near infrared or immunofluorescence microscopy. Median Young’s moduli of the AV layers were 37.1, 15.4, and 26.9 kPa (fibrosa/spongiosa/ventricularis, respectively. The fibrosa and spongiosa Young’s moduli matched the 3D 5% GelMa/1% HAMA UV-crosslinked hydrogels. OM stimulation of VIC-laden bioprinted hydrogels induced microcalcification without apoptosis. We report the first layer-specific measurements of human AV moduli and a novel 3D-bioprinted CAVD model that potentiates microcalcification by mimicking the native AV mechanical environment. This work sheds light on valvular mechanobiology and could facilitate high-throughput drug-screening in CAVD.

  7. State-dependent cellular activity patterns of the cat paraventricular hypothalamus measured by reflectance imaging

    DEFF Research Database (Denmark)

    Kristensen, Morten Pilgaard; Rector, D M; Poe, G R

    1996-01-01

    Activity within the cat paraventricular hypothalamus (PVH) during sleep and waking states was measured by quantifying intrinsic tissue reflectivity. A fiber optic probe consisting of a 1.0 mm coherent image conduit, surrounded by plastic fibers which conducted 660 nm source light, was attached...... to a charge-coupled device camera, and positioned over the PVH in five cats. Electrodes for assessing state variables, including electroencephalographic activity, eye movement, and somatic muscle tone were also placed. After surgical recovery, reflected light intensity was measured continuously at 2.5 Hz...

  8. Effect of. beta. -endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Slavnov, V.N.; Valueva, G.V.; Markov, V.V.; Luchitskii, E.V.

    1986-10-01

    The authors studied the effect of beta-endorphin on catecholamine concentrations in the hypothalmus and cerebral cortex in rats, as a contribution to the explanation of the mechanism of action of this peptide on certain pituitary trophic functions. Concentrations of dopamine, noradrenalin, and adrenalin were determined by a radioenzymatic method. A Mark 3 scintillation system was used for radiometric investigation of the samples. The results of these experiments indicate that beta-endorphin has a marked effect on brain catecholamine levels mainly in the hypothalamus.

  9. Effect of β-endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

    International Nuclear Information System (INIS)

    Slavnov, V.N.; Valueva, G.V.; Markov, V.V.; Luchitskii, E.V.

    1986-01-01

    The authors studied the effect of beta-endorphin on catecholamine concentrations in the hypothalmus and cerebral cortex in rats, as a contribution to the explanation of the mechanism of action of this peptide on certain pituitary trophic functions. Concentrations of dopamine, noradrenalin, and adrenalin were determined by a radioenzymatic method. A Mark 3 scintillation system was used for radiometric investigation of the samples. The results of these experiments indicate that beta-endorphin has a marked effect on brain catecholamine levels mainly in the hypothalamus

  10. Turnover of Biogenic Amines in the Hypothalamus of Rats during Pyrogen Fever

    Science.gov (United States)

    Penn, P. E.; Williams, B. A.

    1979-01-01

    Many pharmacological studies have implicated the biogenic amines in the hypothalamus as playing a role in the production of fever, but few investigations of endogenous neurochemicals have been made during fever. Turnover rates of transmitters utilizing radioactive precursors may be one of the most accurate measurements of activity in brain regions. The present study was designed to measure the turnover of 5-hydroxytryptamine (5-HT) norepinephrine (NE) and dopamine (DA) in the hypothalamus of rats during pyrogen fever. Salmonella typhosa (Wyeth, 8 units) was previously found in our laboratory to produce a significant hyperthermia in most rats by 2.5 hours. This pyrogen (N = l2) or saline control (N = 8) was injected intraperitoneally and the rats killed 2.75 hours later. Rectal temperatures (Tr) were monitored continuously with thermocouples taped to the tail and recorded automatically every 3 minutes. Half of each group received an injection of radioactive precursors, (3)H-tryptophan (0.5 mCi) and (3)H-tryptophan (1.0 mCi), via an indwelling jugular catheter 60 minutes before killing, and the other half at 90 minutes. The rats were killed by near freezing in liquid nitrogen and the brains dissected in the cold. Turnover was measured by the method of Lane (Life Sci 21, 1101, 1977). At the time of killing most of the pyrogen group showed a significant (p pyrogen and saline groups. A significant difference was found in the specific activity of NE between the 60 minute pyrogen and saline groups (4.41 +/- 0.41 vs 2.6 +/- 0.51 dpm/pmole) but no change in turnover. This suggests an increased accumulation of (3)H-NE in the pyrogen group, but no change in utilization. An increased turnover of DA for the pyrogen group (44.5 vs 19.2 pmole/mg protein/hr) was found. However, DA is mainly a precursor in the hypothalamus and measurement was near the limit of sensitivity for the assay; these limitations Must be considered in interpreting this data. The most significant finding was

  11. High affinity complexes of pannexin channels and L-type calcium channel splice-variants in human lung: Possible role in clevidipine-induced dyspnea relief in acute heart failure

    Directory of Open Access Journals (Sweden)

    Gerhard P. Dahl

    2016-08-01

    Research in Context: Clevidipine lowers blood pressure by inhibiting calcium channels in vascular smooth muscle. In patients with acute heart failure, clevidipine was shown to relieve breathing problems. This was only partially related to the blood pressure lowering actions of clevidipine and not conferred by another calcium channel inhibitor. We here found calcium channel variants in human lung that are more selectively inhibited by clevidipine, especially when associated with pannexin channels. This study gives a possible mechanism for clevidipine's relief of breathing problems and supports future clinical trials testing the role of clevidipine in the treatment of acute heart failure.

  12. MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothalamus.

    Directory of Open Access Journals (Sweden)

    Patricia Blanchet

    2017-08-01

    Full Text Available Deletions at chromosome 2p25.3 are associated with a syndrome consisting of intellectual disability and obesity. The smallest region of overlap for deletions at 2p25.3 contains PXDN and MYT1L. MYT1L is expressed only within the brain in humans. We hypothesized that single nucleotide variants (SNVs in MYT1L would cause a phenotype resembling deletion at 2p25.3. To examine this we sought MYT1L SNVs in exome sequencing data from 4, 296 parent-child trios. Further variants were identified through a genematcher-facilitated collaboration. We report 9 patients with MYT1L SNVs (4 loss of function and 5 missense. The phenotype of SNV carriers overlapped with that of 2p25.3 deletion carriers. To identify the transcriptomic consequences of MYT1L loss of function we used CRISPR-Cas9 to create a knockout cell line. Gene Ontology analysis in knockout cells demonstrated altered expression of genes that regulate gene expression and that are localized to the nucleus. These differentially expressed genes were enriched for OMIM disease ontology terms "mental retardation". To study the developmental effects of MYT1L loss of function we created a zebrafish knockdown using morpholinos. Knockdown zebrafish manifested loss of oxytocin expression in the preoptic neuroendocrine area. This study demonstrates that MYT1L variants are associated with syndromic obesity in humans. The mechanism is related to dysregulated expression of neurodevelopmental genes and altered development of the neuroendocrine hypothalamus.

  13. A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence.

    Science.gov (United States)

    Marchant, Nathan J; Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M; Bonci, Antonello; Shaham, Yavin

    2014-05-28

    In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA + GABAB receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse. Copyright © 2014 the authors 0270-6474/14/347447-11$15.00/0.

  14. Oral delivery of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, synthetic peptide leptin mimetics: Immunofluorescent localization in the mouse hypothalamus.

    Science.gov (United States)

    Anderson, Brian M; Jacobson, Lauren; Novakovic, Zachary M; Grasso, Patricia

    2017-06-01

    This study describes the localization of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, synthetic peptide leptin mimetics, in the hypothalamus of Swiss Webster and C57BL/6J wild-type mice, leptin-deficient ob/ob mice, and leptin-resistant diet-induced obese (DIO) mice. The mice were given [D-Leu-4]-OB3 or MA-[D-Leu-4]-OB3 in 0.3% dodecyl maltoside by oral gavage. Once peak serum concentrations were reached, the mice received a lethal dose of pentobarbital and were subjected to intracardiac perfusion fixation. The brains were excised, post-fixed in paraformaldehyde, and cryo-protected in sucrose. Free-floating frozen coronal sections were cut at 25-µm and processed for imaging by immunofluorescence microscopy. In all four strains of mice, dense staining was concentrated in the area of the median eminence, at the base and/or along the inner wall of the third ventricle, and in the brain parenchyma at the level of the arcuate nucleus. These results indicate that [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 cross the blood-brain barrier and concentrate in an area of the hypothalamus known to regulate energy balance and glucose homeostasis. Most noteworthy is the localization of [D-Leu-4]-OB3 immunoreactivity within the hypothalamus of DIO mice via a conduit that is closed to leptin in this rodent model, and in most cases of human obesity. Together with our previous studies describing the effects of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 on energy balance, glucose regulation, and signal transduction pathway activation, these findings are consistent with a central mechanism of action for these synthetic peptide leptin mimetics, and suggest their potential usefulness in the management of leptin-resistant obesity and type 2 diabetes in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Heart valve surgery

    Science.gov (United States)

    ... replacement; Valve repair; Heart valve prosthesis; Mechanical valves; Prosthetic valves ... surgery. Your heart valve has been damaged by infection ( endocarditis ). You have received a new heart valve ...

  16. Heart failure - tests

    Science.gov (United States)

    CHF - tests; Congestive heart failure - tests; Cardiomyopathy - tests; HF - tests ... the best test to: Identify which type of heart failure (systolic, diastolic, valvular) Monitor your heart failure and ...

  17. Sex differences in feeding behavior in rats: the relationship with neuronal activation in the hypothalamus

    Directory of Open Access Journals (Sweden)

    Atsushi eFukushima

    2015-03-01

    Full Text Available There is general agreement that the central nervous system in rodents differs between sexes due to the presence of gonadal steroid hormone during differentiation. Sex differences in feeding seem to occur among species, and responses to fasting (i.e., starvation, gonadal steroids (i.e., testosterone and estradiol, and diet (i.e., western-style diet vary significantly between sexes. The hypothalamus is the center for controlling feeding behavior. We examined the activation of feeding-related peptides in neurons in the hypothalamus. Phosphorylation of cyclic AMP response element-binding protein (CREB is a good marker for neural activation, as is the Fos antigen. Therefore, we predicted that sex differences in the activity of melanin-concentrating hormone (MCH neurons would be associated with feeding behavior. We determined the response of MCH neurons to glucose in the lateral hypothalamic area (LHA and our results suggested MCH neurons play an important role in sex differences in feeding behavior. In addition, fasting increased the number of orexin neurons harboring phosphorylated CREB in female rats (regardless of the estrous day, but not male rats. Glucose injection decreased the number of these neurons with phosphorylated CREB in fasted female rats. Finally, under normal spontaneous food intake, MCH neurons, but not orexin neurons, expressed phosphorylated CREB. These sex differences in response to fasting and glucose, as well as under normal conditions, suggest a vulnerability to metabolic challenges in females.

  18. Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia.

    Science.gov (United States)

    Ihnatko, R; Post, C; Blomqvist, A

    2013-10-01

    Anorexia-cachexia is a common and severe cancer-related complication but the underlying mechanisms are largely unknown. Here, using a mouse model for tumour-induced anorexia-cachexia, we screened for proteins that are differentially expressed in the hypothalamus, the brain's metabolic control centre. The hypothalamus of tumour-bearing mice with implanted methylcholanthrene-induced sarcoma (MCG 101) displaying anorexia and their sham-implanted pair-fed or free-fed littermates was examined using two-dimensional electrophoresis (2-DE)-based comparative proteomics. Differentially expressed proteins were identified by liquid chromatography-tandem mass spectrometry. The 2-DE data showed an increased expression of dynamin 1, hexokinase, pyruvate carboxylase, oxoglutarate dehydrogenase, and N-ethylmaleimide-sensitive factor in tumour-bearing mice, whereas heat-shock 70 kDa cognate protein, selenium-binding protein 1, and guanine nucleotide-binding protein Gα0 were downregulated. The expression of several of the identified proteins was similarly altered also in the caloric-restricted pair-fed mice, suggesting an involvement of these proteins in brain metabolic adaptation to restricted nutrient availability. However, the expression of dynamin 1, which is required for receptor internalisation, and of hexokinase, and pyruvate carboxylase were specifically changed in tumour-bearing mice with anorexia. The identified differentially expressed proteins may be new candidate molecules involved in the pathophysiology of tumour-induced anorexia-cachexia.

  19. Stiletto stabbing: penetrating injury to the hypothalamus with hyperacute diabetes insipidus.

    Science.gov (United States)

    Itshayek, Eyal; Gomori, John Moshe; Spektor, Sergey; Cohen, José E

    2010-12-01

    Diabetes insipidus (DI) is a well documented complication observed after traumatic head injuries. We report a case of hyperacute onset DI in a 19-year-old male who sustained a hypothalamic-pituitary injury when he was stabbed in the head with a 30-cm long thin-bladed knife. At CT, our patient showed significant hemorrhagic contusions of the lower hypothalamus. He developed polydipsia, polyuria, and mild hypernatremia in the Emergency Department. Diagnostic digital subtraction angiography showed a hypervascular congestive pituitary gland with prominent draining veins. On the third day his hypernatremia became severe (183mEq/L). He was managed with parenteral fluids and a regimen of intranasal DDAVP (1-desamino 8-d-arginine vasopressin), leading to improved plasmatic sodium levels, urine output, and urinary specific gravity. In patients presenting with hyperacute posttraumatic DI, emergency room physicians and neurosurgeons should rule out direct injury to the hypothalamus and/or the posterior lobe of the pituitary, and initiate early pharmacological treatment. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Characterization of taurine binding, uptake, and release in the rat hypothalamus

    International Nuclear Information System (INIS)

    Hanretta, A.T.

    1985-01-01

    The neurotransmitter criteria of specific receptors, inactivation, and release were experimentally examined for taurine in the hypothalamus. Specific membrane binding and synaptosomal uptake of taurine both displayed high affinity and low affinity systems. The neurotransmitter criterion of release was studied in superfused synaptosomes. Exposure of synaptosomes which had been preloaded with a concentration of [ 3 H]taurine in the high affinity uptake range (1.5 μM) to either 56 mM K + or 100 μM veratridine evoked a Ca 2+ -independent release. Exposure of synaptosomes which had been preloaded with a concentration of [ 3 H]taurine in the low affinity uptake range (2 mM) to 56 mM K + induced a Ca 2+ -independent release, whereas 100 + M veratridine did not, either in the presence or absence of Ca 2+ . Based on these results, as well as other observations, a model is proposed in which the high affinity uptake system is located on neuronal membranes and the low affinity uptake system is located on glial membranes. The mechanisms of binding, uptake, and release in relation to the cellular location of each are discussed. We conclude that the neurotransmitter criterion of activation by re-uptake is satisfied for taurine in the hypothalamus. However, the failure to demonstrate both a specific taurine receptor site and a Ca 2+ -dependent evoked release, necessitates that we conclude that taurine appears not to function as a hypothalamic neurotransmitter, at least not in the classical sense

  1. Differential requirements for Gli2 and Gli3 in the regional specification of the mouse hypothalamus

    Directory of Open Access Journals (Sweden)

    Roberta eHaddad-Tóvolli

    2015-03-01

    Full Text Available Secreted protein Sonic hedgehog (Shh ventralizes the neural tube by modulating the crucial balance between activating and repressing functions (GliA, GliR of transcription factors Gli2 and Gli3. This balance—the Shh-Gli code—is species- and context-dependent and has been elucidated for the mouse spinal cord. The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation. Here we asked if particular combinations of Gli2 and Gli3 and of GliA and GliR functions contribute to the variety of hypothalamic regions, i.e. we wanted to clarify the hypothalamic version of the Shh-Gli code. Based on mouse mutant analysis, we show that: 1 hypothalamic regional heterogeneity is based in part on differentially stringent requirements for Gli2 or Gli3; 2 another source of diversity are differential requirements for Shh of neural vs non-neural origin; 3 Gli2 is indispensable for the specification of a medial progenitor domain generating several essential hypothalamic nuclei plus the pituitary and median eminence; 4 the suppression of Gli3R by neural and non-neural Shh is essential for hypothalamic specification. Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions. Our data confirm the model and are explained by it.

  2. Reactive oxygen species in the paraventricular nucleus of the hypothalamus alter sympathetic activity during metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    JOSIANE CAMPOS CRUZ

    2015-12-01

    Full Text Available The paraventricular nucleus of the hypothalamus (PVN contains heterogeneous populations of neurons involved in autonomic and neuroendocrine regulation. The PVN plays an important role in the sympathoexcitatory response to increasing circulating levels of angiotensin II (Ang-II, which activates AT1 receptors in the circumventricular organs (OCVs, mainly in the subfornical organ (SFO. Circulating Ang-II induces a de novo synthesis of Ang-II in SFO neurons projecting to pre-autonomic PVN neurons. Activation of AT1 receptors induces intracellular increases in reactive oxygen species (ROS, leading to increases in sympathetic nerve activity (SNA. Chronic sympathetic nerve activation promotes a series of metabolic disorders that characterizes the metabolic syndrome (MetS: dyslipidemia, hyperinsulinemia, glucose intolerance, hyperleptinemia and elevated plasma hormone levels, such as noradrenaline, glucocorticoids, leptin, insulin and Ang-II. This review will discuss the contribution of our laboratory and others regarding the sympathoexcitation caused by peripheral Ang-II-induced reactive oxygen species along the subfornical organ and paraventricular nucleus of the hypothalamus. We hypothesize that this mechanism could be involved in metabolic disorders underlying MetS.

  3. Induction of Autophagy in the Striatum and Hypothalamus of Mice after 835 MHz Radiofrequency Exposure.

    Directory of Open Access Journals (Sweden)

    Ju Hwan Kim

    Full Text Available The extensive use of wireless mobile phones and associated communication devices has led to increasing public concern about potential biological health-related effects of the exposure to electromagnetic fields (EMFs. EMFs emitted by a mobile phone have been suggested to influence neuronal functions in the brain and affect behavior. However, the affects and phenotype of EMFs exposure are unclear. We applied radiofrequency (RF of 835 MHz at a specific absorption rate (SAR of 4.0 W/kg for 5 hours/day for 4 and 12 weeks to clarify the biological effects on mouse brain. Interestingly, microarray data indicated that a variety of autophagic related genes showed fold-change within small range after 835 MHz RF exposure. qRT-PCR revealed significant up-regulation of the autophagic genes Atg5, LC3A and LC3B in the striatum and hypothalamus after a 12-week RF. In parallel, protein expression of LC3B-II was also increased in both brain regions. Autophagosomes were observed in the striatum and hypothalamus of RF-exposed mice, based on neuronal transmission electron microscopy. Taken together, the results indicate that RF exposure of the brain can induce autophagy in neuronal tissues, providing insight into the protective mechanism or adaptation to RF stress.

  4. Genetics of Valvular Heart Disease

    Science.gov (United States)

    LaHaye, Stephanie; Lincoln, Joy

    2015-01-01

    Valvular heart disease is associated with significant morbidity and mortality and often the result of congenital malformations. However, the prevalence is increasing in adults not only because of the growing aging population, but also because of improvements in the medical and surgical care of children with congenital heart valve defects. The success of the Human Genome Project and major advances in genetic technologies, in combination with our increased understanding of heart valve development, has led to the discovery of numerous genetic contributors to heart valve disease. These have been uncovered using a variety of approaches including the examination of familial valve disease and genome-wide association studies to investigate sporadic cases. This review will discuss these findings and their implications in the treatment of valvular heart disease. PMID:24743897

  5. The effects of subchronic acrylamide exposure on gene expression, neurochemistry, hormones, and histopathology in the hypothalamus-pituitary-thyroid axis of male Fischer 344 rats

    International Nuclear Information System (INIS)

    Bowyer, J.F.; Latendresse, J.R.; Delongchamp, R.R.; Muskhelishvili, L.; Warbritton, A.R.; Thomas, M.; Tareke, E.; McDaniel, L.P.; Doerge, D.R.

    2008-01-01

    Acrylamide (AA) is an important industrial chemical that is neurotoxic in rodents and humans and carcinogenic in rodents. The observation of cancer in endocrine-responsive tissues in Fischer 344 rats has prompted hypotheses of hormonal dysregulation, as opposed to DNA damage, as the mechanism for tumor induction by AA. The current investigation examines possible evidence for disruption of the hypothalamic-pituitary-thyroid axis from 14 days of repeated exposure of male Fischer 344 rats to doses of AA that range from one that is carcinogenic after lifetime exposure (2.5 mg/kg/d), an intermediate dose (10 mg/kg/d), and a high dose (50 mg/kg/d) that is neurotoxic for this exposure time. The endpoints selected include: serum levels of thyroid and pituitary hormones; target tissue expression of genes involved in hormone synthesis, release, and receptors; neurotransmitters in the CNS that affect hormone homeostasis; and histopathological evaluation of target tissues. These studies showed virtually no evidence for systematic alteration of the hypothalamic-pituitary-thyroid axis and do not support hormone dysregulation as a plausible mechanism for AA-induced thyroid cancer in the Fischer 344 rat. Specifically, there were no significant changes in: 1) mRNA levels in hypothalamus or pituitary for TRH, TSH, thyroid hormone receptor α and β, as well 10 other hormones or releasing factors; 2) mRNA levels in thyroid for thyroglobulin, thyroid peroxidase, sodium iodide symporter, or type I deiodinases; 3) serum TSH or T3 levels (T4 was decreased at high dose only); 4) dopaminergic tone in the hypothalamus and pituitary or importantly 5) increased cell proliferation (Mki67 mRNA and Ki-67 protein levels were not increased) in thyroid or pituitary. These negative findings are consistent with a genotoxic mechanism of AA carcinogenicity based on metabolism to glycidamide and DNA adduct formation. Clarification of this mechanistic dichotomy may be useful in human cancer risk

  6. Treatment of Children with Protein – Losing Enteropathy After Fontan and Other Complex Congenital Heart Disease Procedures in Condition with Limited Human and Technical Resources

    Science.gov (United States)

    Bejiqi, Ramush; Retkoceri, Ragip; Zeka, Naim; Bejiqi, Hana; Vuqiterna, Armend; Maloku, Arlinda

    2014-01-01

    Background Protein-losing enteropathy (PLE) is a disorder characterized by abnormal and often profound enteric protein loss. It’s relatively uncommon complication of Fontan and other complex congenital heart disease (CCHD) procedures. Because of the complexity and rarity of this disease process, the pathogenesis and pathophysiology of protein-losing enteropathy remain poorly understood, and attempts at treatment seldom yield long-term success. Aim of presentation is to describe single centre experience in diagnosis, evaluation, management and treatment of children with protein-losing enteropathy after Fontan and other CCHD procedures in the current era and in centre with limited human and technical resources, follows with a comprehensive review of protein-losing enteropathy publications, and concludes with suggestions for prevention and treatment. Material and methodology Retrospectively we analyzed patients with CCHD and protein-losing enteropathy in our institution, starting from January 2000 to December 2012. The including criteria were age between two and 17 years, to have a complex congenital heart disease and available complete documentation of cardiac surgery under cardiopulmonary bypass. Results Of all patients we evaluated 18 cases with protein-losing enteropathy, aged 6 to 19 years (mean 14±9); there were three children who had undergone screening procedure for D-transposition, one Tetralogy of Fallot, and remaining 14 patients had undergone Fontan procedures; (anatomic diagnosis are: six with tricuspid atresia, seven with d-transposition, double outlet right ventricle and pulmonary atresia and two with hypoplastic left heart syndrome). The diagnosis of protein-losing enteropathy was made at median age of 5.6 years, ranging from 13 months to 15 years. Diagnosis was made using alpha 1-antitrypsin as a gold marker in stool. By physical examination in 14 patients edema was found, in three ascites, and six patients had pleural effusion. Laboratory findings

  7. The effect of radioactive radiation of the neurotransmitter levels in the hypothalamus, pituitary and pineal glands of sheeps

    International Nuclear Information System (INIS)

    Pastorova, B.; Maracek, I.; Stanikova, A.; Halagan, J.; Sopkova, D.

    2006-01-01

    The effect of the exposure of the whole body to continuous radiation was studied of catecholamines (epinephrine and unepinephrine) in the hypothalamus, pineal and pituitary glands of ewes during the anestric period with synchronized oestrus. The radiation was provided at the rate 0.020 Gy per hour. Catecholamines were separated from the tissue supernatants by the absorption chromatographic method and the catecholamine contents in the eluates were determined spectrofluorometrically. Protracted exposure to gamma radiation and hormone stimulation with SG reduces the concentration of unepinephrine (P<0.001) in the whole hypothalamus of the sheep. A statistically significant decrease (P<0.001) was recorded in the medial and caudal hypothalamus of ewes. If is assumed that the decrease in catecholamine concentration after irradiation (2.4 Gy) is associated with the destroyed metabolism of catecholamines in nervous tissue and activity its degradation enzyme monoaminooxidase. (authors)

  8. Reduced Dietary Sodium Intake Increases Heart Rate

    DEFF Research Database (Denmark)

    Graudal, Niels A; Hubeck-Graudal, Thorbjørn; Jürgens, Gesche

    2016-01-01

    Reduced dietary sodium intake (sodium reduction) increases heart rate in some studies of animals and humans. As heart rate is independently associated with the development of heart failure and increased risk of premature death a potential increase in heart rate could be a harmful side......-effect of sodium reduction. The purpose of the present meta-analysis was to investigate the effect of sodium reduction on heart rate. Relevant studies were retrieved from an updated pool of 176 randomized controlled trials (RCTs) published in the period 1973-2014. Sixty-three of the RCTs including 72 study...... populations reported data on heart rate. In a meta-analysis of these data sodium reduction increased heart rate with 1.65 beats per minute [95% CI: 1.19, 2.11], p heart rate. This effect was independent of baseline blood pressure. In conclusion sodium reduction...

  9. Women's Heart Disease: Heart Attack Symptoms

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Women's Heart Disease Heart Attack Symptoms Past Issues / Winter ... most common heart attack symptom in men and women is chest pain or discomfort. However, women also ...

  10. Heart Health: The Heart Truth Campaign 2009

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Cover Story Heart Health The Heart Truth Campaign 2009 Past Issues / Winter 2009 Table ... one of the celebrities supporting this year's The Heart Truth campaign. Both R&B singer Ashanti (center) ...

  11. Heart Health - Heart Disease: Symptoms, Diagnosis, Treatment

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Cover Story Heart Health Heart Disease: Symptoms, Diagnosis, Treatment Past Issues / Winter 2009 ... of this page please turn Javascript on. Most heart attacks happen when a clot in the coronary ...

  12. Women's Heart Disease: Heart Disease Risk Factors

    Science.gov (United States)

    ... this page please turn JavaScript on. Feature: Women's Heart Disease Heart Disease Risk Factors Past Issues / Winter 2014 Table ... or habits may raise your risk for coronary heart disease (CHD). These conditions are known as risk ...

  13. Variability of Heart Rate in Primitive Horses and Their Relatives as an Indicator of Stress Level, Behavioural Conduct Towards Humans and Adaptation to Living in Wild

    Directory of Open Access Journals (Sweden)

    Pluta Michał

    2014-10-01

    Full Text Available The aim of the study was to evaluate the possibility of using heart rate (HR as a metric parameter that can be used for the characterisation of behaviour of primitive horses and their relatives, related to reactions to the stress resulting from the contact with humans and adaptation to living in various conditions, including natural environment. This characterisation served the authors to expand the knowledge of such behaviour of primitive horses, and to assess the impact of the environmental and genetic factors. Studies were conducted in three populations of horses: two herds of Polish Konik and one herd of Biłgoraj horses. The studies were performed between 1993 and 2010. They concerned the behaviour of horses during grooming - breeding procedures (hooves clearing, body measurements performed cyclically and the daily observations when HR was monitored continuously. HR results for the respective age categories, during particular grooming - breeding procedures and reserve observations indicate that Polish Konik horses, closely related to the primitive Tarpan breed, are genetically better adapted to living in conditions similar to the natural (reserve than the Biłgoraj horses. They show less stress symptoms, which are evidenced by HR values noted during inhabiting the natural environment.

  14. Regulatory Forum Review*: Utility of in Vitro Secondary Pharmacology Data to Assess Risk of Drug-induced Valvular Heart Disease in Humans: Regulatory Considerations.

    Science.gov (United States)

    Papoian, Thomas; Jagadeesh, Gowraganahalli; Saulnier, Muriel; Simpson, Natalie; Ravindran, Arippa; Yang, Baichun; Laniyonu, Adebayo A; Khan, Imran; Szarfman, Ana

    2017-04-01

    Drug-induced valvular heart disease (VHD) is a serious side effect linked to long-term treatment with 5-hydroxytryptamine (serotonin) receptor 2B (5-HT 2B ) agonists. Safety assessment for off-target pharmacodynamic activity is a common approach used to screen drugs for this undesired property. Such studies include in vitro assays to determine whether the drug is a 5-HT 2B agonist, a necessary pharmacological property for development of VHD. Measures of in vitro binding affinity (IC 50 , K i ) or cellular functional activity (EC 50 ) are often compared to maximum therapeutic free plasma drug levels ( fC max ) from which safety margins (SMs) can be derived. However, there is no clear consensus on what constitutes an appropriate SM under various therapeutic conditions of use. The strengths and limitations of SM determinations and current risk assessment methodology are reviewed and evaluated. It is concluded that the use of SMs based on K i values, or those relative to serotonin (5-HT), appears to be a better predictor than the use of EC 50 or EC 50 /human fC max values for determining whether known 5-HT 2B agonists have resulted in VHD. It is hoped that such a discussion will improve efforts to reduce this preventable serious drug-induced toxicity from occurring and lead to more informed risk assessment strategies.

  15. Mechanical unloading of the failing human heart fails to activate the protein kinase B/Akt/glycogen synthase kinase-3beta survival pathway.

    Science.gov (United States)

    Razeghi, Peter; Bruckner, Brian A; Sharma, Saumya; Youker, Keith A; Frazier, O H; Taegtmeyer, Heinrich

    2003-01-01

    Left ventricular assist device (LVAD) support of the failing human heart improves myocyte function and increases cell survival. One potential mechanism underlying this phenomenon is activation of the protein kinase B (PKB)/Akt/glycogen synthase kinase-3beta (GSK-3beta) survival pathway. Left ventricular tissue was obtained both at the time of implantation and explantation of the LVAD (n = 11). Six patients were diagnosed with idiopathic dilated cardiomyopathy, 4 patients with ischemic cardiomyopathy and 1 patient with peripartum cardiomyopathy. The mean duration of LVAD support was 205 +/- 35 days. Myocyte diameter and phosphorylation of ERK were used as indices for reverse remodeling. Transcript levels of genes required for the activation of PKB/Akt (insulin-like growth factor-1, insulin receptor substrate-1) were measured by quantitative RT-PCR. In addition, we measured the relative activity of PKB/Akt and GSK-3beta, and assayed for molecular and histological indices of PKB/Akt activation (cyclooxygenase mRNA levels and glycogen levels). Myocyte diameter and phosphorylation of ERK decreased with LVAD support. In contrast, none of the components of the PKB/Akt/GSK-3beta pathway changed significantly with mechanical unloading. The PKB/Akt/GSK-3beta pathway is not activated during LVAD support. Other signaling pathways must be responsible for the improvement of cellular function and cell survival during LVAD support. Copyright 2003 S. Karger AG, Basel

  16. Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model

    Science.gov (United States)

    Canelles, Sandra; Argente, Jesús; Barrios, Vicente

    2016-01-01

    ABSTRACT Insulin receptor substrate-2-deficient (IRS2−/−) mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I) and insulin on metabolism, mitogenesis and cell survival. The hypothalamus might play a key role in the early onset of diabetes, owing to its involvement in the control of glucose homeostasis and energy balance. Because some inflammatory markers are elevated in the hypothalamus of diabetic IRS2−/− mice, our aim was to analyze whether the diabetes associated with the absence of IRS2 results in hypothalamic injury and to analyze the intracellular mechanisms involved. Only diabetic IRS2−/− mice showed increased cell death and activation of caspase-8 and -3 in the hypothalamus. Regulators of apoptosis such as FADD, Bcl-2, Bcl-xL and p53 were also increased, whereas p-IκB and c-FLIPL were decreased. This was accompanied by increased levels of Nox-4 and catalase, enzymes involved in oxidative stress. In summary, the hypothalamus of diabetic IRS2−/− mice showed an increase in oxidative stress and inflammatory markers that finally resulted in cell death via substantial activation of the extrinsic apoptotic pathway. Conversely, non-diabetic IRS2−/− mice did not show cell death in the hypothalamus, possibly owing to an increase in the levels of circulating IGF-I and in the enhanced hypothalamic IGF-IR phosphorylation that would lead to the stimulation of survival pathways. In conclusion, diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus. PMID:27013528

  17. Modulation of sibutramine-induced increases in extracellular noradrenaline concentration in rat frontal cortex and hypothalamus by α2-adrenoceptors

    Science.gov (United States)

    Wortley, K E; Heal, D J; Stanford, S C

    1999-01-01

    The effects of sibutramine (0.25–10 mg kg−1 i.p.) on extracellular noradrenaline concentration in the frontal cortex and hypothalamus of freely-moving rats were investigated using microdialysis. The role of presynaptic α2-adrenoceptors in modulating the effects of sibutramine in these brain areas was also determined.Sibutramine induced an increase in extracellular noradrenaline concentration, the magnitude of which paralleled dose, in both brain areas. In the cortex, this increase was gradual and sustained, whereas in the hypothalamus it was more rapid and of shorter duration.In both the cortex and hypothalamus, pretreatment of rats with the α2-adrenoceptor antagonist RX821002 (3 mg kg−1 i.p.) potentiated increases in the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.), by 7 and 10 fold respectively. RX821002 also reduced the latency of sibutramine to reach its maximum effect in the cortex, but not in the hypothalamus.Infusion of RX821002 (1 μM) via the probe increased the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.) in both brain areas. In the hypothalamus, the effects of RX821002 on the accumulation of noradrenaline induced by sibutramine were 2 fold greater than those in the cortex.These findings support evidence that sibutramine inhibits the reuptake of noradrenaline in vivo, but that the accumulation of extracellular noradrenaline is limited by noradrenergic activation of presynaptic α2-adrenoceptors. Furthermore, the data suggest that terminal α2-adrenoceptors in the hypothalamus exert a greater inhibitory effect over the control of extracellular noradrenaline accumulation than do those in the cortex. PMID:10516646

  18. Sex differences in androgen receptors of the human mamillary bodies are related to endocrine status rather than to sexual orientation or transsexuality

    NARCIS (Netherlands)

    Kruijver, F. P.; Fernández-Guasti, A.; Fodor, M.; Kraan, E. M.; Swaab, D. F.

    2001-01-01

    In a previous study we found androgen receptor (AR) sex differences in several regions throughout the human hypothalamus. Generally, men had stronger nuclear AR immunoreactivity (AR-ir) than women. The strongest nuclear labeling was found in the caudal hypothalamus in the mamillary body complex

  19. Atrial fibrillation driven by micro-anatomic intramural re-entry revealed by simultaneous sub-epicardial and sub-endocardial optical mapping in explanted human hearts.

    Science.gov (United States)

    Hansen, Brian J; Zhao, Jichao; Csepe, Thomas A; Moore, Brandon T; Li, Ning; Jayne, Laura A; Kalyanasundaram, Anuradha; Lim, Praise; Bratasz, Anna; Powell, Kimerly A; Simonetti, Orlando P; Higgins, Robert S D; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L; Weiss, Raul; Hummel, John D; Fedorov, Vadim V

    2015-09-14

    The complex architecture of the human atria may create physical substrates for sustained re-entry to drive atrial fibrillation (AF). The existence of sustained, anatomically defined AF drivers in humans has been challenged partly due to the lack of simultaneous endocardial-epicardial (Endo-Epi) mapping coupled with high-resolution 3D structural imaging. Coronary-perfused human right atria from explanted diseased hearts (n = 8, 43-72 years old) were optically mapped simultaneously by three high-resolution CMOS cameras (two aligned Endo-Epi views (330 µm2 resolution) and one panoramic view). 3D gadolinium-enhanced magnetic resonance imaging (GE-MRI, 80 µm3 resolution) revealed the atrial wall structure varied in thickness (1.0 ± 0.7-6.8 ± 2.4 mm), transmural fiber angle differences, and interstitial fibrosis causing transmural activation delay from 23 ± 11 to 43 ± 22 ms at increased pacing rates. Sustained AF (>90 min) was induced by burst pacing during pinacidil (30-100 µM) perfusion. Dual-sided sub-Endo-sub-Epi optical mapping revealed that AF was driven by spatially and temporally stable intramural re-entry with 107 ± 50 ms cycle length and transmural activation delay of 67 ± 31 ms. Intramural re-entrant drivers were captured primarily by sub-Endo mapping, while sub-Epi mapping visualized re-entry or 'breakthrough' patterns. Re-entrant drivers were anchored on 3D micro-anatomic tracks (15.4 ± 2.2 × 6.0 ± 2.3 mm2, 2.9 ± 0.9 mm depth) formed by atrial musculature characterized by increased transmural fiber angle differences and interstitial fibrosis. Targeted radiofrequency ablation of the tracks verified these re-entries as drivers of AF. Integrated 3D structural-functional mapping of diseased human right atria ex vivo revealed that the complex atrial microstructure caused significant differences between Endo vs. Epi activation during pacing and sustained AF driven by intramural re-entry anchored to fibrosis-insulated atrial bundles. Published on

  20. Histological changes in the hypothalamus and ependyne in the third ventricle of the brain in sheep after irradiation

    International Nuclear Information System (INIS)

    Stanikova, A.; Pastorova, B.

    2008-01-01

    We focused on changes in the hypothalamic neuro-secretion, morphology of brain ventricle ependyma of sheep after irradiation and hormonal stimulation. We observed sheep in anoestrous. Synchronization was ensured with Agelin for 10 days. On day 5 after instilation of sponges, we started with irradiation lasting for 5 days (2.5 Gy) and on day 10 we stimulated the sheep with SG and FSH. The samples from hypothalamus intended for REM, were processed according to Murakami et al. (1977). Hormonal treatment in combination with irradiation produced qualitative changes, more marked in the ependyma than in the hypothalamus. (authors)

  1. Morphological changes in the neurons of hypothalamus and ependyma of the third cerebral ventricle of sheep after irradiation

    International Nuclear Information System (INIS)

    Stanikova, A.; Pastorova, B.; Maracek, I.; Sopkova, D.; Halagan, J.

    2004-01-01

    We focused on changes in the hypothalamic neuro-secretion, morphology of brain ventricle ependyma of sheep after irradiation and hormonal stimulation. We observed sheep in anoestrus. Synchronization was ensured with Agelin for 10 days. On day 5 after the instillation of sponges, we started with irradiation lasting for 5 days (2.5 Gy) and on day 10 we stimulated the sheep with SG and FSH. The samples from hypothalamus intended for REM, were processed according to Murakami et al. (1977). Hormonal treatment in combination with irradiation produced qualitative changes, more marked in the ependyma than in the hypothalamus. (authors)

  2. Radiation-induced heart injury

    International Nuclear Information System (INIS)

    Suzuki, Yoshihiko; Niibe, Hideo

    1975-01-01

    In order to identify radiation-induced heart injury and to differentiate it from heart disease, an attempt was made to clarify post-irradiation heart injury by investigating the histological changes which occur during the internal between the irradiation and the time of demonstrable histological changes. A study was made of 83 autopsies in which most of the primary neoplasms were breast cancers, lung cancers and mediastinal tumors. In 43 of these autopsies the heart had been irradiated. Sixty eight dd-strain mice were also used for microautoradiographic study. Histological changes in the heart were observed in 27 of the 43 cases receiving irradiation. The limit of the tolerance dose to the heart for indicating histological changes was 1220 ret in humans. The latent period without histological changes was 2.7 months after initiation of radiation therapy. Greater heart injury was observed after re-irradiation or after the combined therapy of radiation and chemotherapy especially mitomycin (MMC). The histological findings after treatment with MMC were similar to those of radiation-induced heart injury. Results of the study indicate that the damage is secondary to radiation-induced changes of the vascula connective tissue. (Evans, G.)

  3. Pericarditis - after heart attack

    Science.gov (United States)

    ... include: A previous heart attack Open heart surgery Chest trauma A heart attack that has affected the thickness of your heart muscle Symptoms Symptoms include: Anxiety Chest pain from the swollen pericardium rubbing on the ...

  4. Heart failure - home monitoring

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000113.htm Heart failure - home monitoring To use the sharing features on ... your high blood pressure Fast food tips Heart failure - discharge Heart failure - fluids and diuretics Heart failure - what to ...

  5. Heart Diseases and Disorders

    Science.gov (United States)

    ... Resources Heart Diseases & Disorders Back to Patient Resources Heart Diseases & Disorders Millions of people experience irregular or abnormal ... harmless and happen in healthy people free of heart disease. However, some abnormal heart rhythms can be serious ...

  6. Heart disease and diet

    Science.gov (United States)

    Diet - heart disease; CAD - diet; Coronary artery disease - diet; Coronary heart disease - diet ... diet and lifestyle can reduce your risk of: Heart disease, heart attacks, and stroke Conditions that lead ...

  7. Coronary heart disease

    Science.gov (United States)

    Heart disease, Coronary heart disease, Coronary artery disease; Arteriosclerotic heart disease; CHD; CAD ... buildup of plaque in the arteries to your heart. This may also be called hardening of the ...

  8. Heart attack first aid

    Science.gov (United States)

    First aid - heart attack; First aid - cardiopulmonary arrest; First aid - cardiac arrest ... A heart attack occurs when the blood flow that carries oxygen to the heart is blocked. The heart muscle ...

  9. The role of the hypothalamus-pituitary-adrenal/interrenal axis in mediating predator-avoidance trade-offs.

    Science.gov (United States)

    Harris, Breanna N; Carr, James A

    2016-05-01

    Maintaining energy balance and reproducing are important for fitness, yet animals have evolved mechanisms by which the hypothalamus-pituitary-adrenal/interrenal (HPA/HPI) axis can shut these activities off. While HPA/HPI axis inhibition of feeding and reproduction may have evolved as a predator defense, to date there has been no review across taxa of the causal evidence for such a relationship. Here we review the literature on this topic by addressing evidence for three predictions: that exposure to predators decreases reproduction and feeding, that exposure to predators activates the HPA/HPI axis, and that predator-induced activation of the HPA/HPI axis inhibits foraging and reproduction. Weight of evidence indicates that exposure to predator cues inhibits several aspects of foraging and reproduction. While the evidence from fish and mammals supports the hypothesis that predator cues activate the HPA/HPI axis, the existing data in other vertebrate taxa are equivocal. A causal role for the HPA axis in predator-induced suppression of feeding and reproduction has not been demonstrated to date, although many studies report correlative relationships between HPA activity and reproduction and/or feeding. Manipulation of HPA/HPI axis signaling will be required in future studies to demonstrate direct mediation of predator-induced inhibition of feeding and reproduction. Understanding the circuitry linking sensory pathways to their control of the HPA/HPI axis also is needed. Finally, the role that fear and anxiety pathways play in the response of the HPA axis to predator cues is needed to better understand the role that predators have played in shaping anxiety related behaviors in all species, including humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Different gene expression in human heart tissue and progenitor cells from control and diabetic subjects: relevance to the pathogenesis of human diabetic cardiomyopathy.

    Science.gov (United States)

    de Cillis, Emanuela; Leonardini, Anna; Laviola, Luigi; Giorgino, Francesco; Tupputi Schinosa, Luigi de Luca; Bortone, Alessandro Santo

    2010-04-01

    The The aim of our study is to investigate the molecular mechanisms of diabetic cardiomyopathy through the identification of remarkable genes for the myocardial function that are expressed differently between diabetic and normal subjects. Moreover, we intend to characterize both in human myocardial tissue and in the related cardiac progenitor cells the pattern of gene expression and the levels of expression and protein activation of molecular effectors involved in the regulation of the myocardial function and differentiation to clarify whether in specific human pathological conditions (type 2 diabetes mellitus, cardiac failure, coronary artery disease) specific alterations of the aforementioned factors could take place. Thirty-five patients scheduled for coronary artery bypass grafting (CABG) or for aortic or mitral valve replacement were recruited into the study. There were 13 men and 22 women with a mean age of 64.8 +/- 13.4 years. A list of anamnestic, anthropometric, clinical, and instrumental data required for an optimal phenotypical characterization of the patients is reported. The small cardiac biopsy specimens were placed in the nourishing buffer, in a sterile tube provided the day of the procedure, to maintain the stability of the sample for several hours at room temperature. The cells were isolated by a dedicated protocol and then cultured in vitro. The sample was processed for total RNA extraction and levels of gene expression and protein activation of molecular effectors involved in the regulation of function and differentiation of human myocardium was analyzed. In particular, cardiac genes that modulate the oxidative stress response or the stress induced by pro-inflammatory cytokines (p66Shc, SOCS-1, SOCS-3) were analyzed. From a small sample of myocardium cardiac stem cells and cardiomyoblasts were also isolated and characterized. These cells showed a considerable proliferative capacity due to the fact that they demonstrate stability up to the

  11. Opioid systems in the lateral hypothalamus regulate feeding behavior through orexin and GABA neurons.

    Science.gov (United States)

    Ardianto, C; Yonemochi, N; Yamamoto, S; Yang, L; Takenoya, F; Shioda, S; Nagase, H; Ikeda, H; Kamei, J

    2016-04-21

    The hypothalamus controls feeding behavior. Since central opioid systems may regulate feeding behavior, we examined the role of μ-, δ- and κ-opioid receptors in the lateral hypothalamus (LH), the hunger center, in feeding behavior of mice. Non-selective (naloxone; 3 mg/kg, s.c.) and selective μ- (β-funaltrexamine, β-FNA; 10 mg/kg, s.c.), δ- (naltrindole; 3 mg/kg, s.c.) and κ- (norbinaltorphimine, norBNI; 20 mg/kg, s.c.) opioid receptor antagonists significantly decreased food intake in food-deprived mice. The injection of naloxone (20 μg/side) into the LH significantly decreased food intake whereas the injection of naloxone (20 μg/side) outside of the LH did not affect food intake. The injection of β-FNA (2 μg/side), naltrindole (1 μg/side) or norBNI (2 μg/side) into the LH significantly decreased food intake. Furthermore, all these antagonists significantly decreased the mRNA level of preproorexin, but not those of other hypothalamic neuropeptides. In addition, the injection of the GABAA receptor agonist muscimol (5 μg/side) into the LH significantly decreased food intake, and this effect was abolished by the GABAA receptor antagonist bicuculline (50 μg/side). Muscimol (1mg/kg, i.p.) decreased the mRNA level of preproorexin in the hypothalamus. Naloxone (3mg/kg, s.c.) significantly increased the GABA level in the LH and both bicuculline and the GABA release inhibitor 3-mercaptopropionic acid (3-MP, 5 μg/side) attenuated the inhibitory effect of naloxone on feeding behavior. 3-MP also attenuated the effects of β-FNA and norBNI, but not that of naltrindole. These results show that opioid systems in the LH regulate feeding behavior through orexin neurons. Moreover, μ- and κ-, but not δ-, opioid receptor antagonists inhibit feeding behavior by activating GABA neurons in the LH. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Pediatric heart surgery

    Science.gov (United States)

    Heart surgery - pediatric; Heart surgery for children; Acquired heart disease; Heart valve surgery - children ... There are many kinds of heart defects. Some are minor, and others are more serious. Defects can occur inside the heart or in the large blood vessels ...

  13. GABA receptors in the region of the dorsomedial hypothalamus of rats regulate anxiety in the elevated plus-maze test. II. Physiological measures.

    Science.gov (United States)

    Shekhar, A; Sims, L S; Bowsher, R R

    1993-11-05

    In the previous report, we had shown that blockade and enhancement of GABAA receptors in the DMH of rats increased or decreased the level of anxiety, respectively, as measured by the elevated plus-maze test. The present study was conducted to assess the effects of enhancing GABAA neurotransmission in the DMH of rats on the physiological concomitants of anxiety such as increases in heart rate (HR), blood pressure (BP) and plasma norepinephrine (NE) levels while the animals were placed on the elevated plus-maze. Male Sprague-Dawley rats were equipped with arterial and venous catheters and stereotaxically implanted with microinjection cannulae in the cardiostimulatory region of the DMH where injection of bicuculline methiodide (BMI) elicited increases in heart rate under anesthesia. After recovery, rats were injected with either saline or the GABAA agonist muscimol and their HR, BP and plasma NE responses were measured when confined in the open or the closed arm of the elevated plus-maze. Injection of muscimol into the DMH reduced the increases seen in HR, BP and plasma NE when the rats were confined to either the closed or the open arms in addition to decreasing 'anxiety' in the plus-maze. Injection of muscimol into the areas of the hypothalamus surrounding the DMH did not significantly affect the changes in HR, BP and plasma NE in the plus-maze. Blocking the changes in HR and BP elicited by microinjecting GABAergic drugs into the DMH of rats, with systemic injections of a combination of atropine and the beta-blocker atenolol, did not block the behavioral effects of the GABAergic drugs in the plus-maze test.

  14. Angiotensin type 1a receptors in the paraventricular nucleus of the hypothalamus control cardiovascular reactivity and anxiety-like behavior in male mice.

    Science.gov (United States)

    Wang, Lei; Hiller, Helmut; Smith, Justin A; de Kloet, Annette D; Krause, Eric G

    2016-09-01

    This study tested the hypothesis that deletion of angiotensin type 1a receptors (AT1a) from the paraventricular nucleus of hypothalamus (PVN) attenuates anxiety-like behavior, hypothalamic-pituitary-adrenal (HPA) axis activity, and cardiovascular reactivity. We used the Cre/LoxP system to generate male mice with AT1a specifically deleted from the PVN. Deletion of the AT1a from the PVN reduced anxiety-like behavior as indicated by increased time spent in the open arms of the elevated plus maze. In contrast, PVN AT1a deletion had no effect on HPA axis activation subsequent to an acute restraint challenge but did reduce hypothalamic mRNA expression for corticotropin-releasing hormone (CRH). To determine whether PVN AT1a deletion inhibits cardiovascular reactivity, we measured systolic blood pressure, heart rate, and heart rate variability (HRV) using telemetry and found that PVN AT1a deletion attenuated restraint-induced elevations in systolic blood pressure and elicited changes in HRV indicative of reduced sympathetic nervous activity. Consistent with the decreased HRV, PVN AT1a deletion also decreased adrenal weight, suggestive of decreased adrenal sympathetic outflow. Interestingly, the altered stress responsivity of mice with AT1a deleted from the PVN was associated with decreased hypothalamic microglia and proinflammatory cytokine expression. Collectively, these results suggest that deletion of AT1a from the PVN attenuates anxiety, CRH gene transcription, and cardiovascular reactivity and reduced brain inflammation may contribute to these effects. Copyright © 2016 the American Physiological Society.

  15. Pedophilia is linked to reduced activation in hypothalamus and lateral prefrontal cortex during visual erotic stimulation.

    Science.gov (United States)

    Walter, Martin; Witzel, Joachim; Wiebking, Christine; Gubka, Udo; Rotte, Michael; Schiltz, Kolja; Bermpohl, Felix; Tempelmann, Claus; Bogerts, Bernhard; Heinze, Hans Jochen; Northoff, Georg

    2007-09-15

    Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral prefrontal cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala-hippocampus and dorsomedial prefrontal cortex. Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.

  16. Macronutrients and the FTO gene expression in hypothalamus; a systematic review of experimental studies

    Directory of Open Access Journals (Sweden)

    Saeid Doaei

    2017-03-01

    Full Text Available The various studies have examined the relationship between FTO gene expression and macronutrients levels. In order to obtain better viewpoint from this interactions, all of existing studies were reviewed systematically. All published papers have been obtained and reviewed using standard and sensitive keywords from databases such as CINAHL, Embase, PubMed, PsycInfo, and the Cochrane, from 1990 to 2016. The results indicated that all of 6 studies that met the inclusion criteria (from a total of 428 published article found FTO gene expression changes at short-term follow-ups. Four of six studies found an increased FTO gene expression after calorie restriction, while two of them indicated decreased FTO gene expression. The effect of protein, carbohydrate and fat were separately assessed and suggested by all of six studies. In Conclusion, The level of FTO gene expression in hypothalamus is related to macronutrients levels. Future research should evaluate the long-term impact of dietary interventions.

  17. Structural and Ultrastructural Analysis of Cerebral Cortex, Cerebellum, and Hypothalamus from Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Juan P. Hernández-Fonseca

    2009-01-01

    Full Text Available Autonomic and peripheral neuropathies are well-described complications in diabetes. Diabetes mellitus is also associated to central nervous system damage. This little-known complication is characterized by impairment of brain functions and electrophysiological changes associated with neurochemical and structural abnormalities. The purpose of this study was to investigate brain structural and ultrastructural changes in rats with streptozotocin-induced diabetes. Cerebral cortex, hypothalamus, and cerebellum were obtained from controls and 8 weeks diabetic rats. Light and electron microscope studies showed degenerative changes of neurons and glia, perivascular and mitochondrial swelling, disarrangement of myelin sheath, increased area of myelinated axons, presynaptic vesicle dispersion in swollen axonal boutoms, fragmentation of neurofilaments, and oligodendrocyte abnormalities. In addition, depressive mood was observed in diabetic animals. The brain morphological alterations observed in diabetic animals could be related to brain pathologic process leading to abnormal function, cellular death, and depressive behavioral.

  18. State-dependent cellular activity patterns of the cat paraventricular hypothalamus measured by reflectance imaging

    DEFF Research Database (Denmark)

    Kristensen, Morten Pilgaard; Rector, D M; Poe, G R

    1996-01-01

    Activity within the cat paraventricular hypothalamus (PVH) during sleep and waking states was measured by quantifying intrinsic tissue reflectivity. A fiber optic probe consisting of a 1.0 mm coherent image conduit, surrounded by plastic fibers which conducted 660 nm source light, was attached...... to a charge-coupled device camera, and positioned over the PVH in five cats. Electrodes for assessing state variables, including electroencephalographic activity, eye movement, and somatic muscle tone were also placed. After surgical recovery, reflected light intensity was measured continuously at 2.5 Hz...... changes with behavioral state in a regionally specific manner, and that overall activity increases during quiet sleep, and is even more enhanced in active sleep. PVH activation could be expected to stimulate pituitary release of adrenocorticotropic hormone (ACTH) and affect input to autonomic regulatory...

  19. Metabolic activity in the insular cortex and hypothalamus predicts hot flashes: an FDG-PET study.

    Science.gov (United States)

    Joffe, Hadine; Deckersbach, Thilo; Lin, Nancy U; Makris, Nikos; Skaar, Todd C; Rauch, Scott L; Dougherty, Darin D; Hall, Janet E

    2012-09-01

    Hot flashes are a common side effect of adjuvant endocrine therapies (AET; leuprolide, tamoxifen, aromatase inhibitors) that reduce quality of life and treatment adherence in breast cancer patients. Because hot flashes affect only some women, preexisting neurobiological traits might predispose to their development. Previous studies have implicated the insula during the perception of hot flashes and the hypothalamus in thermoregulatory dysfunction. The aim of the study was to understand whether neurobiological factors predict hot flashes. [18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET) brain scans coregistered with structural magnetic resonance imaging were used to determine whether metabolic activity in the insula and hypothalamic thermoregulatory and estrogen-feedback regions measured before and in response to AET predict hot flashes. Findings were correlated with CYP2D6 genotype because of CYP2D6 polymorphism associations with tamoxifen-induced hot flashes. We measured regional cerebral metabolic rate of glucose uptake (rCMRglu) in the insula and hypothalamus on FDG-PET. Of 18 women without hot flashes who began AET, new-onset hot flashes were reported by 10 (55.6%) and were detected objectively in nine (50%) participants. Prior to the use of all AET, rCMRglu in the insula (P ≤ 0.01) and hypothalamic thermoregulatory (P = 0.045) and estrogen-feedback (P = 0.007) regions was lower in women who reported developing hot flashes. In response to AET, rCMRglu was further reduced in the insula in women developing hot flashes (P ≤ 0.02). Insular and hypothalamic rCMRglu levels were lower in intermediate than extensive CYP2D6 metabolizers. Trait neurobiological characteristics predict hot flashes. Genetic variability in CYP2D6 may underlie the neurobiological predisposition to hot flashes induced by AET.

  20. Nutritional status affects the microRNA profile of the hypothalamus of female sheep.

    Science.gov (United States)

    Yang, Heng; Lin, Shan; Lei, Xiaoping; Yuan, Cong; Yu, Yaosheng; Zhao, Zongsheng; Chen, Jingbo

    2018-01-25

    Recent studies on the seasonal regulation of the oestrous cycle in sheep have focussed mainly on the responses to photoperiod. However, the brain systems that control reproductive activity also respond to nutritional inputs, although the molecular mechanisms involved are not completely understood. One possibility is that small, non-coding RNAs, such as micro-RNAs (miRNAs), have significant influence. In the present study, the amounts and characteristics of miRNAs in hypothalamus from oestrous and anestrous ewes, fed low- or high-nutrient diets, were compared using Illumina HiSeq sequencing technology. In total, 398 miRNAs, including 261 novel miRNAs, were identified in ewes with an enhanced nutritional status (HEN), whereas 384 miRNAs, including 247 novel miRNAs, were identified in the ewes with a lesser nutritional status (HAN). There were eight conserved and 140 novel miRNAs expressed differentially between the two libraries. Based on quantitative real-time polymerase chain reaction, six miRNAs were assessed to verify the accuracy of the library database. Moreover, the correlation between the miRNA target and several upstream and downstream genes in the oestrus-related pathways were also verified in hypothalamus nerve cells. According to the results, nutritional status plays an important role in oestrous regulation in sheep, and the hypothalamic processes and pathways induced by nutritional signals (folic acid and tyrosine) are different from those induced by photoperiodic regulation of oestrus. We have expanded the repertoire of sheep miRNAs that could contribute to the molecular mechanisms that regulate the initiation of oestrous cycles in anestrous ewes in response to the influence of nutritional status.

  1. Topography of somatostatin gene expression relative to molecular progenitor domains during ontogeny of the mouse hypothalamus

    Directory of Open Access Journals (Sweden)

    Nicanor eMorales-Delgado

    2011-02-01

    Full Text Available The hypothalamus comprises alar, basal and floor plate developmental compartments. Recent molecular data support a rostro-caudal subdivision into rostral (terminal and caudal (peduncular halves. In this context, the distribution of neuronal populations expressing somatostatin (Sst mRNA was analyzed in the developing mouse hypothalamus, comparing with the expression pattern of the genes Orthopedia (Otp, Distal-less 5 (Dlx5, Sonic Hedgehog (Shh and Nk2 homeobox 1 (Nkx2.1. At embryonic day 10.5 (E10.5, Sst mRNA was first detectable in the anterobasal nucleus, a Nkx2.1-, Shh- and Otp- positive basal domain. By E13.5, nascent Sst expression was also related to two additional Otp-positive domains within the alar plate and one in the basal plate. In the alar plate, Sst-positive cells were observed in rostral and caudal ventral subdomains of the Otp-positive paraventricular complex. An additional basal Sst-expressing cell group was found within a longitudinal Otp-positive periretromamillary band that separates the retromamillary area from tuberal areas. Apart of subsequent growth of these initial populations, at E13.5 and E15.5 some Sst-positive derivatives migrate tangentially into neighboring regions. A subset of cells produced at the anterobasal nucleus disperses ventralwards into the shell of the ventromedial hypothalamic nucleus and the arcuate nucleus. Cells from the rostroventral paraventricular subdomain reach the suboptic nucleus, whereas a caudal contingent migrates radially into lateral paraventricular, perifornical and entopeduncular nuclei. Our data provide a topologic map of molecularly-defined progenitor areas originating a specific neuron type during early hypothalamic development. Identification of four main separate sources helps to understand causally its complex adult organization.

  2. Sexually dimorphic transcriptomic responses in the teleostean hypothalamus: a case study with the organochlorine pesticide dieldrin.

    Science.gov (United States)

    Martyniuk, Christopher J; Doperalski, Nicholas J; Kroll, Kevin J; Barber, David S; Denslow, Nancy D

    2013-01-01

    Organochlorine pesticides (OCPs) such as dieldrin are a persistent class of aquatic pollutants that cause adverse neurological and reproductive effects in vertebrates. In this study, female and male largemouth bass (Micropterus salmoides) (LMB) were exposed to 3mg dieldrin/kg feed in a 2 month feeding exposure (August-October) to (1) determine if the hypothalamic transcript responses to dieldrin were conserved between the sexes; (2) characterize cell signaling cascades underlying dieldrin neurotoxicity; and (3) determine whether or not co-feeding with 17β-estradiol (E(2)), a hormone with neuroprotective roles, mitigates responses in males to dieldrin. Despite also being a weak estrogen, dieldrin treatments did not elicit changes in reproductive endpoints (e.g. gonadosomatic index, vitellogenin, or plasma E(2)). Sub-network (SNEA) and gene set enrichment analysis (GSEA) revealed that neuro-hormone networks, neurotransmitter and nuclear receptor signaling, and the activin signaling network were altered by dieldrin exposure. Most striking was that the majority of cell pathways identified by the gene set enrichment were significantly increased in females while the majority of cell pathways were significantly decreased in males fed dieldrin. These data suggest that (1) there are sexually dimorphic responses in the teleost hypothalamus; (2) neurotransmitter systems are a target of dieldrin at the transcriptomics level; and (3) males co-fed dieldrin and E(2) had the fewest numbers of genes and cell pathways altered in the hypothalamus, suggesting that E(2) may mitigate the effects of dieldrin in the central nervous system. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Alterations in opioid parameters in the hypothalamus of rats with estradiol-induced polycystic ovarian disease

    International Nuclear Information System (INIS)

    Desjardins, G.C.; Beaudet, A.; Brawer, J.R.

    1990-01-01

    The distribution and density of selectively labeled mu-, delta-, and kappa-opioid binding sites were examined by in vitro radioautography in the hypothalamus of normal, estradiol valerate (EV)-injected, and estradiol (E2)-implanted female rats. Hypothalamic beta-endorphin concentration was also examined by RIA in these three groups of animals. Quantitative analysis of film radioautographs demonstrated a selective increase in mu-opioid binding in the medial preoptic area of EV-treated, but not of E2-implanted rats. However, both these estrogenized groups exhibited a reduction in the density of delta-opioid binding in the suprachiasmatic nucleus. Statistically significant changes between either estrogenized groups were not observed for kappa-opioid binding. Results on the hypothalamic concentration of beta-endorphin indicated a marked reduction in EV-injected animals with respect to controls. In contrast, the E2-implanted animals exhibited beta-endorphin concentrations similar to controls. The present results confirm the increase in opioid receptor binding previously reported in the hypothalamus of EV-treated rats and further demonstrate that this increase is confined to the medial preoptic area and exclusively concerns mu-opioid receptors. The concomitant reduction in beta-endorphin levels observed in the same group of animals suggests that the observed increase in mu-opioid binding could reflect a chronic up-regulation of the receptor in response to compromised beta-endorphin input. Given the restriction of this effect to the site of origin of LHRH neurons and the demonstrated inhibitory role of opioids on LHRH release, it is tempting to postulate that such up-regulation could lead to the suppression of the plasma LH pattern that characterizes polycystic ovarian disease in the EV-treated rat

  4. Alterations in opioid parameters in the hypothalamus of rats with estradiol-induced polycystic ovarian disease

    Energy Technology Data Exchange (ETDEWEB)

    Desjardins, G.C.; Beaudet, A.; Brawer, J.R. (McGill Univ., Quebec (Canada))

    1990-12-01

    The distribution and density of selectively labeled mu-, delta-, and kappa-opioid binding sites were examined by in vitro radioautography in the hypothalamus of normal, estradiol valerate (EV)-injected, and estradiol (E2)-implanted female rats. Hypothalamic beta-endorphin concentration was also examined by RIA in these three groups of animals. Quantitative analysis of film radioautographs demonstrated a selective increase in mu-opioid binding in the medial preoptic area of EV-treated, but not of E2-implanted rats. However, both these estrogenized groups exhibited a reduction in the density of delta-opioid binding in the suprachiasmatic nucleus. Statistically significant changes between either estrogenized groups were not observed for kappa-opioid binding. Results on the hypothalamic concentration of beta-endorphin indicated a marked reduction in EV-injected animals with respect to controls. In contrast, the E2-implanted animals exhibited beta-endorphin concentrations similar to controls. The present results confirm the increase in opioid receptor binding previously reported in the hypothalamus of EV-treated rats and further demonstrate that this increase is confined to the medial preoptic area and exclusively concerns mu-opioid receptors. The concomitant reduction in beta-endorphin levels observed in the same group of animals suggests that the observed increase in mu-opioid binding could reflect a chronic up-regulation of the receptor in response to compromised beta-endorphin input. Given the restriction of this effect to the site of origin of LHRH neurons and the demonstrated inhibitory role of opioids on LHRH release, it is tempting to postulate that such up-regulation could lead to the suppression of the plasma LH pattern that characterizes polycystic ovarian disease in the EV-treated rat.

  5. Estrogen- and Satiety State-Dependent Metabolic Lateralization in the Hypothalamus of Female Rats.

    Directory of Open Access Journals (Sweden)

    Istvan Toth

    Full Text Available Hypothalamus is the highest center and the main crossroad of numerous homeostatic regulatory pathways including reproduction and energy metabolism. Previous reports indicate that some of these functions may be driven by the synchronized but distinct functioning of the left and right hypothalamic sides. However, the nature of interplay between the hemispheres with regard to distinct hypothalamic functions is still unclear. Here we investigated the metabolic asymmetry between the left and right hypothalamic sides of ovariectomized female rats by measuring mitochondrial respiration rates, a parameter that reflects the intensity of cell and tissue metabolism. Ovariectomized (saline injected and ovariectomized+estrogen injected animals were fed ad libitum or fasted to determine 1 the contribution of estrogen to metabolic asymmetry of hypothalamus; and 2 whether the hypothalamic asymmetry is modulated by the satiety state. Results show that estrogen-priming significantly increased both the proportion of animals with detected hypothalamic lateralization and the degree of metabolic difference between the hypothalamic sides causing a right-sided dominance during state 3 mitochondrial respiration (St3 in ad libitum fed animals. After 24 hours of fasting, lateralization in St3 values was clearly maintained; however, instead of the observed right-sided dominance that was detected in ad libitum fed animals here appeared in form of either right- or left-sidedness. In conclusion, our results revealed estrogen- and satiety state-dependent metabolic differences between the two hypothalamic hemispheres in female rats showing that the hypothalamic hemispheres drive the reproductive and satiety state related functions in an asymmetric manner.

  6. Crosstalks between kisspeptin neurons and somatostatin neurons are not photoperiod dependent in the ewe hypothalamus.

    Science.gov (United States)

    Dufourny, Laurence; Lomet, Didier

    2017-12-01

    Seasonal reproduction is under the control of gonadal steroid feedback, itself synchronized by day-length or photoperiod. As steroid action on GnRH neurons is mostly indirect and therefore exerted through interneurons, we looked for neuroanatomical interactions between kisspeptin (KP) neurons and somatostatin (SOM) neurons, two populations targeted by sex steroids, in three diencephalic areas involved in the central control of ovulation and/or sexual behavior: the arcuate nucleus (ARC), the preoptic area (POA) and the ventrolateral part of the ventromedial hypothalamus (VMHvl). KP is the most potent secretagogue of GnRH secretion while SOM has been shown to centrally inhibit LH pulsatile release. Notably, hypothalamic contents of these two neuropeptides vary with photoperiod in specific seasonal species. Our hypothesis is that SOM inhibits KP neuron activity and therefore indirectly modulate GnRH release and that this effect may be seasonally regulated. We used sections from ovariectomized estradiol-replaced ewes killed after photoperiodic treatment mimicking breeding or anestrus season. We performed triple immunofluorescent labeling to simultaneously detect KP, SOM and synapsin, a marker for synaptic vesicles. Sections from the POA and from the mediobasal hypothalamus were examined using a confocal microscope. Randomly selected KP or SOM neurons were observed in the POA and ARC. SOM neurons were also observed in the VMHvl. In both the ARC and POA, nearly all KP neurons presented numerous SOM contacts. SOM neurons presented KP terminals more frequently in the ARC than in the POA and VMHvl. Quantitative analysis failed to demonstrate major seasonal variations of KP and SOM interactions. Our data suggest a possible inhibitory action of SOM on all KP neurons in both photoperiodic statuses. On the other hand, the physiological significance of KP modulation of SOM neuron activity and vice versa remain to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Influence of radon (222Rn) on hypothalamus, hypophysis, ovaries and uterus in Balb C strain mice

    International Nuclear Information System (INIS)

    Koziorowski, A.

    1997-01-01

    Curative properties of radon waters have been applied in balneotherapy for a long time. Therapeutic action is connected with radioactive properties of radon and the products of its degradation. All of them are the source of ionizing radiation, the alpha rays in particular. Radon therapy is widely applied to the treatment of many illnesses, especially of the circulatory system, rheumatism, and arthritis, bronchial asthma and many others. Good therapeutic results have also been achieved in gynecology to mention chronic inflammation of female reproductive organs and endocrinological disorders (of the ovary and during the period of sterilization). Positive results of radon therapy can also be associated with the influence of ionizing radiation on the activity of endocrine glands, mainly the axis hypothalamus - hypophysis - adrenal gland - ovary. There has been neither regular investigation into this problem nor into the morphology of the organs mentioned above. The present paper is an attempt to evaluate the influence of radon inhalations on the structure and function of hypothalamus, hypophysis ovary and uterus. This investigation was performed on hypothalamus, hypophysis, ovary and uterus in Balb C virgin mice. The total population of the mice under study was 140; with a control group of 40. The mice inhalated radon for 30 min. a day, starting with a single irradiation up to a 30-fold. I applied traditional histological techniques and immunocytochemical localization of selected hormones (FSH, LH, ADH). I also tried to evaluate the quantitative activity of mentioned glands by means of the computer morphometric and densitometric analyses of the immunocytochemical slides using an image analyzer Vidas 25 manufactured by Kontron. The results underwent statistical analysis. In order to examine the uterus the ultrastructural evaluation of its functioning was made. Moreover, I analyzed the concentration of FSH, LH, estrogens and progesterone in the serum by means of the

  8. Defective functional connectivity between posterior hypothalamus and regions of the diencephalic-mesencephalic junction in chronic cluster headache.

    Science.gov (United States)

    Ferraro, Stefania; Nigri, Anna; Bruzzone, Maria Grazia; Brivio, Luca; Proietti Cecchini, Alberto; Verri, Mattia; Chiapparini, Luisa; Leone, Massimo

    2018-01-01

    Objective We tested the hypothesis of a defective functional connectivity between the posterior hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache based on: a) clinical and neuro-endocrinological findings in cluster headache patients; b) neuroimaging findings during cluster headache attacks; c) neuroimaging findings in drug-refractory chronic cluster headache patients improved after successful deep brain stimulation. Methods Resting state functional magnetic resonance imaging, associated with a seed-based approach, was employed to investigate the functional connectivity of the posterior hypothalamus in chronic cluster headache patients (n = 17) compared to age and sex-matched healthy subjects (n = 16). Random-effect analyses were performed to study differences between patients and controls in ipsilateral and contralateral-to-the-pain posterior hypothalamus functional connectivity. Results Cluster headache patients showed an increased functional connectivity between the ipsilateral posterior hypothalamus and a number of diencephalic-mesencephalic structures, comprising ventral tegmental area, dorsal nuclei of raphe, and bilateral substantia nigra, sub-thalamic nucleus, and red nucleus ( p cluster headache patients mainly involves structures that are part of (i.e. ventral tegmental area, substantia nigra) or modulate (dorsal nuclei of raphe, sub-thalamic nucleus) the midbrain dopaminergic systems. The midbrain dopaminergic systems could play a role in cluster headache pathophysiology and in particular in the chronicization process. Future studies are needed to better clarify if this finding is specific to cluster headache or if it represents an unspecific response to chronic pain.

  9. Ascending Projections from the Solitary Tract Nucleus to the Hypothalamus : A Phaseolus vulgaris Lectin Tracing Study in the Rat

    NARCIS (Netherlands)

    Horst, G.J. ter; de Boer, P.; Luiten, P.G.M.; Willigen, J.D. van

    1989-01-01

    The course of the ascending pathways originating from the anterior gustatory and posterior visceral sensory part of the solitary tract nucleus and the topographic organization of the projections to the hypothalamus in the rat were studied with anterogradely transported Phuseolus vulgaris lectin. In

  10. Atrazine alters expression of reproductive and stress genes in the developing hypothalamus of the snapping turtle, Chelydra serpentina.

    Science.gov (United States)

    Russart, Kathryn L G; Rhen, Turk

    2016-07-29

    Atrazine is an herbicide used to control broadleaf grasses and a suspected endocrine disrupting chemical. Snapping turtles lay eggs between late May and early June, which could lead to atrazine exposure via field runoff. Our goal was to determine whether a single exposure to 2ppb or 40ppb atrazine during embryogenesis could induce short- and long-term changes in gene expression within the hypothalamus of snapping turtles. We treated eggs with atrazine following sex determination and measured gene expression within the hypothalamus. We selected genes a priori for their role in the hypothalamus-pituitary-gonad or the hypothalamus-pituitary-adrenal axes of the endocrine system. We did not identify any changes in gene expression 24-h after treatment. However, at hatching AR, Kiss1R, and POMC expression was upregulated in both sexes, while expression of CYP19A1 and PDYN was increased in females. Six months after hatching, CYP19A1 and PRLH expression was increased in animals treated with 2ppb atrazine. Our study shows persistent changes in hypothalamic gene expression due to low-dose embryonic exposure to the herbicide atrazine with significant effects in both the HPG and HPA axes. Effects reported here appear to be conserved among vertebrates. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. An adeno-associated viral vector transduces the rat hypothalamus and amygdala more efficient than a lentiviral vector

    Directory of Open Access Journals (Sweden)

    Vreugdenhil Erno

    2010-07-01

    Full Text Available Abstract Background This study compared the transduction efficiencies of an adeno-associated viral (AAV vector, which was pseudotyped with an AAV1 capsid and encoded the green fluorescent protein (GFP, with a lentiviral (LV vector, which was pseudotyped with a VSV-G envelop and encoded the discosoma red fluorescent protein (dsRed, to investigate which viral vector transduced the lateral hypothalamus or the amygdala more efficiently. The LV-dsRed and AAV1-GFP vector were mixed and injected into the lateral hypothalamus or into the amygdala of adult rats. The titers that were injected were 1 × 108 or 1 × 109 genomic copies of AAV1-GFP and 1 × 105 transducing units of LV-dsRed. Results Immunostaining for GFP and dsRed showed that AAV1-GFP transduced significantly more cells than LV-dsRed in both the lateral hypothalamus and the amygdala. In addition, the number of LV particles that were injected can not easily be increased, while the number of AAV1 particles can be increased easily with a factor 100 to 1000. Both viral vectors appear to predominantly transduce neurons. Conclusions This study showed that AAV1 vectors are better tools to overexpress or knockdown genes in the lateral hypothalamus and amygdala of adult rats, since more cells can be transduced with AAV1 than with LV vectors and the titer of AAV1 vectors can easily be increased to transduce the area of interest.

  12. Energy balance affects luteinizing hormone pulses and expression of neurokinin B in the hypothalamus of ovariectomized gilts

    Science.gov (United States)

    The pubertal transition of gonadotropin secretion in pigs is metabolically gated, but the mechanisms that underpin this regulation are unknown. Kisspeptin and neurokinin B (NKB) are coexpressed in neurons within the arcuate nucleus of the hypothalamus (ARC) and are thought to play an important role ...

  13. Music exposure differentially alters the levels of brain-derived neurotrophic factor and nerve growth factor in the mouse hypothalamus.

    Science.gov (United States)

    Angelucci, Francesco; Ricci, Enzo; Padua, Luca; Sabino, Andrea; Tonali, Pietro Attilio

    2007-12-18

    It has been reported that music may have physiological effects on blood pressure, cardiac heartbeat, respiration, and improve mood state in people affected by anxiety, depression and other psychiatric disorders. However, the physiological bases of these phenomena are not clear. Hypothalamus is a brain region involved in the regulation of body homeostasis and in the pathophysiology of anxiety and depression through the modulation of hypothalamic-pituitary-adrenal (HPA) axis. Hypothalamic functions are also influenced by the presence of the neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are proteins involved in the growth, survival and function of neurons in the central nervous system. The aim of this study was to investigate the effect of music exposure in mice on hypothalamic levels of BDNF and NGF. We exposed young adult mice to slow rhythm music (6h per day; mild sound pressure levels, between 50 and 60 dB) for 21 consecutive days. At the end of the treatment mice were sacrificed and BDNF and NGF levels in the hypothalamus were measured by enzyme-linked immunosorbent assay (ELISA). We found that music exposure significantly enhanced BDNF levels in the hypothalamus. Furthermore, we observed that music-exposed mice had decreased NGF hypothalamic levels. Our results demonstrate that exposure to music in mice can influence neurotrophin production in the hypothalamus. Our findings also suggest that physiological effects of music might be in part mediated by modulation of neurotrophins.

  14. The Abnormal Functional Connectivity between the Hypothalamus and the Temporal Gyrus Underlying Depression in Alzheimer's Disease Patients.

    Science.gov (United States)

    Liu, Xiaozheng; Chen, Wei; Tu, Yunhai; Hou, Hongtao; Huang, Xiaoyan; Chen, Xingli; Guo, Zhongwei; Bai, Guanghui; Chen, Wei

    2018-01-01

    Hypothalamic communication with the rest of the brain is critical for accomplishing a wide variety of physiological and psychological functions, including the maintenance of neuroendocrine circadian rhythms and the management of affective processes. Evidence has shown that major depressive disorder (MDD) patients exhibit increased functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Neurofibrillary tangles are also found in the hypothalamus of Alzheimer's disease (AD) patients, and AD patients exhibit abnormal changes in the HPA. However, little is known of how the hypothalamus interacts with other brain regions in AD patients with depression (D-AD). Functional connectivity (FC) analysis explores the connectivity between brain regions that share functional properties. Here, we used resting-state (rs) magnetic resonance imaging (MRI) technology and the FC method to measure hypothalamic connectivity across the whole brain in 22 D-AD patients and 21 non-depressed AD patients (nD-AD). Our results showed that D-AD patients had reduced FC among the hypothalamus, the right middle temporal gyrus (MTG) and the right superior temporal gyrus (STG) compared with the FC of nD-AD patients, suggesting that the abnormal FC between the hypothalamus and the temporal lobe may play a key role in the pathophysiology of depression in AD patients.

  15. PPARg mRNA in the adult mouse hypothalamus: distribution and regulation in response to dietary challenges

    Directory of Open Access Journals (Sweden)

    Yang eLiu

    2015-09-01

    Full Text Available Peroxisome proliferator-activated receptor gamma (PPARg is a ligand-activated transcription factor that was originally identified as a regulator of peroxisome proliferation and adipocyte differentiation. Emerging evidence suggests that functional PPARg signaling also occurs within the hypothalamus. However, the exact distribution and identities of PPARg-expressing hypothalamic cells remains under debate. The present study systematically mapped PPARg mRNA expression in the adult mouse brain using in situ hybridization histochemistry. PPARg mRNA was found to be expressed at high levels outside the hypothalamus including the neocortex, the olfactory bulb, the organ of the vasculosum of the lamina terminalis, and the subfornical organ. Within the hypothalamus, PPARg was present at moderate levels in the suprachiasmatic nucleus and the ependymal of the 3rd ventricle. In all examined feeding-related hypothalamic nuclei, PPARg was expressed at very low levels that were close to the limit of detection. Using qPCR techniques, we demonstrated that PPARg mRNA expression was upregulated in the suprachiasmatic nucleus in response to fasting. Double in situ hybridization further demonstrated that PPARg was primarily expressed in neurons. Collectively, our observations provide a comprehensive map of PPARg distribution and regulation in the intact adult mouse hypothalamus.

  16. Differential contribution of CBP:CREB binding to corticotropin-releasing hormone expression in the infant and adult hypothalamus

    NARCIS (Netherlands)

    Cope, J.L.; Regev, L.; Chen, Y.; Korosi, A.; Rice, C.J.; Ji, S.; Rogge, G.A.; Wood, M.A.; Baram, T.Z.

    2014-01-01

    Corticotropin-releasing hormone (CRH) contributes crucially to the regulation of central and peripheral responses to stress. Because of the importance of a finely-tuned stress system, CRH expression is tightly regulated in an organ- and brain region-specific manner. Thus, in hypothalamus, CRH is

  17. Time-dependent effects of neuropeptide Y infusion in the paraventricular hypothalamus on ingestive and associated behaviors in rats

    NARCIS (Netherlands)

    van Dijk, G; Strubbe, JH

    In this study the role of neuropeptide Y (NPY) in the paraventricular nucleus of the hypothalamus (PVN) in the daily regulation of feeding, drinking, locomotor activity, and nestbox occupation was investigated. These behaviors were recorded during and after bilateral infusion of NPY into the PVN of

  18. Specific expression of an oxytocin-enhanced cyan fluorescent protein fusion transgene in the rat hypothalamus and posterior pituitary

    Czech Academy of Sciences Publication Activity Database

    Katoh, A.; Fujihara, H.; Ohbuchi, T.; Onaka, T.; Scott, W. S. III.; Dayanithi, Govindan; Yamasaki, Y.; Kawata, M.; Suzuki, H.; Otsubo, H.; Suzuki, Hi.; Murphy, D.; Ueta, Y.

    2010-01-01

    Roč. 204, č. 3 (2010), s. 275-285 ISSN 0022-0795 Institutional research plan: CEZ:AV0Z50390703 Keywords : magnocellular neurons * neurosecretory-cells * hypothalamus Subject RIV: FH - Neurology Impact factor: 3.099, year: 2010

  19. Short-arm human centrifugation with 0.4g at eye and 0.75g at heart level provides similar cerebrovascular and cardiovascular responses to standing.

    Science.gov (United States)

    Goswami, Nandu; Bruner, Michelle; Xu, Da; Bareille, Marie-Pierre; Beck, Arnaud; Hinghofer-Szalkay, Helmut; Blaber, Andrew P

    2015-07-01

    Orthostatic intolerance continues to be a problem with astronauts upon return to Earth as a result of cerebral and cardiovascular adaptations to weightlessness. We tested the hypothesis that artificial gravity from a short-arm human centrifuge (SAHC) could provide cerebral and cardiovascular stimuli similar to upright posture and thereby serve as a suitable countermeasure. We compared cardiovascular and cerebrovascular responses before, during, and after exposure to hyper-G with that of standing in healthy young participants. The head was positioned such that the middle cerebral artery (MCA) was 0.46 m from the center of rotation. Two levels of hyper-G that provided 1g and 2g at foot level were investigated. Continuous blood pressure, heart rate, calf blood volume, MCA mean blood flow velocity (MFV) and end-tidal CO2 were measured. Blood pressure at the level of the MCA (BP-MCA) and MFV was reduced during stand and at 2g. The relationship between MFV and BP-MCA at 2g was different from supine and similar to standing, while 1g centrifugation was not different from supine. The cardiovascular system was also not different from supine at 1g but was similarly challenged in 2g compared to stand. Our data suggest that short-arm centrifugation 2g at the feet, with the head offset 0.5 m from the center, provides similar cardiovascular and cerebral responses to standing. This supports the hypothesis that passive 2g SAHC exposure at the feet could be used as a countermeasure for in-flight cardiovascular and cerebrovascular deconditioning.

  20. Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, X.Q. [Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Department of Cardiology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, Hubei (China); Hong, H.S. [Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Lin, X.H. [Department of Emergency Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Chen, L.L. [Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Li, Y.H. [Department of Cardiology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, Hubei (China)

    2014-07-11

    The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

  1. Changes in orexinergic immunoreactivity of the piglet hypothalamus and pons after exposure to chronic postnatal nicotine and intermittent hypercapnic hypoxia.

    Science.gov (United States)

    Hunt, Nicholas J; Russell, Benjamin; Du, Man K; Waters, Karen A; Machaalani, Rita

    2016-06-01

    We recently showed that orexin expression in sudden infant death syndrome (SIDS) infants was reduced by 21% in the hypothalamus and by 40-50% in the pons as compared with controls. Orexin maintains wakefulness/sleeping states, arousal, and rapid eye movement sleep, abnormalities of which have been reported in SIDS. This study examined the effects of two prominent risk factors for SIDS, intermittent hypercapnic hypoxia (IHH) (prone-sleeping) and chronic nicotine exposure (cigarette-smoking), on orexin A (OxA) and orexin B (OxB) expression in piglets. Piglets were randomly assigned to five groups: saline control (n = 7), air control (n = 7), nicotine [2 mg/kg per day (14 days)] (n = 7), IHH (6 min of 7% O2 /8% CO2 alternating with 6-min periods of breathing air, for four cycles) (n = 7), and the combination of nicotine and IHH (N + IHH) (n = 7). OxA/OxB expression was quantified in the central tuberal hypothalamus [dorsal medial hypothalamus (DMH), perifornical area (PeF), and lateral hypothalamus], and the dorsal raphe, locus coeruleus of the pons. Nicotine and N + IHH exposures significantly increased: (i) orexin expression in the hypothalamus and pons; and (ii) the total number of neurons in the DMH and PeF. IHH decreased orexin expression in the hypothalamus and pons without changing neuronal numbers. Linear relationships existed between the percentage of orexin-positive neurons and the area of pontine orexin immunoreactivity of control and exposure piglets. These results demonstrate that postnatal nicotine exposure increases the proportion of orexin-positive neurons in the hypothalamus and fibre expression in the pons, and that IHH exposure does not prevent the nicotine-induced increase. Thus, although both nicotine and IHH are risk factors for SIDS, it appears they have opposing effects on OxA and OxB expression, with the IHH exposure closely mimicking what we recently found in SIDS. © 2016 Federation of European Neuroscience Societies and John

  2. Anti-TNF-alpha antibody attenuates subarachnoid hemorrhage-induced apoptosis in the hypothalamus by inhibiting the activation of Erk

    Directory of Open Access Journals (Sweden)

    Ma L

    2018-02-01

    Full Text Available Ling Ma,1 Yong Jiang,2 Yanan Dong,2 Jun Gao,2 Bin Du,2 Dianwei Liu2 1Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China Background: Subarachnoid hemorrhage (SAH can induce apoptosis in many regions of the brain including the cortex and hippocampus. However, few studies have focused on apoptosis in the hypothalamus after SAH. Although some antiapoptotic strategies have been developed for SAH, such as anti-tumor necrosis factor-alpha (TNF-α antibody, the molecular mechanisms underlying this condition have yet to be elucidated. Therefore, the purpose of this study was to evaluate whether SAH could induce apoptosis in the hypothalamus and identify the potential molecular mechanisms underlying the actions of anti-TNF-α antibody, as a therapeutic regimen, upon apoptosis. Materials and methods: SAH was induced in a rat model. Thirty minutes prior to SAH, anti-TNF-α antibody or U0126, an extracellular signal-regulated kinase (Erk inhibitor, was microinjected into the left lateral cerebral ventricle. In addition, phorbol-12-myristate-13-acetate was injected intraperitoneally immediately after the anti-TNF-α antibody microinjection. Then, real-time polymerase chain reaction, Western blotting and immunohistochemistry were used to detect the expression of caspase-3, bax, bcl-2, phosphorylated Erk (p-Erk and Erk. Finally, anxiety-like behavior was identified by using open field. Results: Levels of caspase-3, bax and bcl-2, all showed a temporary rise after SAH in the hypothalamus, indicating the induction of apoptosis in this brain region. Interestingly, we found that the microinjection of anti-TNF-α antibody could selectively block the elevated levels of bax, suggesting the potential role of anti-TNF-α antibody in the inhibition of SAH

  3. Division for Heart Disease and Stroke Prevention: Data Trends & Maps

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CDC Division for Heart Disease and Stroke Prevention's Data Trends & Maps online tool allows searching for and view of health indicators related to Heart...

  4. Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

    Science.gov (United States)

    Mahmoud, Ahmed I; O'Meara, Caitlin C; Gemberling, Matthew; Zhao, Long; Bryant, Donald M; Zheng, Ruimao; Gannon, Joseph B; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Poss, Kenneth D; Lee, Richard T

    2015-08-24

    Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Effects of amino acids and vitamins on the ultrastructure of the hypothalamus and neurotransmitter in exhausted rats

    Directory of Open Access Journals (Sweden)

    Jian-wei CHEN

    2012-01-01

    Full Text Available Objective  To investigate the effects of amino acids and vitamins on the ultrastructure of the hypothalamus and neurotransmitter in exhausted rats. Methods  After adaptive swimming, 36 male SD rats were randomly divided into three groups, namely, capsule, control, and granules, with 12 rats in each group. Rats in 3 groups were given respectively amino acids capsule (8 kinds of essential amino acids and 11 kinds of vitamins were contained, normal drinking water, or amino acid-fructose beverage (2.5ml/100g, 2 times per day by gavage for 14 days. Exhaustion of rats was produced by non-loading swimming. The duration of the experiment lasted 14 days. After the last exhaustive swimming, the hypothalamus of the rats was removed for the observation of its ultrastructure under electron microscope. The contents of 5-hydroxytryptamine (5-HT, 5-hydroxyindole acetic acid (5HIAA, hydroxyphenyl acetic acid (HOPAC, and γ-aminobutyric acid (GABA in the hypothalamus were measured with high performance liquid chromatography (HPLC-ECD. Results  The mitochondrial structure in the brain cells of the capsule and granules groups were basically intact. On the other hand, the cells in the control group swelled and degenerated. Different degrees of swelling could be seen in the mitochondria. In addition, obvious morphological changes of the ultrastructure were observed under electron microscopy. Dissolution and rupture of the mitochondrial membrane and cristae were noted, even with the whole mitochondria disrupted and vacuolated. The contents of 5-HT, 5-HTAA, HOPAC, and GABA in the hypothalamus of rats in the capsule and the granules groups were significantly lower than those in the control group (PConclusion  Amino acids and vitamins compound can increase the resistance of the nerve center to fatigue by alleviating pathological changes of ultrastructure and changes in neurotransmitter levels of the hypothalamus.

  6. Heart failure - surgeries and devices

    Science.gov (United States)

    ... surgery; HF - surgery; Intra-aortic balloon pumps - heart failure; IABP - heart failure; Catheter based assist devices - heart failure ... problem may cause heart failure or make heart failure worse. Heart valve surgery may be needed to repair or ...

  7. Dogs with macroadenomas have lower body temperature and heart rate than dogs with microadenomas.

    Science.gov (United States)

    Benchekroun, Ghita; Desquilbet, Loic; Herrtage, Michael E; Jeffery, Nick D; Rosenberg, Dan; Granger, Nicolas

    2017-09-01

    Pituitary macroadenomas compress the hypothalamus, which partly regulates heart rate and body temperature. The aim of this study was to investigate whether heart rate and/or body temperature could aid in clinically differentiating dogs with macroadenomas from dogs with microadenomas (i.e. small non-compressive pituitary mass). Two groups of dogs diagnosed with pituitary-dependent hyperadrenocorticism (i.e. Cushing's disease) were included. Heart rate and body temperature were collected on initial presentation before any procedure. Dogs with macroadenoma had a significantly lower heart rate and body temperature (Pdogs with microadenoma. We suggest that the combined cut-off values of 84 beats per minutes and 38.3°C in dogs with Cushing's disease, especially with vague neurological signs (nine of 12 dogs=75%), might help to suspect the presence of a macroadenoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Valvular Heart Disease in Heart Failure

    Directory of Open Access Journals (Sweden)

    Giuseppe MC Rosano

    2017-01-01

    Full Text Available Structural valvular heart disease may be the cause of heart failure or may worsen the clinical status of patients with heart failure. Heart failure may also develop in patients treated with valve surgery. Patients with heart failure with valvular heart disease are at increased risk of events including sudden cardiac death. Before considering intervention (surgical or percutaneous all patients should receive appropriate medical and device therapy taking into account that vasodilators must be used with caution in patients with severe aortic stenosis. Numerous percutaneous and/or hybrid procedures have been introduced in the past few years and they are changing the management of valvular heart disease. In patients with heart failure and valvular heart disease, either primary or functional, the whole process of decision-making should be staged through a comprehensive evaluation of the risk– benefit ratio of different treatment strategies and should be made by a multidisciplinary ‘heart team’ with a particular expertise in valvular heart disease. The heart team should include heart failure cardiologists, cardiac surgeons/structural valve interventionists, imaging specialists, anaesthetists, geriatricians and intensive care specialists. This article will review recent developments and distill practical guidance in the management of this important heart failure co-morbidity.

  9. Creatine Depletion and Altered Fatty Acid Metabolism in Diseased Human Hearts: Clinical Investigation Using 1H Magnetic Resonance Spectroscopy and 123I BMIPP Myocardial Scintigraphy

    International Nuclear Information System (INIS)

    Nakae, I.; Mitsunami, K.; Matsuo, S.; Horie, M.

    2007-01-01

    Background: In the heart, the creatine kinase system plays an important role in energy reserves, and myocardial energy production essentially depends upon fatty acid metabolism. Purpose: To examine myocardial creatine (CR) concentration and altered cardiac fatty acid metabolism in various forms of heart disease. Material and Methods: Myocardial CR concentration of the septum was measured by gated 1 H magnetic resonance spectroscopy (MRS), applying a point-resolved spectroscopy (PRESS) sequence in 34 patients with heart disease. Of these patients, 14 underwent 123 I BMIPP (radioactive fatty acid analogue) myocardial scintigraphy to evaluate myocardial fatty acid metabolism. Cardiac 123 I BMIPP uptake was calculated as the heart-to-mediastinum count ratio. Results: Myocardial CR concentration correlated positively with the left ventricular ejection fraction (LVEF) by echocardiography (R = 0.61, P 123 I BMIPP uptake also correlated positively with LVEF (initial image, R 0.60, P 123 I BMIPP uptake (initial image, R = 0.77, P<0.01; delayed image, R = 0.82, P<0.001; n = 14). Conclusion: Our study suggests an association between CR depletion and impaired fatty acid metabolism in various forms of heart diseases

  10. Galanin-Expressing GABA Neurons in the Lateral Hypothalamus Modulate Food Reward and Noncompulsive Locomotion.

    Science.gov (United States)

    Qualls-Creekmore, Emily; Yu, Sangho; Francois, Marie; Hoang, John; Huesing, Clara; Bruce-Keller, Annadora; Burk, David; Berthoud, Hans-Rudolf; Morrison, Christopher D; Münzberg, Heike

    2017-06-21

    The lateral hypothalamus (LHA) integrates reward and appetitive behavior and is composed of many overlapping neuronal populations. Recent studies associated LHA GABAergic neurons (LHA GABA ), which densely innervate the ventral tegmental area (VTA), with modulation of food reward and consumption; yet, LHA GABA projections to the VTA exclusively modulated food consumption, not reward. We identified a subpopulation of LHA GABA neurons that coexpress the neuropeptide galanin (LHA Gal ). These LHA Gal neurons also modulate food reward, but lack direct VTA innervation. We hypothesized that LHA Gal neurons may represent a subpopulation of LHA GABA neurons that mediates food reward independent of direct VTA innervation. We used chemogenetic activation of LHA Gal or LHA GABA neurons in mice to compare their role in feeding behavior. We further analyzed locomotor behavior to understand how differential VTA connectivity and transmitter release in these LHA neurons influences this behavior. LHA Gal or LHA GABA neuronal activation both increased operant food-seeking behavior, but only activation of LHA GABA neurons increased overall chow consumption. Additionally, LHA Gal or LHA GABA neuronal activation similarly induced locomotor activity, but with striking differences in modality. Activation of LHA GABA neurons induced compulsive-like locomotor behavior; while LHA Gal neurons induced locomotor activity without compulsivity. Thus, LHA Gal neurons define a subpopulation of LHA GABA neurons without direct VTA innervation that mediate noncompulsive food-seeking behavior. We speculate that the striking difference in compulsive-like locomotor behavior is also based on differential VTA innervation. The downstream neural network responsible for this behavior and a potential role for galanin as neuromodulator remains to be identified. SIGNIFICANCE STATEMENT The lateral hypothalamus (LHA) regulates motivated feeding behavior via GABAergic LHA neurons. The molecular identity of LHA

  11. Restoring Serotonergic Homeostasis in the Lateral Hypothalamus Rescues Sleep Disturbances Induced by Early-Life Obesity.

    Science.gov (United States)

    Gazea, Mary; Patchev, Alexandre V; Anderzhanova, Elmira; Leidmaa, Este; Pissioti, Anna; Flachskamm, Cornelia; Almeida, Osborne F X; Kimura, Mayumi

    2018-01-10

    Early-life obesity predisposes to obesity in adulthood, a condition with broad medical implications including sleep disorders, which can exacerbate metabolic disturbances and disrupt cognitive and affective behaviors. In this study, we examined the long-term impact of transient peripubertal diet-induced obesity (ppDIO, induced between 4 and 10 weeks of age) on sleep-wake behavior in male mice. EEG and EMG recordings revealed that ppDIO increases sleep during the active phase but reduces resting-phase sleep quality. This impaired sleep phenotype persisted for up to 1 year, although animals were returned to a non-obesiogenic diet from postnatal week 11 onwards. To better understand the mechanisms responsible for the ppDIO-induced alterations in sleep, we focused on the lateral hypothalamus (LH). Mice exposed to ppDIO did not show altered mRNA expression levels of orexin and melanin-concentrating hormone, two peptides that are important for sleep-wake behavior and food intake. Conversely, the LH of ppDIO-exposed mice had reduced contents of serotonin (5-hydroxytryptamine, 5-HT), a neurotransmitter involved in both sleep-wake and satiety regulation. Interestingly, an acute peripheral injection of the satiety-signaling peptide YY 3-36 increased 5-HT turnover in the LH and ameliorated the ppDIO-induced sleep disturbances, suggesting the therapeutic potential of this peptide. These findings provide new insights into how sleep-wake behavior is programmed during early life and how peripheral and central signals are integrated to coordinate sleep. SIGNIFICANCE STATEMENT Adult physiology and behavior are strongly influenced by dynamic reorganization of the brain during puberty. The present work shows that obesity during puberty leads to persistently dysregulated patterns of sleep and wakefulness by blunting serotonergic signaling in the lateral hypothalamus. It also shows that pharmacological mimicry of satiety with peptide YY 3-36 can reverse this neurochemical imbalance and

  12. Yoga and the heart

    Directory of Open Access Journals (Sweden)

    Rahul Mehrotra

    2016-01-01

    Full Text Available The concept of "Yoga" is currently gaining a lot of popularity worldwide owing to its various health benefits and other advantages such as safety and ease of practice. There is considerable evidence accumulating related to its benefits on health, especially cardiovascular health. There is, however, a lot of confusion related to the term "Yoga" in the various studies as it comprises several different practices. More good quality studies are needed utilizing different components of "Yoga" investigating their effects on cardiovascular disease. There is also a change in the understanding of the role of the heart in the human body.

  13. Getting a New Heart

    Science.gov (United States)

    ... may be able to replace it with an artificial (man-made) valve. Cardiac size reduction . During this procedure, your doctor removes a piece of the heart muscle from an enlarged heart. This makes your heart ...

  14. Heart-Health Screenings

    Science.gov (United States)

    ... Tools For Your Heart Health • Watch, Learn & Live Animations Library Subscribe to Heart Insight magazine and monthly ... in Spanish . Popular Articles 1 Understanding Blood Pressure Readings 2 Sodium and Salt 3 Heart Attack Symptoms ...

  15. Heart Attack Recovery FAQs

    Science.gov (United States)

    ... recommendations to make a full recovery. View an animation of a heart attack . Heart Attack Recovery Questions ... Support Network Popular Articles 1 Understanding Blood Pressure Readings 2 Sodium and Salt 3 Heart Attack Symptoms ...

  16. Open heart surgery

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002950.htm Open heart surgery To use the sharing features on this ... large arteries connected to the heart. The term "open heart surgery" means that you are connected to a ...

  17. Pediatric heart surgery - discharge

    Science.gov (United States)

    ... discharge; Heart valve surgery - children - discharge; Heart surgery - pediatric - discharge; Heart transplant - pediatric - discharge ... Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, PA: Elsevier; 2016:chap 434. ...

  18. Congenital Heart Information Network

    Science.gov (United States)

    ... heart defects. Important Notice The Congenital Heart Information Network website is temporarily out of service. Please join ... and Uwe Baemayr for The Congenital Heart Information Network Exempt organization under Section 501(c)3. Copyright © ...

  19. Heart disease and depression

    Science.gov (United States)

    ... gov/ency/patientinstructions/000790.htm Heart disease and depression To use the sharing features on this page, ... a heart attack or heart surgery Signs of Depression It is pretty common to feel down or ...

  20. Hypertensive heart disease

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000163.htm Hypertensive heart disease To use the sharing features on this page, please enable JavaScript. Hypertensive heart disease refers to heart problems that occur because of ...

  1. Left heart catheterization

    Science.gov (United States)

    Catheterization - left heart ... to help guide the catheters up into your heart and arteries. Dye (sometimes called "contrast") will be ... in the blood vessels that lead to your heart. The catheter is then moved through the aortic ...

  2. Right heart ventriculography

    Science.gov (United States)

    Angiography - right heart ... moved forward into the right side of the heart. As the catheter is advanced, the doctor can ... is injected into the right side of the heart. It helps the cardiologist determine the size and ...

  3. Congenital heart disease

    Science.gov (United States)

    Congenital heart disease (CHD) is a problem with the heart's structure and function that is present at birth. ... Fraser CD, Kane LC. Congenital heart disease. In: Townsend CM Jr, ... Sabiston Textbook of Surgery: The Biological Basis of Modern ...

  4. Heart Disease Risk Factors

    Science.gov (United States)

    ... About CDC.gov . Home About Heart Disease Coronary Artery Disease Heart Attack Heart Attack Signs and Symptoms ... Privacy FOIA No Fear Act OIG 1600 Clifton Road Atlanta , GA 30329-4027 USA 800-CDC-INFO ( ...

  5. Correcting human heart 31P NMR spectra for partial saturation. Evidence that saturation factors for PCr/ATP are homogeneous in normal and disease states

    Science.gov (United States)

    Bottomley, Paul A.; Hardy, Christopher J.; Weiss, Robert G.

    Heart PCr/ATP ratios measured from spatially localized 31P NMR spectra can be corrected for partial saturation effects using saturation factors derived from unlocalized chest surface-coil spectra acquired at the heart rate and approximate Ernst angle for phosphor creatine (PCr) and again under fully relaxed conditions during each 31P exam. To validate this approach in studies of normal and disease states where the possibility of heterogeneity in metabolite T1 values between both chest muscle and heart and normal and disease states exists, the properties of saturation factors for metabolite ratios were investigated theoretically under conditions applicable in typical cardiac spectroscopy exams and empirically using data from 82 cardiac 31P exams in six study groups comprising normal controls ( n = 19) and patients with dilated ( n = 20) and hypertrophic ( n = 5) cardiomyopathy, coronary artery disease ( n = 16), heart transplants ( n = 19), and valvular heart disease ( n = 3). When TR ≪ T1,(PCr), with T1(PCr) ⩾ T1(ATP), the saturation factor for PCr/ATP lies in the range 1.5 ± 0.5, regardless of the T1 values. The precise value depends on the ratio of metabolite T1 values rather than their absolute values and is insensitive to modest changes in TR. Published data suggest that the metabolite T1 ratio is the same in heart and muscle. Our empirical data reveal that the saturation factors do not vary significantly with disease state, nor with the relative fractions of muscle and heart contributing to the chest surface-coil spectra. Also, the corrected myocardial PCr/ATP ratios in each normal or disease state bear no correlation with the corresponding saturation factors nor the fraction of muscle in the unlocalized chest spectra. However, application of the saturation correction (mean value, 1.36 ± 0.03 SE) significantly reduced scatter in myocardial PCr/ATP data by 14 ± 11% (SD) ( p ⩽ 0.05). The findings suggest that the relative T1 values of PCr and ATP are

  6. Sizing up the Grinch's Heart

    Science.gov (United States)

    Cox, Dana C.; Edwards, Michael Todd

    2012-01-01

    The opening lines of "How the Grinch Stole Christmas!" (Geisel 1957) set the tone for an inspiring change-of-heart story about a grumpy creature that comes to value humanity and the Christmas spirit. Although the book is often considered inspirational for other reasons, the authors were particularly moved by Dr. Seuss's interesting conjecture…

  7. Target Heart Rates

    Science.gov (United States)

    ... Check Recipe Certification Program Nutrition Requirements Heart-Check Professional Resources Contact the Heart-Check Certification Program Simple Cooking and Recipes Dining Out Choosing a Restaurant Deciphering ...

  8. Alcohol and Heart Health

    Science.gov (United States)

    ... Check Recipe Certification Program Nutrition Requirements Heart-Check Professional Resources Contact the Heart-Check Certification Program Simple Cooking and Recipes Dining Out Choosing a Restaurant Deciphering ...

  9. Caffeine and Heart Disease

    Science.gov (United States)

    ... Check Recipe Certification Program Nutrition Requirements Heart-Check Professional Resources Contact the Heart-Check Certification Program Simple Cooking and Recipes Dining Out Choosing a Restaurant Deciphering ...

  10. Protein and Heart Health

    Science.gov (United States)

    ... Check Recipe Certification Program Nutrition Requirements Heart-Check Professional Resources Contact the Heart-Check Certification Program Simple Cooking and Recipes Dining Out Choosing a Restaurant Deciphering ...

  11. Heart failure - medicines

    Science.gov (United States)

    CHF - medicines; Congestive heart failure - medicines; Cardiomyopathy - medicines; HF - medicines ... You will need to take most of your heart failure medicines every day. Some medicines are taken ...

  12. Inhibition of serotonin release by bombesin-like peptides in rat hypothalamus in vitro

    International Nuclear Information System (INIS)

    Saporito, M.S.; Warwick, R.O. Jr.

    1989-01-01

    We investigated the activity of bombesin (BN), neuromedin-C (NM-C) and neuromedin-B (NM-B) on serotonin (5-HT) release and reuptake in rat hypothalamus (HYP) in vitro. BN and NM-C but not NM-B decreased K + evoked 3 H-5-HT release from superfused HYP slices by 25%. Bacitracin, a nonspecific peptidase inhibitor, reversed the inhibitory effect of BN on K + evoked 3 H-5-HT release. Phosphoramidon (PAN, 10 μM) an endopeptidase 24.11 inhibitor, abolished the inhibitory effect of BN, but not NM-C, on K + evoked 3 H-5-HT release. The peptidyl dipeptidase A inhibitor enalaprilat (ENP, 10 μM), enhanced both BN and NM-C inhibition of 3 H-5-HT release. Bestatin (BST, 10 μM) had no effect on BN or NM-C inhibitory activity on 3 H-5-HT release. Neither BN, NM-C nor NM-B affected reuptake of 3 H-5-HT into HYP synaptosomes alone or in combination with any of the peptidase inhibitors, nor did these peptides alter the ability of fluoxetine to inhibit 3 H-5-HT uptake

  13. Effects of estradiol on norepinephrine and prostaglandin efflux in medial basal hypothalamus of ovariectomized rats

    International Nuclear Information System (INIS)

    Cardinali, D.P.; Fernandez Pardal, J.; Gimeno, M.F.; Gimeno, A.L.

    1982-01-01

    The spontaneous and K + -stimulated efflux of norepinephrine (NE) and the release of PGE 2 and PGF 2 α were examined in medial basal hypothalamus (MBH) of ovariectomized rats killed before and during the LH release that follows estradiol treatment. As compared to vehicle-treated, ovariectomized rats, estradiol-primed rats exhibited a 60% more increase in K + -stimulated 3 H-overflow of MBH slices preloaded with 3 H-NE at morning hours (1000 hours). Estradiol treatment did not result in further increase of K + -induced 3 H release from MBH slices at the time of LH release (1700 hours), nor affected labelled NE release in occipital cortex slices. A significant difference between K + -stimulated NE release of vehicle-treated spayed rats killed at 1000 and 1700 hours was observed, the latter showing 54% more release upon stimulus. PGE 2 efflux was time-dependent being highest at the evening in both vehicle- and estradiol-treated animals. The MBH of estrogenized rats released significantly more PGE 2 at the evening as compared to the controls. The release of PGF 2 α remained essentially unchanged regardless of estradiol treatment or time of day. The present results offer additional support to the involvement of MBH catecholamines and prostaglandins in the mechanism of LH secretion in the rat. (author)

  14. Single-Cell Gene Expression Analysis of Cholinergic Neurons in the Arcuate Nucleus of the Hypothalamus.

    Directory of Open Access Journals (Sweden)

    Jae Hoon Jeong

    Full Text Available The cholinoceptive system in the hypothalamus, in particular in the arcuate nucleus (ARC, plays a role in regulating food intake. Neurons in the ARC contain multiple neuropeptides, amines, and neurotransmitters. To study molecular and neurochemical heterogeneity of ARC neurons, we combine single-cell qRT-PCR and single-cell whole transcriptome amplification methods to analyze expression patterns of our hand-picked 60 genes in individual neurons in the ARC. Immunohistochemical and single-cell qRT-PCR analyses show choline acetyltransferase (ChAT-expressing neurons in the ARC. Gene expression patterns are remarkably distinct in each individual cholinergic neuron. Two-thirds of cholinergic neurons express tyrosine hydroxylase (Th mRNA. A large subset of these Th-positive cholinergic neurons is GABAergic as they express the GABA synthesizing enzyme glutamate decarboxylase and vesicular GABA transporter transcripts. Some cholinergic neurons also express the vesicular glutamate transporter transcript gene. POMC and POMC-processing enzyme transcripts are found in a subpopulation of cholinergic neurons. Despite this heterogeneity, gene expression patterns in individual cholinergic cells appear to be highly regulated in a cell-specific manner. In fact, membrane receptor transcripts are clustered with their respective intracellular signaling and downstream targets. This novel population of cholinergic neurons may be part of the neural circuitries that detect homeostatic need for food and control the drive to eat.

  15. Effect of parenteral glutamate treatment on the localization of neurotransmitters in the mediobasal hypothalamus

    Energy Technology Data Exchange (ETDEWEB)

    Walaas, I; Fonnum, F

    1978-01-01

    The localization of cholinergic, aminergic and amino acid-ergic neurones in the mediobasal hypothalamus has been studied in normal rat brain and in brains where neurones in nucleus arcuatus were destroyed by repeated administration of 2 mg/g body weight monosodium glutamate to newborn animals. In normal animals acetylcholinesterase staining, choline acetyltransferase and aromatic L-amino acid decarboxylase were concentrated in the median eminence and the arcuate nucleus. Glutamate decarboxylase was concentrated at the boundary between the ventromedial and the arcuate nuclei, with lower activity in the arcuate nucleus and very low activity in the median eminence. Nucleus arcuatus contained an intermediate level of high affinity glutamate uptake. In the lesioned animals, there were significant decreases in choline acetyltransferase, acetylcholinesterase staining and glutamate decarboxylase in the median eminence, whereas choline acetyltransferase activity and acetylcholinesterase staining, but not glutamate decarboxylase activity, were decreased in nucleus arcuatus. Aromatic L-amino acid decarboxylase was unchanged in all regions studied. The high affinity uptakes of glutamate, dopamine and noradrenaline, and the endogenous amino acid levels were also unchanged in the treated animals. The results indicate the existence of acetylcholine- and GABA-containing elements in the tuberoinfundibular tract. They further indicate that the dopamine cells in the arcuate nucleus are less sensitive to the toxic effect of glutamate than other cell types, possibly because they contain less glutamate receptors.

  16. α/β-Hydrolase Domain 6 in the Ventromedial Hypothalamus Controls Energy Metabolism Flexibility

    Directory of Open Access Journals (Sweden)

    Alexandre Fisette

    2016-10-01

    Full Text Available α/β-Hydrolase domain 6 (ABHD6 is a monoacylglycerol hydrolase that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG. Although complete or peripheral ABHD6 loss of function is protective against diet-induced obesity and insulin resistance, the role of ABHD6 in the central control of energy balance is unknown. Using a viral-mediated knockout approach, targeted endocannabinoid measures, and pharmacology, we discovered that mice lacking ABHD6 from neurons of the ventromedial hypothalamus (VMHKO have higher VMH 2-AG levels in conditions of endocannabinoid recruitment and fail to physiologically adapt to key metabolic challenges. VMHKO mice exhibited blunted fasting-induced feeding and reduced food intake, energy expenditure, and adaptive thermogenesis in response to cold exposure, high-fat feeding, and dieting (transition to a low-fat diet. Our findings identify ABHD6 as a regulator of the counter-regulatory responses to major metabolic shifts, including fasting, nutrient excess, cold, and dieting, thereby highlighting the importance of ABHD6 in the VMH in mediating energy metabolism flexibility.

  17. Self-administration of morphine into the lateral hypothalamus in the mouse.

    Science.gov (United States)

    Cazala, P; Darracq, C; Saint-Marc, M

    1987-07-28

    BALB/c mice were chronically and unilaterally implanted with a guide cannula, the tip of which was positioned 1 mm above the lateral hypothalamus (LH). On each experimental day, a stainless-steel injection cannula was inserted into the LH, and self-administration of morphine or vehicle in this brain area was studied by using a spatial discrimination test in a Y-maze. In a first experiment, we observed that when mice had access to morphine (0.1 microgram by injection) they rapidly discriminated the reinforced arm from the neutral arm of the maze in order to self administer, with increasing frequency, the drug into the LH. In contrast when only vehicle was present, the two arms were no longer discriminated. In a second experiment we compared the effects of 3 doses of morphine (0.1 microgram, 0.05 microgram and 0.025 microgram by injection); optimal discrimination was obtained with the lowest dose used. In a third experiment we observed that subcutaneous injections of naloxone (4 mg/kg) progressively reduced the number of self-administrations of morphine into the LH, a result which suggests that this response is dependent on an opiate receptor mechanism.

  18. Lateral hypothalamus contains two types of palatability-related taste responses with distinct dynamics.

    Science.gov (United States)

    Li, Jennifer X; Yoshida, Takashi; Monk, Kevin J; Katz, Donald B

    2013-05-29

    The taste of foods, in particular the palatability of these tastes, exerts a powerful influence on our feeding choices. Although the lateral hypothalamus (LH) has long been known to regulate feeding behavior, taste processing in LH remains relatively understudied. Here, we examined single-unit LH responses in rats subjected to a battery of taste stimuli that differed in both chemical composition and palatability. Like neurons in cortex and amygdala, LH neurons produced a brief epoch of nonspecific responses followed by a protracted period of taste-specific firing. Unlike in cortex, however, where palatability-related information only appears 500 ms after the onset of taste-specific firing, taste specificity in LH was dominated by palatability-related firing, consistent with LH's role as a feeding center. Upon closer inspection, taste-specific LH neurons fell reliably into one of two subtypes: the first type showed a reliable affinity for palatable tastes, low spontaneous firing rates, phasic responses, and relatively narrow tuning; the second type showed strongest modulation to aversive tastes, high spontaneous firing rates, protracted responses, and broader tuning. Although neurons producing both types of responses were found within the same regions of LH, cross-correlation analyses suggest that they may participate in distinct functional networks. Our data shed light on the implementation of palatability processing both within LH and throughout the taste circuit, and may ultimately have implications for LH's role in the formation and maintenance of taste preferences and aversions.

  19. Macronutrients and the FTO gene expression in hypothalamus; a systematic review of experimental studies.

    Science.gov (United States)

    Doaei, Saeid; Kalantari, Naser; Mohammadi, Nastaran Keshavarz; Tabesh, Ghasem Azizi; Gholamalizadeh, Maryam

    The various studies have examined the relationship between FTO gene expression and macronutrients levels. In order to obtain better viewpoint from this interactions, all of existing studies were reviewed systematically. All published papers have been obtained and reviewed using standard and sensitive keywords from databases such as CINAHL, Embase, PubMed, PsycInfo, and the Cochrane, from 1990 to 2016. The results indicated that all of 6 studies that met the inclusion criteria (from a total of 428 published article) found FTO gene expression changes at short-term follow-ups. Four of six studies found an increased FTO gene expression after calorie restriction, while two of them indicated decreased FTO gene expression. The effect of protein, carbohydrate and fat were separately assessed and suggested by all of six studies. In Conclusion, The level of FTO gene expression in hypothalamus is related to macronutrients levels. Future research should evaluate the long-term impact of dietary interventions. Copyright © 2017. Published by Elsevier B.V.

  20. Leptin and glucocorticoid signaling pathways in the hypothalamus of female and male fructose-fed rats

    Directory of Open Access Journals (Sweden)

    Vojnović-Milutinović Danijela

    2014-01-01

    Full Text Available Alterations in leptin and glucocorticoid signaling pathways in the hypothalamus of male and female rats subjected to a fructose-enriched diet were studied. The level of expression of the key components of the leptin signaling pathway (neuropeptide Y /NPY/ and suppressor of cytokine signaling 3 /SOCS3/, and the glucocorticoid signaling pathway (glucocorticoid receptor /GR/, 11β-hydroxysteroid dehydrogenase type 1 /11βHSD1/ and hexose-6-phosphate dehydrogenase /H6PDH/ did not differ between fructose-fed rats and control animals of both genders. However, in females, a fructose-enriched diet provoked increases in the adiposity index, plasma leptin and triglyceride concentrations, and displayed a tendency to decrease the leptin receptor (ObRb protein and mRNA levels. In male rats, the fructose diet caused elevations in plasma non-esterified fatty acids and triglycerides, as well as in both plasma and hypothalamic leptin concentrations. Our results suggest that a fructose-enriched diet can induce hyperleptinemia in both female and male rats, but with a more pronounced effect on hypothalamic leptin sensitivity in females, probably contributing to the observed development of visceral adiposity. [Projekat Ministarstva nauke Republike Srbije, br. III41009