Sample records for human hypothalamus heart
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Imaging of serotonin transporters with [123I]FP-CIT SPECT in the human hypothalamus
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
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Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus
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
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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...
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Activation and degeneration during aging: a morphometric study of the human hypothalamus
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
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Sex differences in the hypothalamus in the different stages of human life
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
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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.
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Sexual differentiation of the human hypothalamus
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
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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
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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.
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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)
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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....
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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.
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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.
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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
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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
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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.
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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.
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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
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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
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Restoration of heart functions using human embryonic stem cells derived heart muscle cells.
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.
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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.
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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 ...
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File list: Unc.Neu.20.AllAg.Hypothalamus [Chip-atlas[Archive
Lifescience Database Archive (English)
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File list: Unc.Neu.05.AllAg.Hypothalamus [Chip-atlas[Archive
Lifescience Database Archive (English)
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File list: Unc.Neu.50.AllAg.Hypothalamus [Chip-atlas[Archive
Lifescience Database Archive (English)
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File list: ALL.Neu.10.AllAg.Hypothalamus [Chip-atlas[Archive
Lifescience Database Archive (English)
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File list: ALL.Neu.05.AllAg.Hypothalamus [Chip-atlas[Archive
Lifescience Database Archive (English)
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File list: ALL.Neu.50.AllAg.Hypothalamus [Chip-atlas[Archive
Lifescience Database Archive (English)
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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 ...
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M(o)TOR of aging: MTOR as a universal molecular hypothalamus.
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.
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The hypothalamus at the crossroads of psychopathology and neurosurgery.
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
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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
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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....
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Total excitation of the isolated human heart
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
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Anatomy of the human hypothalamus (chiasmatic and tuberal region).
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).
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Human heart disease : lessons from human pluripotent stem cell-derived cardiomyocytes
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
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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)
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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.
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The anterior hypothalamus in cluster headache.
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.
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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...
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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
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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 ...
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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.
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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.
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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.
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The Visible Heart® project and free-access website 'Atlas of Human Cardiac Anatomy'.
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.
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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.
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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.
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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.)
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Adrenergic innervation of the rat hypothalamus
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
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Myocardial bridges of the coronary arteries in the human fetal heart.
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.
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Noradrenergic and GABAergic systems in the medial hypothalamus are activated during hypoglycemia
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
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The lateral hypothalamus : A site for integration of nutrient and fluid balance
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)
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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.
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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
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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.
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One-day high-fat diet induces inflammation in the nodose ganglion and hypothalamus of mice.
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.
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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.
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Short-term fasting promotes insulin expression in rat hypothalamus.
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.
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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...
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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.
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Visualization of human heart conduction system by means of fluorescence spectroscopy
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.
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Epicardial excitation pattern as observed in the isolated revived and perfused fetal human heart
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
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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
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General anesthesia suppresses normal heart rate variability in humans
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.
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Social Control of Hypothalamus-Mediated Male Aggression.
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.
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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
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The role of gut hormones and the hypothalamus in appetite regulation.
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.
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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.
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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.
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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
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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.
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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
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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.
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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.
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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.
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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
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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
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Tracking fusion of human mesenchymal stem cells after transplantation to the heart.
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
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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.
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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.
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The human heart: application of the golden ratio and angle.
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.
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Resonance of about-weekly human heart rate rhythm with solar activity change.
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.
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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
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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)
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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....
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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
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Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts
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
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Inspiration from heart development: Biomimetic development of functional human cardiac organoids.
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.
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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
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Neuroregulatory and neuroendocrine GnRH pathways in the hypothalamus and forebrain of the baboon.
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.
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ILK induces cardiomyogenesis in the human heart.
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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
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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...
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Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds.
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.
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Phenotyping of nNOS neurons in the postnatal and adult female mouse hypothalamus.
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.
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A semi-automated algorithm for hypothalamus volumetry in 3 Tesla magnetic resonance images.
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.
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Dogs with macroadenomas have lower body temperature and heart rate than dogs with microadenomas.
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.
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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
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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
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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.
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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.
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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.
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A new look at the comparative physiology of insect and human hearts.
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
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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
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Prosomeric organization of the hypothalamus in an elasmobranch, the catshark Scyliorhinus canicula.
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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.
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Prosomeric organization of the hypothalamus in an elasmobranch, the catshark Scyliorhinus canicula.
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.
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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.
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Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia
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...
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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.
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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
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Active coping with stress suppresses glucose metabolism in the rat hypothalamus.
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.
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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)
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Distinct types of feeding related neurons in mouse hypothalamus
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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.
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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)
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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)
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Distribution of melatonin receptor in human fetal brain
Institute of Scientific and Technical Information of China (English)
WANG Guo-quan; SHAO Fu-yuan; ZHAO Ying; LIU Zhi-min
2001-01-01
Objective: To study the distribution of 2 kinds of melatonin receptor subtypes (mtl and MT2) in human fetal brain. Methods: The fetal brain tissues were sliced and the distribution ofmelatonin receptors in human fetal brain were detected using immunohistochemistry and in situ hybridization. Results: Melatonin receptor mtl existed in the cerebellun and hypothalamus, melatonin receptor MT2 exists in hypothalamus, occipital and medulla. Conclusion: Two kinds of melatonin receptors, mtl and MT2 exist in the membrane and cytosol of brain cells, indicating that human fetal brain is a target organ of melatonin.
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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
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Participation of the hypothalamus-hypophysis axis in the sympathetic activation of human obesity.
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.
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Plasma vs heart tissue concentration in humans - literature data analysis of drugs distribution.
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.
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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...
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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.
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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.
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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...
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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.
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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
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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...
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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.
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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.)
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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.
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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.
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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.
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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
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Cardiac re-entry dynamics and self-termination in DT-MRI based model of Human Foetal Heart
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.
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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
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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)
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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...
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Metabolic mystery: Aging, obesity, diabetes and ventromedial hypothalamus
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...
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Auvinen, H E; Romijn, J A; Biermasz, N R; Havekes, L M; Smit, J W A; Rensen, P C N; Pereira, A M
2011-12-01
Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the hypothalamus-pituitary-adrenal-axis activation. The aim of this review was to assess the effects of high fat feeding on the activity of the hypothalamus-pituitary-adrenal-axis in mice. PubMed, EMBASE, Web of Science, the Cochrane database, and Science Direct were electronically searched and reviewed by 2 individual researchers. We included only original mouse studies reporting parameters of the hypothalamus-pituitary-adrenal-axis after high fat feeding, and at least 1 basal corticosterone level with a proper control group. Studies with adrenalectomized mice, transgenic animals only, high fat diet for less than 2 weeks, or other interventions besides high fat diet, were excluded. 20 studies were included. The hypothalamus-pituitary-adrenal-axis evaluation was the primary research question in only 5 studies. Plasma corticosterone levels were unchanged in 40%, elevated in 30%, and decreased in 20% of the studies. The effects in the peripheral tissues and the central nervous system were also inconsistent. However, major differences were found between mouse strains, experimental conditions, and the content and duration of the diets. This systematic review demonstrates that the effects of high fat feeding on the basal activity of the hypothalamus-pituitary-adrenal-axis in mice are limited and inconclusive. Differences in experimental conditions hamper comparisons and accentuate the need for standardized evaluations to discern the effects of diet-induced obesity on the hypothalamus-pituitary-adrenal-axis. © Georg Thieme Verlag KG Stuttgart · New York.
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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.
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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
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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.
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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...
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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
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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.
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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...
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THERP and HEART integrated methodology for human error assessment
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.
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Angiotensinergic and noradrenergic neurons in the rat and human heart.
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.
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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.
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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
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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.
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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.
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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...
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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.
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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
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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.
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Optimization of viral vector technology to study gene function in the hypothalamus
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
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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
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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...
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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
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Impact of space weather on human heart rate during the years 2011-2013
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.
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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
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Analysis of cardiac myosin binding protein-C phosphorylation in human heart muscle.
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
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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.
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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.
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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
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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.
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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.
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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...
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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)
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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)
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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.
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Energy metabolism of rat cerebral cortex, hypothalamus and hypophysis during ageing.
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
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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)
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Stiletto stabbing: penetrating injury to the hypothalamus with hyperacute diabetes insipidus.
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.
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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
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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
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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.
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The neuroanatomical function of leptin in the hypothalamus.
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.
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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.
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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...
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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.
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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.
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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
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Turnover of Biogenic Amines in the Hypothalamus of Rats during Pyrogen Fever
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
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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
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Baquedano, Eva; García-Cáceres, Cristina; Diz-Chaves, Yolanda; Lagunas, Natalia; Calmarza-Font, Isabel; Azcoitia, Iñigo; Garcia-Segura, Luis M.; Argente, Jesús; Chowen, Julie A.; Frago, Laura M.
2011-01-01
Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID:22096592
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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...
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Neonatal maternal separation up-regulates protein signalling for cell survival in rat hypothalamus.
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.
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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.
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Profile of Heart Donors from the Human Valve Bank of the Santa Casa de Misericórdia de Curitiba.
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.
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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.
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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.
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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,…
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Defining the molecular signatures of human right heart failure.
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.
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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.
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Morphometry of the pituitary gland and hypothalamus in long-term survivors of childhood trauma.
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.
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Insulin in the arcuate nucleus of the hypothalamus reduces fat consumption in rats
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
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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.
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[Healthcare and Christianity, the human person at the heart of God's concerns].
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.
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Heart Attack Payment - Hospital
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...
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Simulation of Blood flow in Artificial Heart Valve Design through Left heart
Hafizah Mokhtar, N.; Abas, Aizat
2018-05-01
In this work, an artificial heart valve is designed for use in real heart with further consideration on the effect of thrombosis, vorticity, and stress. The design of artificial heart valve model is constructed by Computer-aided design (CAD) modelling and simulated using Computational fluid dynamic (CFD) software. The effect of blood flow pattern, velocity and vorticity of the artificial heart valve design has been analysed in this research work. Based on the results, the artificial heart valve design shows that it has a Doppler velocity index that is less than the allowable standards for the left heart with values of more than 0.30 and less than 2.2. These values are safe to be used as replacement of the human heart valve.
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Heart Attack Payment - National
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...
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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...
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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
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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.
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Improvement of Heart Failure by Human Amniotic Mesenchymal Stromal Cell Transplantation in Rats.
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.
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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.
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Artificial heart for humanoid robot
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.
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Directory of Open Access Journals (Sweden)
Emilie Sapin
Full Text Available We recently discovered, using Fos immunostaining, that the tuberal and mammillary hypothalamus contain a massive population of neurons specifically activated during paradoxical sleep (PS hypersomnia. We further showed that some of the activated neurons of the tuberal hypothalamus express the melanin concentrating hormone (MCH neuropeptide and that icv injection of MCH induces a strong increase in PS quantity. However, the chemical nature of the majority of the neurons activated during PS had not been characterized. To determine whether these neurons are GABAergic, we combined in situ hybridization of GAD(67 mRNA with immunohistochemical detection of Fos in control, PS deprived and PS hypersomniac rats. We found that 74% of the very large population of Fos-labeled neurons located in the tuberal hypothalamus after PS hypersomnia were GAD-positive. We further demonstrated combining MCH immunohistochemistry and GAD(67in situ hybridization that 85% of the MCH neurons were also GAD-positive. Finally, based on the number of Fos-ir/GAD(+, Fos-ir/MCH(+, and GAD(+/MCH(+ double-labeled neurons counted from three sets of double-staining, we uncovered that around 80% of the large number of the Fos-ir/GAD(+ neurons located in the tuberal hypothalamus after PS hypersomnia do not contain MCH. Based on these and previous results, we propose that the non-MCH Fos/GABAergic neuronal population could be involved in PS induction and maintenance while the Fos/MCH/GABAergic neurons could be involved in the homeostatic regulation of PS. Further investigations will be needed to corroborate this original hypothesis.
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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)
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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)
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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.
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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)
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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
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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
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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.
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Forkhead box transcription factors in embryonic heart development and congenital heart disease.
Zhu, Hong
2016-01-01
Embryonic heart development is a very complicated process regulated precisely by a network composed of many genes and signaling pathways in time and space. Forkhead box (Fox, FOX) proteins are a family of transcription factors characterized by the presence of an evolutionary conserved "forkhead"or "winged-helix" DNA-binding domain and able to organize temporal and spatial gene expression during development. They are involved in a wide variety of cellular processes, such as cell cycle progression, proliferation, differentiation, migration, metabolism and DNA damage response. An abundance of studies in model organisms and systems has established that Foxa2, Foxc1/c2, Foxh1 and Foxm1, Foxos and Foxps are important components of the signaling pathways that instruct cardiogenesis and embryonic heart development, playing paramount roles in heart development. The previous studies also have demonstrated that mutations in some of the forkhead box genes and the aberrant expression of forkhead box gene are heavily implicated in the congenital heart disease (CHD) of humans. This review primarily focuses on the current understanding of heart development regulated by forkhead box transcription factors and molecular genetic mechanisms by which forkhead box factors modulate heart development during embryogenesis and organogenesis. This review also summarizes human CHD related mutations in forkhead box genes as well as the abnormal expression of forkhead box gene, and discusses additional possible regulatory mechanisms of the forkhead box genes during embryonic heart development that warrant further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.
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Pedroso, Amanda P; Souza, Adriana P; Dornellas, Ana P S; Oyama, Lila M; Nascimento, Cláudia M O; Santos, Gianni M S; Rosa, José C; Bertolla, Ricardo P; Klawitter, Jelena; Christians, Uwe; Tashima, Alexandre K; Ribeiro, Eliane B
2017-04-07
Programming of hypothalamic functions regulating energy homeostasis may play a role in intrauterine growth restriction (IUGR)-induced adulthood obesity. The present study investigated the effects of IUGR on the hypothalamus proteome and metabolome of adult rats submitted to 50% protein-energy restriction throughout pregnancy. Proteomic and metabolomic analyzes were performed by data independent acquisition mass spectrometry and multiple reaction monitoring, respectively. At age 4 months, the restricted rats showed elevated adiposity, increased leptin and signs of insulin resistance. 1356 proteins were identified and 348 quantified while 127 metabolites were quantified. The restricted hypothalamus showed down-regulation of 36 proteins and 5 metabolites and up-regulation of 21 proteins and 9 metabolites. Integrated pathway analysis of the proteomics and metabolomics data indicated impairment of hypothalamic glucose metabolism, increased flux through the hexosamine pathway, deregulation of TCA cycle and the respiratory chain, and alterations in glutathione metabolism. The data suggest IUGR modulation of energy metabolism and redox homeostasis in the hypothalamus of male adult rats. The present results indicated deleterious consequences of IUGR on hypothalamic pathways involved in pivotal physiological functions. These results provide guidance for future mechanistic studies assessing the role of intrauterine malnutrition in the development of metabolic diseases later in life.
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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...
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International Nuclear Information System (INIS)
Pastorova, B.; Arendarcik, J.
1989-01-01
The effects were studied of exposure to whole body continuous irradiation and of the administration of serum gonadotropin (SG) on the concentration of catecholamines (epinephrine and norepinephrine) in the hypothalamus, epiphysis and adrenal glands of ewes during the anestric period with synchronized estrus. The first group (young barren ewes) and second group (older ewes) were exposed to continuous radiation of 60 Co for five days. The radiation was applied at a rate of 0.020 Gy per hour. After the termination of irradiation the ewes were subjected to hormonal stimulation by fractionated administration of 1500 I.U. SG. The third and fourth experimental groups of ewes were stimulated with 1500 I.U. SG without irradiation. Catecholamines were separated from the tissue supernatants by adsorption chromatography and the catecholamine contents in the eluates were determined spectrofluorometrically. Chronic exposure to gamma radiation and hormonal stimulation with SG reduced the concentration of norepinephrine in the whole hypothalamus of the sheep. A statistically significant decrease (P<0.001) was recorded in the medial and caudal hypothalamus of the adult ewes and in the rostral and caudal hypothalamus regions of the young ewes. A decrease in norepinephrine concentration, statistically significant in the caudal (P<0.01) and medial hypothalamus was recorded in the group of adult ewes after hormonal stimulation with SG without irradiation. The experimental group of young ewes responded to hormonal stimulation by a greater reduction of norepinephrine contents as compared with combined exposure to radiation and hormonal stimulation. It is assumed that the decrease in catecholamine concentration after hormonal stimulation with SG is associated with the increase in the contents of estrogens which act on the adrenergic receptors of the hypothalamus. (author). 4 figs., 21 refs
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Stability Analysis for an Extended Model of the Hypothalamus-Pituitary-Thyroid Axis
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...
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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
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Sone, Hideyuki; Kamiyama, Shin; Higuchi, Mutsumi; Fujino, Kaho; Kubo, Shizuka; Miyazawa, Masami; Shirato, Saya; Hiroi, Yuka; Shiozawa, Kota
2016-07-29
It is known that biotin prevents the development of diabetes by increasing the functions of pancreatic beta-cells and improving insulin sensitivity in the periphery. However, its anti-obesity effects such as anorectic effects remain to be clarified. Acetyl CoA carboxylase (ACC), a biotin-dependent enzyme, has two isoforms (ACC1 and ACC2) and serves to catalyze the reaction of acetyl CoA to malonyl CoA. In the hypothalamus, ACC2 increases the production of malonyl CoA, which acts as a satiety signal. In this study, we investigated whether biotin increases the gene expression of ACC2 in the hypothalamus and suppresses food intake in mice administered excessive biotin. Food intake was significantly decreased by biotin, but plasma regulators of appetite, including glucose, ghrelin, and leptin, were not affected. On the other hand, biotin notably accumulated in the hypothalamus and enhanced ACC2 gene expression there, but it did not change the gene expression of ACC1, malonyl CoA decarboxylase (a malonyl CoA-degrading enzyme), and AMP-activated protein kinase α-2 (an ACC-inhibitory enzyme). These findings strongly suggest that biotin potentiates the suppression of appetite by upregulating ACC2 gene expression in the hypothalamus. This effect of biotin may contribute to the prevention of diabetes by biotin treatment. Copyright © 2016 Elsevier Inc. All rights reserved.
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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.
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Energy Technology Data Exchange (ETDEWEB)
Esquifino, A.I. [Dept. de Bioquimica y Biologia Molecular III, Universidad Complutense, Madrid (Spain); Seara, R.; Fernandez-Rey, E.; Lafuente, A. [Lab. de Toxicologia, Universidad de Vigo, Orense (Spain)
2001-05-01
This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)
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International Nuclear Information System (INIS)
Esquifino, A.I.; Seara, R.; Fernandez-Rey, E.; Lafuente, A.
2001-01-01
This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)
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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
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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.
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Amaral, Maria E; Barbuio, Raquel; Milanski, Marciane; Romanatto, Talita; Barbosa, Helena C; Nadruz, Wilson; Bertolo, Manoel B; Boschero, Antonio C; Saad, Mario J A; Franchini, Kleber G; Velloso, Licio A
2006-07-01
Tumor necrosis factor-alpha (TNF-alpha) is known to participate in the wastage syndrome that accompanies cancer and severe infectious diseases. More recently, a role for TNF-alpha in the pathogenesis of type 2 diabetes mellitus and obesity has been shown. Much of the regulatory action exerted by TNF-alpha upon the control of energy stores depends on its action on the hypothalamus. In this study, we show that TNF-alpha activates canonical pro-inflammatory signal transduction pathways in the hypothalamus of rats. These signaling events lead to the transcriptional activation of an early responsive gene and to the induction of expression of cytokines and a cytokine responsive protein such as interleukin-1beta, interleukin-6, interleukin-10 and suppressor of cytokine signalling-3, respectively. In addition, TNF-alpha induces the expression of neurotransmitters involved in the control of feeding and thermogenesis. Thus, TNF-alpha may act directly in the hypothalamus inducing a pro-inflammatory response and the modulation of expression of neurotransmitters involved in energy homeostasis.
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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.
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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.
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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...
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International Nuclear Information System (INIS)
Lasmoles, Francoise
1974-01-01
The spontaneous and evoked electrical activities of the hypothalamus were studied in 18 adult rabbits chronically implanted with electrodes. The graphic study of the EEG was completed by digital analyses of the signal considered as a random process and processed both by statistical analysis in order to know the distribution function of the signal amplitude and harmonic analysis allowing classification of power density spectra by the calculation of the autocorrelation function and its Fourier transform. Absolute values and percentage of energy distribution were obtained from 0 to 40 Hz for each frequency rate (0.25 Hz) and in various frequency bands (0-3, 3-6, 7-9, 9-15, 15-20, 20-30 and 30-40 Hz). The experimental methods (electrode implantation, data acquisition and processing) are described: 240 sequences corresponding to stable physiological states were analyzed after analogical-digital conversion (sampling rate: 10 ms, period of integration: 20 s). Whatever the state of vigilance, the hypothalamus had a fairly homogeneous function different from the spontaneous electrical activity of the cortex. The signal characteristics both in amplitude and frequency allowed to distinguish the hypothalamic areas studied (supra-optic area, mammillary body, postero-lateral hypothalamus). The results were reproducible and verified the information supplied by visual examination of the EEG. Following light stimulus, the evoked potentials were collected in the hypothalamus; there should therefore be convergence, yet since the answers are unstable and long latent, the neuronal paths followed by the impulse must not be direct. (author) [fr
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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
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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)
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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.
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Leptin-dependent neuronal NO signaling in the preoptic hypothalamus facilitates reproduction.
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.
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Follin, Cecilia; Erfurth, Eva Marie
2016-09-01
Survival rates of childhood cancer have improved markedly, and today more than 80 % of those diagnosed with a pediatric malignancy will become 5-year survivors. Nevertheless, survivors exposed to cranial radiotherapy (CRT) are at particularly high risk for long-term morbidity, such as endocrine insufficiencies, metabolic complications, and cardiovascular morbidity. Deficiencies of one or more anterior pituitary hormones have been described following therapeutic CRT for primary brain tumors, nasopharyngeal tumors, and following prophylactic CRT for childhood acute lymphoblastic leukemia (ALL). Studies have consistently shown a strong correlation between the total radiation dose and the development of pituitary deficits. Further, age at treatment and also time since treatment has strong implications on pituitary hormone deficiencies. There is evidence that the hypothalamus is more radiosensitive than the pituitary and is damaged by lower doses of CRT. With doses of CRT hypothalamus and this usually causes isolated GH deficiency (GHD). Higher doses (>50 Gy) may produce direct anterior pituitary damage, which contributes to multiple pituitary deficiencies. The large group of ALL survivors treated with CRT in the 70-80-ties has now reached adulthood, and these survivors were treated mainly with 24 Gy, and the vast majority of these patients suffer from GHD. Further, after long-term follow-up, insufficiencies in prolactin (PRL) and thyroid stimulating hormone (TSH) have also been reported and a proportion of these patients were also adrenocoticotrophic hormone (ACTH) deficient. CRT to the hypothalamus causes neuroendocrine dysfunction, which means that the choice of GH test is crucial for the diagnosis of GHD.
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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)
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A Role for Glucocorticoids in Stress-Impaired Reproduction: Beyond the Hypothalamus and Pituitary
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...
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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.
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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)
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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)
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Regenerating the human heart: direct reprogramming strategies and their current limitations.
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.
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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
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The Development of the circadian heart rate rhytm (CDR) in Asian infants
Stanislaus Sandarupa, Drs., M.A., Ph.D.
2011-01-01
Although the human fetus can follow the maternal circadian thythm, the enterained expression of the circadian clock, based in the suprachiasmatic nucleus (SCN) of the hypothalamus awaits postnatal maturation of the retinal hypothalamic tract, and melatonin neurotransmission. Objective: To test the hypothesis that term-born Asian Infants, at reduced risk to die of Sudden Infant Death Syndrome (SIDS) exhibit a circadian heat rate thythm (CHR) at a later age than non-Asian term infants.
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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.
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Directory of Open Access Journals (Sweden)
Min Zheng
Full Text Available BACKGROUND: The paraventricular nucleus (PVN of the hypothalamus plays an important role in the progression of heart failure (HF. We investigated whether cyclooxygenase-2 (COX-2 inhibition in the PVN attenuates the activities of sympathetic nervous system (SNS and renin-angiotensin system (RAS in rats with adriamycin-induced heart failure. METHODOLOGY/PRINCIPAL FINDING: Heart failure was induced by intraperitoneal injection of adriamycin over a period of 2 weeks (cumulative dose of 15 mg/kg. On day 19, rats received intragastric administration daily with either COX-2 inhibitor celecoxib (CLB or normal saline. Treatment with CLB reduced mortality and attenuated both myocardial atrophy and pulmonary congestion in HF rats. Compared with the HF rats, ventricle to body weight (VW/BW and lung to body weight (LW/BW ratios, heart rate (HR, left ventricular end-diastolic pressure (LVEDP, left ventricular peak systolic pressure (LVPSP and maximum rate of change in left ventricular pressure (LV±dp/dtmax were improved in HF+CLB rats. Angiotensin II (ANG II, norepinephrine (NE, COX-2 and glutamate (Glu in the PVN were increased in HF rats. HF rats had higher levels of ANG II and NE in plasma, higher level of ANG II in myocardium, and lower levels of ANP in plasma and myocardium. Treatment with CLB attenuated these HF-induced changes. HF rats had more COX-2-positive neurons and more corticotropin releasing hormone (CRH positive neurons in the PVN than did control rats. Treatment with CLB decreased COX-2-positive neurons and CRH positive neurons in the PVN of HF rats. CONCLUSIONS: These results suggest that PVN COX-2 may be an intermediary step for PVN neuronal activation and excitatory neurotransmitter release, which further contributes to sympathoexcitation and RAS activation in adriamycin-induced heart failure. Treatment with COX-2 inhibitor attenuates sympathoexcitation and RAS activation in adriamycin-induced heart failure.
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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.)
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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.
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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.
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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
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HE4 Serum Levels Are Associated with Heart Failure Severity in Patients With Chronic Heart Failure
Piek, Arnold; Meijers, Wouter C.; Schroten, Nicolas F.; Gansevoort, Ron T.; de Boer, Rudolf A.; Sillje, Herman H. W.
Background: The novel biomarker human epididymis protein 4 (HE4) shows prognostic value in acute heart failure (HF) patients. We measured HE4 levels in patients with chronic heart failure (CHF) and correlated them to HF severity, kidney function, and HF biomarkers, and determined its predictive
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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...
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Schmidt, T A; Allen, P D; Colucci, W S; Marsh, J D; Kjeldsen, K
1993-01-01
Speculations about development of tolerance to the inotropic effect of digitalis have been engendered since studies in various in vitro systems and tissues not representative of the heart have shown up-regulation of sodium potassium adenosine triphosphatase (Na,K-ATPase) when exposed to digitalis. Moreover the digitalis receptor (i.e., Na,K-ATPase) concentration in the normal, vital human left ventricle has not been previously determined. On this basis, digitalis receptor concentration was quantified in the left ventricle of explanted hearts from subjects without heart disease and from patients with end-stage heart failure who had received digitalis therapy. This was performed using vanadate-facilitated 3H-ouabain binding to intact tissue samples giving values of 728 +/- 58 (n = 5) and 467 +/- 55 pmol/g wet weight (n = 6) (mean +/- SEM) (p digitalization was associated with occupancy of digitalis receptors in the failing human heart of 24% (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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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.
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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.
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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
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Cittadini, A; Longobardi, S; Fazio, S; Saccà, L
1999-01-01
Until a few years ago, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) were considered essential only to the control of linear growth, glucose homeostasis, and for the maintenance of skeletal muscle mass. A large body of evidence recently coming from animal and human studies has unequivocally proven that the heart is a target organ for the GH/IGF-1 axis. Specifically GH exerts both direct and indirect cardiovascular actions. Among the direct effects, the ability of GH to trigger cardiac tissue growth plays a pivotal role. Another direct effect is to augment cardiac contractility, independent of myocardial growth. Direct effects of GH also include the improvement of myocardial energetics and mechanical efficiency. Indirect effects of GH on the heart include decreased peripheral vascular resistance (PVR), expansion of blood volume, increased glomerular filtration rate, enhanced respiratory activity, increased skeletal muscle performance, and psychological well-being. Among them, the most consistently found is the decrease of PVR. GH may also raise preload through its sodium-retaining action and its interference with the hormonal system that regulates water and electrolyte metabolism. Particularly important is the effect of GH on skeletal muscle mass and performance. Taking into account that heart failure is characterized by left ventricular dilation, reduced cardiac contractility, and increase of wall stress and peripheral vascular resistance, GH may be beneficial for treatment of heart failure. Animal studies and preliminary human trials have confirmed the validity of the GH approach to the treatment of heart failure. Larger placebo-controlled human studies represent the main focus of future investigations.
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Lee, Jaemeun; Kim, Kyungchan; Yu, Seong-Woon; Kim, Eun-Kyoung
2016-03-08
Insulin plays diverse roles in the brain. Although insulin produced by pancreatic β-cells that crosses the blood-brain barrier is a major source of brain insulin, recent studies suggest that insulin is also produced locally within the brain. However, the mechanisms underlying the production of brain-derived insulin (BDI) are not yet known. Here, we examined the effect of Wnt3a on BDI production in a hypothalamic cell line and hypothalamic tissue. In N39 hypothalamic cells, Wnt3a treatment significantly increased the expression of the Ins2 gene, which encodes the insulin isoform predominant in the mouse brain, by activating Wnt/β-catenin signaling. The concentration of insulin was higher in culture medium of Wnt3a-treated cells than in that of untreated cells. Interestingly, neurogenic differentiation 1 (NeuroD1), a target of Wnt/β-catenin signaling and one of transcription factors for insulin, was also induced by Wnt3a treatment in a time- and dose-dependent manner. In addition, the treatment of BIO, a GSK3 inhibitor, also increased the expression of Ins2 and NeuroD1. Knockdown of NeuroD1 by lentiviral shRNAs reduced the basal expression of Ins2 and suppressed Wnt3a-induced Ins2 expression. To confirm the Wnt3a-induced increase in Ins2 expression in vivo, Wnt3a was injected into the hypothalamus of mice. Wnt3a increased the expression of NeuroD1 and Ins2 in the hypothalamus in a manner similar to that observed in vitro. Taken together, these results suggest that BDI production is regulated by the Wnt/β-catenin/NeuroD1 pathway in the hypothalamus. Our findings will help to unravel the regulation of BDI production in the hypothalamus.
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Tu, Wei-Lin; Cheng, Chuen-Yu; Wang, Shih-Han; Tang, Pin-Chi; Chen, Chih-Feng; Chen, Hsin-Hsin; Lee, Yen-Pai; Chen, Shuen-Ei; Huang, San-Yuan
2016-02-01
Acute heat stress severely impacts poultry production. The hypothalamus acts as a crucial center to regulate body temperature, detect temperature changes, and modulate the autonomic nervous system and endocrine loop for heat retention and dissipation. The purpose of this study was to investigate global gene expression in the hypothalamus of broiler-type B strain Taiwan country chickens after acute heat stress. Twelve 30-week-old hens were allocated to four groups. Three heat-stressed groups were subjected to acute heat stress at 38 °C for 2 hours without recovery (H2R0), with 2 hours of recovery (H2R2), and with 6 hours of recovery (H2R6). The control hens were maintained at 25 °C. At the end, hypothalamus samples were collected for gene expression analysis. The results showed that 24, 11, and 25 genes were upregulated and 41, 15, and 42 genes were downregulated in H2R0, H2R2, and H2R6 treatments, respectively. The expressions of gonadotropin-releasing hormone 1 (GNRH1), heat shock 27-kDa protein 1 (HSPB1), neuropeptide Y (NPY), and heat shock protein 25 (HSP25) were upregulated at all recovery times after heat exposure. Conversely, the expression of TPH2 was downregulated at all recovery times. A gene ontology analysis showed that most of the differentially expressed genes were involved in biological processes including cellular processes, metabolic processes, localization, multicellular organismal processes, developmental processes, and biological regulation. A functional annotation analysis showed that the differentially expressed genes were related to the gene networks of responses to stress and reproductive functions. These differentially expressed genes might be essential and unique key factors in the heat stress response of the hypothalamus in chickens. Copyright © 2016 Elsevier Inc. All rights reserved.
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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.
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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...
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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.
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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
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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.
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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)
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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 ...
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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
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Localisation of SCN10A gene product Na(v)1.8 and novel pain-related ion channels in human heart.
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.
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Genetics of Valvular Heart Disease
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
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Tan, Yusuf Ziya; Ozdemir, Semra; Temiz, Ahmet; Celik, Fatmanur
2015-05-01
The positive changes in human behavior caused by relaxing music demonstrate the psychological effect of music on human body. A meta-analytical study has shown that relaxing music affects blood pressure and heart rate in coronary heart patients and cancer patients. The aim of our study is to research whether there is a significant effect on heart rate and heart rate variability due to listening to relaxing music during ECG GATED MPS imaging under gamma camera. The music group (n = 50 patients) could choose from 15 different musical types including folk music (no lyric). The other 50 patients were placed in a "no music group" and did not get headphones or any music. There was a statistically significant reduction in the heart rate of patients in the music group compared to those in the control group. Relaxing music provides great benefits to both patient and clinician. There is close relationship between relaxing music and health procedure, can use every area of the health noninvasiv, safe, cheap and is a method don't have side effect. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Machines versus medication for biventricular heart failure: focus on the total artificial heart.
Arabia, Francisco A; Moriguchi, Jaime D
2014-09-01
The medical/surgical management of advanced heart failure has evolved rapidly over the last few decades. With better understanding of heart failure pathophysiology, new pharmacological agents have been introduced that have resulted in improvements in survival. For those patients that fail to improve, mechanical circulatory support with left ventricular assist devices and total artificial hearts (TAHs) have served as a beneficial bridge to transplantation. The TAH has continued to play a significant role as a bridge to transplantation in patients with biventricular failure and more selected indications that could not be completely helped with left ventricular assist devices. Improved survival with the TAH has resulted in more patients benefiting from this technology. Improvements will eventually lead to a totally implantable device that will permanently replace the failing human heart.
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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.
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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.
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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
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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.
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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
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Human technology after cardiac epigenesis. Artificial heart versus cardiac transplantation.
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.
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Flavell, D M; Wells, T; Wells, S E; Carmignac, D F; Thomas, G B; Robinson, I C
1996-01-01
Expression of human growth hormone (hGH) was targeted to growth hormone-releasing (GRF) neurons in the hypothalamus of transgenic rats. This induced dominant dwarfism by local feedback inhibition of GRF. One line, bearing a single copy of a GRF-hGH transgene, has been characterized in detail, and has been termed Tgr (for Transgenic growth-retarded). hGH was detected by immunocytochemistry in the brain, restricted to the median eminence of the hypothalamus. Low levels were also detected in the...
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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...
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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.
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Salgado-Delgado, Roberto; Nadia, Saderi; Angeles-Castellanos, M; Buijs, Ruud M; Escobar, Carolina
2010-12-01
Internal synchrony among external cycles and internal oscillators allows adaptation of physiology to cyclic demands for homeostasis. Night work and shift work lead to a disrupted phase relationship between external time cues and internal rhythms, also losing internal coherence among oscillations. This process results in internal desynchrony (ID) in which behavioral, hormonal, and metabolic variables cycle out of phase. It is still not clear whether ID originates at a peripheral or at a central level. In order to determine the possible role of hypothalamic oscillators in ID, we explored with a rat model of "night work" daily rhythms of activity and clock gene expression in the hypothalamus. This study provides evidence that wakefulness and activity during the normal resting phase lead to a shift in the diurnal rhythms of c-Fos and induce a rhythm of PER1 in the arcuate and dorsomedial nucleus of the hypothalamus, both associated with metabolism and regulation of the sleep/wake cycle. Moreover, the number of orexin (ORX)-positive neurons and c-Fos in the perifornical area increased during the working period, suggesting a relevant switch of activity in this brain region induced by the scheduled activity; however, the colocalization of c-Fos in ORX-positive cells was not increased. In contrast, the suprachiasmatic nucleus and the paraventricular nucleus remained locked to the light/dark cycle, resulting in ID in the hypothalamus. Present data suggest that ID occurs already at the level of the first output projections from the SCN, relaying nuclei that transmit temporal signals to other brain areas and to the periphery.
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Directory of Open Access Journals (Sweden)
Hong-Zai Guan
2017-01-01
Full Text Available Alpha-melanocyte-stimulating hormone (α-MSH is processed from proopiomelanocortin (POMC and acts on the melanocortin receptors, MC3 and MC4. α-MSH plays a key role in energy homeostasis. In the present study, to shed light on the mechanisms by which α-MSH exerts its anorectic effects, extracellular neuronal activity was recorded in the hypothalamus and the dorsal vagal complex (DVC of anesthetized rats. We examined the impact of α-MSH on glucose-sensing neurons and gastric distension (GD sensitive neurons. In the lateral hypothalamus (LHA, α-MSH inhibited 75.0% of the glucose-inhibited (GI neurons. In the ventromedial nucleus (VMN, most glucose-sensitive neurons were glucose-excited (GE neurons, which were mainly activated by α-MSH. In the paraventricular nucleus (PVN, α-MSH suppressed the majority of GI neurons and excited most GE neurons. In the DVC, among the 20 GI neurons examined for a response to α-MSH, 1 was activated, 16 were depressed, and 3 failed to respond. Nineteen of 24 GE neurons were activated by α-MSH administration. Additionally, among the 42 DVC neurons examined for responses to GD, 23 were excited (GD-EXC and 19 were inhibited (GD-INH. Fifteen of 20 GD-EXC neurons were excited, whereas 11 out of 14 GD-INH neurons were suppressed by α-MSH. All these responses were abolished by pretreatment with the MC3/4R antagonist, SHU9119. In conclusion, the activity of glucose-sensitive neurons and GD-sensitive neurons in the hypothalamus and DVC can be modulated by α-MSH.
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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
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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.
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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.
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Human engineered heart tissue as a model system for drug testing.
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.
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Babichev, V N; Ignatkov, V Ia
1978-01-01
Experiments were conducted on rats; estradiol brought to the arcuate region of the hypothalamus by means of microionophoresis led to the increase of the region of the hypothalamus by means of microionophoresis led to the increase of the blood luteinizing hormone (LH) level during the following stages of the estral cycle-diestrus 1, diestrus 2, and the first half day of the proestrus; as to the second half of the proestrus day--estradiol decreased its level. Changes in the LH level in the hypophysis under the influence of the microionophoretic introduction of estradiol into the arcuate region occurred during the second half of the day of diestrus 2 (reduction), and during the estrus (elevation). In the majority of cases a rise of the blood level was combined with the neuron activation in the arcuate region under the influence of estradiol.
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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.
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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
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Genome-wide analysis of DHEA- and DHT-induced gene expression in mouse hypothalamus and hippocampus.
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
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International Nuclear Information System (INIS)
Fedorov, N.A.; Likhovetskaya, Z.M.; Kurbanova, G.N.; Prigozhina, T.A.; L'vovich, A.I.
1982-01-01
Colony formation capability of serum from animals with destructed nuclei of the posterior hypothalamus was studied in lethally irradiated mice. Male-rats of Wistar line and hybrid mice (CBA x C57 BL) were used in the experiments. The serum from rats with destructed nuclei of the posterior hypothalamus was injected simultaneously with bone marrow transplantation into lethally irradiated mice. The number of macrocolonies in the spleen was counted on the 9th day. It was ascertained that the serum from rats with destructed nuclei of the posterior hypothalamus caused an increase of the number of macroscopically visible colonies in the spleen of lethally irradiated mice. The determination of hemopoetic types of colonies showed that the effect of the serum from those animals caused an increase of the number of granulocytic-type colonies. The initiation of colony stimulating and leukopoetic activity in the blood of animals after the destruction of mammillary body nuclei and posterior hypothalamic nucleus attested, according to the authors point of view, that humoral mediators (humoral mediator) could participated in the mechanism of hypothalamus effect on leulopoiesis
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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.
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Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia.
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.
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Hemodynamic simulation of the heart using a 2D model and MR data
DEFF Research Database (Denmark)
Adeler, Pernille Thorup
2002-01-01
Computational models of the blood flow in the heart are a useful tool for studying the functioning of the heart. The purpose of this thesis is to achieve a better understanding of hemodynamics of the normal and diseased hearts through the use of a computational model and magnetic resonance (MR......) data. We present a 2D computational model of the blood flow in the left side of the heart. The work is based on Peskin and McQueen's 2D model dimensioned to data on the dog heart, which we improve and adjust using physiological knowledge and MR velocity data to achieve a model of the human heart...... by letting the apical region be inactive. In both of these cases the simulation results compare well with clinically observed data on dogs and humans. We present Peskin and McQueen's 3D model of the entire human heart and the nearby great vessels. We perform a simulation with the model, where we adjust...
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International Nuclear Information System (INIS)
Zhao Hui; Chen Zhixi; Chen Jinyan; Li Zhiqiang; He Zanhou
2007-01-01
Objective: To investigate the effects of qiangji jianli yin on hypothalamus CRH contents and plasma ACTH, Cortisol levels in rat models with kidney-yang deficiency syndrome. Methods: Rat models of kidney-yang deficiency syndrome were prepared with intramuscular injuection of hydroeortisone and divided into 5 groups: (1) no further treatment, n=13 (2) treated with high dosage d qiangji jiandi yin, n=12 (3) treated with medium dosage of qiangji jianli yin, n=12 (4) treated with low dosage of qiangji jianli yin n=12, (5) treated with yougui wan, n=12. Ten rats injuected with intramuscular distilled water only served as controls. The animals were sacrificied 14 days later and the hypothalamus CRH contents as well as plasma AOM and cortisol levels were measured with RIA. The thymus gland weight index and the adrenal gland index were calculated. Results: (1) The hypothalamus CRH contents and plasma ACTH, cortisol levels were significantly lower (P<0.01) in the rat models of kidney-yang deficiency syndrome without any treatment thas those in controls rats; the thymus and adrenal gland weight index were significantly decreased too (P <0.01). The CRH conteats and ACTH, cortisol levels in all the three group of rat model treated with different dosage of qiangji jianli yin were significantly higher than those in the models without any treatment (P<0.05-0.01). Conclusion: In rat models of kidney-yang deficiency syndrome, dysfunction of the hypothalamus-pituitary-adrenal axis (HPAA) led to decreased secretion of related hormones. The HPAA function might be partially restored with administation of qiangji jianli yin. (authors)
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Sound Heart: Spiritual Nursing Care Model from Religious Viewpoint.
Asadzandi, Minoo
2017-12-01
Different methods of epistemology create different philosophical views. None of the nursing theories have employed the revelational epistemology and the philosophical views of Abrahamic religions. According to Abrahamic religions, the universe and human being have been created based on God's affection. Human being should deserve the position of God's representative on earth after achieving all ethical merits. Humans have willpower to shape their destiny by choosing manner of their relationship with God, people, themselves and the whole universe. They can adopt the right behavior by giving a divine color to their thoughts and intentions and thus attain peace and serenity in their heart. Health means having a sound heart (calm spirit with a sense of hope and love, security and happiness) that is achievable through faith and piety. Moral vices lead to diseases. Human beings are able to purge their inside (heart) through establishing a relationship with God and then take actions to reform the outside world. The worlds are run by God's will based on prudence and mercy. All events happen with God's authorization, and human beings have to respond to them. Nurses should try to recognize the patient's spiritual response to illness that can appear as symptoms of an unsound heart (fear, sadness, disappointment, anger, jealousy, cruelty, grudge, suspicion, etc.) due to the pains caused by illness and then alleviate the patient's suffering by appropriate approaches. Nurses help the patient to achieve the sound heart by hope in divine mercy and love, and they help the patient see good in any evil and relieve their fear and sadness by viewing their illness positively and then attain the status of calm, satisfaction, peace and serenity in their heart and being content with the divine fate. By invitation to religious morality, the model leads the patients to spiritual health.
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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.
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Control of an air pressure actuated disposable bioreactor for cultivating heart valves
Beelen, M.J.; Neerincx, P.E.; Molengraft, van de M.J.G.
2011-01-01
A disposable injection molded bioreactor for growing tissue-engineered heart valves is controlled to mimic the physiological heart cycle. Tissue-engineered heart valves, cultured from human stem cells, are a possible alternative for replacing failing aortic heart valves, where nowadays biological
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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
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Li, Hong-mian; Liang, Zi-qian; Luo, Zuo-jie
2003-06-01
To investigate the postburn dynamic changes in the hypothalamus-pituitary-adrenal hormones in severely burned patients. Fifty burn patients were enrolled in the study. The plasma contents of total GC (cortisol), ACTH and aldosterone (ALDO) and urinary contents of 17-OHO and 17-KS were determined with radio-immunological assay (RIA) method after burn injury to compare with the normal values which were well established clinically. The postburn plasma and urinary contents of the above indices were increased evidently with two peak values in shock and infectious stages, whilst the majority of he indices were lower than the normal values after 6 postburn weeks (PBWs). The values of these hormones were the lowest in dying patients. On the other hand, the values approached normal levels in those patients whose burn wounds were healing. Increases of the plasma and urinary levels of hypothalamus-pituitary -adrenal hormones in severely burned patients were constantly seen. Burn shock and infection seemed to be the two major factors in inducing postburn stress reaction in burn victims. Abrupt decrease of the hormone levels in plasma and or urine indicated adrenal failure predicting a poor prognosis of the burn patients.
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Revealing the cerebello-ponto-hypothalamic pathway in the human brain.
Kamali, Arash; Karbasian, Niloofar; Rabiei, Pejman; Cano, Andres; Riascos, Roy F; Tandon, Nitin; Arevalo, Octavio; Ocasio, Laura; Younes, Kyan; Khayat-Khoei, Mahsa; Mirbagheri, Saeedeh; Hasan, Khader M
2018-04-16
The cerebellum is shown to be involved in some limbic functions of the human brain such as emotion and affect. The major connection of the cerebellum with the limbic system is known to be through the cerebello-hypothalamic pathways. The consensus is that the projections from the cerebellar nuclei to the limbic system, and particularly the hypothalamus, or from the hypothalamus to the cerebellar nuclei, are through multisynaptic pathways in the bulbar reticular formation. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. Diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of the cerebello-ponto-hypothalamic (CPH) pathway. This study aimed to investigate the utility of high-spatial-resolution diffusion tensor tractography for mapping the trajectory of the CPH tract in the human brain. Fifteen healthy adults were studied. We delineated, for the first time, the detailed trajectory of the CPH tract of the human brain in fifteen normal adult subjects using high-spatial-resolution diffusion tensor tractography. We further revealed the close relationship of the CPH tract with the optic tract, temporo-pontine tract, amygdalofugal tract and the fornix in the human brain. Copyright © 2018. Published by Elsevier B.V.
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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
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Energy Technology Data Exchange (ETDEWEB)
Rainov, A; Boschkov, B; Nikolov, N [Meditsinska Akademiya, Sofia (Bulgaria)
1980-04-01
The dynamics and the distribution of /sup 3/H-dopamine in the serum and tissues of the heart, hypothalamus, cerebral cortex and adrenal glands were studied in 60 Wistar rats. The rats received intravenously 7.4 MBq /sup 3/H-dopamine/kg body weight 10 minutes before they were killed. The experimental animals were subjected to endotoxic shock by injecting them with 2 mg endotoxin of E. coli O 111:B/sub 4//kg body weight, and killed after 5, 10, 15, 20 and 30 min, respectively. Maximum increase of the tritium activity in the organs investigated was observed 20 min after the shock.
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Bielau, Hendrik; Brisch, Ralf; Gos, Tomasz; Dobrowolny, Henrik; Baumann, Bruno; Mawrin, Christian; Kreutzmann, Peter; Bernstein, Hans-Gert; Bogerts, Bernhard; Steiner, Johann
2013-11-01
In recent years, the hypothalamus, amygdala and hippocampus have attracted increased interest with regard to the effects of stress on neurobiological systems in individuals with depression and suicidal behaviour. A large body of evidence indicates that these subcortical regions are involved in the pathogenetic mechanisms of mood disorders and suicide. The current neuroimaging techniques inadequately resolve the structural components of small and complex brain structures. In previous studies, our group was able to demonstrate a structural and neuronal pathology in mood disorders. However, the impact of suicide remains unclear. In the current study we used volumetric measurements of serial postmortem sections with combined Nissl-myelin staining to investigate the hypothalamus, amygdala and hippocampus in suicide victims with mood disorders (n = 11), non-suicidal mood disorder patients (n = 9) and control subjects (n = 23). Comparisons between the groups by using an ANCOVA showed a significant overall difference for the hypothalamus (p = 0.001) with reduced volumes in non-suicidal patients compared to suicide victims (p = 0.018) and controls (p = 0.006). To our surprise, the volumes between the suicide victims and controls did not differ significantly. For the amygdala and hippocampus no volume changes between the groups could be detected (all p values were n. s.). In conclusion our data suggest a structural hypothalamic pathology in non-suicidal mood disorder patients. The detected differences between suicidal and non-suicidal patients suggest that suicidal performances might be related to the degree of structural deficits.
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Energy Technology Data Exchange (ETDEWEB)
Walaas, I; Fonnum, F
1980-01-01
The effects of bilateral transection of the fornix bundle on the high affinity uptake of glutamate and on the amino acid content in several nuclei of rat forebrain and hypothalamus were studied in order to investigate the possible role of glutamate as a transmitter of these fibres. This lesion decreased the high affinity uptake of L-glutamate by 60 to 70% in the mammillary body and lateral septum, and by 40 to 50% in the anterior diagonal band nucleus, the bed nucleus of the stria terminalis, the mediobasal hypothalamus and the nucleus accumbens. The content of endogenous glutamate in samples dissected from freeze-dried tissue also decreased significantly in these regions. Endogenous aspartate was slightly decreased in the anterior diagonal band nucleus and the mammillary body, but unchanged in the other regions. No significant changes were seen in the levels of serine, ..gamma..-aminobutyric acid, glutamine and taurine, except for an increase in glutamine and taurine in the bed nucleus of the stria terminalis. The high affinity uptake of ..gamma..-aminobutyric acid, tested in the bed nucleus of the stria terminalis, the mediobasal hypothalamus and the mammillary body, was unchanged after the lesion. The results indicate that allocortical efferents innervating subcortial nuclei through the fornix might use glutamate as a transmitter. The study further supports the concept that glutamate plays an important role as transmitter of several different corticofugal fibre systems in mammalian brain.
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Radiation-induced heart injury. Radiopathological study
Energy Technology Data Exchange (ETDEWEB)
Suzuki, Y; Niibe, H [Gunma Univ., Maebashi (Japan). School of Medicine
1975-11-01
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 interval 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.
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DeAtley, Kasey L; Colgrave, Michelle L; Cánovas, Angela; Wijffels, Gene; Ashley, Ryan L; Silver, Gail A; Rincon, Gonzalo; Medrano, Juan F; Islas-Trejo, Alma; Fortes, Marina R S; Reverter, Antonio; Porto-Neto, Laercio; Lehnert, Sigrid A; Thomas, Milton G
2018-05-04
Puberty in cattle is regulated by an endocrine axis, which includes a complex milieu of neuropeptides in the hypothalamus and pituitary gland. The neuropeptidome of hypothalamic-pituitary gland tissue of pre- (PRE) and postpubertal (POST) Bos indicus-influenced heifers was characterized, followed by quantitative analysis of 51 fertility-related neuropeptides in these tissues. Comparison of peptide abundances with gene expression levels allowed assessment of post-transcriptional peptide processing. On the basis of classical cleavage, 124 mature neuropeptides from 35 precursor proteins were detected in hypothalamus and pituitary gland tissues of three PRE and three POST Brangus heifers. An additional 19 peptides (cerebellins, PEN peptides) previously reported as neuropeptides that did not follow classical cleavage were also identified. In the pre-pubertal hypothalamus, a greater diversity of neuropeptides (25.8%) was identified relative to post-pubertal heifers, while in the pituitary gland, 38.6% more neuropeptides were detected in the post-pubertal heifers. Neuro-tissues of PRE and POST heifers revealed abundance differences ( p pituitary before and after puberty.
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Functional Neuroanatomy of Human Cortex Cerebri in Relation to Wanting Sex and Having It
Georgiadis, Janniko R.
Neuroanatomical textbooks typically restrict the central nervous system control of sexual responsiveness to the hypothalamus, brainstem and spinal cord. However, for all its primitive functions human sex is surprisingly complex and versatile. This review aims to extend the neuroanatomy of sexual
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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.
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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.
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Leite, Marlon R; Cechella, José L; Pinton, Simone; Nogueira, Cristina W; Zeni, Gilson
2016-09-01
Aging is a process characterized by deterioration of the homeostasis of various physiological systems; although being a process under influence of multiple factors, the mechanisms involved in aging are not well understood. Here we investigated the effect of a (PhSe)2-supplemented diet (1ppm, 4weeks) and swimming exercise (1% of body weight, 20min per day, 4weeks) on proteins related to glial cells activation, apoptosis and neuroprotection in the hypothalamus of old male Wistar rats (27month-old). Old rats had activation of astrocytes and microglia which was demonstrated by the increase in the levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba-1) in hypothalamus. A decrease of B-cell lymphoma 2 (Bcl-2) and procaspase-3 levels as well as an increase of the cleaved PARP/full length PARP ratio (poly (ADP-ribose) polymerase, PARP) and the pJNK/JNK ratio (c-Jun N-terminal kinase, JNK) were observed. The levels of mature brain-derived neurotrophic factor (mBDNF), the pAkt/Akt ratio (also known as protein kinase B) and NeuN (neuronal nuclei), a neuron marker, were decreased in the hypothalamus of old rats. Old rats that received a (PhSe)2-supplemented diet and performed swimming exercise had the hypothalamic levels of Iba-1 and GFAP decreased. The combined treatment also increased the levels of Bcl-2 and procaspase-3 and decreased the ratios of cleaved PARP/full length PARP and pJNK/JNK in old rats. The levels of mBDNF and NeuN, but not the pAkt/Akt ratio, were increased by combined treatment. In conclusion, a (PhSe)2-supplemented diet and swimming exercise promoted neuroprotection in the hypothalamus of old rats, reducing apoptosis and glial cell activation. Copyright © 2016 Elsevier Inc. All rights reserved.
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Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.
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.
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Directory of Open Access Journals (Sweden)
Kamran Rakhshan
2015-10-01
Full Text Available Exposure to stress leads to physiological changes called “stress response” which are the result ofthe changes in the adrenomedullary hormone system, hypothalamus-pituitary-adrenal (HPA and sympatheticnervous system (SNS activity. In the present study, the effects of chronic physical and psychological stressand also the role of sympathetic system effects in stress on ischemia/reperfusion (I/R injuries have beenstudied in isolated rat heart. Rat heart was isolated and subjected to 30 min regional ischemia and 120 minreperfusion. The daily stress was induced for one week prior to I/R induction. Sympathectomy was donechemically by injection of hydroxyl-dopamine prior to stress induction. There were no significant changes inheart rate and Coronary Flow between groups. Left ventricular developed pressure (LVDP and rate productpressure (RPP in both physical and psychological stress groups decreased significantly compared to those incontrol group (Pgroups. Infarct size significantly increased in both physical and psychological stress groups and control group(Pas compared with stress groups (Ppsychological stress prior to ischemia/reperfusion causes enhancement of myocardial injuries and it seemsthat increased sympathetic activity in response to stress is responsible for these adverse effects of stress onischemic/reperfused heart.
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Zhou, Dongsheng; Zhuo, Yong; Che, Lianqiang; Lin, Yan; Fang, Zhengfeng; Wu, De
2014-07-01
People on a diet to lose weight may be at risk of reproductive failure. To investigate the effects of nutrient restriction on reproductive function and the underlying mechanism, changes of reproductive traits, hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis were examined in postpubertal gilts at anestrus induced by nutrient restriction. Gilts having experienced two estrus cycles were fed a normal (CON, 2.86 kg/d) or nutrient restricted (NR, 1 kg/d) food regimens to expect anestrus. NR gilts experienced another three estrus cycles, but did not express estrus symptoms at the anticipated fourth estrus. Blood samples were collected at 5 days' interval for consecutive three times for measurement of hormone concentrations at the 23th day of the fourth estrus cycle. Individual progesterone concentrations of NR gilts from three consecutive blood samples were below 1.0 ng/mL versus 2.0 ng/mL in CON gilts, which was considered anestrus. NR gilts had impaired development of reproductive tract characterized by absence of large follicles (diameter ≥ 6 mm), decreased number of corepus lutea and atrophy of uterus and ovary tissues. Circulating concentrations of IGF-I, kisspeptin, estradiol, progesterone and leptin were significantly lower in NR gilts than that in CON gilts. Nutrient restriction down-regulated gene expressions of kiss-1, G-protein coupled protein 54, gonadotropin-releasing hormone, estrogen receptor α, progesterone receptor, leptin receptor, follicle-stimulating hormone and luteinizing hormone and insulin-like growth factor I in hypothalamus-pituitary-gonadal axis of gilts. Collectively, nutrient restriction resulted in impairment of reproductive function and changes of hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis, which shed light on the underlying mechanism by which nutrient restriction influenced reproductive function.
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Iodine-131 metaiodobenzylguanidine intra- and extravesicular accumulation in the rat heart
International Nuclear Information System (INIS)
Nakajo, M.; Shimabukuro, K.; Yoshimura, H.; Yonekura, R.; Nakabeppu, Y.; Tanoue, P.; Shinohara, S.
1986-01-01
In order to establish the appropriate time for [ 123 I]MIBG human myocardial imaging to assess the adrenergic nerve activity, the time courses of metaiodobenzylguanidine (MIBG) intra- and extravesicular accumulation in the rat heart were estimated by using [ 131 I]MIBG and reserpine. In the heart, the intravesicular accumulation was relatively constant, while the extravesicular accumulation decreased rapidly from 5 min to 6 hr. The intravesicular percentage of the total cardiac tissue concentration reached a plateau value of 50% at 4 hr after i.v. injection of [ 131 I]MIBG. In the spleen, similar time courses were observed as those in the heart, both of these organs being richly innervated by adrenergic nerves. Along with the time activity difference previously observed in the human hearts, these results suggest that at 4 hr post i.v. injection, [ 123 I]MIBG myocardial imaging will best express the neuronal accumulation of the tracer and may be useful for the assessment of adrenergic function in various pathological conditions of the human heart
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Turenius, Christine I; Charles, Jonathan R; Tsai, Donna H; Ebersole, Priscilla L; Htut, Myat H; Ngo, Phuong T; Lara, Raul N; Stanley, B Glenn
2009-08-04
The lateral hypothalamus (LH) is a site of integration for control mechanisms of feeding behavior as it has extensive reciprocal connections with multiple intrahypothalamic and extrahypothalamic brain areas. Evidence suggests that blockade of ionotropric gamma-aminobutyric acid (GABA) receptors in the LH elicits eating in satiated rats. To determine whether this GABA(A) receptor antagonist effect is specific to the LH, the antagonist picrotoxin was injected into one of six nearby sites and food intake was measured. Picrotoxin at 133 pmol elicited eating in the LH, but not in surrounding sites (thalamus, lateral preoptic area, ventral tegmental area, dorsomedial hypothalamus, and entopeduncular nucleus). More specifically, picrotoxin injected into the tuberal LH (tLH) elicited eating, but was ineffective when injected into the anterior or posterior LH. We also investigated whether GABA(B) receptors in the LH participated in the control of food intake and found that neither blockade nor activation of these receptors under multiple conditions changed food intake. Collectively, our findings suggest that GABA(A) but not GABA(B) receptors in the tLH act to suppress feeding behavior.
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DEFF Research Database (Denmark)
Dragano, Nathalia R V; Solon, Carina; Ramalho, Albina F
2017-01-01
BACKGROUND: The consumption of large amounts of dietary fats is one of the most important environmental factors contributing to the development of obesity and metabolic disorders. GPR120 and GPR40 are polyunsaturated fatty acid receptors that exert a number of systemic effects that are beneficial...... for metabolic and inflammatory diseases. Here, we evaluate the expression and potential role of hypothalamic GPR120 and GPR40 as targets for the treatment of obesity. METHODS: Male Swiss (6-weeks old), were fed with a high fat diet (HFD, 60% of kcal from fat) for 4 weeks. Next, mice underwent stereotaxic...... the treatment period. At the end of the experiment, the hypothalamus was collected for real-time PCR analysis. RESULTS: We show that both receptors are expressed in the hypothalamus; GPR120 is primarily present in microglia, whereas GPR40 is expressed in neurons. Upon intracerebroventricular treatment, GW9508...
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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...
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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
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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...
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Prieto, Ruth; Pascual, José M; Rosdolsky, Maria; Barrios, Laura
2018-02-01
Craniopharyngioma (CP) adherence represents a heterogeneous pathologic feature that critically influences the potentially safe and radical resection. The aim of this study was to define the magnetic resonance imaging (MRI) predictors of CP adherence severity. This study retrospectively investigated a cohort of 200 surgically treated CPs with their corresponding preoperative conventional MRI scans. MRI findings related to the distortions of anatomic structures along the sella turcica-third ventricle axis caused by CPs, in addition to the tumor's shape and calcifications, were analyzed and correlated with the definitive type of CP adherence observed during the surgical procedures. CP adherence is defined by 3 components, as follows: 1) the specific structures attached to the tumor, 2) the adhesion's extent, and 3) its strength. Combination of these 3 components determines 5 hierarchical levels of adherence severity with gradually increasing surgical risk of hypothalamic injury. Multivariate analysis identified 4 radiologic variables that allowed a correct overall prediction of the levels of CP adherence severity in 81.5% of cases: 1) the position of the hypothalamus in relation to the tumor-the most discriminant factor; 2) the type of pituitary stalk distortion; 3) the tumor shape; and 4) the presence of calcifications. A binary logistic regression model including the first 3 radiologic variables correctly identified the CPs showing the highest level of adherence severity (severe/critical) in almost 90% of cases. A position of the hypothalamus around the middle portion of the tumor, an amputated or infiltrated appearance of the pituitary stalk, and the elliptical shape of the tumor are reliable predictors of strong and extensive CP adhesions to the hypothalamus. Copyright © 2017 Elsevier Inc. All rights reserved.
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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
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White, B D; Du, F; Higginbotham, D A
2003-12-01
Moderately low-protein diets lead to a rapid increase in food intake and body fat. The increase in feeding is associated with a decrease in the concentration of serum urea nitrogen, suggesting that the low-protein-induced increase in food intake may be related to the decreased metabolism of nitrogen from amino acids. We hypothesized that low dietary protein would be associated with a decrease in the synaptic release of two nitrogen-containing neurotransmitters, GABA and glutamate, whose nitrogen can be derived from amino acids. In this study, we examined the effects of a low-protein diet (10% casein) in Sprague-Dawley rats on the in vitro release of 3H-GABA and 14C-glutamate from the lateral and medial hypothalamus. The low-protein diet increased food intake by about 25% after one day. After four days, the in vitro release of radiolabeled GABA and glutamate was assessed. The calcium-dependent, potassium-stimulated release of radiolabeled GABA and glutamate from the lateral hypothalamus was decreased in rats fed the low-protein diet. The magnitude of neurotransmitter release from the lateral hypothalamus inversely correlated with food intake. No dietary differences in the release of neurotransmitters from the medial hypothalamus were observed. These results support the contention that alterations in nitrogen metabolism are associated with low-protein-induced feeding.
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International Nuclear Information System (INIS)
Angel, I.; Hauger, R.L.; Luu, M.D.; Giblin, B.; Skolnick, P.; Paul, S.M.
1985-01-01
Preincubation of rat hypothalamic slices in glucose-free Krebs-Ringer buffer (37 0 C) resulted in a time-dependent decrease in specific (+)-[ 3 H]amphetamine binding in the crude synaptosomal fraction prepared from these slices. The addition of D-glucose resulted in a dose- and time-dependent stimulation of (+)-[ 3 H]amphetamine binding, whereas incubations with L-glucose, 2-deoxy-D-glucose, or 3-O-methyl-D-glucose failed to increase the number of (+)-[ 3 H]amphetamine binding sites. Ouabain potently inhibited the glucose-induced stimulation of (+)-[ 3 H]amphetamine binding, suggesting the involvement of Na + , K + -ATPase. Preincubation of hypothalamic slices with glucose also resulted in an increase in Na + ,K + -ATPase activity and the number of specific high-affinity binding sites for [ 3 H]ouabain, and a good correlation was observed between the glucose-stimulated increase in (+)-[ 3 H]amphetamine and [ 3 H]ouabain binding. These data suggest that the (+)-[ 3 H]amphetamine binding site in hypothalamus, previously linked to the anorectic actions of various phenylethylamines, is regulated both in vitro and in vivo by physiological concentrations of glucose. Glucose and amphetamine appear to interact at common sites in the hypothalamus to stimulate Na + ,K + -ATPase activity, and the latter may be involved in the glucostatic regulation of appetite
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Directory of Open Access Journals (Sweden)
Jennifer A. Felsted
2017-12-01
Full Text Available Summary: The central mechanisms controlling glucose and lipid homeostasis are inadequately understood. We show that α2δ-1 is an essential regulator of glucose and lipid balance, acting in steroidogenic factor-1 (SF1 neurons of the ventromedial hypothalamus (VMH. These effects are body weight independent and involve regulation of SF1+ neuronal activity and sympathetic output to metabolic tissues. Accordingly, mice with α2δ-1 deletion in SF1 neurons exhibit glucose intolerance, altered lipolysis, and decreased cholesterol content in adipose tissue despite normal energy balance regulation. Profound reductions in the firing rate of SF1 neurons, decreased sympathetic output, and elevated circulating levels of serotonin are associated with these alterations. Normal calcium currents but reduced excitatory postsynaptic currents in mutant SF1 neurons implicate α2δ-1 in the promotion of excitatory synaptogenesis separate from its canonical role as a calcium channel subunit. Collectively, these findings identify an essential mechanism that regulates VMH neuronal activity and glycemic and lipid control and may be a target for tackling metabolic disease. : Felsted et al. show a required role of the calcium channel subunit and thrombospondin receptor α2δ-1 in regulating glucose and lipid homeostasis in the ventromedial hypothalamus (VMH. These effects are caused by regulation of SF1+ neuronal activity in the VMH through non-canonical mechanisms and concomitant influences on sympathetic output. Keywords: diabetes, VMH, hypothalamus, glucose, norepinephrine, serotonin, excitability, lipid, SF1
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Division for Heart Disease and Stroke Prevention: Data Trends & Maps
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...
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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.
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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.)
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Auvinen, H.E.; Romijn, J.A.; Biermasz, N.R.; Havekes, L.M.; Smit, J.W.A.; Rensen, P.C.N.; Pereira, A.M.
2011-01-01
Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the
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Vortex ring behavior provides the epigenetic blueprint for the human heart.
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.
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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
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Nutritional status affects the microRNA profile of the hypothalamus of female sheep.
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.
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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.
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What Is Coronary Heart Disease?
... 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 ...
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Mu opioid receptor binding sites in human brain
International Nuclear Information System (INIS)
Pilapil, C.; Welner, S.; Magnan, J.; Zamir, N.; Quirion, R.
1986-01-01
Our experiments focused on the examination of the distribution of mu opioid receptor binding sites in normal human brain using the highly selective ligand [ 3 H]DAGO, in both membrane binding assay and in vitro receptor autoradiography. Mu opioid binding sites are very discretely distributed in human brain with high densities of sites found in the posterior amygdala, caudate, putamen, hypothalamus and certain cortical areas. Moreover the autoradiographic distribution of [ 3 H]DAGO binding sites clearly reveals the discrete lamination (layers I and III-IV) of mu sites in cortical areas
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Heart-specific expression of laminopathic mutations in transgenic zebrafish.
Verma, Ajay D; Parnaik, Veena K
2017-07-01
Lamins are key determinants of nuclear organization and function in the metazoan nucleus. Mutations in human lamin A cause a spectrum of genetic diseases that affect cardiac muscle and skeletal muscle as well as other tissues. A few laminopathies have been modeled using the mouse. As zebrafish is a well established model for the study of cardiac development and disease, we have investigated the effects of heart-specific lamin A mutations in transgenic zebrafish. We have developed transgenic lines of zebrafish expressing conserved lamin A mutations that cause cardiac dysfunction in humans. Expression of zlamin A mutations Q291P and M368K in the heart was driven by the zebrafish cardiac troponin T2 promoter. Homozygous mutant embryos displayed nuclear abnormalities in cardiomyocyte nuclei. Expression analysis showed the upregulation of genes involved in heart regeneration in transgenic mutant embryos and a cell proliferation marker was increased in adult heart tissue. At the physiological level, there was deviation of up to 20% from normal heart rate in transgenic embryos expressing mutant lamins. Adult homozygous zebrafish were fertile and did not show signs of early mortality. Our results suggest that transgenic zebrafish models of heart-specific laminopathies show cardiac regeneration and moderate deviations in heart rate during embryonic development. © 2017 International Federation for Cell Biology.
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Kromin, A A; Zenina, O Yu
2013-09-01
In chronic experiments on rabbits, the effect of electric stimulation of the hunger center in the lateral hypothalamus on myoelectric activity of the fundal and antral parts of the stomach was studied under conditions of hunger and satiation in the absence of food. Stimulation of the lateral hypothalamus in rabbits subjected to 24-h food deprivation and in previously fed rabbits produced incessant seeking behavior, which was followed by reorganization of the structure of temporal organization of slow wave electric activity of muscles of the stomach body and antrum specific for hungry and satiated animals. Increased hunger motivation during electric stimulation of the lateral hypothalamus manifested in the structure of temporal organization of slow wave electric activity of the stomach body and antrum muscles in rabbits subjected to 24-h food deprivation in the replacement of bimodal distribution of slow wave periods to a trimodal type typical of 2-day deprivation, while transition from satiation to hunger caused by electric stimulation of the lateral hypothalamus was associated with a shift from monomodal distributions of slow wave periods to a bimodal type typical of 24-h deprivation. Reorganization of the structure of temporal organization of slow wave electric activity of the stomach body and antrum muscles during electric stimulation of the lateral hypothalamus was determined by descending inhibitory influences of food motivational excitation on activity of the myogenic pacemaker of the lesser curvature of the stomach.
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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
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... 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 ...
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Xenopus: An Emerging Model for Studying Congenital Heart Disease
Kaltenbrun, Erin; Tandon, Panna; Amin, Nirav M.; Waldron, Lauren; Showell, Chris; Conlon, Frank L.
2011-01-01
Congenital heart defects affect nearly 1% of all newborns and are a significant cause of infant death. Clinical studies have identified a number of congenital heart syndromes associated with mutations in genes that are involved in the complex process of cardiogenesis. The African clawed frog, Xenopus, has been instrumental in studies of vertebrate heart development and provides a valuable tool to investigate the molecular mechanisms underlying human congenital heart diseases. In this review, we discuss the methodologies that make Xenopus an ideal model system to investigate heart development and disease. We also outline congenital heart conditions linked to cardiac genes that have been well-studied in Xenopus and describe some emerging technologies that will further aid in the study of these complex syndromes. PMID:21538812
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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.
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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.
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Zaretsky, Dmitry V; Kline, Hannah; Zaretskaia, Maria V; Brown, Mary Beth; Durant, Pamela J; Alves, Nathan J; Rusyniak, Daniel E
2018-06-15
Stimulants cause hyperthermia, in part, by increasing heat generation through exercise. Stimulants also delay the onset of fatigue and exhaustion allowing animals to exercise longer. If used in a warm environment, this combination (increased exercise and decreased fatigue) can cause heat stroke. The dorsomedial hypothalamus (DMH) is involved in mediating locomotion from stimulants. Furthermore, inhibiting the DMH decreases locomotion and prevents hyperthermia in rats given stimulants in a warm environment. Whether the DMH is involved in mediating exercise-induced fatigue and exhaustion is not known. We hypothesized that disinhibiting neurons in the dorsomedial hypothalamus (DMH) would delay the onset of fatigue and exhaustion in animals exercising in a warm environment. To test this hypothesis, we used automated video tracking software to measure fatigue and exhaustion. In rats, using wearable mini-pumps, we demonstrated that disinhibiting the DMH, via bicuculline perfusion (5 µM), increased the duration of exercise in a warm environment as compared to control animals (25 ± 3 min vs 15 ± 2 min). Bicuculline-perfused animals also had higher temperatures at exhaustion (41.4 ± 0.2 °C vs 40.0 ± 0.4 °C). Disinhibiting neurons in the DMH also increased the time to fatigue. Our data show that the same region of the hypothalamus that is involved in mediating locomotion to stimulants, is also involved in controlling exhaustion and fatigue. These findings have implications for understanding the cause and treatment of stimulant-induced-hyperthermia. Copyright © 2018 Elsevier B.V. All rights reserved.
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Lucas, N; Legrand, R; Breton, J; Déchelotte, P; Edwards-Lévy, F; Fetissov, S O
2015-04-02
Chronic delivery of neuropeptides in the brain is a useful experimental approach to study their long-term effects on various biological parameters. In this work, we tested albumin-alginate microparticles, as a potential delivery system, to study if continuous release in the hypothalamus of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, may result in a long-term decrease in food intake and body weight. The 2-week release of α-MSH from peptide-loaded particles was confirmed by an in vitro assay. Then, daily food intake and body weight were studied for 18 days in rats injected bilaterally into the paraventricular hypothalamic nucleus with particles loaded or not with α-MSH. A decrease in body weight gain, persisting throughout the study, was found in rats injected with α-MSH-charged particles as compared with rats receiving non-charged particles and with rats injected with the same dose of α-MSH in solution. Food intake was significantly decreased for 3 days in rats receiving α-MSH-loaded particles and it was not followed by the feeding rebound effect which appears after food restriction. The presence of α-MSH-loaded particles in the hypothalamus was confirmed by immunohistochemistry. In conclusion, our study validates albumin-alginate microparticles as a new carrier system for long-term delivery of neuropeptides in the brain and demonstrates that chronic delivery of α-MSH in the hypothalamus results in a prolonged suppression of food intake and a decrease of body weight gain in rats. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
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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.
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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
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Wilson, Yvette M.; Gunnersen, Jenny M.; Murphy, Mark
2015-01-01
Memory formation is thought to occur via enhanced synaptic connectivity between populations of neurons in the brain. However, it has been difficult to localize and identify the neurons that are directly involved in the formation of any specific memory. We have previously used fos-tau-lacZ (FTL) transgenic mice to identify discrete populations of neurons in amygdala and hypothalamus, which were specifically activated by fear conditioning to a context. Here we have examined neuronal activation due to fear conditioning to a more specific auditory cue. Discrete populations of learning-specific neurons were identified in only a small number of locations in the brain, including those previously found to be activated in amygdala and hypothalamus by context fear conditioning. These populations, each containing only a relatively small number of neurons, may be directly involved in fear learning and memory. PMID:26179231
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Directory of Open Access Journals (Sweden)
Andrzej P. Herman
2014-01-01
Full Text Available The study was designed to determine the effects of peripheral injection of SB203580 on the synthesis of interleukin- (IL- 1β, IL-6, and tumor necrosis factor (TNF α in the hypothalamus of ewes during prolonged inflammation. Inflammation was induced by the administration of lipopolysaccharide (LPS (400 ng/kg over 7 days. SB203580 is a selective ATP-competitive inhibitor of the p38 mitogen-activated protein kinase (MAPK, which is involved in the regulation of proinflammatory cytokines IL-1β, IL-6 and TNFα synthesis. Intravenous injection of SB203580 successfully inhibited (P<0.01 synthesis of IL-1β and reduced (P<0.01 the production of IL-6 in the hypothalamus. The p38 MAPK inhibitor decreased (P<0.01 gene expression of TNFα but its effect was not observed at the level of TNFα protein synthesis. SB203580 also reduced (P<0.01 LPS-stimulated IL-1 receptor type 1 gene expression. The conclusion that inhibition of p38 MAPK blocks LPS-induced proinflammatory cytokine synthesis seems to initiate new perspectives in the treatment of chronic inflammatory diseases also within the central nervous system. However, potential proinflammatory effects of SB203580 treatment suggest that all therapies using p38 MAPK inhibitors should be introduced very carefully with analysis of all expected and unexpected consequences of treatment.
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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
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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
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Modeling the Human Scarred Heart In Vitro: Toward New Tissue Engineered Models.
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.
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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)
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Pre-mRNA mis-splicing of sarcomeric genes in heart failure.
Zhu, Chaoqun; Chen, Zhilong; Guo, Wei
2017-08-01
Pre-mRNA splicing is an important biological process that allows production of multiple proteins from a single gene in the genome, and mainly contributes to protein diversity in eukaryotic organisms. Alternative splicing is commonly governed by RNA binding proteins to meet the ever-changing demands of the cell. However, the mis-splicing may lead to human diseases. In the heart of human, mis-regulation of alternative splicing has been associated with heart failure. In this short review, we focus on alternative splicing of sarcomeric genes and review mis-splicing related heart failure with relatively well studied Sarcomeric genes and splicing mechanisms with identified regulatory factors. The perspective of alternative splicing based therapeutic strategies in heart failure has also been discussed. Copyright © 2016 Elsevier B.V. All rights reserved.
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Plasma urocortin in human systolic heart failure.
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.
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Arduino-based noise robust online heart-rate detection.
Das, Sangita; Pal, Saurabh; Mitra, Madhuchhanda
2017-04-01
This paper introduces a noise robust real time heart rate detection system from electrocardiogram (ECG) data. An online data acquisition system is developed to collect ECG signals from human subjects. Heart rate is detected using window-based autocorrelation peak localisation technique. A low-cost Arduino UNO board is used to implement the complete automated process. The performance of the system is compared with PC-based heart rate detection technique. Accuracy of the system is validated through simulated noisy ECG data with various levels of signal to noise ratio (SNR). The mean percentage error of detected heart rate is found to be 0.72% for the noisy database with five different noise levels.
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Activity of vasopressinergic neurones of the human supraoptic nucleus is age- and sex-dependent
Ishunina, T. A.; Salehi, A.; Hofman, M. A.; Swaab, D. F.
1999-01-01
In the human hypothalamus, arginine-vasopressin (AVP) is produced for a major part by the neurones of the supraoptic nucleus (SON). Since plasma AVP levels in men were reported to be higher than those of women and we did not find a sex difference in the neurone number, a higher vasopressinergic
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Camera-cinematography of the heart
International Nuclear Information System (INIS)
Adam, W.E.; Meyer, G.; Bitter, F.; Kampmann, H.; Bargon, G.; Stauch, M.; Ulm Univ.
1975-01-01
By 'camera-cinematography' of the heart, we mean an isotope method which permits detailed observation of cardiac mechanics without the use of a catheter. All that is necessary is an intravenous injection of 10 to 15 mCisup(99m)Tc human serum albumin followed after ten minutes by a five to ten minute period of observation with a scintillation camera. At this time the isotope has become distributed in the blood. Variations in the precordial impulses correspond with intra-cardiac changes of blood volume during a cardiac cycle. Analysis of the R-wave provides adequate information of cyclical volume changes in limited portions of the heart. This is achieved by a monitor with a pseudo-3-dimensional display; contraction and relaxation of the myocardium can be shown for any chosen longitudinal or horizontal diameter of the heart. Our programme allows simultaneous presentation of the movement of any point on the myocardium as a time-activity curve. The method is recommended as an addition to chest radiography, heart screening or cardiac kymography before carrying out cardiac catheterisation. (orig.) [de
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Effect of halofantrine administration on some liver and heart ...
African Journals Online (AJOL)
The effect of halofantrine on liver and the heart was evaluated in 15 healthy adult human volunteers (11 females and 4 males), after a single oral dose of halofantrine given to each volunteer. Blood samples were collected at predetermined time intervals and analysed for the various liver and heart enzyme activities ...
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Potentialities of radioisotope aniocardiography in diagnosis of acquired heart diseases
International Nuclear Information System (INIS)
Malov, G.A.; Mikaelyan, R.S.; Dumpe, A.N.
1980-01-01
On the base of the examination of 40 patients with acquired heart diseases and 5 people without heart diseases for control determined are the most charactreristic signs of the acquired heart disease of visual observation on RPP transit (albumin of human serum labelled by sup(99m)Tc) through the heart cavities and magistral vessels. It is shown that there is a close connection between central and intracardial hemodynamics which permjts to judge on the cardiac output on the base of mean circulation time (MCT). Radioisotopic angiocardiography permits to find redistribution of lung blood flow in patients with acquired heart diseases, which can serve as indirect index of long hypertension
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Cardiac septation: a late contribution of the embryonic primary myocardium to heart morphogenesis
Lamers, Wouter H.; Moorman, Antoon F. M.
2002-01-01
Heart morphogenesis comprises 2 major consecutive steps, viz. chamber formation followed by septation. Septation is the remodeling of the heart from a single-channel peristaltic pump to a dual-channel, synchronously contracting device with 1-way valves. In the human heart, septation occurs between 4
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Asimes, AnnaDorothea; Torcaso, Audrey; Pinceti, Elena; Kim, Chun K; Zeleznik-Le, Nancy J; Pak, Toni R
2017-05-01
Teenage binge drinking is a major health concern in the United States, with 21% of teenagers reporting binge-pattern drinking behavior in the previous 30 days. Recently, our lab showed that alcohol-naïve offspring of rats exposed to alcohol during adolescence exhibited altered gene expression profiles in the hypothalamus, a brain region involved in stress regulation. We employed Enhanced Reduced Representation Bisulfite Sequencing as an unbiased approach to test the hypothesis that parental exposure to binge-pattern alcohol during adolescence alters DNA methylation profiles in their alcohol-naïve offspring. Wistar rats were administered a repeated binge-ethanol exposure paradigm during early (postnatal day (PND) 37-44) and late (PND 67-74) adolescent development. Animals were mated 24 h after the last ethanol dose and subsequent offspring were produced. Analysis of male PND7 offspring revealed that offspring of alcohol-exposed parents exhibited differential DNA methylation patterns in the hypothalamus. The differentially methylated cytosines (DMCs) were distinct between offspring depending on which parent was exposed to ethanol. Moreover, novel DMCs were observed when both parents were exposed to ethanol and many DMCs from single parent ethanol exposure were not recapitulated with dual parent exposure. We also measured mRNA expression of several differentially methylated genes and some, but not all, showed correlative changes in expression. Importantly, methylation was not a direct predictor of expression levels, underscoring the complexity of transcriptional regulation. Overall, we demonstrate that adolescent binge ethanol exposure causes altered genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve offspring. Copyright © 2016 Elsevier Inc. All rights reserved.
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Ciechanowska, Magdalena; Lapot, Magdalena; Malewski, Tadeusz; Mateusiak, Krystyna; Misztal, Tomasz; Przekop, Franciszek
2008-11-01
Data exists showing that seasonal changes in the innervations of GnRH cells in the hypothalamus and functions of some neural systems affecting GnRH neurons are associated with GnRH release in ewes. Consequently, we put the question as to how the expression of GnRH gene and GnRH-R gene in the hypothalamus and GnRH-R gene in the anterior pituitary gland is reflected with LH secretion in anestrous and luteal phase ewes. Analysis of GnRH gene expression by RT-PCR in anestrous ewes indicated comparable levels of GnRH mRNA in the preoptic area, anterior and ventromedial hypothalamus. GnRH-R mRNA at different concentrations was found throughout the preoptic area, anterior and ventromedial hypothalamus, stalk/median eminence and in the anterior pituitary gland. The highest GnRH-R mRNA levels were detected in the stalk/median eminence and in the anterior pituitary gland. During the luteal phase of the estrous cycle in ewes, the levels of GnRH mRNA and GnRH-R mRNA in all structures were significantly higher than in anestrous ewes. Also LH concentrations in blood plasma of luteal phase ewes were significantly higher than those of anestrous ewes. In conclusion, results from this study suggest that low expression of the GnRH and GnRH-R genes in the hypothalamus and of the GnRH-R gene in the anterior pituitary gland, amongst others, may be responsible for a decrease in LH secretion and the anovulatory state in ewes during the long photoperiod.
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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.
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Hsu, Chuan-Chih; Chen, Sheng-Hsien; Lin, Cheng-Hsien; Yung, Ming-Chi
2014-10-01
Intolerance to heat exposure is believed to be associated with hypothalamo-pituitary-adrenocortical (HPA) axis impairment [reflected by decreases in blood concentrations of both adrenocorticotrophic-hormone (ACTH) and corticosterone]. The purpose of this study was to determine the effect of human recombinant factor VIIa (rfVIIa) on heat intolerance, HPA axis impairment, and hypothalamic inflammation, ischemic and oxidative damage, and apoptosis in mice under heat stress. Immediately after heat stress (41.2 °C for 1 h), mice were treated with vehicle (1 mL/kg of body weight) or rfVIIa (65-270 µg/kg of body weight) and then returned to room temperature (26 °C). Mice still alive on day 4 of heat exposure were considered survivors. Cellular ischemia markers (e.g., glutamate, lactate-to-pyruvate ratio), oxidative damage markers (e.g., nitric oxide metabolite, hydroxyl radials), and pro-inflammatory cytokines (e.g., interleukin-6, interleukin-1β, tumor necrosis factor-α) in hypothalamus were determined. In addition, blood concentrations of both ACTH and corticosterone were measured. Hypothalamic cell damage was assessed by determing the neuronal damage scores, whereas the hypothalamic cell apoptosis was determined by assessing the numbers of cells stained with terminal deoxynucleotidyl transferase-mediated αUTP nick-end labeling, caspase-3-positive cells, and platelet endothelial cell adhesion molecula-1-positive cells in hypothalamus. Compared with vehicle-treated heated mice, rfVIIa-treated heated mice had significantly higher fractional survival (8/10 vs 1/10), lesser thermoregulatory deficit (34.1 vs 24.8 °C), lesser extents of ischemic, oxidative, and inflammatory markers in hypothalamus, lesser neuronal damage scores and apoptosis in hypothalamus, and lesser HPA axis impairment. Human recombinant factor VIIa appears to exert a protective effect against heatstroke by attenuating hypothalamic cell apoptosis (due to ischemic, inflammatory, and oxidative damage
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Directory of Open Access Journals (Sweden)
Sweta Ramachandran
Full Text Available Biomarkers of heart failure in adults have been extensively studied. However, biomarkers to monitor the progression of heart failure in children with univentricular physiology are less well understood. We proposed that as mediators of diverse pathophysiology, miRNAs contained within circulating microvesicles could serve as biomarkers for the presence and progression of heart failure in univentricular patients. To test this, we studied the association of heart failure with elevations in specific miRNAs isolated from circulating microvesicles in a cohort of children with univentricular heart disease and heart failure. We conducted a single site cross-sectional observational study of 71 children aged 1 month-7 years with univentricular heart disease and heart failure. We demonstrated that levels of miR129-5p isolated from plasma microvesicles were inversely related to the degree of clinical heart failure as assessed by Ross score. We then showed that miR129-5p levels are downregulated in HL1 cells and human embryonic stem cell-derived cardiomyocytes exposed to oxidative stress. We demonstrated that bone morphogenetic protein receptor 2, which has been implicated in the development of pulmonary vascular disease, is a target of miR129-5p, and conversely regulated in response to oxidative stress in cell culture. Levels of miR129-5p were inversely related to the degree of clinical heart failure in patients with univentricular heart disease. This study demonstrates that miR129-5p is a sensitive and specific biomarker for heart failure in univentricular heart disease independent of ventricular morphology or stage of palliation. Further study is warranted to understand the targets affected by miR129-5p with the development of heart failure in patients with univentricular physiology.
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Streptococcal pharyngitis and rheumatic heart disease: the superantigen hypothesis revisited.
Hurst, Jacklyn R; Kasper, Katherine J; Sule, Akshay N; McCormick, John K
2018-07-01
Streptococcus pyogenes is a human-specific and globally prominent bacterial pathogen that despite causing numerous human infections, this bacterium is normally found in an asymptomatic carrier state. This review provides an overview of both bacterial and human factors that likely play an important role in nasopharyngeal colonization and pharyngitis, as well as the development of acute rheumatic fever and rheumatic heart disease. Here we highlight a recently described role for bacterial superantigens in promoting acute nasopharyngeal infection, and discuss how these immune system activating toxins could be crucial to initiate the autoimmune process in rheumatic heart disease. Copyright © 2018. Published by Elsevier B.V.
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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
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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.
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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.
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Biofeedback in the treatment of heart failure.
McKee, Michael G; Moravec, Christine S
2010-07-01
Biofeedback training can be used to reduce activation of the sympathetic nervous system (SNS) and increase activation of the parasympathetic nervous system (PNS). It is well established that hyperactivation of the SNS contributes to disease progression in chronic heart failure. It has been postulated that underactivation of the PNS may also play a role in heart failure pathophysiology. In addition to autonomic imbalance, a chronic inflammatory process is now recognized as being involved in heart failure progression, and recent work has established that activation of the inflammatory process may be attenuated by vagal nerve stimulation. By interfering with both autonomic imbalance and the inflammatory process, biofeedback-assisted stress management may be an effective treatment for patients with heart failure by improving clinical status and quality of life. Recent studies have suggested that biofeedback and stress management have a positive impact in patients with chronic heart failure, and patients with higher perceived control over their disease have been shown to have better quality of life. Our ongoing study of biofeedback-assisted stress management in the treatment of end-stage heart failure will also examine biologic end points in treated patients at the time of heart transplant, in order to assess the effects of biofeedback training on the cellular and molecular components of the failing heart. We hypothesize that the effects of biofeedback training will extend to remodeling the failing human heart, in addition to improving quality of life.
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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.
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Effect of human leukocyte antigen-C and -DQ matching on pediatric heart transplant graft survival.
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
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New Trends in Heart Regeneration: A Review
Directory of Open Access Journals (Sweden)
Kochegarov A
2016-11-01
Full Text Available In this review, we focus on new approaches that could lead to the regeneration of heart muscle and the restoration of cardiac muscle function derived from newly-formed cardiomyocytes. Various strategies for the production of cardiomyocytes from embryonic stem cells, induced pluripotent stem cells, adult bone marrow stem cells and cardiac spheres from human heart biopsies are described. Pathological conditions which lead to atherosclerosis and coronary artery disease often are followed by myocardial infarction causing myocardial cell death. After cell death, there is very little self-regeneration of the cardiac muscle tissue, which is replaced by non-contractile connective tissue, thus weakening the ability of the heart muscle to contract fully and leading to heart failure. A number of experimental research approaches to stimulate heart muscle regeneration with the hope of regaining normal or near normal heart function in the damaged heart muscle have been attempted. Some of these very interesting studies have used a variety of stem cell types in combination with potential cardiogenic differentiation factors in an attempt to promote differentiation of new cardiac muscle for possible future use in the clinical treatment of patients who have suffered heart muscle damage from acute myocardial infarctions or related cardiovascular diseases. Although progress has been made in recent years relative to promoting the differentiation of cardiac muscle tissue from non-muscle cells, much work remains to be done for this technology to be used routinely in translational clinical medicine to treat patients with damaged heart muscle tissue and return such individuals to pre-heart-attack activity levels.
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DEFF Research Database (Denmark)
Kastrup, Jens; Haack-Sørensen, Mandana; Juhl, Morten
2017-01-01
and ischemic heart failure (IHF). Batches of CSCC_ASC were isolated from three healthy donors by liposuction from abdominal adipose tissue. Adipose mesenchymal stromal cells were culture expanded in bioreactors without the use of animal constituents, cryopreserved, and stored in vials in nitrogen dry......The present first-in-human clinical trial evaluated the safety and feasibility of a newly developed and cryopreserved Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors for intramyocardial injection in ten patients with ischemic heart disease......-storage containers until use. Direct injection of CSCC_ASC into the myocardium did not cause any complications or serious adverse events related to either treatment or cell administration in a 6-month follow-up period. Four out of ten heart failure patients developed donor-specific de novo human leukocyte antigen...
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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
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Garrott, Kara; Dyavanapalli, Jhansi; Cauley, Edmund; Dwyer, Mary Kate; Kuzmiak-Glancy, Sarah; Wang, Xin; Mendelowitz, David; Kay, Matthew W
2017-09-01
A distinctive hallmark of heart failure (HF) is autonomic imbalance, consisting of increased sympathetic activity, and decreased parasympathetic tone. Recent work suggests that activation of hypothalamic oxytocin (OXT) neurons could improve autonomic balance during HF. We hypothesized that a novel method of chronic selective activation of hypothalamic OXT neurons will improve cardiac function and reduce inflammation and fibrosis in a rat model of HF. Two groups of male Sprague-Dawley rats underwent trans-ascending aortic constriction (TAC) to induce left ventricular (LV) hypertrophy that progresses to HF. In one TAC group, OXT neurons in the paraventricular nucleus of the hypothalamus were chronically activated by selective expression and activation of excitatory DREADDs receptors with daily injections of clozapine N-oxide (CNO) (TAC + OXT). Two additional age-matched groups received either saline injections (Control) or CNO injections for excitatory DREADDs activation (OXT NORM). Heart rate (HR), LV developed pressure (LVDP), and coronary flow rate were measured in isolated heart experiments. Isoproterenol (0.01 nM-1.0 µM) was administered to evaluate β-adrenergic sensitivity. We found that increases in cellular hypertrophy and myocardial collagen density in TAC were blunted in TAC + OXT animals. Inflammatory cytokine IL-1β expression was more than twice higher in TAC than all other hearts. LVDP, rate pressure product (RPP), contractility, and relaxation were depressed in TAC compared with all other groups. The response of TAC and TAC + OXT hearts to isoproterenol was blunted, with no significant increase in RPP, contractility, or relaxation. However, HR in TAC + OXT animals increased to match Control at higher doses of isoproterenol. Activation of hypothalamic OXT neurons to elevate parasympathetic tone reduced cellular hypertrophy, levels of IL-1β, and fibrosis during TAC-induced HF in rats. Cardiac contractility parameters were
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Tiesjema, Birgitte; Adan, Roger A. H.; Luijendijk, Mieneke C. M.; Kalsbeek, Andries; la Fleur, Susanne E.
2007-01-01
It is well known that neuropeptide Y (NPY) increases food intake. The hypothalamic paraventricular nucleus (PVN) and the lateral hypothalamus (LH) are both involved in the acute, hyperphagic effects of NPY. Although it is obvious that increased energy intake may lead to obesity, it is less
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Hofman, M. A.; Fliers, E.; Goudsmit, E.; Swaab, D. F.
1988-01-01
The size, shape and cellular morphology of the suprachiasmatic (SCN) and paraventricular nuclei (PVN) in the human hypothalamus were examined in relation to sex and age. In both nuclear regions the following parameters were determined: length of the rostrocaudal axis, maximum cross sectional area,
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Exhaled nitric oxide concentration in patients after heart transplantation.
Nadziakiewicz, P; Knapik, P; Zakliczyński, M; Zembala, M; Urbańska, E; Pacholewicz, J
2007-11-01
Nitric oxide (NO) is present in exhaled air in humans and its level may decrease in heart diseases. In the present study we prospectively investigated how heart transplantation treated with oral immunosuppresive drugs based on ciclosporine A influences the exhaled NO concentration (exNO). The study was performed in 17 patients after heart transplantation in various time after procedure and 15 nonsmoking healthy volunteers as a control group. Patients after heart transplantation were free of clinical signs of rejection. End-tidal concentration of exNO was measured by the use of a chemiluminescence method. We found no statistically significant differences in the exNO level between patients after heart transplantation and healthy controls (6.81+/-2.70 part per billion (ppb) in the transplant group vs. 6.01+/-3.43 ppb in the control group). We conclude that heart transplantation and immunosuppresive therapy do not influence the exhaled NO concentration.
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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.
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Myocardial Polyploidization Creates a Barrier to Heart Regeneration in Zebrafish.
González-Rosa, Juan Manuel; Sharpe, Michka; Field, Dorothy; Soonpaa, Mark H; Field, Loren J; Burns, Caroline E; Burns, C Geoffrey
2018-02-26
Correlative evidence suggests that polyploidization of heart muscle, which occurs naturally in post-natal mammals, creates a barrier to heart regeneration. Here, we move beyond a correlation by demonstrating that experimental polyploidization of zebrafish cardiomyocytes is sufficient to suppress their proliferative potential during regeneration. Initially, we determined that zebrafish myocardium becomes susceptible to polyploidization upon transient cytokinesis inhibition mediated by dominant-negative Ect2. Using a transgenic strategy, we generated adult animals containing mosaic hearts composed of differentially labeled diploid and polyploid-enriched cardiomyocyte populations. Diploid cardiomyocytes outcompeted their polyploid neighbors in producing regenerated heart muscle. Moreover, hearts composed of equivalent proportions of diploid and polyploid cardiomyocytes failed to regenerate altogether, demonstrating that a critical percentage of diploid cardiomyocytes is required to achieve heart regeneration. Our data identify cardiomyocyte polyploidization as a barrier to heart regeneration and suggest that mobilizing rare diploid cardiomyocytes in the human heart will improve its regenerative capacity. Copyright © 2018 Elsevier Inc. All rights reserved.
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Cardona-Gómez, G P; Chowen, J A; Garcia-Segura, L M
2000-06-05
Gonadal hormones interact with insulin-like growthfactor-I (IGF-I) to regulate synaptic plasticity during the estrous cycle in the rat mediobasal hypothalamus. It has been proposed that tanycytes, specialized glial cells lining the ventral region of the third ventricle, may regulate the availability of IGF-I to hypothalamic neurons. IGF-I levels in tanycytes fluctuate during the estrous cycle. Furthermore, estrogen administration to ovariectomized rats increases IGF-I levels in tanycytes, while progesterone, injected simultaneously with estrogen, blocks the estrogen-induced increase of IGF-I levels in tanycytes. To test whether hormonal regulation of IGF-I receptor (IGF-IR) and IGF binding protein-2 (IGFBP-2) may be involved in the accumulation of IGF-I in tanycytes, we assessed the effect of ovarian hormones on the levels of these molecules in the mediobasal hypothalamus of adult female rats. Ovariectomized animals were treated with either oil, estrogen, progesterone, or estrogen and progesterone simultaneously and then killed 6 or 24 h later. Some neurons, some astrocytes, and many tanycytes in the mediobasal hypothalamus were found by confocal microscopy to be immunoreactive for IGF-IR. IGFBP-2 immunoreactivity was restricted almost exclusively to tanycytes and ependymal cells and was colocalized with IGF-IR immunoreactivity in tanycytes. By electron microscope immunocytochemistry using colloidal gold labeling, IGF-IR and IGFBP-2 immunoreactivities were observed in the microvilli of tanycytes in the lumen of the third ventricle. IGF-IR and IGFBP-2 immunoreactive levels on the apical surface of tanycytes were significantly decreased by the administration of progesterone, either alone or in the presence of estradiol. IGF-IR levels in the mediobasal hypothalamus, measured by Western blotting, were not significantly affected by the separate administration of estradiol or progesterone to ovariectomized rats. However, the simultaneous administration of both hormones
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Hippo pathway deficiency reverses systolic heart failure after infarction.
Leach, John P; Heallen, Todd; Zhang, Min; Rahmani, Mahdis; Morikawa, Yuka; Hill, Matthew C; Segura, Ana; Willerson, James T; Martin, James F
2017-10-12
Mammalian organs vary widely in regenerative capacity. Poorly regenerative organs, such as the heart are particularly vulnerable to organ failure. Once established, heart failure commonly results in mortality. The Hippo pathway, a kinase cascade that prevents adult cardiomyocyte proliferation and regeneration, is upregulated in human heart failure. Here we show that deletion of the Hippo pathway component Salvador (Salv) in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function compared with controls. Using translating ribosomal affinity purification, we isolate cardiomyocyte-specific translating messenger RNA. Hippo-deficient cardiomyocytes have increased expression of proliferative genes and stress response genes, such as the mitochondrial quality control gene, Park2. Genetic studies indicate that Park2 is essential for heart repair, suggesting a requirement for mitochondrial quality control in regenerating myocardium. Gene therapy with a virus encoding Salv short hairpin RNA improves heart function when delivered at the time of infarct or after ischaemic heart failure following myocardial infarction was established. Our findings indicate that the failing heart has a previously unrecognized reparative capacity involving more than cardiomyocyte renewal.
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Brain calcium - Role in temperature regulation.
Hanegan, J. L.; Williams, B. A.
1973-01-01
Perfusion of the preoptic-anterior hypothalamus with excess calcium ion in ground squirrels produces a drop in core temperature. The magnitude of the drop is directly dependent on ambient temperature. Respiration, heart rate, and oxygen consumption are also reduced during perfusion of calcium ion. It is concluded that the depression of body temperature during calcium ion perfusion is due to generalized depression of the neurons of the preoptic-anterior hypothalamus.
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Karsdorp, Petra A; Kindt, Merel; Everaerd, Walter; Mulder, Barbara J M
2007-08-01
The present study was aimed at clarifying whether preattentive processing of heart cues results in biased perception of heart sensations in patients with congenital heart disease (ConHD) who are also highly trait anxious. Twenty-six patients with ConHD and 22 healthy participants categorized heart-related (heart rate) or neutral sensations (constant vibration) as either heart or neutral. Both sensations were evoked using a bass speaker that was attached on the chest of the participant. Before each physical sensation, a subliminal heart-related or neutral prime was presented. Biased perception of heart-sensations would become evident by a delayed categorization of the heart-related sensations. In line with the prediction, a combination of high trait anxiety and ConHD resulted in slower responses after a heart-related sensation that was preceded by a subliminal heart cue. Preattentive processing of harmless heart cues may easily elicit overperception of heart symptoms in highly trait anxious patients with ConHD.
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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.
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Proteasomal and Lysosomal Protein Degradation and Heart Disease
Wang, Xuejun; Robbins, Jeffrey
2013-01-01
In the cell, the proteasome and lysosomes represent the most important proteolytic machineries, responsible for the protein degradation in the ubiquitin-proteasome system (UPS) and autophagy, respectively. Both the UPS and autophagy are essential to protein quality and quantity control. Alterations in cardiac proteasomal and lysosomal degradation are remarkably associated with most heart disease in humans and are implicated in the pathogenesis of congestive heart failure. Studies carried out ...
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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.
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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.)
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{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.
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cholesterol, coronary heart disease and oestrogens
African Journals Online (AJOL)
1971-04-03
Apr 3, 1971 ... atheromatosis and coronalY heart disease in the human female are reviewed. Aspects ... For example, Barr' recorded mean levels of 197 in normal women aged 18 ..... Epstein, F. H. (1965): J. Chron. Dis.. 18. 735. 26. Kanne!
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Using the Human Activity Profile to Assess Functional Performance in Heart Failure.
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.
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Energy Technology Data Exchange (ETDEWEB)
Bruecke, T; Asenbaum, S; Frassine, H; Podreka, I [Vienna Univ. (Austria). Neurologische Klinik; Kornhuber, J [Wuerzburg Univ. (Germany); Angelberger, P [Oesterreichisches Forschungszentrum Seibersdorf GmbH (Austria)
1993-01-01
Single photon emission computerized tomography (SPECT) studies in non-human primates have previously shown that the cocaine derivative [[sup 123]I]-2-[beta]-carbomethoxy-3-[beta]-(4-iodophenyl)-tropane ([[sup 123]I][beta]-CIT) labels dopamine transporters in the striatum and serotonin transporters in the hypothalamus-midbrain area. Here, we report on the regional kinetic uptake of [[sup 123]I][beta]-CIT in the brain of 4 normal volunteers and 2 patients with Parkinson's disease. In healthy subjects striatal activity increased slowly to reach peak values at about 20 hours post injection. In the hypothalamus-midbrain area peak activities were observed at about 4 hours with a slow decrease thereafter. Low activity was observed in cortical and cerebellar areas. The striatal to cerebellar ratio was about 4 after 5 hours and 9 after 20 hours. In 2 patients with idiopathic Parkinson's disease striatal activity was markedly decreased while the activity in hypothalamus-midbrain areas was only diminished. Uptake into cortical and cerebellar areas appeared to be unchanged in Parkinson's disease. Consequently, in Parkinson's disease the striatal to cerebellar ratio was decreased to values around 2.5 after 20 hours. These preliminary methodological studies suggest that [[sup 123]I][beta]-CIT is a useful SPECT ligand for studying dopamine and possibly also serotonin transporters in the living human brain.
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Heart transplantation in adults with congenital heart disease.
Houyel, Lucile; To-Dumortier, Ngoc-Tram; Lepers, Yannick; Petit, Jérôme; Roussin, Régine; Ly, Mohamed; Lebret, Emmanuel; Fadel, Elie; Hörer, Jürgen; Hascoët, Sébastien
2017-05-01
With the advances in congenital cardiac surgery and postoperative care, an increasing number of children with complex congenital heart disease now reach adulthood. There are already more adults than children living with a congenital heart defect, including patients with complex congenital heart defects. Among these adults with congenital heart disease, a significant number will develop ventricular dysfunction over time. Heart failure accounts for 26-42% of deaths in adults with congenital heart defects. Heart transplantation, or heart-lung transplantation in Eisenmenger syndrome, then becomes the ultimate therapeutic possibility for these patients. This population is deemed to be at high risk of mortality after heart transplantation, although their long-term survival is similar to that of patients transplanted for other reasons. Indeed, heart transplantation in adults with congenital heart disease is often challenging, because of several potential problems: complex cardiac and vascular anatomy, multiple previous palliative and corrective surgeries, and effects on other organs (kidney, liver, lungs) of long-standing cardiac dysfunction or cyanosis, with frequent elevation of pulmonary vascular resistance. In this review, we focus on the specific problems relating to heart and heart-lung transplantation in this population, revisit the indications/contraindications, and update the long-term outcomes. Copyright © 2017. Published by Elsevier Masson SAS.
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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.
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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)
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Women's Heart Disease: Heart Attack Symptoms
... 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 ...
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Physiological characterization of the SynCardia total artificial heart in a mock circulation system.
Crosby, Jessica R; DeCook, Katrina J; Tran, Phat L; Smith, Richard G; Larson, Douglas F; Khalpey, Zain I; Burkhoff, Daniel; Slepian, Marvin J
2015-01-01
The SynCardia total artificial heart (TAH) has emerged as an effective, life-saving biventricular replacement system for a wide variety of patients with end-stage heart failure. Although the clinical performance of the TAH is established, modern physiological characterization, in terms of elastance behavior and pressure-volume (PV) characterization has not been defined. Herein, we examine the TAH in terms of elastance using a nonejecting left ventricle, and then characterize the PV relation of the TAH by varying preload and afterload parameters using a Donovan Mock Circulatory System. We demonstrate that the TAH does not operate with time-varying elastance, differing from the human heart. Furthermore, we show that the TAH has a PV relation behavior that also differs from that of the human heart. The TAH does exhibit Starling-like behavior, with output increasing via preload-dependent mechanisms, without reliance on an alteration of inotropic state within the operating window of the TAH. Within our testing range, the TAH is insensitive to variations in afterload; however, this insensitivity has a limit, the limit being the maximum driving pressure of the pneumatic driver. Understanding the physiology of the TAH affords insight into the functional parameters that govern artificial heart behavior providing perspective on differences compared with the human heart.
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Growth and remodeling play opposing roles during postnatal human heart valve development.
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.
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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
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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.
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Ciechanowska, Magdalena; Łapot, Magdalena; Malewski, Tadeusz; Mateusiak, Krystyna; Misztal, Tomasz; Przekop, Franciszek
2011-01-01
There is no information in the literature regarding the effect of corticotropin-releasing hormone (CRH) on genes encoding gonadotrophin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) in the hypothalamus or on GnRHR gene expression in the pituitary gland in vivo. Thus, the aim of the present study was to investigate, in follicular phase ewes, the effects of prolonged, intermittent infusion of small doses of CRH or its antagonist (α-helical CRH 9-41; CRH-A) into the third cerebral ventricle on GnRH mRNA and GnRHR mRNA levels in the hypothalamo-pituitary unit and on LH secretion. Stimulation or inhibition of CRH receptors significantly decreased or increased GnRH gene expression in the hypothalamus, respectively, and led to different responses in GnRHR gene expression in discrete hypothalamic areas. For example, CRH increased GnRHR gene expression in the preoptic area, but decreased it in the hypothalamus/stalk median eminence and in the anterior pituitary gland. In addition, CRH decreased LH secretion. Blockade of CRH receptors had the opposite effect on GnRHR gene expression. The results suggest that activation of CRH receptors in the hypothalamus of follicular phase ewes can modulate the biosynthesis and release of GnRH through complex changes in the expression of GnRH and GnRHR genes in the hypothalamo-anterior pituitary unit. © CSIRO 2011 Open Access
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Géranton, Sandrine M; Heal, David J; Stanford, S Clare
2004-03-01
There is extensive evidence for functional interactions between central noradrenergic and serotonergic neurones. Here, dual-probe microdialysis was used in freely-moving rats to compare the effects of 5-HT on noradrenergic transmission in the rat frontal cortex and hypothalamus. We studied the effects of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA; which depleted 5-HT stores in both the frontal cortex and the hypothalamus), on spontaneous efflux of noradrenaline and on the noradrenergic responses to d-amphetamine, and the monoamine reuptake inhibitor, BTS 54 354. pCPA pretreatment alone did not affect spontaneous noradrenaline efflux in either brain region, whether or not alpha2-autoreceptors were inactivated by administration of the alpha2-antagonist, atipamezole (1 mg/kg i.p). However, in the frontal cortex, pCPA pretreatment augmented the amplitude of, and prolonged, the noradrenergic response to local infusion of d-amphetamine (10 microM). In contrast, pCPA abolished the increase in cortical noradrenaline efflux induced by local infusion of BTS 54 354 (50 microM). In the hypothalamus, pCPA did not affect the amplitude of the response to either of these agents but did prolong the effects of d-amphetamine on noradrenaline efflux. These findings suggest that serotonergic transmission has complex effects on the noradrenergic response to drugs that increase noradrenergic transmission in the frontal cortex, but has less influence in the hypothalamus.
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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...
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A Zebrafish Heart Failure Model for Assessing Therapeutic Agents.
Zhu, Xiao-Yu; Wu, Si-Qi; Guo, Sheng-Ya; Yang, Hua; Xia, Bo; Li, Ping; Li, Chun-Qi
2018-03-20
Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.
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Imaging of heart acoustic based on the sub-space methods using a microphone array.
Moghaddasi, Hanie; Almasganj, Farshad; Zoroufian, Arezoo
2017-07-01
Heart disease is one of the leading causes of death around the world. Phonocardiogram (PCG) is an important bio-signal which represents the acoustic activity of heart, typically without any spatiotemporal information of the involved acoustic sources. The aim of this study is to analyze the PCG by employing a microphone array by which the heart internal sound sources could be localized, too. In this paper, it is intended to propose a modality by which the locations of the active sources in the heart could also be investigated, during a cardiac cycle. In this way, a microphone array with six microphones is employed as the recording set up to be put on the human chest. In the following, the Group Delay MUSIC algorithm which is a sub-space based localization method is used to estimate the location of the heart sources in different phases of the PCG. We achieved to 0.14cm mean error for the sources of first heart sound (S 1 ) simulator and 0.21cm mean error for the sources of second heart sound (S 2 ) simulator with Group Delay MUSIC algorithm. The acoustical diagrams created for human subjects show distinct patterns in various phases of the cardiac cycles such as the first and second heart sounds. Moreover, the evaluated source locations for the heart valves are matched with the ones that are obtained via the 4-dimensional (4D) echocardiography applied, to a real human case. Imaging of heart acoustic map presents a new outlook to indicate the acoustic properties of cardiovascular system and disorders of valves and thereby, in the future, could be used as a new diagnostic tool. Copyright © 2017. Published by Elsevier B.V.
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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
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Robust efficient estimation of heart rate pulse from video
Xu, Shuchang; Sun, Lingyun; Rohde, Gustavo Kunde
2014-01-01
We describe a simple but robust algorithm for estimating the heart rate pulse from video sequences containing human skin in real time. Based on a model of light interaction with human skin, we define the change of blood concentration due to arterial pulsation as a pixel quotient in log space, and successfully use the derived signal for computing the pulse heart rate. Various experiments with different cameras, different illumination condition, and different skin locations were conducted to demonstrate the effectiveness and robustness of the proposed algorithm. Examples computed with normal illumination show the algorithm is comparable with pulse oximeter devices both in accuracy and sensitivity. PMID:24761294
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Molecular Epidemiology of Heart Failure
Directory of Open Access Journals (Sweden)
J. Gustav Smith, MD, PhD
2017-12-01
Full Text Available Heart failure (HF is the end-stage of all heart disease and arguably constitutes the greatest unmet therapeutic need in cardiovascular medicine today. Classic epidemiological studies have established clinical risk factors for HF, but the cause remains poorly understood in many cases. Biochemical analyses of small case-control series and animal models have described a plethora of molecular characteristics of HF, but a single unifying pathogenic theory is lacking. Heart failure appears to result not only from cardiac overload or injury but also from a complex interplay among genetic, neurohormonal, metabolic, inflammatory, and other biochemical factors acting on the heart. Recent development of robust, high-throughput tools in molecular biology provides opportunity for deep molecular characterization of population-representative cohorts and HF cases (molecular epidemiology, including genome sequencing, profiling of myocardial gene expression and chromatin modifications, plasma composition of proteins and metabolites, and microbiomes. The integration of such detailed information holds promise for improving understanding of HF pathophysiology in humans, identification of therapeutic targets, and definition of disease subgroups beyond the current classification based on ejection fraction which may benefit from improved individual tailoring of therapy. Challenges include: 1 the need for large cohorts with deep, uniform phenotyping; 2 access to the relevant tissues, ideally with repeated sampling to capture dynamic processes; and 3 analytical issues related to integration and analysis of complex datasets. International research consortia have formed to address these challenges and combine datasets, and cohorts with up to 1 million participants are being collected. This paper describes the molecular epidemiology of HF and provides an overview of methods and tissue types and examples of published and ongoing efforts to systematically evaluate molecular
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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.
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Large Mammalian Animal Models of Heart Disease
Directory of Open Access Journals (Sweden)
Paula Camacho
2016-10-01
Full Text Available Due to the biological complexity of the cardiovascular system, the animal model is an urgent pre-clinical need to advance our knowledge of cardiovascular disease and to explore new drugs to repair the damaged heart. Ideally, a model system should be inexpensive, easily manipulated, reproducible, a biological representative of human disease, and ethically sound. Although a larger animal model is more expensive and difficult to manipulate, its genetic, structural, functional, and even disease similarities to humans make it an ideal model to first consider. This review presents the commonly-used large animals—dog, sheep, pig, and non-human primates—while the less-used other large animals—cows, horses—are excluded. The review attempts to introduce unique points for each species regarding its biological property, degrees of susceptibility to develop certain types of heart diseases, and methodology of induced conditions. For example, dogs barely develop myocardial infarction, while dilated cardiomyopathy is developed quite often. Based on the similarities of each species to the human, the model selection may first consider non-human primates—pig, sheep, then dog—but it also depends on other factors, for example, purposes, funding, ethics, and policy. We hope this review can serve as a basic outline of large animal models for cardiovascular researchers and clinicians.
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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 ...
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Karimi, Sara; Mesdaghinia, Azam; Farzinpour, Zahra; Hamidi, Gholamali; Haghparast, Abbas
2017-11-01
The Lateral hypothalamus (LH) is an important component of the networks underlying the control of feeding and other motivated behaviors. Cost-benefit decision-making is mediated largely by the prefrontal cortex (PFC) which strongly innervates the LH. Therefore, in the current study, we conducted a series of experiments to elucidate the role of the perifornical area of the lateral hypothalamus (PeF-LH) in effort and/or delay-based decision-making. We trained different groups of rats in a delay-based and/or an effort-based form of cost-benefit T-maze decision- making task in which they could either choose to pay the cost to obtain a high reward in one arm or could obtain a low reward in the other arm with no cost. During test days, the rats received local injections of either vehicle or lidocaine4% (0.5 μl/side), in the PeF-LH. In an effort-based decision task, PeF-LH inactivation led to decrease in high reward choice. Similarly, in a delay-based decision task animals' preference changed to a low but immediately available reward. This was not caused by a spatial memory or motor deficit. PeF-LH inactivation modified decision behavior. The results imply that PeF-LH is important for allowing the animal to pay a cost to acquire greater rewards. Copyright © 2017 Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
Jennifer eRainville
2015-02-01
Full Text Available The estrogen receptor (ER and glucocorticoid receptor (GR are members of the nuclear receptor superfamily that can signal using both non-genomic and genomic transcriptional modes. Though genomic modes of signaling have been well characterized and several behaviors attributed to this signaling mechanism, the physiological significance of non-genomic modes of signaling has not been well understood. This has partly been due to the controversy regarding the identity of the membrane ER (mER or membrane GR (mGR that may mediate rapid, non-genomic signaling and the downstream signaling cascades that may result as a consequence of steroid ligands binding the mER or the mGR. Both estrogens and glucocorticoids exert a number of actions on the hypothalamus, including feedback. This review focuses on the various candidates for the mER or mGR in the hypothalamus and the contribution of non-genomic signaling to classical hypothalamically-driven behaviors and changes in neuronal morphology. It also attempts to categorize some of the possible functions of non-genomic signaling at both the cellular level and at the organismal level that are relevant for behavior, including some behaviors that are regulated by both estrogens and glucocorticoids in a potentially synergistic manner. Lastly, it attempts to show that steroid signaling via non-genomic modes may provide the organism with rapid behavioral responses to stimuli.
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Prospective Heart Tracking for Whole-heart Magnetic Resonance Angiography
Moghari, Mehdi H.; Geva, Tal; Powell, Andrew J.
2015-01-01
Purpose To develop a prospective respiratory-gating technique (Heart-NAV) for use with contrast-enhanced 3D inversion recovery (IR) whole-heart magnetic resonance angiography (MRA) acquisitions that directly tracks heart motion without creating image inflow artifact. Methods With Heart-NAV, 1 of the startup pulses for the whole-heart steady-state free precession MRA sequence is used to collect the centerline of k-space, and its 1-dimensional reconstruction is fed into the standard diaphragm-navigator (NAV) signal analysis process to prospectively gate and track respiratory-induced heart displacement. Ten healthy volunteers underwent non-contrast whole-heart MRA acquisitions using the conventional diaphragm-NAV and Heart-NAV with 5 and 10 mm acceptance windows in a 1.5T scanner. Five patients underwent contrast-enhanced IR whole-heart MRA using a diaphragm-NAV and Heart-NAV with a 5 mm acceptance window. Results For non-contrast whole-heart MRA with both the 5 and 10 mm acceptance windows, Heart-NAV yielded coronary artery vessel sharpness and subjective visual scores that were not significantly different than those using a conventional diaphragm-NAV. Scan time for Heart-NAV was 10% shorter (p<0.05). In patients undergoing contrast-enhanced IR whole-heart MRA, inflow artifact was seen with the diaphragm-NAV but not with Heart-NAV. Conclusion Compared to a conventional diaphragm-NAV, Heart-NAV achieves similar image quality in a slightly shorter scan time and eliminates inflow artifact. PMID:26843458
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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…
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Directory of Open Access Journals (Sweden)
Chih-Yang Huang
2018-02-01
Full Text Available In association with the published article “Inhibition of HSF2 SUMOylation via MEL18 upregulates IGF-IIR and leads to hypertension-induced cardiac hypertrophy” (Huang et al., 2017 [1], this data article contains information about deSUMOylation of HSF2 on lysine 82 on angiotensin II (ANG II -induced cardiac hypertrophy, which is mediated by MEL18. Isolated adult human whole heart tissue showed MEL18-mediated HSF2-IGF-IIR pathway is upregulated in hypertension human heart, compared to health human heart.
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DEFF Research Database (Denmark)
Justinussen, J L; Holm, A; Kornum, B R
2015-01-01
an optimized peptide quantification method for hypocretin-1 extracted from different mouse brain areas and use this method for investigating circadian fluctuations of hypocretin-1 levels in these areas. The results show that hypocretin-1 peptide can be extracted from small pieces of intact tissue...... as does prepro-hypocretin mRNA in the hypothalamus. However, in midbrain and brainstem tissue caudal to the hypothalamus, there was less circadian fluctuation and a tendency for higher levels during the light phase. These data suggest that regulation of the hypocretin system differs between brain areas.......The hypocretin/orexin system regulates, among other things, sleep and energy homeostasis. The system is likely regulated by both homeostatic and circadian mechanisms. Little is known about local differences in the regulation of hypocretin activity. The aim of this study was to establish...
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A PKM2 signature in the failing heart
Rees, Meredith L.; Subramaniam, Janani; Li, Yuanteng; Hamilton, Dale J.; Frazier, O. Howard; Taegtmeyer, Heinrich
2015-01-01
A salient feature of the failing heart is metabolic remodeling towards predominant glucose metabolism and activation of the fetal gene program. Sunitinib is a multitargeted receptor tyrosine kinase inhibitor used for the treatment of highly vascularized tumors. In diabetic patients, sunitinib significantly decreases blood glucose. However, a considerable proportion of sunitinib-treated patients develop cardiac dysfunction or failure. We asked whether sunitinib treatment results in shift towards glycolysis in the heart. Glucose uptake by the heart was increased fivefold in mice treated with sunitinib. Transcript analysis by qPCR revealed an induction of genes associated with glycolysis and reactivation of the fetal gene program. Additionally, we observed a shift in the enzyme pyruvate kinase from the adult M1 (PKM1) isoform to the fetal M2 (PKM2) isoform, a hallmark of the Warburg Effect. This novel observation led us to examine whether a similar shift occurs in human heart failure. Examination of tissue from patients with heart failure similarly displayed an induction of PKM2. Moreover, this phenomenon was partially reversed following mechanical unloading. We propose that pyruvate kinase isoform switching represents a novel feature of the fetal gene program in the failing heart. PMID:25735978
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Morine, Kevin J; Qiao, Xiaoying; York, Sam; Natov, Peter S; Paruchuri, Vikram; Zhang, Yali; Aronovitz, Mark J; Karas, Richard H; Kapur, Navin K
2018-02-27
Background -Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counter-regulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ co-receptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3 and further that neutralizing endoglin activity promotes BMP9 activity. Methods -We examined BMP9 expression and signaling in human cardiac fibroblasts and human subjects with heart failure. We utilized the thoracic aortic constriction (TAC) induced model of heart failure to evaluate the functional effect of BMP9 signaling on cardiac remodeling. Results -BMP9 expression is increased in the circulation and left ventricle (LV) of human subjects with heart failure and is expressed by cardiac fibroblasts. Next, we observed that BMP9 attenuates Type I collagen synthesis in human cardiac fibroblasts using recombinant human BMP9 and an siRNA approach. In BMP9 -/- mice subjected to TAC, loss of BMP9 activity promotes cardiac fibrosis, impairs LV function, and increases LV levels of phosphorylated Smad3 (pSmad3), not pSmad1. In contrast, treatment of wild-type mice subjected to TAC with recombinant BMP9 limits progression of cardiac fibrosis, improves LV function, enhances myocardial capillary density, and increases LV levels of pSmad1, not pSmad3 compared to vehicle treated controls. Since endoglin binds BMP9 with high affinity, we explored the effect of reduced endoglin activity on BMP9 activity. Neutralizing endoglin activity in human cardiac fibroblasts or in wild-type mice subjected to TAC induced heart failure limits collagen production, increases BMP9 protein levels, and increases
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Nonlinear and Stochastic Dynamics in the Heart
Qu, Zhilin; Hu, Gang; Garfinkel, Alan; Weiss, James N.
2014-01-01
In a normal human life span, the heart beats about 2 to 3 billion times. Under diseased conditions, a heart may lose its normal rhythm and degenerate suddenly into much faster and irregular rhythms, called arrhythmias, which may lead to sudden death. The transition from a normal rhythm to an arrhythmia is a transition from regular electrical wave conduction to irregular or turbulent wave conduction in the heart, and thus this medical problem is also a problem of physics and mathematics. In the last century, clinical, experimental, and theoretical studies have shown that dynamical theories play fundamental roles in understanding the mechanisms of the genesis of the normal heart rhythm as well as lethal arrhythmias. In this article, we summarize in detail the nonlinear and stochastic dynamics occurring in the heart and their links to normal cardiac functions and arrhythmias, providing a holistic view through integrating dynamics from the molecular (microscopic) scale, to the organelle (mesoscopic) scale, to the cellular, tissue, and organ (macroscopic) scales. We discuss what existing problems and challenges are waiting to be solved and how multi-scale mathematical modeling and nonlinear dynamics may be helpful for solving these problems. PMID:25267872
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Nonlinear and stochastic dynamics in the heart
Energy Technology Data Exchange (ETDEWEB)
Qu, Zhilin, E-mail: zqu@mednet.ucla.edu [Department of Medicine (Cardiology), David Geffen School of Medicine, University of California, Los Angeles, CA 90095 (United States); Hu, Gang [Department of Physics, Beijing Normal University, Beijing 100875 (China); Garfinkel, Alan [Department of Medicine (Cardiology), David Geffen School of Medicine, University of California, Los Angeles, CA 90095 (United States); Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095 (United States); Weiss, James N. [Department of Medicine (Cardiology), David Geffen School of Medicine, University of California, Los Angeles, CA 90095 (United States); Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 (United States)
2014-10-10
In a normal human life span, the heart beats about 2–3 billion times. Under diseased conditions, a heart may lose its normal rhythm and degenerate suddenly into much faster and irregular rhythms, called arrhythmias, which may lead to sudden death. The transition from a normal rhythm to an arrhythmia is a transition from regular electrical wave conduction to irregular or turbulent wave conduction in the heart, and thus this medical problem is also a problem of physics and mathematics. In the last century, clinical, experimental, and theoretical studies have shown that dynamical theories play fundamental roles in understanding the mechanisms of the genesis of the normal heart rhythm as well as lethal arrhythmias. In this article, we summarize in detail the nonlinear and stochastic dynamics occurring in the heart and their links to normal cardiac functions and arrhythmias, providing a holistic view through integrating dynamics from the molecular (microscopic) scale, to the organelle (mesoscopic) scale, to the cellular, tissue, and organ (macroscopic) scales. We discuss what existing problems and challenges are waiting to be solved and how multi-scale mathematical modeling and nonlinear dynamics may be helpful for solving these problems.
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Nonlinear and stochastic dynamics in the heart
International Nuclear Information System (INIS)
Qu, Zhilin; Hu, Gang; Garfinkel, Alan; Weiss, James N.
2014-01-01
In a normal human life span, the heart beats about 2–3 billion times. Under diseased conditions, a heart may lose its normal rhythm and degenerate suddenly into much faster and irregular rhythms, called arrhythmias, which may lead to sudden death. The transition from a normal rhythm to an arrhythmia is a transition from regular electrical wave conduction to irregular or turbulent wave conduction in the heart, and thus this medical problem is also a problem of physics and mathematics. In the last century, clinical, experimental, and theoretical studies have shown that dynamical theories play fundamental roles in understanding the mechanisms of the genesis of the normal heart rhythm as well as lethal arrhythmias. In this article, we summarize in detail the nonlinear and stochastic dynamics occurring in the heart and their links to normal cardiac functions and arrhythmias, providing a holistic view through integrating dynamics from the molecular (microscopic) scale, to the organelle (mesoscopic) scale, to the cellular, tissue, and organ (macroscopic) scales. We discuss what existing problems and challenges are waiting to be solved and how multi-scale mathematical modeling and nonlinear dynamics may be helpful for solving these problems
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Application of HEART technique in health care system and accuracy of its results
Directory of Open Access Journals (Sweden)
Mohammad Beiruti
2016-12-01
Full Text Available Introduction: Human error is considered as a crucial challenge in occupational settings. Health care system is amongst occupational environments with high rate of human errors. Numerous preceding studies noted that more than 2/3 of medical errors are preventable. Accordingly, different methods are suggested to evaluate human errors, especially in nuclear industries. The aim of this study was to evaluate the application and accuracy of HEART technique in medical health system. Material and Method: This qualitative study was conducted in surgical intensive care units of a hospital in Shiraz city. All nurses recorded errors were categorized regarding the given tasks and then all tasks were ranked based on the number of errors. The probability of nurses’ tasks error was estimated through AHP-HEART method and the resultant ranking was compared with the recorded errors. Additionally, the prioritization of contributing factors to errors, determined by AHP and AHP-HEART methods, was compared employing Pearson statistical test. Results: Based on the results, there was a concordance in the rate of nurses’ error determined by HEART method and the recorded errors. However, no significant correlation was between errors contributing factors determined by AHP and AHP-HEART methods. Conclusion: This study suggested that although HEART technique was successful to rank the tasks considering the magnitude of error probability, but the coefficients of error producing conditions should be customized for nurses’ tasks in order to provide appropriate control measures.
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Mathematical Model Analysis of Heart-Arterial Interaction in Hypertension
2001-10-25
conscious dogs with dilated cardiomyopathy ,” ! " # , vol. 260, pp. H1903-H1911, 1991. [7] P. Segers, N...with data measured in the isolated canine [14] or cat [15] heart, pumping into an artificial load or in the intact sheep [16] and human [7]. Left...instantaneous pressure-volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio,” , vol. 32, pp. 314
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DEFF Research Database (Denmark)
Kupers, Ron; Frokjaer, Vibe G.; Erritzoe, David
2010-01-01
There is a large body of evidence that the serotonergic system plays an important role in the transmission and regulation of pain. Here we used positron emission tomography (PET) with the serotonin transporter (SERT) tracer [11C]DASB to study the relationship between SERT binding in the brain and....... The negative correlation between SERT binding in the hypothalamus and insula with tonic pain ratings suggests a possible serotonergic control of the role of these areas in the modulation or in the affective appreciation of pain.......) tonic noxious heat stimulus. PET data were analyzed using both volume-of-interest (VOI) and voxel-based approaches. VOI analysis revealed a significant negative correlation between tonic pain ratings and SERT binding in the hypothalamus (r = −0.59; p = 0.008), a finding confirmed by the parametric...... analysis. The parametric analysis also revealed a negative correlation between tonic pain ratings and SERT binding in the right anterior insula. Measures of regional SERT binding did not correlate with pain threshold or with responses to short phasic suprathreshold phasic heat stimuli. Finally, the VOI...
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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 ...
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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
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Increased Heme Levels in the Heart Lead to Exacerbated Ischemic Injury.
Sawicki, Konrad Teodor; Shang, Meng; Wu, Rongxue; Chang, Hsiang-Chun; Khechaduri, Arineh; Sato, Tatsuya; Kamide, Christine; Liu, Ting; Naga Prasad, Sathyamangla V; Ardehali, Hossein
2015-07-31
Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart. We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to nontransgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death observed with ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to nonischemic cardiomyopathy. Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a novel approach for protection against the
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Metabolic activity in the insular cortex and hypothalamus predicts hot flashes: an FDG-PET study.
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.
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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.
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A mighty small heart: the cardiac proteome of adult Drosophila melanogaster.
Directory of Open Access Journals (Sweden)
Anthony Cammarato
2011-04-01
Full Text Available Drosophila melanogaster is emerging as a powerful model system for the study of cardiac disease. Establishing peptide and protein maps of the Drosophila heart is central to implementation of protein network studies that will allow us to assess the hallmarks of Drosophila heart pathogenesis and gauge the degree of conservation with human disease mechanisms on a systems level. Using a gel-LC-MS/MS approach, we identified 1228 protein clusters from 145 dissected adult fly hearts. Contractile, cytostructural and mitochondrial proteins were most abundant consistent with electron micrographs of the Drosophila cardiac tube. Functional/Ontological enrichment analysis further showed that proteins involved in glycolysis, Ca(2+-binding, redox, and G-protein signaling, among other processes, are also over-represented. Comparison with a mouse heart proteome revealed conservation at the level of molecular function, biological processes and cellular components. The subsisting peptidome encompassed 5169 distinct heart-associated peptides, of which 1293 (25% had not been identified in a recent Drosophila peptide compendium. PeptideClassifier analysis was further used to map peptides to specific gene-models. 1872 peptides provide valuable information about protein isoform groups whereas a further 3112 uniquely identify specific protein isoforms and may be used as a heart-associated peptide resource for quantitative proteomic approaches based on multiple-reaction monitoring. In summary, identification of excitation-contraction protein landmarks, orthologues of proteins associated with cardiovascular defects, and conservation of protein ontologies, provides testimony to the heart-like character of the Drosophila cardiac tube and to the utility of proteomics as a complement to the power of genetics in this growing model of human heart disease.
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Heart Health - Heart Disease: Symptoms, Diagnosis, Treatment
... 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 ...
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Heart Health: The Heart Truth Campaign 2009
... 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) ...
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Women's Heart Disease: Heart Disease Risk Factors
... 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 ...
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Wijnen, H.J.L.M.; Kloet, E.R. de; Versteeg, D.H.G.; Jong, Wybren de
1980-01-01
The noradrenaline concentration and the α-methyl-para-tyrosine (α-MPT)-induced disappearance of noradrenaline were determined in several nuclei of the hypothalamus and the medulla oblongata of renal hypertensive rats (two-kidney Goldblatt hypertension). A decreased α-MPT-induced disappearance of
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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)
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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.
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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.
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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.
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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.
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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.
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Diarra, A; Lefauconnier, J M; Valens, M; Georges, P; Gripois, D
1989-10-01
The influence of neonatal hypo- and hyperthyroidism on different aspects of tyrosine metabolism in the hypothalamus, striatum, brainstem, adrenal glands, heart and brown adipose tissue (BAT) were studied in 14-day old rats. The synthesis rate of catecholamines (CA) was also determined in vivo after the injection of labelled tyrosine. Hypothyroidism increases tyrosinaemia and endogenous tyrosine concentration in the hypothalamus and BAT. Hyperthyroidism decreases tyrosinaemia and endogenous tyrosine levels in the striatum, adrenals and heart. The accumulation rate of tyrosine determined 30 min after an intravenous injection of the labelled amino acid has been determined in the organs, together with the influx of the amino acid, determined within 20s. Hypothyroidism increases tyrosine accumulation rate in all the organs studied, and tyrosine clearance is decreased in the striatum and brainstem; together with an increased tyrosinaemia, this leads to a normal influx. The influx of tyrosine is increased in the hypothalamus. Hyperthyroidism decreases tyrosine accumulation rate in all the organs except the adrenals. These results indicate that the thyroid status of the young rat can influence tyrosine uptake mechanisms, without modifying an organ's tyrosine content. The fact that hypothyroidism increases tyrosine influx in the hypothalamus without modifying it in the brainstem and striatum reflects an heterogeneous reactivity to the lack of thyroid hormones in different brain structures. Neonatal hypothyroidism decreases the CA synthesis rate in the striatum, the heart and the interscapular brown adipose tissue, while synthesis was enhanced in the brainstem and the adrenals. It is likely that these variations in CA synthesis are due to thyroid hormone modulation of tyrosine hydroxylase activity, the enzyme which catalyses the rate limiting step in CA biosynthesis.
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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.
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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.
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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.
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Fuzzy Expert System for Heart Attack Diagnosis
Hassan, Norlida; Arbaiy, Nureize; Shah, Noor Aziyan Ahmad; Afizah Afif@Afip, Zehan
2017-08-01
Heart attack is one of the serious illnesses and reported as the main killer disease. Early prevention is significant to reduce the risk of having the disease. The prevention efforts can be strengthen through awareness and education about risk factor and healthy lifestyle. Therefore the knowledge dissemination is needed to play role in order to distribute and educate public in health care management and disease prevention. Since the knowledge dissemination in medical is important, there is a need to develop a knowledge based system that can emulate human intelligence to assist decision making process. Thereby, this study utilized hybrid artificial intelligence (AI) techniques to develop a Fuzzy Expert System for Diagnosing Heart Attack Disease (HAD). This system integrates fuzzy logic with expert system, which helps the medical practitioner and people to predict the risk and as well as diagnosing heart attack based on given symptom. The development of HAD is expected not only providing expert knowledge but potentially become one of learning resources to help citizens to develop awareness about heart-healthy lifestyle.
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[Camera-cinematography of the heart (author's transl)].
Adam, W E; Meyer, G; Bitter, F; Kampmann, H; Bargon, G; Stauch, M
1975-07-01
By "camera-cinematography" of the heart, we mean an isotope method which permits detailed observation of cardiac mechanics without the use of a catheter. All that is necessary is an intravenous injection of 10 to 15 mCi 99mTc human serum albumen followed after ten minutes by a five to ten minute period of observation with a scintilation camera. At this time the isotope has become distributed in the blood. Variations in the precordial impulses correspond with intra-cardiac changes of blood volume during a cardiac cycle. Analysis of the R-wave provides adequate information of cyclical volume changes in limited portions of the heart. This is achieved by a monitor with a pseudo-3-dimensional display; contraction and relaxation of the myocardium can be shown for any chosen longitudinal or horizontal diameter of the heart. Our programme allows simultaneous presentation of the movement of any point on the myocardium as a time-activity curve. The method is recommended as an addition to chest radiography, heart screening or cardiac kymography before carrying out cardiac catheterisation.
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How Heart Valves Evolve to Adapt to an Extreme-Pressure System
DEFF Research Database (Denmark)
Amstrup Funder, Jonas; Christian Danielsen, Carl; Baandrup, Ulrik
2017-01-01
BACKGROUND: Heart valves which exist naturally in an extreme-pressure system must have evolved in a way to resist the stresses of high pressure. Giraffes are interesting as they naturally have a blood pressure twice that of humans. Thus, knowledge regarding giraffe heart valves may aid...... in developing techniques to design improved pressure-resistant biological heart valves. METHODS: Heart valves from 12 giraffes and 10 calves were explanted and subjected to either biomechanical or morphological examinations. Strips from the heart valves were subjected to cyclic loading tests, followed...... in giraffes than in calves, which would make giraffe valves more resistant to the high-pressure forces. However, collagen also stiffens and thickens the valves. The mitral leaflets showed similar (but mostly insignificant) trends in strength, stiffness, and collagen content....
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Murine Models of Heart Failure With Preserved Ejection Fraction
Directory of Open Access Journals (Sweden)
Maria Valero-Muñoz, PhD
2017-12-01
Full Text Available Heart failure with preserved ejection fraction (HFpEF is characterized by signs and symptoms of heart failure in the presence of a normal left ventricular ejection fraction. Despite accounting for up to 50% of all clinical presentations of heart failure, the mechanisms implicated in HFpEF are poorly understood, thus precluding effective therapy. The pathophysiological heterogeneity in the HFpEF phenotype also contributes to this disease and likely to the absence of evidence-based therapies. Limited access to human samples and imperfect animal models that completely recapitulate the human HFpEF phenotype have impeded our understanding of the mechanistic underpinnings that exist in this disease. Aging and comorbidities such as atrial fibrillation, hypertension, diabetes and obesity, pulmonary hypertension, and renal dysfunction are highly associated with HFpEF, yet the relationship and contribution between them remains ill-defined. This review discusses some of the distinctive clinical features of HFpEF in association with these comorbidities and highlights the advantages and disadvantage of commonly used murine models used to study the HFpEF phenotype.
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Reassessing Phase II Heart Failure Clinical Trials: Consensus Recommendations
Butler, Javed; Hamo, Carine E.; Udelson, James E.; O’Connor, Christopher; Sabbah, Hani N.; Metra, Marco; Shah, Sanjiv J.; Kitzman, Dalane W.; Teerlink, John; Bernstein, Harold S.; Brooks, Gabriel; Depre, Christophe; DeSouza, Mary M.; Dinh, Wilfried; Donovan, Mark; Frische-Danielson, Regina; Frost, Robert J.; Garza, Dahlia; Gohring, Udo-Michael; Hellawell, Jennifer; Hsia, Judith; Ishihara, Shiro; Kay-Mugford, Patricia; Koglin, Joerg; Kozinn, Marc; Larson, Christopher J.; Mayo, Martha; Gan, Li-Ming; Mugnier, Pierrre; Mushonga, Sekayi; Roessig, Lothar; Russo, Cesare; Salsali, Afshin; Satler, Carol; Shi, Victor; Ticho, Barry; van der Laan, Michael; Yancy, Clyde; Stockbridge, Norman; Gheorghiade, Mihai
2017-01-01
The increasing burden and the continued suboptimal outcomes for patients with heart failure underlines the importance of continued research to develop novel therapeutics for this disorder. This can only be accomplished with successful translation of basic science discoveries into direct human application through effective clinical trial design and execution that results in a substantially improved clinical course and outcomes. In this respect, phase II clinical trials play a pivotal role in determining which of the multitude of potential basic science discoveries should move to the large and expansive registration trials in humans. A critical examination of the phase II trials in heart failure reveals multiple shortcomings in their concept, design, execution, and interpretation. To further a dialogue regarding the challenges and potential for improvement and the role of phase II trials in patients with heart failure, the Food and Drug Administration facilitated a meeting on October 17th 2016 represented by clinicians, researchers, industry members, and regulators. This document summarizes the discussion from this meeting and provides key recommendations for future directions. PMID:28356300
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Multigated radionuclide study of the total artificial heart
International Nuclear Information System (INIS)
Datz, F.L.; Christian, P.E.; Taylor, A. Jr.; Hastings, W.L.; De Vries, W.C.
1987-01-01
A permanent total artificial heart, the Jarvik-7, was implanted into a 61-year-old male with a severe cardiomyopathy. Gated radionuclide studies were performed in the patient both prior to surgery and following implantation. Preoperative gated radionuclide cardiac studies revealed marked left ventricular enlargement, severe hypokinesis and a left ventricular ejection fraction of 10%. The right ventricle was moderately enlarged with a 27% ejection fraction. Following implantation of the Jarvik-7 artificial heart, gated cardiac studies were performed with a computer gated by a signal from the heart controller. The left ventricular ejection fraction was 69% and the right ventricular ejection fraction was 62%. This compared to a theoretical ejection fraction of 74% for each ventricle based on chamber anatomy. There was excellent ventricular emptying. Phase analysis showed uniform diaphragm motion. The use of gated cardiac studies in humans may prove helpful in evaluating mechanical problems with the artificial heart, such as manlfunction of the diaphragm, before they become clinically apparent. (orig.)
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Multigated radionuclide study of the total artificial heart
Energy Technology Data Exchange (ETDEWEB)
Datz, F L; Christian, P E; Taylor, A Jr; Hastings, W L; De Vries, W C
1987-07-01
A permanent total artificial heart, the Jarvik-7, was implanted into a 61-year-old male with a severe cardiomyopathy. Gated radionuclide studies were performed in the patient both prior to surgery and following implantation. Preoperative gated radionuclide cardiac studies revealed marked left ventricular enlargement, severe hypokinesis and a left ventricular ejection fraction of 10%. The right ventricle was moderately enlarged with a 27% ejection fraction. Following implantation of the Jarvik-7 artificial heart, gated cardiac studies were performed with a computer gated by a signal from the heart controller. The left ventricular ejection fraction was 69% and the right ventricular ejection fraction was 62%. This compared to a theoretical ejection fraction of 74% for each ventricle based on chamber anatomy. There was excellent ventricular emptying. Phase analysis showed uniform diaphragm motion. The use of gated cardiac studies in humans may prove helpful in evaluating mechanical problems with the artificial heart, such as manlfunction of the diaphragm, before they become clinically apparent.
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... 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 ...
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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 ...
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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...
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Embryonic stem cell therapy of heart failure in genetic cardiomyopathy.
Yamada, Satsuki; Nelson, Timothy J; Crespo-Diaz, Ruben J; Perez-Terzic, Carmen; Liu, Xiao-Ke; Miki, Takashi; Seino, Susumu; Behfar, Atta; Terzic, Andre
2008-10-01
Pathogenic causes underlying nonischemic cardiomyopathies are increasingly being resolved, yet repair therapies for these commonly heritable forms of heart failure are lacking. A case in point is human dilated cardiomyopathy 10 (CMD10; Online Mendelian Inheritance in Man #608569), a progressive organ dysfunction syndrome refractory to conventional therapies and linked to mutations in cardiac ATP-sensitive K(+) (K(ATP)) channel subunits. Embryonic stem cell therapy demonstrates benefit in ischemic heart disease, but the reparative capacity of this allogeneic regenerative cell source has not been tested in inherited cardiomyopathy. Here, in a Kir6.2-knockout model lacking functional K(ATP) channels, we recapitulated under the imposed stress of pressure overload the gene-environment substrate of CMD10. Salient features of the human malignant heart failure phenotype were reproduced, including compromised contractility, ventricular dilatation, and poor survival. Embryonic stem cells were delivered through the epicardial route into the left ventricular wall of cardiomyopathic stressed Kir6.2-null mutants. At 1 month of therapy, transplantation of 200,000 cells per heart achieved teratoma-free reversal of systolic dysfunction and electrical synchronization and halted maladaptive remodeling, thereby preventing end-stage organ failure. Tracked using the lacZ reporter transgene, stem cells engrafted into host heart. Beyond formation of cardiac tissue positive for Kir6.2, transplantation induced cell cycle activation and halved fibrotic zones, normalizing sarcomeric and gap junction organization within remuscularized hearts. Improved systemic function induced by stem cell therapy translated into increased stamina, absence of anasarca, and benefit to overall survivorship. Embryonic stem cells thus achieve functional repair in nonischemic genetic cardiomyopathy, expanding indications to the therapy of heritable heart failure. Disclosure of potential conflicts of interest is
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Immunostaining of dissected zebrafish embryonic heart.
Yang, Jingchun; Xu, Xiaolei
2012-01-10
Zebrafish embryo becomes a popular in vivo vertebrate model for studying cardiac development and human heart diseases due to its advantageous embryology and genetics. About 100-200 embryos are readily available every week from a single pair of adult fish. The transparent embryos that develop ex utero make them ideal for assessing cardiac defects. The expression of any gene can be manipulated via morpholino technology or RNA injection. Moreover, forward genetic screens have already generated a list of mutants that affect different perspectives of cardiogenesis. Whole mount immunostaining is an important technique in this animal model to reveal the expression pattern of the targeted protein to a particular tissue. However, high resolution images that can reveal cellular or subcellular structures have been difficult, mainly due to the physical location of the heart and the poor penetration of the antibodies. Here, we present a method to address these bottlenecks by dissecting heart first and then conducting the staining process on the surface of a microscope slide. To prevent the loss of small heart samples and to facilitate solution handling, we restricted the heart samples within a circle on the surface of the microscope slides drawn by an immEdge pen. After the staining, the fluorescence signals can be directly observed by a compound microscope. Our new method significantly improves the penetration for antibodies, since a heart from an embryonic fish only consists of few cell layers. High quality images from intact hearts can be obtained within a much reduced procession time for zebrafish embryos aged from day 2 to day 6. Our method can be potentially extended to stain other organs dissected from either zebrafish or other small animals. Copyright © 2012 Journal of Visualized Experiments
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2013 update on congenital heart disease, clinical cardiology, heart failure, and heart transplant.
Subirana, M Teresa; Barón-Esquivias, Gonzalo; Manito, Nicolás; Oliver, José M; Ripoll, Tomás; Lambert, Jose Luis; Zunzunegui, José L; Bover, Ramon; García-Pinilla, José Manuel
2014-03-01
This article presents the most relevant developments in 2013 in 3 key areas of cardiology: congenital heart disease, clinical cardiology, and heart failure and transplant. Within the area of congenital heart disease, we reviewed contributions related to sudden death in adult congenital heart disease, the importance of specific echocardiographic parameters in assessing the systemic right ventricle, problems in patients with repaired tetralogy of Fallot and indication for pulmonary valve replacement, and confirmation of the role of specific factors in the selection of candidates for Fontan surgery. The most recent publications in clinical cardiology include a study by a European working group on correct diagnostic work-up in cardiomyopathies, studies on the cost-effectiveness of percutaneous aortic valve implantation, a consensus document on the management of type B aortic dissection, and guidelines on aortic valve and ascending aortic disease. The most noteworthy developments in heart failure and transplantation include new American guidelines on heart failure, therapeutic advances in acute heart failure (serelaxin), the management of comorbidities such as iron deficiency, risk assessment using new biomarkers, and advances in ventricular assist devices. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.
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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
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Normalization of NAD+ Redox Balance as a Therapy for Heart Failure.
Lee, Chi Fung; Chavez, Juan D; Garcia-Menendez, Lorena; Choi, Yongseon; Roe, Nathan D; Chiao, Ying Ann; Edgar, John S; Goo, Young Ah; Goodlett, David R; Bruce, James E; Tian, Rong
2016-09-20
Impairments of mitochondrial function in the heart are linked intricately to the development of heart failure, but there is no therapy for mitochondrial dysfunction. We assessed the reduced/oxidized ratio of nicotinamide adenine dinucleotide (NADH/NAD(+) ratio) and protein acetylation in the failing heart. Proteome and acetylome analyses were followed by docking calculation, mutagenesis, and mitochondrial calcium uptake assays to determine the functional role of specific acetylation sites. The therapeutic effects of normalizing mitochondrial protein acetylation by expanding the NAD(+) pool also were tested. Increased NADH/NAD(+) and protein hyperacetylation, previously observed in genetic models of defective mitochondrial function, also are present in human failing hearts as well as in mouse hearts with pathologic hypertrophy. Elevation of NAD(+) levels by stimulating the NAD(+) salvage pathway suppressed mitochondrial protein hyperacetylation and cardiac hypertrophy, and improved cardiac function in responses to stresses. Acetylome analysis identified a subpopulation of mitochondrial proteins that was sensitive to changes in the NADH/NAD(+) ratio. Hyperacetylation of mitochondrial malate-aspartate shuttle proteins impaired the transport and oxidation of cytosolic NADH in the mitochondria, resulting in altered cytosolic redox state and energy deficiency. Furthermore, acetylation of oligomycin-sensitive conferring protein at lysine-70 in adenosine triphosphate synthase complex promoted its interaction with cyclophilin D, and sensitized the opening of mitochondrial permeability transition pore. Both could be alleviated by normalizing the NAD(+) redox balance either genetically or pharmacologically. We show that mitochondrial protein hyperacetylation due to NAD(+) redox imbalance contributes to the pathologic remodeling of the heart via 2 distinct mechanisms. Our preclinical data demonstrate a clear benefit of normalizing NADH/NAD(+) imbalance in the failing hearts
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The hippo pathway in heart development, regeneration, and diseases.
Zhou, Qi; Li, Li; Zhao, Bin; Guan, Kun-Liang
2015-04-10
The heart is the first organ formed during mammalian development. A properly sized and functional heart is vital throughout the entire lifespan. Loss of cardiomyocytes because of injury or diseases leads to heart failure, which is a major cause of human morbidity and mortality. Unfortunately, regenerative potential of the adult heart is limited. The Hippo pathway is a recently identified signaling cascade that plays an evolutionarily conserved role in organ size control by inhibiting cell proliferation, promoting apoptosis, regulating fates of stem/progenitor cells, and in some circumstances, limiting cell size. Interestingly, research indicates a key role of this pathway in regulation of cardiomyocyte proliferation and heart size. Inactivation of the Hippo pathway or activation of its downstream effector, the Yes-associated protein transcription coactivator, improves cardiac regeneration. Several known upstream signals of the Hippo pathway such as mechanical stress, G-protein-coupled receptor signaling, and oxidative stress are known to play critical roles in cardiac physiology. In addition, Yes-associated protein has been shown to regulate cardiomyocyte fate through multiple transcriptional mechanisms. In this review, we summarize and discuss current findings on the roles and mechanisms of the Hippo pathway in heart development, injury, and regeneration. © 2015 American Heart Association, Inc.
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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)
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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. ...
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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
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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 ...
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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.
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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.
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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.
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Joint Modelling of Longitudinal and Survival Data with Applications in Heart Valve Data
E-R. Andrinopoulou (Eleni-Rosalina)
2014-01-01
markdownabstract__Abstract__ The heart is one of the most important organs in the entire human body. Specifically, it is a pump composed of muscle which pumps blood throughout the blood vessels to various parts of the body by repeated rhythmic contractions. The four heart valves determine the
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Combined heart-kidney transplantation after total artificial heart insertion.
Ruzza, A; Czer, L S C; Ihnken, K A; Sasevich, M; Trento, A; Ramzy, D; Esmailian, F; Moriguchi, J; Kobashigawa, J; Arabia, F
2015-01-01
We present the first single-center report of 2 consecutive cases of combined heart and kidney transplantation after insertion of a total artificial heart (TAH). Both patients had advanced heart failure and developed dialysis-dependent renal failure after implantation of the TAH. The 2 patients underwent successful heart and kidney transplantation, with restoration of normal heart and kidney function. On the basis of this limited experience, we consider TAH a safe and feasible option for bridging carefully selected patients with heart and kidney failure to combined heart and kidney transplantation. Recent FDA approval of the Freedom driver may allow outpatient management at substantial cost savings. The TAH, by virtue of its capability of providing pulsatile flow at 6 to 10 L/min, may be the mechanical circulatory support device most likely to recover patients with marginal renal function and advanced heart failure. Copyright © 2015 Elsevier Inc. All rights reserved.
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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.
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Maternal Cortisol Mediates Hypothalamus-Pituitary-Interrenal Axis Development in Zebrafish
Nesan, Dinushan; Vijayan, Mathilakath M.
2016-01-01
In zebrafish (Danio rerio), de novo synthesis of cortisol in response to stressor exposure commences only after hatch. Maternally deposited cortisol is present during embryogenesis, but a role for this steroid in early development is unclear. We tested the hypothesis that maternal cortisol is essential for the proper development of hypothalamus-pituitary-interrenal (HPI) axis activity and the onset of the stressor-induced cortisol response in larval zebrafish. In this study, zygotic cortisol content was manipulated by microinjecting antibody to sequester this steroid, thereby making it unavailable during embryogenesis. This was compared with embryos containing excess cortisol by microinjection of exogenous steroid. The resulting larval phenotypes revealed distinct treatment effects, including deformed mesoderm structures when maternal cortisol was unavailable and cardiac edema after excess cortisol. Maternal cortisol unavailability heightened the cortisol stress response in post-hatch larvae, whereas excess cortisol abolished the stressor-mediated cortisol elevation. This contrasting hormonal response corresponded with altered expression of key HPI axis genes, including crf, 11B hydroxylase, pomca, and star, which were upregulated in response to reduced cortisol availability and downregulated when embryos had excess cortisol. These findings for the first time underscore a critical role for maternally deposited cortisol in programming HPI axis development and function in zebrafish. PMID:26940285
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Positron emission tomography of the heart
International Nuclear Information System (INIS)
Budinger, T.F.; Yano, Y.; Huesman, R.H.; Derenzo, S.E.; Moyer, B.R.; Mathis, C.A.; Ganz, E.; Knittel, B.
1983-01-01
Positron emission tomography (PET) of the heart can measure blood perfusion, metabolism of fatty acids, metabolism of sugars, uptake of amino acids and can quantitate infarction volume. The principles are reviewed which are basic to PET instrumentation and procedures for quantitative studies of human physiology with examples of measurements of myocardial flow and metabolism
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Insulin action in the human brain: evidence from neuroimaging studies.
Kullmann, S; Heni, M; Fritsche, A; Preissl, H
2015-06-01
Thus far, little is known about the action of insulin in the human brain. Nonetheless, recent advances in modern neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG), have made it possible to investigate the action of insulin in the brain in humans, providing new insights into the pathogenesis of brain insulin resistance and obesity. Using MEG, the clinical relevance of the action of insulin in the brain was first identified, linking cerebral insulin resistance with peripheral insulin resistance, genetic predisposition and weight loss success in obese adults. Although MEG is a suitable tool for measuring brain activity mainly in cortical areas, fMRI provides high spatial resolution for cortical as well as subcortical regions. Thus, the action of insulin can be detected within all eating behaviour relevant regions, which include regions deeply located within the brain, such as the hypothalamus, midbrain and brainstem, as well as regions within the striatum. In this review, we outline recent advances in the field of neuroimaging aiming to investigate the action of insulin in the human brain using different routes of insulin administration. fMRI studies have shown a significant insulin-induced attenuation predominantly in the occipital and prefrontal cortical regions and the hypothalamus, successfully localising insulin-sensitive brain regions in healthy, mostly normal-weight individuals. However, further studies are needed to localise brain areas affected by insulin resistance in obese individuals, which is an important prerequisite for selectively targeting brain insulin resistance in obesity. © 2015 British Society for Neuroendocrinology.
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Review Article Heart failure - an inflammatory paradigm
African Journals Online (AJOL)
1999-02-01
Feb 1, 1999 ... Together with the growing clinical problem of heart failure, new information at a .... nificantly raised in the prevention as well as the treatment arms when .... tricular dysfunction and pulmonary oedema in humans; experimentally ... adenine dinucleotide (reduced) and the rate-limiting amino acid (L-arginine).
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Healthy Body, Happy Heart: Improve Your Heart Health
... November 2017 Print this issue Healthy Body, Happy Heart Improve Your Heart Health En español Send us your comments Every moment of the day, your heart is pumping blood throughout your body. In silent ...
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Arslanian-Engoren, Cynthia; Eastwood, Jo-Ann; De Jong, Marla J; Berra, Kathy
2015-01-01
The American Heart Association created Go Red Heart Match, a free and secure online program that enables women to connect with each other to fight heart disease either personally or as a caregiver for someone with heart disease. Through these connections, participants have an opportunity to develop a personal, private, and supportive relationship with other women; share common experiences; and motivate and encourage each other to follow a heart-healthy lifestyle. The aims of this study were to describe the demographic characteristics of the Go Red Heart Match responders and to determine whether participation in the program prompted participants to engage in heart-healthy behaviors. A secondary analysis of data collected as part of a needs assessment survey from the American Heart Association Go Red Heart Match was conducted. A total of 117 (35%) of the 334 invited women completed the survey. Most responders were female, married, and college educated. A total of 105 (90%) responders were diagnosed with a type of heart disease or stroke and 77 (73%) responders had undergone treatment. As a result of participating in the program, 75% of the responders reported the following improvements in heart-healthy behaviors: eating a more heart-healthy diet (54%), exercising more frequently (53%), losing weight (47%), and quitting smoking (10%). Responders who had a diagnosis of heart attack (n = 48) were more likely (P = .003) to quit smoking than were those with other diagnoses (n = 69). Notably, 48% of responders reported encouraging someone else in their life to speak to their doctor about their risk for heart disease. Most women who participated in Heart Match reported engaging in new heart-healthy behaviors. The findings support expanding the existing program in a more diverse population as a potentially important way to reach women and encourage cardiovascular disease risk reduction for those with heart disease and stroke.
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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
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... 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 ...
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Hospital Value-Based Purchasing (HVBP) – Heart Failure Scores
U.S. Department of Health & Human Services — A list of hospitals participating in the Hospital VBP Program and their performance rates and scores for the Clinical Process of Care Heart Failure measures.
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Myocardial Expression of Macrophage Migration Inhibitory Factor in Patients with Heart Failure
Directory of Open Access Journals (Sweden)
Julia Pohl
2017-10-01
Full Text Available Macrophage migration inhibitory factor (MIF is a pleiotropic inflammatory protein and contributes to several different inflammatory and ischemic/hypoxic diseases. MIF was shown to be cardioprotective in experimental myocardial ischemia/reperfusion injury and its expression is regulated by the transcription factor hypoxia-inducible factor (HIF-1α. We here report on MIF expression in the failing human heart and assess myocardial MIF in different types of cardiomyopathy. Myocardial tissue samples from n = 30 patients were analyzed by quantitative Real-Time PCR. MIF and HIF-1α mRNA expression was analyzed in myocardial samples from patients with ischemic (ICM and non-ischemic cardiomyopathy (NICM and from patients after heart transplantation (HTX. MIF expression was elevated in myocardial samples from patients with ICM compared to NICM. Transplanted hearts showed lower MIF levels compared to hearts from patients with ICM. Expression of HIF-1α was analyzed and was shown to be significantly increased in ICM patients compared to patients with NICM. MIF and HIF-1α mRNA is expressed in the human heart. MIF and HIF-1α expression depends on the underlying type of cardiomyopathy. Patients with ICM show increased myocardial MIF and HIF-1α expression.
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International Nuclear Information System (INIS)
Martyn, C.N.
1979-01-01
Female rats given a single injection of testosterone propionate (TP) in the first few days of post-natal life exhibit post-pubertally, persistent vaginal oestrous, sterility, disordered secretion of gonadotrophins and modified patterns of sexual behaviour. The effects of TP on the incorporation of 14 C-uridine in the CNS of 5 and 61/2 day old litter mate triads consisting of male, female and TP treated female rats were investigated. Low resolution autoradiographs of serial sections of brain were prepared and analysed. A sexual dimorphism in cell nuclear size was found in the suprachiasmatic, arcuate and paraventricular nuclei of the hypothalamus. TP treatment resulted in an increase in nuclear size towards the male pattern in the latter two areas. A decrease in cell nuclear size was found in the ventromedial and suprachiasmatic nuclei. Neither sex differences nor changes following TP injection were detected in rate of incorporation of 14 C-uridine in any areas of the brain, although a significant (p<0.02) reduction in uridine incorporation in the adrenal of the female animal 24 hours after TP injection was demonstrated. The results suggested an immediate direct action of TP on the hypothalamus and peripheral tissues of the neonatal rat. (author)
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Women's Heart Disease: Join the Heart Truth Community
... this page please turn JavaScript on. Feature: Women's Heart Disease Join The Heart Truth Community Past Issues / Winter 2014 Table of Contents National Symbol The centerpiece of The Heart Truth ® is The Red Dress ® which was introduced ...
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Self-administration of morphine into the lateral hypothalamus in the mouse.
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.
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Deregulated Cardiac Specific MicroRNAs in Postnatal Heart Growth
Directory of Open Access Journals (Sweden)
Pujiao Yu
2016-01-01
Full Text Available The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs, as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs—miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p—were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases.
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Relationship between stroke volume, cardiac output and filling of the heart during tilt
DEFF Research Database (Denmark)
Bundgaard-Nielsen, M.; Sorensen, H.; Dalsgaard, M.
2009-01-01
. With the supine resting position as a reference, we assessed stroke volume (SV), cardiac output (CO) and filling of the heart during graded tilt to evaluate whether SV and CO are maintained during an assumed maximal physiological filling of the heart elicited by 90 degrees HDT in healthy resting humans. METHODS...
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Laperrousaz, Elise; Moullé, Valentine S; Denis, Raphaël G; Kassis, Nadim; Berland, Chloé; Colsch, Benoit; Fioramonti, Xavier; Philippe, Erwann; Lacombe, Amélie; Vanacker, Charlotte; Butin, Noémie; Bruce, Kimberley D; Wang, Hong; Wang, Yongping; Gao, Yuanqing; Garcia-Caceres, Cristina; Prévot, Vincent; Tschöp, Matthias H; Eckel, Robert H; Le Stunff, Hervé; Luquet, Serge; Magnan, Christophe; Cruciani-Guglielmacci, Céline
2017-07-01
Regulation of energy balance involves the participation of many factors, including nutrients, among which are circulating lipids, acting as peripheral signals informing the central nervous system of the energy status of the organism. It has been shown that neuronal lipoprotein lipase (LPL) participates in the control of energy balance by hydrolysing lipid particles enriched in triacylglycerols. Here, we tested the hypothesis that LPL in the mediobasal hypothalamus (MBH), a well-known nucleus implicated in the regulation of metabolic homeostasis, could also contribute to the regulation of body weight and glucose homeostasis. We injected an adeno-associated virus (AAV) expressing Cre-green fluorescent protein into the MBH of Lpl-floxed mice (and wild-type mice) to specifically decrease LPL activity in the MBH. In parallel, we injected an AAV overexpressing Lpl into the MBH of wild-type mice. We then studied energy homeostasis and hypothalamic ceramide content. The partial deletion of Lpl in the MBH in mice led to an increase in body weight compared with controls (37.72 ± 0.7 g vs 28.46 ± 0.12, p < 0.001) associated with a decrease in locomotor activity. These mice developed hyperinsulinaemia and glucose intolerance. This phenotype also displayed reduced expression of Cers1 in the hypothalamus as well as decreased concentration of several C18 species of ceramides and a 3-fold decrease in total ceramide intensity. Conversely, overexpression of Lpl specifically in the MBH induced a decrease in body weight. Our study shows that LPL in the MBH is an important regulator of body weight and glucose homeostasis.
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Mercury Exposure and Heart Diseases
Genchi, Giuseppe; Sinicropi, Maria Stefania; Carocci, Alessia; Lauria, Graziantonio; Catalano, Alessia
2017-01-01
Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive, and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease, and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence has shown that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system. PMID:28085104
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Mercury Exposure and Heart Diseases.
Genchi, Giuseppe; Sinicropi, Maria Stefania; Carocci, Alessia; Lauria, Graziantonio; Catalano, Alessia
2017-01-12
Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive, and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease, and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence has shown that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.
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Mercury Exposure and Heart Diseases
Directory of Open Access Journals (Sweden)
Giuseppe Genchi
2017-01-01
Full Text Available Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive, and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease, and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence has shown that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.
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Heart Health: Learn the Truth About Your Heart
... Bar Home Current Issue Past Issues Cover Story Heart Health Learn the Truth About Your Heart Past Issues / Winter 2009 Table of Contents For ... turn Javascript on. Photo: iStock February is American Heart Month. Now is the time to make sure ...
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Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta
International Nuclear Information System (INIS)
Robinson, B.G.; Emanuel, R.L.; Frim, D.M.; Majzoub, J.A.
1988-01-01
Primary cultures of purified human cytotrophoblasts have been used to examine the expression of the corticotropin-releasing hormone (CRH) gene in placenta. The authors report here that glucocorticoids stimulate placental CRH synthesis and secretion in primary cultures of human placenta. This stimulation is in contrast to the glucocorticoid suppression of CRH expression in hypothalamus. The positive regulation of CRH by glucocorticoids suggests that the rise in CRH preceding parturition could result from the previously described rise in fetal glucocorticoids. Furthermore, this increase in placental CRH could stimulate, via adrenocorticotropic hormone, a further rise in fetal glucocorticoids, completing a positive feedback loop that would be terminated by delivery
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Directory of Open Access Journals (Sweden)
Germán Domínguez-Vías
2016-07-01
Full Text Available High-fat diets are associated with the development of hypertension. However, a high intake of monounsaturated fat has been proposed to be a dietary factor that can decrease the incidence of hypertension. The renin-angiotensin system (RAS and vasopressin interact to regulate blood pressure at central and peripheral level. In this study, we investigated the effect of different degrees of dietary fatty acid saturation in the control of RAS and vasopressin on brain-blood. To improve our understanding of their interaction and their relationship, we analyzed angiotensin- and vasopressin-metabolizing activities in hypothalamus and plasma, collected from Wistar rats fed during 24 weeks with diets enriched with extra virgin olive oil (monounsaturated fat or butter plus cholesterol (saturated fat compared with a standard diet. As results no angiotensinase and vasopressinase activities were found in hypothalamus and plasma, however significant correlations between enzymatic activities in both regions were noticed. They indicated that our results do not support the beneficial influence of extra virgin olive oil on central and systemic level to regulate blood pressure. Therefore, the substrates hydrolyzed by these activities as well as their functions may be similarly affected and suggest that these studies should be continued because of beneficial of Mediterranean diet, found previously in different works, which may also be an effective tool in the treatment of hypertension.
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Directory of Open Access Journals (Sweden)
Cristina Otero-Rodiño
Full Text Available We hypothesize that glucosensor mechanisms other than that mediated by glucokinase (GK operate in hypothalamus and hindbrain of the carnivorous fish species rainbow trout and stress affected them. Therefore, we evaluated in these areas changes in parameters which could be related to putative glucosensor mechanisms based on liver X receptor (LXR, mitochondrial activity, sweet taste receptor, and sodium/glucose co-transporter 1 (SGLT-1 6 h after intraperitoneal injection of 5 mL x Kg(-1 of saline solution alone (normoglycaemic treatment or containing insulin (hypoglycaemic treatment, 4 mg bovine insulin x Kg(-1 body mass, or D-glucose (hyperglycaemic treatment, 500 mg x Kg(-1 body mass. Half of tanks were kept at a 10 Kg fish mass x m(-3 and denoted as fish under normal stocking density (NSD whereas the remaining tanks were kept at a stressful high stocking density (70 kg fish mass x m(-3 denoted as HSD. The results obtained in non-stressed rainbow trout provide evidence, for the first time in fish, that manipulation of glucose levels induce changes in parameters which could be related to putative glucosensor systems based on LXR, mitochondrial activity and sweet taste receptor in hypothalamus, and a system based on SGLT-1 in hindbrain. Stress altered the response of parameters related to these systems to changes in glycaemia.
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Entrainment of the circadian clock in humans: mechanism and implications for sleep disorders.
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David Metcalfe
2007-01-01
Full Text Available Humans exhibit behaviour and physiology controlled by a circadian clock. The circadian period is genetically determined and administered by a series of interlocked autoregulatory feedback loops largely in the suprachiasmatic nuclei of the hypothalamus. The phase of the clock is, however, synchronised by a number of external environmental cues such as light. A failure or change in any one of the requisite clock components may result in the onset of a long-term sleep disorder. This review discusses the mechanism regulating circadian physiology in humans and explores how disturbances of this mechanism may result in sleep pathologies.
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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.
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The emperor's new clothes: PDE5 and the heart.
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Chantal V Degen
Full Text Available Phosphodiesterase-5 (PDE5 is highly expressed in the pulmonary vasculature, but its expression in the myocardium is controversial. Cyclic guanosine monophosphate (cGMP activates protein kinase G (PKG, which has been hypothesized to blunt cardiac hypertrophy and negative remodeling in heart failure. Although PDE5 has been suggested to play a significant role in the breakdown of cGMP in cardiomyocytes and hence PKG regulation in the myocardium, the RELAX trial, which tested effect of PDE5 inhibition on exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF failed to show a beneficial effect. These results highlight the controversy regarding the role and expression of PDE5 in the healthy and failing heart. This study used one- and two-dimensional electrophoresis and Western blotting to examine PDE5 expression in mouse (before and after trans-aortic constriction, dog (control and HFpEF as well as human (healthy and failing heart. We were unable to detect PDE5 in any cardiac tissue lysate, whereas PDE5 was present in the murine and bovine lung samples used as positive controls. These results indicate that if PDE5 is expressed in cardiac tissue, it is present in very low quantities, as PDE5 was not detected in either humans or any model of heart failure examined. Therefore in cardiac muscle, it is unlikely that PDE5 is involved the regulation of cGMP-PKG signaling, and hence PDE5 does not represent a suitable drug target for the treatment of cardiac hypertrophy. These results highlight the importance of rigorous investigation prior to clinical trial design.