Sample records for abnormal fluid homeostasis

  1. The (pro)renin receptor and body fluid homeostasis

    PubMed Central

    Cao, Theresa

    2013-01-01

    The renin-angiotensin system (RAS) has long been established as one of the major mechanisms of hypertension through the increased levels of angiotensin (ANG) II and its resulting effect on the sympathetic nerve activity, arterial vasoconstriction, water reabsorption, and retention, etc. In the central nervous system, RAS activation affects body fluid homeostasis through increases in sympathetic nerve activity, water intake, food intake, and arginine vasopressin secretion. Previous studies, however, have shown that ANG II can be made in the brain, and it could possibly be through a new component called the (pro)renin receptor. This review intends to summarize the central and peripheral effects of the PRR on body fluid homeostasis. PMID:23678024

  2. Energy Homeostasis and Abnormal RNA Metabolism in Amyotrophic Lateral Sclerosis

    PubMed Central

    Liu, Yu-Ju; Tsai, Po-Yi; Chern, Yijuang

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that is clinically characterized by progressive muscle weakness and impaired voluntary movement due to the loss of motor neurons in the brain, brain stem and spinal cord. To date, no effective treatment is available. Ample evidence suggests that impaired RNA homeostasis and abnormal energy status are two major pathogenesis pathways in ALS. In the present review article, we focus on recent studies that report molecular insights of both pathways, and discuss the possibility that energy dysfunction might negatively regulate RNA homeostasis via the impairment of cytoplasmic-nuclear shuttling in motor neurons and subsequently contribute to the development of ALS. PMID:28522961

  3. Neural Control Mechanisms and Body Fluid Homeostasis

    NASA Technical Reports Server (NTRS)

    Johnson, Alan Kim

    1998-01-01

    The goal of the proposed research was to study the nature of afferent signals to the brain that reflect the status of body fluid balance and to investigate the central neural mechanisms that process this information for the activation of response systems which restore body fluid homeostasis. That is, in the face of loss of fluids from intracellular or extracellular fluid compartments, animals seek and ingest water and ionic solutions (particularly Na(+) solutions) to restore the intracellular and extracellular spaces. Over recent years, our laboratory has generated a substantial body of information indicating that: (1) a fall in systemic arterial pressure facilitates the ingestion of rehydrating solutions and (2) that the actions of brain amine systems (e.g., norepinephrine; serotonin) are critical for precise correction of fluid losses. Because both acute and chronic dehydration are associated with physiological stresses, such as exercise and sustained exposure to microgravity, the present research will aid in achieving a better understanding of how vital information is handled by the nervous system for maintenance of the body's fluid matrix which is critical for health and well-being.

  4. Homeostasis and the concept of 'interstitial fluids hierarchy': Relevance of cerebrospinal fluid sodium concentrations and brain temperature control (Review)

    PubMed Central

    Agnati, Luigi F.; Marcoli, Manuela; Leo, Giuseppina; Maura, Guido; Guidolin, Diego

    2017-01-01

    In this review, the aspects and further developments of the concept of homeostasis are discussed also in the perspective of their possible impact in the clinical practice, particularly as far as psychic homeostasis is concerned. A brief historical survey and comments on the concept of homeostasis and allostasis are presented to introduce our proposal that is based on the classical assumption of the interstitial fluid (ISF) as the internal medium for multicellular organisms. However, the new concept of a hierarchic role of ISF of the various organs is introduced. Additionally, it is suggested that particularly for some chemico-physical parameters, oscillatory rhythms within their proper set-ranges should be considered a fundamental component of homeostasis. Against this background, we propose that the brain ISF has the highest hierarchic role in human beings, providing the optimal environment, not simply for brain cell survival, but also for brain complex functions and the oscillatory rhythms of some parameters, such as cerebrospinal fluid sodium and brain ISF pressure waves, which may play a crucial role in brain physio-pathological states. Thus, according to this proposal, the brain ISF represents the real internal medium since the maintenance of its dynamic intra-set-range homeostasis is the main factor for a free and independent life of higher vertebrates. Furthermore, the evolutionary links between brain and kidney and their synergistic role in H2O/Na balance and brain temperature control are discussed. Finally, it is surmised that these two interrelated parameters have deep effects on the Central Nervous System (CNS) higher integrative actions such those linked to psychic homeostasis. PMID:28204813

  5. The Role of Follicular Fluid Thiol/Disulphide Homeostasis in Polycystic Ovary Syndrome.

    PubMed

    Tola, Esra Nur; Köroğlu, Nadiye; Ergin, Merve; Oral, Hilmi Baha; Turgut, Abdülkadir; Erel, Özcan

    2018-04-04

    Oxidative stress is suggested as a potential triggering factor in the etiopathogenesis of Polycystic ovary syndrome related infertility. Thiol/disulphide homeostasis, a recently oxidative stress marker, is one of the antioxidant mechanism in human which have critical roles in folliculogenesis and ovulation. The aim of our study is to investigate follicular fluid thiol/disulphide homeostasis in the etiopathogenesis of Polycystic ovary syndrome and to determine its' association with in vitro fertilization outcome. The study procedures were approved by local ethic committee. Cross sectional design Methods: Follicular fluid of twenty-two Polycystic ovary syndrome women and twenty ovulatory controls undergoing in vitro fertilization treatment were recruited. Thiol/disulphide homeostasis was analyzed via a novel spectrophotometric method. Follicular native thiol levels were found to be lower in Polycystic ovary syndrome group than non- Polycystic ovary syndrome group (p=0.041) as well as native thiol/total thiol ratio (p<0.0001). Disulphide level, disulphide/native thiol and disulphide/total thiol ratios were increased in Polycystic ovary syndrome group (p<0.0001). A positive correlation between fertilization rate and native thiol (p=0.01, r=0.53) and total thiol (p=0.01, r=0.052) among Polycystic ovary syndrome patients was found. A positive predictive effect of native thiol on fertilization rate among Polycystic ovary syndrome group was also found (p=0.03, β=0.45, 95% CI=0.031-0.643). Deterioration in thiol/disulphide homeostasis, especially elevated disulphide levels could be one of the etiopathogenetic mechanism in Polycystic ovary syndrome. Increased native thiol levels is related to fertilization rate among Polycystic ovary syndrome patients and also positive predictor marker of fertilization rate among Polycystic ovary syndrome patients. Improvement of thiol/disulphide homeostasis could be of importance in the treatment of Polycystic ovary syndrome to increase in

  6. Homeostasis and the concept of 'interstitial fluids hierarchy': Relevance of cerebrospinal fluid sodium concentrations and brain temperature control (Review).

    PubMed

    Agnati, Luigi F; Marcoli, Manuela; Leo, Giuseppina; Maura, Guido; Guidolin, Diego

    2017-03-01

    In this review, the aspects and further developments of the concept of homeostasis are discussed also in the perspective of their possible impact in the clinical practice, particularly as far as psychic homeostasis is concerned. A brief historical survey and comments on the concept of homeostasis and allostasis are presented to introduce our proposal that is based on the classical assumption of the interstitial fluid (ISF) as the internal medium for multicellular organisms. However, the new concept of a hierarchic role of ISF of the various organs is introduced. Additionally, it is suggested that particularly for some chemico‑physical parameters, oscillatory rhythms within their proper set‑ranges should be considered a fundamental component of homeostasis. Against this background, we propose that the brain ISF has the highest hierarchic role in human beings, providing the optimal environment, not simply for brain cell survival, but also for brain complex functions and the oscillatory rhythms of some parameters, such as cerebrospinal fluid sodium and brain ISF pressure waves, which may play a crucial role in brain physio‑pathological states. Thus, according to this proposal, the brain ISF represents the real internal medium since the maintenance of its dynamic intra-set-range homeostasis is the main factor for a free and independent life of higher vertebrates. Furthermore, the evolutionary links between brain and kidney and their synergistic role in H2O/Na balance and brain temperature control are discussed. Finally, it is surmised that these two interrelated parameters have deep effects on the Central Nervous System (CNS) higher integrative actions such those linked to psychic homeostasis.

  7. The plasticity of extracellular fluid homeostasis in insects.

    PubMed

    Beyenbach, Klaus W

    2016-09-01

    In chemistry, the ratio of all dissolved solutes to the solution's volume yields the osmotic concentration. The present Review uses this chemical perspective to examine how insects deal with challenges to extracellular fluid (ECF) volume, solute content and osmotic concentration (pressure). Solute/volume plots of the ECF (hemolymph) reveal that insects tolerate large changes in all three of these ECF variables. Challenges beyond those tolerances may be 'corrected' or 'compensated'. While a correction simply reverses the challenge, compensation accommodates the challenge with changes in the other two variables. Most insects osmoregulate by keeping ECF volume and osmotic concentration within a wide range of tolerance. Other insects osmoconform, allowing the ECF osmotic concentration to match the ambient osmotic concentration. Aphids are unique in handling solute and volume loads largely outside the ECF, in the lumen of the gut. This strategy may be related to the apparent absence of Malpighian tubules in aphids. Other insects can suspend ECF homeostasis altogether in order to survive extreme temperatures. Thus, ECF homeostasis in insects is highly dynamic and plastic, which may partly explain why insects remain the most successful class of animals in terms of both species number and biomass. © 2016. Published by The Company of Biologists Ltd.

  8. Regulation of body fluid and salt homeostasis--from observations in space to new concepts on Earth.

    PubMed

    Gerzer, R; Heer, M

    2005-08-01

    The present manuscript summarizes recent discoveries that were made by studying salt and fluid homeostasis in weightlessness. These data indicate that 1. atrial natriuretic peptide appears not to play an important role in natriuresis in physiology, 2. the distribution of body fluids appears to be tightly coupled with hunger and thirst regulation, 3. intrathoracic pressure may be an important co-regulator of body fluid homeostasis, 4. a so far unknown low-affinity, high capacity osmotically inactive sodium storage mechanism appears to be present in humans that is acting through sodium/hydrogen exchange on glycosaminoglycans and might explain the pathophysiology, e.g., of salt sensitive hypertension. The surprising and unexpected data underline that weightlessness is an excellent tool to investigate the physiology of our human body: If we knew it, we should be able to predict changes that occur when gravity is absent. But, as data from space demonstrate, we do not.

  9. Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using /sup 111/In-DTPA ventriculography

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grossman, S.A.; Trump, D.L.; Chen, D.C.

    1982-11-01

    Cerebrospinal fluid flow dynamics were evaluated by /sup 111/In-diethylenetriamine pentaacetic acid (/sup 111/In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that /sup 111/In-DTPA cerebrospinal fluid flow imaging is useful in characterizingmore » these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis.« less

  10. Copeptin in the diagnosis of vasopressin-dependent disorders of fluid homeostasis.

    PubMed

    Christ-Crain, Mirjam; Fenske, Wiebke

    2016-03-01

    Copeptin and arginine vasopressin (AVP) are derived from a common precursor molecule and have equimolar secretion and response to osmotic, haemodynamic and stress-related stimuli. Plasma concentrations of copeptin and AVP in relation to serum osmolality are highly correlated. The physiological functions of AVP with respect to homeostasis of fluid balance, vascular tonus and regulation of the endocrine stress response are well known, but the exact function of copeptin is undetermined. Quantification of AVP can be difficult, but copeptin is stable in plasma and can be easily measured with a sandwich immunoassay. For this reason, copeptin has emerged as a promising marker for the diagnosis of AVP-dependent fluid disorders. Copeptin measurements can enable differentiation between various conditions within the polyuria-polydipsia syndrome. In the absence of prior fluid deprivation, baseline copeptin levels >20 pmol/l identify patients with nephrogenic diabetes insipidus. Conversely, copeptin levels measured upon osmotic stimulation differentiate primary polydipsia from partial central diabetes insipidus. In patients with hyponatraemia, low levels of copeptin together with low urine osmolality identify patients with primary polydipsia, and the ratio of copeptin to urinary sodium can distinguish the syndrome of inappropriate antidiuretic hormone secretion from other AVP-dependent forms of hyponatraemia.

  11. Abnormal myocardial fluid retention as an early manifestation of ischemic injury.

    PubMed Central

    Willerson, J. T.; Scales, F.; Mukherjee, A.; Platt, M.; Templeton, G. H.; Fink, G. S.; Buja, L. M.

    1977-01-01

    Fifty-seven isolated, blood perfused, continuously weighed canine hearts have been utilized to study the development of abnormal myocardial fluid retention during early myocardial ischemic injury. Inflatable balloon catheters were positioned around the left anterior descending coronary arteries (LAD) of 54 hearts or the proximal left circumflex coronary arteries of three hearts for study of the following intervals of coronary occlusion: a) 10 minutes followed by 20 minutes of reflow, b) 40 minutes followed by either no reflow or by 20 minutes of reflow, and c) 60 minutes without reflow. After 60 minutes of fixed coronary occlusion, histologic and ultrastructural examination revealed mild swelling of many ischemic cardiac muscle cells in the absence of interstitial edema, cardiac weight gain, and obvious structural defects in cell membrane integrity. After 40 minutes of coronary occlusion and 20 minutes of reflow, significant cardiac weight gain occurred in association with characteristic alterations in the ischemic region, including widespread interstitial edema and focal vascular congestion and hemorrhage and swelling of cardiac muscle cells. Focal structural defects in cell membrane integrity were also noted. The development of abnormal myocardial fluid retention after 40 minutes of LAD occlusion occurred in association with a significant reduction in sodium-potassium-ATPase activity in the ischemic area, but with no significant alteration in either creatine phosphokinase or citrate synthase activity in the same region. Despite the abnormal myocardial fluid retention in these hearts, it was possible pharmacologically to vasodilate coronary vessels with adenosine and nitroglycerin infusion to maintain a consistently high coronary flow following release of the coronary occlusion after 40 minutes and to even exceed initial hyperemic flow values following release of the occlusion when adenosine and nitroglycerin infusion was delayed until 15 minutes after reflow

  12. Aging-related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance

    PubMed Central

    Zolla, Valerio; Nizamutdinova, Irina Tsoy; Scharf, Brian; Clement, Cristina C; Maejima, Daisuke; Akl, Tony; Nagai, Takashi; Luciani, Paola; Leroux, Jean-Christophe; Halin, Cornelia; Stukes, Sabriya; Tiwari, Sangeeta; Casadevall, Arturo; Jacobs, William R; Entenberg, David; Zawieja, David C; Condeelis, John; Fooksman, David R; Gashev, Anatoliy A; Santambrogio, Laura

    2015-01-01

    The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle cells in aged collectors resulting in a decrease in contraction frequency, systolic lymph flow velocity, and pumping activity, as measured in vivo in lymphatic collectors. Functionally, this impairment also translated into a reduced ability for in vivo bacterial transport as determined by time-lapse microscopy. Ultrastructural and proteomic analysis also indicates a decrease in the thickness of the endothelial cell glycocalyx and loss of gap junction proteins in aged lymph collectors. Redox proteomic analysis mapped an aging-related increase in the glycation and carboxylation of lymphatic’s endothelial cell and matrix proteins. Functionally, these modifications translate into apparent hyperpermeability of the lymphatics with pathogen escaping from the collectors into the surrounding tissue and a decreased ability to control tissue fluid homeostasis. Altogether, our data provide a mechanistic analysis of how the anatomical and biochemical changes, occurring in aged lymphatic vessels, compromise lymph flow, tissue fluid homeostasis, and pathogen transport. PMID:25982749

  13. Systemic PPARγ deletion causes severe disturbance in fluid homeostasis in mice

    PubMed Central

    Zhou, Li; Panasiuk, Alexandra; Downton, Maicy; Zhao, Daqiang; Yang, Baoxue; Jia, Zhanjun

    2015-01-01

    The pharmacological action of peroxisome proliferator-activated receptor (PPAR)γ in promoting sodium and water retention is well documented as highlighted by the major side-effect of body weight gain and edema associated with thiazolidinedione use. However, a possible physiological role of PPARγ in regulation of fluid metabolism has not been reported by previous studies. Here we analyzed fluid metabolism in inducible whole-body PPARγ knockout mice. The null mice developed severe polydipsia and polyuria, reduced urine osmolality, and modest hyperphagia. The phenomenon persisted during 3 days of pair feeding and pair drinking, accompanied by progressive weight loss. After 24 h water deprivation, the null mice had a lower urine osmolality, a higher urine volume, a greater weight loss, and a greater rise in hematocrit than the floxed control. Urinary vasopressin (AVP) excretion was not different between the genotypes under basal condition or after WD. The response of urine osmolality to acute and chronic 1-desamino-8-d-arginine vasopressin treatment was attenuated in the null mice, but the total abundance or phosphorylation of aquaporin 2 (AQP2) in the kidney or AVP-induced cAMP production in inner medullary collecting duct suspensions was unaffected. Overall, PPARγ participates in physiological control of fluid homeostasis through an unknown mechanism involving cAMP/AQP2-independent enhancement of AVP response. PMID:26330489

  14. B-type natriuretic peptide and acute heart failure: Fluid homeostasis, biomarker and therapeutics.

    PubMed

    Torres-Courchoud, I; Chen, H H

    2016-10-01

    Natriuretic peptides are a family of peptides with similar structures, but are genetically distinct with diverse actions in cardiovascular, renal and fluid homeostasis. The family consists of an atrial natriuretic peptide (ANP) and a brain natriuretic peptide (BNP) of myocardial cell origin, a C-type natriuretic peptide (CNP) of endothelial origin, and a urodilatin (Uro) which is processed from a prohormone ANP in the kidney. Nesiritide, a human recombinant BNP, was approved by the Federal Drug Administration (FDA) for the management of acute heart failure (AHF) in 2001. Human recombinant ANP (Carperitide) was approved for the same clinical indication in Japan in 1995, and human recombinant Urodilatin (Ularitide) is currently undergoing phase III clinical trial (TRUE AHF). This review will provide an update on important issues regarding the role of BNP in fluid hemostasis as a biomarker and therapeutics in AHF. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  15. Second-trimester IL-15 and IL-18 levels in the amniotic fluid of fetuses with normal karyotypes and with chromosome abnormalities.

    PubMed

    Klimkiewicz-Blok, Dominika; Florjański, Jerzy; Zalewski, Jerzy; Blok, Radosław

    2012-01-01

    Little is known about the behavior of interleukin 15 (IL-15) and 18 (IL-18) in the amniotic fluid in the second trimester of gestations complicated by chromosomal defects in the fetus. Likewise, it has not yet been established whether a fetus with chromosome abnormalities creates its immunity mechanisms in the same way as a fetus with a normal karyotype. The aim of this work was to assess the concentration of IL-15 and IL-18 in the amniotic fluid in the second trimester of gestation in fetuses with normal karyotypes and with chromosome abnormalities. The material consisted of 51 samples of amniotic fluid obtained from genetic amniocenteses carried out between the 15th and the 19th weeks of gestation. On the basis of cytogenetic screening, two groups were singled out: Group I--45 fetuses with normal karyotypes, and Group II--6 fetuses with abnormal karyotypes. The concentrations of IL-15 and IL-18 in the amniotic fluid were assessed with ready-made assays and analyzed, and the results from both groups were compared. The differences between the IL-15 levels in the amniotic fluid from Groups I and II proved to be statistically insignificant (p = 0.054). However, the average IL-18 levels in the amniotic fluid of the fetuses with normal karyotypes were significantly higher than in the amniotic fluid of the fetuses with chromosome abnormalities (p = 0.032). Some defense mechanisms in the second trimester of gestation in fetuses with chromosome abnormalities may develop in a different way than in fetuses with normal karyotypes.

  16. Acute effects of head-down tilt and hypoxia on modulators of fluid homeostasis

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Cintron, N. M.; Pietrzyk, R. A.; Scotto, P.; Loeppky, J. A.

    1994-01-01

    In an effort to understand the interaction between acute postural fluid shifts and hypoxia on hormonal regulation of fluid homeostasis, the authors measured the responses to head-down tilt with and without acute exposure to normobaric hypoxia. Plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP), plasma aldosterone (ALD), and plasma renin activity (PRA) were measured in six healthy male volunteers who were exposed to a head-down tilt protocol during normoxia and hypoxia. The tilt protocol consisted of a 17 degrees head-up phase (30 minutes), a 28 degrees head-down phase (1 hour), and a 17 degrees head-up recovery period (2 hours, with the last hour normoxic in both experiments). Altitude equivalent to 14,828 ft was simulated by having the subjects breathe an inspired gas mixture with 13.9% oxygen. The results indicate that the postural fluid redistribution associated with a 60-minute head-down tilt induces the release of ANP and cGMP during both hypoxia and normoxia. Hypoxia increased cGMP, cAMP, ALD, and PRA throughout the protocol and significantly potentiated the increase in cGMP during head-down tilt. Hypoxia had no overall effect on the release of ANP, but appeared to attenuate the increase with head-down tilt. This study describes the acute effects of hypoxia on the endocrine response during fluid redistribution and suggests that the magnitude, but not the direction, of these changes with posture is affected by hypoxia.

  17. [Kidney, Fluid, and Acid-Base Balance].

    PubMed

    Shioji, Naohiro; Hayashi, Masao; Morimatsu, Hiroshi

    2016-05-01

    Kidneys play an important role to maintain human homeostasis. They contribute to maintain body fluid, electrolytes, and acid-base balance. Especially in fluid control, we, physicians can intervene body fluid balance using fluid resuscitation and diuretics. In recent years, one type of fluid resuscitation, hydroxyl ethyl starch has been extensively studied in the field of intensive care. Although their effects on fluid resuscitation are reasonable, serious complications such as kidney injury requiring renal replacement therapy occur frequently. Now we have to pay more attention to this important complication. Another topic of fluid management is tolvaptan, a selective vasopressin-2 receptor antagonist Recent randomized trial suggested that tolvaptan has a similar supportive effect for fluid control and more cost effective compared to carperitide. In recent years, Stewart approach is recognized as one important tool to assess acid-base balance in critically ill patients. This approach has great value, especially to understand metabolic components in acid-base balance. Even for assessing the effects of kidneys on acid-base balance, this approach gives us interesting insight. We should appropriately use this new approach to treat acid-base abnormality in critically ill patients.

  18. Effects of 30 day simulated microgravity and recovery on fluid homeostasis and renal function in the rat

    NASA Technical Reports Server (NTRS)

    Tucker, Bryan J.; Mendonca, Margarida M.

    1995-01-01

    Transition from a normal gravitational environment to that of microgravity eventually results in decreased plasma and blood volumes, increasing with duration of exposure to microgravity. This loss of vascular fluid is presumably due to negative fluid and electrolyte balance and most likely contributes to the orthostatic intolerance associated with the return to gravity. The decrease in plasma volume is presumed to be a reflection of a concurrent decrease in extracellular fluid volume with maintenance of normal plasma-interstitial fluid balance. In addition, the specific alterations in renal function contributing to these changes in fluid and electrolyte homeostasis are potentially responding to neuro-humoral signals that are not consistent with systemic fluid volume status. We have previously demonstrated an early increase in both glomerular filtration rate and extracellular fluid volume and that this decreases towards control values by 7 days of simulated microgravity. However, longer duration studies relating these changes to plasma volume alterations and the response to return to orthostasis have not been fully addressed. Male Wistar rats were chronically cannulated, submitted to 30 days heat-down tilt (HDT) and followed for 7 days after return to orthostasis from HDT. Measurements of renal function and extracellular and blood volumes were performed in the awake rat.

  19. Effects of Beer, Non-Alcoholic Beer and Water Consumption before Exercise on Fluid and Electrolyte Homeostasis in Athletes.

    PubMed

    Castro-Sepulveda, Mauricio; Johannsen, Neil; Astudillo, Sebastián; Jorquera, Carlos; Álvarez, Cristian; Zbinden-Foncea, Hermann; Ramírez-Campillo, Rodrigo

    2016-06-07

    Fluid and electrolyte status have a significant impact on physical performance and health. Pre-exercise recommendations cite the possibility of consuming beverages with high amounts of sodium. In this sense, non-alcoholic beer can be considered an effective pre-exercise hydration beverage. This double-blind, randomized study aimed to compare the effect of beer, non-alcoholic beer and water consumption before exercise on fluid and electrolyte homeostasis. Seven male soccer players performed 45 min of treadmill running at 65% of the maximal heart rate, 45 min after ingesting 0.7 L of water (W), beer (AB) or non-alcoholic beer (NAB). Body mass, plasma Na⁺ and K⁺ concentrations and urine specific gravity (USG) were assessed before fluid consumption and after exercise. After exercise, body mass decreased (p < 0.05) in W (-1.1%), AB (-1.0%) and NAB (-1.0%). In the last minutes of exercise, plasma Na⁺ was reduced (p < 0.05) in W (-3.9%) and AB (-3.7%), plasma K⁺ was increased (p < 0.05) in AB (8.5%), and USG was reduced in W (-0.9%) and NAB (-1.0%). Collectively, these results suggest that non-alcoholic beer before exercise could help maintain electrolyte homeostasis during exercise. Alcoholic beer intake reduced plasma Na⁺ and increased plasma K⁺ during exercise, which may negatively affect health and physical performance, and finally, the consumption of water before exercise could induce decreases of Na⁺ in plasma during exercise.

  20. Research into the Physiology of Cerebrospinal Fluid Reaches a New Horizon: Intimate Exchange between Cerebrospinal Fluid and Interstitial Fluid May Contribute to Maintenance of Homeostasis in the Central Nervous System

    PubMed Central

    MATSUMAE, Mitsunori; SATO, Osamu; HIRAYAMA, Akihiro; HAYASHI, Naokazu; TAKIZAWA, Ken; ATSUMI, Hideki; SORIMACHI, Takatoshi

    2016-01-01

    Cerebrospinal fluid (CSF) plays an essential role in maintaining the homeostasis of the central nervous system. The functions of CSF include: (1) buoyancy of the brain, spinal cord, and nerves; (2) volume adjustment in the cranial cavity; (3) nutrient transport; (4) protein or peptide transport; (5) brain volume regulation through osmoregulation; (6) buffering effect against external forces; (7) signal transduction; (8) drug transport; (9) immune system control; (10) elimination of metabolites and unnecessary substances; and finally (11) cooling of heat generated by neural activity. For CSF to fully mediate these functions, fluid-like movement in the ventricles and subarachnoid space is necessary. Furthermore, the relationship between the behaviors of CSF and interstitial fluid in the brain and spinal cord is important. In this review, we will present classical studies on CSF circulation from its discovery over 2,000 years ago, and will subsequently introduce functions that were recently discovered such as CSF production and absorption, water molecule movement in the interstitial space, exchange between interstitial fluid and CSF, and drainage of CSF and interstitial fluid into both the venous and the lymphatic systems. Finally, we will summarize future challenges in research. This review includes articles published up to February 2016. PMID:27245177

  1. Connective tissue spectrum abnormalities associated with spontaneous cerebrospinal fluid leaks: a prospective study.

    PubMed

    Reinstein, Eyal; Pariani, Mitchel; Bannykh, Serguei; Rimoin, David L; Schievink, Wouter I

    2013-04-01

    We aimed to assess the frequency of connective tissue abnormalities among patients with cerebrospinal fluid (CSF) leaks in a prospective study using a large cohort of patients. We enrolled a consecutive group of 50 patients, referred for consultation because of CSF leak. All patients have been carefully examined for the presence of connective tissue abnormalities, and based on findings, patients underwent genetic testing. Ancillary diagnostic studies included echocardiography, eye exam, and histopathological examinations of skin and dura biopsies in selected patients. We identified nine patients with heritable connective tissue disorders, including Marfan syndrome, Ehlers-Danlos syndrome and other unclassified forms. In seven patients, spontaneous CSF leak was the first noted manifestation of the genetic disorder. We conclude that spontaneous CSF leaks are associated with a spectrum of connective tissue abnormalities and may be the first noted clinical presentation of the genetic disorder. We propose that there is a clinical basis for considering spontaneous CSF leak as a clinical manifestation of heritable connective tissue disorders, and we suggest that patients with CSF leaks should be screened for connective tissue and vascular abnormalities.

  2. Fluid-attenuated inversion recovery: correlations of hippocampal cell densities with signal abnormalities.

    PubMed

    Diehl, B; Najm, I; Mohamed, A; Wyllie, E; Babb, T; Ying, Z; Hilbig, A; Bingaman, W; Lüders, H O; Ruggieri, P

    2001-09-25

    Hippocampal sclerosis (HS) is characterized by hippocampal atrophy and increased signal on T2-weighted images and on fluid-attenuated inversion recovery (FLAIR) images. To quantitate cell loss and compare it with signal abnormalities on FLAIR images. Thirty-one patients with temporal lobe resection, pathologically proven HS, and Engel class I and II outcome were included: 20 with HS only and 11 with HS associated with pathologically proven cortical dysplasia (dual pathology). The signal intensity on FLAIR was rated as present or absent in the hippocampus and correlated with the neuronal losses in the hippocampus. FLAIR signal increases were present in 77% (24/31) of all patients studied. In patients with isolated HS, 90% (18/20) had ipsilateral signal increases, but in patients with dual pathology, only 55% (6/11; p < 0.02) showed FLAIR signal increase. Hippocampal cell losses were significantly higher in the isolated HS group. The average cell loss in patients with FLAIR signal abnormalities was 64.8 +/- 8.0% as compared with only 32.7 +/- 5.1% in patients with no FLAIR signal abnormalities. There was a significant positive correlation between the presence of signal abnormality and average hippocampal cell loss in both pathologic groups. Ipsilateral FLAIR signal abnormalities occur in the majority of patients with isolated HS but are less frequent in those with dual pathology. The presence of increased FLAIR signal is correlated with higher hippocampal cell loss.

  3. Structural Brain Abnormalities in Successfully Treated HIV Infection: Associations With Disease and Cerebrospinal Fluid Biomarkers.

    PubMed

    van Zoest, Rosan A; Underwood, Jonathan; De Francesco, Davide; Sabin, Caroline A; Cole, James H; Wit, Ferdinand W; Caan, Matthan W A; Kootstra, Neeltje A; Fuchs, Dietmar; Zetterberg, Henrik; Majoie, Charles B L M; Portegies, Peter; Winston, Alan; Sharp, David J; Gisslén, Magnus; Reiss, Peter

    2017-12-27

    Brain structural abnormalities have been reported in persons living with human immunodeficiency virus (HIV; PLWH) who are receiving suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear. We investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PLWH receiving suppressive cART and 79 comparable HIV-negative controls, aged ≥45 years, from the Comorbidity in Relation to AIDS cohort, using multimodal neuroimaging and cerebrospinal fluid biomarkers. Compared with controls, PLWH had lower gray matter volumes (-13.7 mL; 95% confidence interval, -25.1 to -2.2) and fractional anisotropy (-0.0073; 95% confidence interval, -.012 to -.0024), with the largest differences observed in those with prior clinical AIDS. Hypertension and the soluble CD14 concentration in cerebrospinal fluid were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (Pinteraction = .32 and Pinteraction = .59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV infection. The presence of lower gray matter volumes and more white matter microstructural abnormalities in well-treated PLWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors, such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  4. Amniotic fluid-AFP in Down syndrome and other chromosome abnormalities.

    PubMed

    Crandall, B F; Matsumoto, M; Perdue, S

    1988-05-01

    80.2 Per cent of 111 Down syndrome pregnancies had anmiotic fluid (AF) alpha fetoprotein (AFP) levels on or below the median and 10.8 per cent at or below 0.5 MoM compared with 41.9 and 1.4 per cent of controls. These differences were even more striking when the gestational age was less than 18 weeks compared with greater than or equal to 18 weeks. No such association was seen for other chromosome abnormalities including trisomy 18,45,X and mosaics, 47,XXY,47,XXX, and other structural abnormalities and triploidy, even when high levels due to defects such as omphalocele and cystic hygroma were excluded. All cases of trisomy 13 and 80 per cent with 47,XYY had AF-AFP levels above the median. Selection of cases for karyotyping by a low level of AF-AFP would clearly fail to detect aneuploidies other than Down syndrome and is not recommended. A possible weak association between low maternal serum (MS) and AF-AFPs in Down syndrome was most evident at less than 18 weeks, suggesting that MS screening between 16 and 18 weeks may be the most informative time.

  5. Tissue mechanics regulate brain development, homeostasis and disease

    PubMed Central

    Barnes, J. Matthew

    2017-01-01

    ABSTRACT All cells sense and integrate mechanical and biochemical cues from their environment to orchestrate organismal development and maintain tissue homeostasis. Mechanotransduction is the evolutionarily conserved process whereby mechanical force is translated into biochemical signals that can influence cell differentiation, survival, proliferation and migration to change tissue behavior. Not surprisingly, disease develops if these mechanical cues are abnormal or are misinterpreted by the cells – for example, when interstitial pressure or compression force aberrantly increases, or the extracellular matrix (ECM) abnormally stiffens. Disease might also develop if the ability of cells to regulate their contractility becomes corrupted. Consistently, disease states, such as cardiovascular disease, fibrosis and cancer, are characterized by dramatic changes in cell and tissue mechanics, and dysregulation of forces at the cell and tissue level can activate mechanosignaling to compromise tissue integrity and function, and promote disease progression. In this Commentary, we discuss the impact of cell and tissue mechanics on tissue homeostasis and disease, focusing on their role in brain development, homeostasis and neural degeneration, as well as in brain cancer. PMID:28043968

  6. Abnormal pressures as hydrodynamic phenomena

    USGS Publications Warehouse

    Neuzil, C.E.

    1995-01-01

    So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

  7. Clinically severe Epstein-Barr virus encephalitis with mild cerebrospinal fluid abnormalities in an immunocompetent adolescent: a case report.

    PubMed

    Engelmann, Ilka; Nasser, Hala; Belmiloudi, Soufien; Le Guern, Rémi; Dewilde, Anny; Vallée, Louis; Hober, Didier

    2013-06-01

    A 15-year-old boy developed Epstein-Barr virus (EBV) encephalitis, a rare complication of infectious mononucleosis. The severe clinical picture and the marked neuroimaging changes were in contrast with mild cerebrospinal fluid abnormalities: leukocyte count was normal and protein level was only slightly elevated. EBV DNA was detected in cerebrospinal fluid by polymerase chain reaction. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Mechanisms of mammalian iron homeostasis

    PubMed Central

    Pantopoulos, Kostas; Porwal, Suheel Kumar; Tartakoff, Alan; Devireddy, L.

    2012-01-01

    Iron is vital for almost all organisms because of its ability to donate and accept electrons with relative ease. It serves as a cofactor for many proteins and enzymes necessary for oxygen and energy metabolism, as well as for several other essential processes. Mammalian cells utilize multiple mechanisms to acquire iron. Disruption of iron homeostasis is associated with various human diseases: iron deficiency resulting from defects in acquisition or distribution of the metal causes anemia; whereas iron surfeit resulting from excessive iron absorption or defective utilization causes abnormal tissue iron deposition, leading to oxidative damage. Mammals utilize distinct mechanisms to regulate iron homeostasis at the systemic and cellular levels. These involve the hormone hepcidin and iron regulatory proteins, which collectively ensure iron balance. This review outlines recent advances in iron regulatory pathways, as well as in mechanisms underlying intracellular iron trafficking, an important but less-studied area of mammalian iron homeostasis. PMID:22703180

  9. Neural mechanisms in body fluid homeostasis.

    PubMed

    DiBona, G F

    1986-12-01

    Under steady-state conditions, urinary sodium excretion matches dietary sodium intake. Because extracellular fluid osmolality is tightly regulated, the quantity of sodium in the extracellular fluid determines the volume of this compartment. The left atrial volume receptor mechanism is an example of a neural mechanism of volume regulation. The left atrial mechanoreceptor, which functions as a sensor in the low-pressure vascular system, is located in the left atrial wall, which has a well-defined compliance relating intravascular volume to filling pressure. The left atrial mechanoreceptor responds to changes in wall left atrial tension by discharging into afferent vagal fibers. These fibers have suitable central nervous system representation whose related efferent neurohumoral mechanisms regulate thirst, renal excretion of water and sodium, and redistribution of the extracellular fluid volume. Efferent renal sympathetic nerve activity undergoes appropriate changes to facilitate renal sodium excretion during sodium surfeit and to facilitate renal sodium conservation during sodium deficit. By interacting with other important determinants of renal sodium excretion (e.g., renal arterial pressure), changes in efferent renal sympathetic nerve activity can significantly modulate the final renal sodium excretion response with important consequences in pathophysiological states (e.g., hypertension, edema-forming states).

  10. Serum and Glucocorticoid Regulated Kinase 1 in Sodium Homeostasis

    PubMed Central

    Lou, Yiyun; Zhang, Fan; Luo, Yuqin; Wang, Liya; Huang, Shisi; Jin, Fan

    2016-01-01

    The ubiquitously expressed serum and glucocorticoid regulated kinase 1 (SGK1) is tightly regulated by osmotic and hormonal signals, including glucocorticoids and mineralocorticoids. Recently, SGK1 has been implicated as a signal hub for the regulation of sodium transport. SGK1 modulates the activities of multiple ion channels and carriers, such as epithelial sodium channel (ENaC), voltage-gated sodium channel (Nav1.5), sodium hydrogen exchangers 1 and 3 (NHE1 and NHE3), sodium-chloride symporter (NCC), and sodium-potassium-chloride cotransporter 2 (NKCC2); as well as the sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) and type A natriuretic peptide receptor (NPR-A). Accordingly, SGK1 is implicated in the physiology and pathophysiology of Na+ homeostasis. Here, we focus particularly on recent findings of SGK1’s involvement in Na+ transport in renal sodium reabsorption, hormone-stimulated salt appetite and fluid balance and discuss the abnormal SGK1-mediated Na+ reabsorption in hypertension, heart disease, edema with diabetes, and embryo implantation failure. PMID:27517916

  11. ATG3-dependent autophagy mediates mitochondrial homeostasis in pluripotency acquirement and maintenance

    PubMed Central

    Liu, Kun; Zhao, Qian; Liu, Pinglei; Cao, Jiani; Gong, Jiaqi; Wang, Chaoqun; Wang, Weixu; Li, Xiaoyan; Sun, Hongyan; Zhang, Chao; Li, Yufei; Jiang, Minggui; Zhu, Shaohua; Sun, Qingyuan; Jiao, Jianwei; Hu, Baoyang; Zhao, Xiaoyang; Li, Wei; Chen, Quan; Zhou, Qi; Zhao, Tongbiao

    2016-01-01

    ABSTRACT Pluripotent stem cells, including induced pluripotent and embryonic stem cells (ESCs), have less developed mitochondria than somatic cells and, therefore, rely more heavily on glycolysis for energy production.1-3 However, how mitochondrial homeostasis matches the demands of nuclear reprogramming and regulates pluripotency in ESCs is largely unknown. Here, we identified ATG3-dependent autophagy as an executor for both mitochondrial remodeling during somatic cell reprogramming and mitochondrial homeostasis regulation in ESCs. Dysfunctional autophagy by Atg3 deletion inhibited mitochondrial removal during pluripotency induction, resulting in decreased reprogramming efficiency and accumulation of abnormal mitochondria in established iPSCs. In Atg3 null mouse ESCs, accumulation of aberrant mitochondria was accompanied by enhanced ROS generation, defective ATP production and attenuated pluripotency gene expression, leading to abnormal self-renewal and differentiation. These defects were rescued by reacquisition of wild-type but not lipidation-deficient Atg3 expression. Taken together, our findings highlight a critical role of ATG3-dependent autophagy for mitochondrial homeostasis regulation in both pluripotency acquirement and maintenance. PMID:27575019

  12. ATG3-dependent autophagy mediates mitochondrial homeostasis in pluripotency acquirement and maintenance.

    PubMed

    Liu, Kun; Zhao, Qian; Liu, Pinglei; Cao, Jiani; Gong, Jiaqi; Wang, Chaoqun; Wang, Weixu; Li, Xiaoyan; Sun, Hongyan; Zhang, Chao; Li, Yufei; Jiang, Minggui; Zhu, Shaohua; Sun, Qingyuan; Jiao, Jianwei; Hu, Baoyang; Zhao, Xiaoyang; Li, Wei; Chen, Quan; Zhou, Qi; Zhao, Tongbiao

    2016-11-01

    Pluripotent stem cells, including induced pluripotent and embryonic stem cells (ESCs), have less developed mitochondria than somatic cells and, therefore, rely more heavily on glycolysis for energy production. 1-3 However, how mitochondrial homeostasis matches the demands of nuclear reprogramming and regulates pluripotency in ESCs is largely unknown. Here, we identified ATG3-dependent autophagy as an executor for both mitochondrial remodeling during somatic cell reprogramming and mitochondrial homeostasis regulation in ESCs. Dysfunctional autophagy by Atg3 deletion inhibited mitochondrial removal during pluripotency induction, resulting in decreased reprogramming efficiency and accumulation of abnormal mitochondria in established iPSCs. In Atg3 null mouse ESCs, accumulation of aberrant mitochondria was accompanied by enhanced ROS generation, defective ATP production and attenuated pluripotency gene expression, leading to abnormal self-renewal and differentiation. These defects were rescued by reacquisition of wild-type but not lipidation-deficient Atg3 expression. Taken together, our findings highlight a critical role of ATG3-dependent autophagy for mitochondrial homeostasis regulation in both pluripotency acquirement and maintenance.

  13. Disrupting mitochondrial Ca2+ homeostasis causes tumor-selective TRAIL sensitization through mitochondrial network abnormalities.

    PubMed

    Ohshima, Yohei; Takata, Natsuhiko; Suzuki-Karasaki, Miki; Yoshida, Yukihiro; Tokuhashi, Yasuaki; Suzuki-Karasaki, Yoshihiro

    2017-10-01

    The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising anticancer agent with high tumor-selective cytotoxicity. The congenital and acquired resistance of some cancer types including malignant melanoma and osteosarcoma impede the current TRAIL therapy of these cancers. Since fine tuning of the intracellular Ca2+ level is essential for cell function and survival, Ca2+ dynamics could be a promising target for cancer treatment. Recently, we demonstrated that mitochondrial Ca2+ removal increased TRAIL efficacy toward malignant melanoma and osteosarcoma cells. Here we report that mitochondrial Ca2+ overload leads to tumor-selective sensitization to TRAIL cytotoxicity. Treatment with the mitochondrial Na+/Ca2+ exchanger inhibitor CGP-37157 and oxidative phosphorylation inhibitor antimycin A and FCCP resulted in a rapid and persistent mitochondrial Ca2+ rise. These agents also increased TRAIL sensitivity in a tumor-selective manner with a switching from apoptosis to a nonapoptotic cell death. Moreover, we found that mitochondrial Ca2+ overload led to increased mitochondrial fragmentation, while mitochondrial Ca2+ removal resulted in mitochondrial hyperfusion. Regardless of their reciprocal actions on the mitochondrial dynamics, both interventions commonly exacerbated TRAIL-induced mitochondrial network abnormalities. These results expand our previous study and suggest that an appropriate level of mitochondrial Ca2+ is essential for maintaining the mitochondrial dynamics and the survival of these cells. Thus, disturbing mitochondrial Ca2+ homeostasis may serve as a promising approach to overcome the TRAIL resistance of these cancers with minimally compromising the tumor-selectivity.

  14. Fluid shear stress as a regulator of gene expression in vascular cells: possible correlations with diabetic abnormalities

    NASA Technical Reports Server (NTRS)

    Papadaki, M.; Eskin, S. G.; Ruef, J.; Runge, M. S.; McIntire, L. V.

    1999-01-01

    Diabetes mellitus is associated with increased frequency, severity and more rapid progression of cardiovascular diseases. Metabolic perturbations from hyperglycemia result in disturbed endothelium-dependent relaxation, activation of coagulation pathways, depressed fibrinolysis, and other abnormalities in vascular homeostasis. Atherosclerosis is localized mainly at areas of geometric irregularity at which blood vessels branch, curve and change diameter, and where blood is subjected to sudden changes in velocity and/or direction of flow. Shear stress resulting from blood flow is a well known modulator of vascular cell function. This paper presents what is currently known regarding the molecular mechanisms responsible for signal transduction and gene regulation in vascular cells exposed to shear stress. Considering the importance of the hemodynamic environment of vascular cells might be vital to increasing our understanding of diabetes.

  15. Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism.

    PubMed

    Chen, Tzu-Ling; Yang, Hung-Chi; Hung, Cheng-Yu; Ou, Meng-Hsin; Pan, Yi-Yun; Cheng, Mei-Ling; Stern, Arnold; Lo, Szecheng J; Chiu, Daniel Tsun-Yee

    2017-01-12

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a commonly pervasive inherited disease in many parts of the world. The complete lack of G6PD activity in a mouse model causes embryonic lethality. The G6PD-deficient Caenorhabditis elegans model also shows embryonic death as indicated by a severe hatching defect. Although increased oxidative stress has been implicated in both cases as the underlying cause, the exact mechanism has not been clearly delineated. In this study with C. elegans, membrane-associated defects, including enhanced permeability, defective polarity and cytokinesis, were found in G6PD-deficient embryos. The membrane-associated abnormalities were accompanied by impaired eggshell structure as evidenced by a transmission electron microscopic study. Such loss of membrane structural integrity was associated with abnormal lipid composition as lipidomic analysis revealed that lysoglycerophospholipids were significantly increased in G6PD-deficient embryos. Abnormal glycerophospholipid metabolism leading to defective embryonic development could be attributed to the increased activity of calcium-independent phospholipase A 2 (iPLA) in G6PD-deficient embryos. This notion is further supported by the fact that the suppression of multiple iPLAs by genetic manipulation partially rescued the embryonic defects in G6PD-deficient embryos. In addition, G6PD deficiency induced disruption of redox balance as manifested by diminished NADPH and elevated lipid peroxidation in embryos. Taken together, disrupted lipid metabolism due to abnormal redox homeostasis is a major factor contributing to abnormal embryonic development in G6PD-deficient C. elegans.

  16. Regulation of Blood Pressure and Salt Homeostasis by Endothelin

    PubMed Central

    KOHAN, DONALD E.; ROSSI, NOREEN F.; INSCHO, EDWARD W.; POLLOCK, DAVID M.

    2011-01-01

    Endothelin (ET) peptides and their receptors are intimately involved in the physiological control of systemic blood pressure and body Na homeostasis, exerting these effects through alterations in a host of circulating and local factors. Hormonal systems affected by ET include natriuretic peptides, aldosterone, catecholamines, and angiotensin. ET also directly regulates cardiac output, central and peripheral nervous system activity, renal Na and water excretion, systemic vascular resistance, and venous capacitance. ET regulation of these systems is often complex, sometimes involving opposing actions depending on which receptor isoform is activated, which cells are affected, and what other prevailing factors exist. A detailed understanding of this system is important; disordered regulation of the ET system is strongly associated with hypertension and dysregulated extracellular fluid volume homeostasis. In addition, ET receptor antagonists are being increasingly used for the treatment of a variety of diseases; while demonstrating benefit, these agents also have adverse effects on fluid retention that may substantially limit their clinical utility. This review provides a detailed analysis of how the ET system is involved in the control of blood pressure and Na homeostasis, focusing primarily on physiological regulation with some discussion of the role of the ET system in hypertension. PMID:21248162

  17. Abnormal oxygen homeostasis in the nucleus tractus solitarii of the spontaneously hypertensive rat.

    PubMed

    Hosford, Patrick S; Millar, Julian; Ramage, Andrew G; Marina, Nephtali

    2017-04-01

    What is the central question of this study? Arterial hypertension is associated with impaired neurovascular coupling in the somatosensory cortex. Abnormalities in activity-dependent oxygen consumption in brainstem regions involved in the control of cardiovascular reflexes have not been explored previously. What is the main finding and its importance? Using fast-cyclic voltammetry, we found that changes in local tissue PO2 in the nucleus tractus solitarii induced by electrical stimulation of the vagus nerve are significantly impaired in spontaneously hypertensive rats. This is consistent with previous observations showing that brainstem hypoxia plays an important role in the pathogenesis of arterial hypertension. The effects of arterial hypertension on cerebral blood flow remain poorly understood. Haemodynamic responses within the somatosensory cortex have been shown to be impaired in the spontaneously hypertensive rat (SHR) model. However, it is unknown whether arterial hypertension affects oxygen homeostasis in vital brainstem areas that control cardiovascular reflexes. In this study, we assessed vagus nerve stimulation-induced changes in local tissue PO2 (PtO2) in the caudal nucleus tractus solitarii (cNTS) of SHRs and normotensive Wistar rats. Measurements of PtO2 were performed using a novel application of fast-cyclic voltammetry, which allows higher temporal resolution of O 2 changes than traditional optical fluorescence techniques. Electrical stimulation of the central cut end of the vagus nerve (ESVN) caused profound reductions in arterial blood pressure along with biphasic changes in PtO2 in the cNTS, characterized by a rapid decrease in PtO2 ('initial dip') followed by a post-stimulus overshoot above baseline. The initial dip was found to be significantly smaller in SHRs compared with normotensive Wistar rats even after ganglionic blockade. The post-ESVN overshoot was similar in both groups but was reduced in Wistar rats after ganglionic blockade. In

  18. SLC20A2 DEFICIENCY IN MICE LEADS TO ELEVATED PHOSPHATE LEVELS IN CEREBROSPINAL FLUID AND GLYMPHATIC PATHWAY-ASSOCIATED ARTERIOLAR CALCIFICATION, AND RECAPITULATES HUMAN IDIOPATHIC BASAL GANGLIA CALCIFICATION

    PubMed Central

    Wallingford, MC; Chia, J; Leaf, EM; Borgeia, S; Chavkin, NW; Sawangmake, C; Marro, K; Cox, TC; Speer, MY; Giachelli, CM

    2016-01-01

    Idiopathic basal ganglia calcification is a brain calcification disorder that has been genetically linked to autosomal dominant mutations in the sodium-dependent phosphate co-transporter, SLC20A2. The mechanisms whereby deficiency of Slc20a2 leads to basal ganglion calcification are unknown. In the mouse brain, we found that Slc20a2 was expressed in tissues that produce and/or regulate cerebrospinal fluid, including choroid plexus, ependyma and arteriolar smooth muscle cells. Haploinsufficient Slc20a2 +/− mice developed age-dependent basal ganglia calcification that formed in glymphatic pathway-associated arterioles. Slc20a2 deficiency uncovered phosphate homeostasis dysregulation characterized by abnormally high cerebrospinal fluid phosphate levels and hydrocephalus, in addition to basal ganglia calcification. Slc20a2 siRNA knockdown in smooth muscle cells revealed increased susceptibility to high phosphate-induced calcification. These data suggested that loss of Slc20a2 led to dysregulated phosphate homeostasis and enhanced susceptibility of arteriolar smooth muscle cells to elevated phosphate-induced calcification. Together, dysregulated cerebrospinal fluid phosphate and enhanced smooth muscle cell susceptibility may predispose to glymphatic pathway-associated arteriolar calcification. PMID:26822507

  19. Perilymph Kinetics of FITC-Dextran Reveals Homeostasis Dominated by the Cochlear Aqueduct and Cerebrospinal Fluid.

    PubMed

    Salt, A N; Gill, R M; Hartsock, J J

    2015-06-01

    Understanding how drugs are distributed in perilymph following local applications is important as local drug therapies are increasingly used to treat disorders of the inner ear. The potential contribution of cerebrospinal fluid (CSF) entry to perilymph homeostasis has been controversial for over half a century, largely due to artifactual contamination of collected perilymph samples with CSF. Measures of perilymph flow and of drug distribution following round window niche applications have both suggested a slow, apically directed flow occurs along scala tympani (ST) in the normal, sealed cochlea. In the present study, we have used fluorescein isothiocyanate-dextran as a marker to study perilymph kinetics in guinea pigs. Dextran is lost from perilymph more slowly than other substances so far quantified. Dextran solutions were injected from pipettes sealed into the lateral semicircular canal (SCC), the cochlear apex, or the basal turn of ST. After varying delays, sequential perilymph samples were taken from the cochlear apex or lateral SCC, allowing dextran distribution along the perilymphatic spaces to be quantified. Variability was low and findings were consistent with the injection procedure driving volume flow towards the cochlear aqueduct, and with volume flow during perilymph sampling driven by CSF entry at the aqueduct. The decline of dextran with time in the period between injection and sampling was consistent with both a slow volume influx of CSF (~30 nL/min) entering the basal turn of ST at the cochlear aqueduct and a CSF-perilymph exchange driven by pressure-driven fluid oscillation across the cochlear aqueduct. Sample data also allowed contributions of other processes, such as communications with adjacent compartments, to be quantified. The study demonstrates that drug kinetics in the basal turn of ST is complex and is influenced by a considerable number of interacting processes.

  20. Pleural fluid Gram stain

    MedlinePlus

    Gram stain of pleural fluid ... mixing it with a violet stain (called a Gram stain). A laboratory specialist uses a microscope to ... reveals an abnormal collection of pleural fluid. The Gram stain can help identify the bacteria that might ...

  1. Reevaluation of the non-lesional dry skin in atopic dermatitis by acute barrier disruption: an abnormal permeability barrier homeostasis with defective processing to generate ceramide.

    PubMed

    Sugiura, Ayumi; Nomura, Tsuyoshi; Mizuno, Atsuko; Imokawa, Genji

    2014-07-01

    Atopic dermatitis is characterized by disruption of the cutaneous barrier due to reduced ceramide levels even in non-lesional dry skin. Following further acute barrier disruption by repeated tape strippings, we re-characterized the non-lesional dry skin of subjects with atopic dermatitis, which shows significantly reduced levels of barrier function and ceramide but not of beta-glucocerebrosidase activity. For the first time, we report an abnormal trans-epidermal water loss homeostasis in which delayed recovery kinetics of trans-epidermal water loss occurred on the first day during the 4 days after acute barrier disruption compared with healthy control skin. Interestingly, whereas the higher ceramide level in the stratum corneum of healthy control skin was further significantly up-regulated at 4 days post-tape stripping, the lower ceramide level in the stratum corneum of subjects with atopic dermatitis was not significantly changed. In a parallel study, whereas beta-glucocerebrosidase activity at 4 days post-tape stripping was significantly up-regulated in healthy control skin compared with before tape stripping, the level of that activity remained substantially unchanged in atopic dermatitis. These findings indicate that subjects with atopic dermatitis have a defect in sphingolipid-metabolic processing that generates ceramide in the interface between the stratum corneum and the epidermis. The results also support the notion that the continued disruption of barrier function in atopic dermatitis non-lesional skin is associated with the impaired homeostasis of a ceramide-generating process, which underscores an atopy-specific inflammation-triggered ceramide deficiency that is distinct from other types of dermatitis.

  2. Abnormal vascularization in mouse retina with dysregulated retinal cholesterol homeostasis

    PubMed Central

    Omarova, Saida; Charvet, Casey D.; Reem, Rachel E.; Mast, Natalia; Zheng, Wenchao; Huang, Suber; Peachey, Neal S.; Pikuleva, Irina A.

    2012-01-01

    Several lines of evidence suggest a link between age-related macular degeneration and retinal cholesterol maintenance. Cytochrome P450 27A1 (CYP27A1) is a ubiquitously expressed mitochondrial sterol 27-hydroxylase that plays an important role in the metabolism of cholesterol and cholesterol-related compounds. We conducted a comprehensive ophthalmic evaluation of mice lacking CYP27A1. We found that the loss of CYP27A1 led to dysregulation of retinal cholesterol homeostasis, including unexpected upregulation of retinal cholesterol biosynthesis. Cyp27a1–/– mice developed retinal lesions characterized by cholesterol deposition beneath the retinal pigment epithelium. Further, Cyp27a1-null mice showed pathological neovascularization, which likely arose from both the retina and the choroid, that led to the formation of retinal-choroidal anastomosis. Blood flow alterations and blood vessel leakage were noted in the areas of pathology. The Cyp27a1–/– retina was hypoxic and had activated Müller cells. We suggest a mechanism whereby abolished sterol 27-hydroxylase activity leads to vascular changes and identify Cyp27a1–/– mice as a model for one of the variants of type 3 retinal neovascularization occurring in some patients with age-related macular degeneration. PMID:22820291

  3. Presenilin 1 Maintains Lysosomal Ca(2+) Homeostasis via TRPML1 by Regulating vATPase-Mediated Lysosome Acidification.

    PubMed

    Lee, Ju-Hyun; McBrayer, Mary Kate; Wolfe, Devin M; Haslett, Luke J; Kumar, Asok; Sato, Yutaka; Lie, Pearl P Y; Mohan, Panaiyur; Coffey, Erin E; Kompella, Uday; Mitchell, Claire H; Lloyd-Evans, Emyr; Nixon, Ralph A

    2015-09-01

    Presenilin 1 (PS1) deletion or Alzheimer's disease (AD)-linked mutations disrupt lysosomal acidification and proteolysis, which inhibits autophagy. Here, we establish that this phenotype stems from impaired glycosylation and instability of vATPase V0a1 subunit, causing deficient lysosomal vATPase assembly and function. We further demonstrate that elevated lysosomal pH in Presenilin 1 knockout (PS1KO) cells induces abnormal Ca(2+) efflux from lysosomes mediated by TRPML1 and elevates cytosolic Ca(2+). In WT cells, blocking vATPase activity or knockdown of either PS1 or the V0a1 subunit of vATPase reproduces all of these abnormalities. Normalizing lysosomal pH in PS1KO cells using acidic nanoparticles restores normal lysosomal proteolysis, autophagy, and Ca(2+) homeostasis, but correcting lysosomal Ca(2+) deficits alone neither re-acidifies lysosomes nor reverses proteolytic and autophagic deficits. Our results indicate that vATPase deficiency in PS1 loss-of-function states causes lysosomal/autophagy deficits and contributes to abnormal cellular Ca(2+) homeostasis, thus linking two AD-related pathogenic processes through a common molecular mechanism. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Fluid and Electrolyte Nutrition

    NASA Technical Reports Server (NTRS)

    Lane, Helen W.; Smith, Scott M.; Leach, Carolyn S.; Rice, Barbara L.

    1999-01-01

    Studies of fluid and electrolyte homeostasis have been completed since the early human space flight programs, with comprehensive research completed on the Spacelab Life Sciences missions SLS-1 and SLS-2 flights, and more recently on the Mir 18 mission. This work documented the known shifts in fluids, the decrease in total blood volume, and indications of reduced thirst. Data from these flights was used to evaluate the nutritional needs for water, sodium, and potassium. Interpretations of the data are confounded by the inadequate energy intakes routinely observed during space flight. This in turn results in reduced fluid intake, as food provides approximately 70% water intake. Subsequently, body weight, lean body mass, total body water, and total body potassium may decrease. Given these issues, there is evidence to support a minimum required water intake of 2 L per day. Data from previous Shuttle flights indicated that water intake is 2285 +/- 715 ml/day (mean +/- SD, n=26). There are no indications that sodium intake or homeostasis is compromised during space flight. The normal or low aldosterone and urinary sodium levels suggest adequate sodium intake (4047 +/- 902 mg/day, n=26). Because excessive sodium intake is associated with hypercalciuria, the recommended maximum amount of sodium intake during flight is 3500 mg/day (i.e., similar to the Recommended Dietary Allowance, RDA). Potassium metabolism appears to be more complex. Data indicate loss of body potassium related to muscle atrophy and low dietary intake (2407 +/- 548 mg/day, n=26). Although possibly related to measurement error, the elevations in blood potassium suggest alterations in potassium homeostasis. The space RDA for minimum potassium intake is 3500 mg/day. With the documented inadequate intakes, efforts are being made to increase dietary consumption of potassium.

  5. Abnormal Chloride Homeostasis in the Substancia Nigra Pars Reticulata Contributes to Locomotor Deficiency in a Model of Acute Liver Injury

    PubMed Central

    Wei, Yan-Yan; Chen, Jing; Dou, Ke-Feng; Wang, Ya-Yun

    2013-01-01

    Background Altered chloride homeostasis has been thought to be a risk factor for several brain disorders, while less attention has been paid to its role in liver disease. We aimed to analyze the involvement and possible mechanisms of altered chloride homeostasis of GABAergic neurons within the substantia nigra pars reticulata (SNr) in the motor deficit observed in a model of encephalopathy caused by acute liver failure, by using glutamic acid decarboxylase 67 - green fluorescent protein knock-in transgenic mice. Methods Alterations in intracellular chloride concentration in GABAergic neurons within the SNr and changes in the expression of two dominant chloride homeostasis-regulating genes, KCC2 and NKCC1, were evaluated in mice with hypolocomotion due to hepatic encephalopathy (HE). The effects of pharmacological blockade and/or activation of KCC2 and NKCC1 functions with their specific inhibitors and/or activators on the motor activity were assessed. Results In our mouse model of acute liver injury, chloride imaging indicated an increase in local intracellular chloride concentration in SNr GABAergic neurons. In addition, the mRNA and protein levels of KCC2 were reduced, particularly on neuronal cell membranes; in contrast, NKCC1 expression remained unaffected. Furthermore, blockage of KCC2 reduced motor activity in the normal mice and led to a further deteriorated hypolocomotion in HE mice. Blockade of NKCC1 was not able to normalize motor activity in mice with liver failure. Conclusion Our data suggest that altered chloride homeostasis is likely involved in the pathophysiology of hypolocomotion following HE. Drugs aimed at restoring normal chloride homeostasis would be a potential treatment for hepatic failure. PMID:23741482

  6. Extrastriatal dopaminergic abnormalities of DA homeostasis in Parkinson’s patients with medication-induced pathological gambling: A [11C] FLB-457 and PET study

    PubMed Central

    Ray, Nicola J.; Miyasaki, Janis M.; Zurowski, Mateusz; Ko, Ji Hyun; Cho, Sang Soo; Pellecchia, Giovanna; Antonelli, Francesca; Houle, Sylvain; Lang, Anthony E.; Strafella, Antonio P.

    2012-01-01

    Impulse control disorders such as pathological gambling (PG) are a serious and common adverse effect of dopamine (DA) replacement medication in Parkinson’s disease (PD). Patients with PG have increased impulsivity and abnormalities in striatal DA, in common with behavioural and substance addictions in the non-PD population. To date, no studies have investigated the role of extrastriatal dopaminergic abnormalities in PD patients with PG. We used the PET radiotracer, [11C] FLB-457, with high-affinity for extrastriatal DA D2/3 receptors. 14 PD patients on DA agonists were imaged while they performed a gambling task involving real monetary reward and a control task. Trait impulsivity was measured with the Barratt Impulsivity Scale (BIS). Seven of the patients had a history of PG that developed subsequent to DA agonist medication. Change in [11C] FLB-457 binding potential (BP) during gambling was reduced in PD with PG patients in the midbrain, where D2/D3 receptors are dominated by autoreceptors. The degree of change in [11C] FLB-457 binding in this region correlated with impulsivity. In the cortex, [11C] FLB-457 BP was significantly greater in the anterior cingulate cortex (ACC) in PD patients with PG during the control task, and binding in this region was also correlated with impulsivity. Our findings provide the first evidence that PD patients with PG have dysfunctional activation of DA autoreceptors in the midbrain and low DA tone in the ACC. Thus, altered striatal and cortical DA homeostasis may incur vulnerability for the development of PG in PD, linked with the impulsive personality trait. PMID:22766031

  7. Mechanism of gastrointestinal abnormal motor activity induced by cisplatin in conscious dogs.

    PubMed

    Ando, Hiroyuki; Mochiki, Erito; Ohno, Tetsuro; Yanai, Mitsuhiro; Toyomasu, Yoshitaka; Ogata, Kyoichi; Tabe, Yuichi; Aihara, Ryuusuke; Nakabayashi, Toshihiro; Asao, Takayuki; Kuwano, Hiroyuki

    2014-11-14

    To investigate whether 5-hydroxytryptamine (serotonin; 5-HT) is involved in mediating abnormal motor activity in dogs after cisplatin administration. After the dogs had been given a 2-wk recovery period, all of them were administered cisplatin, and the motor activity was recorded using strain gauge force transducers. Blood and intestinal fluid samples were collected to measure 5-HT for 24 h. To determine whether 5-HT in plasma or that in intestinal fluids is more closely related to abnormal motor activity we injected 5-HT into the bloodstream and the intestinal tract of the dogs. Cisplatin given intravenously produced abnormal motor activity that lasted up to 5 h. From 3 to 4 h after cisplatin administration, normal intact dogs exhibited retropropagation of motor activity accompanied by emesis. The concentration of 5-HT in plasma reached the peak at 4 h, and that in intestinal fluids reached the peak at 3 h. In normal intact dogs with resection of the vagus nerve that were administered kytril, cisplatin given intravenously did not produce abnormal motor activity. Intestinal serotonin administration did not produce abnormal motor activity, but intravenous serotonin administration did. After the intravenous administration of cisplatin, abnormal motor activity was produced in the involved vagus nerve and in the involved serotonergic neurons via another pathway. This study was the first to determine the relationship between 5-HT and emesis-induced motor activity.

  8. Chronobiology, endocrinology, and energy- and food-reward homeostasis.

    PubMed

    Gonnissen, H K J; Hulshof, T; Westerterp-Plantenga, M S

    2013-05-01

    Energy- and food-reward homeostasis is the essential component for maintaining energy balance and its disruption may lead to metabolic disorders, including obesity and diabetes. Circadian alignment, quality sleep and sleep architecture in relation to energy- and food-reward homeostasis are crucial. A reduced sleep duration, quality sleep and rapid-eye movement sleep affect substrate oxidation, leptin and ghrelin concentrations, sleeping metabolic rate, appetite, food reward, hypothalamic-pituitary-adrenal (HPA)-axis activity, and gut-peptide concentrations, enhancing a positive energy balance. Circadian misalignment affects sleep architecture and the glucose-insulin metabolism, substrate oxidation, homeostasis model assessment of insulin resistance (HOMA-IR) index, leptin concentrations and HPA-axis activity. Mood disorders such as depression occur; reduced dopaminergic neuronal signaling shows decreased food reward. A good sleep hygiene, together with circadian alignment of food intake, a regular meal frequency, and attention for protein intake or diets, contributes in curing sleep abnormalities and overweight/obesity features by preventing overeating; normalizing substrate oxidation, stress, insulin and glucose metabolism including HOMA-IR index, and leptin, GLP-1 concentrations, lipid metabolism, appetite, energy expenditure and substrate oxidation; and normalizing food reward. Synchrony between circadian and metabolic processes including meal patterns plays an important role in the regulation of energy balance and body-weight control. Additive effects of circadian alignment including meal patterns, sleep restoration, and protein diets in the treatment of overweight and obesity are suggested. © 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.

  9. The importance of the renin-angiotensin system in normal cardiovascular homeostasis

    NASA Technical Reports Server (NTRS)

    Haber, E.

    1975-01-01

    Studies were carried out on adult mongrel dogs (20 to 30 kilograms) to investigate the importance of the renin-angiotensin system. Results indicate that the renin-angiotensin system plays a major role in the maintenance of circulatory homeostasis when extracellular fluid volume is depleted. It was also found that angiotensin II concentration, in addition to renal perfusion pressure, is a factor in the regulation of renin release.

  10. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism

    PubMed Central

    Park, Hyeong-Kyu; Ahima, Rexford S.

    2014-01-01

    Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases. PMID:25199978

  11. Homeostasis of metals in the progression of Alzheimer's disease.

    PubMed

    González-Domínguez, Raúl; García-Barrera, Tamara; Gómez-Ariza, José Luis

    2014-06-01

    In order to study the involvement of metals in the progression of Alzheimer's disease, serum samples from patients with Alzheimer and mild cognitive impairment were investigated. For this purpose, metal content was analyzed after size-fractionation of species and then, inter-element and inter-fraction ratios were computed. In this way, the analysis allowed discovering changes that could be used as markers of disease, but also provided a new insight into the interactions in the homeostasis of elements in neurodegeneration and its progression. Aluminum and labile forms of iron and copper were increased in demented patients, while manganese, zinc and selenium were reduced. Interestingly, levels of different elements, principally iron, aluminum and manganese, were closely inter-related, which could evidence a complex interdependency between the homeostasis of the different metals in this disorder. On the other hand, imbalances in metabolism of copper, zinc and selenium could be associated to abnormal redox status. Therefore, this study may contribute to our understanding of the pathological mechanisms related to metals in Alzheimer's disease.

  12. Does fluid resuscitation with balanced solutions induce electrolyte and metabolic abnormalities? An in vitro assessment.

    PubMed

    Krzych, Łukasz J; Czempik, Piotr F

    2017-01-01

    Popular intravenous fluids in clinical use may have an impact on electrolyte concentration and metabolic balance and should be considered as powerful pharmacological agents. There is a growing body of evidence that fluid therapy should be more individualised and preferably based on balanced solutions. We sought to investigate the impact of three commonly used balanced fluids on electrolytes and metabolic equilibrium in an in vitro setting. Study group comprised 32 healthy male volunteers (without history of any acute/chronic disorder or known metabolic abnormality), aged 21-35 (29 ± 4) years, weight 59-103 (81.2 ± 9.8) kg, from whom blood samples were withdrawn. The whole blood was diluted in 4:1 ratio with the study solutions to make an end-concentration of 20 vol.% of each solution. The test solutions included balanced crystalloid (Plasmalyte®, Baxter, Poland [PL]), succinylated gelatin (Geloplasma®, Fresenius Kabi, Poland [GEL]) and 6% HES 130/0.4 (Volulyte®, Fresenius Kabi, Poland [HES]). All fluids caused comparable degree of haemodilution. PL and GEL decreased (104 mmol/L, interquartile range [IQR] 103-105; and 106 mmol/L, IQR 105-107.5, respectively), whereas HES increased the concentration of Cl- to 109 (IQR 108-110) mmol/L. PL and HES decreased (136, IQR 136-137 mmol/L; and 138 mmol/L, IQR 137-139, respectively), whereas GEL increased the Na+ level to 140.5 (IQR 140-141) mmol/L. PL and HES decreased osmolality (277.2 mOsm/kg, IQR 275.7-278.4; and 280.9 mOsm/kg, IQR 279.3-282.0, respectively). GEL increased it to 285.7 (IQR 283.7-286.8) mOsm/kg. All test solutions caused a similar statistically significant (p < 0.05) drop in base excess and bicarbonate concentration, and these fell outside the reference values. Due to its composition, GEL caused a significant increase in lactate concentration. HES and GEL caused a statistically significant drop in strong ion difference value. Due to high lactate level, the effect of GEL was most pronounced. Balanced

  13. Mechanism of gastrointestinal abnormal motor activity induced by cisplatin in conscious dogs

    PubMed Central

    Ando, Hiroyuki; Mochiki, Erito; Ohno, Tetsuro; Yanai, Mitsuhiro; Toyomasu, Yoshitaka; Ogata, Kyoichi; Tabe, Yuichi; Aihara, Ryuusuke; Nakabayashi, Toshihiro; Asao, Takayuki; Kuwano, Hiroyuki

    2014-01-01

    AIM: To investigate whether 5-hydroxytryptamine (serotonin; 5-HT) is involved in mediating abnormal motor activity in dogs after cisplatin administration. METHODS: After the dogs had been given a 2-wk recovery period, all of them were administered cisplatin, and the motor activity was recorded using strain gauge force transducers. Blood and intestinal fluid samples were collected to measure 5-HT for 24 h. To determine whether 5-HT in plasma or that in intestinal fluids is more closely related to abnormal motor activity we injected 5-HT into the bloodstream and the intestinal tract of the dogs. RESULTS: Cisplatin given intravenously produced abnormal motor activity that lasted up to 5 h. From 3 to 4 h after cisplatin administration, normal intact dogs exhibited retropropagation of motor activity accompanied by emesis. The concentration of 5-HT in plasma reached the peak at 4 h, and that in intestinal fluids reached the peak at 3 h. In normal intact dogs with resection of the vagus nerve that were administered kytril, cisplatin given intravenously did not produce abnormal motor activity. Intestinal serotonin administration did not produce abnormal motor activity, but intravenous serotonin administration did. CONCLUSION: After the intravenous administration of cisplatin, abnormal motor activity was produced in the involved vagus nerve and in the involved serotonergic neurons via another pathway. This study was the first to determine the relationship between 5-HT and emesis-induced motor activity. PMID:25400453

  14. Respiratory Adaptations in Acid-base Disturbances: Role of Cerebral Fluids,

    DTIC Science & Technology

    1979-06-19

    The respiratory and metabolic components of acid-base homeostasis are defined. A quantitative empirical description of the (incomplete) mutual...literature. Respiratory adaptations in steady acid-base disturbances of metabolic origin (hyperventilation with hypocapnia in primary metabolic acidosis, and...hypoventilation with hypercapnia in metabolic alkalosis ) are analyzed as a function of the acidity of the cerebral fluids (cerebrospinal and cerebral interstitial fluid). (Author)

  15. Abnormal Eu behavior at formation of H2O- and Cl-bearing fluids during degassing of granite magmas

    NASA Astrophysics Data System (ADS)

    Lukanin, Oleg

    2010-05-01

    One of the important features of REE behavior in the process of decompression degassing of granite melts is the presence of europium anomalies in REE spectrum of forming fluid phase. Negative Eu anomaly in REE spectrum of fluids enriched by chlorine that were formed under high pressures at early stages of degassing relative to REE spectrum of granite melts may take place. Negative Eu anomaly in fluid is replaced by positive one with pressure decrease and decline of Cl concentration in fluid [1, 2]. Observable unique features of europium redistribution between fluid and melt find an explanation in such a fact that Eu in contrast to the other REE under oxidation-reduction conditions, being typical for magmatic process, is present in acidic silica-alumina melts in two valency forms Eu3+ and Eu2+ whereas the dominant form for the other REE in such a melts is (REE)3+ [3, 4]. From the analysis of melt-fluid exchange reactions with participation of two valency forms of europium Eu3+ and Eu2+ follows that the total distribution coefficient of Eu between fluid and melt D(Eu)f-m is equal as a first approximation to [5, 6]: D(Eu)f-m = a1α [C(Cl)f]3 + a2 (1 - α)[C(Cl)f]2, where C(Cl)f - the concentration of Cl in fluid, α = Eu3+/(Eu3+ + Eu2+), i.e. fraction of Eu3+ from the general amount of europium in the melt, and, a1anda2- constants that can be approximately estimated from empirical data upon Eu fluid/melt distribution. The equation given allows to estimate the influence of oxidizing condition of europium on sign and size of Eu anomaly, which is expressed by Eu/Eu# ratio, where Eu is real concentration of europium in fluid being in equilibrium with melt with constant Eu3+/(Eu3+ + Eu2+) ratio, and Eu# is possible "virtual" concentration of europium that could be in the same fluid provided that all europium as other REE as well were exclusively present in trivalent form. The sign and size of Eu anomaly in fluid depends upon Cl concentration in fluid and Eu3+/Eu2+ ratio in

  16. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism.

    PubMed

    Park, Hyeong-Kyu; Ahima, Rexford S

    2015-01-01

    Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Targeting TGFβ Signaling in Subchondral Bone and Articular Cartilage Homeostasis

    PubMed Central

    Zhen, Gehau; Cao, Xu

    2014-01-01

    Osteoarthritis (OA) is the most common degenerative joint disease, and there is no disease-modifying therapy for OA currently available. Targeting of articular cartilage alone may not be sufficient to halt this disease progression. Articular cartilage and subchondral bone act as a functional unit. Increasing evidence indicates that transforming growth factor β (TGFβ) plays a crucial role in maintaining homeostasis of both articular cartilage and subchondral bone. Activation of extracellular matrix latent TGFβ at the appropriate time and location is the prerequisite for its function. Aberrant activation of TGFβ in the subchondral bone in response to abnormal mechanical loading environment induces formation of osteroid islets at onset of osteoarthritis. As a result, alteration of subchondral bone structure changes the stress distribution on the articular cartilage and leads to its degeneration. Thus, inhibition of TGFβ activity in the subchondral bone may provide a new avenue of treatment for OA. In this review, we will respectively discuss the role of TGFβ in homeostasis of articular cartilage and subchondral bone as a novel target for OA therapy. PMID:24745631

  18. Precision Fluid Management in Continuous Renal Replacement Therapy.

    PubMed

    Murugan, Raghavan; Hoste, Eric; Mehta, Ravindra L; Samoni, Sara; Ding, Xiaoqiang; Rosner, Mitchell H; Kellum, John A; Ronco, Claudio

    2016-01-01

    Fluid management during continuous renal replacement therapy (CRRT) in critically ill patients is a dynamic process that encompasses 3 inter-related goals: maintenance of the patency of the CRRT circuit, maintenance of plasma electrolyte and acid-base homeostasis and regulation of patient fluid balance. In this article, we report the consensus recommendations of the 2016 Acute Disease Quality Initiative XVII conference on 'Precision Fluid Management in CRRT'. We discuss the principles of fluid management, describe various prescription methods to achieve circuit integrity and introduce the concept of integrated fluid balance for tailoring fluid balance to the needs of the individual patient. We suggest that these recommendations could serve to develop the best clinical practice and standards of care for fluid management in patients undergoing CRRT. Finally, we identify and highlight areas of uncertainty in fluid management and set an agenda for future research. © 2016 S. Karger AG, Basel.

  19. Fluid and electrolyte homeostasis during spaceflight: Elucidation of mechanisms in a primate

    NASA Technical Reports Server (NTRS)

    Churchill, Susanne

    1990-01-01

    Although it is now well accepted that exposure to the hypogravic environment of space induces a shift of fluid from the lower extremities toward the upper body, the actual physiological responses to this central volume expansion have not been well characterized. Because it is likely that the fluid and electrolyte response to hypogravity plays a critical role in the development of Cardiovascular Deconditioning, elucidation of these mechanisms is of critical importance. The goal of flight experiment 223, scheduled to fly on SLS-2, is the definition of the basic renal, fluid and electrolyte response to spaceflight in four instrumented squirrel monkeys. The studies were those required to support the development of flight hardware and optimal inflight procedures, and to evaluate a ground-based model for weightlessness, lower body positive pressure (LBPP).

  20. Cardioprotection Via Modulation of Calcium Homeostasis by Thiopental in Hypoxia-Reoxygenated Neonatal Rat Cardiomyocytes

    PubMed Central

    Kim, Hyun-Soo; Hwang, Ki-Chul

    2010-01-01

    Purpose Ca2+ homeostasis plays an important role in myocardial cell injury induced by hypoxia-reoxygenation, and prevention of intracellular Ca2+ overload is key to cardioprotection. Even though thiopental is a frequently used anesthetic agent, little is known about its cardioprotective effects, particulary in association with Ca2+ homeostasis. We investigated whether thiopental protects cardiomyocytes against hypoxia-reoxygenation injury by regulating Ca2+ homeostasis. Materials and Methods Neonatal rat cardiomyocytes were isolated. Cardiomyocytes were exposed to different concentrations of thiopental and immediately replaced in the hypoxic chamber to maintain hypoxia. After 1 hour of exposure, a culture dish was transferred to the CO2 incubator and cells were incubated at 37℃ for 5 hours. At the end of the experiments, the authors assessed cell protection using immunoblot analysis and caspase activity. The mRNA of genes involved in Ca2+ homeostasis, mitochondrial membrane potential, and cellular Ca2+ levels were examined. Results In thiopental-treated cardiomyocytes, there was a decrease in expression of the proapoptotic protein Bax, caspase-3 activation, and intracellular Ca2+ content. In addition, both enhancement of anti-apoptotic protein Bcl-2 and activation of Erk concerned with survival were shown. Furthermore, thiopental attenuated alterations of genes involving Ca2+ regulation and significantly modulated abnormal changes of NCX and SERCA2a genes in hypoxia-reoxygenated neonatal cardiomyocytes. Thiopental suppressed disruption of mitochondrial membrane potential (ΔΨm) induced by hypoxia-reoxygenation. Conclusion Thiopental is likely to modulate expression of genes that regulate Ca2+ homeostasis, which reduces apoptotic cell death and results in cardioprotection. PMID:20191008

  1. Airway surface liquid homeostasis in cystic fibrosis: pathophysiology and therapeutic targets.

    PubMed

    Haq, Iram J; Gray, Michael A; Garnett, James P; Ward, Christopher; Brodlie, Malcolm

    2016-03-01

    Cystic fibrosis (CF) is a life-limiting disease characterised by recurrent respiratory infections, inflammation and lung damage. The volume and composition of the airway surface liquid (ASL) are important in maintaining ciliary function, mucociliary clearance and antimicrobial properties of the airway. In CF, these homeostatic mechanisms are impaired, leading to a dehydrated and acidic ASL. ASL volume depletion in CF is secondary to defective anion transport by the abnormal cystic fibrosis transmembrane conductance regulator protein (CFTR). Abnormal CFTR mediated bicarbonate transport creates an unfavourable, acidic environment, which impairs antimicrobial function and alters mucus properties and clearance. These disease mechanisms create a disordered airway milieu, consisting of thick mucopurulent secretions and chronic bacterial infection. In addition to CFTR, there are additional ion channels and transporters in the apical airway epithelium that play a role in maintaining ASL homeostasis. These include the epithelial sodium channel (ENaC), the solute carrier 26A (SLC26A) family of anion exchangers, and calcium-activated chloride channels. In this review we discuss how the ASL is abnormal in CF and how targeting these alternative channels and transporters could provide an attractive therapeutic strategy to correct the underlying ASL abnormalities evident in CF. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Abnormal cerebrospinal fluid protein indices in schizophrenia.

    PubMed

    Kirch, D G; Kaufmann, C A; Papadopoulos, N M; Martin, B; Weinberger, D R

    1985-10-01

    Determinations of albumin and immunoglobulin G (IgG) were performed in paired cerebrospinal fluid (CSF) and serum samples from 24 subjects with schizophrenia. These determinations allowed calculation of two indices, one that is an indicator of integrity of the blood-brain barrier and the other a measure of selective IgG production within the central nervous system (CNS). In comparison with previously determined reference values, 7 of 24 (29%) subjects showed increased blood-brain barrier permeability, and 8 of 24 (33%) demonstrated elevated endogenous CNS IgG production. One of these eight also demonstrated oligoclonal banding on high-resolution protein electrophoresis of the CSF.

  3. Sleep and bodily functions: the physiological interplay between body homeostasis and sleep homeostasis.

    PubMed

    Amici, R; Bastianini, S; Berteotti, C; Cerri, M; Del Vecchio, F; Lo Martire, V; Luppi, M; Perez, E; Silvani, A; Zamboni, G; Zoccoli, G

    2014-01-01

    Body homeostasis and sleep homeostasis may both rely on the complex integrative activity carried out by the hypothalamus. Thus, the three main wake-sleep (WS) states (i.e. wakefulness, NREM sleep, and REM sleep) may be better understood if the different cardio-respiratory and metabolic parameters, which are under the integrated control of the autonomic and the endocrine systems, are studied during sleep monitoring. According to this view, many physiological events can be considered as an expression of the activity that physiological regulations should perform in order to cope with the need to fulfill body and sleep homeostasis. This review is aimed at making an assessment of data showing the existence of a physiological interplay between body homeostasis and sleep homeostasis, starting from the spontaneous changes observed in the somatic and autonomic activity during sleep, through evidence showing the deep changes occurring in the central integration of bodily functions during the different WS states, to the changes in the WS states observed when body homeostasis is challenged by the external environment and when the return to normal ambient conditions allows sleep homeo- stasis to run without apparent physiological restrictions. The data summarized in this review suggest that an approach to the dichotomy between NREM and REM sleep based on physiological regulations may offer a framework within which observations that a traditional behavioral approach may overlook can be interpreted. The study of the interplay between body and sleep homeostasis appears, therefore, to be a way to understand the function of complex organisms beyond that of the specific regulations.

  4. Altered transition metal homeostasis in Niemann-Pick disease, Type C1

    PubMed Central

    Hung, Ya Hui; Faux, Noel G.; Killilea, David W.; Yanjanin, Nicole; Firnkes, Sally; Volitakis, Irene; Ganio, George; Walterfang, Mark; Hastings, Caroline; Porter, Forbes D.; Ory, Daniel S.; Bush, Ashley I.

    2014-01-01

    The loss of NPC1 protein function is the predominant cause of Niemann-Pick type C1 disease (NP-C1), a systemic and neurodegenerative disorder characterized by late-endosomal/lysosomal accumulation of cholesterol and other lipids. Limited evidence from post-mortem human tissues, an Npc1−/− mouse model, and cell culture studies also suggest failure of metal homeostasis in NP-C1. To investigate these findings, we performed a comprehensive transition metal analysis of cerebrospinal fluid (CSF), plasma and tissue samples from human NP-C1 patients and an Npc1−/− mouse model. NPC1 deficiency in the Npc1−/− mouse model resulted in a perturbation of transition metal homeostasis in the plasma and key organs (brain, liver, spleen, heart, lungs, and kidneys). Analysis of human patient CSF, plasma and post-mortem brain tissues also indicated disrupted metal homeostasis. There was a disparity in the direction of metal changes between the human and the Npc1−/− mouse samples, which may reflect species-specific metal metabolism. Nevertheless, common to both species is brain zinc accumulation. Furthermore, treatment with the glucosylceramide synthase inhibitor miglustat, the only drug shown in a controlled clinical trial to have some efficacy for NP-C1, did not correct the alterations in CSF and plasma transition metal and ceruloplasmin (CP) metabolism in NP-C1 patients. These findings highlight the importance of NPC1 function in metal homeostasis, and indicate that metal-targeting therapy may be of value as a treatment for NP-C. PMID:24343124

  5. Homeostasis, singularities, and networks.

    PubMed

    Golubitsky, Martin; Stewart, Ian

    2017-01-01

    Homeostasis occurs in a biological or chemical system when some output variable remains approximately constant as an input parameter [Formula: see text] varies over some interval. We discuss two main aspects of homeostasis, both related to the effect of coordinate changes on the input-output map. The first is a reformulation of homeostasis in the context of singularity theory, achieved by replacing 'approximately constant over an interval' by 'zero derivative of the output with respect to the input at a point'. Unfolding theory then classifies all small perturbations of the input-output function. In particular, the 'chair' singularity, which is especially important in applications, is discussed in detail. Its normal form and universal unfolding [Formula: see text] is derived and the region of approximate homeostasis is deduced. The results are motivated by data on thermoregulation in two species of opossum and the spiny rat. We give a formula for finding chair points in mathematical models by implicit differentiation and apply it to a model of lateral inhibition. The second asks when homeostasis is invariant under appropriate coordinate changes. This is false in general, but for network dynamics there is a natural class of coordinate changes: those that preserve the network structure. We characterize those nodes of a given network for which homeostasis is invariant under such changes. This characterization is determined combinatorially by the network topology.

  6. Abnormal placentation.

    PubMed

    Bauer, Samuel T; Bonanno, Clarissa

    2009-04-01

    Abnormal placentation poses a diagnostic and treatment challenge for all providers caring for pregnant women. As one of the leading causes of postpartum hemorrhage, abnormal placentation involves the attachment of placental villi directly to the myometrium with potentially deeper invasion into the uterine wall or surrounding organs. Surgical procedures that disrupt the integrity of uterus, including cesarean section, dilatation and curettage, and myomectomy, have been implicated as key risk factors for placenta accreta. The diagnosis is typically made by gray-scale ultrasound and confirmed with magnetic resonance imaging, which may better delineate the extent of placental invasion. It is critical to make the diagnosis before delivery because preoperative planning can significantly decrease blood loss and avoid substantial morbidity associated with placenta accreta. Aggressive management of hemorrhage through the use of uterotonics, fluid resuscitation, blood products, planned hysterectomy, and surgical hemostatic agents can be life-saving for these patients. Conservative management, including the use of uterine and placental preservation and subsequent methotrexate therapy or pelvic artery embolization, may be considered when a focal accreta is suspected; however, surgical management remains the current standard of care.

  7. Alternative indices of glucose homeostasis as biochemical diagnostic tests for abnormal glucose tolerance in an African setting.

    PubMed

    Kengne, Andre Pascal; Erasmus, Rajiv T; Levitt, Naomi S; Matsha, Tandi E

    2017-04-01

    Accurate diabetes diagnosis is important in Africa, where rates are increasing, and the disease largely undiagnosed. The cumbersome oral glucose tolerance test (OGTT) remains the reference standard, while alternative diagnostic methods are not yet established in Africans. We assessed the ability of fasting plasma glucose (FPG), HbA1c and fructosamine, to diagnose OGTT-based abnormal glucose tolerance in mixed-ancestry South Africans. Mixed-ancestry adults, residing in Cape Town were examined between February and November 2015. OGTT values were used to classify glucose tolerance status as: screen-detected diabetes, prediabetes, dysglycaemia (combination of diabetes and prediabetes) and normal glucose tolerance. Of the 793 participants included, 65 (8.2%) had screen-detected diabetes, 157 (19.8%) prediabetes and 571 (72.0%) normal glucose tolerance. Correlations of FPG and 2-h glucose with HbA1c (r=0.51 and 0.52) were higher than those with fructosamine (0.34 and 0.30), both p<0.0001. The highest c-statistic for the prediction of abnormal glucose tolerance was recorded with 2-h glucose [c-statistic=0.997 (screen-detected diabetes), 0.979 (prediabetes) and 0.984 (dysglycaemia)] and the lowest with fructosamine (0.865, 0.596 and 0.677). At recommended or data-specific optimal cut-offs, no combination of FPG, HbA1c and fructosamine did better than 2-h glucose, while FPG was better than HbA1c and fructosamine on a range of performance measures. Abnormal glucose tolerance in this population is overwhelmingly expressed through 2-h glucose's abnormalities; and no combination of FPG, HbA1c and fructosamine was effective at accurately discriminating OGTT-defined abnormal glucose tolerance. Tested non-glucose based strategies are unreliable alternatives to OGTT for dysglycaemia diagnosis in this population. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  8. Fluid compartment and renal function alterations in the rat during 7 and 14 day head down tilt

    NASA Technical Reports Server (NTRS)

    Tucker, Bryan J.

    1991-01-01

    Exposure to conditions of microgravity for any extended duration can modify the distribution of fluid within the vascular and interstitial spaces, and eventually intracellular volume. Whether the redistribution of fluid and resetting of volume homeostasis mechanisms is appropriate for the long term environmental requirements of the body in microgravity remains to be fully defined. The event that initiates the change in fluid volume homeostasis is the cephalad movement of fluid which potentially triggers volume sensors and stretch receptors (atrial stretch with the resulting release of atrial natriuretic peptide) and suppresses adrenergic activity via the carotid and aortic arch baroreceptors. All these events act in concert to reset blood and interstitial volume to new levels, which in turn modify the renin-angiotensin system. All these factors have an influence on the kidney, the end organ for fluid volume control. How the fluid compartment volume changes interrelate with alterations in renal functions under conditions of simulated microgravity is the focus of the present investigation which utilizes 25-30 deg head-down tilt in the rat.

  9. Creatine maintains intestinal homeostasis and protects against colitis.

    PubMed

    Turer, Emre; McAlpine, William; Wang, Kuan-Wen; Lu, Tianshi; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Wang, Tao; Zhan, Xiaowei; Bu, Chun-Hui; Murray, Anne R; Beutler, Bruce

    2017-02-14

    Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: the transfer of an amidino group from arginine to glycine to form ornithine and guanidinoacetate. We screened 36,530 third-generation germline mutant mice derived from N -ethyl- N -nitrosourea-mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS). Among 27 colitis susceptibility phenotypes identified and mapped, one was strongly correlated with a missense mutation in Gatm in a recessive model of inheritance, and causation was confirmed by CRISPR/Cas9 gene targeting. Supplementation of homozygous Gatm mutants with exogenous creatine ameliorated the colitis phenotype. CRISPR/Cas9-targeted ( Gatm c/c ) mice displayed a normal peripheral immune response and immune cell homeostasis. However, the intestinal epithelium of the Gatm c/c mice displayed increased cell death and decreased proliferation during DSS treatment. In addition, Gatm c/c colonocytes showed increased metabolic stress in response to DSS with higher levels of phospho-AMPK and lower levels of phosphorylation of mammalian target of rapamycin (phospho-mTOR). These findings establish an in vivo requirement for rapid replenishment of cytoplasmic ATP within colonic epithelial cells in the maintenance of the mucosal barrier after injury.

  10. Creatine maintains intestinal homeostasis and protects against colitis

    PubMed Central

    Turer, Emre; McAlpine, William; Wang, Kuan-wen; Lu, Tianshi; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Wang, Tao; Zhan, Xiaowei; Bu, Chun-Hui; Murray, Anne R.; Beutler, Bruce

    2017-01-01

    Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: the transfer of an amidino group from arginine to glycine to form ornithine and guanidinoacetate. We screened 36,530 third-generation germline mutant mice derived from N-ethyl-N-nitrosourea–mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS). Among 27 colitis susceptibility phenotypes identified and mapped, one was strongly correlated with a missense mutation in Gatm in a recessive model of inheritance, and causation was confirmed by CRISPR/Cas9 gene targeting. Supplementation of homozygous Gatm mutants with exogenous creatine ameliorated the colitis phenotype. CRISPR/Cas9-targeted (Gatmc/c) mice displayed a normal peripheral immune response and immune cell homeostasis. However, the intestinal epithelium of the Gatmc/c mice displayed increased cell death and decreased proliferation during DSS treatment. In addition, Gatmc/c colonocytes showed increased metabolic stress in response to DSS with higher levels of phospho-AMPK and lower levels of phosphorylation of mammalian target of rapamycin (phospho-mTOR). These findings establish an in vivo requirement for rapid replenishment of cytoplasmic ATP within colonic epithelial cells in the maintenance of the mucosal barrier after injury. PMID:28137860

  11. Secondary Abnormalities of Neurotransmitters in Infants with Neurological Disorders

    ERIC Educational Resources Information Center

    Garcia-Cazorla, A.; Serrano, M.; Perez-Duenas, B.; Gonzalez, V.; Ormazabal, A.; Pineda, M.; Fernandez-Alvarez, E.; Campistol, J. M. D.; Artuch, R. M. D.

    2007-01-01

    Neurotransmitters are essential in young children for differentiation and neuronal growth of the developing nervous system. We aimed to identify possible factors related to secondary neurotransmitter abnormalities in pediatric patients with neurological disorders. We analyzed cerebrospinal fluid (CSF) and biogenic amine metabolites in 56 infants…

  12. Thiol Disulfide Homeostasis in Schizophrenic Patients Using Atypical Antipsychotic Drugs

    PubMed Central

    Ersan, Etem Erdal; Aydin, Hüseyin; Erdoğan, Serpil; Erşan, Serpil; Alişik, Murat; Bakir, Sevtap; Erel, Özcan; Koç, Derya

    2018-01-01

    Objective Schizophrenia is a severe, debilitating mental disorder characterized by behavioral abnormalities. Although several studies have investigated the role of oxidative stress and the effects of antipsychotic drugs on oxidative markers in schizophrenia, adequate information is not available on these issues. The aim of this study is to determine the changes in oxidative status and thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs. Methods Thirteen schizophrenic patients using atypical antipsychotic drugs and 30 healthy controls were included this study. The concentrations of total oxidant status (TOS), total antioxidant status (TAS), native thiol, total thiol, and disulfide levels were determined in the study population. Results The TAS (p=0.001), total thiol, and native thiol levels (p<0.001) were higher in the patients compared to the controls, whereas the TOS and disulfide levels were lower in the patients than in the controls (p<0.001). Conclusion These results may suggest that atypical antipsychotic drugs have a useful therapeutic effect by reducing oxidative stress via the inhibition of the formation of disulfide bonds. The study population number was one of the limitations of this study. Therefore, further studies are needed to establish the association between thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs. PMID:29397665

  13. DIRECTIONAL FLUID TRANSPORT ACROSS ORGAN-BLOOD BARRIERS: PHYSIOLOGY AND CELL BIOLOGY

    PubMed Central

    Caceres, Paulo S.; Benedicto, Ignacio; Lehmann, Guillermo L.; Rodriguez-Boulan, Enrique J.

    2018-01-01

    Directional fluid flow is an essential process for embryo development as well as for organ and organism homeostasis. Here, we review the diverse structure of various organ-blood barriers, the driving forces, transporters and polarity mechanisms that regulate fluid transport across them, focusing on kidney-, eye- and brain-blood barriers. We end by discussing how cross-talk between barrier epithelial and endothelial cells, perivascular cells and basement membrane signaling contribute to generate and maintain organ-blood barriers. PMID:28003183

  14. [Hormonal homeostasis and intraocular pressure in chronic emotional stress caused by influences acting on the amygdala].

    PubMed

    Isakova, L S; Danilov, G E; Egorkina, S B; Butolin, E G

    1989-01-01

    Changes in intraocular pressure, eye hydrodynamics and the amount of hypophyseal, thyroid, adrenal and pancreatic hormones were studied during continuous stimulation of amygdaloid complex or after administration of angiotensin II into the structure in rabbits. The effects involved changes in hormonal homeostasis and elevation of intraocular pressure due to a hypersecretion of intraocular fluid. The administration of angiotensin II during the amygdala stimulation enhanced the changes.

  15. Personalised fluid resuscitation in the ICU: still a fluid concept?

    PubMed

    van Haren, Frank

    2017-12-28

    The administration of intravenous fluid to critically ill patients is one of the most common, but also one of the most fiercely debated, interventions in intensive care medicine. Even though many thousands of patients have been enrolled in large trials of alternative fluid strategies, consensus remains elusive and practice is widely variable. Critically ill patients are significantly heterogeneous, making a one size fits all approach unlikely to be successful.New data from basic, animal, and clinical research suggest that fluid resuscitation could be associated with significant harm. There are several important limitations and concerns regarding fluid bolus therapy as it is currently being used in clinical practice. These include, but are not limited to: the lack of an agreed definition; limited and short-lived physiological effects; no evidence of an effect on relevant patient outcomes; and the potential to contribute to fluid overload, specifically when fluid responsiveness is not assessed and when targets and safety limits are not used.Fluid administration in critically ill patients requires clinicians to integrate abnormal physiological parameters into a clinical decision-making model that also incorporates the likely diagnosis and the likely risk or benefit in the specific patient's context. Personalised fluid resuscitation requires careful attention to the mnemonic CIT TAIT: context, indication, targets, timing, amount of fluid, infusion strategy, and type of fluid.The research agenda should focus on experimental and clinical studies to: improve our understanding of the physiological effects of fluid infusion, e.g. on the glycocalyx; evaluate new types of fluids; evaluate novel fluid minimisation protocols; study the effects of a no-fluid strategy for selected patients and scenarios; and compare fluid therapy with other interventions. The adaptive platform trial design may provide us with the tools to evaluate these types of interventions in the intrinsically

  16. Loss of polyubiquitin gene Ubb leads to metabolic and sleep abnormalities in mice

    PubMed Central

    Ryu, K.-Y.; Fujiki, N.; Kazantzis, M.; Garza, J. C.; Bouley, D. M.; Stahl, A.; Lu, X.-Y.; Nishino, S.; Kopito, R. R.

    2010-01-01

    Aims Ubiquitin performs essential roles in a myriad of signalling pathways required for cellular function and survival. Recently, we reported that disruption of the stress-inducible ubiquitin-encoding gene Ubb reduces ubiquitin content in the hypothalamus and leads to adult-onset obesity coupled with a loss of arcuate nucleus neurones and disrupted energy homeostasis in mice. Neuropeptides expressed in the hypothalamus control both metabolic and sleep behaviours. In order to demonstrate that the loss of Ubb results in broad hypothalamic abnormalities, we attempted to determine whether metabolic and sleep behaviours were altered in Ubb knockout mice. Methods Metabolic rate and energy expenditure were measured in a metabolic chamber, and sleep stage was monitored via electroencephalographic/electromyographic recording. The presence of neurodegeneration and increased reactive gliosis in the hypothalamus were also evaluated. Results We found that Ubb disruption leads to early-onset reduced activity and metabolic rate. Additionally, we have demonstrated that sleep behaviour is altered and sleep homeostasis is disrupted in Ubb knockout mice. These early metabolic and sleep abnormalities are accompanied by persistent reactive gliosis and the loss of arcuate nucleus neurones, but are independent of neurodegeneration in the lateral hypothalamus. Conclusions Ubb knockout mice exhibit phenotypes consistent with hypothalamic dysfunction. Our data also indicate that Ubb is essential for the maintenance of the ubiquitin levels required for proper regulation of metabolic and sleep behaviours in mice. PMID:20002312

  17. Bolus fluid therapy and sodium homeostasis in paediatric gastroenteritis.

    PubMed

    Freedman, Stephen B; Geary, Denis F

    2013-03-01

    The study aims to assess the risk of developing hyponatraemia when large-volume bolus fluid rehydration therapy is administered. We conducted a prospective randomised study in a tertiary-care centre emergency department. Participants included children with gastroenteritis and dehydration requiring intravenous rehydration. They were randomised to receive 60 mL/kg (large) or 20 mL/kg (standard) 0.9% saline bolus followed by maintenance 0.9% saline for 3 h. Biochemical tests were performed at baseline and 4 h. The primary outcome measure was the development of hyponatraemia at 4 h. Secondary outcome measures were (i) change in sodium relative to baseline value; (ii) magnitude of decrease among those who experienced a decrease; (iii) risk of hypernatraemia; (iv) correlations between urine parameters and hyponatraemia; and (v) fluid overload. Eighty-four of 224 (38%) participants were hyponatraemic at baseline. At 4 h, 22% (48/217) had a dysnatraemia, and similar numbers of children were hyponatraemic in both groups: large (23% (26/112)) versus standard (21% (22/105)) (P = 0.69). Among initially hyponatraemic children, 63% (30/48) who received large-volume rehydration and 44% (15/34) of those administered standard rehydration were isonatraemic at 4 h (P = 0.10). Overall, children who received 60 mL/kg experienced a larger mean increase (1.6 ± 2.4 mEq/L vs. 0.9 ± 2.2 mEq/L; P = 0.04) and were less likely to experience a sodium decrease of ≥2 mEq/L (8/112 vs. 17/105; P = 0.04) than those administered 20 mL/kg. Large-volume bolus rehydration therapy with 0.9% saline is safe. It does not promote the development of hyponatraemia over the short term, but hastens the resolution of baseline hyponatraemia. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  18. Oxytocin-receptor-expressing neurons in the parabrachial nucleus regulate fluid intake.

    PubMed

    Ryan, Philip J; Ross, Silvano I; Campos, Carlos A; Derkach, Victor A; Palmiter, Richard D

    2017-12-01

    Brain regions that regulate fluid satiation are not well characterized, yet are essential for understanding fluid homeostasis. We found that oxytocin-receptor-expressing neurons in the parabrachial nucleus of mice (Oxtr PBN neurons) are key regulators of fluid satiation. Chemogenetic activation of Oxtr PBN neurons robustly suppressed noncaloric fluid intake, but did not decrease food intake after fasting or salt intake following salt depletion; inactivation increased saline intake after dehydration and hypertonic saline injection. Under physiological conditions, Oxtr PBN neurons were activated by fluid satiation and hypertonic saline injection. Oxtr PBN neurons were directly innervated by oxytocin neurons in the paraventricular hypothalamus (Oxt PVH  neurons), which mildly attenuated fluid intake. Activation of neurons in the nucleus of the solitary tract substantially suppressed fluid intake and activated Oxtr PBN neurons. Our results suggest that Oxtr PBN neurons act as a key node in the fluid satiation neurocircuitry, which acts to decrease water and/or saline intake to prevent or attenuate hypervolemia and hypernatremia.

  19. Modeling tensional homeostasis in multicellular clusters.

    PubMed

    Tam, Sze Nok; Smith, Michael L; Stamenović, Dimitrije

    2017-03-01

    Homeostasis of mechanical stress in cells, or tensional homeostasis, is essential for normal physiological function of tissues and organs and is protective against disease progression, including atherosclerosis and cancer. Recent experimental studies have shown that isolated cells are not capable of maintaining tensional homeostasis, whereas multicellular clusters are, with stability increasing with the size of the clusters. Here, we proposed simple mathematical models to interpret experimental results and to obtain insight into factors that determine homeostasis. Multicellular clusters were modeled as one-dimensional arrays of linearly elastic blocks that were either jointed or disjointed. Fluctuating forces that mimicked experimentally measured cell-substrate tractions were obtained from Monte Carlo simulations. These forces were applied to the cluster models, and the corresponding stress field in the cluster was calculated by solving the equilibrium equation. It was found that temporal fluctuations of the cluster stress field became attenuated with increasing cluster size, indicating that the cluster approached tensional homeostasis. These results were consistent with previously reported experimental data. Furthermore, the models revealed that key determinants of tensional homeostasis in multicellular clusters included the cluster size, the distribution of traction forces, and mechanical coupling between adjacent cells. Based on these findings, we concluded that tensional homeostasis was a multicellular phenomenon. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Cerebrospinal fluid and neuroimaging biomarker abnormalities suggest early neurological injury in a subset of individuals during primary HIV infection.

    PubMed

    Peluso, Michael J; Meyerhoff, Dieter J; Price, Richard W; Peterson, Julia; Lee, Evelyn; Young, Andrew C; Walter, Rudy; Fuchs, Dietmar; Brew, Bruce J; Cinque, Paola; Robertson, Kevin; Hagberg, Lars; Zetterberg, Henrik; Gisslén, Magnus; Spudich, Serena

    2013-06-01

    Cerebrospinal fluid (CSF) and neuroimaging abnormalities demonstrate neuronal injury during chronic AIDS, but data on these biomarkers during primary human immunodeficiency virus (HIV) infection is limited. We compared CSF concentrations of neurofilament light chain, t-tau, p-tau, amyloid precursor proteins, and amyloid-beta 42 in 92 subjects with primary HIV infection and 25 controls. We examined relationships with disease progression and neuroinflammation, neuropsychological testing, and proton-magnetic resonance spectroscopy (MRS)-based metabolites. Neurofilament light chain was elevated in primary HIV infection compared with controls (P = .0004) and correlated with CSF neopterin (r = 0.38; P = .0005), interferon gamma-induced protein 10 (r = 0.39; P = .002), white blood cells (r = 0.32; P = .004), protein (r = 0.59; P < .0001), and CSF/plasma albumin ratio (r = 0.60; P < .0001). Neurofilament light chain correlated with decreased N-acteylaspartate/creatine and glutamate/creatine in the anterior cingulate (r = -0.35, P = .02; r = -0.40, P = .009, respectively), frontal white matter (r = -0.43, P = .003; r = -0.30, P = .048, respectively), and parietal gray matter (r = -0.43, P = .003; r = -0.47, P = .001, respectively). Beta-amyloid was elevated in the primary infection group (P = .0005) and correlated with time infected (r = 0.34; P = .003). Neither marker correlated with neuropsychological abnormalities. T-tau and soluble amyloid precursor proteins did not differ between groups. Elevated neurofilament light chain and its correlation with MRS-based metabolites suggest early neuronal injury in a subset of participants with primary HIV infection through mechanisms involving central nervous system inflammation.

  1. Osmotic Homeostasis

    PubMed Central

    Zeidel, Mark L.

    2015-01-01

    Alterations in water homeostasis can disturb cell size and function. Although most cells can internally regulate cell volume in response to osmolar stress, neurons are particularly at risk given a combination of complex cell function and space restriction within the calvarium. Thus, regulating water balance is fundamental to survival. Through specialized neuronal “osmoreceptors” that sense changes in plasma osmolality, vasopressin release and thirst are titrated in order to achieve water balance. Fine-tuning of water absorption occurs along the collecting duct, and depends on unique structural modifications of renal tubular epithelium that confer a wide range of water permeability. In this article, we review the mechanisms that ensure water homeostasis as well as the fundamentals of disorders of water balance. PMID:25078421

  2. Preoperative octreotide therapy and surgery in acromegaly: associations between glucose homeostasis and treatment response.

    PubMed

    Helseth, R; Carlsen, S M; Bollerslev, J; Svartberg, J; Øksnes, M; Skeie, S; Fougner, S L

    2016-02-01

    In acromegaly, high GH/IGF-1 levels associate with abnormal glucose metabolism. Somatostatin analogs (SSAs) reduce GH and IGF-1 but inhibit insulin secretion. We studied glucose homeostasis in de novo patients with acromegaly and changes in glucose metabolism after treatment with SSA and surgery. In this post hoc analysis from a randomized controlled trial, 55 de novo patients with acromegaly, not using antidiabetic medication, were included. Before surgery, 26 patients received SSAs for 6 months. HbA1c, fasting glucose, and oral glucose tolerance test were performed at baseline, after SSA pretreatment and at 3 months postoperative. Area under curve of glucose (AUC-G) was calculated. Glucose homeostasis was compared to baseline levels of GH and IGF-1, change after SSA pretreatment, and remission both after SSA pretreatment and 3 months postoperative. In de novo patients, IGF-1/GH levels did not associate with baseline glucose parameters. After SSA pretreatment, changes in GH/IGF-1 correlated positively to change in HbA1c levels (both p < 0.03). HbA1c, fasting glucose, and AUC-G increased significantly during SSA pretreatment in patients not achieving hormonal control (all p < 0.05) but did not change significantly in patients with normalized hormone levels. At 3 months postoperative, HbA1c, fasting glucose, and AUC-G were significantly reduced in both cured and not cured patients (all p < 0.05). To conclude, in de novo patients with acromegaly, disease activity did not correlate with glucose homeostasis. Surgical treatment of acromegaly improved glucose metabolism in both cured and not cured patients, while SSA pretreatment led to deterioration in glucose homeostasis in patients not achieving biochemical control.

  3. Controversies in fluid therapy: Type, dose and toxicity

    PubMed Central

    McDermid, Robert C; Raghunathan, Karthik; Romanovsky, Adam; Shaw, Andrew D; Bagshaw, Sean M

    2014-01-01

    Fluid therapy is perhaps the most common intervention received by acutely ill hospitalized patients; however, a number of critical questions on the efficacy and safety of the type and dose remain. In this review, recent insights derived from randomized trials in terms of fluid type, dose and toxicity are discussed. We contend that the prescription of fluid therapy is context-specific and that any fluid can be harmful if administered inappropriately. When contrasting ‘‘crystalloid vs colloid’’, differences in efficacy are modest but differences in safety are significant. Differences in chloride load and strong ion difference across solutions appear to be clinically important. Phases of fluid therapy in acutely ill patients are recognized, including acute resuscitation, maintaining homeostasis, and recovery phases. Quantitative toxicity (fluid overload) is associated with adverse outcomes and can be mitigated when fluid therapy based on functional hemodynamic parameters that predict volume responsiveness and minimization of non-essential fluid. Qualitative toxicity (fluid type), in particular for iatrogenic acute kidney injury and metabolic acidosis, remain a concern for synthetic colloids and isotonic saline, respectively. Physiologically balanced crystalloids may be the ‘‘default’’ fluid for acutely ill patients and the role for colloids, in particular hydroxyethyl starch, is increasingly unclear. We contend the prescription of fluid therapy is analogous to the prescription of any drug used in critically ill patients. PMID:24834399

  4. Regulatory mechanisms of anthrax toxin receptor 1-dependent vascular and connective tissue homeostasis.

    PubMed

    Besschetnova, Tatiana Y; Ichimura, Takaharu; Katebi, Negin; St Croix, Brad; Bonventre, Joseph V; Olsen, Bjorn R

    2015-03-01

    It is well known that angiogenesis is linked to fibrotic processes in fibroproliferative diseases, but insights into pathophysiological processes are limited, due to lack of understanding of molecular mechanisms controlling endothelial and fibroblastic homeostasis. We demonstrate here that the matrix receptor anthrax toxin receptor 1 (ANTXR1), also known as tumor endothelial marker 8 (TEM8), is an essential component of these mechanisms. Loss of TEM8 function in mice causes reduced synthesis of endothelial basement membrane components and hyperproliferative and leaky blood vessels in skin. In addition, endothelial cell alterations in mutants are almost identical to those of endothelial cells in infantile hemangioma lesions, including activated VEGF receptor signaling in endothelial cells, increased expression of the downstream targets VEGF and CXCL12, and increased numbers of macrophages and mast cells. In contrast, loss of TEM8 in fibroblasts leads to increased rates of synthesis of fiber-forming collagens, resulting in progressive fibrosis in skin and other organs. Compromised interactions between TEM8-deficient endothelial and fibroblastic cells cause dramatic reduction in the activity of the matrix-degrading enzyme MMP2. In addition to insights into mechanisms of connective tissue homeostasis, our data provide molecular explanations for vascular and connective tissue abnormalities in GAPO syndrome, caused by loss-of-function mutations in ANTXR1. Furthermore, the loss of MMP2 activity suggests that fibrotic skin abnormalities in GAPO syndrome are, in part, the consequence of pathophysiological mechanisms underlying syndromes (NAO, Torg and Winchester) with multicentric skin nodulosis and osteolysis caused by homozygous loss-of-function mutations in MMP2. Copyright © 2014 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  5. A Physiologist's View of Homeostasis

    ERIC Educational Resources Information Center

    Modell, Harold; Cliff, William; Michael, Joel; McFarland, Jenny; Wenderoth, Mary Pat; Wright, Ann

    2015-01-01

    Homeostasis is a core concept necessary for understanding the many regulatory mechanisms in physiology. Claude Bernard originally proposed the concept of the constancy of the "milieu interieur," but his discussion was rather abstract. Walter Cannon introduced the term "homeostasis" and expanded Bernard's notion of…

  6. A humanized system to expand in vitro amniotic fluid-derived stem cells intended for clinical application.

    PubMed

    Martinelli, Daniela; Pereira, Rui Cruz; Mogni, Massimo; Benelli, Roberto; Mastrogiacomo, Maddalena; Coviello, Domenico; Cancedda, Ranieri; Gentili, Chiara

    2016-03-01

    The amniotic fluid is a new source of multipotent stem cells with therapeutic potential for human diseases. In agreement with the regulatory requirement to reduce and possibly to avoid animal-derived reagents in the culture of cells intended for cell therapy, bovine serum, the most common supplement in the culture medium, was replaced by human platelet-derived growth factors. We tested a new culture medium to expand monolayers of human amniotic fluid stem cells (hAFSC) for clinical use. The AFSC were isolated by c-Kit selection and expanded in media supplemented with either bovine serum or a human platelet lysate (Lyset). We compared proliferation kinetics, colony-forming unit percentage, multilineage differentiation, immunophenotypic characterization and inhibition of peripheral blood mononuclear cell proliferation of the two AFSC cell cultures and we found no significant differences. Moreover, the karyotype analysis of the cells expanded in the presence of the platelet lysate did not present cytogenetic abnormalities and in vitro and in vivo studies revealed no cell tumorigenicity. Platelet derivatives represent a rich source of growth factors that can play a safety role in the homeostasis, proliferation and remodeling of tissue healing. We propose human platelet extracts as a preferential alternative to animal serum for the expansion of stem cells for clinical applications. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  7. Exacerbated immune stress response during experimental magnesium deficiency results from abnormal cell calcium homeostasis.

    PubMed

    Malpuech-Brugère, C; Rock, E; Astier, C; Nowacki, W; Mazur, A; Rayssiguier, Y

    1998-01-01

    The aim of this study was to assess the potential mechanism underlying the enhanced inflammatory processes during magnesium deficit. In this study, exacerbated response to live bacteria and platelet activating factors was shown in rats fed a magnesium-deficient diet. Peritoneal cells from these animals also showed enhanced superoxide anion production and calcium mobilising potency following in vitro stimulation. The latter effect occurred very early in the course of magnesium deficiency. These studies first showed that an abnormal calcium handling induced by extracellular magnesium depression in vivo may be at the origin of exacerbated inflammatory response.

  8. Importance of Abnormal Chloride Homeostasis in Stable Chronic Heart Failure.

    PubMed

    Grodin, Justin L; Verbrugge, Frederik H; Ellis, Stephen G; Mullens, Wilfried; Testani, Jeffrey M; Tang, W H Wilson

    2016-01-01

    The aim of this analysis was to determine the long-term prognostic value of lower serum chloride in patients with stable chronic heart failure. Electrolyte abnormalities are prevalent in patients with chronic heart failure. Little is known regarding the prognostic implications of lower serum chloride. Serum chloride was measured in 1673 consecutively consented stable patients with a history of heart failure undergoing elective diagnostic coronary angiography. All patients were followed for 5-year all-cause mortality, and survival models were adjusted for variables that confounded the chloride-risk relationship. The average chloride level was 102 ± 4 mEq/L. Over 6772 person-years of follow-up, there were 547 deaths. Lower chloride (per standard deviation decrease) was associated with a higher adjusted risk of mortality (hazard ratio 1.29, 95% confidence interval 1.12-1.49; P < 0.001). Chloride levels net-reclassified risk in 10.4% (P = 0.03) when added to a multivariable model (with a resultant C-statistic of 0.70), in which sodium levels were not prognostic (P = 0.30). In comparison to those with above first quartile chloride (≥ 101 mEq/L) and sodium (≥ 138 meq/L), subjects with first quartile chloride had a higher adjusted mortality risk, whether they had first quartile sodium (hazard ratio 1.35, 95% confidence interval 1.08-1.69; P = 0.008) or higher (hazard ratio 1.43, 95% confidence interval 1.12-1.85; P = 0.005). However, subjects with first quartile sodium but above first quartile chloride had no association with mortality (P = 0.67). Lower serum chloride levels are independently and incrementally associated with increased mortality risk in patients with chronic heart failure. A better understanding of the biological role of serum chloride is warranted. © 2015 American Heart Association, Inc.

  9. Mathematical modelling of fluid transport and its regulation at multiple scales.

    PubMed

    Chara, Osvaldo; Brusch, Lutz

    2015-04-01

    Living matter equals water, to a first approximation, and water transport across barriers such as membranes and epithelia is vital. Water serves two competing functions. On the one hand, it is the fundamental solvent enabling random mobility of solutes and therefore biochemical reactions and intracellular signal propagation. Homeostasis of the intracellular water volume is required such that messenger concentration encodes the stimulus and not inverse volume fluctuations. On the other hand, water flow is needed for transport of solutes to and away from cells in a directed manner, threatening volume homeostasis and signal transduction fidelity of cells. Feedback regulation of fluid transport reconciles these competing objectives. The regulatory mechanisms often span across multiple spatial scales from cellular interactions up to the architecture of organs. Open questions relate to the dependency of water fluxes and steady state volumes on control parameters and stimuli. We here review selected mathematical models of feedback regulation of fluid transport at the cell scale and identify a general "core-shell" structure of such models. We propose that fluid transport models at other spatial scales can be constructed in a generalised core-shell framework, in which the core accounts for the biophysical effects of fluid transport whilst the shell reflects the regulatory mechanisms. We demonstrate the applicability of this framework for tissue lumen growth and suggest future experiments in zebrafish to test lumen size regulation mechanisms. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Oxygen Sensing and Homeostasis

    PubMed Central

    Semenza, Gregg L.

    2015-01-01

    The discovery of carotid bodies as sensory receptors for detecting arterial blood oxygen levels, and the identification and elucidation of the roles of hypoxia-inducible factors (HIFs) in oxygen homeostasis have propelled the field of oxygen biology. This review highlights the gas-messenger signaling mechanisms associated with oxygen sensing, as well as transcriptional and non-transcriptional mechanisms underlying the maintenance of oxygen homeostasis by HIFs and their relevance to physiology and pathology. PMID:26328879

  11. Fluid therapy in small ruminants and camelids.

    PubMed

    Jones, Meredyth; Navarre, Christine

    2014-07-01

    Body water, electrolytes, and acid-base balance are important considerations in the evaluation and treatment of small ruminants and camelids with any disease process, with restoration of these a priority as adjunctive therapy. The goals of fluid therapy should be to maintain cardiac output and tissue perfusion, and to correct acid-base and electrolyte abnormalities. Hypoglycemia, hyperkalemia, and acidosis are the most life-threatening abnormalities, and require most immediate correction. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Cerebrospinal Fluid and Neuroimaging Biomarker Abnormalities Suggest Early Neurological Injury in a Subset of Individuals During Primary HIV Infection

    PubMed Central

    Peluso, Michael J.; Meyerhoff, Dieter J.; Price, Richard W.; Peterson, Julia; Lee, Evelyn; Young, Andrew C.; Walter, Rudy; Fuchs, Dietmar; Brew, Bruce J.; Cinque, Paola; Robertson, Kevin; Hagberg, Lars; Zetterberg, Henrik; Gisslén, Magnus; Spudich, Serena

    2013-01-01

    Background. Cerebrospinal fluid (CSF) and neuroimaging abnormalities demonstrate neuronal injury during chronic AIDS, but data on these biomarkers during primary human immunodeficiency virus (HIV) infection is limited. Methods. We compared CSF concentrations of neurofilament light chain, t-tau, p-tau, amyloid precursor proteins, and amyloid-beta 42 in 92 subjects with primary HIV infection and 25 controls. We examined relationships with disease progression and neuroinflammation, neuropsychological testing, and proton-magnetic resonance spectroscopy (MRS)–based metabolites. Results. Neurofilament light chain was elevated in primary HIV infection compared with controls (P = .0004) and correlated with CSF neopterin (r = 0.38; P = .0005), interferon gamma-induced protein 10 (r = 0.39; P = .002), white blood cells (r = 0.32; P = .004), protein (r = 0.59; P < .0001), and CSF/plasma albumin ratio (r = 0.60; P < .0001). Neurofilament light chain correlated with decreased N-acteylaspartate/creatine and glutamate/creatine in the anterior cingulate (r = −0.35, P = .02; r = −0.40, P = .009, respectively), frontal white matter (r = −0.43, P = .003; r = −0.30, P = .048, respectively), and parietal gray matter (r = −0.43, P = .003; r = −0.47, P = .001, respectively). Beta-amyloid was elevated in the primary infection group (P = .0005) and correlated with time infected (r = 0.34; P = .003). Neither marker correlated with neuropsychological abnormalities. T-tau and soluble amyloid precursor proteins did not differ between groups. Conclusions. Elevated neurofilament light chain and its correlation with MRS-based metabolites suggest early neuronal injury in a subset of participants with primary HIV infection through mechanisms involving central nervous system inflammation. PMID:23460748

  13. Cellular copper homeostasis: current concepts on its interplay with glutathione homeostasis and its implication in physiology and human diseases.

    PubMed

    Bhattacharjee, Ashima; Chakraborty, Kaustav; Shukla, Aditya

    2017-10-18

    Copper is a trace element essential for almost all living organisms. But the level of intracellular copper needs to be tightly regulated. Dysregulation of cellular copper homeostasis leading to various diseases demonstrates the importance of this tight regulation. Copper homeostasis is regulated not only within the cell but also within individual intracellular compartments. Inactivation of export machinery results in excess copper being redistributed into various intracellular organelles. Recent evidence suggests the involvement of glutathione in playing an important role in regulating copper entry and intracellular copper homeostasis. Therefore interplay of both homeostases might play an important role within the cell. Similar to copper, glutathione balance is tightly regulated within individual cellular compartments. This review explores the existing literature on the role of glutathione in regulating cellular copper homeostasis. On the one hand, interplay of glutathione and copper homeostasis performs an important role in normal physiological processes, for example neuronal differentiation. On the other hand, perturbation of the interplay might play a key role in the pathogenesis of copper homeostasis disorders.

  14. Intermittent Hypoxia Impairs Glucose Homeostasis in C57BL6/J Mice: Partial Improvement with Cessation of the Exposure

    PubMed Central

    Polak, Jan; Shimoda, Larissa A.; Drager, Luciano F.; Undem, Clark; McHugh, Holly; Polotsky, Vsevolod Y.; Punjabi, Naresh M.

    2013-01-01

    Objectives: Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued. Interventions: C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14 days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of intermittent air (recovery paradigm). Glucose and insulin tolerance tests were performed to estimate whole-body insulin sensitivity and calculate measures of beta cell function. Oxidative stress in pancreatic tissue and glucose output from isolated hepatocytes were also assessed. Results: Intermittent hypoxia increased fasting glucose levels and worsened glucose tolerance by 67% and 27%, respectively. Furthermore, intermittent hypoxia exposure was associated with impairments in insulin sensitivity and beta cell function, an increase in liver glycogen, higher hepatocyte glucose output, and an increase in oxidative stress in the pancreas. While fasting glucose levels and hepatic glucose output normalized after discontinuation of the hypoxic exposure, glucose intolerance, insulin resistance, and impairments in beta cell function persisted. Conclusions: Intermittent hypoxia induces insulin resistance, impairs beta cell function, enhances hepatocyte glucose output, and increases oxidative stress in the pancreas. Cessation of the hypoxic exposure does not fully reverse the observed changes in glucose metabolism. Citation: Polak J; Shimoda LA; Drager LF; Undem C; McHugh H; Polotsky VY; Punjabi NM

  15. Embryonic blood-cerebrospinal fluid barrier formation and function

    PubMed Central

    Bueno, David; Parvas, Maryam; Hermelo, Ismaïl; Garcia-Fernàndez, Jordi

    2014-01-01

    During embryonic development and adult life, brain cavities and ventricles are filled with cerebrospinal fluid (CSF). CSF has attracted interest as an active signaling medium that regulates brain development, homeostasis and disease. CSF is a complex protein-rich fluid containing growth factors and signaling molecules that regulate multiple cell functions in the central nervous system (CNS). The composition and substance concentrations of CSF are tightly controlled. In recent years, it has been demonstrated that embryonic CSF (eCSF) has a key function as a fluid pathway for delivering diffusible signals to the developing brain, thus contributing to the proliferation, differentiation and survival of neural progenitor cells, and to the expansion and patterning of the brain. From fetal stages through to adult life, CSF is primarily produced by the choroid plexus. The development and functional activities of the choroid plexus and other blood–brain barrier (BBB) systems in adults and fetuses have been extensively analyzed. However, eCSF production and control of its homeostasis in embryos, from the closure of the anterior neuropore when the brain cavities become physiologically sealed, to the formation of the functional fetal choroid plexus, has not been studied in as much depth and remains open to debate. This review brings together the existing literature, some of which is based on experiments conducted by our research group, concerning the formation and function of a temporary embryonic blood–CSF barrier in the context of the crucial roles played by the molecules in eCSF. PMID:25389383

  16. Concept analysis of family homeostasis.

    PubMed

    Kim, Heejung; Rose, Karen M

    2014-11-01

    To report a concept analysis of family homeostasis. As family members are a majority of informal caregivers, negative consequences from caregiving duty create a vicious cycle in the family unit resulting in ongoing health crises and care challenges. Concept analysis. Forty empirical studies published from 1956-2012 were selected by searching five electronic bibliographical databases and by a manual search conducted from 2012-2013. Search terms included 'family homeostasis', 'homeostasis in family', 'homeostatic care' and 'family equilibrium'. Clinical experiences in nursing practice were used for constructing cases and clinical implications. Walker and Avant's method guided this analysis. Family homeostasis is defined as the capacity and mechanisms by which equilibrium is re-established in the family after a change occurs. Five critical attributes are identified: (1) predetermined setpoint; (2) self-appraised antecedents; (3) interdependence; (4) tendency to stability; and (5) feedback mechanisms. Antecedents include any type of causative change beyond the tolerable limit, while consequences encompass intermediate and long-term outcomes as well as equilibrium itself. Family homeostasis provides a conceptual rationale of family caregiving. While care recipients remain the primary beneficiaries of healthcare provision, homeostatic mechanisms are required to support the family caregiver's valuable contribution in the caring process to enhance family well-being. Further study should expand the definition and settings of family to reflect healthcare needs of diverse types of families and from the perspectives of different healthcare providers. © 2014 John Wiley & Sons Ltd.

  17. Glucose Homeostasis and Effect of Chelation on β Cell Function in Children With β-Thalassemia Major.

    PubMed

    Gomber, Sunil; Dabas, Aashima; Bagmar, Shilpa; Madhu, Sri Venkata

    2018-01-01

    To assess the prevalence of impaired glucose tolerance in β-thalassemia major and correlate it with chelation therapy. Sixty-seven subjects with β-thalassemia major, aged 1 to 20 years, were enrolled in our prospective cohort. Clinical details were recorded. Baseline oral glucose tolerance test, serum insulin, C peptide, and insulin resistance were measured. The biochemical profile was repeated after 6 months. The mean age of subjects was 7.43±4.48 years. Eight (11.9%) subjects had impaired fasting glucose, 7 (10.4%) had impaired glucose tolerance, and 1 (1.4%) subject had diabetes at baseline. Subjects with abnormal glucose profile had longer disease duration (95% confidence interval [CI] of difference=-6.64 to -0.68; P=0.019) and higher fasting blood glucose (95% CI of difference=-32.1 to -10.5; P=0.001) and serum ferritin (95% CI of difference=-219.8 to -3.4; P=0.001) than normoglycemic subjects. Insulin resistance and serum ferritin showed significant increase at 6 months (P<0.001 and P=0.001, respectively). Patients on deferiprone alone significantly improved glucose homeostasis on follow-up than those on desferrioxamine or combination therapy of desferrioxamine and deferiprone (P<0.05). Prolonged disease duration and higher serum ferritin adversely affects glucose homeostasis in thalassemic children. Deferiprone was the most effective chelator to improve glucose homeostasis in chronically transfused thalassemics.

  18. Amniotic fluid gamma-glutamyl transpeptidase activity during the second trimester.

    PubMed

    Legge, M; Potter, H C

    1986-03-12

    Gamma glutamyl transpeptidase (GGTP) activity was determined in second trimester amniotic fluid taken from normal fetuses and those with fetal abnormalities. GGTP activity decreased with advancing gestation. Increasing meconium contamination correlated with an increase in GGTP activity as did increasing fetal blood contamination. Maternal blood did not affect GGTP activity. Anencephaly did not significantly alter the GGTP activity, however, fetuses with spina bifida had significantly lower activity. Klinefelters and Turners syndromes both had GGTP activity close to the 50th percentile, and two trisomy 21 fetuses had GGTP activity below the 40th percentile. Two trisomy 18 fetuses and two translocation Downs syndromes (46 XY, t (14;21) had GGTP activities considerably lower than the 20th percentile as did a fetus with gastroschisis. Second trimester amniotic fluid GGTP activity may provide an easy preliminary test to screen amniotic fluids for the possibility of certain fetal chromosome abnormalities.

  19. A conceptual framework for homeostasis: development and validation

    PubMed Central

    Wenderoth, Mary Pat; Michael, Joel; Cliff, William; Wright, Ann; Modell, Harold

    2016-01-01

    We have developed and validated a conceptual framework for understanding and teaching organismal homeostasis at the undergraduate level. The resulting homeostasis conceptual framework details critical components and constituent ideas underlying the concept of homeostasis. It has been validated by a broad range of physiology faculty members from community colleges, primarily undergraduate institutions, research universities, and medical schools. In online surveys, faculty members confirmed the relevance of each item in the framework for undergraduate physiology and rated the importance and difficulty of each. The homeostasis conceptual framework was constructed as a guide for teaching and learning of this critical core concept in physiology, and it also paves the way for the development of a concept inventory for homeostasis. PMID:27105740

  20. Genetic defects disrupting glial ion and water homeostasis in the brain.

    PubMed

    Min, Rogier; van der Knaap, Marjo S

    2018-05-01

    Electrical activity of neurons in the brain, caused by the movement of ions between intracellular and extracellular compartments, is the basis of all our thoughts and actions. Maintaining the correct ionic concentration gradients is therefore crucial for brain functioning. Ion fluxes are accompanied by the displacement of osmotically obliged water. Since even minor brain swelling leads to severe brain damage and even death, brain ion and water movement has to be tightly regulated. Glial cells, in particular astrocytes, play a key role in ion and water homeostasis. They are endowed with specific channels, pumps and carriers to regulate ion and water flow. Glial cells form a large panglial syncytium to aid the uptake and dispersal of ions and water, and make extensive contacts with brain fluid barriers for disposal of excess ions and water. Genetic defects in glial proteins involved in ion and water homeostasis disrupt brain functioning, thereby leading to neurological diseases. Since white matter edema is often a hallmark disease feature, many of these diseases are characterized as leukodystrophies. In this review we summarize our current understanding of inherited glial diseases characterized by disturbed brain ion and water homeostasis by integrating findings from MRI, genetics, neuropathology and animal models for disease. We discuss how mutations in different glial proteins lead to disease, and highlight the similarities and differences between these diseases. To come to effective therapies for this group of diseases, a better mechanistic understanding of how glial cells shape ion and water movement in the brain is crucial. © 2018 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

  1. Mesothalamic discharge in a chronic pain, allergy and fluid retention syndrome (case report).

    PubMed

    Andy, O J; Nicholas, W; Dearman, C

    1995-01-01

    A 32-year-old woman was bedridden for a year because of chronic pain and headaches. She had insomnia, depression, suicidal thoughts and a severe chemical allergy. She had been on steroid therapy for two years and became Cushingoid with striae in the arm pits, groins and abdomen. However, she had no hypertension, nor the buffalo fat and hirsutism. She was very edematous, with a weight gain from 112 to 180 lbs. The fluid retention did not conform to the syndrome of inappropriate antidiuretic hormone. Studies revealed abnormal scalp EEG discharges and high-voltage seizure discharges in the posterior thalamus. Electrothalamic stimulation suppressed the thalamic discharges and relieved the patient's pelvic pain and headaches. After one month of several thalamic stimulations per day, she was able to get out of bed and ambulate. In addition, the patient no longer was edematous and was tolerating perfumes and floor detergents. Steroids were progressively reduced without complications of withdrawal. She went from a completely steroid dependent state to independent during the first 1-1/2 yrs of thalamic stimulation. With continued thalamic stimulation she has done well for 8-1/2 yrs, weighs 112 lbs, keeps house and drives a car. It's speculated the illness is a chronic pain multiple syndrome predominantly due to mesothalamic discharges and body infirmities. The mesothalamic discharge implicated neural networks, which represent biologic systems, i.e. pain, sleep, fluid retention, etc. Therapeutic stimulation attenuates the discharges and the neural networks return to their normal set points of homeostasis.

  2. [Perioperative fluid therapy for surgical patients with chronic kidney disease].

    PubMed

    Iijima, Takehiko

    2013-11-01

    Chronic kidney disease (CKD) often accompanies cardiovascular complications, causing postoperative morbidity and even mortality. Since fluid and electrolyte homeostasis is deregulated in CKD patients, fluid therapy itself may cause postoperative morbidity. Recent studies have shown that forced diuresis through fluid overload offers no renoprotective effect and instead has harmful consequences. Fluid overload should be avoided, and the volume load should be used as the rationale for controlling hemodynamics. The emerging concept of a "zero-fluid balance policy" may be beneficial even for CKD patients. Hydroxyethylstarch might not be preferentially used for CKD patients. Hydroxyethylstarch is not contraindicated for CKD patients except in cases with long-term accumulation caused by increased vascular permeability, such as cases with sepsis, as long as an efficient volume expansion is beneficial to the patient. The regulation of renal function through the endocrine system (i.e., renin-angiotensin-aldosterone and vasopressin) is a key target for protecting the kidney in CKD. The recent development of a receptor blocker targeting these endocrine systems may be beneficial for correcting the fluid balance caused by excess intraoperative fluid therapy. The main issue for fluid therapy in surgical CKD patients may not be the quantity of fluid, but rational intervention affecting the endocrine system.

  3. Immune Abnormalities in Autism Spectrum Disorder-Could They Hold Promise for Causative Treatment?

    PubMed

    Gładysz, Dominika; Krzywdzińska, Amanda; Hozyasz, Kamil K

    2018-01-06

    Autism spectrum disorders (ASD) are characterized by impairments in language and communication development, social behavior, and the occurrence of stereotypic patterns of behavior and interests. Despite substantial speculation about causes of ASD, its exact etiology remains unknown. Recent studies highlight a link between immune dysfunction and behavioral traits. Various immune anomalies, including humoral and cellular immunity along with abnormalities at the molecular level, have been reported. There is evidence of altered immune function both in cerebrospinal fluid and peripheral blood. Several studies hypothesize a role for neuroinflammation in ASD and are supported by brain tissue and cerebrospinal fluid analysis, as well as evidence of microglial activation. It has been shown that immune abnormalities occur in a substantial number of individuals with ASD. Identifying subgroups with immune system dysregulation and linking specific cellular immunophenotypes to different symptoms would be key to defining a group of patients with immune abnormalities as a major etiology underlying behavioral symptoms. These determinations would provide the opportunity to investigate causative treatments for a defined patient group that may specifically benefit from such an approach. This review summarizes recent insights into immune system dysfunction in individuals with ASD and discusses the potential implications for future therapies.

  4. A conceptual framework for homeostasis: development and validation.

    PubMed

    McFarland, Jenny; Wenderoth, Mary Pat; Michael, Joel; Cliff, William; Wright, Ann; Modell, Harold

    2016-06-01

    We have developed and validated a conceptual framework for understanding and teaching organismal homeostasis at the undergraduate level. The resulting homeostasis conceptual framework details critical components and constituent ideas underlying the concept of homeostasis. It has been validated by a broad range of physiology faculty members from community colleges, primarily undergraduate institutions, research universities, and medical schools. In online surveys, faculty members confirmed the relevance of each item in the framework for undergraduate physiology and rated the importance and difficulty of each. The homeostasis conceptual framework was constructed as a guide for teaching and learning of this critical core concept in physiology, and it also paves the way for the development of a concept inventory for homeostasis. Copyright © 2016 The American Physiological Society.

  5. Texture Analysis of T1-Weighted and Fluid-Attenuated Inversion Recovery Images Detects Abnormalities That Correlate With Cognitive Decline in Small Vessel Disease.

    PubMed

    Tozer, Daniel J; Zeestraten, Eva; Lawrence, Andrew J; Barrick, Thomas R; Markus, Hugh S

    2018-06-04

    Magnetic resonance imaging may be useful to assess disease severity in cerebral small vessel disease (SVD), identify those individuals who are most likely to progress to dementia, monitor disease progression, and act as surrogate markers to test new therapies. Texture analysis extracts information on the relationship between signal intensities of neighboring voxels. A potential advantage over techniques, such as diffusion tensor imaging, is that it can be used on clinically obtained magnetic resonance sequences. We determined whether texture parameters (TP) were abnormal in SVD, correlated with cognitive impairment, predicted cognitive decline, or conversion to dementia. In the prospective SCANS study (St George's Cognition and Neuroimaging in Stroke), we assessed TP in 121 individuals with symptomatic SVD at baseline, 99 of whom attended annual cognitive testing for 5 years. Conversion to dementia was recorded for all subjects during the 5-year period. Texture analysis was performed on fluid-attenuated inversion recovery and T1-weighted images. The TP obtained from the SVD cohort were cross-sectionally compared with 54 age-matched controls scanned on the same magnetic resonance imaging system. There were highly significant differences in several TP between SVD cases and controls. Within the SVD population, TP were highly correlated to other magnetic resonance imaging parameters (brain volume, white matter lesion volume, lacune count). TP correlated with executive function and global function at baseline and predicted conversion to dementia, after controlling for age, sex, premorbid intelligence quotient, and magnetic resonance parameters. TP, which can be obtained from routine clinical images, are abnormal in SVD, and the degree of abnormality correlates with executive dysfunction and global cognition at baseline and decline during 5 years. TP may be useful to assess disease severity in clinically collected data. This needs testing in data clinically acquired

  6. Fluid balance within the canine anterolateral compartment and its relationship to compartment syndromes.

    PubMed

    Hargens, A R; Akeson, W H; Mubarak, S J; Owen, C A; Evans, K L; Garetto, L P; Gonsalves, M R; Schmidt, D A

    1978-06-01

    Fluid homeostasis within muscle compartments is maintained by four pressures: capillary blood pressure, capillary blood oncotic pressure, tissue-fluid pressure, and tissue fluid oncotic pressure. As determined in the canine anterolateral compartment, capillary blood pressure is 25 +/- 3 millimeters of mercury; capillary blood oncotic pressure, 26 +/- 3 millimeters of mercury, tissue-pbessure, -2 +/- 2 millimeters of mercury; and tissue-fluid oncotic pressure, 11 +/- 1 millimeters of mercury. The wick technique allows direct measurement of tissue-fluid pressure in skeletal muscle and, with minor modifications, is adapted to collect microsamples of interstitial fluid for determinations of tissue-fluid oncotic pressure. The wick technique detects very slight fluctuations in intracompartmental pressure such as light finger compression, injection of small volumes of fluid, and even pulsation due to adjacent arterial pressure. Adjacent muscle compartments may contain different tissue-fluid pressure due to impermeable osseofascial barriers. Our results obtained in canine muscle compartments pressurized by infusion of autologous plasma suggest that risks of muscle damage are significant at intracompartmental pressures greater than thirty millimeters of mercury.

  7. Interstitial ion homeostasis and acid-base balance are maintained in oedematous brain of mice with acute toxic liver failure.

    PubMed

    Obara-Michlewska, Marta; Ding, Fengfei; Popek, Mariusz; Verkhratsky, Alexei; Nedergaard, Maiken; Zielinska, Magdalena; Albrecht, Jan

    2018-05-14

    Acute toxic liver failure (ATLF) rapidly leads to brain oedema and neurological decline. We evaluated the ability of ATLF-affected brain to control the ionic composition and acid-base balance of the interstitial fluid. ATLF was induced in 10-12 weeks old male C57Bl mice by single intraperitoneal (i.p.) injection of 100 μg/g azoxymethane (AOM). Analyses were carried out in cerebral cortex of precomatous mice 20-24 h after AOM administration. Brain fluid status was evaluated by measuring apparent diffusion coefficient [ADC] using NMR spectroscopy, Evans Blue extravasation, and accumulation of an intracisternally-injected fluorescent tracer. Extracellular pH ([pH] e ) and ([K + ] e ) were measured in situ with ion-sensitive microelectrodes. Cerebral cortical microdialysates were subjected to photometric analysis of extracellular potassium ([K + ] e ), sodium ([Na + ] e ) and luminometric assay of extracellular lactate ([Lac] e ). Potassium transport in cerebral cortical slices was measured ex vivo as 86 Rb uptake. Cerebral cortex of AOM-treated mice presented decreased ADC supporting the view that ATLF-induced brain oedema is primarily cytotoxic in nature. In addition, increased Evans blue extravasation indicated blood brain barrier leakage, and increased fluorescent tracer accumulation suggested impaired interstitial fluid passage. However, [K + ] e , [Na + ] e , [Lac] e , [pH] e and potassium transport in brain of AOM-treated mice was not different from control mice. We conclude that in spite of cytotoxic oedema and deregulated interstitial fluid passage, brain of mice with ATLF retains the ability to maintain interstitial ion homeostasis and acid-base balance. Tentatively, uncompromised brain ion homeostasis and acid-base balance may contribute to the relatively frequent brain function recovery and spontaneous survival rate in human patients with ATLF. Copyright © 2018. Published by Elsevier Ltd.

  8. Abnormal cerebrospinal fluid biochemistry in biotinidase deficiency causing diagnostic conundrum.

    PubMed

    Krishnakumar, Deepa; Maw, Anna; Brown, Richard; Hogg, Sarah; Calvin, Jackie; Parker, Alasdair P J

    2014-01-01

    Biotinidase deficiency is a treatable cause of infantile epilepsy and the presentation can be nonspecific. The seizures are difficult to differentiate from other causes of epileptic encephalopathy, which generally have a poor prognosis. We report 2 infants who presented with seizures, and whose low cerebrospinal fluid glucose and high cerebrospinal lactate caused a diagnostic dilemma. Subsequent urine organic acids pointed to the correct diagnosis and avoided invasive investigation. The children had a good clinical outcome with resolution of their seizures on biotin treatment.

  9. Neural control of breathing and CO2 homeostasis

    PubMed Central

    Guyenet, P.G.; Bayliss, D.A

    2015-01-01

    Summary Recent advances have clarified how the brain detects CO2 to regulate breathing (central respiratory chemoreception). These mechanisms are reviewed and their significance is presented in the general context of CO2/pH homeostasis through breathing. At rest, respiratory chemoreflexes initiated at peripheral and central sites mediate rapid stabilization of arterial PCO2 and pH. Specific brainstem neurons (e.g., retrotrapezoid nucleus, RTN; serotonergic) are activated by PCO2 and stimulate breathing. RTN neurons detect CO2 via intrinsic proton receptors (TASK-2, GPR4), synaptic input from peripheral chemoreceptors and signals from astrocytes. Respiratory chemoreflexes are arousal state-dependent whereas chemoreceptor stimulation produces arousal. When abnormal, these interactions lead to sleep-disordered breathing. During exercise, “central command” and reflexes from exercising muscles produce the breathing stimulation required to maintain arterial PCO2 and pH despite elevated metabolic activity. The neural circuits underlying central command and muscle afferent control of breathing remain elusive and represent a fertile area for future investigation. PMID:26335642

  10. Neuronal regulation of homeostasis by nutrient sensing.

    PubMed

    Lam, Tony K T

    2010-04-01

    In type 2 diabetes and obesity, the homeostatic control of glucose and energy balance is impaired, leading to hyperglycemia and hyperphagia. Recent studies indicate that nutrient-sensing mechanisms in the body activate negative-feedback systems to regulate energy and glucose homeostasis through a neuronal network. Direct metabolic signaling within the intestine activates gut-brain and gut-brain-liver axes to regulate energy and glucose homeostasis, respectively. In parallel, direct metabolism of nutrients within the hypothalamus regulates food intake and blood glucose levels. These findings highlight the importance of the central nervous system in mediating the ability of nutrient sensing to maintain homeostasis. Futhermore, they provide a physiological and neuronal framework by which enhancing or restoring nutrient sensing in the intestine and the brain could normalize energy and glucose homeostasis in diabetes and obesity.

  11. The Importance of Abnormal Chloride Homeostasis in Stable Chronic Heart Failure

    PubMed Central

    Grodin, Justin L.; Verbrugge, Frederik H.; Ellis, Stephen G.; Mullens, Wilfried; Testani, Jeffrey M.; Wilson Tang MD, W. H.

    2015-01-01

    Background The aim of this analysis was to determine the long-term prognostic value of lower serum chloride in patients with stable chronic heart failure. Electrolyte abnormalities are prevalent in patients with chronic heart failure. Little is known regarding the prognostic implications of lower serum chloride. Methods and Results Serum chloride was measured in 1,673 consecutively consented stable patients with a history of heart failure undergoing elective diagnostic coronary angiography. All patients were followed for 5-year all-cause mortality, and survival models were adjusted for variables that confounded the chloride-risk relationship. The average chloride level was 102±4 mEq/L. Over 6,772 person-years of follow-up, there were 547 deaths. Lower chloride (per standard deviation decrease) was associated with a higher adjusted risk of mortality (HR 1.29, 95%CI 1.12–1.49, P<0.001). Chloride levels net-reclassified risk in 10.4% (P=0.03) when added to a multivariable model (with a resultant C-statistic of 0.70), in which sodium levels were not prognostic (P=0.30). In comparison to those with above first quartile chloride (≥101 mEq/L) and sodium (≥138 meq/L), subjects with first quartile chloride had a higher adjusted mortality risk, whether they had first quartile sodium (HR 1.35, 95%CI 1.08–1.69, P=0.008) or higher (HR 1.43, 95%CI 1.12–1.85, P=0.005). However, subjects with first quartile sodium but above first quartile chloride had no association with mortality (P=0.67). Conclusions Lower serum chloride levels are independently and incrementally associated with increased mortality risk in patients with chronic heart failure. A better understanding of the biological role of serum chloride is warranted. PMID:26721916

  12. Pharmacological modulation of mitochondrial calcium homeostasis.

    PubMed

    Arduino, Daniela M; Perocchi, Fabiana

    2018-01-10

    Mitochondria are pivotal organelles in calcium (Ca 2+ ) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca 2+ homeostasis have been linked to a variety of pathological conditions and are critical in the aetiology of several human diseases. Efforts have been taken to harness mitochondrial Ca 2+ transport mechanisms for therapeutic intervention, but pharmacological compounds that direct and selectively modulate mitochondrial Ca 2+ homeostasis are currently lacking. New avenues have, however, emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca 2+ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca 2+ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progress towards a systems-level pharmacological targeting of mitochondrial Ca 2+ homeostasis. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

  13. Manganese and selenium concentrations in cerebrospinal fluid of seriously ill children.

    PubMed

    Franěk, Tomáš; Kotaška, Karel; Průša, Richard

    2017-11-01

    The homeostasis of essential trace elements such as selenium and manganese may be altered in patients with severe diseases of various etiologies (trauma brain injuries, tumors, leukemias, lymphomas, neurological diseases). Concentration of manganese and selenium were determined in cerebrospinal fluid by electrothermal atomic absorption spectrometry in 50 hospitalized children with various clinical ethiologies including oncological, neurological, and brain related diseases. The concentrations of manganese in cerebrospinal fluid of children were 0.97±0.67 μg/L. The concentrations of selenium were 13.3±3.5 μg/L. The concentrations were similar as published in adults. The values did not correlated with the age, gender and severity of the disease. We evaluated values of selenium and manganese in cerebrospinal fluid of seriously diseased children. © 2017 Wiley Periodicals, Inc.

  14. LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis

    PubMed Central

    Nakamura, Takahiro; Hamuro, Junji; Takaishi, Mikiro; Simmons, Szandor; Maruyama, Kazuichi; Zaffalon, Andrea; Bentley, Adam J.; Kawasaki, Satoshi; Nagata-Takaoka, Maho; Fullwood, Nigel J.; Itami, Satoshi; Sano, Shigetoshi; Ishii, Masaru; Barrandon, Yann; Kinoshita, Shigeru

    2013-01-01

    Corneal integrity and transparency are indispensable for good vision. Cornea homeostasis is entirely dependent upon corneal stem cells, which are required for complex wound-healing processes that restore corneal integrity following epithelial damage. Here, we found that leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is highly expressed in the human holoclone-type corneal epithelial stem cell population and sporadically expressed in the basal cells of ocular-surface epithelium. In murine models, LRIG1 regulated corneal epithelial cell fate during wound repair. Deletion of Lrig1 resulted in impaired stem cell recruitment following injury and promoted a cell-fate switch from transparent epithelium to keratinized skin-like epidermis, which led to corneal blindness. In addition, we determined that LRIG1 is a negative regulator of the STAT3-dependent inflammatory pathway. Inhibition of STAT3 in corneas of Lrig1–/– mice rescued pathological phenotypes and prevented corneal opacity. Additionally, transgenic mice that expressed a constitutively active form of STAT3 in the corneal epithelium had abnormal features, including corneal plaques and neovascularization similar to that found in Lrig1–/– mice. Bone marrow chimera experiments indicated that LRIG1 also coordinates the function of bone marrow–derived inflammatory cells. Together, our data indicate that LRIG1 orchestrates corneal-tissue transparency and cell fate during repair, and identify LRIG1 as a key regulator of tissue homeostasis. PMID:24316976

  15. Patterns of pulmonary maturation in normal and abnormal pregnancy.

    PubMed

    Goldkrand, J W; Slattery, D S

    1979-03-01

    Fetal pulmonary maturation may be a variable event depending on various feto-maternal environmental and biochemical influences. The patterns of maturation were studied in 211 amniotic fluid samples from 123 patients (normal 55; diabetes 23; Rh sensitization 19; preeclampsia 26). The phenomenon of globule formation from the amniotic fluid lipid extract and is relation to pulmonary maturity was utilized for this analysis. Validation of this technique is presented. A normal curve was constructed from 22 to 42 weeks; gestation and compared to the abnormal pregnancies. Patients with class A, B, and C diabetes and Rh-sensitized pregnancies had delayed pulmonary maturation. Patients with class D diabetes and preclampsia paralleled the normal course of maturation. A discussion of these results and their possible cause is presented.

  16. Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome.

    PubMed

    Vootla, Vamshidhar R; Daniel, Myrta

    2015-01-01

    Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome.

  17. Diseases of Pulmonary Surfactant Homeostasis

    PubMed Central

    Whitsett, Jeffrey A.; Wert, Susan E.; Weaver, Timothy E.

    2015-01-01

    Advances in physiology and biochemistry have provided fundamental insights into the role of pulmonary surfactant in the pathogenesis and treatment of preterm infants with respiratory distress syndrome. Identification of the surfactant proteins, lipid transporters, and transcriptional networks regulating their expression has provided the tools and insights needed to discern the molecular and cellular processes regulating the production and function of pulmonary surfactant prior to and after birth. Mutations in genes regulating surfactant homeostasis have been associated with severe lung disease in neonates and older infants. Biophysical and transgenic mouse models have provided insight into the mechanisms underlying surfactant protein and alveolar homeostasis. These studies have provided the framework for understanding the structure and function of pulmonary surfactant, which has informed understanding of the pathogenesis of diverse pulmonary disorders previously considered idiopathic. This review considers the pulmonary surfactant system and the genetic causes of acute and chronic lung disease caused by disruption of alveolar homeostasis. PMID:25621661

  18. Maintenance of Mitochondrial Oxygen Homeostasis by Cosubstrate Compensation

    PubMed Central

    Kueh, Hao Yuan; Niethammer, Philipp; Mitchison, Timothy J.

    2013-01-01

    Mitochondria maintain a constant rate of aerobic respiration over a wide range of oxygen levels. However, the control strategies underlying oxygen homeostasis are still unclear. Using mathematical modeling, we found that the mitochondrial electron transport chain (ETC) responds to oxygen level changes by undergoing compensatory changes in reduced electron carrier levels. This emergent behavior, which we named cosubstrate compensation (CSC), enables the ETC to maintain homeostasis over a wide of oxygen levels. When performing CSC, our ETC models recapitulated a classic scaling relationship discovered by Chance [Chance B (1965) J. Gen. Physiol. 49:163-165] relating the extent of oxygen homeostasis to the kinetics of mitochondrial electron transport. Analysis of an in silico mitochondrial respiratory system further showed evidence that CSC constitutes the dominant control strategy for mitochondrial oxygen homeostasis during active respiration. Our findings indicate that CSC constitutes a robust control strategy for homeostasis and adaptation in cellular biochemical networks. PMID:23528093

  19. Redox homeostasis: The Golden Mean of healthy living

    PubMed Central

    Ursini, Fulvio; Maiorino, Matilde; Forman, Henry Jay

    2016-01-01

    The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve “reactive oxygen species” rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles (parahormesis). In summary

  20. 2013 AAHA/AAFP fluid therapy guidelines for dogs and cats.

    PubMed

    Davis, Harold; Jensen, Tracey; Johnson, Anthony; Knowles, Pamela; Meyer, Robert; Rucinsky, Renee; Shafford, Heidi

    2013-01-01

    Fluid therapy is important for many medical conditions in veterinary patients. The assessment of patient history, chief complaint, physical exam findings, and indicated additional testing will determine the need for fluid therapy. Fluid selection is dictated by the patient's needs, including volume, rate, fluid composition required, and location the fluid is needed (e.g., interstitial versus intravascular). Therapy must be individualized, tailored to each patient, and constantly re-evaluated and reformulated according to changes in status. Needs may vary according to the existence of either acute or chronic conditions, patient pathology (e.g., acid-base, oncotic, electrolyte abnormalities), and comorbid conditions. All patients should be assessed for three types of fluid disturbances: changes in volume, changes in content, and/or changes in distribution. The goals of these guidelines are to assist the clinician in prioritizing goals, selecting appropriate fluids and rates of administration, and assessing patient response to therapy. These guidelines provide recommendations for fluid administration for anesthetized patients and patients with fluid disturbances.

  1. Abnormal Barrier Function in Gastrointestinal Disorders.

    PubMed

    Farré, Ricard; Vicario, María

    2017-01-01

    There is increasing concern in identifying the mechanisms underlying the intimate control of the intestinal barrier, as deregulation of its function is strongly associated with digestive (organic and functional) and a number of non-digestive (schizophrenia, diabetes, sepsis, among others) disorders. The intestinal barrier is a complex and effective defensive functional system that operates to limit luminal antigen access to the internal milieu while maintaining nutrient and electrolyte absorption. Intestinal permeability to substances is mainly determined by the physicochemical properties of the barrier, with the epithelium, mucosal immunity, and neural activity playing a major role. In functional gastrointestinal disorders (FGIDs), the absence of structural or biochemical abnormalities that explain chronic symptoms is probably close to its end, as recent research is providing evidence of structural gut alterations, at least in certain subsets, mainly in functional dyspepsia (FD) and irritable bowel syndrome (IBS). These alterations are associated with increased permeability, which seems to reflect mucosal inflammation and neural activation. The participation of each anatomical and functional component of barrier function in homeostasis and intestinal dysfunction is described, with a special focus on FGIDs.

  2. A new look at cerebrospinal fluid circulation

    PubMed Central

    2014-01-01

    According to the traditional understanding of cerebrospinal fluid (CSF) physiology, the majority of CSF is produced by the choroid plexus, circulates through the ventricles, the cisterns, and the subarachnoid space to be absorbed into the blood by the arachnoid villi. This review surveys key developments leading to the traditional concept. Challenging this concept are novel insights utilizing molecular and cellular biology as well as neuroimaging, which indicate that CSF physiology may be much more complex than previously believed. The CSF circulation comprises not only a directed flow of CSF, but in addition a pulsatile to and fro movement throughout the entire brain with local fluid exchange between blood, interstitial fluid, and CSF. Astrocytes, aquaporins, and other membrane transporters are key elements in brain water and CSF homeostasis. A continuous bidirectional fluid exchange at the blood brain barrier produces flow rates, which exceed the choroidal CSF production rate by far. The CSF circulation around blood vessels penetrating from the subarachnoid space into the Virchow Robin spaces provides both a drainage pathway for the clearance of waste molecules from the brain and a site for the interaction of the systemic immune system with that of the brain. Important physiological functions, for example the regeneration of the brain during sleep, may depend on CSF circulation. PMID:24817998

  3. Cellular Homeostasis and Aging.

    PubMed

    Hartl, F Ulrich

    2016-06-02

    Aging and longevity are controlled by a multiplicity of molecular and cellular signaling events that interface with environmental factors to maintain cellular homeostasis. Modulation of these pathways to extend life span, including insulin-like signaling and the response to dietary restriction, identified the cellular machineries and networks of protein homeostasis (proteostasis) and stress resistance pathways as critical players in the aging process. A decline of proteostasis capacity during aging leads to dysfunction of specific cell types and tissues, rendering the organism susceptible to a range of chronic diseases. This volume of the Annual Review of Biochemistry contains a set of two reviews addressing our current understanding of the molecular mechanisms underlying aging in model organisms and humans.

  4. The ICET-A Recommendations for the Diagnosis and Management of Disturbances of Glucose Homeostasis in Thalassemia Major Patients

    PubMed Central

    De Sanctis, Vincenzo; Soliman, Ashraf T.; Elsedfy, Heba; Yaarubi, Saif AL; Skordis, Nicos; Khater, Doaa; El Kholy, Mohamed; Stoeva, Iva; Fiscina, Bernadette; Angastiniotis, Michael; Daar, Shahina; Kattamis, Christos

    2016-01-01

    Iron overload in patients with thalassemia major (TM) affects glucose regulation and is mediated by several mechanisms. The pathogenesis of glycaemic abnormalities in TM is complex and multifactorial. It has been predominantly attributed to a combination of reduced insulin secretory capacity and insulin resistance. The exact mechanisms responsible for progression from norm glycaemia to overt diabetes in these patients are still poorly understood but are attributed mainly to insulin deficiency resulting from the toxic effects of iron deposited in the pancreas and insulin resistance. A group of endocrinologists, haematologists and paediatricians, members of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A) convened to formulate recommendations for the diagnosis and management of abnormalities of glucose homeostasis in thalassemia major patients on the basis of available evidence from clinical and laboratory data and consensus practice. The results of their work and discussions are described in this article. PMID:27872738

  5. Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome

    PubMed Central

    Vootla, Vamshidhar R.; Daniel, Myrta

    2015-01-01

    Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome. PMID:26351414

  6. Redox homeostasis: The Golden Mean of healthy living.

    PubMed

    Ursini, Fulvio; Maiorino, Matilde; Forman, Henry Jay

    2016-08-01

    The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve "reactive oxygen species" rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles (parahormesis). In summary

  7. The Effects of High Level Magnesium Dialysis/Substitution Fluid on Magnesium Homeostasis under Regional Citrate Anticoagulation in Critically Ill

    PubMed Central

    Los, Ferdinand; Brodska, Helena

    2016-01-01

    Background The requirements for magnesium (Mg) supplementation increase under regional citrate anticoagulation (RCA) because citrate acts by chelation of bivalent cations within the blood circuit. The level of magnesium in commercially available fluids for continuous renal replacement therapy (CRRT) may not be sufficient to prevent hypomagnesemia. Methods Patients (n = 45) on CRRT (2,000 ml/h, blood flow (Qb) 100 ml/min) with RCA modality (4% trisodium citrate) using calcium free fluid with 0.75 mmol/l of Mg with additional magnesium substitution were observed after switch to the calcium-free fluid with magnesium concentration of 1.50 mmol/l (n = 42) and no extra magnesium replenishment. All patients had renal indications for CRRT, were treated with the same devices, filters and the same postfilter ionized calcium endpoint (<0.4 mmol/l) of prefilter citrate dosage. Under the high level Mg fluid the Qb, dosages of citrate and CRRT were consequently escalated in 9h steps to test various settings. Results Median balance of Mg was -0.91 (-1.18 to -0.53) mmol/h with Mg 0.75 mmol/l and 0.2 (0.06–0.35) mmol/h when fluid with Mg 1.50 mmol/l was used. It was close to zero (0.02 (-0.12–0.18) mmol/h) with higher blood flow and dosage of citrate, increased again to 0.15 (-0.11–0.25) mmol/h with 3,000 ml/h of high magnesium containing fluid (p<0.001). The arterial levels of Mg were mildly increased after the change for high level magnesium containing fluid (p<0.01). Conclusions Compared to ordinary dialysis fluid the mildly hypermagnesemic fluid provided even balances and adequate levels within ordinary configurations of CRRT with RCA and without a need for extra magnesium replenishment. Trial Registration ClinicalTrials.gov Identifier: NCT01361581 PMID:27391902

  8. Pathophysiology, treatment, and prevention of fluid and electrolyte abnormalities during refeeding syndrome.

    PubMed

    Parli, Sara E; Ruf, Kathryn M; Magnuson, Barbara

    2014-01-01

    Refeeding syndrome may occur after the reintroduction of carbohydrates in chronically malnourished or acutely hypermetabolic patients as a result of a rapid shift to glucose utilization as an energy source. Electrolyte abnormalities of phosphorus, potassium, and magnesium occur, leading to complications of various organ systems, and may result in death. Patients should be screened for risk factors of malnutrition to prevent refeeding syndrome. For those at risk, nutrition should be initiated and slowly advanced toward the patient's goal over several days. Electrolyte disturbances should be aggressively corrected.

  9. Fluid therapy in vomiting and diarrhea.

    PubMed

    Brown, Andrew J; Otto, Cynthia M

    2008-05-01

    Fluid therapy in the patient with vomiting and diarrhea is essential to correct hypovolemia, dehydration, acid-base imbalance, and serum electrolyte abnormalities. Prediction of acid-base or electrolyte disturbances is difficult; therefore, point of care testing is beneficial to optimize therapy. This article focuses on the pathophysiology and treatment of hypovolemia, dehydration, electrolyte disturbances, and acid-base derangements resulting from and associated with vomiting and diarrhea.

  10. The Role of Aquaporins in Ocular Lens Homeostasis

    PubMed Central

    Schey, Kevin L.; Petrova, Rosica S.; Gletten, Romell B.; Donaldson, Paul J.

    2017-01-01

    Aquaporins (AQPs), by playing essential roles in the maintenance of ocular lens homeostasis, contribute to the establishment and maintenance of the overall optical properties of the lens over many decades of life. Three aquaporins, AQP0, AQP1 and AQP5, each with distinctly different functional properties, are abundantly and differentially expressed in the different regions of the ocular lens. Furthermore, the diversity of AQP functionality is increased in the absence of protein turnover by age-related modifications to lens AQPs that are proposed to alter AQP function in the different regions of the lens. These regional differences in AQP functionality are proposed to contribute to the generation and directionality of the lens internal microcirculation; a system of circulating ionic and fluid fluxes that delivers nutrients to and removes wastes from the lens faster than could be achieved by passive diffusion alone. In this review, we present how regional differences in lens AQP isoforms potentially contribute to this microcirculation system by highlighting current areas of investigation and emphasizing areas where future work is required. PMID:29231874

  11. [Acid-base homeostasis and the thyro-parathyroid glands].

    PubMed

    Cuisinier-Gleizes, P; George, A; Thomasset, M; Mathieu, H

    1975-05-12

    Chronic metabolic acidosis entails hyperparathyroidism and osteopathy. In order to elucidate the role of the thyroparathyroids in this bone lesion production the effects of acidic diet for 7 weeks were studied in parathyroidectomized (PTX), thyroparathyroidectomized (TPTX) and shamoperated (Sh-O) growing rats. In all animals urinary excretion of calcium, phosphate, ammonium and titrable acidity was similarly increased. The rise in hydroxyproline excretion and urinary 85-sr (that was injected previous to acidic feeding) was more marked in PTX and TPTX rats. Moreover, in these animals the serum calcium level was increased, the blood pH was decreased. According to these data, an acidic diet intake that is not sufficient to elicit a fall in blood pH of normal young rats can induce severe acidosis in chronically parathyroidectomized or thyroparathyroidectomized animals; moreover the bone resorption appears more marked. It is concluded that parathyroids are involved in the extra-cellular fluid defense mechanism against acidosis by a no bone resorptive mechanism. We hypothesize that the parathyroids permit the necessary and adequate supply of bicarbonates by the bone to maintain blood pH homeostasis.

  12. Alcohol disrupts sleep homeostasis.

    PubMed

    Thakkar, Mahesh M; Sharma, Rishi; Sahota, Pradeep

    2015-06-01

    Alcohol is a potent somnogen and one of the most commonly used "over the counter" sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to unravel the mechanism of alcohol-induced sleep disruptions. We have conducted a series of experiments using two different species, rats and mice, as animal models. We performed microdialysis, immunohistochemical, pharmacological, sleep deprivation and lesion studies which suggest that the sleep-promoting effects of alcohol may be mediated via alcohol's action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that sleep disruptions observed during acute withdrawal, are caused due to impaired

  13. The GLP-1 response to glucose does not mediate beta and alpha cell dysfunction in Hispanics with abnormal glucose metabolism.

    PubMed

    Adams, Elizabeth; Genter, Pauline; Keefe, Emma; Sandow, Kevin; Gray, Virginia; Rotter, Jerome I; Chen, Yii-Der Ida; Ipp, Eli

    2018-01-01

    Glucagon-like peptide-1 (GLP-1) contributes to insulin secretion after meals. Though Hispanics have increased risk for type 2 diabetes mellitus, it is unknown if impaired GLP-1 secretion contributes to this risk. We therefore studied plasma GLP-1 secretion and action in Hispanic adults. Hispanic (H; n = 31) and non-Hispanic (nH; n = 15) participants underwent an oral glucose tolerance test (OGTT). All participants were categorized by glucose tolerance into four groups: normal glucose tolerant non-Hispanic (NGT-nH; n = 15), normal glucose tolerant Hispanic (NGT-H; n = 12), impaired glucose tolerant Hispanic (IGT-H; n = 11), or newly diagnosed type 2 diabetes mellitus, Hispanic (T2D-H; n = 8). Glucose-induced increments in plasma GLP-1 (Δ-GLP-1) were not different in NGT-H and NGT-nH (p = .38), nor amongst Hispanic subgroups with varying degrees of glucose homeostasis (p = .6). In contrast, the insulinogenic index in T2D-H group was lower than the other groups (p = .016). Subjects with abnormal glucose homeostasis (AGH), i.e., T2D-H plus IGT-H, had a diminished glucagon suppression index compared to patients with normal glucose homeostasis (NGT-H plus NGT-nH) (p = .035). GLP-1 responses to glucose were similar in Hispanic and Non-Hispanic NGT. Despite similar glucose-induced Δ-GLP-1, insulin and glucagon responses were abnormal in T2D-H and AGH, respectively. Thus, impaired GLP-1 secretion is unlikely to play a role in islet dysfunction in T2D. Although GLP-1 therapeutics enhance insulin secretion and glucagon suppression, it is likely due to pharmacological amplification of the GLP-1 pathways rather than treatment of hormonal deficiency. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Mechanosensitive subcellular rheostasis drives emergent single-cell mechanical homeostasis

    NASA Astrophysics Data System (ADS)

    Weng, Shinuo; Shao, Yue; Chen, Weiqiang; Fu, Jianping

    2016-09-01

    Mechanical homeostasis--a fundamental process by which cells maintain stable states under environmental perturbations--is regulated by two subcellular mechanotransducers: cytoskeleton tension and integrin-mediated focal adhesions (FAs). Here, we show that single-cell mechanical homeostasis is collectively driven by the distinct, graduated dynamics (rheostasis) of subcellular cytoskeleton tension and FAs. Such rheostasis involves a mechanosensitive pattern wherein ground states of cytoskeleton tension and FA determine their distinct reactive paths through either relaxation or reinforcement. Pharmacological perturbations of the cytoskeleton and molecularly modulated integrin catch-slip bonds biased the rheostasis and induced non-homeostasis of FAs, but not of cytoskeleton tension, suggesting a unique sensitivity of FAs in regulating homeostasis. Theoretical modelling revealed myosin-mediated cytoskeleton contractility and catch-slip-bond-like behaviours in FAs and the cytoskeleton as sufficient and necessary mechanisms for quantitatively recapitulating mechanosensitive rheostasis. Our findings highlight the previously underappreciated physical nature of the mechanical homeostasis of cells.

  15. Homeostasis in a feed forward loop gene regulatory motif.

    PubMed

    Antoneli, Fernando; Golubitsky, Martin; Stewart, Ian

    2018-05-14

    The internal state of a cell is affected by inputs from the extra-cellular environment such as external temperature. If some output, such as the concentration of a target protein, remains approximately constant as inputs vary, the system exhibits homeostasis. Special sub-networks called motifs are unusually common in gene regulatory networks (GRNs), suggesting that they may have a significant biological function. Potentially, one such function is homeostasis. In support of this hypothesis, we show that the feed-forward loop GRN produces homeostasis. Here the inputs are subsumed into a single parameter that affects only the first node in the motif, and the output is the concentration of a target protein. The analysis uses the notion of infinitesimal homeostasis, which occurs when the input-output map has a critical point (zero derivative). In model equations such points can be located using implicit differentiation. If the second derivative of the input-output map also vanishes, the critical point is a chair: the output rises roughly linearly, then flattens out (the homeostasis region or plateau), and then starts to rise again. Chair points are a common cause of homeostasis. In more complicated equations or networks, numerical exploration would have to augment analysis. Thus, in terms of finding chairs, this paper presents a proof of concept. We apply this method to a standard family of differential equations modeling the feed-forward loop GRN, and deduce that chair points occur. This function determines the production of a particular mRNA and the resulting chair points are found analytically. The same method can potentially be used to find homeostasis regions in other GRNs. In the discussion and conclusion section, we also discuss why homeostasis in the motif may persist even when the rest of the network is taken into account. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Clinical Findings Documenting Cellular and Molecular Abnormalities of Glia in Depressive Disorders

    PubMed Central

    Czéh, Boldizsár; Nagy, Szilvia A.

    2018-01-01

    Depressive disorders are complex, multifactorial mental disorders with unknown neurobiology. Numerous theories aim to explain the pathophysiology. According to the “gliocentric theory”, glial abnormalities are responsible for the development of the disease. The aim of this review article is to summarize the rapidly growing number of cellular and molecular evidences indicating disturbed glial functioning in depressive disorders. We focus here exclusively on the clinical studies and present the in vivo neuroimaging findings together with the postmortem molecular and histopathological data. Postmortem studies demonstrate glial cell loss while the in vivo imaging data reveal disturbed glial functioning and altered white matter microstructure. Molecular studies report on altered gene expression of glial specific genes. In sum, the clinical findings provide ample evidences on glial pathology and demonstrate that all major glial cell types are affected. However, we still lack convincing theories explaining how the glial abnormalities develop and how exactly contribute to the emotional and cognitive disturbances. Abnormal astrocytic functioning may lead to disturbed metabolism affecting ion homeostasis and glutamate clearance, which in turn, affect synaptic communication. Abnormal oligodendrocyte functioning may disrupt the connectivity of neuronal networks, while microglial activation indicates neuroinflammatory processes. These cellular changes may relate to each other or they may indicate different endophenotypes. A theory has been put forward that the stress-induced inflammation—mediated by microglial activation—triggers a cascade of events leading to damaged astrocytes and oligodendroglia and consequently to their dysfunctions. The clinical data support the “gliocentric” theory, but future research should clarify whether these glial changes are truly the cause or simply the consequences of this devastating disorder. PMID:29535607

  17. Leptin and Hormones: Energy Homeostasis.

    PubMed

    Triantafyllou, Georgios A; Paschou, Stavroula A; Mantzoros, Christos S

    2016-09-01

    Leptin, a 167 amino acid adipokine, plays a major role in human energy homeostasis. Its actions are mediated through binding to leptin receptor and activating JAK-STAT3 signal transduction pathway. It is expressed mainly in adipocytes, and its circulating levels reflect the body's energy stores in adipose tissue. Recombinant methionyl human leptin has been FDA approved for patients with generalized non-HIV lipodystrophy and for compassionate use in subjects with congenital leptin deficiency. The purpose of this review is to outline the role of leptin in energy homeostasis, as well as its interaction with other hormones. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Peroxisomal abnormalities in the immortalized human hepatocyte (IHH) cell line.

    PubMed

    Klouwer, Femke C C; Koster, Janet; Ferdinandusse, Sacha; Waterham, Hans R

    2017-04-01

    The immortalized human hepatocyte (IHH) cell line is increasingly used for studies related to liver metabolism, including hepatic glucose, lipid, lipoprotein and triglyceride metabolism, and the effect of therapeutic interventions. To determine whether the IHH cell line is a good model to investigate hepatic peroxisomal metabolism, we measured several peroxisomal parameters in IHH cells and, for comparison, HepG2 cells and primary skin fibroblasts. This revealed a marked plasmalogen deficiency and a deficient fatty acid α-oxidation in the IHH cells, due to a defect of PEX7, a cytosolic receptor protein required for peroxisomal import of a subset of peroxisomal proteins. These abnormalities have consequences for the lipid homeostasis of these cells and thus should be taken into account for the interpretation of data previously generated by using this cell line and when considering using this cell line for future research.

  19. Copper homeostasis gene discovery in Drosophila melanogaster.

    PubMed

    Norgate, Melanie; Southon, Adam; Zou, Sige; Zhan, Ming; Sun, Yu; Batterham, Phil; Camakaris, James

    2007-06-01

    Recent studies have shown a high level of conservation between Drosophila melanogaster and mammalian copper homeostasis mechanisms. These studies have also demonstrated the efficiency with which this species can be used to characterize novel genes, at both the cellular and whole organism level. As a versatile and inexpensive model organism, Drosophila is also particularly useful for gene discovery applications and thus has the potential to be extremely useful in identifying novel copper homeostasis genes and putative disease genes. In order to assess the suitability of Drosophila for this purpose, three screening approaches have been investigated. These include an analysis of the global transcriptional response to copper in both adult flies and an embryonic cell line using DNA microarray analysis. Two mutagenesis-based screens were also utilized. Several candidate copper homeostasis genes have been identified through this work. In addition, the results of each screen were carefully analyzed to identify any factors influencing efficiency and sensitivity. These are discussed here with the aim of maximizing the efficiency of future screens and the most suitable approaches are outlined. Building on this information, there is great potential for the further use of Drosophila for copper homeostasis gene discovery.

  20. Three-component homeostasis control

    NASA Astrophysics Data System (ADS)

    Xu, Jin; Hong, Hyunsuk; Jo, Junghyo

    2014-03-01

    Two reciprocal components seem to be sufficient to maintain a control variable constant. However, pancreatic islets adapt three components to control glucose homeostasis. They are α (secreting glucagon), β (insulin), and δ (somatostatin) cells. Glucagon and insulin are the reciprocal hormones for increasing and decreasing blood glucose levels, while the role of somatostatin is unknown. However, it has been known how each hormone affects other cell types. Based on the pulsatile hormone secretion and the cellular interactions, this system can be described as coupled oscillators. In particular, we used the Landau-Stuart model to consider both amplitudes and phases of hormone oscillations. We found that the presence of the third component, δ cell, was effective to resist under glucose perturbations, and to quickly return to the normal glucose level once perturbed. Our analysis suggested that three components are necessary for advanced homeostasis control.

  1. The change in serum Thiol/Disulphide homeostasis after transrectal ultrasound guided prostate biopsy

    PubMed Central

    Tokgöz, Hüsnü; Taş, Selim; Giray, Özlem; Yalçınkaya, Soner; Tokgöz, Özlem; Koca, Cemile; Savaş, Murat; Erel, Özcan

    2017-01-01

    ABSTRACT Objectives The aim of this prospective clinical study was to investigate variations in a novel oxidative stress marker (thiol/disulphide homeostasis) in men who underwent transrectal ultrasound guided prostate biopsy (TRUSB). Materials and Methods A total of 22 men undergoing TRUSB of the prostate were enrolled in the study. Patients with abnormal digital rectal examination and/or total prostate specific antigen (PSA) over 4ng/mL underwent TRUSB with 12 cores. Serum samples were obtained before and just after the procedure to evaluate the possible changes in thiol/disulphide homeostasis. Mean age, total PSA and free PSA, prostate volume and histopathological data were also recorded. Results Mean age of the study population was 65.05±8.89 years. Significant decreases in native and total thiol levels were documented after the biopsy procedure. However, serum disulphide levels and disulphide/native thiol, disulphide/total thiol and native/total thiol ratios did not significantly change after TRUSB. No correlation was observed between oxidative parameters and total PSA and free PSA levels, prostate volume and histopathology of the prostate. However, mean patient age was significantly correlated with mean native and total thiol levels. Conclusion Significant decreases in serum native and total thiol levels related to the prostate biopsy procedure suggest that TRUSB causes acute oxidative stress in the human body. Since our trial is the first in the current literature to investigate these oxidative stress markers in urology practice, additional studies are warranted. PMID:28128906

  2. The change in serum Thiol/Disulphide homeostasis after transrectal ultrasound guided prostate biopsy.

    PubMed

    Tokgöz, Hüsnü; Taş, Selim; Giray, Özlem; Yalçınkaya, Soner; Tokgöz, Özlem; Koca, Cemile; Savaş, Murat; Erel, Özcan

    2017-01-01

    The aim of this prospective clinical study was to investigate variations in a novel oxidative stress marker (thiol/disulphide homeostasis) in men who underwent transrectal ultrasound guided prostate biopsy (TRUSB). A total of 22 men undergoing TRUSB of the prostate were enrolled in the study. Patients with abnormal digital rectal examination and/or total prostate specific antigen (PSA) over 4ng/mL underwent TRUSB with 12 cores. Serum samples were obtained before and just after the procedure to evaluate the possible changes in thiol/disulphide homeostasis. Mean age, total PSA and free PSA, prostate volume and histopathological data were also recorded. Mean age of the study population was 65.05±8.89 years. Significant decreases in native and total thiol levels were documented after the biopsy procedure. However, serum disulphide levels and disulphide/native thiol, disulphide/total thiol and native / total thiol ratios did not significantly change after TRUSB. No correlation was observed between oxidative parameters and total PSA and free PSA levels, prostate volume and histopathology of the prostate. However, mean patient age was significantly correlated with mean native and total thiol levels. Significant decreases in serum native and total thiol levels related to the prostate biopsy procedure suggest that TRUSB causes acute oxidative stress in the human body. Since our trial is the first in the current literature to investigate these oxidative stress markers in urology practice, additional studies are warranted. Copyright® by the International Brazilian Journal of Urology.

  3. Abnormal passive chloride absorption in cystic fibrosis jejunum functionally opposes the classic chloride secretory defect

    PubMed Central

    Russo, Michael A.; Högenauer, Christoph; Coates, Stephen W.; Santa Ana, Carol A.; Porter, Jack L.; Rosenblatt, Randall L.; Emmett, Michael; Fordtran, John S.

    2003-01-01

    Due to genetic defects in apical membrane chloride channels, the cystic fibrosis (CF) intestine does not secrete chloride normally. Depressed chloride secretion leaves CF intestinal absorptive processes unopposed, which results in net fluid hyperabsorption, dehydration of intestinal contents, and a propensity to inspissated intestinal obstruction. This theory is based primarily on in vitro studies of jejunal mucosa. To determine if CF patients actually hyperabsorb fluid in vivo, we measured electrolyte and water absorption during steady-state perfusion of the jejunum. As expected, chloride secretion was abnormally low in CF, but surprisingly, there was no net hyperabsorption of sodium or water during perfusion of a balanced electrolyte solution. This suggested that fluid absorption processes are reduced in CF jejunum, and further studies revealed that this was due to a marked depression of passive chloride absorption. Although Na+-glucose cotransport was normal in the CF jejunum, absence of passive chloride absorption completely blocked glucose-stimulated net sodium absorption and reduced glucose-stimulated water absorption 66%. This chloride absorptive abnormality acts in physiological opposition to the classic chloride secretory defect in the CF intestine. By increasing the fluidity of intraluminal contents, absence of passive chloride absorption may reduce the incidence and severity of intestinal disease in patients with CF. PMID:12840066

  4. Development and Validation of the Homeostasis Concept Inventory

    ERIC Educational Resources Information Center

    McFarland, Jenny L.; Price, Rebecca M.; Wenderoth, Mary Pat; Martinková, Patrícia; Cliff, William; Michael, Joel; Modell, Harold; Wright, Ann

    2017-01-01

    We present the Homeostasis Concept Inventory (HCI), a 20-item multiple-choice instrument that assesses how well undergraduates understand this critical physiological concept. We used an iterative process to develop a set of questions based on elements in the Homeostasis Concept Framework. This process involved faculty experts and undergraduate…

  5. Total alpha-fetoprotein and Lens culinaris agglutinin-reactive alpha-fetoprotein in fetal chromosomal abnormalities.

    PubMed

    Yamamoto, R; Azuma, M; Kishida, T; Yamada, H; Satomura, S; Fujimoto, S

    2001-11-01

    To examine the differences in multiples of the median (MoM) of total alpha-fetoprotein, and the proportion of Lens culinaris agglutinin reactive alpha-fetoprotein (% alpha-fetoprotein-L2 + L3) in the maternal serum and amniotic fluid of pregnant women whose fetuses were diagnosed with autosomal or sex chromosomal abnormalities. Prospective consecutive series. University hospital. Maternal sera and amniotic fluids from 46 pregnant women with trisomy 21 fetuses, 10 pregnant women with trisomy 18 fetuses, one pregnant woman with a trisomy 13 fetus, six pregnant women with fetal sex chromosomal abnormalities, and 100 pregnant women for whom the fetal karyotype was diagnosed as normal following a genetic amniocentesis. The proportion of alpha-fetoprotein-L2 + L3 in maternal serum for trisomy 21 (40.3%. P < 0.0001) and trisomy 18 (39.8%, P < 0.05) showed a significantly higher value compared with normal (32.6%). The proportion of alpha-fetoprotein-L2 + L3 in amniotic fluid was significantly higher (P < 0.0001) for trisomy 21 (46.6%) than for a normal karyotype (41.5%). Only for the trisomy 21 group was there a strong correlation in the % alpha-fetoprotein-L2 + L3 between maternal serum and amniotic fluid (r = 0.840, P < 0.0001). For all groups, there was no correlation between alpha-fetoprotein MoM and % alpha-fetoprotein-L2 + L3 in maternal serum and amniotic fluid. The proportion of alpha-fetoprotein-L2 + L3 in maternal serum is an appropriate choice for a trisomy 21 biochemical marker, and it is possible that combining alpha-fetoprotein-L2 + L3 analysis with assays of alpha-fetoprotein in maternal serum could further improve the sensitivity and specificity of multiple marker screening.

  6. Effects of irregular cerebrospinal fluid production rate in human brain ventricular system

    NASA Astrophysics Data System (ADS)

    Hadzri, Edi Azali; Shamsudin, Amir Hamzah; Osman, Kahar; Abdul Kadir, Mohammed Rafiq; Aziz, Azian Abd

    2012-06-01

    Hydrocephalus is an abnormal accumulation of fluid in the ventricles and cavities in the brain. It occurs when the cerebrospinal fluid (CSF) flow or absorption is blocked or when excessive CSF is secreted. The excessive accumulation of CSF results in an abnormal widening of the ventricles. This widening creates potentially harmful pressure on the tissues of the brain. In this study, flow analysis of CSF was conducted on a three-dimensional model of the third ventricle and aqueduct of Sylvius, derived from MRI scans. CSF was modeled as Newtonian Fluid and its flow through the region of interest (ROI) was done using EFD. Lab software. Different steady flow rates through the Foramen of Monro, classified by normal and hydrocephalus cases, were modeled to investigate its effects. The results show that, for normal and hydrocephalus cases, the pressure drop of CSF flow across the third ventricle was observed to be linearly proportionally to the production rate increment. In conclusion, flow rates that cause pressure drop of 5 Pa was found to be the threshold for the initial sign of hydrocephalus.

  7. Abnormality in glutamine-glutamate cycle in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder: a 3-year follow-up study.

    PubMed

    Hashimoto, K; Bruno, D; Nierenberg, J; Marmar, C R; Zetterberg, H; Blennow, K; Pomara, N

    2016-03-01

    Major depressive disorder (MDD), common in the elderly, is a risk factor for dementia. Abnormalities in glutamatergic neurotransmission via the N-methyl-D-aspartate receptor (NMDA-R) have a key role in the pathophysiology of depression. This study examined whether depression was associated with cerebrospinal fluid (CSF) levels of NMDA-R neurotransmission-associated amino acids in cognitively intact elderly individuals with MDD and age- and gender-matched healthy controls. CSF was obtained from 47 volunteers (MDD group, N=28; age- and gender-matched comparison group, N=19) at baseline and 3-year follow-up (MDD group, N=19; comparison group, N=17). CSF levels of glutamine, glutamate, glycine, L-serine and D-serine were measured by high-performance liquid chromatography. CSF levels of amino acids did not differ across MDD and comparison groups. However, the ratio of glutamine to glutamate was significantly higher at baseline in subjects with MDD than in controls. The ratio decreased in individuals with MDD over the 3-year follow-up, and this decrease correlated with a decrease in the severity of depression. No correlations between absolute amino-acid levels and clinical variables were observed, nor were correlations between amino acids and other biomarkers (for example, amyloid-β42, amyloid-β40, and total and phosphorylated tau protein) detected. These results suggest that abnormalities in the glutamine-glutamate cycle in the communication between glia and neurons may have a role in the pathophysiology of depression in the elderly. Furthermore, the glutamine/glutamate ratio in CSF may be a state biomarker for depression.

  8. Alzheimer’s disease cerebrospinal fluid biomarker in cognitively normal subjects

    PubMed Central

    Toledo, Jon B.; Zetterberg, Henrik; van Harten, Argonde C.; Glodzik, Lidia; Martinez-Lage, Pablo; Bocchio-Chiavetto, Luisella; Rami, Lorena; Hansson, Oskar; Sperling, Reisa; Engelborghs, Sebastiaan; Osorio, Ricardo S.; Vanderstichele, Hugo; Vandijck, Manu; Hampel, Harald; Teipl, Stefan; Moghekar, Abhay; Albert, Marilyn; Hu, William T.; Monge Argilés, Jose A.; Gorostidi, Ana; Teunissen, Charlotte E.; De Deyn, Peter P.; Hyman, Bradley T.; Molinuevo, Jose L.; Frisoni, Giovanni B.; Linazasoro, Gurutz; de Leon, Mony J.; van der Flier, Wiesje M.; Scheltens, Philip; Blennow, Kaj; Shaw, Leslie M.

    2015-01-01

    In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer’s disease biomarkers including: total tau, phosphorylated tau and amyloid-β1-42. Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or Luminex® measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-β1-42 in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40–84 years old). Amyloid-β amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer’s disease cut-off values for cerebrospinal fluid amyloid-β1-42 and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE ε4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-β1-42 values and APOE ε2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-β1-42 levels were already frequent in midlife and APOE genotype

  9. The importance of sensitive screening for abnormal glucose metabolism in patients with IgA nephropathy.

    PubMed

    Jia, Xiaoyuan; Pan, Xiaoxia; Xie, Jingyuan; Shen, Pingyan; Wang, Zhaohui; Li, Ya; Wang, Weiming; Chen, Nan

    2016-01-01

    To investigate the prevalence of abnormal glucose metabolism, insulin resistance (IR) and the related risk factors in IgA nephropathy (IgAN) patients. We analyzed oral glucose tolerance test (OGTT) and clinical data of 107 IgAN patients and 106 healthy controls. Glucose metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) and the insulin sensitivity index (ISI) of both groups were evaluated. The prevalence of abnormal glucose metabolism was significantly higher in the IgAN group than in the control group (41.12% vs. 9.43%, p < 0.001), while the prevalence of IR between the two groups was not significantly different. IgAN patients have significantly higher fasting blood glucose, fasting insulin, OGTT 2-hour blood glucose, OGTT 2-hour insulin, HOMA-IR, and lower ISI than healthy controls. Triglyceride (OR = 2.55), 24-hour urine protein excretion (OR = 1.39), and age (OR = 1.06) were independent risk factors for abnormal glucose metabolism in IgAN patients. BMI, eGFR, 24-hour urine protein excretion, triglyceride, fasting blood glucose, fasting insulin, OGTT 2-hour blood glucose, and OGTT 2-hour insulin were significantly higher in IgAN patients with IR than in IgAN patients without IR, while HDL and ISI were significantly lower. BMI, serum albumin, and 24-hour urine protein excretion were correlated factors of IR in IgAN patients. Our study highlighted that abnormal glucose metabolism was common in IgAN patients. Triglyceride and 24-hour urine protein excretion were significant risk factors for abnormal glucose metabolism. Therefore, sensitive screening for glucose metabolism status and timely intervention should be carried out in clinical work.

  10. Aluminium exposure disrupts elemental homeostasis in Caenorhabditis elegans†

    PubMed Central

    Page, Kathryn E.; White, Keith N.; McCrohan, Catherine R.

    2013-01-01

    Aluminium (Al) is highly abundant in the environment and can elicit a variety of toxic responses in biological systems. Here we characterize the effects of Al on Caenorhabditis elegans by identifying phenotypic abnormalities and disruption in whole-body metal homeostasis (metallostasis) following Al exposure in food. Widespread changes to the elemental content of adult nematodes were observed when chronically exposed to Al from the first larval stage (L1). Specifically, we saw increased barium, chromium, copper and iron content, and a reduction in calcium levels. Lifespan was decreased in worms exposed to low levels of Al, but unexpectedly increased when the Al concentration reached higher levels (4.8 mM). This bi-phasic phenotype was only observed when Al exposure occurred during development, as lifespan was unaffected by Al exposure during adulthood. Lower levels of Al slowed C. elegans developmental progression, and reduced hermaphrodite self-fertility and adult body size. Significant developmental delay was observed even when Al exposure was restricted to embryogenesis. Similar changes in Al have been noted in association with Al toxicity in humans and other mammals, suggesting that C. elegans may be of use as a model for understanding the mechanisms of Al toxicity in mammalian systems. PMID:22534883

  11. The S-Lagrangian and a theory of homeostasis in living systems

    NASA Astrophysics Data System (ADS)

    Sandler, U.; Tsitolovsky, L.

    2017-04-01

    A major paradox of living things is their ability to actively counteract degradation in a continuously changing environment or being injured through homeostatic protection. In this study, we propose a dynamic theory of homeostasis based on a generalized Lagrangian approach (S-Lagrangian), which can be equally applied to physical and nonphysical systems. Following discoverer of homeostasis Cannon (1935), we assume that homeostasis results from tendency of the organisms to decrease of the stress and avoid of death. We show that the universality of homeostasis is a consequence of analytical properties of the S-Lagrangian, while peculiarities of the biochemical and physiological mechanisms of homeostasis determine phenomenological parameters of the S-Lagrangian. Additionally, we reveal that plausible assumptions about S-Lagrangian features lead to good agreement between theoretical descriptions and observed homeostatic behavior. Here, we have focused on homeostasis of living systems, however, the proposed theory is also capable of being extended to social systems.

  12. The Emerging Relationship Between Interstitial Fluid-Cerebrospinal Fluid Exchange, Amyloid-β, and Sleep.

    PubMed

    Boespflug, Erin L; Iliff, Jeffrey J

    2018-02-15

    Amyloid-β (Aβ) plaques are a key histopathological hallmark of Alzheimer's disease (AD), and soluble Aβ species are believed to play an important role in the clinical development of this disease. Emerging biomarker data demonstrate that Aβ plaque deposition begins decades before the onset of clinical symptoms, suggesting that understanding the biological determinants of the earliest steps in the development of AD pathology may provide key opportunities for AD treatment and prevention. Although a clinical association between sleep disruption and AD has long been appreciated, emerging clinical studies and insights from the basic neurosciences have shed important new light on how sleep and Aβ homeostasis may be connected in the setting of AD. Aβ, like many interstitial solutes, is cleared in part through the exchange of brain interstitial fluid and cerebrospinal fluid along a brain-wide network of perivascular pathways recently termed the glymphatic system. Glymphatic function is primarily a feature of the sleeping brain, rather than the waking brain, and is slowed in the aging and posttraumatic brain. These changes may underlie the diurnal fluctuations in interstitial and cerebrospinal fluid Aβ levels observed in both the rodent and the human. These and other emerging studies suggest that age-related sleep disruption may be one key factor that renders the aging brain vulnerable to Aβ deposition and the development of AD. If this is true, sleep may represent a key modifiable risk factor or therapeutic target in the preclinical phases of AD. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Spectral luminescence analysis of amniotic fluid

    NASA Astrophysics Data System (ADS)

    Slobozhanina, Ekaterina I.; Kozlova, Nataly M.; Kasko, Leonid P.; Mamontova, Marina V.; Chernitsky, Eugene A.

    1997-12-01

    It is shown that the amniotic fluid has intensive ultra-violet luminescence caused by proteins. Along with it amniotic fluid radiated in the field of 380 - 650 nm with maxima at 430 - 450 nm and 520 - 560 nm. The first peak of luminescence ((lambda) exc equals 350 nm; (lambda) em equals 430 - 440 nm) is caused (most probably) by the presence in amniotic fluid of some hormones, NADH2 and NADPH2. A more long-wave component ((lambda) exc equals 460 nm; (lambda) em equals 520 - 560 nm) is most likely connected with the presence in amniotic fluid pigments (bilirubin connected with protein and other). It is shown that intensity and maximum of ultra-violet luminescence spectra of amniotic fluid in normality and at pathology are identical. However both emission spectra and excitation spectra of long-wave ((lambda) greater than 450 nm) luminescence of amniotic fluid from pregnant women with such prenatal abnormal developments of a fetus as anencephaly and spina bifida are too long-wave region in comparison with the norm. Results of research testify that spectral luminescent analysis of amniotic fluid can be used for screening of malformations of the neural tube. It is very difficult for a practical obstetrician to reveal pregnant women with a high risk of congenital malformations of the fetus. Apart from ultrasonic examination, cytogenetic examination of amniotic fluid and defumination of concentrations of alpha-fetoprotein and acetylcholin-esterases in the amniotic fluid and blood plasma are the most widely used diagnostic approaches. However, biochemical and cytogenetic diagnostic methods are time-consuming. In the present work spectral luminescence properties of the amniotic fluid are investigated to determine spectral parameters that can be used to reveal pregnant women with a high risk of congenital malformations of their offsprings.

  14. [Preoperative fasting and fluid management in pediatric patients].

    PubMed

    Sumiyoshi, Rieko

    2013-09-01

    Preoperative fasting is principally intended to minimize the risk of pulmonary aspiration of gastric contents and facilitate the safe and efficient conduct of anesthesia. Liberalization of fasting guidelines has been implemented in most countries. In general, clear fluids are allowed up to 2h before anesthesia, and light meals up to 6h. In infants, most recommendations now allow breast milk feeding up to 4h and other kinds of milk up to 6h. Recently, the concept of preoperative oral rehydration using a carbohydrate-rich beverage up to 2h has also gained support. Drinking carbohydrate-rich fluids before elective surgery may reduce dehydration, improve hemodynamic stability under anesthesia, facilitate intravenous access, maintain glucose homeostasis, reduce patient irritability, and improve child and parent satisfaction. These guidelines apply to healthy children only. Exclusion criteria included obesity, diabetes, gastroesophageal reflux, ileus, bowel obstruction and emergency care. In particular, trauma and other emergency cases are at higher risk for aspiration regardless of fasting interval and should be managed appropriately.

  15. Development and Validation of the Homeostasis Concept Inventory

    PubMed Central

    McFarland, Jenny L.; Price, Rebecca M.; Wenderoth, Mary Pat; Martinková, Patrícia; Cliff, William; Michael, Joel; Modell, Harold; Wright, Ann

    2017-01-01

    We present the Homeostasis Concept Inventory (HCI), a 20-item multiple-choice instrument that assesses how well undergraduates understand this critical physiological concept. We used an iterative process to develop a set of questions based on elements in the Homeostasis Concept Framework. This process involved faculty experts and undergraduate students from associate’s colleges, primarily undergraduate institutions, regional and research-intensive universities, and professional schools. Statistical results provided strong evidence for the validity and reliability of the HCI. We found that graduate students performed better than undergraduates, biology majors performed better than nonmajors, and students performed better after receiving instruction about homeostasis. We used differential item analysis to assess whether students from different genders, races/ethnicities, and English language status performed differently on individual items of the HCI. We found no evidence of differential item functioning, suggesting that the items do not incorporate cultural or gender biases that would impact students’ performance on the test. Instructors can use the HCI to guide their teaching and student learning of homeostasis, a core concept of physiology. PMID:28572177

  16. Epidermal development, growth control, and homeostasis in the face of centrosome amplification.

    PubMed

    Kulukian, Anita; Holland, Andrew J; Vitre, Benjamin; Naik, Shruti; Cleveland, Don W; Fuchs, Elaine

    2015-11-17

    As nucleators of the mitotic spindle and primary cilium, centrosomes play crucial roles in equal segregation of DNA content to daughter cells, coordination of growth and differentiation, and transduction of homeostatic cues. Whereas the majority of mammalian cells carry no more than two centrosomes per cell, exceptions to this rule apply in certain specialized tissues and in select disease states, including cancer. Centrosome amplification, or the condition of having more than two centrosomes per cell, has been suggested to contribute to instability of chromosomes, imbalance in asymmetric divisions, and reorganization of tissue architecture; however, the degree to which these conditions are a direct cause of or simply a consequence of human disease is poorly understood. Here we addressed this issue by generating a mouse model inducing centrosome amplification in a naturally proliferative epithelial tissue by elevating Polo-like kinase 4 (Plk4) expression in the skin epidermis. By altering centrosome numbers, we observed multiciliated cells, spindle orientation errors, and chromosome segregation defects within developing epidermis. None of these defects was sufficient to impart a proliferative advantage within the tissue, however. Rather, impaired mitoses led to p53-mediated cell death and contributed to defective growth and stratification. Despite these abnormalities, mice remained viable and healthy, although epidermal cells with centrosome amplification were still appreciable. Moreover, these abnormalities were insufficient to disrupt homeostasis and initiate or enhance tumorigenesis, underscoring the powerful surveillance mechanisms in the skin.

  17. The SH2B1 obesity locus and abnormal glucose homeostasis: lack of evidence for association from a meta-analysis in individuals of European ancestry.

    PubMed

    Prudente, S; Copetti, M; Morini, E; Mendonca, C; Andreozzi, F; Chandalia, M; Baratta, R; Pellegrini, F; Mercuri, L; Bailetti, D; Abate, N; Frittitta, L; Sesti, G; Florez, J C; Doria, A; Trischitta, V

    2013-11-01

    The development of type 2 diabetes (T2D) is influenced both by environmental and by genetic determinants. Obesity is an important risk factor for T2D, mostly mediated by obesity-related insulin resistance. Obesity and insulin resistance are also modulated by the genetic milieu; thus, genes affecting risk of obesity and insulin resistance might also modulate risk of T2D. Recently, 32 loci have been associated with body mass index (BMI) by genome-wide studies, including one locus on chromosome 16p11 containing the SH2B1 gene. Animal studies have suggested that SH2B1 is a physiological enhancer of the insulin receptor and humans with rare deletions or mutations at SH2B1 are obese with a disproportionately high insulin resistance. Thus, the role of SH2B1 in both obesity and insulin resistance makes it a strong candidate for T2D. However, published data on the role of SH2B1 variability on the risk for T2D are conflicting, ranging from no effect at all to a robust association. The SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was genotyped in 6978 individuals from six studies for abnormal glucose homeostasis (AGH), including impaired fasting glucose, impaired glucose tolerance or T2D, from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) consortium. Data from these studies were then meta-analyzed, in a Bayesian fashion, with those from DIAGRAM+ (n = 47,117) and four other published studies (n = 39,448). Variability at the SH2B1 obesity locus was not associated with AGH either in the GENIUS consortium (overall odds ratio (OR) = 0.96; 0.89-1.04) or in the meta-analysis (OR = 1.01; 0.98-1.05). Our data exclude a role for the SH2B1 obesity locus in the modulation of AGH. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    ERIC Educational Resources Information Center

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  19. Hepatic miRNA profiles and thyroid hormone homeostasis in rats exposed to dietary potassium perfluorooctanesulfonate (PFOS).

    PubMed

    Dong, Hongyan; Curran, Ivan; Williams, Andrew; Bondy, Genevieve; Yauk, Carole L; Wade, Michael G

    2016-01-01

    Perfluorooctanesulfonate (PFOS) has been widely used in a variety of industrial and commercial applications as a surfactant and stain repellent. PFOS causes liver damage (including liver tumors) in experimental animals, primarily via interaction with PPARα and CAR/PXR. We investigated the involvement of microRNAs (miRNAs) in PFOS-induced hepatotoxicity, and mechanisms involved in abnormal thyroid hormone (TH) homeostasis, in the livers of adult male rats exposed in feed to 50mg PFOS/kg diet for 28 days. PFOS-treated rats exhibited expected histopathological and clinical chemistry changes, and global gene expression changes consistent with the involvement of PPARα and CAR/PXR. Thirty-eight miRNAs were significantly altered. Three members of the miR-200 family were the most increased, while miR-122-5p and miR-21-5p were the most decreased, in PFOS-treated rats. Expression of the miR-23b-3p/27b-3p/24-3p cluster also decreased in PFOS-treated animals. Pathway analysis of miRNAs and associated gene expression changes suggests involvement of epithelial to mesenchymal transition (EMT), which is a primary process of tumor cell motility and cancer metastasis. Our analysis also revealed transcripts that may mediate PFOS-induced effects on TH homeostasis including: activation of the CAR/PXR pathway, phase II/III enzymes, and deiodinase. These changes are consistent with low serum TH due to enhanced metabolic clearance of TH. However, most TH hepatic target genes were not altered in a manner consistent with reduced TH signaling, suggesting that PFOS exposure did not induce functional hypothyroidism. Collectively, the study suggests an important role for miRNAs in PFOS-induced hepatotoxicity and provides insight into the effects of PFOS on TH homeostasis. Copyright © 2015. Published by Elsevier B.V.

  20. Achieving global perfect homeostasis through transporter regulation

    PubMed Central

    Springer, Michael

    2017-01-01

    Nutrient homeostasis—the maintenance of relatively constant internal nutrient concentrations in fluctuating external environments—is essential to the survival of most organisms. Transcriptional regulation of plasma membrane transporters by internal nutrient concentrations is typically assumed to be the main mechanism by which homeostasis is achieved. While this mechanism is homeostatic we show that it does not achieve global perfect homeostasis—a condition where internal nutrient concentrations are completely independent of external nutrient concentrations for all external nutrient concentrations. We show that the criterion for global perfect homeostasis is that transporter levels must be inversely proportional to net nutrient flux into the cell and that downregulation of active transporters (activity-dependent regulation) is a simple and biologically plausible mechanism that meets this criterion. Activity-dependent transporter regulation creates a trade-off between robustness and efficiency, i.e., the system's ability to withstand perturbation in external nutrients and the transporter production rate needed to maintain homeostasis. Additionally, we show that a system that utilizes both activity-dependent transporter downregulation and regulation of transporter synthesis by internal nutrient levels can create a system that mitigates the shortcomings of each of the individual mechanisms. This analysis highlights the utility of activity-dependent regulation in achieving homeostasis and calls for a re-examination of the mechanisms of regulation of other homeostatic systems. PMID:28414718

  1. [A comparative analysis of anti-N-methyl-D-aspartate receptor encephalitis with or without abnormal findings on cranial magnetic resonance imaging].

    PubMed

    Zhang, Jian-Zhao; Chen, Qian; Zheng, Ping; Xie, Li-Na; Yi, Xiao-Li; Ren, Hai-Tao; Yang, Jian

    2018-01-01

    To investigate the clinical features of children with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis with normal or abnormal cranial magnetic resonance imaging (MRI) findings via a comparative analysis. A retrospective analysis was performed for the clinical data of 33 children with anti-NMDAR encephalitis. The clinical features and prognosis were compared between the children with normal and abnormal cranial MRI findings. In the 33 children with anti-NMDAR encephalitis, the most common initial symptoms were seizures (61%) and involuntary movement (61%), followed by language disorder (54%), mental and behavioral abnormalities (52%), and disturbance of consciousness (30%). All children had positive anti-NMDAR antibody in the cerebrospinal fluid, and 29 children (88%) had positive serum antibody. Of all the children, 15 (46%) had increased leukocytes in the cerebrospinal fluid, 3 (9%) had an increase in protein, and 29 (88%) had positive oligoclonal band; 26 children (79%) had electroencephalographic abnormalities (epileptic wave, slow wave, or a combination of these two types of waves). One child experienced respiratory failure. One child was found to have germinoma in the sellar region during follow-up. Of all the 33 children, 13 (39%) had abnormal cranial MRI findings, with hypointensity or isointensity on T1W1 and hyperintensity on T2WI and T2-FLAIR; 2 children had dural enhancement. As for the location of lesion, 5 children (38%) had lesions in the temporal lobe, 3 (23%) in the frontal lobe, 3 (23%) in the basal ganglia, 2 (15%) in the parietal lobe, 2 (15%) in the occipital lobe, 2 (15%) in the brainstem, 1 (8%) in the thalamus, and 1 (8%) in the cerebellum. Among the 13 children with abnormal cranial MRI findings, 5 (38%) had lesions mainly in the grey matter and 8 (62%) had lesions mainly in the white matter. Compared with the children with normal cranial MRI findings, the children with abnormal cranial MRI findings had significantly higher

  2. Association of Dyslipidemia and Glucose Abnormalities with Antiretroviral Treatment in a Cohort of HIV-infected Latin American Children

    PubMed Central

    Paganella, MP; Cohen, RA; Harris, DR; Kuchenbecker, RS; Sperhacke, RD; Kato, SK; Silva, CLO; Sturzbecher, FT; Oliveira, RHS; Pavía Ruz, N; Hazra, R

    2016-01-01

    Objective(s) To estimate the incidence of lipid and glucose abnormalities and assess their association with exposure to antiretroviral (ARV) regimens among perinatally HIV-infected Latin American children. Design Longitudinal cohort study. Methods Data were analyzed from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) International Site Development Initiative (NISDI) Pediatric Latin American Countries Epidemiologic Study (PLACES). The incidence of dyslipidemia (total cholesterol>200mg/dL, HDL<35mg/dL, LDL≥130mg/dL, triglycerides>110mg/dL [age<10 years] or >150mg/dL [≥10 years]) and fasting glucose abnormalities (homeostasis model assessment of insulin resistance >2.5 [Tanner Stage 1] or >4.0 [Tanner Stage>1]; impaired glucose: 110 to <126mg/dL; diabetes: ≥126 mg/dL) was estimated. Proportional hazards regression was used to evaluate the risk of abnormalities associated with ARV regimen, adjusted for covariates. Results There were 385 children eligible for analysis (mean age 6.6 years). Incident cholesterol abnormalities were reported in 18.1% of participants (95% confidence interval [CI] 14.1–22.8%), HDL and LDL cholesterol abnormalities in 19.6% (15.1–24.7%) and 15.0% (11.3–19.5%), respectively, and triglyceride abnormalities in 44.2% (37.7–50.8%). In multivariable analysis, ARV regimen was only associated with triglyceride abnormalities; participants receiving a protease inhibitor-containing (PI) regimen were 3.6 times as likely to experience a triglyceride abnormality as those receiving no ARVs (95% CI: 1.3–10.5; p=0.0167). The cumulative incidence of insulin resistance was 3.8% (1.8–7.1%); there were no incident cases of diabetes and only two of impaired fasting glucose. Conclusions Children receiving PI-containing regimens were at increased risk of developing triglyceride abnormalities. Continued monitoring of lipid levels in children receiving PI-containing regimens appears warranted. PMID:27570910

  3. Abnormal Uterine Bleeding

    MedlinePlus

    ... abnormal uterine bleeding? Abnormal uterine bleeding is any heavy or unusual bleeding from the uterus (through your ... one symptom of abnormal uterine bleeding. Having extremely heavy bleeding during your period can also be considered ...

  4. A Formal Explication of the Concept of Family Homeostasis.

    ERIC Educational Resources Information Center

    Ariel, Shlomo; And Others

    1984-01-01

    Presents three articles discussing the concept of family homeostasis and the related concepts of family rules and family feedback. Includes a reply by Paul Dell citing the need for family therapy to go beyond homeostasis and further comments by Ariel, Carel, and Tyano. (JAC)

  5. The antioxidant system of seminal fluid during in vitro storage of sterlet Acipenser ruthenus sperm.

    PubMed

    Dzyuba, Viktoriya; Cosson, Jacky; Dzyuba, Borys; Yamaner, Gunes; Rodina, Marek; Linhart, Otomar

    2016-04-01

    The role of the seminal fluid antioxidant system in protection against damage to spermatozoa during in vitro sperm storage is unclear. This study investigated the effect of in vitro storage of sterlet Acipenser ruthenus spermatozoa together with seminal fluid for 36 h at 4 °C on spermatozoon motility rate and curvilinear velocity, thiobarbituric acid reactive substance level, and components of enzyme and non-enzyme antioxidant system (superoxide dismutase and catalase activity and uric acid concentration) in seminal fluid. Spermatozoon motility parameters after sperm storage were significantly decreased, while the level of thiobarbituric acid reactive substances, activity of superoxide dismutase and catalase, and uric acid concentration did not change. Our findings suggest that the antioxidant system of sterlet seminal fluid is effective in preventing oxidative stress during short-term sperm storage and prompt future investigations of changes in spermatozoon homeostasis and in spermatozoon plasma membrane structure which are other possible reasons of spermatozoon motility deterioration upon sperm storage.

  6. Physiology and pathophysiology of potassium homeostasis.

    PubMed

    Palmer, Biff F; Clegg, Deborah J

    2016-12-01

    Total body potassium content and proper distribution of potassium across the cell membrane is of critical importance for normal cellular function. Potassium homeostasis is maintained by several different methods. In the kidney, total body potassium content is achieved by alterations in renal excretion of potassium in response to variations in intake. Insulin and beta-adrenergic tone play critical roles in maintaining the internal distribution of potassium under normal conditions. Despite homeostatic pathways designed to maintain potassium levels within the normal range, disorders of altered potassium homeostasis are common. The clinical approach to designing effective treatments relies on understanding the pathophysiology and regulatory influences which govern the internal distribution and external balance of potassium. Here we provide an overview of the key regulatory aspects of normal potassium physiology. This review is designed to provide an overview of potassium homeostasis as well as provide references of seminal papers to guide the reader into a more in depth discussion of the importance of potassium balance. This review is designed to be a resource for educators and well-informed clinicians who are teaching trainees about the importance of potassium balance. Copyright © 2016 the American Physiological Society.

  7. Pseudomonas aeruginosa Trent and zinc homeostasis.

    PubMed

    Davies, Corey B; Harrison, Mark D; Huygens, Flavia

    2017-09-01

    Pseudomonas aeruginosa is a Gram-negative pathogen and the major cause of mortality in patients with cystic fibrosis. The mechanisms that P. aeruginosa strains use to regulate intracellular zinc have an effect on infection, antibiotic resistance and the propensity to form biofilms. However, zinc homeostasis in P. aeruginosa strains of variable infectivity has not been compared. In this study, zinc homeostasis in P. aeruginosa Trent, a highly infectious clinical strain, was compared to that of a laboratory P. aeruginosa strain, ATCC27853. Trent was able to tolerate higher concentrations of additional zinc in rich media than ATCC27853. Further, pre-adaptation to additional zinc enhanced the growth of Trent at non-inhibitory concentrations but the impact of pre-adaption on the growth of ATCC27853 under the same conditions was minimal. The results establish clear differences in zinc-induced responses in Trent and ATCC27853, and how zinc homeostasis can be a promising target for the development of novel antimicrobial strategies for P. aeruginosa infection in cystic fibrosis patients. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Thiol/disulfide homeostasis in postmenopausal osteoporosis.

    PubMed

    Korkmaz, V; Kurdoglu, Z; Alisik, M; Turgut, E; Sezgın, O O; Korkmaz, H; Ergun, Y; Erel, O

    2017-04-01

    To evaluate the impact of postmenopausal osteoporosis on thiol/disulfide homeostasis. A total of 75 participants were divided into two groups: Group 1 (n = 40) was composed of healthy postmenopausal women, and group 2 (n = 35) was composed of women with postmenopausal osteoporosis. Clinical findings and thiol/disulfide homeostasis were compared between the two groups. The disulfide/native thiol ratio was 8.6% ± 3.6 in group 1 and 12.7% ± 8.4 in group 2 (p = 0.04). The disulfide/native thiol percent ratio was significantly higher in group 2 after adjustment for the years since menopause and age (p < 0.05). The native thiol/total thiol percent ratio was 85.6% ± 4.8 in group 1 and 73.8% ± 24.9 in group 2 (p = 0.01). The native thiol/total thiol percent ratio was significantly lower in group 2 after adjustment for the years since menopause and age (p < 0.05). Thiol/disulfide homeostasis shifted to the disulfide side independent of age and years since menopause in postmenopausal osteoporosis.

  9. Metabolomic profiling in inner ear fluid by gas chromatography/mass spectrometry in guinea pig cochlea.

    PubMed

    Fujita, Takeshi; Yamashita, Daisuke; Irino, Yasuhiro; Kitamoto, Junko; Fukuda, Yuriko; Inokuchi, Go; Hasegawa, Shingo; Otsuki, Naoki; Yoshida, Masaru; Nibu, Ken-ichi

    2015-10-08

    The composition and homeostasis of inner ear fluids are important in hearing function. The purpose of this study was to perform metabolomic analysis of the inner ear fluid in guinea pig cochlea, which has not been previously reported in literature, using gas chromatography/mass spectrometry (GC/MS). Seventy-seven kinds of metabolites were detected in the inner ear fluid. Six metabolites, ascorbic acid, fructose, galactosamine, inositol, pyruvate+oxaloacetic acid, and meso-erythritol, were significantly more abundant, and nine metabolites, phosphate, valine, glycine, glycerol, ornithine, glucose, citric acid+isocitric acid, mannose, and trans-4-hydroxy-L-proline, were less abundant in the inner ear fluid than in plasma. The levels of ten metabolites, 3-hydroxy-butyrate, glycerol, fumaric acid, galactosamine, pyruvate+oxaloacetic acid, phosphate, meso-erythritol, citric acid+isocitric acid, mannose, and inositol, in the inner ear fluid significantly changed after loud noise exposure. These observations may help to elucidate various clinical conditions of sensorineural hearing loss, including noise-induced hearing loss. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Acid-Base Homeostasis

    PubMed Central

    Nakhoul, Nazih; Hering-Smith, Kathleen S.

    2015-01-01

    Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3− and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3− is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys. PMID:26597304

  11. Snapshot: implications for melatonin in endoplasmic reticulum homeostasis

    PubMed Central

    Hu, Wei; Ma, Zhiqiang; Di, Shouyin; Jiang, Shuai; Li, Yue; Fan, Chongxi

    2016-01-01

    The endoplasmic reticulum (ER) is an important intracellular membranous organelle. Previous studies have demonstrated that the ER is responsible for protein folding and trafficking, lipid synthesis and the maintenance of calcium homeostasis. Interestingly, the morphology and structure of the ER were recently found to be important. Melatonin is a hormone that anticipates the daily onset of darkness in mammals, and it is well known that melatonin acts as an antioxidant by scavenging free radicals and increasing the activity of antioxidant enzymes in the body. Notably, the existing evidence demonstrates that melatonin is involved in ER homeostasis, particularly in the morphology of the ER, indicating a potential protective role of melatonin. This review discusses the existing knowledge regarding the implications for the involvement of melatonin in ER homeostasis. PMID:27759160

  12. FAT/CD36: a major regulator of neuronal fatty acid sensing and energy homeostasis in rats and mice.

    PubMed

    Le Foll, Christelle; Dunn-Meynell, Ambrose; Musatov, Serguei; Magnan, Christophe; Levin, Barry E

    2013-08-01

    Hypothalamic "metabolic-sensing" neurons sense glucose and fatty acids (FAs) and play an integral role in the regulation of glucose, energy homeostasis, and the development of obesity and diabetes. Using pharmacologic agents, we previously found that ~50% of these neurons responded to oleic acid (OA) by using the FA translocator/receptor FAT/CD36 (CD36). For further elucidation of the role of CD36 in neuronal FA sensing, ventromedial hypothalamus (VMH) CD36 was depleted using adeno-associated viral (AAV) vector expressing CD36 short hairpin RNA (shRNA) in rats. Whereas their neuronal glucosensing was unaffected by CD36 depletion, the percent of neurons that responded to OA was decreased specifically in glucosensing neurons. A similar effect was seen in total-body CD36-knockout mice. Next, weanling rats were injected in the VMH with CD36 AAV shRNA. Despite significant VMH CD36 depletion, there was no effect on food intake, body weight gain, or total carcass adiposity on chow or 45% fat diets. However, VMH CD36-depleted rats did have increased plasma leptin and subcutaneous fat deposition and markedly abnormal glucose tolerance. These results demonstrate that CD36 is a critical factor in both VMH neuronal FA sensing and the regulation of energy and glucose homeostasis.

  13. Ephrin-B2 governs morphogenesis of endolymphatic sac and duct epithelia in the mouse inner ear.

    PubMed

    Raft, Steven; Andrade, Leonardo R; Shao, Dongmei; Akiyama, Haruhiko; Henkemeyer, Mark; Wu, Doris K

    2014-06-01

    Control over ionic composition and volume of the inner ear luminal fluid endolymph is essential for normal hearing and balance. Mice deficient in either the EphB2 receptor tyrosine kinase or the cognate transmembrane ligand ephrin-B2 (Efnb2) exhibit background strain-specific vestibular-behavioral dysfunction and signs of abnormal endolymph homeostasis. Using various loss-of-function mouse models, we found that Efnb2 is required for growth and morphogenesis of the embryonic endolymphatic epithelium, a precursor of the endolymphatic sac (ES) and duct (ED), which mediate endolymph homeostasis. Conditional inactivation of Efnb2 in early-stage embryonic ear tissues disrupted cell proliferation, cell survival, and epithelial folding at the origin of the endolymphatic epithelium. This correlated with apparent absence of an ED, mis-localization of ES ion transport cells relative to inner ear sensory organs, dysplasia of the endolymph fluid space, and abnormally formed otoconia (extracellular calcite-protein composites) at later stages of embryonic development. A comparison of Efnb2 and Notch signaling-deficient mutant phenotypes indicated that these two signaling systems have distinct and non-overlapping roles in ES/ED development. Homozygous deletion of the Efnb2 C-terminus caused abnormalities similar to those found in the conditional Efnb2 null homozygote. Analyses of fetal Efnb2 C-terminus deletion heterozygotes found mis-localized ES ion transport cells only in the genetic background exhibiting vestibular dysfunction. We propose that developmental dysplasias described here are a gene dose-sensitive cause of the vestibular dysfunction observed in EphB-Efnb2 signaling-deficient mice. Published by Elsevier Inc.

  14. Ephrin-B2 governs morphogenesis of endolymphatic sac and duct epithelia in the mouse inner ear

    PubMed Central

    Raft, Steven; Andrade, Leonardo R.; Shao, Dongmei; Akiyama, Haruhiko; Henkemeyer, Mark; Wu, Doris K.

    2014-01-01

    Control over ionic composition and volume of the inner ear luminal fluid endolymph is essential for normal hearing and balance. Mice deficient in either the EphB2 receptor tyrosine kinase or the cognate transmembrane ligand ephrin-B2 (Efnb2) exhibit background strain-specific vestibular behavioral dysfunction and signs of abnormal endolymph homeostasis. Using various loss-of-function mouse models, we found that Efnb2 is required for growth and morphogenesis of the embryonic endolymphatic epithelium, a precursor of the endolymphatic sac (ES) and duct (ED), which mediate endolymph homeostasis. Conditional inactivation of Efnb2 in early-stage embryonic ear tissues disrupted cell proliferation, cell survival, and epithelial folding at the origin of the endolymphatic epithelium. This correlated with apparent absence of an ED, mis-localization of ES ion transport cells relative to inner ear sensory organs, dysplasia of the endolymph fluid space, and abnormally formed otoconia (extracellular calcite protein composites) at later stages of embryonic development. A comparison of Efnb2 and Notch signaling deficient mutant phenotypes indicated that these two signaling systems have distinct and non overlapping roles in ES/ED development. Homozygous deletion of the Efnb2 C terminus caused abnormalities similar to those found in the conditional Efnb2 null homozygote. Analyses of fetal Efnb2 C-terminus deletion heterozygotes found mis-localized ES ion transport cells only in the genetic background exhibiting vestibular dysfunction. We propose that developmental dysplasias described here are a gene dose sensitive cause of the vestibular dysfunction observed in EphB-Efnb2 signaling-deficient mice. PMID:24583262

  15. EGFR signaling regulates cell proliferation, differentiation and morphogenesis during planarian regeneration and homeostasis.

    PubMed

    Fraguas, Susanna; Barberán, Sara; Cebrià, Francesc

    2011-06-01

    Similarly to development, the process of regeneration requires that cells accurately sense and respond to their external environment. Thus, intrinsic cues must be integrated with signals from the surrounding environment to ensure appropriate temporal and spatial regulation of tissue regeneration. Identifying the signaling pathways that control these events will not only provide insights into a fascinating biological phenomenon but may also yield new molecular targets for use in regenerative medicine. Among classical models to study regeneration, freshwater planarians represent an attractive system in which to investigate the signals that regulate cell proliferation and differentiation, as well as the proper patterning of the structures being regenerated. Recent studies in planarians have begun to define the role of conserved signaling pathways during regeneration. Here, we extend these analyses to the epidermal growth factor (EGF) receptor pathway. We report the characterization of three epidermal growth factor (EGF) receptors in the planarian Schmidtea mediterranea. Silencing of these genes by RNA interference (RNAi) yielded multiple defects in intact and regenerating planarians. Smed-egfr-1(RNAi) resulted in decreased differentiation of eye pigment cells, abnormal pharynx regeneration and maintenance, and the development of dorsal outgrowths. In contrast, Smed-egfr-3(RNAi) animals produced smaller blastemas associated with abnormal differentiation of certain cell types. Our results suggest important roles for the EGFR signaling in controlling cell proliferation, differentiation and morphogenesis during planarian regeneration and homeostasis. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Brainstem abnormalities and vestibular nerve enhancement in acute neuroborreliosis.

    PubMed

    Farshad-Amacker, Nadja A; Scheffel, Hans; Frauenfelder, Thomas; Alkadhi, Hatem

    2013-12-21

    Borreliosis is a widely distributed disease. Neuroborreliosis may present with unspecific symptoms and signs and often remains difficult to diagnose in patients with central nervous system symptoms, particularly if the pathognomonic erythema chronica migrans does not develop or is missed. Thus, vigilance is mandatory in cases with atypical presentation of the disease and with potentially severe consequences if not recognized early. We present a patient with neuroborreliosis demonstrating brain stem and vestibular nerve abnormalities on magnetic resonance imaging. A 28-year-old Caucasian female presented with headaches, neck stiffness, weight loss, nausea, tremor, and gait disturbance. Magnetic resonance imaging showed T2-weighted hyperintense signal alterations in the pons and in the vestibular nerves as well as bilateral post-contrast enhancement of the vestibular nerves. Serologic testing of the cerebrospinal fluid revealed the diagnosis of neuroborreliosis. Patients infected with neuroborreliosis may present with unspecific neurologic symptoms and magnetic resonance imaging as a noninvasive imaging tool showing signal abnormalities in the brain stem and nerve root enhancement may help in establishing the diagnosis.

  17. Regulation of brain copper homeostasis by the brain barrier systems: Effects of Fe-overload and Fe-deficiency

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Monnot, Andrew D.; Behl, Mamta; Ho, Sanna

    2011-11-15

    Maintaining brain Cu homeostasis is vital for normal brain function. The role of systemic Fe deficiency (FeD) or overload (FeO) due to metabolic diseases or environmental insults in Cu homeostasis in the cerebrospinal fluid (CSF) and brain tissues remains unknown. This study was designed to investigate how blood-brain barrier (BBB) and blood-SCF barrier (BCB) regulated Cu transport and how FeO or FeD altered brain Cu homeostasis. Rats received an Fe-enriched or Fe-depleted diet for 4 weeks. FeD and FeO treatment resulted in a significant increase (+ 55%) and decrease (- 56%) in CSF Cu levels (p < 0.05), respectively; however,more » neither treatment had any effect on CSF Fe levels. The FeD, but not FeO, led to significant increases in Cu levels in brain parenchyma and the choroid plexus. In situ brain perfusion studies demonstrated that the rate of Cu transport into the brain parenchyma was significantly faster in FeD rats (+ 92%) and significantly slower (- 53%) in FeO rats than in controls. In vitro two chamber Transwell transepithelial transport studies using primary choroidal epithelial cells revealed a predominant efflux of Cu from the CSF to blood compartment by the BCB. Further ventriculo-cisternal perfusion studies showed that Cu clearance by the choroid plexus in FeD animals was significantly greater than control (p < 0.05). Taken together, our results demonstrate that both the BBB and BCB contribute to maintain a stable Cu homeostasis in the brain and CSF. Cu appears to enter the brain primarily via the BBB and is subsequently removed from the CSF by the BCB. FeD has a more profound effect on brain Cu levels than FeO. FeD increases Cu transport at the brain barriers and prompts Cu overload in the CNS. The BCB plays a key role in removing the excess Cu from the CSF.« less

  18. The lipid accumulation product as a useful index for identifying abnormal glucose regulation in young Korean women.

    PubMed

    Oh, J-Y; Sung, Y-A; Lee, H J

    2013-04-01

    The lipid accumulation product, a combination of waist circumference and triglycerides concentration, has been suggested as a better marker for abnormal glucose regulation than BMI. We aimed to compare the lipid accumulation product and BMI as useful markers for abnormal glucose regulation in young Korean women. The lipid accumulation product was calculated using the formula [waist circumference (cm) - 58] × triglycerides (mmol/l). Glucose tolerance status was determined using a 75-g oral glucose tolerance test in 2810 Korean women aged 18-39 years from the general population. The prevalence of abnormal glucose regulation was 6.8% (isolated impaired fasting glucose 1.8%, isolated impaired glucose tolerance 4.0%; impaired fasting glucose + impaired glucose tolerance 0.4% and diabetes mellitus 0.6%). According to the quintile distributions of the lipid accumulation product and BMI, women with a lipid accumulation product quintile greater than their BMI quintile exhibited significantly greater areas under the curve and higher levels of 2-h post-load glucose, insulin, homeostasis model analysis of insulin resistance and lipid profiles than did women with a BMI quintile greater than their lipid accumulation product quintile. Multiple logistic regression revealed that the lipid accumulation product exhibited a higher odds ratio for abnormal glucose regulation than did BMI after adjusting for age, systolic blood pressure, HDL cholesterol, previous history of gestational diabetes and family history of diabetes (odds ratios 3.5 and 2.6 of the highest vs. the lowest quintiles of lipid accumulation product and BMI, respectively). The lipid accumulation product could be useful for identifying the young Korean women with abnormal glucose regulation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  19. Thermal relaxation and critical instability of near-critical fluid microchannel flow.

    PubMed

    Chen, Lin; Zhang, Xin-Rong; Okajima, Junnosuke; Maruyama, Shigenao

    2013-04-01

    We present two-dimensional numerical investigations of the temperature and velocity evolution of a pure near-critical fluid confined in microchannels. The fluid is subjected to two sides heating after it reached isothermal steady state. We focus on the abnormal behaviors of the near-critical fluid in response to the sudden imposed heat flux. New thermal-mechanical effects dominated by fluid instability originating from the boundary and local equilibrium process are reported. Near the microchannel boundaries, the instability grows very quickly and an unexpected vortex formation mode is identified when near-critical thermal-mechanical effect is interacting with the microchannel shear flow. The mechanism of the new kind of Kelvin-Helmholtz instability induced by boundary expansion and density stratification processes is also discussed in detail. This mechanism may bring about innovations in the field of microengineering.

  20. Thermal relaxation and critical instability of near-critical fluid microchannel flow

    NASA Astrophysics Data System (ADS)

    Chen, Lin; Zhang, Xin-Rong; Okajima, Junnosuke; Maruyama, Shigenao

    2013-04-01

    We present two-dimensional numerical investigations of the temperature and velocity evolution of a pure near-critical fluid confined in microchannels. The fluid is subjected to two sides heating after it reached isothermal steady state. We focus on the abnormal behaviors of the near-critical fluid in response to the sudden imposed heat flux. New thermal-mechanical effects dominated by fluid instability originating from the boundary and local equilibrium process are reported. Near the microchannel boundaries, the instability grows very quickly and an unexpected vortex formation mode is identified when near-critical thermal-mechanical effect is interacting with the microchannel shear flow. The mechanism of the new kind of Kelvin-Helmholtz instability induced by boundary expansion and density stratification processes is also discussed in detail. This mechanism may bring about innovations in the field of microengineering.

  1. Association of SSTR2 Polymorphisms and Glucose Homeostasis Phenotypes

    PubMed Central

    Sutton, Beth S.; Palmer, Nicholette D.; Langefeld, Carl D.; Xue, Bingzhong; Proctor, Alexandria; Ziegler, Julie T.; Haffner, Steven M.; Norris, Jill M.; Bowden, Donald W.

    2009-01-01

    OBJECTIVE This study evaluated the influence of somatostatin receptor type 2 (SSTR2) polymorphisms on measures of glucose homeostasis in the Insulin Resistance Atherosclerosis Family Study (IRASFS). SSTR2 is a G-protein–coupled receptor that, in response to somatostatin, mediates inhibition of insulin, glucagon, and growth hormone release and thus may affect glucose homeostasis. RESEARCH DESIGN AND METHODS Ten single nucleotide polymorphisms (SNPs) spanning the gene were chosen using a SNP density selection algorithm and genotyped on 1,425 Hispanic-American individuals from 90 families in the IRASFS. These families comprised two samples (set 1 and set 2), which were analyzed individually and as a combined set. Single SNP tests of association were performed for four glucose homeostasis measures—insulin sensitivity (SI), acute insulin response (AIR), disposition index (DI), and fasting blood glucose (FBG)—using generalized estimating equations. RESULTS The SSTR2 locus was encompassed by a single linkage disequilibrium (LD) block (D′ = 0.91–1.00; r2 = 0.09–0.97) that contained four of the ten SNPs evaluated. Within the SSTR2-containing LD block, evidence of association was observed in each of the two sets and in a combined analysis with decreased SI(βhomozygous = −0.16; Pmeta-analysis = 0.0024–0.0030), decreased DI (βhomozygous = −0.35 to −5.16; Pmeta-analysis = 0.0075–0.027), and increased FBG (βhomozygous = 2.30; Pmeta-analysis = 0.045). SNPs outside the SSTR2-containing LD block were not associated with measures of glucose homeostasis. CONCLUSIONS We observed evidence for association of SSTR2 polymorphisms with measures of glucose homeostasis. Thus, variants in SSTR2 may influence pathways of SIto modulate glucose homeostasis. PMID:19324939

  2. The Interplay between Feedback and Buffering in Cellular Homeostasis.

    PubMed

    Hancock, Edward J; Ang, Jordan; Papachristodoulou, Antonis; Stan, Guy-Bart

    2017-11-22

    Buffering, the use of reservoirs of molecules to maintain concentrations of key molecular species, and negative feedback are the primary known mechanisms for robust homeostatic regulation. To our knowledge, however, the fundamental principles behind their combined effect have not been elucidated. Here, we study the interplay between buffering and negative feedback in the context of cellular homeostasis. We show that negative feedback counteracts slow-changing disturbances, whereas buffering counteracts fast-changing disturbances. Furthermore, feedback and buffering have limitations that create trade-offs for regulation: instability in the case of feedback and molecular noise in the case of buffering. However, because buffering stabilizes feedback and feedback attenuates noise from slower-acting buffering, their combined effect on homeostasis can be synergistic. These effects can be explained within a traditional control theory framework and are consistent with experimental observations of both ATP homeostasis and pH regulation in vivo. These principles are critical for studying robustness and homeostasis in biology and biotechnology. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Impact of intermittent fasting on glucose homeostasis.

    PubMed

    Varady, Krista A

    2016-07-01

    This article provides an overview of the most recent human trials that have examined the impact of intermittent fasting on glucose homeostasis. Our literature search retrieved one human trial of alternate day fasting, and three trials of Ramadan fasting published in the past 12 months. Current evidence suggests that 8 weeks of alternate day fasting that produces mild weight loss (4% from baseline) has no effect on glucose homeostasis. As for Ramadan fasting, decreases in fasting glucose, insulin, and insulin resistance have been noted after 4 weeks in healthy normal weight individuals with mild weight loss (1-2% from baseline). However, Ramadan fasting may have little impact on glucoregulatory parameters in women with polycystic ovarian syndrome who failed to observe weight loss. Whether intermittent fasting is an effective means of regulating glucose homeostasis remains unclear because of the scarcity of studies in this area. Large-scale, longer-term randomized controlled trials will be required before the use of fasting can be recommended for the prevention and treatment of metabolic diseases.

  4. Oxidative Stress and Autophagy in Cardiovascular Homeostasis

    PubMed Central

    Morales, Cyndi R.; Pedrozo, Zully; Lavandero, Sergio

    2014-01-01

    Abstract Significance: Autophagy is an evolutionarily ancient process of intracellular protein and organelle recycling required to maintain cellular homeostasis in the face of a wide variety of stresses. Dysregulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to oxidative damage. Both autophagy and ROS/RNS serve pathological or adaptive roles within cardiomyocytes, depending on the context. Recent Advances: ROS/RNS and autophagy communicate with each other via both transcriptional and post-translational events. This cross talk, in turn, regulates the structural integrity of cardiomyocytes, promotes proteostasis, and reduces inflammation, events critical to disease pathogenesis. Critical Issues: Dysregulation of either autophagy or redox state has been implicated in many cardiovascular diseases. Cardiomyocytes are rich in mitochondria, which make them particularly sensitive to oxidative damage. Maintenance of mitochondrial homeostasis and elimination of defective mitochondria are each critical to the maintenance of redox homeostasis. Future Directions: The complex interplay between autophagy and oxidative stress underlies a wide range of physiological and pathological events and its elucidation holds promise of potential clinical applicability. Antioxid. Redox Signal. 20, 507–518. PMID:23641894

  5. Genetics of hereditary disorders of magnesium homeostasis.

    PubMed

    Schlingmann, Karl P; Konrad, Martin; Seyberth, Hannsjörg W

    2004-01-01

    Magnesium plays an essential role in many biochemical and physiological processes. Homeostasis of magnesium is tightly regulated and depends on the balance between intestinal absorption and renal excretion. During the last decades, various hereditary disorders of magnesium handling have been clinically characterized and genetic studies in affected individuals have led to the identification of some molecular components of cellular magnesium transport. In addition to these hereditary forms of magnesium deficiency, recent studies have revealed a high prevalence of latent hypomagnesemia in the general population. This finding is of special interest in view of the association between hypomagnesemia and common chronic diseases such as diabetes, coronary heart disease, hypertension, and asthma. However, valuable methods for the diagnosis of body and tissue magnesium deficiency are still lacking. This review focuses on clinical and genetic aspects of hereditary disorders of magnesium homeostasis. We will review primary defects of epithelial magnesium transport, disorders associated with defects in Ca(2+)/ Mg(2+) sensing, as well as diseases characterized by renal salt wasting and hypokalemic alkalosis, with special emphasis on disturbed magnesium homeostasis.

  6. Meiotic abnormalities

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  7. Molecular cytogenetic studies in structural abnormalities of chromosome 13

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lozzio, C.B.; Bamberger, E.; Anderson, I.

    1994-09-01

    A partial trisomy 13 was detected prenatally in an amniocentesis performed due to the following ultrasound abnormalities: open sacral neural tube defect (NTD), a flattened cerebellum, and lumbar/thoracic hemivertebrae. Elevated AFP and positive acetylcholinesterase in amniotic fluid confirmed the open NTD. Chromosome analysis showed an extra acrocentric chromosome marker. FISH analysis with the painting probe 13 showed that most of the marker was derived from this chromosome. Chromosomes on the parents revealed that the mother had a balanced reciprocal translocation t(2;13)(q23;q21). Dual labeling with painting chromosomes 2 and 13 on cells from the mother and from the amniotic fluid identifiedmore » the marker as a der(13)t(2;13)(p23;q21). Thus, the fetus had a partial trisomy 13 and a small partial trisomy 2p. The maternal grandfather was found to be a carrier for this translocation. Fetal demise occurred a 29 weeks of gestation. The fetus had open lumbar NTD and showed dysmorphic features, overlapping fingers and imperforate anus. This woman had a subsequent pregnancy and chorionic villi sample showed that this fetus was normal. Another case with an abnormal chromosome 13 was a newborn with partial monosomy 13 due to the presence of a ring chromosome 13. This infant had severe intrauterine growth retardation, oligohydramnios, dysmorphic features and multiple congenital microphthalmia, congenital heart disease, absent thumbs and toes and cervical vertebral anomalies. Chromosome studies in blood and skin fibroblast cultures showed that one chromosome 3 was replaced by a ring chromosome of various sizes. This ring was confirmed to be derived from chromosome 13 using the centromeric 21/13 probe.« less

  8. Fluid-Structure Interactions of the Mitral Valve and Left Heart: Comprehensive Strategies, Past, Present and Future

    PubMed Central

    Einstein, Daniel R.; Del Pin, Facundo; Jiao, Xiangmin; Kuprat, Andrew P.; Carson, James P.; Kunzelman, Karyn S.; Cochran, Richard P.; Guccione, Julius M.; Ratcliffe, Mark B.

    2009-01-01

    SUMMARY The remodeling that occurs after a posterolateral myocardial infarction can alter mitral valve function by creating conformational abnormalities in the mitral annulus and in the posteromedial papillary muscle, leading to mitral regurgitation (MR). It is generally assumed that this remodeling is caused by a volume load and is mediated by an increase in diastolic wall stress. Thus, mitral regurgitation can be both the cause and effect of an abnormal cardiac stress environment. Computational modeling of ischemic MR and its surgical correction is attractive because it enables an examination of whether a given intervention addresses the correction of regurgitation (fluid-flow) at the cost of abnormal tissue stress. This is significant because the negative effects of an increased wall stress due to the intervention will only be evident over time. However, a meaningful fluid-structure interaction model of the left heart is not trivial; it requires a careful characterization of the in-vivo cardiac geometry, tissue parameterization though inverse analysis, a robust coupled solver that handles collapsing Lagrangian interfaces, automatic grid-generation algorithms that are capable of accurately discretizing the cardiac geometry, innovations in image analysis, competent and efficient constitutive models and an understanding of the spatial organization of tissue microstructure. In this manuscript, we profile our work toward a comprehensive fluid-structure interaction model of the left heart by reviewing our early work, presenting our current work and laying out our future work in four broad categories: data collection, geometry, fluid-structure interaction and validation. PMID:20454531

  9. Bicuspid aortic valve hemodynamics: a fluid-structure interaction study

    NASA Astrophysics Data System (ADS)

    Chandra, Santanu; Seaman, Clara; Sucosky, Philippe

    2011-11-01

    The bicuspid aortic valve (BAV) is a congenital defect in which the aortic valve forms with two leaflets instead of three. While calcific aortic valve disease (CAVD) also develops in the normal tricuspid aortic valve (TAV), its progression in the BAV is more rapid. Although studies have suggested a mechano-potential root for the disease, the native BAV hemodynamics remains largely unknown. This study aimed at characterizing BAV hemodynamics and quantifying the degree of wall-shear stress (WSS) abnormality on BAV leaflets. Fluid-structure interaction models validated with particle-image velocimetry were designed to predict the flow and leaflet dynamics in idealized TAV and BAV anatomies. Valvular function was quantified in terms of the effective orifice area. The regional leaflet WSS was characterized in terms of oscillatory shear index, temporal shear magnitude and temporal shear gradient. The predictions indicate the intrinsic degree of stenosis of the BAV anatomy, reveal drastic differences in shear stress magnitude and pulsatility on BAV and TAV leaflets and confirm the side- and site-specificity of the leaflet WSS. Given the ability of abnormal fluid shear stress to trigger valvular inflammation, these results support the existence of a mechano-etiology of CAVD in the BAV.

  10. Neuronal control of energy homeostasis

    PubMed Central

    Gao, Qian; Horvath, Tamas L.

    2013-01-01

    Neuronal control of body energy homeostasis is the key mechanism by which animals and humans regulate their long-term energy balance. Various hypothalamic neuronal circuits (which include the hypothalamic melanocortin, midbrain dopamine reward and caudal brainstem autonomic feeding systems) control energy intake and expenditure to maintain body weight within a narrow range for long periods of a life span. Numerous peripheral metabolic hormones and nutrients target these structures providing feedback signals that modify the default “settings” of neuronal activity to accomplish this balance. A number of molecular genetic tools for manipulating individual components of brain energy homeostatic machineries, in combination with anatomical, electrophysiological, pharmacological and behavioral techniques, have been developed, which provide a means for elucidating the complex molecular and cellular mechanisms of feeding behavior and metabolism. This review will highlight some of these advancements and focus on the neuronal circuitries of energy homeostasis. PMID:18061579

  11. Tumour necrosis factor-alpha expression by activated monocytes and altered T-cell homeostasis in ascitic alcoholic cirrhosis: amelioration with norfloxacin.

    PubMed

    Albillos, Agustín; Hera Ad, Antonio de la; Reyes, Eduardo; Monserrat, Jorge; Muñoz, Leticia; Nieto, Mónica; Prieto, Alfredo; Sanz, Eva; Alvarez-Mon, Melchor

    2004-04-01

    To investigate the distribution and activation state of circulating monocytes and T-cell subsets, their contribution to tumour necrosis factor-alpha (TNFalpha) production, and their potential relationship with bacterial products of enteric origin in alcoholic cirrhosis. Peripheral blood monocytes and T-lymphocytes from 60 cirrhotic patients and 24 controls were characterized by four-color flow-cytometry after labelling of differentiation antigens and cytokines, before and after a 4-week course of norfloxacin or placebo. Monocytes from ascitic patients showed increased number, enhanced CD80 and HLA-DR surface levels, and spontaneous intracytoplasmic TNFalpha expression, when compared to non-ascitic patients and controls. Blood TNFalpha levels directly correlated with the amount of TNFalpha expressed by monocytes. In ascitic patients, there was a collapse of virgin CD4(+) and CD8(+) T-cell subsets; and, an expansion of activated CD4(+) T-cells. The above abnormalities were mainly restricted to ascitic patients with high serum levels of lypolysaccharide-binding-protein. Norfloxacin normalized the number of monocytes, reduced their activated phenotype and ability to produce TNFalpha and improved the abnormal T-cell homeostasis. In ascitic cirrhosis with high lipolysaccharide-binding-protein, monocytes are spontaneously activated to produce TNFalpha and are major contributors to the elevated serum TNFalpha. The T-cell compartment is profoundly depleted. Enteric bacterial products play a relevant role in these immune cellular abnormalities.

  12. Abnormal branching and regression of the notochord and its relationship to foregut abnormalities.

    PubMed

    Vleesch Dubois, V N; Quan Qi, B; Beasley, S W; Williams, A

    2002-04-01

    An abnormally positioned notochord has been reported in embryos that develop foregut abnormalities, vertebral defects and other abnormalities of the VATER association. This study examines the patterns of regression of the abnormal notochord in the rat model of the VATER association and investigates the relationship between developmental abnormalities of the notochord and those of the vertebra and foregut. Timed-pregnant Sprague-Dawley rats were given daily intraperitoneal injections of 1.75 mg/kg adriamycin on gestational days 6 - 9 inclusive. Rats were sacrificed between days 14 and 20 and their embryos harvested, histologically sectioned and stained and examined serially. The location and appearance of the degenerating notochord and its relationship to regional structural defects were analysed. All 26 embryos exposed to adriamycin developed foregut abnormalities and had an abnormal notochord. The notochord disappeared by a process of apoptotic degeneration that lagged behind that of the normal embryo: the notochord persisted in the abnormal embryo beyond day 17, whereas in the normal rat it had already disappeared. Similarly, formation of the nucleus pulposus was delayed. Vertebral abnormalities occurred when the notochord was ventrally-positioned. The notochord disappears during day 16 in the normal embryo whereas abnormal branches of the notochord persist until day 19 in the adriamycin-treated embryo. Degeneration of the notochord is dominated by apoptosis. An excessively ventrally-placed notochord is closely associated with abnormalities of the vertebral column, especially hemivertebrae.

  13. Disruption of the mouse Jhy gene causes abnormal ciliary microtubule patterning and juvenile hydrocephalus

    PubMed Central

    Appelbe, Oliver K.; Bollman, Bryan; Attarwala, Ali; Triebes, Lindy A.; Muniz-Talavera, Hilmarie; Curry, Daniel J.; Schmidt, Jennifer V.

    2013-01-01

    SUMMARY Congenital hydrocephalus, the accumulation of excess cerebrospinal fluid (CSF) in the ventricles of the brain, affects one of every 1,000 children born today, making it one of the most common human developmental disorders. Genetic causes of hydrocephalus are poorly understood in humans, but animal models suggest a broad genetic program underlying the regulation of CSF balance. In this study, the random integration of a transgene into the mouse genome led to the development of an early onset and rapidly progressive hydrocephalus. Juvenile hydrocephalus transgenic mice (JhylacZ) inherit communicating hydrocephalus in an autosomal recessive fashion with dilation of the lateral ventricles observed as early as postnatal day 1.5. Ventricular dilation increases in severity over time, becoming fatal at 4-8 weeks of age. The ependymal cilia lining the lateral ventricles are morphologically abnormal and reduced in number in JhylacZ/lacZ brains, and ultrastructural analysis revealed disorganization of the expected 9+2 microtubule pattern. Rather, the majority of JhylacZ/lacZ cilia develop axonemes with 9+0 or 8+2 microtubule structures. Disruption of an unstudied gene, 4931429I11Rik (now named Jhy) appears to underlie the hydrocephalus of JhylacZ/lacZ mice, and the Jhy transcript and protein are decreased in JhylacZ/lacZ mice. Partial phenotypic rescue was achieved in JhylacZ/lacZ mice by the introduction of a bacterial artificial chromosome (BAC) carrying 60-70% of the JHY protein coding sequence. Jhy is evolutionarily conserved from humans to basal vertebrates, but the predicted JHY protein lacks identifiable functional domains. Ongoing studies are directed at uncovering the physiological function of JHY and its role in CSF homeostasis. PMID:23906841

  14. Neutrophils in Homeostasis, Immunity, and Cancer.

    PubMed

    Nicolás-Ávila, José Ángel; Adrover, José M; Hidalgo, Andrés

    2017-01-17

    Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation. These properties are revealing unanticipated roles for neutrophils in supporting homeostasis, as well as complex disease states such as cancer. We focus this review on these emerging functions in order to define the true roles of neutrophils in homeostasis, immunity, and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Thiol/disulfide homeostasis in asphalt workers.

    PubMed

    Yilmaz, Ömer Hınç; Bal, Ceylan; Neşelioglu, Salim; Büyükşekerci, Murat; Gündüzöz, Meşide; Eren, Funda; Tutkun, Lutfiye; Yilmaz, Fatma Meric

    2016-09-02

    The aim of this study was to investigate thiol/disulfide homeostasis in asphalt workers who are exposed to polycyclic aromatic hydrocarbons occupationally. The study was carried out in 34 nonsmoker asphalt workers. Additionally, 35 healthy nonsmoker volunteers were recruited as control group. Thiol and disulfide concentrations were determined using the novel automated measurement method. Levels of urinary 1-OH-pyrene were analyzed by liquid chromatography. Disulfide/thiol ratio was significantly higher in exposed group (p = .034). Also, a positive correlation was detected between disulfide/thiol ratio and 1-OH-pyrene values (r = .249, p = .036). Thiol/disulfide homeostasis was found to be disturbed in asphalt workers. The novel test used in this study may be useful for evaluating the oxidative status in polycyclic aromatic hydrocarbon (PAH) exposure.

  16. Sleep duration and sleep quality are associated differently with alterations of glucose homeostasis.

    PubMed

    Byberg, S; Hansen, A-L S; Christensen, D L; Vistisen, D; Aadahl, M; Linneberg, A; Witte, D R

    2012-09-01

    Studies suggest that inadequate sleep duration and poor sleep quality increase the risk of impaired glucose regulation and diabetes. However, associations with specific markers of glucose homeostasis are less well explained. The objective of this study was to explore possible associations of sleep duration and sleep quality with markers of glucose homeostasis and glucose tolerance status in a healthy population-based study sample. The study comprised 771 participants from the Danish, population-based cross-sectional 'Health2008' study. Sleep duration and sleep quality were measured by self-report. Markers of glucose homeostasis were derived from a 3-point oral glucose tolerance test and included fasting plasma glucose, 2-h plasma glucose, HbA(1c), two measures of insulin sensitivity (the insulin sensitivity index(0,120) and homeostasis model assessment of insulin sensitivity), the homeostasis model assessment of β-cell function and glucose tolerance status. Associations of sleep duration and sleep quality with markers of glucose homeostasis and tolerance were analysed by multiple linear and logistic regression. A 1-h increment in sleep duration was associated with a 0.3 mmol/mol (0.3%) decrement in HbA(1c) and a 25% reduction in the risk of having impaired glucose regulation. Further, a 1-point increment in sleep quality was associated with a 2% increase in both the insulin sensitivity index(0,120) and homeostasis model assessment of insulin sensitivity, as well as a 1% decrease in homeostasis model assessment of β-cell function. In the present study, shorter sleep duration was mainly associated with later alterations in glucose homeostasis, whereas poorer sleep quality was mainly associated with earlier alterations in glucose homeostasis. Thus, adopting healthy sleep habits may benefit glucose metabolism in healthy populations. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  17. Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis

    PubMed Central

    2017-01-01

    Protein-depleted states generate allosteric inhibition of liver cystathionine β-synthase (CBS), which governs the first enzymatic step of the transsulfuration cascade, resulting in upstream accretion of homocysteine (Hcy) in body fluids. A similar Hcy increase may arise from normal hepatocytes undergoing experimentally-induced impairment of betaine-homocysteine methyltransferase (BHTM) activity or from components of lean body mass (LBM) submitted to any inflammatory disorder. LBM comprises a composite agglomeration of extrarenal tissues characterized by naturally occurring BHTM inactivity. As a result of cellular injury, LBM releases high concentrations of Hcy into the extracellular space, contrasting with the disruption of normal remethylation pathways. Hyperhomocysteinemia acts as a biomarker, reflecting the severity of insult and operating as an alarm signal. Elevated Hcy levels constitute a precursor pool recognized by a CBS coding region that reacts to meet increased methionine requirements in LBM tissues, using its enhanced production in hepatocytes. Preservation of methionine homeostasis benefits from its high metabolic priority and survival value. PMID:28930162

  18. Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis.

    PubMed

    Ingenbleek, Yves

    2017-09-20

    Protein-depleted states generate allosteric inhibition of liver cystathionine β-synthase (CBS), which governs the first enzymatic step of the transsulfuration cascade, resulting in upstream accretion of homocysteine (Hcy) in body fluids. A similar Hcy increase may arise from normal hepatocytes undergoing experimentally-induced impairment of betaine-homocysteine methyltransferase (BHTM) activity or from components of lean body mass (LBM) submitted to any inflammatory disorder. LBM comprises a composite agglomeration of extrarenal tissues characterized by naturally occurring BHTM inactivity. As a result of cellular injury, LBM releases high concentrations of Hcy into the extracellular space, contrasting with the disruption of normal remethylation pathways. Hyperhomocysteinemia acts as a biomarker, reflecting the severity of insult and operating as an alarm signal. Elevated Hcy levels constitute a precursor pool recognized by a CBS coding region that reacts to meet increased methionine requirements in LBM tissues, using its enhanced production in hepatocytes. Preservation of methionine homeostasis benefits from its high metabolic priority and survival value.

  19. Feline chronic renal failure: calcium homeostasis in 80 cases diagnosed between 1992 and 1995.

    PubMed

    Barber, P J; Elliott, J

    1998-03-01

    Eighty cats with chronic renal failure (CRF) were evaluated in a prospective study to investigate the prevalence and aetiopathogenesis of renal secondary hyperparathyroidism (RHPTH), using routine plasma biochemistry and assays of parathyroid hormone (PTH), blood ionised calcium and 1,25 dihydroxycholecalciferol (1,25[OH]2D3). Hyperparathyroidism was a frequent sequela of CRF, affecting 84 per cent of cats with CRF, the severity and prevalence of RHPTH increasing with the degree of renal dysfunction. Compared with an age-matched control population, plasma concentrations of phosphate and PTH were significantly higher and 1,25(OH)2D3 concentrations were significantly lower in the two groups of cats presenting with clinical signs of CRF. Significant ionised hypocalcaemia was present only in cats with end-stage renal failure. However, a number of cats were hyperparathyroid in the absence of abnormalities in the parameters of calcium homeostasis measured in this study. There was a significant correlation between plasma phosphate and PTH concentrations.

  20. Thiol/disulfide homeostasis in patients with ankylosing spondylitis

    PubMed Central

    Dogru, Atalay; Balkarli, Ayse; Cetin, Gozde Yildirim; Neselioglu, Salim; Erel, Ozcan; Tunc, Sevket Ercan; Sahin, Mehmet

    2016-01-01

    Ankylosing spondylitis (AS) is a chronic inflammatory disease. In many inflammatory diseases, increased production of pro-inflammatory cytokines is associated with an increase in oxidative stress mediators. Thiol/disulfide homeostasis is a marker for oxidative stress. The aim of this study was to examine the dynamic thiol/disulfide homeostasis in AS. Sixty-nine patients with AS and 60 age- and sex-matched controls were included in the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and visual analogue scale (VAS) were used to determine the disease activity. Native thiol, total thiol, and disulfide levels were measured with a novel automated method recently described by Erel and Neselioglu. The aforementioned method is also optionally manual spectrophotometric assay. The total thiol levels were significantly lower in the AS group compared with the control group (p = 0.03). When the patients were divided into active (n = 35) and inactive (n = 34) subgroups using BASDAI scores, the native plasma thiol and total thiol levels were significantly lower in the active AS patients compared to the inactive AS patients (p = 0.02, p = 0.03 respectively). There was a negative correlation between the plasma native thiol levels and VAS, BASDAI scores. Thiol/disulfide homeostasis may be used for elucidating the effects of oxidative stress in AS. Understanding the role of thiol/disulfide homeostasis in AS might provide new therapeutic intervention strategies for patients. PMID:27186972

  1. Prenatal diagnosis of brain abnormalities in Wolf-Hirschhorn (4p-) syndrome.

    PubMed

    De Keersmaecker, B; Albert, M; Hillion, Y; Ville, Y

    2002-05-01

    Although there have been occasional reports of prenatal diagnosis of this syndrome, most cases are diagnosed postnatally. The objective was to evaluate the presence of brain abnormalities in the prenatal diagnosis of Wolf-Hirschhorn syndrome. Prenatal ultrasound and MRI examination of the fetal brain were performed in a case of Wolf-Hirschhorn syndrome. A comprehensive review of Wolf-Hirschhorn syndrome reported between 1960 and 2000 in the literature was carried out. The late diagnosis of a growth-retarded fetus with normal amniotic fluid volume, normal Doppler and negative infection screen calls for a detailed examination of the fetal brain and heart. Multifocal white matter lesions and periventricular cystic changes, which are often attributed to perinatal distress, are possible prenatal features causing suspicion of 4p- syndrome in an IUGR fetus. Subtle abnormalities on ultrasound may suggest a chromosomal problem. Standard cytogenetics cannot always demonstrate a microdeletion. High-resolution banding and molecular analysis can help to confirm the diagnosis. Copyright 2002 John Wiley & Sons, Ltd.

  2. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult

    PubMed Central

    Carreira, Vinicius S.; Fan, Yunxia; Kurita, Hisaka; Wang, Qin; Ko, Chia-I; Naticchioni, Mindi; Jiang, Min; Koch, Sheryl; Zhang, Xiang; Biesiada, Jacek; Medvedovic, Mario; Xia, Ying; Rubinstein, Jack; Puga, Alvaro

    2015-01-01

    The Developmental Origins of Health and Disease (DOHaD) Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr -/- and in utero TCDD-exposed Ahr +/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr -/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease. PMID:26555816

  3. Cortical firing and sleep homeostasis.

    PubMed

    Vyazovskiy, Vladyslav V; Olcese, Umberto; Lazimy, Yaniv M; Faraguna, Ugo; Esser, Steve K; Williams, Justin C; Cirelli, Chiara; Tononi, Giulio

    2009-09-24

    The need to sleep grows with the duration of wakefulness and dissipates with time spent asleep, a process called sleep homeostasis. What are the consequences of staying awake on brain cells, and why is sleep needed? Surprisingly, we do not know whether the firing of cortical neurons is affected by how long an animal has been awake or asleep. Here, we found that after sustained wakefulness cortical neurons fire at higher frequencies in all behavioral states. During early NREM sleep after sustained wakefulness, periods of population activity (ON) are short, frequent, and associated with synchronous firing, while periods of neuronal silence are long and frequent. After sustained sleep, firing rates and synchrony decrease, while the duration of ON periods increases. Changes in firing patterns in NREM sleep correlate with changes in slow-wave activity, a marker of sleep homeostasis. Thus, the systematic increase of firing during wakefulness is counterbalanced by staying asleep.

  4. Cerebrospinal Fluid Mechanics and Its Coupling to Cerebrovascular Dynamics

    NASA Astrophysics Data System (ADS)

    Linninger, Andreas A.; Tangen, Kevin; Hsu, Chih-Yang; Frim, David

    2016-01-01

    Cerebrospinal fluid (CSF) is not stagnant but displays fascinating oscillatory flow patterns inside the ventricular system and reversing fluid exchange between the cranial vault and spinal compartment. This review provides an overview of the current knowledge of pulsatile CSF motion. Observations contradicting classical views about its bulk production and clearance are highlighted. A clinical account of diseases of abnormal CSF flow dynamics, including hydrocephalus, syringomyelia, Chiari malformation type 1, and pseudotumor cerebri, is also given. We survey medical imaging modalities used to observe intracranial dynamics in vivo. Additionally, we assess the state of the art in predictive models of CSF dynamics. The discussion addresses open questions regarding CSF dynamics as they relate to the understanding and management of diseases.

  5. Genetically determined schizophrenia is not associated with impaired glucose homeostasis.

    PubMed

    Polimanti, Renato; Gelernter, Joel; Stein, Dan J

    2018-05-01

    Here, we used data from large genome-wide association studies to test the presence of causal relationships, conducting a Mendelian randomization analysis; and shared molecular mechanisms, calculating the genetic correlation, among schizophrenia, type 2 diabetes (T2D), and impaired glucose homeostasis. Although our Mendelian randomization analysis was well-powered, no causal relationship was observed between schizophrenia and T2D, or traits related to glucose impaired homeostasis. Similarly, we did not observe any global genetic overlap among these traits. These findings indicate that there is no causal relationships or shared mechanisms between schizophrenia and impaired glucose homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Ketoacidosis due to a Low-carbohydrate Diet in an Elderly Woman with Dementia and Abnormal Eating Behavior

    PubMed Central

    Iwata, Hitoshi; Tsuzuki, Seiichiro; Iwata, Mitsunaga; Terasawa, Teruhiko

    2017-01-01

    Strict restriction of carbohydrates can induce symptomatic ketoacidosis. We herein report a 76-year-old demented woman who developed ketoacidosis after 1 month of abnormal eating behavior involving selectively eating hamburger steak (estimated carbohydrate =12.7 g/day). Laboratory tests showed high-anion-gap metabolic acidosis with elevated blood ketone levels. She was successfully treated with intravenous fluids followed by oral intake of a regular diet. She remained relapse-free after correcting her eating habits. Healthcare providers should know that abnormal eating behavior in demented people can lead to an extremely-low-carbohydrate diet and cause atypical ketoacidosis unexplained by diabetes, heavy alcohol intake, or starvation conditions. PMID:28883241

  7. Ketoacidosis due to a Low-carbohydrate Diet in an Elderly Woman with Dementia and Abnormal Eating Behavior.

    PubMed

    Iwata, Hitoshi; Tsuzuki, Seiichiro; Iwata, Mitsunaga; Terasawa, Teruhiko

    2017-10-01

    Strict restriction of carbohydrates can induce symptomatic ketoacidosis. We herein report a 76-year-old demented woman who developed ketoacidosis after 1 month of abnormal eating behavior involving selectively eating hamburger steak (estimated carbohydrate =12.7 g/day). Laboratory tests showed high-anion-gap metabolic acidosis with elevated blood ketone levels. She was successfully treated with intravenous fluids followed by oral intake of a regular diet. She remained relapse-free after correcting her eating habits. Healthcare providers should know that abnormal eating behavior in demented people can lead to an extremely-low-carbohydrate diet and cause atypical ketoacidosis unexplained by diabetes, heavy alcohol intake, or starvation conditions.

  8. [The glymphatic system: concept, function and research progresses].

    PubMed

    Wang, Lin-Hui; Wang, Zi-Lan; Chen, Wen-Yue; Chen, Ming-Jia; Xu, Guang-Yin

    2018-02-25

    The glymphatic system is a cerebrospinal fluid-interstitial fluid exchange system dependent on the water channel aquaporin-4 polarized on astrocyte endfeet, which is proposed to account for the clearance of abnormal proteins (e.g. β-amyloid) and metabolites (e.g. lactate) from the brain. Accumulating studies have revealed that glymphatic activity during sleep and general anesthesia is dramatically enhanced, while its function is significantly damaged during aging, traumatic brain injury, Alzheimer's disease, stroke, and diabetes. The glymphatic hypothesis is a breakthrough in the field of neuroscience recently, which would considerably enhance our comprehension on the cerebrospinal fluid circulation and its role in the maintenance of brain homeostasis. In this review, we briefly introduced the conceptualization of glymphatic system, summarized the recent progresses, and prospected its future investigation and potential clinical application.

  9. Neuronal and molecular mechanisms of sleep homeostasis.

    PubMed

    Donlea, Jeffrey M

    2017-12-01

    Sleep is necessary for survival, and prolonged waking causes a homeostatic increase in the need for recovery sleep. Homeostasis is a core component of sleep regulation and has been tightly conserved across evolution from invertebrates to man. Homeostatic sleep regulation was first identified among insects in cockroaches several decades ago, but the characterization of sleep rebound in Drosophila melanogaster opened the use of insect model species to understand homeostatic functions and regulation of sleep. This review describes circuits in two neuropil structures, the central complex and mushroom bodies, that influence sleep homeostasis and neuromodulatory systems that influence the accrual of homeostatic sleep need. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Roles of interstitial fluid pH in diabetes mellitus: Glycolysis and mitochondrial function

    PubMed Central

    Marunaka, Yoshinori

    2015-01-01

    The pH of body fluids is one the most important key factors regulating various cell function such as enzyme activity and protein-protein interaction via modification of its binding affinity. Therefore, to keep cell function normal, the pH of body fluids is maintained constant by various systems. Insulin resistance is one of the most important, serious factors making the body condition worse in diabetes mellitus. I have recently found that the pH of body (interstitial) fluids is lower in diabetes mellitus than that in non-diabetic control, and that the lowered pH is one of the causes producing insulin resistance. In this review article, I introduce importance of body (interstitial) fluid pH in regulation of body function, evidence on abnormal regulation of body fluid pH in diabetes mellitus, and relationship between the body fluid pH and insulin resistance. Further, this review proposes perspective therapies on the basis of regulation of body fluid pH including propolis (honeybee product) diet. PMID:25685283

  11. Antiviral treatment normalizes neurophysiological but not movement abnormalities in simian immunodeficiency virus–infected monkeys

    PubMed Central

    Fox, Howard S.; Weed, Michael R.; Huitron-Resendiz, Salvador; Baig, Jamal; Horn, Thomas F.W.; Dailey, Peter J.; Bischofberger, Norbert; Henriksen, Steven J.

    2000-01-01

    Simian immunodeficiency virus (SIV) infection of rhesus monkeys provides an excellent model of the central nervous system (CNS) consequences of HIV infection. To discern the relationship between viral load and abnormalities induced in the CNS by the virus, we infected animals with SIV and later instituted antiviral treatment to lower peripheral viral load. Measurement of sensory-evoked potentials, assessing CNS neuronal circuitry, revealed delayed latencies after infection that could be reversed by lowering viral load. Cessation of treatment led to the reappearance of these abnormalities. In contrast, the decline in general motor activity induced by SIV infection was unaffected by antiviral treatment. An acute increase in the level of the chemokine monocyte chemoattractant protein-1 (MCP-1) was found in the cerebrospinal fluid (CSF) relative to plasma in the infected animals at the peak of acute viremia, likely contributing to an early influx of immune cells into the CNS. Examination of the brains of the infected animals after return of the electrophysiological abnormalities revealed diverse viral and inflammatory findings. Although some of the physiological abnormalities resulting from SIV infection can be at least temporarily reversed by lowering viral load, the viral-host interactions initiated by infection may result in long-lasting changes in CNS-mediated functions. PMID:10880046

  12. Antiviral treatment normalizes neurophysiological but not movement abnormalities in simian immunodeficiency virus-infected monkeys.

    PubMed

    Fox, H S; Weed, M R; Huitron-Resendiz, S; Baig, J; Horn, T F; Dailey, P J; Bischofberger, N; Henriksen, S J

    2000-07-01

    Simian immunodeficiency virus (SIV) infection of rhesus monkeys provides an excellent model of the central nervous system (CNS) consequences of HIV infection. To discern the relationship between viral load and abnormalities induced in the CNS by the virus, we infected animals with SIV and later instituted antiviral treatment to lower peripheral viral load. Measurement of sensory-evoked potentials, assessing CNS neuronal circuitry, revealed delayed latencies after infection that could be reversed by lowering viral load. Cessation of treatment led to the reappearance of these abnormalities. In contrast, the decline in general motor activity induced by SIV infection was unaffected by antiviral treatment. An acute increase in the level of the chemokine monocyte chemoattractant protein-1 (MCP-1) was found in the cerebrospinal fluid (CSF) relative to plasma in the infected animals at the peak of acute viremia, likely contributing to an early influx of immune cells into the CNS. Examination of the brains of the infected animals after return of the electrophysiological abnormalities revealed diverse viral and inflammatory findings. Although some of the physiological abnormalities resulting from SIV infection can be at least temporarily reversed by lowering viral load, the viral-host interactions initiated by infection may result in long-lasting changes in CNS-mediated functions.

  13. Abnormal Uterine Bleeding FAQ

    MedlinePlus

    ... Abnormal Uterine Bleeding • What is a normal menstrual cycle? • When is bleeding abnormal? • At what ages is ... abnormal bleeding? •Glossary What is a normal menstrual cycle? The normal length of the menstrual cycle is ...

  14. Cardiovascular and Body Fluid Adjustments During Bed Rest and Space Flight

    NASA Technical Reports Server (NTRS)

    Greenleaf, John E.; Tomko, David L. (Technical Monitor)

    1995-01-01

    fainting. Various pre-reentry hyperhydration procedures have been utilized to counteract the GRS. Thus, the somewhat decreased central venous pressure and lack of diuresis early in spaceflight suggests mechanisms other than the Gauer-Henry reflex are more important for maintaining fluid volume homeostasis in astronauts. Inflight hypohydration and hypovolemia are more important for maintaining fluid volume homeostasis in astronauts.

  15. Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect.

    PubMed

    Peca, Donatella; Petrini, Stefania; Tzialla, Chryssoula; Boldrini, Renata; Morini, Francesco; Stronati, Mauro; Carnielli, Virgilio P; Cogo, Paola E; Danhaive, Olivier

    2011-08-25

    Mutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored. We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant. The subject was an infant with severe neonatal respiratory distress syndrome followed by recurrent respiratory failure episodes, hypopituitarism and neurological abnormalities. Lung histology and ultrastructure were assessed by surgical biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing and array chromatine genomic hybridization (aCGH). Surfactant protein expression in lung tissue was analyzed by confocal immunofluorescence microscopy. For kinetics studies, surfactant protein B and disaturated phosphatidylcholine (DSPC) were isolated from serial tracheal aspirates after intravenous administration of stable isotope-labeled (2)H(2)O and (13)C-leucine; fractional synthetic rate was derived from gas chromatography/mass spectrometry (2)H and (13)C enrichment curves. Six intubated infants with no primary lung disease were used as controls. Lung biopsy showed desquamative interstitial pneumonitis and lamellar body abnormalities suggestive of genetic surfactant deficiency. Genetic studies identified a heterozygous ABCA3 mutation, L941P, previously unreported. No SFTPB, SFTPC or NKX2.1 mutations or deletions were found. However, immunofluorescence studies showed TTF-1 prevalently expressed in type II cell cytoplasm instead of nucleus, indicating defective nuclear targeting. This pattern has not been reported in human and was not found in two healthy controls and

  16. Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect

    PubMed Central

    2011-01-01

    Background Mutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1) - critical for lung, thyroid and central nervous system morphogenesis and function - causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored. We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant. Methods The subject was an infant with severe neonatal respiratory distress syndrome followed by recurrent respiratory failure episodes, hypopituitarism and neurological abnormalities. Lung histology and ultrastructure were assessed by surgical biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing and array chromatine genomic hybridization (aCGH). Surfactant protein expression in lung tissue was analyzed by confocal immunofluorescence microscopy. For kinetics studies, surfactant protein B and disaturated phosphatidylcholine (DSPC) were isolated from serial tracheal aspirates after intravenous administration of stable isotope-labeled 2H2O and 13C-leucine; fractional synthetic rate was derived from gas chromatography/mass spectrometry 2H and 13C enrichment curves. Six intubated infants with no primary lung disease were used as controls. Results Lung biopsy showed desquamative interstitial pneumonitis and lamellar body abnormalities suggestive of genetic surfactant deficiency. Genetic studies identified a heterozygous ABCA3 mutation, L941P, previously unreported. No SFTPB, SFTPC or NKX2.1 mutations or deletions were found. However, immunofluorescence studies showed TTF-1 prevalently expressed in type II cell cytoplasm instead of nucleus, indicating defective nuclear targeting. This pattern has not been reported in human and was not found in two

  17. Upper intestinal lipids regulate energy and glucose homeostasis.

    PubMed

    Cheung, Grace W C; Kokorovic, Andrea; Lam, Tony K T

    2009-09-01

    Upon the entry of nutrients into the small intestine, nutrient sensing mechanisms are activated to allow the body to adapt appropriately to the incoming nutrients. To date, mounting evidence points to the existence of an upper intestinal lipid-induced gut-brain neuronal axis to regulate energy homeostasis. Moreover, a recent discovery has also revealed an upper intestinal lipid-induced gut-brain-liver neuronal axis involved in the regulation of glucose homeostasis. In this mini-review, we will focus on the mechanisms underlying the activation of these respective neuronal axes by upper intestinal lipids.

  18. Clarifying the Roles of Homeostasis and Allostasis in Physiological Regulation

    PubMed Central

    Ramsay, Douglas S.; Woods, Stephen C.

    2014-01-01

    Homeostasis, the dominant explanatory framework for physiological regulation, has undergone significant revision in recent years, with contemporary models differing significantly from the original formulation. Allostasis, an alternative view of physiological regulation, goes beyond its homeostatic roots, offering novel insights relevant to our understanding and treatment of several chronic health conditions. Despite growing enthusiasm for allostasis, the concept remains diffuse, due in part to ambiguity as to how the term is understood and used, impeding meaningful translational and clinical research on allostasis. Here we provide a more focused understanding of homeostasis and allostasis by explaining how both play a role in physiological regulation, and a critical analysis of regulation suggests how homeostasis and allostasis can be distinguished. Rather than focusing on changes in the value of a regulated variable (e.g., body temperature, body adiposity, or reward), research investigating the activity and relationship among the multiple regulatory loops that influence the value of these regulated variables may be the key to distinguishing homeostasis and allostasis. The mechanisms underlying physiological regulation and dysregulation are likely to have important implications for health and disease. PMID:24730599

  19. Petri net based model of the body iron homeostasis.

    PubMed

    Formanowicz, Dorota; Sackmann, Andrea; Formanowicz, Piotr; Błazewicz, Jacek

    2007-10-01

    The body iron homeostasis is a not fully understood complex process. Despite the fact that some components of this process have been described in the literature, the complete model of the whole process has not been proposed. In this paper a Petri net based model of the body iron homeostasis is presented. Recently, Petri nets have been used for describing and analyzing various biological processes since they allow modeling the system under consideration very precisely. The main result presented in the paper is twofold, i.e., an informal description of the main part of the whole iron homeostasis process is described, and then it is also formulated in the formal language of Petri net theory. This model allows for a possible simulation of the process, since Petri net theory provides a lot of established analysis techniques.

  20. Role of Caspase-3 Cleaved IP3R1 on Ca2+ Homeostasis and Developmental Competence of Mouse Oocytes and Eggs

    PubMed Central

    Zhang, Nan; Fissore, Rafael. A.

    2014-01-01

    Apoptosis in most cell types is accompanied by altered Ca2+ homeostasis. During apoptosis, caspase-3 mediated cleavage of the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) generates a 95-kDa C-terminal fragment (C-IP3R1), which represents the channel domain of the receptor. Aged mouse eggs display abnormal Ca2+ homeostasis and express C-IP3R1, although whether or not C-IP3R1 expression contributes to Ca2+ misregulation or a decrease in developmental competency is unknown. We sought to answer these questions by injecting in mouse oocytes and eggs cRNAs encoding CIP3R1. We found that: 1) expression of C-IP3R1 in eggs lowered the Ca2+ content of the endoplasmic reticulum (ER), although, as C-IP3R1 is quickly degraded at this stage, its expression did not impair pre-implantation embryo development; 2) expression of CIP3R1 in eggs enhanced fragmentation associated with aging; 3) endogenous IP3R1 is required for aging associated apoptosis, as its down-regulation prevented fragmentation, and expression of C-IP3R1 in eggs with downregulated IP3R1 partly restored fragmentation; 4) C-IP3R1 expression in GV oocytes resulted in persistent levels of protein, which abolished the increase in the ER releasable Ca2+ pool that occurs during maturation, undermined the Ca2+ oscillatory ability of matured eggs and their activation potential. Collectively, this study supports a role for IP3R1 and C-IP3R1 in regulating Ca2+ homeostasis and the ER Ca2+ content during oocyte maturation. Nevertheless, the role of C-IP3R1 on Ca2+ homeostasis in aged eggs seems minor, as in MII eggs the majority of endogenous IP3R1 remains intact and C-IP3R1 undergoes rapid turnover. PMID:24692207

  1. Urine - abnormal color

    MedlinePlus

    ... medlineplus.gov/ency/article/003139.htm Urine - abnormal color To use the sharing features on this page, please enable JavaScript. The usual color of urine is straw-yellow. Abnormally colored urine ...

  2. Air pollution particles and iron homeostasis

    EPA Science Inventory

    Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, fun...

  3. Long-term results after endoscopic drainage and necrosectomy of symptomatic pancreatic fluid collections.

    PubMed

    Seewald, Stefan; Ang, Tiing Leong; Richter, Hugo; Teng, Karl Yu Kim; Zhong, Yan; Groth, Stefan; Omar, Salem; Soehendra, Nib

    2012-01-01

    To determine the immediate and long-term results of endoscopic drainage and necrosectomy for symptomatic pancreatic fluid collections. The data of 80 patients with symptomatic pancreatic fluid collections (mean diameter: 11.7 cm, range 3-20; pseudocysts: 24/80, abscess: 20/80, infected walled-off necrosis: 36/80) referred for endoscopic management from October 1997 to March 2008 were analyzed retrospectively. Endoscopic drainage techniques included endoscopic ultrasound (EUS)-guided aspiration (2/80), EUS-guided transenteric drainage (70/80) and non-EUS-guided drainage across a spontaneous transenteric fistula (8/80). Endoscopic necrosectomy was carried out in 49/80 (abscesses: 14/20; infected necrosis: 35/36). Procedural complications were bleeding (12/80), perforation (7/80), portal air embolism (1/80) and Ogilvie Syndrome (1/80). Initial technical success was achieved in 78/80 (97.5%) and clinical resolution of the collections was achieved endoscopically in 67/80 (83.8%), with surgery required in 13/80 (perforation: four; endoscopically inaccessible areas: two; inadequate drainage: seven). Within 6 months five patients required surgery due to recurrent fluid collections; over a mean follow up of 31 months, surgery was required in four more patients due to recurrent collections as a consequence of underlying pancreatic duct abnormalities that could not be treated endoscopically. The long-term success of endoscopic treatment was 58/80 (72.5%). Endoscopic drainage of symptomatic pancreatic fluid collections is safe and effective, with excellent immediate and long-term results. Endoscopic necrosectomy has a risk of serious complications. The underlying pancreatic duct abnormalities must be addressed to prevent recurrence of fluid collections. © 2011 The Authors. Digestive Endoscopy © 2011 Japan Gastroenterological Endoscopy Society.

  4. The Th17 Lineage: From Barrier Surfaces Homeostasis to Autoimmunity, Cancer, and HIV-1 Pathogenesis.

    PubMed

    Wacleche, Vanessa Sue; Landay, Alan; Routy, Jean-Pierre; Ancuta, Petronela

    2017-10-19

    The T helper 17 (Th17) cells represent a subset of CD4+ T-cells with unique effector functions, developmental plasticity, and stem-cell features. Th17 cells bridge innate and adaptive immunity against fungal and bacterial infections at skin and mucosal barrier surfaces. Although Th17 cells have been extensively studied in the context of autoimmunity, their role in various other pathologies is underexplored and remains an area of open investigation. This review summarizes the history of Th17 cell discovery and the current knowledge relative to the beneficial role of Th17 cells in maintaining mucosal immunity homeostasis. We further discuss the concept of Th17 pathogenicity in the context of autoimmunity, cancer, and HIV infection, and we review the most recent discoveries on molecular mechanisms regulating HIV replication/persistence in pathogenic Th17 cells. Finally, we stress the need for novel fundamental research discovery-based Th17-specific therapeutic interventions to treat pathogenic conditions associated with Th17 abnormalities, including HIV infection.

  5. Essential role of FBXL5-mediated cellular iron homeostasis in maintenance of hematopoietic stem cells

    PubMed Central

    Muto, Yoshiharu; Nishiyama, Masaaki; Nita, Akihiro; Moroishi, Toshiro; Nakayama, Keiichi I.

    2017-01-01

    Hematopoietic stem cells (HSCs) are maintained in a hypoxic niche to limit oxidative stress. Although iron elicits oxidative stress, the importance of iron homeostasis in HSCs has been unknown. Here we show that iron regulation by the F-box protein FBXL5 is required for HSC self-renewal. Conditional deletion of Fbxl5 in mouse HSCs results in cellular iron overload and a reduced cell number. Bone marrow transplantation reveals that FBXL5-deficient HSCs are unable to reconstitute the hematopoietic system of irradiated recipients as a result of stem cell exhaustion. Transcriptomic analysis shows abnormal activation of oxidative stress responses and the cell cycle in FBXL5-deficient mouse HSCs as well as downregulation of FBXL5 expression in HSCs of patients with myelodysplastic syndrome. Suppression of iron regulatory protein 2 (IRP2) accumulation in FBXL5-deficient mouse HSCs restores stem cell function, implicating IRP2 as a potential therapeutic target for human hematopoietic diseases associated with FBXL5 downregulation. PMID:28714470

  6. Does Cigarette Smoking Affect Seminal Fluid Parameters? A Comparative Study

    PubMed Central

    Meri, Zakarya Bani; Irshid, Ibrahim Bani; Migdadi, Mohammad; Irshid, Ayat Bani; Mhanna, Somia A.

    2013-01-01

    Objective To study the effect of cigarette smoking on seminal fluid parameters, namely; volume, sperm concentration, and motility, as well as morphology, leukocyte infiltration, among males complaining of infertility. Methods Between August 2010 and July 2011, seminal fluid analysis was done for 1438 males who are partners of couples who visited the infertility clinic at Prince Rashid Ben Al Hassan Hospital (PRH) for infertility. The men who fit the inclusion criteria (n=960) were classified into two groups: group a (non-smokers; n=564) and group B (smokers; n=396), which represents 41.25% of the study group. Seminal fluid was collected using masturbation after 3-5 days of abstinence then analyzed for volume, sperm count, sperm concentration, motility and morphology. In order to analyze whether the number of cigarettes smoked per day has an effect on the spermatogram; the smoking men were divided into two subgroups: the heavy smokers (n=266) and non-heavy smokers (n=130). Results A total of 960 adult males were enrolled. Their age ranged between 21 and 76 years, 564 were non-smokers with mean age of 36. 45±6.27 (Mean±SD). Three-hundred-and-ninety-six were smokers with a mean age of 34.35±4.25 (Mean±SD). There was a significant effect of smoking on the motility of sperms and the ratios of abnormality (p<0.005). Concentration appeared not to be affected by smoking. Furthermore, the group of heavy smokers were found to have lower sperm concentrations and a higher percentage of abnormal sperms compared to the non-heavy smokers. Conclusion Cigarette smoking has a deleterious effect on some of the seminal fluid parameters (motility, morphology and leukocyte count) which in turn may result in male subfertility. PMID:23386938

  7. Extracellular Potassium Homeostasis: Insights from Hypokalemic Periodic Paralysis

    PubMed Central

    Cheng, Chih-Jen; Kuo, Elizabeth; Huang, Chou-Long

    2014-01-01

    The extracellular potassium makes up only about 2% of the total body potassium store. The majority of the body potassium is distributed in the intracellular space, and of which about 80% is in skeletal muscle. Movement of potassium in and out of skeletal muscle thus plays a pivotal role in extracellular potassium homeostasis. The exchange of potassium between the extracellular space and skeletal muscle is mediated by specific membrane transporters. These include potassium uptake by Na+, K+-ATPase and release by inward rectifier K+ channels. These processes are regulated by circulating hormones, peptides, ions, and by physical activity of muscle as well as dietary potassium intake. Pharmaceutical agents, poisons and disease conditions also affect the exchange and alter extracellular potassium concentration. Here, we review extracellular potassium homeostasis focusing on factors and conditions that influence the balance of potassium movement in skeletal muscle. Recent findings that mutations of a skeletal muscle-specific inward rectifier K+ channel cause hypokalemic periodic paralysis provide interesting insights into the role of skeletal muscle in extracellular potassium homeostasis. These recent findings will be reviewed. PMID:23953801

  8. Notch Signaling Regulates Late-Stage Epidermal Differentiation and Maintains Postnatal Hair Cycle Homeostasis

    PubMed Central

    Lin, Hsien-Yi; Kao, Cheng-Heng; Lin, Kurt Ming-Chao; Kaartinen, Vesa; Yang, Liang-Tung

    2011-01-01

    Background Notch signaling involves ligand-receptor interactions through direct cell-cell contact. Multiple Notch receptors and ligands are expressed in the epidermis and hair follicles during embryonic development and the adult stage. Although Notch signaling plays an important role in regulating differentiation of the epidermis and hair follicles, it remains unclear how Notch signaling participates in late-stage epidermal differentiation and postnatal hair cycle homeostasis. Methodology and Principal Findings We applied Cre/loxP system to generate conditional gene targeted mice that allow inactivation of critical components of Notch signaling pathway in the skin. Rbpj, the core component of all four Notch receptors, and Pofut1, an essential factor for ligand-receptor interactions, were inactivated in hair follicle lineages and suprabasal layer of the epidermis using the Tgfb3-Cre mouse line. Rbpj conditional inactivation resulted in granular parakeratosis and reactive epidermal hyperplasia. Pofut1 conditional inactivation led to ultrastructural abnormalities in the granular layer and altered filaggrin processing in the epidermis, suggesting a perturbation of the granular layer differentiation. Disruption of Pofut1 in hair follicle lineages resulted in aberrant telogen morphology, a decrease of bulge stem cell markers, and a concomitant increase of K14-positive keratinocytes in the isthmus of mutant hair follicles. Pofut1-deficent hair follicles displayed a delay in anagen re-entry and dysregulation of proliferation and apoptosis during the hair cycle transition. Moreover, increased DNA double stand breaks were detected in Pofut1-deficent hair follicles, and real time PCR analyses on bulge keratinocytes isolated by FACS revealed an induction of DNA damage response and a paucity of DNA repair machinery in mutant bulge keratinocytes. Significance our data reveal a role for Notch signaling in regulating late-stage epidermal differentiation. Notch signaling is

  9. TGFβ restores hematopoietic homeostasis after myelosuppressive chemotherapy

    PubMed Central

    Brenet, Fabienne; Kermani, Pouneh; Spektor, Roman; Rafii, Shahin

    2013-01-01

    Myelosuppression is a life-threatening complication of antineoplastic therapy, but treatment is restricted to a few cytokines with unilineage hematopoietic activity. Although hematopoietic stem cells (HSCs) are predominantly quiescent during homeostasis, they are rapidly recruited into cell cycle by stresses, including myelosuppressive chemotherapy. Factors that induce HSCs to proliferate during stress have been characterized, but it is not known how HSC quiescence is then reestablished. In this study, we show that TGFβ signaling is transiently activated in hematopoietic stem and progenitor cells (HSPCs) during hematopoietic regeneration. Blockade of TGFβ signaling after chemotherapy accelerates hematopoietic reconstitution and delays the return of cycling HSCs to quiescence. In contrast, TGFβ blockade during homeostasis fails to induce cycling of HSPCs. We identified the cyclin-dependent kinase inhibitor Cdkn1c (p57) as a key downstream mediator of TGFβ during regeneration because the recovery of chimeric mice, incapable of expressing p57 in HSPCs, phenocopies blockade of TGFβ signaling after chemotherapy. This study demonstrates that context-dependent activation of TGFβ signaling is central to an unrecognized counterregulatory mechanism that promotes homeostasis once hematopoiesis has sufficiently recovered from myelosuppressive chemotherapy. These results open the door to new, potentially superior, approaches to promote multilineage hematopoietic recovery by blocking the TGFβ signaling that dampens regeneration. PMID:23440043

  10. Hypothalamic inflammation and the central nervous system control of energy homeostasis.

    PubMed

    Pimentel, Gustavo D; Ganeshan, Kirthana; Carvalheira, José B C

    2014-11-01

    The control of energy homeostasis relies on robust neuronal circuits that regulate food intake and energy expenditure. Although the physiology of these circuits is well understood, the molecular and cellular response of this program to chronic diseases is still largely unclear. Hypothalamic inflammation has emerged as a major driver of energy homeostasis dysfunction in both obesity and anorexia. Importantly, this inflammation disrupts the action of metabolic signals promoting anabolism or supporting catabolism. In this review, we address the evidence that favors hypothalamic inflammation as a factor that resets energy homeostasis in pathological states. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Anchored phosphatases modulate glucose homeostasis

    PubMed Central

    Hinke, Simon A; Navedo, Manuel F; Ulman, Allison; Whiting, Jennifer L; Nygren, Patrick J; Tian, Geng; Jimenez-Caliani, Antonio J; Langeberg, Lorene K; Cirulli, Vincenzo; Tengholm, Anders; Dell'Acqua, Mark L; Santana, L Fernando; Scott, John D

    2012-01-01

    Endocrine release of insulin principally controls glucose homeostasis. Nutrient-induced exocytosis of insulin granules from pancreatic β-cells involves ion channels and mobilization of Ca2+ and cyclic AMP (cAMP) signalling pathways. Whole-animal physiology, islet studies and live-β-cell imaging approaches reveal that ablation of the kinase/phosphatase anchoring protein AKAP150 impairs insulin secretion in mice. Loss of AKAP150 impacts L-type Ca2+ currents, and attenuates cytoplasmic accumulation of Ca2+ and cAMP in β-cells. Yet surprisingly AKAP150 null animals display improved glucose handling and heightened insulin sensitivity in skeletal muscle. More refined analyses of AKAP150 knock-in mice unable to anchor protein kinase A or protein phosphatase 2B uncover an unexpected observation that tethering of phosphatases to a seven-residue sequence of the anchoring protein is the predominant molecular event underlying these metabolic phenotypes. Thus anchored signalling events that facilitate insulin secretion and glucose homeostasis may be set by AKAP150 associated phosphatase activity. PMID:22940692

  12. Homeostasis, inflammation, and disease susceptibility.

    PubMed

    Kotas, Maya E; Medzhitov, Ruslan

    2015-02-26

    While modernization has dramatically increased lifespan, it has also witnessed the increasing prevalence of diseases such as obesity, hypertension, and type 2 diabetes. Such chronic, acquired diseases result when normal physiologic control goes awry and may thus be viewed as failures of homeostasis. However, while nearly every process in human physiology relies on homeostatic mechanisms for stability, only some have demonstrated vulnerability to dysregulation. Additionally, chronic inflammation is a common accomplice of the diseases of homeostasis, yet the basis for this connection is not fully understood. Here we review the design of homeostatic systems and discuss universal features of control circuits that operate at the cellular, tissue, and organismal levels. We suggest a framework for classification of homeostatic signals that is based on different classes of homeostatic variables they report on. Finally, we discuss how adaptability of homeostatic systems with adjustable set points creates vulnerability to dysregulation and disease. This framework highlights the fundamental parallels between homeostatic and inflammatory control mechanisms and provides a new perspective on the physiological origin of inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Cognitive abnormalities and hippocampal alterations in monoamine oxidase A and B knockout mice

    PubMed Central

    Singh, Chanpreet; Bortolato, Marco; Bali, Namrata; Godar, Sean C.; Scott, Anna L.; Chen, Kevin; Thompson, Richard F.; Shih, Jean C.

    2013-01-01

    The monoamine oxidase isoenzymes (MAOs) A and B play important roles in the homeostasis of monoaminergic neurotransmitters. The combined deficiency of MAO A and B results in significantly elevated levels of serotonin (5-hydroxytryptamine), norepinephrine, dopamine, and β-phenylethylamine; in humans and mice, these neurochemical changes are accompanied by neurodevelopmental perturbations as well as autistic-like responses. Ample evidence indicates that normal levels of monoamines in the hippocampus, amygdala, frontal cortex, and cerebellum are required for the integrity of learning and memory. Thus, in the present study, the cognitive status of MAO A/B knockout (KO) mice was examined with a wide array of behavioral tests. In comparison with male wild-type littermates, MAO A/B KO mice exhibited abnormally high and overgeneralized fear conditioning and enhanced eye-blink conditioning. These alterations were accompanied by significant increases in hippocampal long-term potentiation and alterations in the relative expression of NMDA glutamate receptor subunits. Our data suggest that chronic elevations of monoamines, because of the absence of MAO A and MAO B, cause functional alterations that are accompanied with changes in the cellular mechanisms underlying learning and memory. The characteristics exhibited by MAO A/B KO mice highlight the potential of these animals as a useful tool to provide further insight into the molecular bases of disorders associated with abnormal monoaminergic profiles. PMID:23858446

  14. Cognitive abnormalities and hippocampal alterations in monoamine oxidase A and B knockout mice.

    PubMed

    Singh, Chanpreet; Bortolato, Marco; Bali, Namrata; Godar, Sean C; Scott, Anna L; Chen, Kevin; Thompson, Richard F; Shih, Jean C

    2013-07-30

    The monoamine oxidase isoenzymes (MAOs) A and B play important roles in the homeostasis of monoaminergic neurotransmitters. The combined deficiency of MAO A and B results in significantly elevated levels of serotonin (5-hydroxytryptamine), norepinephrine, dopamine, and β-phenylethylamine; in humans and mice, these neurochemical changes are accompanied by neurodevelopmental perturbations as well as autistic-like responses. Ample evidence indicates that normal levels of monoamines in the hippocampus, amygdala, frontal cortex, and cerebellum are required for the integrity of learning and memory. Thus, in the present study, the cognitive status of MAO A/B knockout (KO) mice was examined with a wide array of behavioral tests. In comparison with male wild-type littermates, MAO A/B KO mice exhibited abnormally high and overgeneralized fear conditioning and enhanced eye-blink conditioning. These alterations were accompanied by significant increases in hippocampal long-term potentiation and alterations in the relative expression of NMDA glutamate receptor subunits. Our data suggest that chronic elevations of monoamines, because of the absence of MAO A and MAO B, cause functional alterations that are accompanied with changes in the cellular mechanisms underlying learning and memory. The characteristics exhibited by MAO A/B KO mice highlight the potential of these animals as a useful tool to provide further insight into the molecular bases of disorders associated with abnormal monoaminergic profiles.

  15. Roles for Hedgehog signaling in adult organ homeostasis and repair

    PubMed Central

    Petrova, Ralitsa; Joyner, Alexandra L.

    2014-01-01

    The hedgehog (HH) pathway is well known for its mitogenic and morphogenic functions during development, and HH signaling continues in discrete populations of cells within many adult mammalian tissues. Growing evidence indicates that HH regulates diverse quiescent stem cell populations, but the exact roles that HH signaling plays in adult organ homeostasis and regeneration remain poorly understood. Here, we review recently identified functions of HH in modulating the behavior of tissue-specific adult stem and progenitor cells during homeostasis, regeneration and disease. We conclude that HH signaling is a key factor in the regulation of adult tissue homeostasis and repair, acting via multiple different routes to regulate distinct cellular outcomes, including maintenance of plasticity, in a context-dependent manner. PMID:25183867

  16. C-reactive protein and homocysteine levels are associated with abnormal heart rate recovery in women with polycystic ovary syndrome.

    PubMed

    Kaya, Cemil; Akgül, Ebru; Pabuccu, Recai

    2010-06-01

    To determine heart rate recovery (HRR) in patients with polycystic ovary syndrome (PCOS) and its relation to C-reactive protein (CRP) and homocysteine (Hcy) levels. Prospective clinical study. University hospital. Sixty-eight women with PCOS and 68 healthy women were included this study. Heart rate recovery was evaluated. We measured serum levels of CRP and Hcy. The presence of insulin resistance was investigated using homeostasis model assesment (HOMA-IR). Heart rate recovery, CRP, Hcy. Heart rate recovery was significantly decreased in women with PCOS compared with control group women. Subjects with abnormal HRR had significantly greater levels of CRP and Hcy. The PCOS patients with HRR in the top tertile compared with the bottom quartile tended to have lower mean CRP and Hcy levels. The HRR was significantly and negatively correlated with age, CRP, Hcy, HOMA-IR, and body mass index. C-reactive protein and Hcy are independent determinants of HRR. The CRP and Hcy levels may affect the development and progression of abnormal HRR in PCOS. Crown Copyright (c) 2010. Published by Elsevier Inc. All rights reserved.

  17. Engineering redox homeostasis to develop efficient alcohol-producing microbial cell factories.

    PubMed

    Zhao, Chunhua; Zhao, Qiuwei; Li, Yin; Zhang, Yanping

    2017-06-24

    The biosynthetic pathways of most alcohols are linked to intracellular redox homeostasis, which is crucial for life. This crucial balance is primarily controlled by the generation of reducing equivalents, as well as the (reduction)-oxidation metabolic cycle and the thiol redox homeostasis system. As a main oxidation pathway of reducing equivalents, the biosynthesis of most alcohols includes redox reactions, which are dependent on cofactors such as NADH or NADPH. Thus, when engineering alcohol-producing strains, the availability of cofactors and redox homeostasis must be considered. In this review, recent advances on the engineering of cellular redox homeostasis systems to accelerate alcohol biosynthesis are summarized. Recent approaches include improving cofactor availability, manipulating the affinity of redox enzymes to specific cofactors, as well as globally controlling redox reactions, indicating the power of these approaches, and opening a path towards improving the production of a number of different industrially-relevant alcohols in the near future.

  18. The Loss of Myocardial Benefit following Ischemic Preconditioning Is Associated with Dysregulation of Iron Homeostasis in Diet-Induced Diabetes

    PubMed Central

    Berenshtein, Eduard; Eliashar, Ron; Chevion, Mordechai

    2016-01-01

    Whether the diabetic heart benefits from ischemic preconditioning (IPC), similar to the non-diabetic heart, is a subject of controversy. We recently proposed new roles for iron and ferritin in IPC-protection in Type 1-like streptozotocin-induced diabetic rat heart. Here, we investigated iron homeostasis in Cohen diabetic sensitive rat (CDs) that develop hyperglycemia when fed on a high-sucrose/low-copper diet (HSD), but maintain normoglycemia on regular-diet (RD). Control Cohen-resistant rats (CDr) maintain normoglycemia on either diet. The IPC procedure improved the post-ischemic recovery of normoglycemic hearts (CDr-RD, CDr-HSD and CDs-RD). CDs-HSD hearts failed to show IPC-associated protection. The recovery of these CDs-HSD hearts following I/R (without prior IPC) was better than their RD controls. During IPC ferritin levels increased in normoglycemic hearts, and its level was maintained nearly constant during the subsequent prolonged ischemia, but decayed to its baseline level during the reperfusion phase. In CDs-HSD hearts the baseline levels of ferritin and ferritin-saturation with iron were notably higher than in the controls, and remained unchanged during the entire experiment. This unique and abnormal pattern of post-ischemic recovery of CDs-HSD hearts is associated with marked changes in myocardial iron homeostasis, and suggests that iron and iron-proteins play a causative role/s in the etiology of diabetes-associated cardiovascular disorders. PMID:27458721

  19. Correlation between blink reflex abnormalities and magnetic resonance imaging findings in patients with multiple sclerosis.

    PubMed

    Degirmenci, Eylem; Erdogan, Cagdas; Bir, Levent Sinan

    2013-09-01

    This study investigates the correlation between brain magnetic resonance imaging findings and blink reflex abnormalities in patients with relapsing remitting multiple sclerosis. Twenty-six patients and 17 healthy subjects were included in this study. Blink reflex test (BRT) results were obtained using right and left stimulations; thus, 52 BRT results were recorded for the patient group, and 34 BRT results were recorded for the control group. The magnetic resonance imaging (MRI) findings were classified based on the existence of brainstem lesions (hyperintense lesion on T2 weighted (W) and fast fluid-attenuated inversion recovery MRI or contrast-enhancing lesion on T1W MRI). Correlation analysis was performed for the BRT and MRI findings. The percentage of individuals with abnormal BRT results (including R1 latency, ipsilateral R2 latency, and contralateral R2 latency) was significantly higher in the patient group as compared to the control group (p values: 0.015, 0.001, and 0.002, respectively). Correlation analysis revealed significant correlations between contralateral R2 latency abnormalities and brainstem lesions (p value: 0.011). Our results showed significant correlation correlations between contralateral R2 latency abnormalities and brainstem lesions and these results may be explained the effects of multiple demyelinating lesions of the brain stem of patients with relapsing remitting multiple sclerosis.

  20. Eosinophil-derived CCL-6 impairs hematopoietic stem cell homeostasis

    PubMed Central

    Zhang, Chao; Yi, Weiwei; Li, Fei; Du, Xufei; Wang, Hu; Wu, Ping; Peng, Chao; Luo, Man; Hua, Wen; Wong, Catherine CL; Lee, James J; Li, Wen; Chen, Zhihua; Ying, Songmin; Ju, Zhenyu; Shen, Huahao

    2018-01-01

    Eosinophils (Eos) have been long considered as end-stage effector cells in the hierarchical hematopoietic system. Numerous lines of evidence have suggested that Eos are multifunctional leukocytes with respect to the initiation, propagation and regulation of various inflammatory or immune reactions, especially in allergic diseases. Recent studies have shown that Eos are also required for maintenance of bone marrow plasma cells and differentiation of B cells. However, it remains unclear whether Eos contributes to regulation of hematopoietic stem cell (HSC) homeostasis. Here, we demonstrate that Eos disrupt HSC homeostasis by impairing HSC quiescence and reconstitution ability in wild-type mice following ovalbumin (OVA) challenge and even by causing bone marrow HSC failure and exhaustion in Cd3δ-Il-5 transgenic mice. The impaired maintenance and function of HSCs were associated with Eos-induced redox imbalance (increased oxidative phosphorylation and decreased anti-oxidants levels). More importantly, using mass spectrometry, we determined that CCL-6 is expressed at a high level under eosinophilia. We demonstrate that CCL-6 is Eos-derived and responsible for the impaired HSC homeostasis. Interestingly, blockage of CCL-6 with a specific neutralizing antibody, restored the reconstitution ability of HSCs while exacerbating eosinophilia airway inflammation in OVA-challenged mice. Thus, our study reveals an unexpected function of Eos/CCL-6 in HSC homeostasis. PMID:29327730

  1. Eosinophil-derived CCL-6 impairs hematopoietic stem cell homeostasis.

    PubMed

    Zhang, Chao; Yi, Weiwei; Li, Fei; Du, Xufei; Wang, Hu; Wu, Ping; Peng, Chao; Luo, Man; Hua, Wen; Wong, Catherine Cl; Lee, James J; Li, Wen; Chen, Zhihua; Ying, Songmin; Ju, Zhenyu; Shen, Huahao

    2018-03-01

    Eosinophils (Eos) have been long considered as end-stage effector cells in the hierarchical hematopoietic system. Numerous lines of evidence have suggested that Eos are multifunctional leukocytes with respect to the initiation, propagation and regulation of various inflammatory or immune reactions, especially in allergic diseases. Recent studies have shown that Eos are also required for maintenance of bone marrow plasma cells and differentiation of B cells. However, it remains unclear whether Eos contributes to regulation of hematopoietic stem cell (HSC) homeostasis. Here, we demonstrate that Eos disrupt HSC homeostasis by impairing HSC quiescence and reconstitution ability in wild-type mice following ovalbumin (OVA) challenge and even by causing bone marrow HSC failure and exhaustion in Cd3δ-Il-5 transgenic mice. The impaired maintenance and function of HSCs were associated with Eos-induced redox imbalance (increased oxidative phosphorylation and decreased anti-oxidants levels). More importantly, using mass spectrometry, we determined that CCL-6 is expressed at a high level under eosinophilia. We demonstrate that CCL-6 is Eos-derived and responsible for the impaired HSC homeostasis. Interestingly, blockage of CCL-6 with a specific neutralizing antibody, restored the reconstitution ability of HSCs while exacerbating eosinophilia airway inflammation in OVA-challenged mice. Thus, our study reveals an unexpected function of Eos/CCL-6 in HSC homeostasis.

  2. Geophysiology, Extended Organisms, and the Problem of Emergent Homeostasis

    NASA Astrophysics Data System (ADS)

    Turner, S.

    2001-12-01

    Physiology may be broadly defined as the managed flow of matter, energy and information. Central to this concept is the attendant phenomenon of homeostasis, doing physiological work to balance the thermodynamically driven flows of matter, energy or information that naturally attend to living things. Organisms in general exhibit what might be termed a "strong" homeostasis, in which well-regulated and complex physiological machines drive the physiological fluxes of matter, energy and information within the organism and at the organism's outermost integumentary boundary. Organisms also structure their environments to manage flows of matter, energy and information between themselves and their environment. In so doing, living things constitute a sort of extended organism, in which an organism's physiology reaches beyond the outermost boundary of the skin. Geophysiology's radical promise is that physiology can arise at levels of organization higher than the organism, ranging from social insect colonies through ecosystems, perhaps even to the biosphere itself. However, a simple demonstration that organisms affect the flows of matter, energy and information in their environments is not sufficient to qualify as physiology. That amounts to a demonstration that organisms do physiological work on their environments, which is neither a radical nor a new idea. To be truly physiological, geophysiology must exhibit physiology's most essential attribute, namely homeostasis. Finding homeostasis and explaining how it works in the extended organism is geophysiology's radical challenge.

  3. Obeticholic acid, a selective farnesoid X receptor agonist, regulates bile acid homeostasis in sandwich-cultured human hepatocytes.

    PubMed

    Zhang, Yuanyuan; Jackson, Jonathan P; St Claire, Robert L; Freeman, Kimberly; Brouwer, Kenneth R; Edwards, Jeffrey E

    2017-08-01

    Farnesoid X receptor (FXR) is a master regulator of bile acid homeostasis through transcriptional regulation of genes involved in bile acid synthesis and cellular membrane transport. Impairment of bile acid efflux due to cholangiopathies results in chronic cholestasis leading to abnormal elevation of intrahepatic and systemic bile acid levels. Obeticholic acid (OCA) is a potent and selective FXR agonist that is 100-fold more potent than the endogenous ligand chenodeoxycholic acid (CDCA). The effects of OCA on genes involved in bile acid homeostasis were investigated using sandwich-cultured human hepatocytes. Gene expression was determined by measuring mRNA levels. OCA dose-dependently increased fibroblast growth factor-19 (FGF-19) and small heterodimer partner (SHP) which, in turn, suppress mRNA levels of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme for de novo synthesis of bile acids. Consistent with CYP7A1 suppression, total bile acid content was decreased by OCA (1 μmol/L) to 42.7 ± 20.5% relative to control. In addition to suppressing de novo bile acids synthesis, OCA significantly increased the mRNA levels of transporters involved in bile acid homeostasis. The bile salt excretory pump (BSEP), a canalicular efflux transporter, increased by 6.4 ± 0.8-fold, and the basolateral efflux heterodimer transporters, organic solute transporter α (OST α ) and OST β increased by 6.4 ± 0.2-fold and 42.9 ± 7.9-fold, respectively. The upregulation of BSEP and OST α and OST β, by OCA reduced the intracellular concentrations of d 8 -TCA, a model bile acid, to 39.6 ± 8.9% relative to control. These data demonstrate that OCA does suppress bile acid synthesis and reduce hepatocellular bile acid levels, supporting the use of OCA to treat bile acid-induced toxicity observed in cholestatic diseases. © 2017 Intercept Pharmaceuticals. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and

  4. Detection of chromosomal abnormalities and the 22q11 microdeletion in fetuses with congenital heart defects.

    PubMed

    Lv, Wei; Wang, Shuyu

    2014-11-01

    Chromosomal abnormalities and the 22q11 microdeletion are implicated in congenital heart defects (CHDs). This study was designed to detect these abnormalities in fetuses and determine the effect of genetic factors on CHD etiology. Between January 2010 and December 2011, 113 fetuses with CHD treated at the Beijing Obstetrics and Gynecology Hospital were investigated, using chromosome karyotyping of either amniotic fluid cell or umbilical cord blood cell samples. Fetuses with a normal result were then investigated for the 22q11 microdeletion by fluorescence in situ hybridization. Of the 113 patients, 12 (10.6%) exhibited chromosomal abnormalities, while 6 (5.3%) of the remaining 101 cases presented with a 22q11 microdeletion. The incidence of chromosomal abnormalities was significantly higher in the group of fetuses presenting with extracardiac malformations in addition to CHD (P<0.001), although the detection of the 22q11 microdeletion was not significantly different between the two groups (P=0.583). In addition, all fetuses with the 22q11 microdeletion occurred de novo. In conclusion, genetic factors are important in the etiology of CHD. Where fetuses present with cardiac defects, additional chromosomal analysis is required to detect extracardiac abnormalities. Fetuses with heart defects should also be considered for 22q11 microdeletion detection to evaluate fetal prognosis, particularly prior to surgery.

  5. Morphometric and functional abnormalities of kidneys in the progeny of mice fed chocolate during pregnancy and lactation.

    PubMed

    Patera, Janusz; Chorostowska-Wynimko, Joanna; Słodkowska, Janina; Borowska, Adamina; Skopiński, Piotr; Sommer, Ewa; Wasiutyński, Aleksander; Skopińska-Rózewska, Ewa

    2006-01-01

    Even most commonly consumed beverages like tea, coffee, chocolate and cocoa contain methylxanthines, biogenic amines and polyphenols, among them catechins, that exhibit significant biological activity and might profoundly affect the organism homeostasis. We have previously shown that 400 mg of bitter chocolate or 6 mg of theobromine added to the daily diet of pregnant and afterwards lactating mice affected embryonic angiogenesis and caused bone mineralization disturbances as well as limb shortening in 4-weeks old offspring. The aim of the present study was the morphometric and functional evaluation of kidneys in the 4-weeks old progeny mice fed according to the protocol mentioned above. Progeny from the mice fed chocolate presented considerable morphometric abnormalities in the kidney structure, with the lower number of glomeruli per mm2 and their increased diameter. Moreover, higher serum creatinine concentration was observed in that group of offspring. No morphometric or functional irregularities were found in the progeny of mice fed theobromine. Abnormalities demonstrated in the offspring of mice fed chocolate are not related to its theobromine content. Consequently, identification of active compound(s) responsible for the observed effects is of vital importance.

  6. Circadian clocks, feeding time, and metabolic homeostasis

    PubMed Central

    Paschos, Georgios K.

    2015-01-01

    Metabolic processes exhibit diurnal variation from cyanobacteria to humans. The circadian clock is thought to have evolved as a time keeping system for the cell to optimize the timing of metabolic events according to physiological needs and environmental conditions. Circadian rhythms temporally separate incompatible cellular processes and optimize cellular and organismal fitness. A modern 24 h lifestyle can run at odds with the circadian rhythm dictated by our molecular clocks and create desynchrony between internal and external timing. It has been suggested that this desynchrony compromises metabolic homeostasis and may promote the development of obesity (Morris et al., 2012). Here we review the evidence supporting the association between circadian misalignment and metabolic homeostasis and discuss the role of feeding time. PMID:26082718

  7. Circadian dysregulation disrupts bile acid homeostasis

    USDA-ARS?s Scientific Manuscript database

    Bile acids are potentially toxic compounds and their levels of hepatic production, uptake, and export are tightly regulated by many inputs, including circadian rhythm. We tested the impact of disrupting the peripheral circadian clock on integral steps of bile acid homeostasis. Both restricted feedi...

  8. Deregulation of ocular nucleotide homeostasis in patients with diabetic retinopathy.

    PubMed

    Loukovaara, Sirpa; Sandholm, Jouko; Aalto, Kristiina; Liukkonen, Janne; Jalkanen, Sirpa; Yegutkin, Gennady G

    2017-02-01

    Clear signaling roles for ATP and adenosine have been established in all tissues, including the eye. The magnitude of signaling responses is governed by networks of enzymes; however, little is known about the regulatory mechanisms of purinergic signaling in the eye. By employing thin-layer chromatographic assays with 3 H-labeled substrates, this study aimed to evaluate the role of nucleotide homeostasis in the pathogenesis of vitreoretinal diseases in humans. We have identified soluble enzymes ecto-5'-nucleotidase/CD73, adenylate kinase-1, and nucleoside diphosphate kinase in the vitreous fluid that control active cycling between pro-inflammatory ATP and anti-inflammatory adenosine. Strikingly, patients with proliferative form of diabetic retinopathy (DR) had higher adenylate kinase activity and ATP concentration, when compared to non-proliferative DR eyes and non-diabetic controls operated for rhegmatogenous retinal detachment, macular hole, and pucker. The non-parametric correlation analysis revealed positive correlations between intravitreal adenylate kinase and concentrations of ATP, ADP, and other angiogenic (angiopoietins-1 and -2), profibrotic (transforming growth factor-β1), and proteolytic (matrix metalloproteinase-9) factors but not erythropoietin and VEGF. Immunohistochemical staining of postmortem human retina additionally revealed selective expression of ecto-5'-nucleotidase/CD73 on the rod-and-cone-containing photoreceptor cells. Collectively, these findings provide novel insights into the regulatory mechanisms that influence purinergic signaling in diseased eye and open up new possibilities in the development of enzyme-targeted therapeutic approaches for prevention and treatment of DR. Ecto-5'-nucleotidase/CD73 and adenylate kinase-1 circulate in human vitreous fluid. Adenylate kinase activity is high in diabetic eyes with proliferative retinopathy. Diabetic eyes display higher intravitreal ATP/ADP ratio than non-diabetic controls. Soluble adenylate

  9. Food intake does not differ between obese women who are metabolically healthy or abnormal.

    PubMed

    Kimokoti, Ruth W; Judd, Suzanne E; Shikany, James M; Newby, P K

    2014-12-01

    Metabolically healthy obesity may confer lower risk of adverse health outcomes compared with abnormal obesity. Diet and race are postulated to influence the phenotype, but their roles and their interrelations on healthy obesity are unclear. We evaluated food intakes of metabolically healthy obese women in comparison to intakes of their metabolically healthy normal-weight and metabolically abnormal obese counterparts. This was a cross-sectional study in 6964 women of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Participants were aged 45-98 y with a body mass index (BMI; kg/m(2)) ≥18.5 and free of cardiovascular diseases, diabetes, and cancer. Food intake was collected by using a food-frequency questionnaire. BMI phenotypes were defined by using metabolic syndrome (MetS) and homeostasis model assessment of insulin resistance (HOMA-IR) criteria. Mean differences in food intakes among BMI phenotypes were compared by using ANCOVA. Approximately one-half of obese women (white: 45%; black: 55%) as defined by MetS criteria and approximately one-quarter of obese women (white: 28%; black: 24%) defined on the basis of HOMA-IR values were metabolically healthy. In age-adjusted analyses, healthy obesity and normal weight as defined by both criteria were associated with lower intakes of sugar-sweetened beverages compared with abnormal obesity among both white and black women (P < 0.05). HOMA-IR-defined healthy obesity and normal weight were also associated with higher fruit and low-fat dairy intakes compared with abnormal obesity in white women (P < 0.05). Results were attenuated and became nonsignificant in multivariable-adjusted models that additionally adjusted for BMI, marital status, residential region, education, annual income, alcohol intake, multivitamin use, cigarette smoking status, physical activity, television viewing, high-sensitivity C-reactive protein, menopausal status, hormone therapy, and food intakes. Healthy obesity was not

  10. Ovarian SAHA syndrome is associated with a more insulin-resistant profile and represents an independent risk factor for glucose abnormalities in women with polycystic ovary syndrome: a prospective controlled study.

    PubMed

    Dalamaga, Maria; Papadavid, Evangelia; Basios, Georgios; Vaggopoulos, Vassilios; Rigopoulos, Dimitrios; Kassanos, Dimitrios; Trakakis, Eftihios

    2013-12-01

    SAHA syndrome is characterized by the tetrad: seborrhea, acne, hirsutism, and androgenetic alopecia. No previous study has examined the prevalence of glucose abnormalities in ovarian SAHA and explored whether it may be an independent risk factor for glucose abnormalities. In a prospective controlled study, we investigated the spectrum of glucose abnormalities in ovarian SAHA and explored whether it is associated with a more insulin-resistant profile. In all, 316 patients with a diagnosis of polycystic ovary syndrome (PCOS) (56 with SAHA) and 102 age-matched healthy women were examined and underwent a 2-hour oral glucose tolerance test. Serum glucose homeostasis parameters, hormones, and adipokines were determined. SAHA prevalence was 17.7% in patients with PCOS and predominance of the severe PCOS phenotype. Ovarian SAHA was independently associated with a more insulin-resistant profile (higher homeostatic model assessment of insulin resistance score, lower quantitative insulin sensitivity check index [QUICKI] and MATSUDA indices, and relative hypoadiponectinemia), and represented an independent risk factor for glucose abnormalities regardless of anthropometric features, age, and PCOS phenotype. There was no performance of skin biopsies. The prompt recognition of SAHA syndrome in women with PCOS permits an earlier diagnosis and surveillance of metabolic abnormalities, especially in Mediterranean PCOS population exhibiting a lower prevalence of glucose abnormalities. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  11. Osmotic/ionic status of body fluids in the euryhaline cephalopod suggest possible parallel evolution of osmoregulation

    PubMed Central

    Sakamoto, Tatsuya; Ogawa, Satoshi; Nishiyama, Yudai; Akada, Chiaki; Takahashi, Hideya; Watanabe, Taro; Minakata, Hiroyuki; Sakamoto, Hirotaka

    2015-01-01

    Acclimation from marine to dilute environments constitutes among the dramatic evolutionary transitions in the history of life. Such adaptations have evolved in multiple lineages, but studies of the blood/hemolymph homeostasis mechanisms are limited to those using evolutionarily advanced Deuterostome (chordates) and Ecdysozoa (crustaceans). Here, we examined hemolymph homeostasis in the advanced Lophotrochozoa/mollusc, the other unexplored taxa, and its possible regulation by the vasopressin/oxytocin superfamily peptides known to be implicated in fluid homeostasis in Chordata and Arthropoda. The hemolymph osmotic and ionic status in the euryhaline cephalopod (Octopus ocellatus) following transfer from 30-ppt normal seawater to 20 ppt salinity indicate hyperosmo- and hyperionoregulatory abilities for more than 1 week, as in crustaceans and teleost fish. While ventilation frequency decreased by 1 day, Na+/K+-ATPase activity, which has been generally implicated in ion transport, was induced in two of the eight posterior gills after 1 week. In addition, the octopuses were intravenously injected with 1 or 100 ng/g octopressin or cephalotocin, which are Octopus vasopressin/oxytocin orthologs. After 1 day, octopressin, but not cephalotocin, decreased the hemolymph osmolality and Ca concentrations, as well as urinary Na concentrations. These data provide evidence for possible parallel evolution in hyperionoregulatory mechanisms and coordination by conserved peptides. PMID:26403952

  12. Theorethical principles of fluid managment according to physicochemical Stewart approach.

    PubMed

    Smuszkiewicz, Piotr; Szrama, Jakub

    2013-01-01

    Interpreting acid base disturbances according to the physicochemical Stewart approach allows the cause of such abnormalities to be discovered. This method is based on three independent variables: SID (strong ion difference), mainly sodium and chloride; weak acids concentration - Atot, mainly albumins and phosphate; and carbon dioxide tension - pCO₂. These three independent variables are responsible for the change of water dissociation and for the change in H+ concentration and, consequently, the change in serum pH value. The SID value of the fluids administered to a patient is responsible for the change of serum SID value and therefore causes a change in the patient's acid base status. During the infusion of a given fluid, the SID value of the serum becomes closer to the SID value of that fluid; on the other hand, the infusion causes a decrease in Atot concentration. In order to avoid acid base disturbances connected with fluid administration, the SID value of fluids being administered should be greater than 0 and lower then the serum SID. It has been suggested that fluids should be given of which the SID value is as close as possible to the actual serum HCO₃ concentration. Knowing the SID value of the fluid administered, and the serum HCO₃ concentration, one can expect a change of serum pH after a fluid infusion. Administering a fluid with a SID greater than the HCO₃ concentration causes a pH increase towards alkalosis. Likewise, administering a a fluid with a SID lower than the HCO₃ concentration causes a pH decrease towards acidosis. It seems that knowledge of the electrolyte concentration and the SID value of an administered fluid is an important factor regarding acid base disturbances.

  13. Abnormal pressure in hydrocarbon environments

    USGS Publications Warehouse

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  14. Iron homeostasis in the liver

    PubMed Central

    Anderson, Erik R; Shah, Yatrik M

    2014-01-01

    Iron is an essential nutrient that is tightly regulated. A principal function of the liver is the regulation of iron homeostasis. The liver senses changes in systemic iron requirements and can regulate iron concentrations in a robust and rapid manner. The last 10 years have led to the discovery of several regulatory mechanisms in the liver which control the production of iron regulatory genes, storage capacity, and iron mobilization. Dysregulation of these functions leads to an imbalance of iron, which is the primary causes of iron-related disorders. Anemia and iron overload are two of the most prevalent disorders worldwide and affect over a billion people. Several mutations in liver-derived genes have been identified, demonstrating the central role of the liver in iron homeostasis. During conditions of excess iron, the liver increases iron storage and protects other tissues, namely the heart and pancreas from iron-induced cellular damage. However, a chronic increase in liver iron stores results in excess reactive oxygen species production and liver injury. Excess liver iron is one of the major mechanisms leading to increased steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. PMID:23720289

  15. Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease.

    PubMed

    Beck, Susanne C; Feng, Yuxi; Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Acar, Niyazi; Shan, Shenliang; Seebauer, Britta; Berger, Wolfgang; Hammes, Hans-Peter; Seeliger, Mathias W

    2017-01-01

    Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects.

  16. Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease

    PubMed Central

    Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Acar, Niyazi; Shan, Shenliang; Seebauer, Britta; Berger, Wolfgang; Hammes, Hans-Peter; Seeliger, Mathias W.

    2017-01-01

    Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects. PMID:28575130

  17. A New Methodology of Viewing Extra-Axial Fluid and Cortical Abnormalities in Children with Autism via Transcranial Ultrasonography

    PubMed Central

    Bradstreet, James Jeffrey; Pacini, Stefania; Ruggiero, Marco

    2014-01-01

    Background: Autism spectrum disorders (ASDs) are developmental conditions of uncertain etiology which have now affected more than 1% of the school-age population of children in many developed nations. Transcranial ultrasonography (TUS) via the temporal bone appeared to be a potential window of investigation to determine the presence of both cortical abnormalities and increased extra-axial fluid (EAF). Methods: TUS was accomplished using a linear probe (10–5 MHz). Parents volunteered ASD subjects (N = 23; males 18, females 5) for evaluations (mean = 7.46 years ± 3.97 years), and 15 neurotypical siblings were also examined (mean = 7.15 years ± 4.49 years). Childhood Autism Rating Scale (CARS2®) scores were obtained and the ASD score mean was 48.08 + 6.79 (Severe). Results: Comparisons of the extra-axial spaces indicated increases in the ASD subjects. For EAF we scored based on the gyral summit distances between the arachnoid membrane and the cortical pia layer (subarachnoid space): (1) <0.05 cm, (2) 0.05–0.07 cm, (3) 0.08–0.10 cm, (4) >0.10 cm. All of the neurotypical siblings scored 1, whereas the ASD mean score was 3.41 ± 0.67. We also defined cortical dysplasia as the following: hypoechoic lesions within the substance of the cortex, or disturbed layering within the gray matter. For cortical dysplasia we scored: (1) none observed, (2) rare hypoechogenic lesions and/or mildly atypical cortical layering patterns, (3) more common, but separated areas of cortical hypoechogenic lesions, (4) very common or confluent areas of cortical hypoechogenicity. Again all of the neurotypical siblings scored 1, while the ASD subjects’ mean score was 2.79 ± 0.93. Conclusion: TUS may be a useful screening technique for children at potential risk of ASDs which, if confirmed with repeated studies and high resolution MRI, provides rapid, non-invasive qualification of EAF, and cortical lesions. PMID:24459462

  18. Development of iron homeostasis in infants and young children.

    PubMed

    Lönnerdal, Bo

    2017-12-01

    Healthy, term, breastfed infants usually have adequate iron stores that, together with the small amount of iron that is contributed by breast milk, make them iron sufficient until ≥6 mo of age. The appropriate concentration of iron in infant formula to achieve iron sufficiency is more controversial. Infants who are fed formula with varying concentrations of iron generally achieve sufficiency with iron concentrations of 2 mg/L (i.e., with iron status that is similar to that of breastfed infants at 6 mo of age). Regardless of the feeding choice, infants' capacity to regulate iron homeostasis is important but less well understood than the regulation of iron absorption in adults, which is inverse to iron status and strongly upregulated or downregulated. Infants who were given daily iron drops compared with a placebo from 4 to 6 mo of age had similar increases in hemoglobin concentrations. In addition, isotope studies have shown no difference in iron absorption between infants with high or low hemoglobin concentrations at 6 mo of age. Together, these findings suggest a lack of homeostatic regulation of iron homeostasis in young infants. However, at 9 mo of age, homeostatic regulatory capacity has developed although, to our knowledge, its extent is not known. Studies in suckling rat pups showed similar results with no capacity to regulate iron homeostasis at 10 d of age when fully nursing, but such capacity occurred at 20 d of age when pups were partially weaned. The major iron transporters in the small intestine divalent metal-ion transporter 1 (DMT1) and ferroportin were not affected by pup iron status at 10 d of age but were strongly affected by iron status at 20 d of age. Thus, mechanisms that regulate iron homeostasis are developed at the time of weaning. Overall, studies in human infants and experimental animals suggest that iron homeostasis is absent or limited early in infancy largely because of a lack of regulation of the iron transporters DMT1 and ferroportin

  19. Viscous Energy Loss in the Presence of Abnormal Aortic Flow

    PubMed Central

    Barker, A.J.; van Ooij, P.; Bandi, K.; Garcia, J.; Albaghdadi, M.; McCarthy, P.; Bonow, R. O.; Carr, J.; Collins, J.; Malaisrie, C.; Markl, M.

    2014-01-01

    Purpose To present a theoretical basis for noninvasively characterizing in vivo fluid-mechanical energy losses, and to apply it in a pilot study of patients known to express abnormal aortic flow patterns. Methods 4D flow MRI was used to characterize laminar viscous energy losses in the aorta of normal controls (n=12, age=37±10), patients with aortic dilation (n=16, age=52±8), and patients with aortic valve stenosis matched for age and aortic size (n=14, age=46±15), using a relationship between the 3D velocity field and viscous energy dissipation. Results Viscous energy loss was significantly elevated in the thoracic aorta for patients with dilated aorta (3.6±1.3 mW, p=0.024) and patients with aortic stenosis (14.3±8.2 mW, p<0.001) compared to healthy volunteers (2.3±0.9 mW). The same pattern of significant differences were seen in the ascending aorta, where viscous energy losses in patients with dilated aortas (2.2±1.1 mW, p=0.021) and patients with aortic stenosis (10.9±6.8 mW, p<0.001) were elevated compared to healthy volunteers (1.2±0.6 mW). Conclusion This technique provides a capability to quantify the contribution of abnormal laminar blood flow to increased ventricular afterload. In this pilot study, viscous energy loss in patient cohorts was significantly elevated and indicates that cardiac afterload is increased due to abnormal flow. PMID:24122967

  20. Sustained Sleep Fragmentation Induces Sleep Homeostasis in Mice

    PubMed Central

    Baud, Maxime O.; Magistretti, Pierre J.; Petit, Jean-Marie

    2015-01-01

    Study Objectives: Sleep fragmentation (SF) is an integral feature of sleep apnea and other prevalent sleep disorders. Although the effect of repetitive arousals on cognitive performance is well documented, the effects of long-term SF on electroencephalography (EEG) and molecular markers of sleep homeostasis remain poorly investigated. To address this question, we developed a mouse model of chronic SF and characterized its effect on EEG spectral frequencies and the expression of genes previously linked to sleep homeostasis including clock genes, heat shock proteins, and plasticity-related genes. Design: N/A. Setting: Animal sleep research laboratory. Participants : Sixty-six C57BL6/J adult mice. Interventions: Instrumental sleep disruption at a rate of 60/h during 14 days Measurements and Results: Locomotor activity and EEG were recorded during 14 days of SF followed by recovery for 2 days. Despite a dramatic number of arousals and decreased sleep bout duration, SF minimally reduced total quantity of sleep and did not significantly alter its circadian distribution. Spectral analysis during SF revealed a homeostatic drive for slow wave activity (SWA; 1–4 Hz) and other frequencies as well (4–40 Hz). Recordings during recovery revealed slow wave sleep consolidation and a transient rebound in SWA, and paradoxical sleep duration. The expression of selected genes was not induced following chronic SF. Conclusions: Chronic sleep fragmentation (SF) increased sleep pressure confirming that altered quality with preserved quantity triggers core sleep homeostasis mechanisms. However, it did not induce the expression of genes induced by sleep loss, suggesting that these molecular pathways are not sustainably activated in chronic diseases involving SF. Citation: Baud MO, Magistretti PJ, Petit JM. Sustained sleep fragmentation induces sleep homeostasis in mice. SLEEP 2015;38(4):567–579. PMID:25325477

  1. Overexpression of p62/SQSTM1 promotes the degradations of abnormally accumulated PrP mutants in cytoplasm and relieves the associated cytotoxicities via autophagy-lysosome-dependent way.

    PubMed

    Xu, Yin; Zhang, Jin; Tian, Chan; Ren, Ke; Yan, Yu-E; Wang, Ke; Wang, Hui; Chen, Cao; Wang, Jing; Shi, Qi; Dong, Xiao-Ping

    2014-04-01

    The protein of p62/sequestosome 1 (SQSTM1), a key cargo adaptor protein involved in autophagy-lysosome degradation, exhibits inclusion bodies structure in cytoplasm and plays a protective role in some models of neurodegenerative diseases. Some PrP mutants, such as PrP-CYTO and PrP-PG14, also form cytosolic inclusion bodies and trigger neuronal apoptosis either in cultured cells or in transgenic mice. Here, we demonstrated that the cellular p62/SQSTM1 incorporated into the inclusion bodies formed by expressing the abnormal PrP mutants, PrP-CYTO and PrP-PG14, in human embryonic kidney 293 cells. Overexpression of p62/SQSTM1 efficiently relieved the cytosolic aggregations and cell apoptosis induced by the abnormal PrPs. Autophagy-lysosome inhibitors instead of proteasome inhibitor sufficiently blocked the p62/SQSTM1-mediated degradations of abnormal PrPs. Overexpression of p62/SQSTM1 did not alter the levels of light chain 3 (LC3) in the cells expressing various PrPs. However, more complexes of p62/SQSTM1 with LC3 were detected in the cells expressing the misfolded PrPs. These data imply that p62/SQSTM1 plays an important role in the homeostasis of abnormal PrPs via autophagy-lysosome-dependent way.

  2. Fluid Mechanical Forces and Endothelial Mitochondria: A Bioengineering Perspective.

    PubMed

    Scheitlin, Christopher G; Nair, Devi M; Crestanello, Juan A; Zweier, Jay L; Alevriadou, B Rita

    2014-12-01

    Endothelial cell dysfunction is the hallmark of every cardiovascular disease/condition, including atherosclerosis and ischemia/reperfusion injury. Fluid shear stress acting on the vascular endothelium is known to regulate cell homeostasis. Altered hemodynamics is thought to play a causative role in endothelial dysfunction. The dysfunction is associated with/preceded by mitochondrial oxidative stress. Studies by our group and others have shown that the form and/or function of the mitochondrial network are affected when endothelial cells are exposed to shear stress in the absence or presence of additional physicochemical stimuli. The present review will summarize the current knowledge on the interconnections among intracellular Ca 2+ - nitric oxide - mitochondrial reactive oxygen species, mitochondrial fusion/fission, autophagy/mitophagy, and cell apoptosis vs. survival. More specifically, it will list the evidence on potential regulation of the above intracellular species and processes by the fluid shear stress acting on the endothelium under either physiological flow conditions or during reperfusion (following a period of ischemia). Understanding how the local hemodynamics affects mitochondrial physiology and the cell redox state may lead to development of novel therapeutic strategies for prevention or treatment of the endothelial dysfunction and, hence, of cardiovascular disease.

  3. High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis.

    PubMed

    McClain, D A; Abraham, D; Rogers, J; Brady, R; Gault, P; Ajioka, R; Kushner, J P

    2006-07-01

    The prevalence and mechanisms of diabetes in hereditary haemochromatosis are not known. We therefore measured glucose tolerance, insulin secretory capacity and insulin sensitivity in adults with haemochromatosis. Subjects recruited from referrals to a haemochromatosis clinic underwent OGTT and frequently sampled IVGTT. A chart review of former clinic patients was also performed. The prevalence of diabetes (23%) and IGT (30%) was increased in haemochromatosis compared with matched control subjects (0% diabetes and 14% IGT). Subjects with haemochromatosis and diabetes were overweight (14%) or obese (86%). The prevalence of diabetes, as determined by chart review of fasting glucose values, in subjects who had haemochromatosis and were in the 40-79 years age range was 26%. Overall, patients with haemochromatosis and control subjects had similar values for acute insulin response to glucose and insulin sensitivity. However, patients with haemochromatosis and IGT had a 68% decrease in acute insulin response to glucose (p<0.02) compared with those with NGT. They were not insulin-resistant, exhibiting instead a 62% increase in insulin sensitivity (NS). Haemochromatosis subjects with diabetes exhibited further declines in acute insulin response to glucose, insulin resistance, or both. Diabetes and IGT are common in haemochromatosis, justifying screening for diabetes and therapeutic phlebotomy. The major abnormality associated with IGT is decreased insulin secretory capacity. Diabetes is usually associated with obesity and concomitant insulin resistance.

  4. Homovanillic acid in cerebrospinal fluid of 1388 children with neurological disorders.

    PubMed

    Molero-Luis, Marta; Serrano, Mercedes; Ormazábal, Aida; Pérez-Dueñas, Belén; García-Cazorla, Angels; Pons, Roser; Artuch, Rafael

    2013-06-01

    To determine the prevalence of dopaminergic abnormalities in 1388 children with neurological disorders, and to analyse their clinical, neuroradiological, and electrophysiological characteristics. We studied biogenic amines in 1388 cerebrospinal fluid (CSF) samples from children with neurological disorders (mean age 3y 10mo, SD 4y 5mo; 712 males, 676 females. Correlations among CSF homovanillic acid (HVA) values and other biochemical, clinical, neuroradiological, and electrophysiological parameters were analysed. Twenty-one patients with primary dopaminergic deficiencies were identified. Of the whole sample, 20% showed altered HVA. We report neurological diseases with abnormal CSF HVA values such as pontocerebellar hypoplasia, perinatal asphyxia, central nervous system infections, mitochondrial disorders, and other genetic diseases. Overlapping HVA levels between primary and secondary dopamine deficiencies were observed. Prevalence of low CSF HVA levels was significantly higher in neonatal patients (χ(2) =84.8, p<0.001). Abnormalities in white matter were associated with low CSF HVA (odds ratio 2.3, 95% confidence interval 1.5-3.5). HVA abnormalities are observed in various neurological diseases, but some are probably an unspecific finding. No clear limits for CSF HVA values pointing towards primary diseases can be stated. We report several neurological diseases showing HVA alterations. No neuroimaging traits were associated with low HVA values, except for white matter abnormalities. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.

  5. Disruption of the intracellular Ca{sup 2+} homeostasis in the cardiac excitation-contraction coupling is a crucial mechanism of arrhythmic toxicity in aconitine-induced cardiomyocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fu Min; Beijing University of Chinese Medicine, Beijing 100029; Wu Meng

    2007-03-23

    Aconitine is an effective ingredient in Aconite tuber, an important traditional Chinese medicine. Aconitine is also known to be a highly toxic diterpenoid alkaloid with arrhythmogenic effects. In the present study, we have characterized the properties of arrhythmic cytotoxicity and explored the possible mechanisms of aconitine-induced cardiomyocytes. Results show that aconitine induces significant abnormity in the spontaneous beating rate, amplitude of spontaneous oscillations and the relative intracellular Ca{sup 2+} concentration. Also, mRNA transcription levels and protein expressions of SR Ca{sup 2+} release channel RyR{sub 2} and sarcolemmal NCX were elevated in aconitine-induced cardiomyocytes. However, co-treatment with ruthenium red (RR), amore » RyR channel inhibitor, could reverse the aconitine-induced abnormity in intracellular Ca{sup 2+} signals. These results demonstrate that disruption of intracellular Ca{sup 2+} homeostasis in the cardiac excitation-contraction coupling (EC coupling) is a crucial mechanism of arrhythmic cytotoxicity in aconitine-induced cardiomyocytes. Moreover, certain inhibitors appear to play an important role in the detoxification of aconitine-induced Ca{sup 2+}-dependent arrhythmias.« less

  6. The contribution of hypothalamic macroglia to the regulation of energy homeostasis

    PubMed Central

    Buckman, Laura B.; Ellacott, Kate L. J.

    2014-01-01

    The hypothalamus is critical for the regulation of energy homeostasis. Genetic and pharmacologic studies have identified a number of key hypothalamic neuronal circuits that integrate signals controlling food intake and energy expenditure. Recently, studies have begun to emerge demonstrating a role for non-neuronal cell types in the regulation of energy homeostasis. In particular the potential importance of different glial cell types is increasingly being recognized. A number of studies have described changes in the activity of hypothalamic macroglia (principally astrocytes and tanycytes) in response to states of positive and negative energy balance, such as obesity and fasting. This article will review these studies and discuss how these findings are changing our understanding of the cellular mechanisms by which energy homeostasis is regulated. PMID:25374514

  7. Bacterial-modulated host immunity and stem cell activation for gut homeostasis.

    PubMed

    Lee, Won-Jae

    2009-10-01

    Although it is widely accepted that dynamic cross-talk between gut epithelia and microorganisms must occur to achieve gut homeostasis, the critical mechanisms by which gut-microbe interactions are regulated remain uncertain. In this issue of Genes & Development, Buchon and colleagues (pp. 2333-2344) revealed that the reaction of the gut to microorganisms is not restricted to activating immune systems, but extends to integrated responses essential for gut tissue homeostasis, including self-renewal and the differentiation of stem cells. Further investigation of the connection between immune response and stem cell regulation at the molecular level in the microbe-laden mucosal epithelia will accelerate our understanding of the regulatory mechanisms of gut homeostasis and of the pathogenesis of diseases such as chronic inflammatory diseases and colorectal cancers.

  8. Deletion of Rab GAP AS160 modifies glucose uptake and GLUT4 translocation in primary skeletal muscles and adipocytes and impairs glucose homeostasis.

    PubMed

    Lansey, Melissa N; Walker, Natalie N; Hargett, Stefan R; Stevens, Joseph R; Keller, Susanna R

    2012-11-15

    Tight control of glucose uptake in skeletal muscles and adipocytes is crucial to glucose homeostasis and is mediated by regulating glucose transporter GLUT4 subcellular distribution. In cultured cells, Rab GAP AS160 controls GLUT4 intracellular retention and release to the cell surface and consequently regulates glucose uptake into cells. To determine AS160 function in GLUT4 trafficking in primary skeletal muscles and adipocytes and investigate its role in glucose homeostasis, we characterized AS160 knockout (AS160(-/-)) mice. We observed increased and normal basal glucose uptake in isolated AS160(-/-) adipocytes and soleus, respectively, while insulin-stimulated glucose uptake was impaired and GLUT4 expression decreased in both. No such abnormalities were found in isolated AS160(-/-) extensor digitorum longus muscles. In plasma membranes isolated from AS160(-/-) adipose tissue and gastrocnemius/quadriceps, relative GLUT4 levels were increased under basal conditions and remained the same after insulin treatment. Concomitantly, relative levels of cell surface-exposed GLUT4, determined with a glucose transporter photoaffinity label, were increased in AS160(-/-) adipocytes and normal in AS160(-/-) soleus under basal conditions. Insulin augmented cell surface-exposed GLUT4 in both. These observations suggest that AS160 is essential for GLUT4 intracellular retention and regulation of glucose uptake in adipocytes and skeletal muscles in which it is normally expressed. In vivo studies revealed impaired insulin tolerance in the presence of normal (male) and impaired (female) glucose tolerance. Concurrently, insulin-elicited increases in glucose disposal were abolished in all AS160(-/-) skeletal muscles and liver but not in AS160(-/-) adipose tissues. This suggests AS160 as a target for differential manipulation of glucose homeostasis.

  9. C-Terminal Truncation of α-COP Affects Functioning of Secretory Organelles and Calcium Homeostasis in Hansenula polymorpha

    PubMed Central

    Chechenova, Maria B.; Romanova, Nina V.; Deev, Alexander V.; Packeiser, Anna N.; Smirnov, Vladimir N.; Agaphonov, Michael O.; Ter-Avanesyan, Michael D.

    2004-01-01

    In eukaryotic cells, COPI vesicles retrieve resident proteins to the endoplasmic reticulum and mediate intra-Golgi transport. Here, we studied the Hansenula polymorpha homologue of the Saccharomyces cerevisiae RET1 gene, encoding α-COP, a subunit of the COPI protein complex. H. polymorpha ret1 mutants, which expressed truncated α-COP lacking more than 300 C-terminal amino acids, manifested an enhanced ability to secrete human urokinase-type plasminogen activator (uPA) and an inability to grow with a shortage of Ca2+ ions, whereas a lack of α-COP expression was lethal. The α-COP defect also caused alteration of intracellular transport of the glycosylphosphatidylinositol-anchored protein Gas1p, secretion of abnormal uPA forms, and reductions in the levels of Pmr1p, a Golgi Ca2+-ATPase. Overexpression of Pmr1p suppressed some ret1 mutant phenotypes, namely, Ca2+ dependence and enhanced uPA secretion. The role of COPI-dependent vesicular transport in cellular Ca2+ homeostasis is discussed. PMID:14871936

  10. Wired on sugar: the role of the CNS in the regulation of glucose homeostasis

    PubMed Central

    Grayson, Bernadette E.; Seeley, Randy J.; Sandoval, Darleen A.

    2014-01-01

    Obesity and type 2 diabetes mellitus (T2DM) — disorders of energy homeostasis and glucose homeostasis, respectively — are tightly linked and the incidences of both conditions are increasing in parallel. The CNS integrates information regarding peripheral nutrient and hormonal changes and processes this information to regulate energy homeostasis. Recent findings indicate that some of the neural circuits and mechanisms underlying energy balance are also essential for the regulation of glucose homeostasis. We propose that disruption of these overlapping pathways links the metabolic disturbances associated with obesity and T2DM. A better understanding of these converging mechanisms may lead to therapeutic strategies that target both T2DM and obesity. PMID:23232606

  11. Enteric Virome Sensing—Its Role in Intestinal Homeostasis and Immunity

    PubMed Central

    Metzger, Rebecca N.; Krug, Anne B.; Eisenächer, Katharina

    2018-01-01

    Pattern recognition receptors (PRRs) sensing commensal microorganisms in the intestine induce tightly controlled tonic signaling in the intestinal mucosa, which is required to maintain intestinal barrier integrity and immune homeostasis. At the same time, PRR signaling pathways rapidly trigger the innate immune defense against invasive pathogens in the intestine. Intestinal epithelial cells and mononuclear phagocytes in the intestine and the gut-associated lymphoid tissues are critically involved in sensing components of the microbiome and regulating immune responses in the intestine to sustain immune tolerance against harmless antigens and to prevent inflammation. These processes have been mostly investigated in the context of the bacterial components of the microbiome so far. The impact of viruses residing in the intestine and the virus sensors, which are activated by these enteric viruses, on intestinal homeostasis and inflammation is just beginning to be unraveled. In this review, we will summarize recent findings indicating an important role of the enteric virome for intestinal homeostasis as well as pathology when the immune system fails to control the enteric virome. We will provide an overview of the virus sensors and signaling pathways, operative in the intestine and the mononuclear phagocyte subsets, which can sense viruses and shape the intestinal immune response. We will discuss how these might interact with resident enteric viruses directly or in context with the bacterial microbiome to affect intestinal homeostasis. PMID:29570694

  12. An evaluation of thiol/disulphide homeostasis in patients with psoriasis

    PubMed Central

    Yorulmaz, Ahu; Erdogan, Serpil; Cakmak, Seray Kulcu; Guney, Elif; Sen, Orhan; Erel, Ozcan

    2017-01-01

    Introduction The role of oxidative stress in the pathogenesis of psoriasis has been investigated in previous studies with conflicting results. On the other hand, well-established treatments currently used in psoriasis exert their effects via a boost of oxidative stress. Recently, a strong positive association between psoriasis, metabolic syndrome and dyslipidemia has also been described showing the complex nature of the disease. Aim To examine thiol/disulphide homeostasis, a newly developed homeostasis assay in psoriasis and evaluate the possible association between thiol/disulphide homeostasis and dyslipidemia in psoriasis. Material and methods The study population included 92 psoriasis patients and 71 healthy subjects. Serum native thiol, total thiol and disulphide levels were investigated in patients with psoriasis and in healthy subjects. In addition, lipid profile (serum total cholesterol, triglyceride, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) levels were investigated in both groups. The association between thiol-disulphide parameters and dyslipidemia was also evaluated. Results Serum total cholesterol and triglyceride levels were found to be higher in patients with psoriasis than in the healthy group. Lower plasma disulphide and higher native thiol levels were found in patients with psoriasis indicating an antioxidant status. Conclusions To our knowledge, this is the first study showing the shift of dynamic thiol/disulphide homeostasis towards the thiol form in psoriasis which indicate higher antioxidant status. PMID:29507562

  13. Molecular aspects of bacterial pH sensing and homeostasis

    PubMed Central

    Krulwich, Terry A.; Sachs, George; Padan, Etana

    2011-01-01

    Diverse mechanisms for pH-sensing and cytoplasmic pH homeostasis enable most bacteria to tolerate or grow at external pH values that are outside the cytoplasmic pH range they must maintain for growth. The most extreme cases are exemplified by the extremophiles that inhabit environments whose pH is below 3 or above 11. Here we describe how recent insights into the structure and function of key molecules and their regulators reveal novel strategies of bacterial pH-homeostasis. These insights may help us better target certain pathogens and better harness the capacities of environmental bacteria. PMID:21464825

  14. A Cross-Age Study of Student Understanding of the Concept of Homeostasis.

    ERIC Educational Resources Information Center

    Westbrook, Susan L.; Marek, Edmund A.

    1992-01-01

    The conceptual views of homeostasis held by students (n=300) in seventh grade life science, tenth grade biology, and college zoology were examined. A biographical questionnaire, the results from two Piagetian-like developmental tasks, and a concept evaluation statement of homeostasis were collected from each student. Understanding of the concept…

  15. Food Intake Does Not Differ between Obese Women Who Are Metabolically Healthy or Abnormal1234

    PubMed Central

    Kimokoti, Ruth W; Judd, Suzanne E; Shikany, James M; Newby, PK

    2014-01-01

    Background: Metabolically healthy obesity may confer lower risk of adverse health outcomes compared with abnormal obesity. Diet and race are postulated to influence the phenotype, but their roles and their interrelations on healthy obesity are unclear. Objective: We evaluated food intakes of metabolically healthy obese women in comparison to intakes of their metabolically healthy normal-weight and metabolically abnormal obese counterparts. Methods: This was a cross-sectional study in 6964 women of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Participants were aged 45–98 y with a body mass index (BMI; kg/m2) ≥18.5 and free of cardiovascular diseases, diabetes, and cancer. Food intake was collected by using a food-frequency questionnaire. BMI phenotypes were defined by using metabolic syndrome (MetS) and homeostasis model assessment of insulin resistance (HOMA-IR) criteria. Mean differences in food intakes among BMI phenotypes were compared by using ANCOVA. Results: Approximately one-half of obese women (white: 45%; black: 55%) as defined by MetS criteria and approximately one-quarter of obese women (white: 28%; black: 24%) defined on the basis of HOMA-IR values were metabolically healthy. In age-adjusted analyses, healthy obesity and normal weight as defined by both criteria were associated with lower intakes of sugar-sweetened beverages compared with abnormal obesity among both white and black women (P < 0.05). HOMA-IR–defined healthy obesity and normal weight were also associated with higher fruit and low-fat dairy intakes compared with abnormal obesity in white women (P < 0.05). Results were attenuated and became nonsignificant in multivariable-adjusted models that additionally adjusted for BMI, marital status, residential region, education, annual income, alcohol intake, multivitamin use, cigarette smoking status, physical activity, television viewing, high-sensitivity C-reactive protein, menopausal status, hormone therapy

  16. Role of perisynaptic parameters in neurotransmitter homeostasis - computational study of a general synapse

    PubMed Central

    Pendyam, Sandeep; Mohan, Ashwin; Kalivas, Peter W.; Nair, Satish S.

    2015-01-01

    Extracellular neurotransmitter concentrations vary over a wide range depending on the type of neurotransmitter and location in the brain. Neurotransmitter homeostasis near a synapse is achieved by a balance of several mechanisms including vesicular release from the presynapse, diffusion, uptake by transporters, non-synaptic production, and regulation of release by autoreceptors. These mechanisms are also affected by the glia surrounding the synapse. However, the role of these mechanisms in achieving neurotransmitter homeostasis is not well understood. A biophysical modeling framework was proposed to reverse engineer glial configurations and parameters related to homeostasis for synapses that support a range of neurotransmitter gradients. Model experiments reveal that synapses with extracellular neurotransmitter concentrations in the micromolar range require non-synaptic neurotransmitter sources and tight synaptic isolation by extracellular glial formations. The model was used to identify the role of perisynaptic parameters on neurotransmitter homeostasis, and to propose glial configurations that could support different levels of extracellular neurotransmitter concentrations. Ranking the parameters based on their effect on neurotransmitter homeostasis, non-synaptic sources were found to be the most important followed by transporter concentration and diffusion coefficient. PMID:22460547

  17. [Glucose homeostasis and gut-brain connection].

    PubMed

    De Vadder, Filipe; Mithieux, Gilles

    2015-02-01

    Since the XIX(th) century, the brain has been known for its role in regulating food intake (via the control of hunger sensation) and glucose homeostasis. Further interest has come from the discovery of gut hormones, which established a clear link between the gut and the brain in regulating glucose and energy homeostasis. The brain has two particular structures, the hypothalamus and the brainstem, which are sensitive to information coming either from peripheral organs or from the gut (via circulating hormones or nutrients) about the nutritional status of the organism. However, the efforts for a better understanding of these mechanisms have allowed to unveil a new gut-brain neural axis as a key regulator of the metabolic status of the organism. Certain nutrients control the hypothalamic homeostatic function via this axis. In this review, we describe how the gut is connected to the brain via different neural pathways, and how the interplay between these two organs drives the energy balance. © 2015 médecine/sciences – Inserm.

  18. Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis.

    PubMed

    Mortha, Arthur; Chudnovskiy, Aleksey; Hashimoto, Daigo; Bogunovic, Milena; Spencer, Sean P; Belkaid, Yasmine; Merad, Miriam

    2014-03-28

    The intestinal microbiota and tissue-resident myeloid cells promote immune responses that maintain intestinal homeostasis in the host. However, the cellular cues that translate microbial signals into intestinal homeostasis remain unclear. Here, we show that deficient granulocyte-macrophage colony-stimulating factor (GM-CSF) production altered mononuclear phagocyte effector functions and led to reduced regulatory T cell (T(reg)) numbers and impaired oral tolerance. We observed that RORγt(+) innate lymphoid cells (ILCs) are the primary source of GM-CSF in the gut and that ILC-driven GM-CSF production was dependent on the ability of macrophages to sense microbial signals and produce interleukin-1β. Our findings reveal that commensal microbes promote a crosstalk between innate myeloid and lymphoid cells that leads to immune homeostasis in the intestine.

  19. Neuronal substrates of sleep homeostasis; lessons from flies, rats and mice.

    PubMed

    Donlea, Jeffrey M; Alam, Md Noor; Szymusiak, Ronald

    2017-06-01

    Sleep homeostasis is a fundamental property of vigilance state regulation that is highly conserved across species. Neuronal systems and circuits that underlie sleep homeostasis are not well understood. In Drosophila, a neuronal circuit involving neurons in the ellipsoid body and in the dorsal Fan-shaped body is a candidate for both tracing sleep need during waking and translating it to increased sleep drive and expression. Sleep homeostasis in rats and mice involves multiple neuromodulators acting on multiple wake- and sleep-promoting neuronal systems. A functional central homeostat emerges from A 1 receptor mediated actions of adenosine on wake-promoting neurons in the basal forebrain and hypothalamus, and A 2A adenosine receptor-mediated actions on sleep-promoting neurons in the preoptic hypothalamus and nucleus accumbens. Copyright © 2017. Published by Elsevier Ltd.

  20. Neural control of renal function in health and disease.

    PubMed

    DiBona, G F

    1994-04-01

    The renal sympathetic innervation of the kidney exerts significant effects on multiple aspects of renal function, including renal haemodynamics, tubular sodium and water reabsorption and renin secretion. These effects constitute an important control system which is important in the physiological regulation of arterial pressure and total body fluid and sodium homeostasis. Abnormalities in this regulatory mechanism have pathophysiological consequences and are manifest in clinically relevant human disease states. Decreased renal sympathetic nerve activity results in impaired renin secretion, the inability to conserve sodium normally and an attenuated ability to dispose of both acute and chronic sodium loads. Increased renal sympathetic nerve activity contributes significantly to the excess renal sodium retention and related renal abnormalities observed in both hypertension and oedema forming conditions, such as cardiac failure, cirrhosis and nephrotic syndrome.

  1. Actin turnover maintains actin filament homeostasis during cytokinetic ring contraction

    PubMed Central

    Palani, Saravanan; Sommese, Ruth; Kamnev, Anton; Hatano, Tomoyuki; Sivaramakrishnan, Sivaraj

    2017-01-01

    Cytokinesis in many eukaryotes involves a tension-generating actomyosin-based contractile ring. Many components of actomyosin rings turn over during contraction, although the significance of this turnover has remained enigmatic. Here, using Schizosaccharomyces japonicus, we investigate the role of turnover of actin and myosin II in its contraction. Actomyosin ring components self-organize into ∼1-µm-spaced clusters instead of undergoing full-ring contraction in the absence of continuous actin polymerization. This effect is reversed when actin filaments are stabilized. We tested the idea that the function of turnover is to ensure actin filament homeostasis in a synthetic system, in which we abolished turnover by fixing rings in cell ghosts with formaldehyde. We found that these rings contracted fully upon exogenous addition of a vertebrate myosin. We conclude that actin turnover is required to maintain actin filament homeostasis during ring contraction and that the requirement for turnover can be bypassed if homeostasis is achieved artificially. PMID:28655757

  2. Using glutamate homeostasis as a target for treating addictive disorders

    PubMed Central

    Reissner, Kathryn J.; Kalivas, Peter W.

    2010-01-01

    Well-developed cellular mechanisms exist to preserve glutamate homeostasis and regulate extrasynaptic glutamate levels. Accumulating evidence indicates that disruptions in glutamate homeostasis are associated with addictive disorders. The disruptions in glutamate concentrations observed following prolonged exposure to drugs of abuse are associated with changes in the function and activity of several key components within the homeostatic control mechanism, including the cystine/glutamate exchanger xc− and the glial glutamate transporter EAAT2/GLT-1. Changes in the balance between synaptic and extrasynaptic glutamate levels in turn influence signaling through pre- and postsynaptic glutamate receptors, and thus affect synaptic plasticity and circuit-level activity. In this review we describe the evidence for impaired glutamate homestasis as a critical mediator of long-term drug-seeking behaviors, how chronic neuroadaptations in xc− and GLT-1 mediate a disruption in glutamate homeostasis, and how targeting these components restores glutamate levels and inhibits drug-seeking behaviors. PMID:20634691

  3. Homeostasis: Beyond Curt Richter1

    PubMed Central

    Woods, Stephen C.; Ramsay, Douglas S.

    2007-01-01

    Curt Richter introduced behavioral control into the concept of homeostasis, thereby opening entire fields of research. The prevailing dogma, and the techniques he used, conspired to lead Richter and others to interpret regulation in strict negative feedback terms. Although this point of view continues to be embraced by many contemporary biologists, we believe that prevailing sentiment favors a broader view in which organisms integrate anticipatory pre-emptive control over regulated variables whenever possible. PMID:17524521

  4. Central insulin action in energy and glucose homeostasis.

    PubMed

    Plum, Leona; Belgardt, Bengt F; Brüning, Jens C

    2006-07-01

    Insulin has pleiotropic biological effects in virtually all tissues. However, the relevance of insulin signaling in peripheral tissues has been studied far more extensively than its role in the brain. An evolving body of evidence indicates that in the brain, insulin is involved in multiple regulatory mechanisms including neuronal survival, learning, and memory, as well as in regulation of energy homeostasis and reproductive endocrinology. Here we review insulin's role as a central homeostatic signal with regard to energy and glucose homeostasis and discuss the mechanisms by which insulin communicates information about the body's energy status to the brain. Particular emphasis is placed on the controversial current debate about the similarities and differences between hypothalamic insulin and leptin signaling at the molecular level.

  5. Targeting Cardiomyocyte Ca2+ Homeostasis in Heart Failure

    PubMed Central

    Røe, Åsmund T.; Frisk, Michael; Louch, William E.

    2015-01-01

    Improved treatments for heart failure patients will require the development of novel therapeutic strategies that target basal disease mechanisms. Disrupted cardiomyocyte Ca2+ homeostasis is recognized as a major contributor to the heart failure phenotype, as it plays a key role in systolic and diastolic dysfunction, arrhythmogenesis, and hypertrophy and apoptosis signaling. In this review, we outline existing knowledge of the involvement of Ca2+ homeostasis in these deficits, and identify four promising targets for therapeutic intervention: the sarcoplasmic reticulum Ca2+ ATPase, the Na+-Ca2+ exchanger, the ryanodine receptor, and t-tubule structure. We discuss experimental data indicating the applicability of these targets that has led to recent and ongoing clinical trials, and suggest future therapeutic approaches. PMID:25483944

  6. Dynamic thiol/disulfide homeostasis and effects of smoking on homeostasis parameters in patients with psoriasis.

    PubMed

    Emre, Selma; Demirseren, Duriye Deniz; Alisik, Murat; Aktas, Akin; Neselioglu, Salim; Erel, Ozcan

    2017-12-01

    Recently, increased reactive oxygen species (ROS), reduced antioxidant capacity, and oxidative stress have been suggested in the pathogenesis of psoriasis. The aim of this study to evaluate the thiol/disulfide homeostasis in patients with psoriasis. Ninety patients with psoriasis who did not receive any systemic treatment in the last six  months were included in the study. Seventy-six age and gender-matched healthy volunteers served as control group. Thiol/disulfide homeostasis was measured in venous blood samples obtained from patient and control groups. Native thiol and total thiol levels were significantly higher in patients than in control group. When thiol/disulfide hemostasis parameters and clinical and demographic characteristics were compared, a negative correlation was detected between native thiol and total thiol with age. The levels of total thiols had also negative correlation with PASI and duration of the disease. When we divided the patients into smokers and non-smokers, native thiol and total thiol levels were significantly higher in smokers than in controls, whereas native thiol and total thiol levels were comparable in non-smoker patients and controls. Thiol/disulfide balance shifted towards thiol in psoriasis patients and this may be responsible for increased keratinocyte proliferation in the pathogenesis of psoriasis.

  7. Electrocardiographic abnormalities in opiate addicts.

    PubMed

    Wallner, Christina; Stöllberger, Claudia; Hlavin, Anton; Finsterer, Josef; Hager, Isabella; Hermann, Peter

    2008-12-01

    To determine in a cross-sectional study the prevalence of electrocardiographic (ECG) abnormalities in opiate addicts who were therapy-seeking and its association with demographic, clinical and drug-specific parameters. In consecutive therapy-seeking opiate addicts, a 12-lead ECG was registered within 24 hours after admission and evaluated according to a pre-set protocol between October 2004 and August 2006. Additionally, demographic, clinical and drug-specific parameters were recorded. Included were 511 opiate-addicts, 25% female, with a mean age of 29 years (range 17-59 years). One or more ECG abnormalities were found in 314 patients (61%). In the 511 patients we found most commonly ST abnormalities (19%), QTc prolongation (13%), tall R- and/or S-waves (11%) and missing R progression (10%). ECG abnormalities were more common in males than in females (64 versus 54%, P < 0.05), and in patients with positive than negative urine findings for cannabis (68 versus 57%, P < 0.05). Patients with ST abnormalities were more often males than females (21 versus 11%, P < 0.05), had a history of seizures less often (16 versus 27%, P < 0.05), had positive than negative urine findings for cannabis more often (26 versus 15%, P < 0.01) and had negative than positive urine findings for methadone more often (21 versus 11%, P < 0.05). QTc prolongation was more frequent in patients with high dosages of maintenance drugs than in patients with medium or low dosages (27 versus 12 versus 10%, P < 0.05) and in patients whose urine findings were positive than negative for methadone (23 versus 11%, P < 0.001) as well as for benzodiazepines (17 versus 9%, P < 0.05). Limitations of the data are that in most cases other risk factors for the cardiac abnormalities were not known. ECG abnormalities are frequent in opiate addicts. The most frequent ECG abnormalities are ST abnormalities, QTc prolongation and tall R- and/or S-waves. ST abnormalities are associated with cannabis, and QTc prolongation

  8. Peripheral Interventions Enhancing Brain Glutamate Homeostasis Relieve Amyloid β- and TNFα- Mediated Synaptic Plasticity Disruption in the Rat Hippocampus.

    PubMed

    Zhang, Dainan; Mably, Alexandra J; Walsh, Dominic M; Rowan, Michael J

    2017-07-01

    Dysregulation of glutamate homeostasis in the interstitial fluid of the brain is strongly implicated in causing synaptic dysfunction in many neurological and psychiatric illnesses. In the case of Alzheimer's disease (AD), amyloid β (Aβ)-mediated disruption of synaptic plasticity and memory can be alleviated by interventions that directly remove glutamate or block certain glutamate receptors. An alternative strategy is to facilitate the removal of excess glutamate from the nervous system by activating peripheral glutamate clearance systems. One such blood-based system, glutamate oxaloacetate transaminase (GOT), is activated by oxaloacetate, which acts as a co-substrate. We report here that synthetic and AD brain-derived Aβ-mediated inhibition of synaptic long-term potentiation in the hippocampus is alleviated by oxaloacetate. Moreover the effect of oxaloacetate was GOT-dependent. The disruptive effects of a general inhibitor of excitatory amino acid transport or TNFα, a pro-inflammatory mediator of Aβ action, were also reversed by oxaloacetate. Furthermore, another intervention that increases peripheral glutamate clearance, peritoneal dialysis, mimicked the beneficial effect of oxaloacetate. These findings lend support to the promotion of the peripheral clearance of glutamate as a means to alleviate synaptic dysfunction that is caused by impaired glutamate homeostasis in the brain. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Disruption of iron homeostasis and lung disease.

    PubMed

    Ghio, Andrew J

    2009-07-01

    As a result of a direct exchange with the external environment, the lungs are exposed to both iron and agents with a capacity to disrupt the homeostasis of this metal (e.g. particles). An increased availability of catalytically reactive iron can result from these exposures and, by generating an oxidative stress, this metal can contribute to tissue injury. By importing this Fe(3+) into cells for storage in a chemically less reactive form, the lower respiratory tract demonstrates an ability to mitigate both the oxidative stress presented by iron and its potential for tissue injury. This means that detoxification is accomplished by chemical reduction to Fe(2+) (e.g. by duodenal cytochrome b and other ferrireductases), iron import (e.g. by divalent metal transporter 1 and other transporters), and storage in ferritin. The metal can subsequently be exported from the cell (e.g. by ferroportin 1) in a less reactive state relative to that initially imported. Iron is then transported out of the lung via the mucociliary pathway or blood and lymphatic pathways to the reticuloendothelial system for long term storage. This coordinated handling of iron in the lung appears to be disrupted in several acute diseases on the lung including infections, acute respiratory distress syndrome, transfusion-related acute lung injury, and ischemia-reperfusion. Exposures to bleomycin, dusts and fibers, and paraquat similarly alter iron homeostasis in the lung to affect an oxidative stress. Finally, iron homeostasis is disrupted in numerous chronic lung diseases including pulmonary alveolar proteinosis, transplantation, cigarette smoking, and cystic fibrosis.

  10. Laminar shear stress promotes mitochondrial homeostasis in endothelial cells.

    PubMed

    Wu, Li-Hong; Chang, Hao-Chun; Ting, Pei-Ching; Wang, Danny L

    2018-06-01

    Vascular endothelial cells (ECs) are constantly subjected to flow-induced shear stress that is crucial for endothelial functions. Laminar shear stress (LSS) exerts atheroprotection to ECs. Mitochondrial homeostasis is essential for cellular survival. However, the effects of LSS on mitochondrial homeostasis in ECs remain unclear. Mitochondrial homeostasis in ECs exposed to LSS was examined. Cultured human umbilical vein ECs were subjected to LSS (12 dynes/cm 2 ) generated by a parallel-plate flow chamber system. ECs subjected to LSS demonstrated an increment of mitochondria in tubular form coupled with the increase of fusion proteins (Mfn2, OPA1) and the decrease of fission protein (Fis1). An increase of both long- and short- OPA1 along with a higher protease YME1L level were observed. LSS triggered a rapid phosphorylation on S637 but a decrease on S616 of fission-controlled protein Drp1. Consistently, Drp1 translocation to mitochondria was decreased in sheared ECs, suggesting that LSS promotes mitochondrial fusion. Enhanced mitochondrial biogenesis in sheared ECs was shown by the increase of mitochondrial mass and its regulatory proeins (PGC1α, TFAM, Nrf1). LSS enhances the expression of mitochondrial antioxidant enzymes and improves mitochondrial functions indicated by the increase of mitochondrial membrane potential (ΔΨm) and ATP generation. TNFα treatment decreased mitochondrial tubular network and its functions in ECs. LSS mitigated TNFα-induced mitochondrial impairments in ECs. Our results clearly indicate that LSS promotes mitochondrial homeostasis and attenuates inflammation-induced mitochondrial impairments in ECs. Our results provide novel insights into the manner of mitochondrial dynamics and functions modulated by LSS that contribute to endothelial integrity. © 2017 Wiley Periodicals, Inc.

  11. Activation of G protein-coupled estrogen receptor 1 (GPER-1) decreases fluid intake in female rats

    PubMed Central

    Santollo, Jessica; Daniels, Derek

    2015-01-01

    Estradiol (E2) decreases fluid intake in the female rat and recent studies from our lab demonstrate that the effect is at least in part mediated by membrane-associated estrogen receptors. Because multiple estrogen receptor subtypes can localize to the cell membrane, it is unclear which receptor(s) is generating the anti-dipsogenic effect of E2. The G protein-coupled estrogen receptor 1 (GPER-1) is a particularly interesting possibility because it has been shown to regulate blood pressure; many drinking-regulatory systems play overlapping roles in the control of blood pressure. Accordingly, we tested the hypothesis that activation of GPER-1 is sufficient to decrease fluid intake in female rats. In support of this hypothesis we found that treatment with the selective GPER-1 agonist G1 reduced AngII-stimulated fluid intake in OVX rats. Given the close association between food and fluid intakes in rats, and previous reports suggesting GPER-1 plays a role in energy homeostasis, we tested the hypothesis that the effect of GPER-1 on fluid intake was caused by a more direct effect on food intake. We found, however, that G1-treatment did not influence short-term or overnight food intake in OVX rats. Together these results reveal a novel effect of GPER-1 in the control of drinking behavior and provide an example of the divergence in the controls of fluid and food intakes in female rats. PMID:26093261

  12. Activation of G protein-coupled estrogen receptor 1 (GPER-1) decreases fluid intake in female rats.

    PubMed

    Santollo, Jessica; Daniels, Derek

    2015-07-01

    Estradiol (E2) decreases fluid intake in the female rat and recent studies from our lab demonstrate that the effect is at least in part mediated by membrane-associated estrogen receptors. Because multiple estrogen receptor subtypes can localize to the cell membrane, it is unclear which receptor(s) is generating the anti-dipsogenic effect of E2. The G protein-coupled estrogen receptor 1 (GPER-1) is a particularly interesting possibility because it has been shown to regulate blood pressure; many drinking-regulatory systems play overlapping roles in the control of blood pressure. Accordingly, we tested the hypothesis that activation of GPER-1 is sufficient to decrease fluid intake in female rats. In support of this hypothesis we found that treatment with the selective GPER-1 agonist G1 reduced AngII-stimulated fluid intake in OVX rats. Given the close association between food and fluid intakes in rats, and previous reports suggesting GPER-1 plays a role in energy homeostasis, we tested the hypothesis that the effect of GPER-1 on fluid intake was caused by a more direct effect on food intake. We found, however, that G1-treatment did not influence short-term or overnight food intake in OVX rats. Together these results reveal a novel effect of GPER-1 in the control of drinking behavior and provide an example of the divergence in the controls of fluid and food intakes in female rats. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Biochemical abnormalities in neonatal seizures.

    PubMed

    Sood, Arvind; Grover, Neelam; Sharma, Roshan

    2003-03-01

    The presence of seizure does not constitute a diagnoses but it is a symptom of an underlying central nervous system disorder due to systemic or biochemical disturbances. Biochemical disturbances occur frequently in the neonatal seizures either as an underlying cause or as an associated abnormality. In their presence, it is difficult to control seizure and there is a risk of further brain damage. Early recognition and treatment of biochemical disturbances is essential for optimal management and satisfactory long term outcome. The present study was conducted in the department of pediatrics in IGMC Shimla on 59 neonates. Biochemical abnormalities were detected in 29 (49.15%) of cases. Primary metabolic abnormalities occurred in 10(16.94%) cases of neonatal seizures, most common being hypocalcaemia followed by hypoglycemia, other metabolic abnormalities include hypomagnesaemia and hyponateremia. Biochemical abnormalities were seen in 19(38.77%) cases of non metabolic seizure in neonates. Associated metabolic abnormalities were observed more often with Hypoxic-ischemic-encephalopathy (11 out of 19) cases and hypoglycemia was most common in this group. No infant had hyponateremia, hyperkelemia or low zinc level.

  14. Delayed sub-aponeurotic fluid collections in infancy: Three cases and a review of the literature.

    PubMed

    Petraglia, Anthony L; Moravan, Michael J; Marky, Andrew H; Silberstein, Howard J

    2010-07-21

    Sub-aponeurotic fluid collections (SFCs) in the neonatal period are poorly described in the literature. We describe the occurrence, possible etiologies and treatment of sub-aponeurotic fluid collections following the neonatal period. We present 3 cases of previously healthy children who developed soft, fluctuant, extracranial masses several weeks after birth. All 3 children were seen by a pediatric neurosurgeon after parents noticed scalp masses between 5 and 9 weeks of age. All 3 children were found to be otherwise healthy. Two of the children were born via C-section and 1 child was born vaginally. The vaginal delivery was described as difficult and utilized vacuum assist. Scalp electrodes were placed in all 3 children for intensive monitoring during labor. These children received plain skull x-rays to assess for abnormalities, and 2 of the children underwent a non-contrast brain CT scan to better characterize the fluid collection. Plain x-rays and CT scans showed no abnormalities of the skull or ventricles. In both patients who underwent a CT scan, a soft tissue prominence was noted with a Hounsfield unit similar to water. All cases resolved between 5 and 9 weeks after initial presentation, with no long-term sequelae. SFCs presenting after the neonatal period are usually associated with benign soft tissue swellings. Use of fetal scalp electrodes has been shown to cause cerebrospinal fluid (CSF) leakage in the neonatal period and may result in delayed SFC. This condition is benign, and the recommended course of treatment is conservative management.

  15. Delayed sub-aponeurotic fluid collections in infancy: Three cases and a review of the literature

    PubMed Central

    Petraglia, Anthony L.; Moravan, Michael J.; Marky, Andrew H.; Silberstein, Howard J.

    2010-01-01

    Background: Sub-aponeurotic fluid collections (SFCs) in the neonatal period are poorly described in the literature. We describe the occurrence, possible etiologies and treatment of sub-aponeurotic fluid collections following the neonatal period. Case Description: We present 3 cases of previously healthy children who developed soft, fluctuant, extracranial masses several weeks after birth. All 3 children were seen by a pediatric neurosurgeon after parents noticed scalp masses between 5 and 9 weeks of age. All 3 children were found to be otherwise healthy. Two of the children were born via C-section and 1 child was born vaginally. The vaginal delivery was described as difficult and utilized vacuum assist. Scalp electrodes were placed in all 3 children for intensive monitoring during labor. These children received plain skull x-rays to assess for abnormalities, and 2 of the children underwent a non-contrast brain CT scan to better characterize the fluid collection. Plain x-rays and CT scans showed no abnormalities of the skull or ventricles. In both patients who underwent a CT scan, a soft tissue prominence was noted with a Hounsfield unit similar to water. All cases resolved between 5 and 9 weeks after initial presentation, with no long-term sequelae. Conclusion: SFCs presenting after the neonatal period are usually associated with benign soft tissue swellings. Use of fetal scalp electrodes has been shown to cause cerebrospinal fluid (CSF) leakage in the neonatal period and may result in delayed SFC. This condition is benign, and the recommended course of treatment is conservative management. PMID:20847915

  16. Milrinone and homeostasis to treat cerebral vasospasm associated with subarachnoid hemorrhage: the Montreal Neurological Hospital protocol.

    PubMed

    Lannes, Marcelo; Teitelbaum, Jeanne; del Pilar Cortés, Maria; Cardoso, Mauro; Angle, Mark

    2012-06-01

    For the treatment of cerebral vasospasm, current therapies have focused on increasing blood flow through blood pressure augmentation, hypervolemia, the use of intra-arterial vasodilators, and angioplasty of proximal cerebral vessels. Through a large case series, we present our experience of treating cerebral vasospasm with a protocol based on maintenance of homeostasis (correction of electrolyte and glucose disturbances, prevention and treatment of hyperthermia, replacement of fluid losses), and the use of intravenous milrinone to improve microcirculation (the Montreal Neurological Hospital protocol). Our objective is to describe the use milrinone in our practice and the neurological outcomes associated with this approach. Large case series based on the review of all patients diagnosed with delayed ischemic neurologic deficits after aneurysmal subarachnoid hemorrhage between April 1999 and April 2006. 88 patients were followed for a mean time of 44.6 months. An intravenous milrinone infusion was used for a mean of 9.8 days without any significant side effects. No medical complications associated with this protocol were observed. There were five deaths; of the surviving patients, 48.9 % were able to go back to their previous baseline and 75 % had a good functional outcome (modified Rankin scale ≤ 2). A protocol using intravenous milrinone, and the maintenance of homeostasis is simple to use and requires less intensive monitoring and resources than the standard triple H therapy. Despite the obvious limitations of this study's design, we believe that it would be now appropriate to proceed with formal prospective studies of this protocol.

  17. Taste Bud Homeostasis in Health, Disease, and Aging

    PubMed Central

    2014-01-01

    The mammalian taste bud is an onion-shaped epithelial structure with 50–100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8–12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging. PMID:24287552

  18. Taste bud homeostasis in health, disease, and aging.

    PubMed

    Feng, Pu; Huang, Liquan; Wang, Hong

    2014-01-01

    The mammalian taste bud is an onion-shaped epithelial structure with 50-100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8-12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging.

  19. CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis.

    PubMed

    Kim, Hyunbae; Zheng, Ze; Walker, Paul D; Kapatos, Gregory; Zhang, Kezhong

    2017-07-15

    Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress. Copyright © 2017 American Society for Microbiology.

  20. CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis

    PubMed Central

    Kim, Hyunbae; Zheng, Ze; Walker, Paul D.; Kapatos, Gregory

    2017-01-01

    ABSTRACT Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress. PMID:28461393

  1. Control of brain development and homeostasis by local and systemic insulin signalling.

    PubMed

    Liu, J; Spéder, P; Brand, A H

    2014-09-01

    Insulin and insulin-like growth factors (IGFs) are important regulators of growth and metabolism. In both vertebrates and invertebrates, insulin/IGFs are made available to various organs, including the brain, through two routes: the circulating systemic insulin/IGFs act on distant organs via endocrine signalling, whereas insulin/IGF ligands released by local tissues act in a paracrine or autocrine fashion. Although the mechanisms governing the secretion and action of systemic insulin/IGF have been the focus of extensive investigation, the significance of locally derived insulin/IGF has only more recently come to the fore. Local insulin/IGF signalling is particularly important for the development and homeostasis of the central nervous system, which is insulated from the systemic environment by the blood-brain barrier. Local insulin/IGF signalling from glial cells, the blood-brain barrier and the cerebrospinal fluid has emerged as a potent regulator of neurogenesis. This review will address the main sources of local insulin/IGF and how they affect neurogenesis during development. In addition, we describe how local insulin/IGF signalling couples neural stem cell proliferation with systemic energy state in Drosophila and in mammals. © 2014 John Wiley & Sons Ltd.

  2. Chorionic villus sampling for abnormal screening compared to historical indications: prevalence of abnormal karyotypes.

    PubMed

    Marshall, Nicole E; Fraley, Gwen; Feist, Cori; Burns, Michael J; Pereira, Leonardo

    2012-08-01

    To determine the prevalence of abnormal karyotype results in women undergoing chorionic villus sampling (CVS) for abnormal first trimester screening compared to CVS for historical indications (advanced maternal age (AMA) or prior aneuploidy). Retrospective cohort of all patients undergoing CVS at Oregon Health & Science University from January 2006 to June 2010. Patients were separated based on CVS indication: (1) positive ultrasound (U/S) or serum screening; or (2) AMA or prior aneuploidy with normal or no screening. Prevalence of abnormal karyotype results were compared between groups. Fetal karyotyping was successful in 500 of 506 CVS procedures performed. 203 CVS were performed for positive screening with 69 abnormal karyotypes (34.0%). 264 CVS were performed for historical indications with 11 abnormal karyotypes (4.2%). This difference was statistically significant (χ(2) 71.9, p < 0.001; OR 11.8 [95% CI 5.8, 24.6]). There were two age-related aneuplodies in AMA women without positive screening. 42 out of 44 AMA women diagnosed with aneuploidy (95.5%) had abnormal U/S and/or serum screening (35 U/S, 4 serum, 3 U/S and serum). Combined ultrasound and serum screening should be recommended to all women, including AMA women, prior to undergoing invasive testing to improve risk-based counseling and minimize morbidity.

  3. Tissues Use Resident Dendritic Cells and Macrophages to Maintain Homeostasis and to Regain Homeostasis upon Tissue Injury: The Immunoregulatory Role of Changing Tissue Environments

    PubMed Central

    Lech, Maciej; Gröbmayr, Regina; Weidenbusch, Marc; Anders, Hans-Joachim

    2012-01-01

    Most tissues harbor resident mononuclear phagocytes, that is, dendritic cells and macrophages. A classification that sufficiently covers their phenotypic heterogeneity and plasticity during homeostasis and disease does not yet exist because cell culture-based phenotypes often do not match those found in vivo. The plasticity of mononuclear phagocytes becomes obvious during dynamic or complex disease processes. Different data interpretation also originates from different conceptual perspectives. An immune-centric view assumes that a particular priming of phagocytes then causes a particular type of pathology in target tissues, conceptually similar to antigen-specific T-cell priming. A tissue-centric view assumes that changing tissue microenvironments shape the phenotypes of their resident and infiltrating mononuclear phagocytes to fulfill the tissue's need to maintain or regain homeostasis. Here we discuss the latter concept, for example, why different organs host different types of mononuclear phagocytes during homeostasis. We further discuss how injuries alter tissue environments and how this primes mononuclear phagocytes to enforce this particular environment, for example, to support host defense and pathogen clearance, to support the resolution of inflammation, to support epithelial and mesenchymal healing, and to support the resolution of fibrosis to the smallest possible scar. Thus, organ- and disease phase-specific microenvironments determine macrophage and dendritic cell heterogeneity in a temporal and spatial manner, which assures their support to maintain and regain homeostasis in whatever condition. Mononuclear phagocytes contributions to tissue pathologies relate to their central roles in orchestrating all stages of host defense and wound healing, which often become maladaptive processes, especially in sterile and/or diffuse tissue injuries. PMID:23251037

  4. The liver in regulation of iron homeostasis.

    PubMed

    Rishi, Gautam; Subramaniam, V Nathan

    2017-09-01

    The liver is one of the largest and most functionally diverse organs in the human body. In addition to roles in detoxification of xenobiotics, digestion, synthesis of important plasma proteins, gluconeogenesis, lipid metabolism, and storage, the liver also plays a significant role in iron homeostasis. Apart from being the storage site for excess body iron, it also plays a vital role in regulating the amount of iron released into the blood by enterocytes and macrophages. Since iron is essential for many important physiological and molecular processes, it increases the importance of liver in the proper functioning of the body's metabolism. This hepatic iron-regulatory function can be attributed to the expression of many liver-specific or liver-enriched proteins, all of which play an important role in the regulation of iron homeostasis. This review focuses on these proteins and their known roles in the regulation of body iron metabolism. Copyright © 2017 the American Physiological Society.

  5. Hypoxia-Inducible Factors Link Iron Homeostasis and Erythropoiesis

    PubMed Central

    Shah, Yatrik M.; Xie, Liwei

    2014-01-01

    Iron is required for efficient oxygen transport, and hypoxia signaling links erythropoiesis with iron homeostasis. Hypoxia induces a highly conserved signaling pathway in cells under conditions of low O2. One component of this pathway, hypoxia-inducible factor (HIF), is a transcription factor that is highly active in hypoxic cells. The first HIF target gene characterized was EPO, which encodes erythropoietin—a glycoprotein hormone that controls erythropoiesis. The past decade has led to fundamental advances in our understanding of how hypoxia regulates iron levels to support erythropoiesis and maintain systemic iron homeostasis. We review the cell-type specific effects of hypoxia and HIFs in adaptive response to changes in oxygen and iron availability, as well as potential uses of HIF modulators for patients with iron-related disorders. PMID:24389303

  6. TMBIM-mediated Ca 2+ homeostasis and cell death

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Qun

    Ca 2+ is a ubiquitous intracellular messenger that regulates numerous physiological activities in humans, animals, plants, and bacteria. Cytosolic Ca 2+ is kept at a low level, but subcellular organelles such as the endoplasmic reticulum (ER) and Golgi Apparatus maintain high-concentration Ca 2+ stores. Under resting conditions, store Ca 2+ homeostasis is dynamically regulated to equilibrate between active Ca 2+ uptake and passive Ca 2+ leak processes. The evolutionarily conserved Transmembrane BAX Inhibitor-1 Motif-containing (TMBIM) proteins mediate Ca 2+ homeostasis and cell death. This review focuses on recent advances in functional and structural analysis of TMBIM proteins in regulation ofmore » the two related functions. The roles of TMBIM proteins in pathogen infection and cancer are also discussed with prospects for treatment.« less

  7. TMBIM-mediated Ca 2+ homeostasis and cell death

    DOE PAGES

    Liu, Qun

    2017-01-05

    Ca 2+ is a ubiquitous intracellular messenger that regulates numerous physiological activities in humans, animals, plants, and bacteria. Cytosolic Ca 2+ is kept at a low level, but subcellular organelles such as the endoplasmic reticulum (ER) and Golgi Apparatus maintain high-concentration Ca 2+ stores. Under resting conditions, store Ca 2+ homeostasis is dynamically regulated to equilibrate between active Ca 2+ uptake and passive Ca 2+ leak processes. The evolutionarily conserved Transmembrane BAX Inhibitor-1 Motif-containing (TMBIM) proteins mediate Ca 2+ homeostasis and cell death. This review focuses on recent advances in functional and structural analysis of TMBIM proteins in regulation ofmore » the two related functions. The roles of TMBIM proteins in pathogen infection and cancer are also discussed with prospects for treatment.« less

  8. Sensitivity and specificity of western blot testing of cerebrospinal fluid and serum for diagnosis of equine protozoal myeloencephalitis in horses with and without neurologic abnormalities.

    PubMed

    Daft, Barbara M; Barr, Bradd C; Gardner, Ian A; Read, Deryck; Bell, William; Peyser, Karen G; Ardans, Alex; Kinde, Hailu; Morrow, Jennifer K

    2002-10-01

    To determine sensitivity and specificity of western blot testing (WBT) of CSF and serum for diagnosis of equine protozoal myeloencephalitis (EPM) in horses with and without neurologic abnormalities. Prospective investigation. 65 horses with and 169 horses without neurologic abnormalities. CSF and serum from horses submitted for necropsy were tested for Sarcocystis neurona-specific antibody with a WBT. Results of postmortem examination were used as the gold standard against which results of the WBT were compared. Sensitivity of WBT of CSF was 87% for horses with and 88% for horses without neurologic abnormalities. Specificity of WBT of CSF was 44% for horses with and 60% for horses without neurologic abnormalities. Regardless of whether horses did or did not have neurologic abnormalities, sensitivity and specificity of WBT of serum were not significantly different from values for WBT of CSF. Ninety-four horses without EPM had histologic evidence of slight CNS inflammation. The low specificity of WBT of CSF indicated that it is inappropriate to diagnose EPM on the basis of a positive test result alone because of the possibility of false-positive test results. The high sensitivity, however, means that a negative result is useful in ruling out EPM. There was no advantage in testing CSF versus serum in horses without neurologic abnormalities. Slight CNS inflammation was common in horses with and without S neurona-specific antibodies in the CSF and should not be considered an indication of CNS infection with S neurona.

  9. Disruption of Calcium Homeostasis During Exercise as a Mediator of Bone Metabolism

    DTIC Science & Technology

    2015-10-01

    Meeting of the American College of Sports Medicine (Appendix A). 15. SUBJECT TERMS calcium homeostasis, exercise, bone resorption, parathyroid hormone ... hormone (PTH). PTH can defend serum Ca by reducing urinary Ca excretion, increasing intestinal Ca absorption, and increasing mobilization of skeletal Ca...certain conditions. It is our contention that disruptions in calcium homeostasis during exercise lead to increases in parathyroid hormone (PTH) and

  10. Gastrointestinal Transit Time, Glucose Homeostasis and Metabolic Health: Modulation by Dietary Fibers

    PubMed Central

    Müller, Mattea; Canfora, Emanuel E.; Blaak, Ellen E.

    2018-01-01

    Gastrointestinal transit time may be an important determinant of glucose homeostasis and metabolic health through effects on nutrient absorption and microbial composition, among other mechanisms. Modulation of gastrointestinal transit may be one of the mechanisms underlying the beneficial health effects of dietary fibers. These effects include improved glucose homeostasis and a reduced risk of developing metabolic diseases such as obesity and type 2 diabetes mellitus. In this review, we first discuss the regulation of gastric emptying rate, small intestinal transit and colonic transit as well as their relation to glucose homeostasis and metabolic health. Subsequently, we briefly address the reported health effects of different dietary fibers and discuss to what extent the fiber-induced health benefits may be mediated through modulation of gastrointestinal transit. PMID:29495569

  11. Proinflammatory and Antimicrobial Nitric Oxide in Gingival Fluid of Diabetic Patients with Periodontal Disease▿

    PubMed Central

    Skaleric, Uros; Gaspirc, Boris; McCartney-Francis, Nancy; Masera, Andrej; Wahl, Sharon M.

    2006-01-01

    Abnormal nitric oxide (NO) synthesis has been implicated in the pathogenesis of both periodontal disease and diabetes mellitus. In diabetic patients, increased inducible NO synthase in inflamed gingiva correlated with NO in gingival crevicular fluid. Although increased NO reflected more-severe inflammation, it was associated with reductions in CFU of Prevotella intermedia, a major periodontopathogen, highlighting dual roles for NO. PMID:17015454

  12. Lipoproteins, cholesterol homeostasis and cardiac health.

    PubMed

    Daniels, Tyler F; Killinger, Karen M; Michal, Jennifer J; Wright, Raymond W; Jiang, Zhihua

    2009-06-29

    Cholesterol is an essential substance involved in many functions, such as maintaining cell membranes, manufacturing vitamin D on surface of the skin, producing hormones, and possibly helping cell connections in the brain. When cholesterol levels rise in the blood, they can, however, have dangerous consequences. In particular, cholesterol has generated considerable notoriety for its causative role in atherosclerosis, the leading cause of death in developed countries around the world. Homeostasis of cholesterol is centered on the metabolism of lipoproteins, which mediate transport of the lipid to and from tissues. As a synopsis of the major events and proteins that manage lipoprotein homeostasis, this review contributes to the substantial attention that has recently been directed to this area. Despite intense scrutiny, the majority of phenotypic variation in total cholesterol and related traits eludes explanation by current genetic knowledge. This is somewhat disappointing considering heritability estimates have established these traits as highly genetic. Thus, the continued search for candidate genes, mutations, and mechanisms is vital to our understanding of heart disease at the molecular level. Furthermore, as marker development continues to predict risk of vascular illness, this knowledge has the potential to revolutionize treatment of this leading human disease.

  13. Iron Homeostasis in Peripheral Nervous System, Still a Black Box?

    PubMed Central

    Taveggia, Carla

    2014-01-01

    Abstract Significance: Iron is the most abundant transition metal in biology and an essential cofactor for many cellular enzymes. Iron homeostasis impairment is also a component of peripheral neuropathies. Recent Advances: During the past years, much effort has been paid to understand the molecular mechanism involved in maintaining systemic iron homeostasis in mammals. This has been stimulated by the evidence that iron dyshomeostasis is an initial cause of several disorders, including genetic and sporadic neurodegenerative disorders. Critical Issues: However, very little has been done to investigate the physiological role of iron in peripheral nervous system (PNS), despite the development of suitable cellular and animal models. Future Directions: To stimulate research on iron metabolism and peripheral neuropathy, we provide a summary of the knowledge on iron homeostasis in the PNS, on its transport across the blood–nerve barrier, its involvement in myelination, and we identify unresolved questions. Furthermore, we comment on the role of iron in iron-related disorder with peripheral component, in demyelinating and metabolic peripheral neuropathies. Antioxid. Redox Signal. 21, 634–648. PMID:24409826

  14. Dynamic thiol/disulphide homeostasis in patients with basal cell carcinoma.

    PubMed

    Demirseren, Duriye Deniz; Cicek, Cagla; Alisik, Murat; Demirseren, Mustafa Erol; Aktaş, Akın; Erel, Ozcan

    2017-09-01

    The aim of this study is to measure and compare the dynamic thiol/disulphide homeostasis of patients with basal cell carcinoma and healthy subjects with a newly developed and original method. Thirty four patients attending our outpatient clinic and clinically and histopathologically diagnosed as nodular basal cell carcinoma, and age and gender matched 30 healthy individuals have been involved in the study. Thiol/disulphide homeostasis tests have been measured with a novel automatic spectrophotometric method developed and the results have been compared statistically. Serum native thiol and disulphide levels in the patient and control group show a considerable variance statistically (p = 0.028, 0.039, respectively). Total thiol levels do not reveal a considerable variation (p = 0.094). Disulphide/native thiol ratios and native thiol/total thiol ratios also show a considerable variance statistically (p = 0.012, 0.013, 0.010, respectively). Thiol disulphide homeostasis in patients with basal cell carcinoma alters in the way that disulphide gets lower and thiols get higher. Thiol/disulphide level is likely to have a role in basal cell carcinoma pathogenesis.

  15. Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity.

    PubMed

    Dalmasso, Giovanni; Marin Zapata, Paula Andrea; Brady, Nathan Ryan; Hamacher-Brady, Anne

    2017-01-01

    Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis) and the removal of damaged mitochondria by selective autophagy (mitophagy). While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM) to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1) mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2) restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3) maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4) our model suggests sources of, and stress conditions amplifying

  16. Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity

    PubMed Central

    Dalmasso, Giovanni; Marin Zapata, Paula Andrea; Brady, Nathan Ryan; Hamacher-Brady, Anne

    2017-01-01

    Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis) and the removal of damaged mitochondria by selective autophagy (mitophagy). While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM) to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1) mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2) restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3) maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4) our model suggests sources of, and stress conditions amplifying

  17. Chloroplast redox homeostasis is essential for lateral root formation in Arabidopsis.

    PubMed

    Ferrández, Julia; González, Maricruz; Cejudo, Francisco Javier

    2012-09-01

    Redox regulation based on dithiol-disulphide interchange is an essential component of the control of chloroplast metabolism. In contrast to heterotrophic organisms, and non-photosynthetic plant tissues, chloroplast redox regulation relies on ferredoxin (Fd) reduced by the photosynthetic electron transport chain, thus being highly dependent on light. The finding of the NADPH-dependent thioredoxin reductase C (NTRC), a chloroplast-localized NTR with a joint thioredoxin domain, showed that NADPH is also used as source of reducing power for chloroplast redox homeostasis. Recently we have found that NTRC is also in plastids of non-photosynthetic tissues. Because these non-green plastids lack photochemical reactions, their redox homeostasis depends exclusively on NADPH produced from sugars and, thus, NTRC may play an essential role maintaining the redox homeostasis in these plastids. The fact that redox regulation occurs in any type of plastids raises the possibility that the functions of chloroplasts and non-green plastids, such as amyloplasts, are integrated to harmonize the growth of the different organs of the plant. To address this question, we generated Arabidopsis plants the redox homeostasis of which is recovered exclusively in chloroplasts, by leaf-specific expression of NTRC in the ntrc mutant, or exclusively in amyloplasts, by root-specific expression of NTRC. The analysis of these plants suggests that chloroplasts exert a pivotal role on plant growth, as expected because chloroplasts constitute the major source of nutrients and energy, derived from photosynthesis, for growth of heterotrophic tissues. However, NTRC deficiency causes impairment of auxin synthesis and lateral root formation. Interestingly, recovery of redox homeostasis of chloroplasts, but not of amyloplasts, was sufficient to restore wild type levels of lateral roots, showing the important signaling function of chloroplasts for the development of heterotrophic organs.

  18. Rapid Morphological Brain Abnormalities during Acute Methamphetamine Intoxication in the Rat. An Experimental study using Light and Electron Microscopy

    PubMed Central

    Sharma, Hari S.; Kiyatkin, Eugene A.

    2009-01-01

    This study describes morphological abnormalities of brain cells during acute methamphetamine (METH) intoxication in the rat and demonstrates the role of hyperthermia, disruption of the blood-brain barrier (BBB) and edema in their development. Rats with chronically implanted brain, muscle and skin temperature probes and an intravenous (iv) catheter were exposed to METH (9 mg/kg) at standard (23°C) and warm (29°C) ambient temperatures, allowing for the observation of hyperthermia ranging from mild to pathological levels (38–42°C). When brain temperature peaked or reached a level suggestive of possible lethality (>41.5°C), rats were injected with Evans blue (EB), rapidly anesthetized, perfused, and their brains were taken for further analyses. Four brain areas (cortex, hippocampus, thalamus and hypothalamus) were analyzed for EB extravasation, water and electrolyte (Na+, K+, Cl−) contents, immunostained for albumin and glial fibrillary acidic protein, and examined for neuronal, glial and axonal alterations using standard light and electron microscopy. These examinations revealed profound abnormalities in neuronal, glial, and endothelial cells, which were stronger with METH administered at 29°C than 23°C and tightly correlated with brain and body hyperthermia. These changes had some structural specificity, but in each structure they tightly correlated with increases in EB levels, the numbers of albumin-positive cells, and water and ion contents, suggesting leakage of the BBB, acutely developing brain edema, and serious shifts in brain ion homeostasis as leading factors underlying brain abnormalities. While most of these acute structural and functional abnormalities appear to be reversible, they could trigger subsequent cellular alterations in the brain and accelerate neurodegeneration—the most dangerous complication of chronic amphetamine-like drug abuse. PMID:18773954

  19. Why do team-sport athletes drink fluid in excess when exercising in cool conditions?

    PubMed

    Bargh, Melissa J; King, Roderick F G J; Gray, Michael P; Jones, Ben

    2017-03-01

    This study assessed the potential physiological and perceptual drivers of fluid intake and thirst sensation during intermittent exercise. Ten male rugby players (17 ± 1 years, stature: 179.1 ± 4.2 cm, body mass (BM): 81.9 ± 8.1 kg) participated in six 6-min small-sided games, interspersed with 2 min rest, where fluid intake was ad libitum during rest periods. Pre- and postmeasurements of BM, subjective ratings (thirst, thermal comfort, thermal sensation, mouth dryness), plasma osmolality (POsm), serum sodium concentration (S[Na + ]), haematocrit and haemoglobin (to calculate plasma volume change; PV) were taken. Fluid intake was measured during rest periods. BM change was -0.17 ± 0.59% and fluid intake was 0.88 ± 0.38 L. Pre- to post-POsm decreased (-3.1 ± 2.3 mOsm·kg -1 ; p = 0.002) and S[Na + ] remained similar (-0.3 ± 0.7 mmol·L -1 , p = 0.193). ΔPV was 5.84 ± 3.65%. Fluid intake displayed a relationship with pre-POsm (r = -0.640, p = 0.046), prethermal comfort (r = 0.651; p = -0.041), ΔS[Na + ] (r = 0.816, p = 0.004), and ΔPV (r = 0.740; p = 0.014). ΔThirst sensation displayed a relationship with premouth dryness (r = 0.861, p = 0.006) and Δmouth dryness (r = 0.878, p = 0.004). Yet a weak positive relationship between Δthirst sensation and fluid intake was observed (r = 0.085, p = 0.841). These data observed in an ambient temperature of 13.6 ± 0.9 °C, suggest team-sport athletes drink in excess of fluid homeostasis requirements and thirst sensation in cool conditions; however, this was not influenced by thermal discomfort.

  20. Chromosomal abnormalities in human sperm

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martin, R.H.

    1985-01-01

    The ability to analyze human sperm chromosome complements after penetration of zona pellucida-free hamster eggs provides the first opportunity to study the frequency and type of chromosomal abnormalities in human gametes. Two large-scale studies have provided information on normal men. We have studied 1,426 sperm complements from 45 normal men and found an abnormality rate of 8.9%. Brandriff et al. (5) found 8.1% abnormal complements in 909 sperm from 4 men. The distribution of numerical and structural abnormalities was markedly dissimilar in the 2 studies. The frequency of aneuploidy was 5% in our sample and only 1.6% in Brandriff's, perhapsmore » reflecting individual variability among donors. The frequency of 24,YY sperm was low: 0/1,426 and 1/909. This suggests that the estimates of nondisjunction based on fluorescent Y body data (1% to 5%) are not accurate. We have also studied men at increased risk of sperm chromosomal abnormalities. The frequency of chromosomally unbalanced sperm in 6 men heterozygous for structural abnormalities varied dramatically: 77% for t11;22, 32% for t6;14, 19% for t5;18, 13% for t14;21, and 0% for inv 3 and 7. We have also studied 13 cancer patients before and after radiotherapy and demonstrated a significant dose-dependent increase of sperm chromosome abnormalities (numerical and structural) 36 months after radiation treatment.« less

  1. Notch signaling modulates sleep homeostasis and learning after sleep deprivation in Drosophila.

    PubMed

    Seugnet, Laurent; Suzuki, Yasuko; Merlin, Gabriel; Gottschalk, Laura; Duntley, Stephen P; Shaw, Paul J

    2011-05-24

    The role of the transmembrane receptor Notch in the adult brain is poorly understood. Here, we provide evidence that bunched, a negative regulator of Notch, is involved in sleep homeostasis. Genetic evidence indicates that interfering with bunched activity in the mushroom bodies (MBs) abolishes sleep homeostasis. Combining bunched and Delta loss-of-function mutations rescues normal homeostasis, suggesting that Notch signaling may be involved in regulating sensitivity to sleep loss. Preventing the downregulation of Delta by overexpressing a wild-type transgene in MBs reduces sleep homeostasis and, importantly, prevents learning impairments induced by sleep deprivation. Similar resistance to sleep loss is observed with Notch(spl-1) gain-of-function mutants. Immunohistochemistry reveals that the Notch receptor is expressed in glia, whereas Delta is localized in neurons. Importantly, the expression in glia of the intracellular domain of Notch, a dominant activated form of the receptor, is sufficient to prevent learning deficits after sleep deprivation. Together, these results identify a novel neuron-glia signaling pathway dependent on Notch and regulated by bunched. These data highlight the emerging role of neuron-glia interactions in regulating both sleep and learning impairments associated with sleep loss. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. The impact of phosphate-balanced crystalloid infusion on acid-base homeostasis (PALANCE study): study protocol for a randomized controlled trial.

    PubMed

    Pagel, Judith-Irina; Hulde, Nikolai; Kammerer, Tobias; Schwarz, Michaela; Chappell, Daniel; Burges, Alexander; Hofmann-Kiefer, Klaus; Rehm, Markus

    2017-07-10

    This study aims to investigate the effects of a modified, balanced crystalloid including phosphate in a perioperative setting in order to maintain a stable electrolyte and acid-base homeostasis in the patient. This is a single-centre, open-label, randomized controlled trial involving two parallel groups of female patients comparing a perioperative infusion regime with sodium glycerophosphate and Jonosteril® (treatment group) or Jonosteril® (comparator) alone. The primary endpoint is to maintain a stable concentration of weak acids [A - ] according to the Stewart approach of acid-base balance. Secondary endpoints are measurement of serum phosphate levels, other acid-base parameters such as the strong ion difference (SID), the onset and severity of postoperative nausea and vomiting (PONV), electrolyte levels and their excretion in the urine, monitoring of renal function and glycocalyx components, haemodynamics, amounts of catecholamines and other vasopressors used and the safety of the infusion regime. Perioperative fluid replacement with the use of currently available crystalloid preparations still fail to maintain a stable acid-base balance and experts agree that common balanced solutions are still not ideal. This study aims to investigate the effectivity and safety of a new crystalloid solution by adding sodium glycerophosphate to a standardized crystalloid preparation in order to maintain a balanced perioperative acid-base homeostasis. EudraCT number 201002422520 . Registered on 30 November 2010.

  3. Fluid dynamics vascular theory of brain and inner-ear function in traumatic brain injury: a translational hypothesis for diagnosis and treatment.

    PubMed

    Shulman, Abraham; Strashun, Arnold M

    2009-01-01

    It is hypothesized that in all traumatic brain injury (TBI) patients with a clinical history of closed or penetrating head injury, the initial head trauma is associated with a vibratory sensation and noise exposure, with resultant alteration in vascular supply to the structures and contents of the fluid compartments of brain and ear (i.e., the fluid dynamics vascular theory of brain-inner-ear function [FDVTBE]). The primary etiology-head trauma-results in an initial fluctuation, interference, or interaction in the normal fluid dynamics between brain and labyrinth of the inner ear, with a resultant clinical diversity of complaints varying in time of onset and severity. Normal function of the brain and ear is a reflection of a normal state of homeostasis between the fluid compartments in the brain of cerebrospinal fluid and perilymph-endolymph in the labyrinth of the ear. The normal homeostasis in the structures and contents between the two fluid compartment systems--intracerebral and intralabyrinthine--is controlled by mechanisms involved in the maintenance of normal pressures, water and electrolyte content, and neurotransmitter activities. The initial pathophysiology (a reflection of an alteration in the vascular supply to the brain-ear) is hypothesized to be an initial acute inflammatory response, persistence of which results in ischemia and an irreversible alteration in the involved neural substrates of brain-ear. Clinically, a chronic multisymptom complex becomes manifest. The multisymptom complex, individual for each TBI patient regardless of the diagnostic TBI category (i.e., mild, moderate, or severe), initially reflects processes of inflammation and ischemia which, in brain, result in brain volume loss identified as neurodegeneration and hydrocephalus ex vacuo or an alteration in cerebrospinal fluid production (i.e., pseudotumor cerebri) and, in ear, secondary endolymphatic hydrops with associated cochleovestibular complaints of hearing loss, tinnitus

  4. The Role of “Leakage” of Tubular Fluid in Anuria Due to Mercury Poisoning*

    PubMed Central

    Bank, Norman; Mutz, Bertrand F.; Aynedjian, Hagop S.

    1967-01-01

    The role of “leakage” of tubular fluid in anuria produced by mercury poisoning was studied in rats by micropuncture techniques. After an initial brisk diuresis, almost all animals were completely anuric 24 hours after HgCl2 injection. Lissamine green injected intravenously in the early stage of anuria appeared in the beginning of the proximal tubule, but the color became progressively lighter as the dye traversed the proximal convolutions. The dye was barely visible in the terminal segments of the proximal tubule; it did not appear at all in the distal tubules. These observations suggest that the proximal epithelium had become abnormally permeable to Lissamine green. Tubular fluid to plasma inulin (TF/PIn) ratios and inulin clearance were measured in individual nephrons at three sites: early proximal tubule, late proximal tubule, and distal tubule. It was found that TF/PIn ratios were abnormally low in the late proximal and distal tubules. Inulin clearance was normal at the beginning of the proximal tubule but fell by more than 60% by the late proximal convolutions. Thus, the proximal tubule had also become permeable to inulin. We conclude from these observations that anuria in mercury poisoning can occur in the presence of a normal glomerular filtration rate. The absence of urine flow appears to be due to complete absorption of the filtrate through an excessively permeable tubular epithelium. The driving force affecting this fluid absorption is probably the colloid oncotic pressure of the peritubular capillary blood. Images PMID:6025476

  5. Cerebrospinal fluid hypersecretion in pediatric hydrocephalus.

    PubMed

    Karimy, Jason K; Duran, Daniel; Hu, Jamie K; Gavankar, Charuta; Gaillard, Jonathan R; Bayri, Yasar; Rice, Hunter; DiLuna, Michael L; Gerzanich, Volodymyr; Marc Simard, J; Kahle, Kristopher T

    2016-11-01

    Hydrocephalus, despite its heterogeneous causes, is ultimately a disease of disordered CSF homeostasis that results in pathological expansion of the cerebral ventricles. Our current understanding of the pathophysiology of hydrocephalus is inadequate but evolving. Over this past century, the majority of hydrocephalus cases has been explained by functional or anatomical obstructions to bulk CSF flow. More recently, hydrodynamic models of hydrocephalus have emphasized the role of abnormal intracranial pulsations in disease pathogenesis. Here, the authors review the molecular mechanisms of CSF secretion by the choroid plexus epithelium, the most efficient and actively secreting epithelium in the human body, and provide experimental and clinical evidence for the role of increased CSF production in hydrocephalus. Although the choroid plexus epithelium might have only an indirect influence on the pathogenesis of many types of pediatric hydrocephalus, the ability to modify CSF secretion with drugs newer than acetazolamide or furosemide would be an invaluable component of future therapies to alleviate permanent shunt dependence. Investigation into the human genetics of developmental hydrocephalus and choroid plexus hyperplasia, and the molecular physiology of the ion channels and transporters responsible for CSF secretion, might yield novel targets that could be exploited for pharmacotherapeutic intervention.

  6. Glucose Homeostasis Variables in Pregnancy versus Maternal and Infant Body Composition

    PubMed Central

    Henriksson, Pontus; Löf, Marie; Forsum, Elisabet

    2015-01-01

    Intrauterine factors influence infant size and body composition but the mechanisms involved are to a large extent unknown. We studied relationships between the body composition of pregnant women and variables related to their glucose homeostasis, i.e., glucose, HOMA-IR (homeostasis model assessment-insulin resistance), hemoglobin A1c and IGFBP-1 (insulin-like growth factor binding protein-1), and related these variables to the body composition of their infants. Body composition of 209 women in gestational week 32 and of their healthy, singleton and full-term one-week-old infants was measured using air displacement plethysmography. Glucose homeostasis variables were assessed in gestational week 32. HOMA-IR was positively related to fat mass index and fat mass (r2 = 0.32, p < 0.001) of the women. Maternal glucose and HOMA-IR values were positively (p ≤ 0.006) associated, while IGFBP-1was negatively (p = 0.001) associated, with infant fat mass. HOMA-IR was positively associated with fat mass of daughters (p < 0.001), but not of sons (p = 0.65) (Sex-interaction: p = 0.042). In conclusion, glucose homeostasis variables of pregnant women are related to their own body composition and to that of their infants. The results suggest that a previously identified relationship between fat mass of mothers and daughters is mediated by maternal insulin resistance. PMID:26184296

  7. Environmental metabolomics with data science for investigating ecosystem homeostasis.

    PubMed

    Kikuchi, Jun; Ito, Kengo; Date, Yasuhiro

    2018-02-01

    A natural ecosystem can be viewed as the interconnections between complex metabolic reactions and environments. Humans, a part of these ecosystems, and their activities strongly affect the environments. To account for human effects within ecosystems, understanding what benefits humans receive by facilitating the maintenance of environmental homeostasis is important. This review describes recent applications of several NMR approaches to the evaluation of environmental homeostasis by metabolic profiling and data science. The basic NMR strategy used to evaluate homeostasis using big data collection is similar to that used in human health studies. Sophisticated metabolomic approaches (metabolic profiling) are widely reported in the literature. Further challenges include the analysis of complex macromolecular structures, and of the compositions and interactions of plant biomass, soil humic substances, and aqueous particulate organic matter. To support the study of these topics, we also discuss sample preparation techniques and solid-state NMR approaches. Because NMR approaches can produce a number of data with high reproducibility and inter-institution compatibility, further analysis of such data using machine learning approaches is often worthwhile. We also describe methods for data pretreatment in solid-state NMR and for environmental feature extraction from heterogeneously-measured spectroscopic data by machine learning approaches. Copyright © 2017. Published by Elsevier B.V.

  8. Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype.

    PubMed

    Ngo, Kevin; Patil, Prashanti; McGowan, Sara J; Niedernhofer, Laura J; Robbins, Paul D; Kang, James; Sowa, Gwendolyn; Vo, Nam

    2017-09-01

    Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular senescence is dramatically increased in the DNA repair-deficient Ercc1 -/Δ mouse model of human progeria. In these accelerated aging mice, increased disc cellular senescence is closely associated with the rapid loss of disc PG. We also directly examine PG homeostasis in oxidative damage-induced senescent human cells using an in vitro cell culture model system. Senescence of human disc cells treated with hydrogen peroxide was confirmed by growth arrest, senescence-associated β-galactosidase activity, γH2AX foci, and acquisition of senescence-associated secretory phenotype. Senescent human disc cells also exhibited perturbed matrix PG homeostasis as evidenced by their decreased capacity to synthesize new matrix PG and enhanced degradation of aggrecan, a major matrix PG. of the disc. Our in vivo and in vitro findings altogether suggest that disc cellular senescence is an important driver of PG matrix homeostatic perturbation and PG loss. Published by Elsevier B.V.

  9. New experimental models of skin homeostasis and diseases.

    PubMed

    Larcher, F; Espada, J; Díaz-Ley, B; Jaén, P; Juarranz, A; Quintanilla, M

    2015-01-01

    Homeostasis, whose regulation at the molecular level is still poorly understood, is intimately related to the functions of epidermal stem cells. Five research groups have been brought together to work on new in vitro and in vivo skin models through the SkinModel-CM program, under the auspices of the Spanish Autonomous Community of Madrid. This project aims to analyze the functions of DNA methyltransferase 1, endoglin, and podoplanin in epidermal stem cell activity, homeostasis, and skin cancer. These new models include 3-dimensional organotypic cultures, immunodeficient skin-humanized mice, and genetically modified mice. Another aim of the program is to use skin-humanized mice to model dermatoses such as Gorlin syndrome and xeroderma pigmentosum in order to optimize new protocols for photodynamic therapy. Copyright © 2013 Elsevier España, S.L.U. and AEDV. All rights reserved.

  10. High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation.

    PubMed

    Kitada, Kento; Daub, Steffen; Zhang, Yahua; Klein, Janet D; Nakano, Daisuke; Pedchenko, Tetyana; Lantier, Louise; LaRocque, Lauren M; Marton, Adriana; Neubert, Patrick; Schröder, Agnes; Rakova, Natalia; Jantsch, Jonathan; Dikalova, Anna E; Dikalov, Sergey I; Harrison, David G; Müller, Dominik N; Nishiyama, Akira; Rauh, Manfred; Harris, Raymond C; Luft, Friedrich C; Wassermann, David H; Sands, Jeff M; Titze, Jens

    2017-05-01

    Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake. We observed that the renal concentration mechanism couples natriuresis with correspondent renal water reabsorption, limits natriuretic osmotic diuresis, and results in concurrent extracellular volume conservation and concentration of salt excreted into urine. This water-conserving mechanism of dietary salt excretion relies on urea transporter-driven urea recycling by the kidneys and on urea production by liver and skeletal muscle. The energy-intense nature of hepatic and extrahepatic urea osmolyte production for renal water conservation requires reprioritization of energy and substrate metabolism in liver and skeletal muscle, resulting in hepatic ketogenesis and glucocorticoid-driven muscle catabolism, which are prevented by increasing food intake. This natriuretic-ureotelic, water-conserving principle relies on metabolism-driven extracellular volume control and is regulated by concerted liver, muscle, and renal actions.

  11. High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation

    PubMed Central

    Kitada, Kento; Daub, Steffen; Zhang, Yahua; Klein, Janet D.; Nakano, Daisuke; Pedchenko, Tetyana; Lantier, Louise; LaRocque, Lauren M.; Marton, Adriana; Neubert, Patrick; Schröder, Agnes; Rakova, Natalia; Jantsch, Jonathan; Dikalova, Anna E.; Dikalov, Sergey I.; Harrison, David G.; Müller, Dominik N.; Nishiyama, Akira; Rauh, Manfred; Harris, Raymond C.; Luft, Friedrich C.; Wasserman, David H.; Sands, Jeff M.

    2017-01-01

    Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake. We observed that the renal concentration mechanism couples natriuresis with correspondent renal water reabsorption, limits natriuretic osmotic diuresis, and results in concurrent extracellular volume conservation and concentration of salt excreted into urine. This water-conserving mechanism of dietary salt excretion relies on urea transporter–driven urea recycling by the kidneys and on urea production by liver and skeletal muscle. The energy-intense nature of hepatic and extrahepatic urea osmolyte production for renal water conservation requires reprioritization of energy and substrate metabolism in liver and skeletal muscle, resulting in hepatic ketogenesis and glucocorticoid-driven muscle catabolism, which are prevented by increasing food intake. This natriuretic-ureotelic, water-conserving principle relies on metabolism-driven extracellular volume control and is regulated by concerted liver, muscle, and renal actions. PMID:28414295

  12. Primary cilia maintain corneal epithelial homeostasis by regulation of the Notch signaling pathway

    PubMed Central

    Grisanti, Laura; Revenkova, Ekaterina; Gordon, Ronald E.

    2016-01-01

    Primary cilia have been linked to signaling pathways involved in cell proliferation, cell motility and cell polarity. Defects in ciliary function result in developmental abnormalities and multiple ciliopathies. Patients affected by severe ciliopathies, such as Meckel syndrome, present several ocular surface disease conditions of unclear pathogenesis. Here, we show that primary cilia are predominantly present on basal cells of the mouse corneal epithelium (CE) throughout development and in the adult. Conditional ablation of cilia in the CE leads to an increase in proliferation and vertical migration of basal corneal epithelial cells (CECs). A consequent increase in cell density of suprabasal layers results in a thicker than normal CE. Surprisingly, in cilia-deficient CE, cilia-mediated signaling pathways, including Hh and Wnt pathways, were not affected but the intensity of Notch signaling was severely diminished. Although Notch1 and Notch2 receptors were expressed normally, nuclear Notch1 intracellular domain (N1ICD) expression was severely reduced. Postnatal development analysis revealed that in cilia-deficient CECs downregulation of the Notch pathway precedes cell proliferation defects. Thus, we have uncovered a function of the primary cilium in maintaining homeostasis of the CE by balancing proliferation and vertical migration of basal CECs through modulation of Notch signaling. PMID:27122169

  13. CFTR and lung homeostasis

    PubMed Central

    Matalon, Sadis

    2014-01-01

    CFTR is a cAMP-activated chloride and bicarbonate channel that is critical for lung homeostasis. Decreases in CFTR expression have dire consequences in cystic fibrosis (CF) and have been suggested to be a component of the lung pathology in chronic obstructive pulmonary disease. Decreases or loss of channel function often lead to mucus stasis, chronic bacterial infections, and the accompanying chronic inflammatory responses that promote progressive lung destruction, and, eventually in CF, lung failure. Here we discuss CFTR's functional role airway surface liquid hydration and pH, in regulation of other channels such as the epithelial sodium channel, and in regulating inflammatory responses in the lung. PMID:25381027

  14. Reactive Oxygen Species and Mitochondrial Homeostasis as Regulators of Stem Cell Fate and Function.

    PubMed

    Tan, Darren Q; Suda, Toshio

    2018-07-10

    The precise role and impact of reactive oxygen species (ROS) in stem cells, which are essential for lifelong tissue homeostasis and regeneration, remain of significant interest to the field. The long-term regenerative potential of a stem cell compartment is determined by the delicate balance between quiescence, self-renewal, and differentiation, all of which can be influenced by ROS levels. Recent Advances: The past decade has seen a growing appreciation for the importance of ROS and redox homeostasis in various stem cell compartments, particularly those of hematopoietic, neural, and muscle tissues. In recent years, the importance of proteostasis and mitochondria in relation to stem cell biology and redox homeostasis has garnered considerable interest. Here, we explore the reciprocal relationship between ROS and stem cells, with significant emphasis on mitochondria as a core component of redox homeostasis. We discuss how redox signaling, involving cell-fate determining protein kinases and transcription factors, can control stem cell function and fate. We also address the impact of oxidative stress on stem cells, especially oxidative damage of lipids, proteins, and nucleic acids. We further discuss ROS management in stem cells, and present recent evidence supporting the importance of mitochondrial activity and its modulation (via mitochondrial clearance, biogenesis, dynamics, and distribution [i.e., segregation and transfer]) in stem cell redox homeostasis. Therefore, elucidating the intricate links between mitochondria, cellular metabolism, and redox homeostasis is envisioned to be critical for our understanding of ROS in stem cell biology and its therapeutic relevance in regenerative medicine. Antioxid. Redox Signal. 00, 000-000.

  15. Mga2 Transcription Factor Regulates an Oxygen-responsive Lipid Homeostasis Pathway in Fission Yeast*

    PubMed Central

    Burr, Risa; Stewart, Emerson V.; Shao, Wei; Zhao, Shan; Hannibal-Bach, Hans Kristian; Ejsing, Christer S.; Espenshade, Peter J.

    2016-01-01

    Eukaryotic lipid synthesis is oxygen-dependent with cholesterol synthesis requiring 11 oxygen molecules and fatty acid desaturation requiring 1 oxygen molecule per double bond. Accordingly, organisms evaluate oxygen availability to control lipid homeostasis. The sterol regulatory element-binding protein (SREBP) transcription factors regulate lipid homeostasis. In mammals, SREBP-2 controls cholesterol biosynthesis, whereas SREBP-1 controls triacylglycerol and glycerophospholipid biosynthesis. In the fission yeast Schizosaccharomyces pombe, the SREBP-2 homolog Sre1 regulates sterol homeostasis in response to changing sterol and oxygen levels. However, notably missing is an SREBP-1 analog that regulates triacylglycerol and glycerophospholipid homeostasis in response to low oxygen. Consistent with this, studies have shown that the Sre1 transcription factor regulates only a fraction of all genes up-regulated under low oxygen. To identify new regulators of low oxygen adaptation, we screened the S. pombe nonessential haploid deletion collection and identified 27 gene deletions sensitive to both low oxygen and cobalt chloride, a hypoxia mimetic. One of these genes, mga2, is a putative transcriptional activator. In the absence of mga2, fission yeast exhibited growth defects under both normoxia and low oxygen conditions. Mga2 transcriptional targets were enriched for lipid metabolism genes, and mga2Δ cells showed disrupted triacylglycerol and glycerophospholipid homeostasis, most notably with an increase in fatty acid saturation. Indeed, addition of exogenous oleic acid to mga2Δ cells rescued the observed growth defects. Together, these results establish Mga2 as a transcriptional regulator of triacylglycerol and glycerophospholipid homeostasis in S. pombe, analogous to mammalian SREBP-1. PMID:27053105

  16. Do exclusively breast fed infants need fluid supplementation?

    PubMed

    Sachdev, H P; Krishna, J; Puri, R K

    1992-04-01

    Exclusive breast feeding in developing countries is used by women for a very short period. The major reason given for supplementation with other fluid is the maintenance of water homeostasis. Theoretically, 80-100 ml/kg is the average daily fluid requirement for the first week; between 3-6 months, the need is for 140-160 ml/kg. the need varies with concentration of the feeds, energy consumption, activity, rate of growth, and environmental temperature and humidity. Because breast milk has a low concentration of sodium, chloride, potassium, and nitrogen only a small amount of fluid intake is needed for excretory functions. Almroth's model of basic fluid needs for a Western 4-month-old male infant are used to calculate fluid requirements; the results indicate that an exclusively breast fed infant in a hot climate would not need additional water. Estimates for an Indian infant weighing 5.5 kg at 4 months support these findings. Other scientific findings are reviewed based on clinical evidence; the risks associated with supplementation and the role of medical personnel in encouraging supplementation are also discussed. Evidence from a survey of 70 physicians and 34 nurses revealed that all considered breast milk superior to bottle feeding. 97% of nurses and 63% of doctors thought that water supplementation was necessary during the summer. The volume recommended by nurses was 180-240 ml, which was almost twice the amount recommended by doctors. Nurses recommended supplementation 1-24 times a day, while doctors suggested adopting it 2-10 times a day. There were 6 studies which tested the validity of water need based on different methodologies: Almroth (2 studies), Armelini, Goldberg, Brown, and Sachdev. Hydration was measured by specific gravity or osmolality in 4 reports, and 2 others considered breast milk intakes and urine output. One study compared exclusive breast feeding with a control receiving water supplementation. The conclusion is that water supplementation in

  17. Cerebrospinal Fluid Levels of Monoamine Metabolites in the Epileptic Baboon

    PubMed Central

    Szabó, C. Ákos; Patel, Mayuri; Uteshev, Victor V.

    2016-01-01

    The baboon represents a natural model for genetic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). In this retrospective study, cerebrospinal fluid (CSF) monoamine metabolites and scalp electroencephalography (EEG) were evaluated in 263 baboons of a pedigreed colony. CSF monoamine abnormalities have been linked to reduced seizure thresholds, behavioral abnormalities and SUDEP in various animal models of epilepsy. The levels of 3-hydroxy-4-methoxyphenylglycol, 5-hydroxyindolacetic acid and homovanillic acid in CSF samples drawn from the cisterna magna were analyzed using high-performance liquid chromatography. These levels were compared between baboons with seizures (SZ), craniofacial trauma (CFT) and asymptomatic, control (CTL) baboons, between baboons with abnormal and normal EEG studies. We hypothesized that the CSF levels of major monoaminergic metabolites (i.e., dopamine, serotonin and norepinephrine) associate with the baboons’ electroclinical status and thus can be used as clinical biomarkers applicable to seizures/epilepsy. However, despite apparent differences in metabolite levels between the groups, usually lower in SZ and CFT baboons and in baboons with abnormal EEG studies, we did not find any statistically significant differences using a logistic regression analysis. Significant correlations between the metabolite levels, especially between 5-HIAA and HVA, were preserved in all electroclinical groups. While we were not able to demonstrate significant differences in monoamine metabolites in relation to seizures or EEG markers of epilepsy, we cannot exclude the monoaminergic system as a potential source of pathogenesis in epilepsy and SUDEP. A prospective study evaluating serial CSF monoamine levels in baboons with recently witnessed seizures, and evaluation of abnormal expression and function of monoaminergic receptors and transporters within epilepsy-related brain regions, may impact the electroclinical status. PMID:26924854

  18. Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder

    PubMed Central

    Brady, Roscoe O; McCarthy, Julie M; Prescot, Andrew P; Jensen, J Eric; Cooper, Alissa J; Cohen, Bruce M; Renshaw, Perry F; Ongür, Dost

    2017-01-01

    Objectives Gamma-aminobutyric acid (GABA) abnormalities have been implicated in bipolar disorder. However, due to discrepant studies measuring postmortem, cerebrospinal fluid, plasma, and in vivo brain levels of GABA, the nature of these abnormalities is unclear. Using proton magnetic resonance spectroscopy, we investigated tissue levels of GABA in the anterior cingulate cortex and parieto-occipital cortex of participants with bipolar disorder and healthy controls. Methods Fourteen stably medicated euthymic outpatients with bipolar disorder type I (mean age 32.6 years, eight male) and 14 healthy control participants (mean age 36.9 years, 10 male) completed a proton magnetic resonance spectroscopy scan at 4-Tesla after providing informed consent. We collected data from two 16.7-mL voxels using MEGAPRESS, and they were analyzed using LCModel. Results GABA/creatine ratios were elevated in bipolar disorder participants compared to healthy controls [F(1,21) = 4.4, p = 0.048] in the anterior cingulate cortex (25.1% elevation) and the parieto-occipital cortex (14.6% elevation). Bipolar disorder participants not taking GABA-modulating medications demonstrated greater GABA/creatine elevations than patients taking GABA-modulating medications. Conclusions We found higher GABA/creatine levels in euthymic bipolar disorder outpatients compared to healthy controls, and the extent of this elevation may be affected by the use of GABA-modulating medications. Our findings suggest that elevated brain GABA levels in bipolar disorder may be associated with GABAergic dysfunction and that GABA-modulating medications reduce GABA levels in this condition. PMID:23634979

  19. The role of ICP monitoring in patients with persistent cerebrospinal fluid leak following spinal surgery: a case series.

    PubMed

    Craven, Claudia; Toma, Ahmed K; Khan, Akbar A; Watkins, Laurence D

    2016-09-01

    Cerebrospinal fluid (CSF) leak following spinal surgery is a relatively common surgical complication. A disturbance in the underlying CSF dynamics could be the causative factor in a small group of patients with refractory CSF leaks that require multiple surgical repairs and prolonged hospital admission. A retrospective case series of patients with persistent post spinal surgery CSF leak referred to the hydrocephalus service for continuous intracranial pressure (ICP) monitoring. Patients' notes were reviewed for medical history, ICP data, radiological data, and subsequent management and outcome. Five patients (two males/three females, mean age, 35.4 years) were referred for ICP monitoring over a 12-month period. These patients had prolonged CSF leak despite multiple repair attempts 252 ± 454 days (mean ± SD). On ICP monitoring, all five patients had abnormal results, with the mean ICP 8.95 ± 4.41 mmHg. Four had abnormal pulse amplitudes, mean 6.15 mmHg ± 1.22 mmHg. All five patients underwent an intervention. Three patients underwent insertion of ventriculoperitoneal (VP) shunts. One patient had venous sinus stent insertion and one patient underwent medical management with acetazolamide. All five of the patients' CSF leak resolved post intervention. The mean time to resolution of CSF leak post intervention was 10.8  ± 12.9 days. Abnormal cerebrospinal fluid dynamics could be the underlying factor in patients with a persistent and treatment-refractory CSF leak post spinal surgery. Treatments aimed at lowering ICP may be beneficial in this group of patients. Whether abnormal pressure and dynamics represent a pre-existing abnormality or is induced by spinal surgery should be a subject of further study.

  20. Homeostasis and Gauss statistics: barriers to understanding natural variability.

    PubMed

    West, Bruce J

    2010-06-01

    In this paper, the concept of knowledge is argued to be the top of a three-tiered system of science. The first tier is that of measurement and data, followed by information consisting of the patterns within the data, and ending with theory that interprets the patterns and yields knowledge. Thus, when a scientific theory ceases to be consistent with the database the knowledge based on that theory must be re-examined and potentially modified. Consequently, all knowledge, like glory, is transient. Herein we focus on the non-normal statistics of physiologic time series and conclude that the empirical inverse power-law statistics and long-time correlations are inconsistent with the theoretical notion of homeostasis. We suggest replacing the notion of homeostasis with that of Fractal Physiology.

  1. Retrospective evaluation of the efficacy of isolating bacteria from synovial fluid in dogs with suspected septic arthritis.

    PubMed

    Scharf, V F; Lewis, S T; Wellehan, J F; Wamsley, H L; Richardson, R; Sundstrom, D A; Lewis, D D

    2015-06-01

    To evaluate the efficacy of synovial fluid culture in obtaining the causative organism from dogs with suspected septic arthritis. In this retrospective evaluation, synovial fluid cytology and microbiology submissions from dogs with suspected septic arthritis from March 2007 to August 2011 were reviewed. Synovial fluid cytology consistent with joint sepsis was identified. Cultures of synovial fluid from dogs with clinical histories and abnormalities consistent with septic arthritis were used to evaluate the efficacy of bacterial isolation. In total, 36 dogs met the inclusion criteria. Initial aerobic cultures of joint fluid yielded bacterial growth in 44% of these dogs. All anaerobic cultures were negative. In 19% of the dogs with positive cultures, antibiotics had been administered prior to arthrocentesis compared with 10% of dogs with negative cultures. There was no association between culture efficacy and the administration of antimicrobial treatment prior to synovial fluid culture or recent surgery involving the affected joint (P=0.637 and P=0.106, respectively). Culture of synovial fluid from dogs with suspected septic arthritis has a low yield, necessitating a more effective means of identifying bacteria from suspected septic joints in dogs. © 2015 Australian Veterinary Association.

  2. Dietary curcumin supplementation counteracts reduction in levels of molecules involved in energy homeostasis after brain trauma.

    PubMed

    Sharma, S; Zhuang, Y; Ying, Z; Wu, A; Gomez-Pinilla, F

    2009-07-21

    Traumatic brain injury (TBI) is followed by an energy crisis that compromises the capacity of the brain to cope with challenges, and often reduces cognitive ability. New research indicates that events that regulate energy homeostasis crucially impact synaptic function and this can compromise the capacity of the brain to respond to challenges during the acute and chronic phases of TBI. The goal of the present study is to determine the influence of the phenolic yellow curry pigment curcumin on molecular systems involved with the monitoring, balance, and transduction of cellular energy, in the hippocampus of animals exposed to mild fluid percussion injury (FPI). Young adult rats were exposed to a regular diet (RD) without or with 500 ppm curcumin (Cur) for four weeks, before an FPI was performed. The rats were assigned to four groups: RD/Sham, Cur/Sham, RD/FPI, and Cur/FPI. We found that FPI decreased the levels of AMP-activated protein kinase (AMPK), ubiquitous mitochondrial creatine kinase (uMtCK) and cytochrome c oxidase II (COX-II) in RD/FPI rats as compared to the RD/sham rats. The curcumin diet counteracted the effects of FPI and elevated the levels of AMPK, uMtCK, COX-II in Cur/FPI rats as compared to RD/sham rats. In addition, in the Cur/sham rats, AMPK and uMtCK increased compared to the RD/sham. Results show the potential of curcumin to regulate molecules involved in energy homeostasis following TBI. These studies may foster a new line of therapeutic treatments for TBI patients by endogenous upregulation of molecules important for functional recovery.

  3. Experimental Evidence that In Vivo Intracerebral Administration of L-2-Hydroxyglutaric Acid to Neonatal Rats Provokes Disruption of Redox Status and Histopathological Abnormalities in the Brain.

    PubMed

    Ribeiro, Rafael Teixeira; Zanatta, Ângela; Amaral, Alexandre Umpierrez; Leipnitz, Guilhian; de Oliveira, Francine Hehn; Seminotti, Bianca; Wajner, Moacir

    2018-04-01

    Tissue accumulation of L-2-hydroxyglutaric acid (L-2-HG) is the biochemical hallmark of L-2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic inherited disease characterized by neurological symptoms and brain white matter abnormalities whose pathogenesis is not yet well established. L-2-HG was intracerebrally administered to rat pups at postnatal day 1 (P1) to induce a rise of L-2-HG levels in the central nervous system (CNS). Thereafter, we investigated whether L-2-HG in vivo administration could disturb redox homeostasis and induce brain histopathological alterations in the cerebral cortex and striatum of neonatal rats. L-2-HG markedly induced the generation of reactive oxygen species (increase of 2',7'-dichloroflurescein-DCFH-oxidation), lipid peroxidation (increase of malondialdehyde concentrations), and protein oxidation (increase of carbonyl formation and decrease of sulfhydryl content), besides decreasing the antioxidant defenses (reduced glutathione-GSH) and sulfhydryl content in the cerebral cortex. Alterations of the activities of various antioxidant enzymes were also observed in the cerebral cortex and striatum following L-2-HG administration. Furthermore, L-2-HG-induced lipid peroxidation and GSH decrease in the cerebral cortex were prevented by the antioxidant melatonin and by the classical antagonist of NMDA glutamate receptor MK-801, suggesting the involvement of reactive species and of overstimulation of NMDA receptor in these effects. Finally, L-2-HG provoked significant vacuolation and edema particularly in the cerebral cortex with less intense alterations in the striatum that were possibly associated with the unbalanced redox homeostasis caused by this metabolite. Taken together, it is presumed that these pathomechanisms may underlie the neurological symptoms and brain abnormalities observed in the affected patients.

  4. Lipid Raft, Regulator of Plasmodesmal Callose Homeostasis.

    PubMed

    Iswanto, Arya Bagus Boedi; Kim, Jae-Yean

    2017-04-03

    A bstract: The specialized plasma membrane microdomains known as lipid rafts are enriched by sterols and sphingolipids. Lipid rafts facilitate cellular signal transduction by controlling the assembly of signaling molecules and membrane protein trafficking. Another specialized compartment of plant cells, the plasmodesmata (PD), which regulates the symplasmic intercellular movement of certain molecules between adjacent cells, also contains a phospholipid bilayer membrane. The dynamic permeability of plasmodesmata (PDs) is highly controlled by plasmodesmata callose (PDC), which is synthesized by callose synthases (CalS) and degraded by β-1,3-glucanases (BGs). In recent studies, remarkable observations regarding the correlation between lipid raft formation and symplasmic intracellular trafficking have been reported, and the PDC has been suggested to be the regulator of the size exclusion limit of PDs. It has been suggested that the alteration of lipid raft substances impairs PDC homeostasis, subsequently affecting PD functions. In this review, we discuss the substantial role of membrane lipid rafts in PDC homeostasis and provide avenues for understanding the fundamental behavior of the lipid raft-processed PDC.

  5. Osmolar relation between cerebrospinal fluid and serum in hyperosmolar hypernatraemic dehydration.

    PubMed Central

    Habel, A H; Simpson, H

    1976-01-01

    The relation between cerebrospinal fluid (CSF) and serum osmolality was studied in 16 patients with hyperosmolar hypernatraemic dehydration before treatment. After correcting shock and acidosis, 0-45% saline in 2-5 or 5% dextrose was infused in each patient over a 48- to 72-hour period. During rehydration, serum osmolality, electrolyte concentrations, urea nitrogen, and blood pH were measured sequentially. Five patients developed severe neurological abnormalities within 48 hours of addmission (convulsions 2, convulsions with hemiplegia 2, hemiplegia 1). Of these, 3 had residual defects on follow-up at least one year later. This group was indistinguishable from the 11 without significant neurological abnormality, both on clinical grounds before rehydration, and after analysis of admission and subsequent serum biochemical variables. A significant osmolar gap (greater than 4 mmol/kg H2O) between serum and CSF was found in 13 patients. Severe neurological disturbance only occurred when CSF osmolality exceeded that of serum by 7 or more mmol/kg H2O. Discriminant analysis of the paired osmolar data showed that D = -117+1-74 X(CSF osmolality) -1-41 X (serum osmolality), and that severe neurological abnormality was predicted when D was positive. PMID:11753

  6. Glyceollin-containing fermented soybeans improve glucose homeostasis in diabetic mice.

    PubMed

    Park, Sunmin; Kim, Da Sol; Kim, Jeong Hwan; Kim, Jong Sang; Kim, Hyo Jung

    2012-02-01

    Our previous in vitro study demonstrated that glyceollins help normalize glucose homeostasis by potentiating β-cell function and survival in insulinoma cells as well as improving glucose utilization in adipocytes. Here, we investigated whether fermented soybeans containing glyceollins had an antidiabetic action in type 2 diabetic animals. The diabetic mice, their diabetes induced by intraperitoneal injections of streptozotocin (20 mg/kg bw), were administered a high fat diet with no soybeans (control), 10% unfermented soybeans and 10% fermented soybeans containing glyceollins, respectively, (FSG) for 8 weeks. As positive controls, rosiglitazone (20 mg/kg/bw) was given to diabetic mice fed a no soybean diet and non-diabetic mice were also placed on the same diet. Among the diabetic mice, FSG-treated mice exhibited the lowest peak for blood glucose levels with an elevation of serum insulin levels during the first part of oral glucose tolerance testing. FSG also made blood glucose levels drop quickly after the peak and it decreased blood glucose levels more than the control during insulin tolerance testing. This improvement was associated with increased hepatic glycogen accumulation and decreased triglyceride storage. The phosphorylation of Akt, AMP-kinase, and acetyl-CoA carboxylase in the liver was potentiated by FSG, whereas phosphoenolpyruvate carboxykinase expression decreased. The enhancement of glucose homeostasis was comparable to the effect induced by rosiglitazone, a commercial peroxisome proliferator-activated receptor-γ agonist, but it did not match the level of glucose homeostasis in the non-diabetic mice. Glyceollin-containing FSG improves glucose homeostasis, partly by enhancing hepatic insulin sensitivity in type 2 diabetic mice. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Imaging characteristics of cervical spine extra-arachnoid fluid collections managed conservatively.

    PubMed

    Lawrence, David A; Trotta, Brian; Shen, Francis H; Druzgal, Jason T; Fox, Michael G

    2016-09-01

    Determine the MRI characteristics of large post-traumatic cervical spine extra-arachnoid collections managed conservatively in clinically stable patients and whether evidence of clinical or imaging deterioration materialized. Following IRB approval, we conducted a retrospective search for all patients (>16 years old) over a 17-months period who had an extra-arachnoid fluid collection reported on a post-traumatic cervical spine MRI. Patients were excluded if they had surgery for an unstable fracture (n = 21), emergent decompression (n = 1) or lacked a follow-up MRI within 15 days (n = 1). Two MSK radiologists recorded the size, morphology and MRI signal characteristics of the collections. Eight patients (5 male, 3 female) met the inclusion criteria (mean age 40 years; range 19-78 years). Seven of the eight patients had fluid collections that demonstrated thin, tapered margins, extended >7 vertebral bodies and involved >180 degrees of the spinal canal. The signal characteristics of these collections varied: hyper-T1/iso-T2 (n = 1), iso-T1/T2 (n = 3), hyper-T1/hypo-T2 (n = 3) and mixed-T1/T2 (n = 1). Six of seven collections were ventral. Follow-up MRI demonstrated resolution/significant decrease in size (n = 4 between 1 and 12 days) or no change/slight decrease in size (n = 3; between 2 and 11 days). None of the seven fluid collections enlarged, no patient had abnormal cord signal, and no patient's neurologic symptoms worsened. One of eight patients had a dorsal "mass-like" collection that was slightly smaller 9 days later. In stable patients with large, tapered post-traumatic cervical spine extra-arachnoid collections managed non-surgically, none developed (1) clinical worsening, (2) abnormal cord signal or (3) collection enlargement, regardless of the collection's signal characteristics.

  8. Influence of task switching costs on colony homeostasis

    NASA Astrophysics Data System (ADS)

    Jeanson, Raphaël; Lachaud, Jean-Paul

    2015-06-01

    In social insects, division of labour allows colonies to optimise the allocation of workers across all available tasks to satisfy colony requirements. The maintenance of stable conditions within colonies (homeostasis) requires that some individuals move inside the nest to monitor colony needs and execute unattended tasks. We developed a simple theoretical model to explore how worker mobility inside the nest and task switching costs influence the maintenance of stable levels of task-associated stimuli. Our results indicate that worker mobility in large colonies generates important task switching costs and is detrimental to colony homeostasis. Our study suggests that the balance between benefits and costs associated with the mobility of workers patrolling inside the nest depends on colony size. We propose that several species of ants with diverse life-history traits should be appropriate to test the prediction that the proportion of mobile workers should vary during colony ontogeny.

  9. Glucocorticoid receptor polymorphism in obesity and glucose homeostasis.

    PubMed

    Majer-Łobodzińska, Agnieszka; Adamiec-Mroczek, Joanna

    2017-01-01

    Glucocorticoid receptor (GR) activity plays a significant role in the etiology of obesity and is essential for glucose homeostasis, the development of hyperinsulinaemia and subsequent increased fat deposition. Several polymorphisms in the GR gene have been described, and at least three of them seem to be associated with altered glucocorticoid sensitivity and changes in glucose homeostasis, and other metabolic parameters. The N363S polymorphism has been associated with increased sensitivity to glucocorticoides, increased insulin response to dexamethasone and increased plasma glucose level. BclI polymorphism is associated with increased abdominal obesity, hyperinsulinaemia and increased insulin resistance. Another polymorphism, ER22/23EK, in contrast to the others, is associated with relative resistance to glucocoricides actions and more beneficial metabolic profile-lower insulin resistance level, decreased lower cardiovascular risk and subseuent prolongation of life time. More research is still needed to understand the mechanisms behind these associations at the molecular level.

  10. Nitric oxide interferes with islet cell zinc homeostasis.

    PubMed

    Tartler, U; Kröncke, K D; Meyer, K L; Suschek, C V; Kolb-Bachofen, V

    2000-12-01

    Zinc is crucial for the biosynthesis, storage, and secretion of insulin in pancreatic islet cells. We have previously presented evidence that NO interferes with cellular Zn(2+) homeostasis and we therefore investigated the influence of chronic NO exposure on the labile islet cell Zn(2+) content. A strong fluorescence activity in a large islet cell subpopulation was found after staining with the Zn(2+)-specific fluorophore Zinquin. Culture for 24 h in the presence of nontoxic concentrations of the slow-releasing NO donor DETA/NO resulted in a significantly reduced Zn(2+)-dependent fluorescence. This appears to be islet specific as in endothelial cells DETA/NO exposure enhanced the Zn(2+)-dependent fluorescence activity in a concentration-dependent manner. These results suggest that NO interferes with cellular Zn(2+) homeostasis, which in islet cells is crucial for proper hormone delivery and thus special cell function. Copyright 2000 Academic Press.

  11. Disrupted iron homeostasis causes dopaminergic neurodegeneration in mice

    PubMed Central

    Matak, Pavle; Matak, Andrija; Moustafa, Sarah; Aryal, Dipendra K.; Benner, Eric J.; Wetsel, William; Andrews, Nancy C.

    2016-01-01

    Disrupted brain iron homeostasis is a common feature of neurodegenerative disease. To begin to understand how neuronal iron handling might be involved, we focused on dopaminergic neurons and asked how inactivation of transport proteins affected iron homeostasis in vivo in mice. Loss of the cellular iron exporter, ferroportin, had no apparent consequences. However, loss of transferrin receptor 1, involved in iron uptake, caused neuronal iron deficiency, age-progressive degeneration of a subset of dopaminergic neurons, and motor deficits. There was gradual depletion of dopaminergic projections in the striatum followed by death of dopaminergic neurons in the substantia nigra. Damaged mitochondria accumulated, and gene expression signatures indicated attempted axonal regeneration, a metabolic switch to glycolysis, oxidative stress, and the unfolded protein response. We demonstrate that loss of transferrin receptor 1, but not loss of ferroportin, can cause neurodegeneration in a subset of dopaminergic neurons in mice. PMID:26929359

  12. A new vesicle trafficking regulator CTL1 plays a crucial role in ion homeostasis.

    PubMed

    Gao, Yi-Qun; Chen, Jiu-Geng; Chen, Zi-Ru; An, Dong; Lv, Qiao-Yan; Han, Mei-Ling; Wang, Ya-Ling; Salt, David E; Chao, Dai-Yin

    2017-12-01

    Ion homeostasis is essential for plant growth and environmental adaptation, and maintaining ion homeostasis requires the precise regulation of various ion transporters, as well as correct root patterning. However, the mechanisms underlying these processes remain largely elusive. Here, we reported that a choline transporter gene, CTL1, controls ionome homeostasis by regulating the secretory trafficking of proteins required for plasmodesmata (PD) development, as well as the transport of some ion transporters. Map-based cloning studies revealed that CTL1 mutations alter the ion profile of Arabidopsis thaliana. We found that the phenotypes associated with these mutations are caused by a combination of PD defects and ion transporter misregulation. We also established that CTL1 is involved in regulating vesicle trafficking and is thus required for the trafficking of proteins essential for ion transport and PD development. Characterizing choline transporter-like 1 (CTL1) as a new regulator of protein sorting may enable researchers to understand not only ion homeostasis in plants but also vesicle trafficking in general.

  13. Copper Homeostasis as a Therapeutic Target in Amyotrophic Lateral Sclerosis with SOD1 Mutations

    PubMed Central

    Tokuda, Eiichi; Furukawa, Yoshiaki

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease affecting both upper and lower motor neurons, and currently, there is no cure or effective treatment. Mutations in a gene encoding a ubiquitous antioxidant enzyme, Cu,Zn-superoxide dismutase (SOD1), have been first identified as a cause of familial forms of ALS. It is widely accepted that mutant SOD1 proteins cause the disease through a gain in toxicity but not through a loss of its physiological function. SOD1 is a major copper-binding protein and regulates copper homeostasis in the cell; therefore, a toxicity of mutant SOD1 could arise from the disruption of copper homeostasis. In this review, we will briefly review recent studies implying roles of copper homeostasis in the pathogenesis of SOD1-ALS and highlight the therapeutic interventions focusing on pharmacological as well as genetic regulations of copper homeostasis to modify the pathological process in SOD1-ALS. PMID:27136532

  14. Copper Homeostasis as a Therapeutic Target in Amyotrophic Lateral Sclerosis with SOD1 Mutations.

    PubMed

    Tokuda, Eiichi; Furukawa, Yoshiaki

    2016-04-28

    Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease affecting both upper and lower motor neurons, and currently, there is no cure or effective treatment. Mutations in a gene encoding a ubiquitous antioxidant enzyme, Cu,Zn-superoxide dismutase (SOD1), have been first identified as a cause of familial forms of ALS. It is widely accepted that mutant SOD1 proteins cause the disease through a gain in toxicity but not through a loss of its physiological function. SOD1 is a major copper-binding protein and regulates copper homeostasis in the cell; therefore, a toxicity of mutant SOD1 could arise from the disruption of copper homeostasis. In this review, we will briefly review recent studies implying roles of copper homeostasis in the pathogenesis of SOD1-ALS and highlight the therapeutic interventions focusing on pharmacological as well as genetic regulations of copper homeostasis to modify the pathological process in SOD1-ALS.

  15. Role of FGF/FGFR signaling in skeletal development and homeostasis: learning from mouse models

    PubMed Central

    Su, Nan; Jin, Min; Chen, Lin

    2014-01-01

    Fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling plays essential roles in bone development and diseases. Missense mutations in FGFs and FGFRs in humans can cause various congenital bone diseases, including chondrodysplasia syndromes, craniosynostosis syndromes and syndromes with dysregulated phosphate metabolism. FGF/FGFR signaling is also an important pathway involved in the maintenance of adult bone homeostasis. Multiple kinds of mouse models, mimicking human skeleton diseases caused by missense mutations in FGFs and FGFRs, have been established by knock-in/out and transgenic technologies. These genetically modified mice provide good models for studying the role of FGF/FGFR signaling in skeleton development and homeostasis. In this review, we summarize the mouse models of FGF signaling-related skeleton diseases and recent progresses regarding the molecular mechanisms, underlying the role of FGFs/FGFRs in the regulation of bone development and homeostasis. This review also provides a perspective view on future works to explore the roles of FGF signaling in skeletal development and homeostasis. PMID:26273516

  16. Phosphate homeostasis in the yeast Saccharomyces cerevisiae, the key role of the SPX domain-containing proteins.

    PubMed

    Secco, David; Wang, Chuang; Shou, Huixia; Whelan, James

    2012-02-17

    In the yeast Saccharomyces cerevisiae, a working model for nutrient homeostasis in eukaryotes, inorganic phosphate (Pi) homeostasis is regulated by the PHO pathway, a set of phosphate starvation induced genes, acting to optimize Pi uptake and utilization. Among these, a subset of proteins containing the SPX domain has been shown to be key regulators of Pi homeostasis. In this review, we summarize the recent progresses in elucidating the mechanisms controlling Pi homeostasis in yeast, focusing on the key roles of the SPX domain-containing proteins in these processes, as well as describing the future challenges and opportunities in this fast-moving field. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  17. An analysis of the Petri net based model of the human body iron homeostasis process.

    PubMed

    Sackmann, Andrea; Formanowicz, Dorota; Formanowicz, Piotr; Koch, Ina; Blazewicz, Jacek

    2007-02-01

    In the paper a Petri net based model of the human body iron homeostasis is presented and analyzed. The body iron homeostasis is an important but not fully understood complex process. The modeling of the process presented in the paper is expressed in the language of Petri net theory. An application of this theory to the description of biological processes allows for very precise analysis of the resulting models. Here, such an analysis of the body iron homeostasis model from a mathematical point of view is given.

  18. Abnormal organic-matter maturation in the Yinggehai Basin, South China Sea: Implications for hydrocarbon expulsion and fluid migration from overpressured systems

    USGS Publications Warehouse

    Hao, F.; Li, S.; Dong, W.; Hu, Z.; Huang, B.

    1998-01-01

    Three superimposed pressure systems are present in the Yinggehai Basin, South China Sea. A number of commercial, thermogenic gas accumulations have been found in an area in which shale diapirs occur. Because the reservoir intervals are shallow and very young, they must have filled with gas rapidly. The thick (up to 17 km) Tertiary and Quaternary sedimentary succession is dominated by shales, and is not disrupted by major faulting in the study area, a factor which seems to have had an important effect on both hydrocarbon generation and fluid migration. Organic-matter maturation in the deepest, most overpressured compartment has been significantly retarded as a result of the combined effects of excess pressure, the presence of large volumes of water, and the retention of generated hydrocarbons. This retardation is indicated by both kerogen-related parameters (vitrinite reflectance and Rock-Eval T(max)); and also by parameters based on the analysis of soluble organic matter (such as the C15+ hydrocarbon content, and the concentration of isoprenoid hydrocarbons relative to adjacent normal alkanes). In contrast to this, organic-matter maturation in shallow, normally-pressured strata in the diapiric area has been enhanced by hydrothermal fluid flow, which is clearly not topography-driven in origin. As a result, the hydrocarbon generation 'window' in the basin is considerably wider than could be expected from traditional geochemical modelling. These two unusual and contrasting anomalies in organic-matter maturation, together with other lines of evidence, suggest that there was a closed fluid system in the overpressured compartment until shale diapirs developed. The diapirs developed as a result of the intense overpressuring, and their growth was triggered by regional extensional stresses. They served as conduits through which fluids (both water and hydrocarbons) retained in the closed system could rapidly migrate. Fluid migration led to the modification of the thermal

  19. Brain glucose sensing, counterregulation, and energy homeostasis.

    PubMed

    Marty, Nell; Dallaporta, Michel; Thorens, Bernard

    2007-08-01

    Neuronal circuits in the central nervous system play a critical role in orchestrating the control of glucose and energy homeostasis. Glucose, beside being a nutrient, is also a signal detected by several glucose-sensing units that are located at different anatomical sites and converge to the hypothalamus to cooperate with leptin and insulin in controlling the melanocortin pathway.

  20. ALTERATIONS OF FE HOMEOSTASIS IN RAT CARDIOVASCULAR DISEASE MODELS AND ITS CONTRIBUTION TO CARDIOPULMONARY TOXICITY

    EPA Science Inventory

    Introduction: Fe homeostasis can be disrupted in human cardiovascular diseases (CVD). We addressed how dysregulation of Fe homeostasis affected the pulmonary inflammation/oxidative stress response and disease progression after exposure to Libby amphibole (LA), an asbestifonn mine...

  1. The effect of polyunsaturated fatty acids on the homeostasis of yolk lipoprotein in C. elegans examined by CARS and two-photon excitation fluorescence (TPE-F) microscopy

    NASA Astrophysics Data System (ADS)

    Chen, Wei-Wen; Yi, Yung-Hsiang; Chien, Cheng-Hao; Hsiung, Kuei-Ching; Lin, Yi-Chun; Ma, Tian-Hsiang; Lo, Szecheng J.; Chang, Ta-Chau

    2016-03-01

    Yolk lipoprotein constitutes the major source of energy and the materials for synthesizing signaling factors for the development of oocytes and embryos in C. elegans. Polyunsaturated fatty acids (PUFAs) packed in yolk lipoprotein have been recently recognized as critical molecules for fertilization and reproduction.1 However, the relation between PUFAs and the homeostasis of yolk lipoprotein is not clear. Here we use coherent anti-Stokes Raman scattering (CARS) microscopy and two-photon excitation fluorescence (TPE-F) microscopy to examine the transportation of yolk lipoprotein. We demonstrate that CARS microscopy is a more sensitive method than the traditional Nile Red staining method in probing the abnormal accumulation of yolk lipoprotein in the body cavity of C. elegans. It is found that the accumulation of yolk lipoprotein is a time-dependent process. In addition, a negative correlation (r = -0.955) between reproductive aging and abnormal accumulation of yolk lipoprotein is established. We further examine wild-type, fat-1, and fat-2 worms with or without the expression of GFP-tagged yolk lipoprotein (VIT-2-GFP). Our data reveal that PUFAs have a positive effect on the synthesis and endocytosis of yolk lipoprotein, confirming the model proposed by Edmonds et al.2

  2. Hypothalamic Vitamin D Improves Glucose Homeostasis and Reduces Weight

    PubMed Central

    Arble, Deanna M.; Chambers, Adam P.; Gutierrez-Aguilar, Ruth; He, Yanlin; Xu, Yong; Gardner, David; Moore, David D.; Seeley, Randy J.; Sandoval, Darleen A.

    2016-01-01

    Despite clear associations between vitamin D deficiency and obesity and/or type 2 diabetes, a causal relationship is not established. Vitamin D receptors (VDRs) are found within multiple tissues, including the brain. Given the importance of the brain in controlling both glucose levels and body weight, we hypothesized that activation of central VDR links vitamin D to the regulation of glucose and energy homeostasis. Indeed, we found that small doses of active vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3) (calcitriol), into the third ventricle of the brain improved glucose tolerance and markedly increased hepatic insulin sensitivity, an effect that is dependent upon VDR within the paraventricular nucleus of the hypothalamus. In addition, chronic central administration of 1,25D3 dramatically decreased body weight by lowering food intake in obese rodents. Our data indicate that 1,25D3-mediated changes in food intake occur through action within the arcuate nucleus. We found that VDR colocalized with and activated key appetite-regulating neurons in the arcuate, namely proopiomelanocortin neurons. Together, these findings define a novel pathway for vitamin D regulation of metabolism with unique and divergent roles for central nervous system VDR signaling. Specifically, our data suggest that vitamin D regulates glucose homeostasis via the paraventricular nuclei and energy homeostasis via the arcuate nuclei. PMID:27217488

  3. Hypothalamic Vitamin D Improves Glucose Homeostasis and Reduces Weight.

    PubMed

    Sisley, Stephanie R; Arble, Deanna M; Chambers, Adam P; Gutierrez-Aguilar, Ruth; He, Yanlin; Xu, Yong; Gardner, David; Moore, David D; Seeley, Randy J; Sandoval, Darleen A

    2016-09-01

    Despite clear associations between vitamin D deficiency and obesity and/or type 2 diabetes, a causal relationship is not established. Vitamin D receptors (VDRs) are found within multiple tissues, including the brain. Given the importance of the brain in controlling both glucose levels and body weight, we hypothesized that activation of central VDR links vitamin D to the regulation of glucose and energy homeostasis. Indeed, we found that small doses of active vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3) (calcitriol), into the third ventricle of the brain improved glucose tolerance and markedly increased hepatic insulin sensitivity, an effect that is dependent upon VDR within the paraventricular nucleus of the hypothalamus. In addition, chronic central administration of 1,25D3 dramatically decreased body weight by lowering food intake in obese rodents. Our data indicate that 1,25D3-mediated changes in food intake occur through action within the arcuate nucleus. We found that VDR colocalized with and activated key appetite-regulating neurons in the arcuate, namely proopiomelanocortin neurons. Together, these findings define a novel pathway for vitamin D regulation of metabolism with unique and divergent roles for central nervous system VDR signaling. Specifically, our data suggest that vitamin D regulates glucose homeostasis via the paraventricular nuclei and energy homeostasis via the arcuate nuclei. © 2016 by the American Diabetes Association.

  4. Fluid mechanics in fluids at rest.

    PubMed

    Brenner, Howard

    2012-07-01

    Using readily available experimental thermophoretic particle-velocity data it is shown, contrary to current teachings, that for the case of compressible flows independent dye- and particle-tracer velocity measurements of the local fluid velocity at a point in a flowing fluid do not generally result in the same fluid velocity measure. Rather, tracer-velocity equality holds only for incompressible flows. For compressible fluids, each type of tracer is shown to monitor a fundamentally different fluid velocity, with (i) a dye (or any other such molecular-tagging scheme) measuring the fluid's mass velocity v appearing in the continuity equation and (ii) a small, physicochemically and thermally inert, macroscopic (i.e., non-Brownian), solid particle measuring the fluid's volume velocity v(v). The term "compressibility" as used here includes not only pressure effects on density, but also temperature effects thereon. (For example, owing to a liquid's generally nonzero isobaric coefficient of thermal expansion, nonisothermal liquid flows are to be regarded as compressible despite the general perception of liquids as being incompressible.) Recognition of the fact that two independent fluid velocities, mass- and volume-based, are formally required to model continuum fluid behavior impacts on the foundations of contemporary (monovelocity) fluid mechanics. Included therein are the Navier-Stokes-Fourier equations, which are now seen to apply only to incompressible fluids (a fact well-known, empirically, to experimental gas kineticists). The findings of a difference in tracer velocities heralds the introduction into fluid mechanics of a general bipartite theory of fluid mechanics, bivelocity hydrodynamics [Brenner, Int. J. Eng. Sci. 54, 67 (2012)], differing from conventional hydrodynamics in situations entailing compressible flows and reducing to conventional hydrodynamics when the flow is incompressible, while being applicable to both liquids and gases.

  5. Neurotoxicity Linked to Dysfunctional Metal Ion Homeostasis and Xenobiotic Metal Exposure: Redox Signaling and Oxidative Stress.

    PubMed

    Garza-Lombó, Carla; Posadas, Yanahi; Quintanar, Liliana; Gonsebatt, María E; Franco, Rodrigo

    2018-06-20

    Essential metals such as copper, iron, manganese, and zinc play a role as cofactors in the activity of a wide range of processes involved in cellular homeostasis and survival, as well as during organ and tissue development. Throughout our life span, humans are also exposed to xenobiotic metals from natural and anthropogenic sources, including aluminum, arsenic, cadmium, lead, and mercury. It is well recognized that alterations in the homeostasis of essential metals and an increased environmental/occupational exposure to xenobiotic metals are linked to several neurological disorders, including neurodegeneration and neurodevelopmental alterations. Recent Advances: The redox activity of essential metals is key for neuronal homeostasis and brain function. Alterations in redox homeostasis and signaling are central to the pathological consequences of dysfunctional metal ion homeostasis and increased exposure to xenobiotic metals. Both redox-active and redox-inactive metals trigger oxidative stress and damage in the central nervous system, and the exact mechanisms involved are starting to become delineated. In this review, we aim to appraise the role of essential metals in determining the redox balance in the brain and the mechanisms by which alterations in the homeostasis of essential metals and exposure to xenobiotic metals disturb the cellular redox balance and signaling. We focus on recent literature regarding their transport, metabolism, and mechanisms of toxicity in neural systems. Delineating the specific mechanisms by which metals alter redox homeostasis is key to understand the pathological processes that convey chronic neuronal dysfunction in neurodegenerative and neurodevelopmental disorders. Antioxid. Redox Signal. 28, 1669-1703.

  6. Neurologic abnormalities in murderers.

    PubMed

    Blake, P Y; Pincus, J H; Buckner, C

    1995-09-01

    Thirty-one individuals awaiting trial or sentencing for murder or undergoing an appeal process requested a neurologic examination through legal counsel. We attempted in each instance to obtain EEG, MRI or CT, and neuropsychological testing. Neurologic examination revealed evidence of "frontal" dysfunction in 20 (64.5%). There were symptoms or some other evidence of temporal lobe abnormality in nine (29%). We made a specific neurologic diagnosis in 20 individuals (64.5%), including borderline or full mental retardation (9) and cerebral palsy (2), among others. Neuropsychological testing revealed abnormalities in all subjects tested. There were EEG abnormalities in eight of the 20 subjects tested, consisting mainly of bilateral sharp waves with slowing. There were MRI or CT abnormalities in nine of the 19 subjects tested, consisting primarily of atrophy and white matter changes. Psychiatric diagnoses included paranoid schizophrenia (8), dissociative disorder (4), and depression (9). Virtually all subjects had paranoid ideas and misunderstood social situations. There was a documented history of profound, protracted physical abuse in 26 (83.8%) and of sexual abuse in 10 (32.3%). It is likely that prolonged, severe physical abuse, paranoia, and neurologic brain dysfunction interact to form the matrix of violent behavior.

  7. Estimation of gestational age from study of amniotic fluid and clinical assessment.

    PubMed Central

    Deshpande, T. V.; Harding, P. G.; Jaco, N. T.

    1977-01-01

    Study of 108 samples of amniotic fluid obtained between 28 and 42 weeks' gestation from 101 patients revealed that in normal pregnancies the creatinine concentration, lecithin/sphingomyelin (L/S) ratio and percentage of fat cells correlated better with the gestational age of the newborn--assessed by clinical criteria--than did the bilirubin and sodium concentrations. A creatinine concentration of 1.75 mg/dL or more, an L/S ratio of 4 or more and a fat cell percentage of 10 or more correlated significantly with a gestational age of 37 weeks or more. In abnormal pregnancies (those with obstetric or medical complications, or both) the mean creatinine concentration in the amniotic fluid was significantly less than expected for gestational age in fetal dysmaturity and greater than expected when the mother had diabetes. The mean L/S ratio in the amniotic fluid was elevated when the mother had hypertension or smoked and in cases of fetal dysmaturity or long interval between rupture of the membranes and delivery, whereas it was significantly lower than normal when the mother had diabetes. The mean bilirubin concentration in the amniotic fluid was significantly lower than normal when the mother had hypertension. When the mother had diabetes, maturity of the fetal lung, liver, skin and brain appeared to be delayed, according to the values for the amniotic fluid constituents. PMID:912615

  8. Resveratrol Ameliorates Abnormalities of Fluid and Electrolyte Secretion in a Hypoxia-Induced Model of Acquired CFTR Deficiency

    PubMed Central

    Woodworth, Bradford A.

    2015-01-01

    OCT). Results Hypoxia significantly decreased ΔISC (in μA/cm2) attributable to CFTR at 12 and 24 hours of exposure in both MNSE [13.55+/− 0.46 (12 hours);12.75+/−0.07(24 hours) vs. 19.23+/−0.18(control);p<0.05] and HSNE [19.55+/−0.56(12 hours);17.67+/− 1.13(24 hours) vs. 25.49+/−1.48(control);p<0.05]. We have shown that resveratrol (100μM) enhanced CFTR-dependent Cl− secretion in HSNE to an extent comparable to the recently FDA-approved CFTR potentiator, ivacaftor. Cl− transport across human sinonasal explants [78.42+/−1.75 vs. 1.75+/−1.5(control);p<0.05] and in vivo murine nasal epithelium [−4+/−1.8 vs. −0.8+/−1.7 mV(control);p<0.05] was also significantly increased by the drug. No increase in cellular cAMP or CFTR R-domain phosphorylation was detected. Inside out patches showed increased CFTR open probability [(NPo/N(N=channel number)] compared to controls in both MNSE [(0.329+/−0.116 vs. 0.119+/−0.059(control);p<0.05)] and HEK293 cells [(0.22+/−0.048 vs. 0.125+/−0.07(control);p<0.05). ASL thickness was decreased under hypoxic conditions when measured by CLSM [4.19+/−0.44 vs. 6.88+/−0.67(control);p<0.05]. A 30 minute apical application of resveratrol increased ASL depth in normal epithelium [8.08+/−1.68 vs. 6.11+/−0.47(control);p<0.05]. Furthermore, hypoxia-induced abnormalities of fluid and electrolyte secretion in sinonasal epithelium were restored with resveratrol treatment [5.55+/−0.74 vs. 3.13+/−0.17(control);p<0.05]. Conclusions CFTR activation with a leading edge Cl− secretagogue such as resveratrol represents an innovative approach to overcoming acquired CFTR defects in sinus and nasal airway disease. This exciting new strategy bears further testing in non-CF individuals with CRS. PMID:25946147

  9. Highly controlled nest homeostasis of honey bees helps deactivate phenolics in nectar

    NASA Astrophysics Data System (ADS)

    Liu, Fanglin; He, Jianzhong; Fu, Wenjun

    2005-06-01

    Honey bees have a highly developed nest homeostasis, for example, maintaining low CO2 levels and stable nest temperatures at 35°C.We investigate the role of nest homeostasis in deactivating phenolic compounds present in the nectar of Aloe littoralis. We show that the phenolic content in nectar was reduced (from 0.65% to 0.49%) after nectar was incubated in a nest of Apis cerana, and that it was reduced still more (from 0.65% to 0.37%) if nectar was mixed with hypopharyngeal gland proteins (HGP) of worker bees before being placed inside a nest. HGP had little effect on samples outside a nest, indicating that nest conditions are necessary for HGP to deactivate phenolics in nectar. Consequently, the highly controlled nest homeostasis of honey bees facilitates direct deactivation of phenolics in nectar, and plays a role in the action of HGP as well.

  10. Dandy-Walker syndrome and chromosomal abnormalities.

    PubMed

    Imataka, George; Yamanouchi, Hideo; Arisaka, Osamu

    2007-12-01

    Dandy-Walker syndrome (DWS) is a brain malformation of unknown etiology, but several reports have been published indicating that there is a causal relationship to various types of chromosomal abnormalities and malformation syndromes. In the present article, we present a bibliographical survey of several previously issued reports on chromosomal abnormalities associated with DWS, including our case of DWS found in trisomy 18. There are various types of chromosomal abnormalities associated with DWS; most of them are reported in chromosome 3, 9, 13 and 18. We also summarize some other chromosomal abnormalities and various congenital malformation syndromes.

  11. Fluid Extravasation in Shoulder Arthroscopic Surgery: A Systematic Review.

    PubMed

    Memon, Muzammil; Kay, Jeffrey; Gholami, Arian; Simunovic, Nicole; Ayeni, Olufemi R

    2018-05-01

    Arthroscopic surgery of the shoulder joint has become increasingly more common given its advantages over open surgery; however, one rare but potentially life-threatening complication is fluid extravasation into the surrounding tissues, causing edema, respiratory compromise, abnormal results on laboratory blood tests, and possibly death. Currently, no systematic review exists that summarizes the existing clinical research on this topic. To perform a systematic review on fluid extravasation as a complication of shoulder arthroscopic surgery, specifically assessing clinical presentation, risk factors, management, and outcomes. Systematic review; Level of evidence, 4. Two reviewers independently searched 3 databases (PubMed, Ovid [MEDLINE], and Embase) from database inception until July 1, 2017. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist guided the reporting and data abstraction. The methodological quality of these studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) checklist. The results are presented in a narrative summary fashion using descriptive statistics including ranges and agreement statistics. A total of 26 studies (20 case reports, 4 case series, and 2 prospective comparative studies) encompassing 205 patients (mean age, 50.8 years [range, 15-83 years]) were included. The most common signs of fluid extravasation included chest wall swelling (n = 86) and neck swelling (n = 116). In 32 patients, observation alone was sufficient. Other patients required airway intubation (n = 16), diuretics (n = 7), steroids (n = 1), and percutaneous drainage of fluid (n = 1). Clinical edema resolved after 2 to 48 hours, and patients were discharged 1 to 20 days postoperatively. Serious complications included transfer to the intensive care unit (n = 14), anterior interosseous nerve palsy (n = 4), rhabdomyolysis (n = 1), and death (n = 1). Fluid extravasation has the potential to be a life

  12. An essential cell-autonomous role for hepcidin in cardiac iron homeostasis

    PubMed Central

    Lakhal-Littleton, Samira; Wolna, Magda; Chung, Yu Jin; Christian, Helen C; Heather, Lisa C; Brescia, Marcella; Ball, Vicky; Diaz, Rebeca; Santos, Ana; Biggs, Daniel; Clarke, Kieran; Davies, Benjamin; Robbins, Peter A

    2016-01-01

    Hepcidin is the master regulator of systemic iron homeostasis. Derived primarily from the liver, it inhibits the iron exporter ferroportin in the gut and spleen, the sites of iron absorption and recycling respectively. Recently, we demonstrated that ferroportin is also found in cardiomyocytes, and that its cardiac-specific deletion leads to fatal cardiac iron overload. Hepcidin is also expressed in cardiomyocytes, where its function remains unknown. To define the function of cardiomyocyte hepcidin, we generated mice with cardiomyocyte-specific deletion of hepcidin, or knock-in of hepcidin-resistant ferroportin. We find that while both models maintain normal systemic iron homeostasis, they nonetheless develop fatal contractile and metabolic dysfunction as a consequence of cardiomyocyte iron deficiency. These findings are the first demonstration of a cell-autonomous role for hepcidin in iron homeostasis. They raise the possibility that such function may also be important in other tissues that express both hepcidin and ferroportin, such as the kidney and the brain. DOI: http://dx.doi.org/10.7554/eLife.19804.001 PMID:27897970

  13. Ghrelin, the proglucagon-derived peptides and peptide YY in nutrient homeostasis.

    PubMed

    Dong, Charlotte X; Brubaker, Patricia L

    2012-12-01

    Dysregulation of nutrient homeostasis is implicated in the current epidemics of obesity and type 2 diabetes mellitus. The maintenance of homeostasis in the setting of repeated cycles of feeding and fasting occurs through complex interactions between metabolic, hormonal and neural factors. Although pancreatic islets, the liver, muscle, adipocytes and the central nervous system are all key players in this network, the gastrointestinal tract is the first tissue exposed to ingested nutrients and thus has an important role. This Review focuses on several of the endocrine hormones released by the gastrointestinal tract prior to or during nutrient ingestion that have key roles in maintaining energy balance. These hormones include the gastric orexigenic hormone, ghrelin, and the distal L cell anorexigenic and metabolic hormones, glucagon-like peptide (GLP)-1, GLP-2, oxyntomodulin and peptide YY. Each of these hormones exerts a distinct set of biological actions to maintain nutrient homeostasis, the properties of which are currently, or might soon be, exploited in the clinic for the treatment of obesity and type 2 diabetes mellitus.

  14. Popliteal cysts and subgastrocnemius bursitis are associated with knee symptoms and structural abnormalities in older adults: a cross-sectional study.

    PubMed

    Cao, Yuelong; Jones, Graeme; Han, Weiyu; Antony, Benny; Wang, Xia; Cicuttini, Flavia; Ding, Changhai

    2014-03-03

    The role of popliteal cysts and subgastrocnemius bursitis in knee joint homeostasis is uncertain. The aim of this study is to describe cross-sectional associations between popliteal cysts, subgastrocnemius bursitis, knee symptoms and structural abnormalities in older adults. A cross-sectional sample of 900 randomly-selected subjects (mean age 63 years, 48% female) were studied. Knee pain, stiffness and dysfunction were assessed by self-administered Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire. Radiographic knee osteophyte and joint space narrowing (JSN) were recorded. Magnetic resonance imaging (MRI) was utilized to assess popliteal cysts, subgastrocnemius bursitis, cartilage defects and bone marrow lesions (BMLs). Popliteal cysts were present in 11.7% and subgastrocnemius bursitis in 12.7% of subjects. Subgastrocnemius bursitis was more common in those with popliteal cyst (36.2% versus 9.7%, P <0.01). In multivariable analyses, popliteal cysts were significantly associated with increased osteophytes in both medial and lateral tibiofemoral compartments while subgastrocnemius bursitis was associated with increased osteophytes and JSN in the medial tibiofemoral compartment. Both were significantly associated with cartilage defects in all compartments, and with BMLs in the medial tibiofemoral compartment. Furthermore, both popliteal cysts and subgastrocnemius bursitis were significantly associated with increased weight-bearing knee pain but these associations became non-significant after adjustment for cartilage defects and BMLs. Popliteal cysts and subgastrocnemius bursitis are associated with increased symptoms as well as radiographic and MRI-detected joint structural abnormalities. Longitudinal data will help resolve if they are a consequence or a cause of knee joint abnormalities.

  15. Popliteal cysts and subgastrocnemius bursitis are associated with knee symptoms and structural abnormalities in older adults: a cross-sectional study

    PubMed Central

    2014-01-01

    Introduction The role of popliteal cysts and subgastrocnemius bursitis in knee joint homeostasis is uncertain. The aim of this study is to describe cross-sectional associations between popliteal cysts, subgastrocnemius bursitis, knee symptoms and structural abnormalities in older adults. Methods A cross-sectional sample of 900 randomly-selected subjects (mean age 63 years, 48% female) were studied. Knee pain, stiffness and dysfunction were assessed by self-administered Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire. Radiographic knee osteophyte and joint space narrowing (JSN) were recorded. Magnetic resonance imaging (MRI) was utilized to assess popliteal cysts, subgastrocnemius bursitis, cartilage defects and bone marrow lesions (BMLs). Results Popliteal cysts were present in 11.7% and subgastrocnemius bursitis in 12.7% of subjects. Subgastrocnemius bursitis was more common in those with popliteal cyst (36.2% versus 9.7%, P <0.01). In multivariable analyses, popliteal cysts were significantly associated with increased osteophytes in both medial and lateral tibiofemoral compartments while subgastrocnemius bursitis was associated with increased osteophytes and JSN in the medial tibiofemoral compartment. Both were significantly associated with cartilage defects in all compartments, and with BMLs in the medial tibiofemoral compartment. Furthermore, both popliteal cysts and subgastrocnemius bursitis were significantly associated with increased weight-bearing knee pain but these associations became non-significant after adjustment for cartilage defects and BMLs. Conclusions Popliteal cysts and subgastrocnemius bursitis are associated with increased symptoms as well as radiographic and MRI-detected joint structural abnormalities. Longitudinal data will help resolve if they are a consequence or a cause of knee joint abnormalities. PMID:24581327

  16. The emerging role of lysosomes in copper homeostasis.

    PubMed

    Polishchuk, Elena V; Polishchuk, Roman S

    2016-09-01

    The lysosomal system operates as a focal point where a number of important physiological processes such as endocytosis, autophagy and nutrient sensing converge. One of the key functions of lysosomes consists of regulating the metabolism/homeostasis of metals. Metal-containing components are carried to the lysosome through incoming membrane flows, while numerous transporters allow metal ions to move across the lysosome membrane. These properties enable lysosomes to direct metal fluxes to the sites where metal ions are either used by cellular components or sequestered. Copper belongs to a group of metals that are essential for the activity of vitally important enzymes, although it is toxic when in excess. Thus, copper uptake, supply and intracellular compartmentalization have to be tightly regulated. An increasing number of publications have indicated that these processes involve lysosomes. Here we review studies that reveal the expanding role of the lysosomal system as a hub for the control of Cu homeostasis and for the regulation of key Cu-dependent processes in health and disease.

  17. Colonic macrophage polarization in homeostasis, inflammation, and cancer

    PubMed Central

    Appleyard, Caroline B.

    2016-01-01

    Our review focuses on the colonic macrophage, a monocyte-derived, tissue-resident macrophage, and the role it plays in health and disease, specifically in inflammatory conditions such as inflammatory bowel disease and cancer of the colon and rectum. We give special emphasis to macrophage polarization, or phenotype, in these different states. We focus on macrophages because they are one of the most numerous leukocytes in the colon, and because they normally contribute to homeostasis through an anti-inflammatory phenotype. However, in conditions such as inflammatory bowel disease, proinflammatory macrophages are increased in the colon and have been linked to disease severity and progression. In colorectal cancer, tumor cells may employ anti-inflammatory macrophages to promote tumor growth and dissemination, whereas proinflammatory macrophages may antagonize tumor growth. Given the key roles that this cell type plays in homeostasis, inflammation, and cancer, the colonic macrophage is an intriguing therapeutic target. As such, potential macrophage-targeting strategies are discussed. PMID:27229123

  18. Cellular Links between Neuronal Activity and Energy Homeostasis.

    PubMed

    Shetty, Pavan K; Galeffi, Francesca; Turner, Dennis A

    2012-01-01

    Neuronal activity, astrocytic responses to this activity, and energy homeostasis are linked together during baseline, conscious conditions, and short-term rapid activation (as occurs with sensory or motor function). Nervous system energy homeostasis also varies during long-term physiological conditions (i.e., development and aging) and with adaptation to pathological conditions, such as ischemia or low glucose. Neuronal activation requires increased metabolism (i.e., ATP generation) which leads initially to substrate depletion, induction of a variety of signals for enhanced astrocytic function, and increased local blood flow and substrate delivery. Energy generation (particularly in mitochondria) and use during ATP hydrolysis also lead to considerable heat generation. The local increases in blood flow noted following neuronal activation can both enhance local substrate delivery but also provides a heat sink to help cool the brain and removal of waste by-products. In this review we highlight the interactions between short-term neuronal activity and energy metabolism with an emphasis on signals and factors regulating astrocyte function and substrate supply.

  19. mTOR Regulates Cellular Iron Homeostasis through Tristetraprolin

    PubMed Central

    Bayeva, Marina; Khechaduri, Arineh; Puig, Sergi; Chang, Hsiang-Chun; Patial, Sonika; Blackshear, Perry J.; Ardehali, Hossein

    2013-01-01

    SUMMARY Iron is an essential cofactor with unique redox properties. Iron regulatory proteins 1 and 2 (IRP1/2) have been established as important regulators of cellular iron homeostasis, but little is known about the role of other pathways in this process. Here we report that the mammalian target of rapamycin (mTOR) regulates iron homeostasis by modulating transferrin receptor 1 (TfR1) stability and altering cellular iron flux. Mechanistic studies identify tristetraprolin (TTP), a protein involved in anti-inflammatory response, as the downstream target of mTOR that binds to and enhances degradation of TfR1 mRNA. We also show that TTP is strongly induced by iron chelation, promotes downregulation of iron-requiring genes in both mammalian and yeast cells, and modulates survival in low-iron states. Taken together, our data uncover a link between metabolic, inflammatory, and iron regulatory pathways, and point towards the existence of a yeast-like TTP-mediated iron conservation program in mammals. PMID:23102618

  20. Fluid imbalance

    MedlinePlus

    ... up in the body. This is called fluid overload (volume overload). This can lead to edema (excess fluid in ... Water imbalance; Fluid imbalance - dehydration; Fluid buildup; Fluid overload; Volume overload; Loss of fluids; Edema - fluid imbalance; ...

  1. Central insulin and leptin-mediated autonomic control of glucose homeostasis

    PubMed Central

    Marino, Joseph S.; Xu, Yong; Hill, Jennifer W.

    2016-01-01

    Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucose and insulin responsiveness. The preponderance of evidence indicates that the brain is the master regulator of glucose homeostasis, and that hypothalamic insulin and leptin signaling in particular play a crucial role in the development of insulin resistance. This review discusses the neuronal crosstalk between the hypothalamus, autonomic nervous system, and tissues associated with the pathogenesis of type 2 diabetes, and how hypothalamic insulin and leptin signaling are integral to maintaining normal glucose homeostasis. PMID:21489811

  2. Prognosis of Pregnant Women with One Abnormal Value on 75g OGTT.

    PubMed

    Kozuma, Yutaka; Inoue, Shigeru; Horinouchi, Takashi; Shinagawa, Takaaki; Nakayama, Hitomi; Kawaguchi, Atsushi; Hori, Daizo; Kamura, Toshiharu; Yamada, Kentaro; Ushijima, Kimio

    2015-01-01

    The aim of this study was to identify risk factors to allow us to detect patients at high risk of requiring insulin therapy, among Japanese pregnant women with one abnormal value (OAV) on a 75-g oral glucose tolerance test (75-g OGTT). A total of 118 pregnant women with OAV on a previous 75-g OGTT between 1997 and 2010 were studied. We identified the factors which can predict patients at high risk of requiring insulin therapy among Japanese pregnant women with OAV, by comparing severe abnormal glucose tolerance (insulin treatment; n=17) with mild glucose tolerance patients (diet only; n=101). The following factors were examined; plasma level of glucose (PG) and immunoreactive insulin (IRI) at fasting, 0.5, 1 and 2 hours after loading glucose, insulinogenic index, homeostasis model assessment insulin resistance (HOMA-IR), insulin sensitivity index-composite (ISI composite), and HbA1c at the time of the 75-g OGTT. Univariate analysis showed a positive correlation between insulin therapy and 2-h PG value, 0.5-h and 1-h IRI values, AUC-IRI and insulinogenic index (p<0.05). Multivariate analysis showed that the PG 2-h value and insulinogenic index were independent predictive factors of insulin therapy. A 2-h PG ≥153 mg / dl and an insulinogenic index of <0.42 had a sensitivity of 81.8%, a specificity of 83.8%, a positive predictive value of 60.0% and a negative predictive value of 93.9% for the prediction of patients who required insulin therapy among pregnant women with OAV. These results suggest that a level of 2-h PG ≥153 mg/dl and an insulinogenic index of <0.42 on 75-g OGTT are predictive factors for insulin therapy in Japanese pregnant women with OAV.

  3. Glucagon-like peptide-1 contributes to increases ABCA1 expression by downregulating miR-758 to regulate cholesterol homeostasis.

    PubMed

    Yao, Yue; Li, Qiang; Gao, Ping; Wang, Wei; Chen, Lili; Zhang, Jinchao; Xu, Yi

    2018-03-04

    Abnormal regulation of lipid metabolism is associated with type 2 diabetes mellitus (T2DM). GLP-1 as a new treatment for T2DM, has unique effects in modulating cholesterol homeostasis. However, the mechanism of this effect is largely missing. The aim of this study was to determine the effects of GLP-1 on cholesterol-induced lipotoxicity in hepatocytes and examine the underlying mechanisms. The cell viability was determined, and caspase-3 was used to detect the effects of GLP-1 on cholesterol-induced apoptosis. The alterations of miR-758 and ATP-binding cassette transporter A1 (ABCA1) resulting from cholesterol incubation or GLP-1 were detected by qRT-PCR and Western blot assays. Overexpression of miR-758 abrogated the GLP-1-mediated ABCA1 expression, and conversely, down-regulation of miR-758 aggravated GLP-1's action and revealed significant promotion effects. BODIPY-Cholesterol efflux assay revealed that treatment with miR-758 inhibitor significantly enhanced ABCA1-dependent cholesterol efflux, resulting in reduced total cholesterol. Furthermore, Oil red O staining and cholesterol measurement were used to detect lipid accumulation. As a result, cholesterol significantly attenuated cell viability, promoted cell apoptosis, and facilitated lipid accumulation, and these effects were reversed by GLP-1. This study provides evidence that, in HepG2 cells, GLP-1 may affect cholesterol homeostasis by regulating the expression of miR-758 and ABCA1. These data can inform the development of biomarkers for miR-758, and potentially other drugs, on the key pathways of lipid metabolism. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. A new vesicle trafficking regulator CTL1 plays a crucial role in ion homeostasis

    PubMed Central

    Gao, Yi-Qun; Chen, Jiu-Geng; Chen, Zi-Ru; An, Dong; Lv, Qiao-Yan; Han, Mei-Ling; Wang, Ya-Ling; Salt, David E.; Chao, Dai-Yin

    2017-01-01

    Ion homeostasis is essential for plant growth and environmental adaptation, and maintaining ion homeostasis requires the precise regulation of various ion transporters, as well as correct root patterning. However, the mechanisms underlying these processes remain largely elusive. Here, we reported that a choline transporter gene, CTL1, controls ionome homeostasis by regulating the secretory trafficking of proteins required for plasmodesmata (PD) development, as well as the transport of some ion transporters. Map-based cloning studies revealed that CTL1 mutations alter the ion profile of Arabidopsis thaliana. We found that the phenotypes associated with these mutations are caused by a combination of PD defects and ion transporter misregulation. We also established that CTL1 is involved in regulating vesicle trafficking and is thus required for the trafficking of proteins essential for ion transport and PD development. Characterizing choline transporter-like 1 (CTL1) as a new regulator of protein sorting may enable researchers to understand not only ion homeostasis in plants but also vesicle trafficking in general. PMID:29284002

  5. Mechanosensitivity of Jagged–Notch signaling can induce a switch-type behavior in vascular homeostasis

    PubMed Central

    Stassen, Oscar M. J. A.; ter Huurne, Fleur M.; Boareto, Marcelo; Sahlgren, Cecilia M.

    2018-01-01

    Hemodynamic forces and Notch signaling are both known as key regulators of arterial remodeling and homeostasis. However, how these two factors integrate in vascular morphogenesis and homeostasis is unclear. Here, we combined experiments and modeling to evaluate the impact of the integration of mechanics and Notch signaling on vascular homeostasis. Vascular smooth muscle cells (VSMCs) were cyclically stretched on flexible membranes, as quantified via video tracking, demonstrating that the expression of Jagged1, Notch3, and target genes was down-regulated with strain. The data were incorporated in a computational framework of Notch signaling in the vascular wall, where the mechanical load was defined by the vascular geometry and blood pressure. Upon increasing wall thickness, the model predicted a switch-type behavior of the Notch signaling state with a steep transition of synthetic toward contractile VSMCs at a certain transition thickness. These thicknesses varied per investigated arterial location and were in good agreement with human anatomical data, thereby suggesting that the Notch response to hemodynamics plays an important role in the establishment of vascular homeostasis. PMID:29610298

  6. Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis.

    PubMed

    Chen, Xiyue; Eslamfam, Shabnam; Fang, Luoyun; Qiao, Shiyan; Ma, Xi

    2017-01-01

    Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Proposed mechanisms of the effects of proanthocyanidins on glucose homeostasis.

    PubMed

    Yang, Kaiyuan; Chan, Catherine B

    2017-08-01

    Proanthocyanidins are a major group of flavonoids in the human diet, known for their strong antioxidant properties. Emerging evidence from clinical studies indicates a role of proanthocyanidins in modulating glucose homeostasis, and higher proanthocyanidin intake has been associated with reduced risk of diabetes. On the other hand, recent studies report limited bioavailability of proanthocyanidins. At relatively low concentrations in the systemic circulation, proanthocyanidins may act as cell-signaling molecules to modulate glucose homeostasis. For example, they affect hepatic glucose production via adenosine monophosphate-activated protein kinase and/or insulin-signaling pathways. There is also evidence for a direct role of proanthocyanidins in modulating several pancreatic β-cell functions: prevention of oxidative stress, enhancement of insulin secretion, and promotion of β-cell survival. Therefore, greater understanding of the potentially beneficial effects of proanthocyanidins on cell-signaling pathways implicated in glucose homeostasis is needed. In addition, further investigation to address the in vivo metabolism of proanthocyanidins and the comparative effectiveness of proanthocyanidin-derived metabolites is warranted. The dosage and the experimental model should be given special attention when results from mechanistic studies using proanthocyanidins are interpreted. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis.

    PubMed

    Kocalis, Heidi E; Hagan, Scott L; George, Leena; Turney, Maxine K; Siuta, Michael A; Laryea, Gloria N; Morris, Lindsey C; Muglia, Louis J; Printz, Richard L; Stanwood, Gregg D; Niswender, Kevin D

    2014-07-01

    Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat mass and adiposity, glucose intolerance and behavioral leptin resistance. Disrupting Rictor in POMC neurons also caused obesity and hyperphagia, fasting hyperglycemia and pronounced glucose intolerance. AgRP neuron specific deletion did not impact energy balance but led to mild glucose intolerance. Collectively, we show that Rictor/mTORC2 signaling, especially in POMC-expressing neurons, is important for central regulation of energy and glucose homeostasis.

  9. Consciousness, endogenous generation of goals and homeostasis

    NASA Astrophysics Data System (ADS)

    Tsitolovsky, Lev E.

    2015-08-01

    Behaviour can be both unpredictable and goal directed, as animals act in correspondence with their motivation. Motivation arises when neurons in specific brain areas leave the state of homeostatic equilibrium and are injured. The basic goal of organisms and living cells is to maintain their life and their functional state is optimal if it does not lead to physiological damage. This can somehow be sensed by neurons and the occurrence of damage elicits homeostatic protection to recover excitability and the ability to produces spikes. It can be argued that the neuron's activity is guided on the scale of "damage-protection" and it behaves as an object possessing minimum awareness. The approach of death increases cellular efforts to operate. Thus, homeostasis may evidently produce both maintenance of life and will. The question is - how does homeostasis reach the optimum? We have no possibility of determining how the cell evaluates its own states, e.g. as "too little free energy" or in terms of "threat" to life. In any case, the approach of death increases cellular efforts to operate. For the outside observer, this is reminiscent of intentional action and a manifestation of will.

  10. Measurement of ROS homeostasis in isolated mitochondria.

    PubMed

    Tretter, L; Ambrus, A

    2014-01-01

    In this chapter, we describe the currently most advanced methods applied for the quantitative assessment of ROS homeostasis inside the mitochondrion. These techniques are of particular interest in the field of oxidative stress. After discussing the importance of quantifying mitochondrial ROS homeostasis, three major aspects of this phenomenon and the pertinent methodologies for detection are delineated in detail. First the most important methods, based on fluorimetric or spectrophotometric approaches, for the detection of mitochondrial ROS are described. Elimination of ROS generated inside the mitochondrion is another crucial mechanism that also needs to be quantified accurately to estimate the antioxidant capacity of mitochondria under specific conditions. Since ROS generation and elimination manifest in concert, there needs to exist independent methods for the estimation of the net effect. Such a sensitive biochemical marker in the mitochondrion is aconitase, a citric acid cycle enzyme which is greatly sensitive to ROS. We describe two procedures for the precise determination of aconitase activity. A few auxiliary techniques and good practices having relevance in the successful accomplishment of the more delicate approaches are also mentioned. All other relevant technical considerations including advantages/disadvantages of the various methods and the most common artifacts are also discussed.

  11. Motor Force Homeostasis in Skeletal Muscle Contraction

    PubMed Central

    Chen, Bin; Gao, Huajian

    2011-01-01

    In active biological contractile processes such as skeletal muscle contraction, cellular mitosis, and neuronal growth, an interesting common observation is that multiple motors can perform coordinated and synchronous actions, whereas individual myosin motors appear to randomly attach to and detach from actin filaments. Recent experiment has demonstrated that, during skeletal muscle shortening at a wide range of velocities, individual myosin motors maintain a force of ∼6 pN during a working stroke. To understand how such force-homeostasis can be so precisely regulated in an apparently chaotic system, here we develop a molecular model within a coupled stochastic-elastic theoretical framework. The model reveals that the unique force-stretch relation of myosin motor and the stochastic behavior of actin-myosin binding cause the average number of working motors to increase in linear proportion to the filament load, so that the force on each working motor is regulated at ∼6 pN, in excellent agreement with experiment. This study suggests that it might be a general principle to use catch bonds together with a force-stretch relation similar to that of myosin motors to regulate force homeostasis in many biological processes. PMID:21767492

  12. The effects of abnormalities of glucose homeostasis on the expression and binding of muscarinic receptors in cerebral cortex of rats.

    PubMed

    Sherin, Antony; Peeyush, Kumar T; Naijil, George; Nandhu, Mohan Sobhana; Jayanarayanan, Sadanandan; Jes, Paul; Paulose, Cheramadathikudiyil Skaria

    2011-01-25

    Glucose homeostasis in humans is an important factor for the functioning of nervous system. Both hypo and hyperglycemia contributes to neuronal functional deficit. In the present study, effect of insulin induced hypoglycemia and streptozotocin induced diabetes on muscarinic receptor binding, cholinergic enzymes; AChE, ChAT expression and GLUT3 in the cerebral cortex of experimental rats were analysed. Total muscarinic, muscarinic M(1) receptor showed a significant decrease and muscarinic M(3) receptor subtype showed a significant increased binding in the cerebral cortex of hypoglycemic rats compared to diabetic and control. Real-Time PCR analysis of muscarinic M(1), M(3) receptor subtypes confirmed the receptor binding studies. Immunohistochemistry of muscarinic M(1), M(3) receptors using specific antibodies were also carried out. AChE and GLUT3 expression up regulated and ChAT expression down regulated in hypoglycemic rats compared to diabetic and control rats. Our results showed that hypo/hyperglycemia caused impaired glucose transport in neuronal cells as shown by altered expression of GLUT3. Increased AChE and decreased ChAT expression is suggested to alter cortical acetylcholine metabolism in experimental rats along with altered muscarinic receptor binding in hypo/hyperglycemic rats, impair cholinergic transmission, which subsequently lead to cholinergic dysfunction thereby causing learning and memory deficits. We observed a prominent cholinergic functional disturbance in hypoglycemic condition than in hyperglycemia. Hypoglycemia exacerbated the neurochemical changes in cerebral cortex induced by hyperglycemia. These findings have implications for both therapy and identification of causes contributing to neuronal dysfunction in diabetes. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Thiol/disulphide homeostasis in celiac disease

    PubMed Central

    Kaplan, Mustafa; Ates, Ihsan; Yuksel, Mahmut; Ozderin Ozin, Yasemin; Alisik, Murat; Erel, Ozcan; Kayacetin, Ertugrul

    2017-01-01

    AIM To determine dynamic thiol/disulphide homeostasis in celiac disease and to examine the associate with celiac autoantibodies and gluten-free diet. METHODS Seventy three patients with celiac disease and 73 healthy volunteers were enrolled in the study. In both groups, thiol/disulphide homeostasis was examined with a new colorimetric method recently developed by Erel and Neselioglu. RESULTS In patients with celiac disease, native thiol (P = 0.027) and total thiol (P = 0.031) levels were lower, while disulphide (P < 0.001) level, disulphide/native thiol (P < 0.001) and disulphide/total thiol (P < 0.001) ratios were higher compared to the control group. In patients who do not comply with a gluten-free diet, disulphide/native thiol ratio was found higher compared to the patients who comply with the diet (P < 0.001). In patients with any autoantibody-positive, disulphide/native thiol ratio was observed higher compared to the patients with autoantibody-negative (P < 0.05). It is found that there is a negative correlation between celiac autoantibodies, and native thiol, total thiol levels and native thiol/total thiol ratio, while a positive correlation is observed between disulphide, disulphide/native thiol and disulphide/total thiol levels. CONCLUSION This study is first in the literature which found that the patients with celiac disease the dynamic thiol/disulphide balance shifts through disulphide form compared to the control group. PMID:28533921

  14. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis.

    PubMed

    Bevins, Charles L; Salzman, Nita H

    2011-05-01

    Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host-microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.

  15. Modulation of intestinal sulfur assimilation metabolism regulates iron homeostasis

    PubMed Central

    Hudson, Benjamin H.; Hale, Andrew T.; Irving, Ryan P.; Li, Shenglan; York, John D.

    2018-01-01

    Sulfur assimilation is an evolutionarily conserved pathway that plays an essential role in cellular and metabolic processes, including sulfation, amino acid biosynthesis, and organismal development. We report that loss of a key enzymatic component of the pathway, bisphosphate 3′-nucleotidase (Bpnt1), in mice, both whole animal and intestine-specific, leads to iron-deficiency anemia. Analysis of mutant enterocytes demonstrates that modulation of their substrate 3′-phosphoadenosine 5′-phosphate (PAP) influences levels of key iron homeostasis factors involved in dietary iron reduction, import and transport, that in part mimic those reported for the loss of hypoxic-induced transcription factor, HIF-2α. Our studies define a genetic basis for iron-deficiency anemia, a molecular approach for rescuing loss of nucleotidase function, and an unanticipated link between nucleotide hydrolysis in the sulfur assimilation pathway and iron homeostasis. PMID:29507250

  16. Seed development, seed germination and seedling growth in the R50 (sym16) pea mutant are not directly linked to altered cytokinin homeostasis.

    PubMed

    Long, Chengli; Held, Mark; Hayward, Allison; Nisler, Jaroslav; Spíchal, Lukas; Neil Emery, R J; Moffatt, Barbara A; Guinel, Frédérique C

    2012-06-01

    R50 (sym16) is a pea nodulation mutant that accumulates cytokinin (CK) in its vegetative organs. Total CK content increases as the plant ages because of the low activity of the enzyme cytokinin oxidase/dehydrogenase (CKX) responsible for CK degradation. R50 exhibits a large seed with high relative water content, and its seedling establishes itself slowly. Whether these two traits are linked to abnormal CK levels was considered here. R50 was found to have a similar germination rate but a much slower epicotyl emergence than Sparkle, its wild-type (WT). At the onset of emergence, the starch grains in R50 cotyledons were larger than those of WT; furthermore, they did not degrade as fast as in WT because of low amylase activity. No differences between the pea lines were observed in the CK forms identified during seed embryogenesis. However, while CK content compared to that of WT was reduced early in R50 embryogenesis, it was elevated later on in its dry seeds where CKX activity was low, although CKX transcript abundance remained high. Transcripts of the two known PsCKX isoforms exhibited tissue- and development-specific profiles with no detectable PsCKX2 expression in cotyledons. There were more of both transcripts in R50 roots than in WT roots, but less of PsCKX2 than PsCKX1 in R50 shoots compared to WT shoots. Thus, although there is a definite CKX post-transcriptional defect in R50 dry seeds, an abnormal CK homeostasis is not the basis of the delay in R50 seedling establishment, which we linked to abnormal amylase activity early in development. Copyright © Physiologia Plantarum 2012.

  17. Ergothioneine maintains redox and bioenergetic homeostasis essential for drug susceptibility and virulence of Mycobacterium tuberculosis

    PubMed Central

    Saini, Vikram; Cumming, Bridgette M.; Guidry, Loni; Lamprecht, Dirk; Adamson, John H.; Reddy, Vineel P.; Chinta, Krishna C.; Mazorodzo, James; Glasgow, Joel N.; Richard-Greenblatt, Melissa; Gomez-Velasco, Anaximandro; Bach, Horacio; Av-Gay, Yossef; Eoh, Hyungjin; Rhee, Kyu; Steyn, Adrie J.C.

    2016-01-01

    SUMMARY The mechanisms by which Mycobacterium tuberculosis (Mtb) maintains metabolic equilibrium to survive during infection and upon exposure to antimycobacterial drugs are poorly characterized. Ergothioneine (EGT) and mycothiol (MSH) are the major redox buffers present in Mtb, but the contribution of EGT to Mtb redox homeostasis and virulence remains unknown. We report that Mtb WhiB3, a 4Fe-4S redox sensor protein, regulates EGT production and maintains bioenergetic homeostasis. We show that central carbon metabolism and lipid precursors regulate EGT production and that EGT modulates drug sensitivity. Notably, EGT and MSH are both essential for redox and bioenergetic homeostasis. Transcriptomic analyses of EGT and MSH mutants indicate overlapping, but distinct functions of EGT and MSH. Lastly, we show that EGT is critical for Mtb survival in both macrophages and mice. This study has uncovered a dynamic balance between Mtb redox and bioenergetic homeostasis, which critically influences Mtb drug susceptibility and pathogenicity. PMID:26774486

  18. Cortical delta-opioid receptors potentiate K+ homeostasis during anoxia and oxygen-glucose deprivation.

    PubMed

    Chao, Dongman; Donnelly, David F; Feng, Yin; Bazzy-Asaad, Alia; Xia, Ying

    2007-02-01

    Central neurons are extremely vulnerable to hypoxic/ischemic insult, which is a major cause of neurologic morbidity and mortality as a consequence of neuronal dysfunction and death. Our recent work has shown that delta-opioid receptor (DOR) is neuroprotective against hypoxic and excitotoxic stress, although the underlying mechanisms remain unclear. Because hypoxia/ischemia disrupts ionic homeostasis with an increase in extracellular K(+), which plays a role in neuronal death, we asked whether DOR activation preserves K(+) homeostasis during hypoxic/ischemic stress. To test this hypothesis, extracellular recordings with K(+)-sensitive microelectrodes were performed in mouse cortical slices under anoxia or oxygen-glucose deprivation (OGD). The main findings in this study are that (1) DOR activation with [D-Ala(2), D-Leu(5)]-enkephalinamide attenuated the anoxia- and OGD-induced increase in extracellular K(+) and decrease in DC potential in cortical slices; (2) DOR inhibition with naltrindole, a DOR antagonist, completely abolished the DOR-mediated prevention of increase in extracellular K(+) and decrease in DC potential; (3) inhibition of protein kinase A (PKA) with N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide dihydrochloride had no effect on the DOR protection; and (4) inhibition of protein kinase C (PKC) with chelerythrine chloride reduced the DOR protection, whereas the PKC activator (phorbol 12-myristate 13-acetate) mimicked the effect of DOR activation on K(+) homeostasis. These data suggest that activation of DOR protects the cortex against anoxia- or ODG-induced derangement of potassium homeostasis, and this protection occurs via a PKC-dependent and PKA-independent pathway. We conclude that an important aspect of DOR-mediated neuroprotection is its early action against derangement of K(+) homeostasis during anoxia or ischemia.

  19. Neuron-Glia Interactions and Nervous System Homeostasis

    DTIC Science & Technology

    1988-06-01

    active neuron states, the mechanisms which glial cells and neurons use to modulate each others metabolic state and the chemical, electrical and... mechanisms by which axons/neurons and their glial cell investments communicate to actively regulate the ionic microenvironment of the nervous system and...of the glial cell in maintenance of the ionic homeostasis of the perineural environment during resting and active neuron states, the mechanisms which

  20. Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis.

    PubMed

    Berglund, Eric D; Liu, Chen; Sohn, Jong-Woo; Liu, Tiemin; Kim, Mi Hwa; Lee, Charlotte E; Vianna, Claudia R; Williams, Kevin W; Xu, Yong; Elmquist, Joel K

    2013-12-01

    Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor agonists on energy and glucose homeostasis are unknown. Here, we show that mice lacking serotonin 2C receptors (Htr2c) specifically in pro-opiomelanocortin (POMC) neurons had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, and insulin resistance. Moreover, these mice did not show anorectic responses to serotonergic agents that suppress appetite and developed hyperphagia and obesity when they were fed a high-fat/high-sugar diet. A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and glucose homeostasis was further demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoxifen-inducible POMC-cre system. These data demonstrate that serotonin 2C receptor-expressing POMC neurons are required to control energy and glucose homeostasis and implicate POMC neurons as the target for the effect of serotonin 2C receptor agonists on weight-loss induction and improved glycemic control.

  1. Electrolyte abnormalities in cystic fibrosis: systematic review of the literature.

    PubMed

    Scurati-Manzoni, Elisabetta; Fossali, Emilio F; Agostoni, Carlo; Riva, Enrica; Simonetti, Giacomo D; Zanolari-Calderari, Maura; Bianchetti, Mario G; Lava, Sebastiano A G

    2014-06-01

    Cystic fibrosis per se can sometimes lead to hyponatremia, hypokalemia, hypochloremia or hyperbicarbonatemia. This tendency was first documented 60 years ago and has subsequently been confirmed in single case reports or small case series, most of which were retrospective. However, this issue has not been addressed analytically. We have therefore systematically reviewed and analyzed the available literature on this subject. This was a systematic review of the literature. The reports included in this review cover 172 subacute and 90 chronic cases of electrolyte imbalances in patients with cystic fibrosis. The male:female ratio was 1.57. Electrolyte abnormalities were mostly associated with clinically inapparent fluid volume depletion, mainly affected patients aged ≤2.5 years, frequently tended to recur and often were found before the diagnosis of cystic fibrosis was established. Subacute presentation often included an history of heat exposure, vomiting, excessive sweating and pulmonary infection. History of chronic presentation, in contrast, was often inconspicuous. The tendency to hypochloremia, hypokalemia and metabolic alkalosis was similar between subacute and chronic patients, with hyponatremia being more pronounced (P < 0.02) in subacute compared to chronic presentations. Subacute cases were treated parenterally; chronic ones were usually managed with oral salt supplementation. Retention of urea and creatinine was documented in 38 % of subacute cases. The findings of our review suggest that physicians should be aware that electrolyte abnormalities can occur both as a presenting and a recurring feature of cystic fibrosis.

  2. Redox and Activation of Protein Kinase A Dysregulates Calcium Homeostasis in Pulmonary Vein Cardiomyocytes of Chronic Kidney Disease.

    PubMed

    Huang, Shih-Yu; Chen, Yao-Chang; Kao, Yu-Hsun; Hsieh, Ming-Hsiung; Lin, Yung-Kuo; Chen, Shih-Ann; Chen, Yi-Jen

    2017-07-12

    Chronic kidney disease (CKD) increases the occurrence of atrial fibrillation and pulmonary vein (PV) arrhythmogenesis. Calcium dysregulation and reactive oxygen species (ROS) enhance PV arrhythmogenic activity. The purposes of this study were to investigate whether CKD modulates PV electrical activity through dysregulation of calcium homeostasis and ROS. Biochemical and electrocardiographic studies were conducted in rabbits with and without CKD (induced by 150 mg/kg per day neomycin sulfate and 500 mg/kg per day cefazolin). Confocal microscopy with fluorescence and a whole-cell patch clamp were applied to study calcium homeostasis and electrical activities in control and CKD isolated single PV cardiomyocytes with or without treatment with H89 (1 μmol/L, a protein kinase A inhibitor) and MPG (N-[2-mercaptopropionyl]glycine; 100 μmol/L, a ROS scavenger). The ROS in mitochondria and cytosol were evaluated via intracellular dye fluorescence and lipid peroxidation. CKD rabbits had excessive atrial premature captures over those of control rabbits. Compared with the control, CKD PV cardiomyocytes had a faster beating rate and larger calcium transient amplitudes, sarcoplasmic reticulum calcium contents, sodium/calcium exchanger currents, and late sodium currents but smaller L-type calcium current densities. CKD PV cardiomyocytes had a higher frequency and longer duration of calcium sparks and more ROS in the mitochondria and cytosol than did controls. Moreover, H89 suppressed all calcium sparks in CKD PV cardiomyocytes, and H89- and MPG-treated CKD PV cardiomyocytes had similar calcium transients compared with control PV cardiomyocytes. CKD increases PV arrhythmogenesis with enhanced calcium-handling abnormalities through activation of protein kinase A and ROS. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  3. Toxicological disruption of signaling homeostasis: Tyrosine phosphatses as targets

    EPA Science Inventory

    The protein tyrosine phosphatases (PTP) comprised a diverse group of enzymes whose activity opposes that of the tyrosine kinases. As such, the PTP have critical roles in maintaining signaling quiescence in resting cells and in restoring homeostasis by effecting signal termination...

  4. Behavioural abnormalities of the hyposulphataemic Nas1 knock-out mouse.

    PubMed

    Dawson, Paul Anthony; Steane, Sarah Elizabeth; Markovich, Daniel

    2004-10-05

    We recently generated a sodium sulphate cotransporter knock-out mouse (Nas1-/-) which has increased urinary sulphate excretion and hyposulphataemia. To examine the consequences of disturbed sulphate homeostasis in the modulation of mouse behavioural characteristics, Nas1-/- mice were compared with Nas1+/- and Nas1+/+ littermates in a series of behavioural tests. The Nas1-/- mice displayed significantly (P < 0.001) decreased marble burying behaviour (4.33 +/- 0.82 buried) when compared to Nas1+/+ (7.86 +/- 0.44) and Nas1+/- (8.40 +/- 0.37) animals, suggesting that Nas1-/- mice may have decreased object-induced anxiety. The Nas1-/- mice also displayed decreased locomotor activity by moving less distance (1.53 +/- 0.27 m, P < 0.05) in an open-field test when compared to Nas1+/+ (2.31 +/- 0.24 m) and Nas1+/- (2.15 +/- 0.19 m) mice. The three genotypes displayed similar spatiotemporal and ethological behaviours in the elevated-plus maze and open-field test, with the exception of a decreased defecation frequency by the Nas1-/- mice (40% reduction, P < 0.01). There were no significant differences between Nas1-/- and Nas1+/+ mice in a rotarod performance test of motor coordination and in the forced swim test assessing (anti-)depressant-like behaviours. This is the first study to demonstrate behavioural abnormalities in the hyposulphataemic Nas1-/- mice.

  5. Setting sail for glucose homeostasis with the AKAP150-PP2B-anchor.

    PubMed

    Teo, Adrian Kee Keong; Kulkarni, Rohit N

    2012-10-17

    Glucose-stimulated insulin secretion, controlled by multiple protein phosphorylation events, is critical for the regulation of glucose homeostasis. Protein kinase A (PKA) is known to play a role in β cell physiology, but the role of its anchoring protein is not fully understood. Hinke et al (2012) illustrate the significance of A-kinase anchoring protein 150 in tethering protein phosphatase 2B to mediate nutrient-stimulated insulin secretion and thus modulate glucose homeostasis.

  6. Pinna abnormalities and low-set ears

    MedlinePlus

    ... Pinna abnormalities; Genetic defect - pinna; Congenital defect - pinna Images Ear abnormalities Pinna of the newborn ear References Haddad J, Keesecker S. Congenital malformations. In: Kliegman RM, Stanton BF, ...

  7. Central insulin and leptin-mediated autonomic control of glucose homeostasis.

    PubMed

    Marino, Joseph S; Xu, Yong; Hill, Jennifer W

    2011-07-01

    Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucose and insulin responsiveness. The preponderance of evidence indicates that the brain is the master regulator of glucose homeostasis, and that hypothalamic insulin and leptin signaling in particular play a crucial role in the development of insulin resistance. This review discusses the neuronal crosstalk between the hypothalamus, autonomic nervous system, and tissues associated with the pathogenesis of type 2 diabetes, and how hypothalamic insulin and leptin signaling are integral to maintaining normal glucose homeostasis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Behavioral sleep-wake homeostasis and EEG delta power are decoupled by chronic sleep restriction in the rat.

    PubMed

    Stephenson, Richard; Caron, Aimee M; Famina, Svetlana

    2015-05-01

    Chronic sleep restriction (CSR) is prevalent in society and is linked to adverse consequences that might be ameliorated by acclimation of homeostatic drive. This study was designed to test the hypothesis that the sleep-wake homeostat will acclimatize to CSR. A four-parameter model of proportional control was used to quantify sleep homeostasis with and without recourse to a sleep intensity function. Animal laboratory, rodent walking-wheel apparatus. Male Sprague-Dawley rats. Acute total sleep deprivation (TSD, 1 day × 18 or 24 h, N = 12), CSR (10 days × 18 h TSD, N = 5, or 5 days × 20 h TSD, N = 6). Behavioral rebounds were consistent with model predictions for proportional control of cumulative times in wake, nonrapid eye movement (NREM) and rapid eye movement (REM). Delta (D) energy homeostasis was secondary to behavioral homeostasis; a biphasic NREM D power rebound contributed to the dynamics (rapid response) but not to the magnitude of the rebound in D energy. REM behavioral homeostasis was little affected by CSR. NREM behavioral homeostasis was attenuated in proportion to cumulative NREM deficit, whereas the biphasic NREM D power rebound was only slightly suppressed, indicating decoupled regulatory mechanisms following CSR. We conclude that sleep homeostasis is achieved through behavioral regulation, that the NREM behavioral homeostat is susceptible to attenuation during CSR and that the concept of sleep intensity is not essential in a model of sleep-wake regulation. Chronic sleep restriction (CSR) is prevalent in society and is linked to adverse consequences that might be ameliorated by acclimation of homeostatic drive. This study was designed to test the hypothesis that the sleep-wake homeostat will acclimatize to CSR. A four-parameter model of proportional control was used to quantify sleep homeostasis with and without recourse to a sleep intensity function. Animal laboratory, rodent walking-wheel apparatus. Male Sprague-Dawley rats. Acute total sleep

  9. Fluids in crustal deformation: Fluid flow, fluid-rock interactions, rheology, melting and resources

    NASA Astrophysics Data System (ADS)

    Lacombe, Olivier; Rolland, Yann

    2016-11-01

    Fluids exert a first-order control on the structural, petrological and rheological evolution of the continental crust. Fluids interact with rocks from the earliest stages of sedimentation and diagenesis in basins until these rocks are deformed and/or buried and metamorphosed in orogens, then possibly exhumed. Fluid-rock interactions lead to the evolution of rock physical properties and rock strength. Fractures and faults are preferred pathways for fluids, and in turn physical and chemical interactions between fluid flow and tectonic structures, such as fault zones, strongly influence the mechanical behaviour of the crust at different space and time scales. Fluid (over)pressure is associated with a variety of geological phenomena, such as seismic cycle in various P-T conditions, hydrofracturing (including formation of sub-horizontal, bedding-parallel veins), fault (re)activation or gravitational sliding of rocks, among others. Fluid (over)pressure is a governing factor for the evolution of permeability and porosity of rocks and controls the generation, maturation and migration of economic fluids like hydrocarbons or ore forming hydrothermal fluids, and is therefore a key parameter in reservoir studies and basin modeling. Fluids may also help the crust partially melt, and in turn the resulting melt may dramatically change the rheology of the crust.

  10. Copper and Iron Homeostasis in Plants: The Challenges of Oxidative Stress

    PubMed Central

    Pilon, Marinus

    2013-01-01

    Abstract Significance: Photosynthesis, the process that drives life on earth, relies on transition metal (e.g., Fe and Cu) containing proteins that participate in electron transfer in the chloroplast. However, the light reactions also generate high levels of reactive oxygen species (ROS), which makes metal use in plants a challenge. Recent Advances: Sophisticated regulatory networks govern Fe and Cu homeostasis in response to metal ion availability according to cellular needs and priorities. Molecular remodeling in response to Fe or Cu limitation leads to its economy to benefit photosynthesis. Fe toxicity is prevented by ferritin, a chloroplastic Fe-storage protein in plants. Recent studies on ferritin function and regulation revealed the interplay between iron homeostasis and the redox balance in the chloroplast. Critical Issues: Although the connections between metal excess and ROS in the chloroplast are established at the molecular level, the mechanistic details and physiological significance remain to be defined. The causality/effect relationship between transition metals, redox signals, and responses is difficult to establish. Future Directions: Integrated approaches have led to a comprehensive understanding of Cu homeostasis in plants. However, the biological functions of several major families of Cu proteins remain unclear. The cellular priorities for Fe use under deficiency remain largely to be determined. A number of transcription factors that function to regulate Cu and Fe homeostasis under deficiency have been characterized, but we have not identified regulators that mediate responses to excess. Importantly, details of metal sensing mechanisms and cross talk to ROS-sensing mechanisms are so far poorly documented in plants. Antioxid. Redox Signal. 19, 919–932. PMID:23199018

  11. Oxygen-sensing PHDs regulate bone homeostasis through the modulation of osteoprotegerin

    PubMed Central

    Wu, Colleen; Rankin, Erinn B.; Castellini, Laura; Fernandez-Alcudia, Javier; LaGory, Edward L.; Andersen, Rebecca; Rhodes, Steven D.; Wilson, Tremika L.S.; Mohammad, Khalid S.; Castillo, Alesha B.; Guise, Theresa A.; Schipani, Ernestina

    2015-01-01

    The bone microenvironment is composed of niches that house cells across variable oxygen tensions. However, the contribution of oxygen gradients in regulating bone and blood homeostasis remains unknown. Here, we generated mice with either single or combined genetic inactivation of the critical oxygen-sensing prolyl hydroxylase (PHD) enzymes (PHD1–3) in osteoprogenitors. Hypoxia-inducible factor (HIF) activation associated with Phd2 and Phd3 inactivation drove bone accumulation by modulating osteoblastic/osteoclastic cross-talk through the direct regulation of osteoprotegerin (OPG). In contrast, combined inactivation of Phd1, Phd2, and Phd3 resulted in extreme HIF signaling, leading to polycythemia and excessive bone accumulation by overstimulating angiogenic–osteogenic coupling. We also demonstrate that genetic ablation of Phd2 and Phd3 was sufficient to protect ovariectomized mice against bone loss without disrupting hematopoietic homeostasis. Importantly, we identify OPG as a HIF target gene capable of directing osteoblast-mediated osteoclastogenesis to regulate bone homeostasis. Here, we show that coordinated activation of specific PHD isoforms fine-tunes the osteoblastic response to hypoxia, thereby directing two important aspects of bone physiology: cross-talk between osteoblasts and osteoclasts and angiogenic–osteogenic coupling. PMID:25846796

  12. Cellular homeostasis in fungi: impact on the aging process.

    PubMed

    Scheckhuber, Christian Q; Hamann, Andrea; Brust, Diana; Osiewacz, Heinz D

    2012-01-01

    Cellular quality control pathways are needed for maintaining the biological function of organisms. If these pathways become compromised, the results are usually highly detrimental. Functional impairments of cell components can lead to diseases and in extreme cases to organismal death. Dysfunction of cells can be induced by a number of toxic by-products that are formed during metabolic activity, like reactive oxygen and nitrogen species, for example. A key source of reactive oxygen species (ROS) are the organelles of oxidative phosphorylation, mitochondria. Therefore mitochondrial function is also directly affected by ROS, especially if there is a compromised ROS-scavenging capacity. Biological systems therefore depend on several lines of defence to counteract the toxic effects of ROS and other damaging agents. The first level is active at the molecular level and consists of various proteases that bind and degrade abnormally modified and / or aggregated mitochondrial proteins. The second level is concerned with maintaining the quality of whole mitochondria. Among the pathways of this level are mitochondrial dynamics and autophagy (mitophagy). Mitochondrial dynamics describes the time-dependent fusion and fission of mitochondria. It is argued that this kind of organellar dynamics has the power to restore the function of impaired organelles by content mixing with intact organelles. If the first and second lines of defence against damage fail and mitochondria become damaged too severely, there is the option to remove affected cells before they can elicit more damage to their surrounding environment by apoptosis. This form of programmed cell death is strictly regulated by a complex network of interacting components and can be divided into mitochondria-dependent and mitochondria-independent modes of action. In this review we give an overview on various biological quality control systems in fungi (yeasts and filamentous fungi) with an emphasis on autophagy (mitophagy) and

  13. The Dehydratase ADT3 Affects ROS Homeostasis and Cotyledon Development1[OPEN

    PubMed Central

    Para, Alessia; Muhammad, DurreShahwar; Naldrett, Michael J.; Warpeha, Katherine M.

    2016-01-01

    During the transition from seed to seedling, emerging embryos strategically balance available resources between building up defenses against environmental threats and initiating the developmental program that promotes the switch to autotrophy. We present evidence of a critical role for the phenylalanine (Phe) biosynthetic activity of AROGENATE DEHYDRATASE3 (ADT3) in coordinating reactive oxygen species (ROS) homeostasis and cotyledon development in etiolated Arabidopsis (Arabidopsis thaliana) seedlings. We show that ADT3 is expressed in the cotyledon and shoot apical meristem, mainly in the cytosol, and that the epidermis of adt3 cotyledons contains higher levels of ROS. Genome-wide proteomics of the adt3 mutant revealed a general down-regulation of plastidic proteins and ROS-scavenging enzymes, corroborating the hypothesis that the ADT3 supply of Phe is required to control ROS concentration and distribution to protect cellular components. In addition, loss of ADT3 disrupts cotyledon epidermal patterning by affecting the number and expansion of pavement cells and stomata cell fate specification; we also observed severe alterations in mesophyll cells, which lack oil bodies and normal plastids. Interestingly, up-regulation of the pathway leading to cuticle production is accompanied by an abnormal cuticle structure and/or deposition in the adt3 mutant. Such impairment results in an increase in cell permeability and provides a link to understand the cell defects in the adt3 cotyledon epidermis. We suggest an additional role of Phe in supplying nutrients to the young seedling. PMID:27540109

  14. Geochemistry of tectonically expelled fluids from the northern Coast ranges, Rumsey Hills, California, USA

    USGS Publications Warehouse

    Davisson, M.L.; Presser, T.S.; Criss, R.E.

    1994-01-01

    Tectonic compression has created abnormally high pressure on deep basinal fluids causing their expulsion from areally exposed Upper Cretaceous rock along the eastern margin of the California Coast ranges. The fluids emerge as near-neutral, perennial sodium chloride springs at high elevations with flow rates as high as 10 L per min. Higher spring discharges are more common around the exposure of a west-vergent fault propagation fold axis. Spring waters range from ~1000 to 27,000 mg/L TDS. The least saline water (??18O = -7.5???) closely represents local meteoric water that mixes with saline fluid (??18O = +5.3???) and forms a slope of ~3.5 on a ??D vs. ??18O plot. A Na (125 to 8000 mg/L) vs. Cl (150 to 17,000 mg/L) plot shows a linear dilution trend that extends close to, but below, the values for modern seawater. Calcium (75-3000 mg/L) is considerably enriched relative to seawater and forms a nonlinear trend with chloride. In detail, the "Na deficit," defined by the difference between the measured Na content and the Na concentration on a hypothetical seawater dilution line, is approximately balanced by the Ca excess, similarly defined by the seawater dilution line. This relationship strongly suggests that the fluid is diluted seawater that is being modified by active albitization of plagioclase at different depths. Simultaneous B and 18O enrichment of the fluids, accompanied by deuterium depletion, further suggest that the seawater modification is influenced by clay diagenesis. Bicarbonate and SiO2 concentrations show an inverse correlation with Cl, with most waters being saturated or slightly oversaturated with calcite and quartz at the discharge temperatures. Some freshwater springs with near-meteoric stable isotope values may represent mixing of young groundwater from perched aquifers, but in many cases, the freshwater springs emerge along the same structures and have the same perennial nature as the saline fluids, and expulsion of an older fresh groundwater

  15. Signalling from the periphery to the brain that regulates energy homeostasis.

    PubMed

    Kim, Ki-Suk; Seeley, Randy J; Sandoval, Darleen A

    2018-04-01

    The CNS regulates body weight; however, we still lack a clear understanding of what drives decisions about when, how much and what to eat. A vast array of peripheral signals provides information to the CNS regarding fluctuations in energy status. The CNS then integrates this information to influence acute feeding behaviour and long-term energy homeostasis. Previous paradigms have delegated the control of long-term energy homeostasis to the hypothalamus and short-term changes in feeding behaviour to the hindbrain. However, recent studies have identified target hindbrain neurocircuitry that integrates the orchestration of individual bouts of ingestion with the long-term regulation of energy balance.

  16. A simulation for teaching the basic and clinical science of fluid therapy.

    PubMed

    Rawson, Richard E; Dispensa, Marilyn E; Goldstein, Richard E; Nicholson, Kimberley W; Vidal, Noni Korf

    2009-09-01

    The course "Management of Fluid and Electrolyte Disorders" is an applied physiology course taught using lectures and paper-based cases. The course approaches fluid therapy from both basic science and clinical perspectives. While paper cases provide a basis for application of basic science concepts, they lack key components of genuine clinical cases that, by nature, are diverse, change over time, and respond in unique ways to therapeutic interventions. We developed a dynamic model using STELLA software that simulates normal and abnormal fluid and electrolyte balance in the dog. Students interact, not with the underlying model, but with a user interface that provides sufficient data (skin turgor, chemistry panel, etc.) for the clinical assessment of patients and an opportunity for treatment. Students administer fluids and supplements, and the model responds in "real time," requiring regular reassessment and, potentially, adaptation of the treatment strategy. The level of success is determined by clinical outcome, including improvement, deterioration, or death. We expected that the simulated cases could be used to teach both the clinical and basic science of fluid therapy. The simulation provides exposure to a realistic clinical environment, and students tend to focus on this aspect of the simulation while, for the most part, ignoring an exploration of the underlying physiological basis for patient responses. We discuss how the instructor's expertise can provide sufficient support, feedback, and scaffolding so that students can extract maximum understanding of the basic science in the context of assessing and treating at the clinical level.

  17. Atmospheric Convective Organization: Self-Organized Criticality or Homeostasis?

    NASA Astrophysics Data System (ADS)

    Yano, Jun-Ichi

    2015-04-01

    Atmospheric convection has a tendency organized on a hierarchy of scales ranging from the mesoscale to the planetary scales, with the latter especially manifested by the Madden-Julian oscillation. The present talk examines two major possible mechanisms of self-organization identified in wider literature from a phenomenological thermodynamic point of view by analysing a planetary-scale cloud-resolving model simulation. The first mechanism is self-organized criticality. A saturation tendency of precipitation rate with the increasing column-integrated water, reminiscence of critical phenomena, indicates self-organized criticality. The second is a self-regulation mechanism that is known as homeostasis in biology. A thermodynamic argument suggests that such self-regulation maintains the column-integrated water below a threshold by increasing the precipitation rate. Previous analyses of both observational data as well as cloud-resolving model (CRM) experiments give mixed results. A satellite data analysis suggests self-organized criticality. Some observational data as well as CRM experiments support homeostasis. Other analyses point to a combination of these two interpretations. In this study, a CRM experiment over a planetary-scale domain with a constant sea-surface temperature is analyzed. This analysis shows that the relation between the column-integrated total water and precipitation suggests self-organized criticality, whereas the one between the column-integrated water vapor and precipitation suggests homeostasis. The concurrent presence of these two mechanisms are further elaborated by detailed statistical and budget analyses. These statistics are scale invariant, reflecting a spatial scaling of precipitation processes. These self-organization mechanisms are most likely be best theoretically understood by the energy cycle of the convective systems consisting of the kinetic energy and the cloud-work function. The author has already investigated the behavior of this

  18. Electromagnetic homeostasis and the role of low-amplitude electromagnetic fields on life organization.

    PubMed

    De Ninno, Antonella; Pregnolato, Massimo

    2017-01-01

    The appearance of endogenous electromagnetic fields in biological systems is a widely debated issue in modern science. The electrophysiological fields have very tiny intensities and it can be inferred that they are rapidly decreasing with the distance from the generating structure, vanishing at very short distances. This makes very hard their detection using standard experimental methods. However, the existence of fast-moving charged particles in the macromolecules inside both intracellular and extracellular fluids may envisage the generation of localized electric currents as well as the presence of closed loops, which implies the existence of magnetic fields. Moreover, the whole set of oscillatory frequencies of various substances, enzymes, cell membranes, nucleic acids, bioelectrical phenomena generated by the electrical rhythm of coherent groups of cells, cell-to-cell communication among population of host bacteria, forms the increasingly complex hierarchies of electromagnetic signals of different frequencies which cover the living being and represent a fundamental information network controlling the cell metabolism. From this approach emerges the concept of electromagnetic homeostasis: that is, the capability of the human body to maintain the balance of highly complex electromagnetic interactions within, in spite of the external electromagnetic noisy environment. This concept may have an important impact on the actual definitions of heal and disease.

  19. CNS-targets in control of energy and glucose homeostasis.

    PubMed

    Kleinridders, André; Könner, A Christine; Brüning, Jens C

    2009-12-01

    The exceeding efforts in understanding the signals initiated by nutrients and hormones in the central nervous system (CNS) to regulate glucose and energy homeostasis have largely revolutionized our understanding of the neurocircuitry in control of peripheral metabolism. The ability of neurons to sense nutrients and hormones and to adopt a coordinated response to these signals is of crucial importance in controlling food intake, energy expenditure, glucose and lipid metabolism. Anatomical lesion experiments, pharmacological inhibition of signaling pathways, and, more recently, the analysis of conditional mouse mutants with modifications of hormone and nutrient signaling in defined neuronal populations have broadened our understanding of these complex neurocircuits. This review summarizes recent findings regarding the role of the CNS in sensing and transmitting nutritional and hormonal signals to control energy and glucose homeostasis and aims to define them as potential novel drug targets for the treatment of obesity and type 2 diabetes mellitus.

  20. Energy homeostasis regulatory peptides in hibernating grizzly bears.

    PubMed

    Gardi, János; Nelson, O Lynne; Robbins, Charles T; Szentirmai, Eva; Kapás, Levente; Krueger, James M

    2011-05-15

    Grizzly bears (Ursus arctos horribilis) are inactive for up to 6 months during hibernation. They undergo profound seasonal changes in food intake, body mass, and energy expenditure. The circa-annual regulation of metabolism is poorly understood. In this study, we measured plasma ghrelin, leptin, obestatin, and neuropeptide-Y (NPY) levels, hormones known to be involved in the regulation of energy homeostasis, in ten grizzly bears. Blood samples were collected during the active summer period, early hibernation and late hibernation. Plasma levels of leptin, obestatin, and NPY did not change between the active and the hibernation periods. Plasma total ghrelin and desacyl-ghrelin concentrations significantly decreased during the inactive winter period compared to summer levels. The elevated ghrelin levels may help enhance body mass during pre-hibernation, while the low plasma ghrelin concentrations during hibernation season may contribute to the maintenance of hypophagia, low energy utilization and behavioral inactivity. Our results suggest that ghrelin plays a potential role in the regulation of metabolic changes and energy homeostasis during hibernation in grizzly bears. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Interleukin-33 in Tissue Homeostasis, Injury, and Inflammation.

    PubMed

    Molofsky, Ari B; Savage, Adam K; Locksley, Richard M

    2015-06-16

    Interleukin-33 (IL-33) is a nuclear-associated cytokine of the IL-1 family originally described as a potent inducer of allergic type 2 immunity. IL-33 signals via the receptor ST2, which is highly expressed on group 2 innate lymphoid cells (ILC2s) and T helper 2 (Th2) cells, thus underpinning its association with helminth infection and allergic pathology. Recent studies have revealed ST2 expression on subsets of regulatory T cells, and for a role for IL-33 in tissue homeostasis and repair that suggests previously unrecognized interactions within these cellular networks. IL-33 can participate in pathologic fibrotic reactions, or, in the setting of microbial invasion, can cooperate with inflammatory cytokines to promote responses by cytotoxic NK cells, Th1 cells, and CD8(+) T cells. Here, we highlight the regulation and function of IL-33 and ST2 and review their roles in homeostasis, damage, and inflammation, suggesting a conceptual framework for future studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Mitochondrial flashes regulate ATP homeostasis in the heart

    PubMed Central

    Wang, Xianhua; Zhang, Xing; Wu, Di; Huang, Zhanglong; Hou, Tingting; Jian, Chongshu; Yu, Peng; Lu, Fujian; Zhang, Rufeng; Sun, Tao; Li, Jinghang; Qi, Wenfeng; Wang, Yanru; Gao, Feng; Cheng, Heping

    2017-01-01

    The maintenance of a constant ATP level (‘set-point’) is a vital homeostatic function shared by eukaryotic cells. In particular, mammalian myocardium exquisitely safeguards its ATP set-point despite 10-fold fluctuations in cardiac workload. However, the exact mechanisms underlying this regulation of ATP homeostasis remain elusive. Here we show mitochondrial flashes (mitoflashes), recently discovered dynamic activity of mitochondria, play an essential role for the auto-regulation of ATP set-point in the heart. Specifically, mitoflashes negatively regulate ATP production in isolated respiring mitochondria and, their activity waxes and wanes to counteract the ATP supply-demand imbalance caused by superfluous substrate and altered workload in cardiomyocytes. Moreover, manipulating mitoflash activity is sufficient to inversely shift the otherwise stable ATP set-point. Mechanistically, the Bcl-xL-regulated proton leakage through F1Fo-ATP synthase appears to mediate the coupling between mitoflash production and ATP set-point regulation. These findings indicate mitoflashes appear to constitute a digital auto-regulator for ATP homeostasis in the heart. DOI: http://dx.doi.org/10.7554/eLife.23908.001 PMID:28692422

  3. Energy homeostasis regulatory peptides in hibernating grizzly bears

    PubMed Central

    Gardi, János; Nelson, O. Lynne; Robbins, Charles T.; Szentirmai, Éva; Kapás, Levente; Krueger, James M.

    2011-01-01

    Grizzly bears (Ursus arctos horribilis) are inactive for up to 6 months during hibernation. They undergo profound seasonal changes in food intake, body mass, and energy expenditure. The circa-annual regulation of metabolism is poorly understood. In the present study, we measured plasma ghrelin, leptin, obestatin, and neuropeptide-Y (NPY) levels, hormones known to be involved in the regulation of energy homeostasis, in ten grizzly bears. Blood samples were collected during the active summer period, early hibernation and late hibernation. Plasma levels of leptin, obestatin, and NPY did not change between the active and the hibernation periods. Plasma total ghrelin and desacyl-ghrelin concentrations significantly decreased during the inactive winter period compared to summer levels. The elevated ghrelin levels may help enhance body mass during pre-hibernation, while the low plasma ghrelin concentrations during hibernation season may contribute to the maintenance of hypophagia, low energy utilization and behavioral inactivity. Our results suggest that ghrelin plays a potential role in the regulation of metabolic changes and energy homeostasis during hibernation in grizzly bears. PMID:21187098

  4. Dysmorphometrics: the modelling of morphological abnormalities.

    PubMed

    Claes, Peter; Daniels, Katleen; Walters, Mark; Clement, John; Vandermeulen, Dirk; Suetens, Paul

    2012-02-06

    The study of typical morphological variations using quantitative, morphometric descriptors has always interested biologists in general. However, unusual examples of form, such as abnormalities are often encountered in biomedical sciences. Despite the long history of morphometrics, the means to identify and quantify such unusual form differences remains limited. A theoretical concept, called dysmorphometrics, is introduced augmenting current geometric morphometrics with a focus on identifying and modelling form abnormalities. Dysmorphometrics applies the paradigm of detecting form differences as outliers compared to an appropriate norm. To achieve this, the likelihood formulation of landmark superimpositions is extended with outlier processes explicitly introducing a latent variable coding for abnormalities. A tractable solution to this augmented superimposition problem is obtained using Expectation-Maximization. The topography of detected abnormalities is encoded in a dysmorphogram. We demonstrate the use of dysmorphometrics to measure abrupt changes in time, asymmetry and discordancy in a set of human faces presenting with facial abnormalities. The results clearly illustrate the unique power to reveal unusual form differences given only normative data with clear applications in both biomedical practice & research.

  5. Role of Galectin-3 in Obesity and Impaired Glucose Homeostasis

    PubMed Central

    Menini, Stefano; Iacobini, Carla; Blasetti Fantauzzi, Claudia; Pesce, Carlo M.; Pugliese, Giuseppe

    2016-01-01

    Galectin-3 is an important modulator of several biological functions. It has been implicated in numerous disease conditions, particularly in the long-term complications of diabetes because of its ability to bind the advanced glycation/lipoxidation end products that accumulate in target organs and exert their toxic effects by triggering proinflammatory and prooxidant pathways. Recent evidence suggests that galectin-3 may also participate in the development of obesity and type 2 diabetes. It has been shown that galectin-3 levels are higher in obese and diabetic individuals and parallel deterioration of glucose homeostasis. Two studies in galectin-3 knockout mice fed a high-fat diet (HFD) have shown increased adiposity and adipose tissue and systemic inflammation associated with altered glucose homeostasis, suggesting that galectin-3 negatively modulates the responsiveness of innate and adaptive immunity to overnutrition. However, these studies have also shown that impaired glucose homeostasis occurs in galectin-3 knockout animals independently of obesity. Moreover, another study reported decreased weight and fat mass in HFD-fed galectin-3 knockout mice. In vitro, galectin-3 was found to stimulate differentiation of preadipocytes into mature adipocytes. Altogether, these data indicate that galectin-3 deserves further attention in order to clarify its role as a potential player and therapeutic target in obesity and type 2 diabetes. PMID:26770660

  6. Hydrogen Sulfide Induced Disruption of Na+ Homeostasis in the Cortex

    PubMed Central

    Chao, Dongman; He, Xiaozhou; Yang, Yilin; Balboni, Gianfranco; Salvadori, Severo; Kim, Dong H.; Xia, Ying

    2012-01-01

    Maintenance of ionic balance is essential for neuronal functioning. Hydrogen sulfide (H2S), a known toxic environmental gaseous pollutant, has been recently recognized as a gasotransmitter involved in numerous biological processes and is believed to play an important role in the neural activities under both physiological and pathological conditions. However, it is unclear if it plays any role in maintenance of ionic homeostasis in the brain under physiological/pathophysiological conditions. Here, we report by directly measuring Na+ activity using Na+ selective electrodes in mouse cortical slices that H2S donor sodium hydrosulfide (NaHS) increased Na+ influx in a concentration-dependent manner. This effect could be partially blocked by either Na+ channel blocker or N-methyl-D-aspartate receptor (NMDAR) blocker alone or almost completely abolished by coapplication of both blockers but not by non-NMDAR blocker. These data suggest that increased H2S in pathophysiological conditions, e.g., hypoxia/ischemia, potentially causes a disruption of ionic homeostasis by massive Na+ influx through Na+ channels and NMDARs, thus injuring neural functions. Activation of delta-opioid receptors (DOR), which reduces Na+ currents/influx in normoxia, had no effect on H2S-induced Na+ influx, suggesting that H2S-induced disruption of Na+ homeostasis is resistant to DOR regulation and may play a major role in neuronal injury in pathophysiological conditions, e.g., hypoxia/ischemia. PMID:22474073

  7. Cooperation between brain and islet in glucose homeostasis and diabetes

    PubMed Central

    Schwartz, Michael W.; Seeley, Randy J.; Tschöp, Matthias H.; Woods, Stephen C.; Morton, Gregory J.; Myers, Martin G.; D'Alessio, David

    2014-01-01

    Although a prominent role for the brain in glucose homeostasis was proposed by scientists in the nineteenth century, research throughout most of the twentieth century focused on evidence that the function of pancreatic islets is both necessary and sufficient to explain glucose homeostasis, and that diabetes results from defects of insulin secretion, action or both. However, insulin-independent mechanisms, referred to as ‘glucose effectiveness’, account for roughly 50% of overall glucose disposal, and reduced glucose effectiveness also contributes importantly to diabetes pathogenesis. Although mechanisms underlying glucose effectiveness are poorly understood, growing evidence suggests that the brain can dynamically regulate this process in ways that improve or even normalize glycaemia in rodent models of diabetes. Here we present evidence of a brain-centred glucoregulatory system (BCGS) that can lower blood glucose levels via both insulin-dependent and -independent mechanisms, and propose a model in which complex and highly coordinated interactions between the BCGS and pancreatic islets promote normal glucose homeostasis. Because activation of either regulatory system can compensate for failure of the other, defects in both may be required for diabetes to develop. Consequently, therapies that target the BCGS in addition to conventional approaches based on enhancing insulin effects may have the potential to induce diabetes remission, whereas targeting just one typically does not. PMID:24201279

  8. Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota

    PubMed Central

    Peterson, C T; Sharma, V; Elmén, L; Peterson, S N

    2015-01-01

    The distal gut harbours ∼1013 bacteria, representing the most densely populated ecosystem known. The functional diversity expressed by these communities is enormous and relatively unexplored. The past decade of research has unveiled the profound influence that the resident microbial populations bestow to host immunity and metabolism. The evolution of these communities from birth generates a highly adapted and highly personalized microbiota that is stable in healthy individuals. Immune homeostasis is achieved and maintained due in part to the extensive interplay between the gut microbiota and host mucosal immune system. Imbalances of gut microbiota may lead to a number of pathologies such as obesity, type I and type II diabetes, inflammatory bowel disease (IBD), colorectal cancer (CRC) and inflammaging/immunosenscence in the elderly. In-depth understanding of the underlying mechanisms that control homeostasis and dysbiosis of the gut microbiota represents an important step in our ability to reliably modulate the gut microbiota with positive clinical outcomes. The potential of microbiome-based therapeutics to treat epidemic human disease is of great interest. New therapeutic paradigms, including second-generation personalized probiotics, prebiotics, narrow spectrum antibiotic treatment and faecal microbiome transplantation, may provide safer and natural alternatives to traditional clinical interventions for chronic diseases. This review discusses host–microbiota homeostasis, consequences of its perturbation and the associated challenges in therapeutic developments that lie ahead. PMID:25345825

  9. Congenital Abnormalities

    MedlinePlus

    ... tube defects. However, there is also a genetic influence to this type of congenital anomaly. Unknown Causes The vast majority of congenital abnormalities have no known cause. This is particularly troubling for parents who plan to have more children, because there is no way to predict if ...

  10. USP5/Leon deubiquitinase confines postsynaptic growth by maintaining ubiquitin homeostasis through Ubiquilin.

    PubMed

    Wang, Chien-Hsiang; Huang, Yi-Chun; Chen, Pei-Yi; Cheng, Ying-Ju; Kao, Hsiu-Hua; Pi, Haiwei; Chien, Cheng-Ting

    2017-05-10

    Synapse formation and growth are tightly controlled processes. How synaptic growth is terminated after reaching proper size remains unclear. Here, we show that Leon, the Drosophila USP5 deubiquitinase, controls postsynaptic growth. In leon mutants, postsynaptic specializations of neuromuscular junctions are dramatically expanded, including the subsynaptic reticulum, the postsynaptic density, and the glutamate receptor cluster. Expansion of these postsynaptic features is caused by a disruption of ubiquitin homeostasis with accumulation of free ubiquitin chains and ubiquitinated substrates in the leon mutant. Accumulation of Ubiquilin (Ubqn), the ubiquitin receptor whose human homolog ubiquilin 2 is associated with familial amyotrophic lateral sclerosis, also contributes to defects in postsynaptic growth and ubiquitin homeostasis. Importantly, accumulations of postsynaptic proteins cause different aspects of postsynaptic overgrowth in leon mutants. Thus, the deubiquitinase Leon maintains ubiquitin homeostasis and proper Ubqn levels, preventing postsynaptic proteins from accumulation to confine postsynaptic growth.

  11. Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis

    PubMed Central

    Chen, Jing; Zhang, Xiaolu; Kusumo, Handojo; Costa, Lucio G.; Guizzetti, Marina

    2012-01-01

    Disruption of cholesterol homeostasis in the central nervous system (CNS) has been associated with neurological, neurodegenerative, and neurodevelopmental disorders. The CNS is a closed system with regard to cholesterol homeostasis, as cholesterol-delivering lipoproteins from the periphery cannot pass the blood-brain-barrier and enter the brain. Different cell types in the brain have different functions in the regulation of cholesterol homeostasis, with astrocytes producing and releasing apolipoprotein E and lipoproteins, and neurons metabolizing cholesterol to 24(S)-hydroxycholesterol. We present evidence that astrocytes and neurons adopt different mechanisms also in regulating cholesterol efflux. We found that in astrocytes cholesterol efflux is induced by both lipid-free apolipoproteins and lipoproteins, while cholesterol removal from neurons is triggered only by lipoproteins. The main pathway by which apolipoproteins induce cholesterol efflux is through ABCA1. By upregulating ABCA1 levels and by inhibiting its activity and silencing its expression, we show that ABCA1 is involved in cholesterol efflux from astrocytes but not from neurons. Furthermore, our results suggest that ABCG1 is involved in cholesterol efflux to apolipoproteins and lipoproteins from astrocytes but not from neurons, while ABCG4, whose expression is much higher in neurons than astrocytes, is involved in cholesterol efflux from neurons but not astrocytes. These results indicate that different mechanisms regulate cholesterol efflux from neurons and astrocytes, reflecting the different roles that these cell types play in brain cholesterol homeostasis. These results are important in understanding cellular targets of therapeutic drugs under development for the treatments of conditions associated with altered cholesterol homeostasis in the CNS. PMID:23010475

  12. TRPM7: channeling the future of cellular magnesium homeostasis?

    PubMed

    Wolf, Federica I

    2004-05-11

    A recent paper by Schmitz and colleagues provides persuasive evidence that the ion channel transient receptor potential melastatin 7 (TRPM7) may be the long-sought regulator of magnesium (Mg) homeostasis in mammalian cells. This finding is not unexpected, because TRPM channels contain a kinase domain that allows them to participate in signal transduction pathways and regulatory networks. However, these studies introduce an exciting new twist into our understanding of Mg homeostasis; TRPM7 facilitates Mg entry into the cell, whereas other putative Mg transporters apparently operate in the opposite direction. By combining electrophysiological, biochemical, and genetic approaches, Schmitz and colleagues characterized most of the key features that demonstrate a well-defined and biologically plausible regulator of Mg homeostasis. TRPM7 genetics are well in hand, its regulation by intracellular free Mg2+ unravels the mechanisms of regulatory feedback loops, and its kinase domain modulates its sensitivity to free Mg2+. These findings are discussed in light of the indirect and descriptive information we had about Mg regulation before this rigorous characterization of TRPM7 brought it to the center of the Mg stage. Although the molecular events downstream of TRPM7 phosphorylation and dephosphorylation await in-depth elucidation, these results open up exciting perspectives in Mg research and may provide a much-needed tool with which to reexamine the role of Mg in cell proliferation and other important pathophysiologic events. Likewise, these findings will offer guidelines for research on disease states that are characterized by Mg imbalance.

  13. A closed-loop multi-level model of glucose homeostasis

    PubMed Central

    Uluseker, Cansu; Simoni, Giulia; Dauriz, Marco; Matone, Alice

    2018-01-01

    Background The pathophysiologic processes underlying the regulation of glucose homeostasis are considerably complex at both cellular and systemic level. A comprehensive and structured specification for the several layers of abstraction of glucose metabolism is often elusive, an issue currently solvable with the hierarchical description provided by multi-level models. In this study we propose a multi-level closed-loop model of whole-body glucose homeostasis, coupled with the molecular specifications of the insulin signaling cascade in adipocytes, under the experimental conditions of normal glucose regulation and type 2 diabetes. Methodology/Principal findings The ordinary differential equations of the model, describing the dynamics of glucose and key regulatory hormones and their reciprocal interactions among gut, liver, muscle and adipose tissue, were designed for being embedded in a modular, hierarchical structure. The closed-loop model structure allowed self-sustained simulations to represent an ideal in silico subject that adjusts its own metabolism to the fasting and feeding states, depending on the hormonal context and invariant to circadian fluctuations. The cellular level of the model provided a seamless dynamic description of the molecular mechanisms downstream the insulin receptor in the adipocytes by accounting for variations in the surrounding metabolic context. Conclusions/Significance The combination of a multi-level and closed-loop modeling approach provided a fair dynamic description of the core determinants of glucose homeostasis at both cellular and systemic scales. This model architecture is intrinsically open to incorporate supplementary layers of specifications describing further individual components influencing glucose metabolism. PMID:29420588

  14. Congenital abnormality of the vagina complicated by haemato-pyocolpos in a 1-year labrador retriever.

    PubMed

    Alonge, S; Romussi, S; Grieco, V; Luvoni, G C

    2015-06-01

    A 1-year-old female Labrador retriever was referred with a few days history of haematic-like vulvar discharge. Physical examination, vaginal inspection and palpation did not reveal any remarkable finding. Transabdominal ultrasound showed echogenic fluid accumulation in the vagina suggesting haemato-pyocolpos. An exploratory laparotomy was performed: a well-delimited ectasic vagina was identified. Ovariohysterectomy and partial vaginectomy and vaginoplasty were performed to spay the bitch and to remove the ectasic vagina. Post-operative recovery and 12-month follow-up were uneventful. Clinical, morphological and histological findings were consistent with a congenital abnormality of the muscular layer of the vagina complicated by haemato-pyocolpos. The disorganization of the vaginal tunica muscularis may have acted as locus minoris resistentiae in the vaginal wall. The organ was dilated and atonic due to the gradual accumulation of physiological fluids complicated by an overgrowth of genital bacteria. This congenital disorder has to be taken into account as differential diagnosis of haemato-pyocolpos with vaginal discharge in young bitches. © 2015 Blackwell Verlag GmbH.

  15. Frequency of metabolic abnormalities in urinary stones patients.

    PubMed

    Ahmad, Iftikhar; Pansota, Mudassar Saeed; Tariq, Muhammad; Tabassum, Shafqat Ali

    2013-11-01

    To determine the frequency of metabolic abnormalities in the serum and urine of patients with urinary stones disease. Two hundred patients with either multiple or recurrent urolithiasis diagnosed on ultrasonography and intravenous urography were included in this study. 24 hour urine sample were collected from each patient and sent for PH, specific gravity, Creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. In addition, blood sample of each patient was also sent for serum levels of urea, creatinine, uric acid, phosphate and calcium. Mean age of patients was 38 ± 7.75 years with male to female ratio of 2:1. The main presenting complaint was lumber pain and 82.5% patients were found to have calcium oxalate stones on chemical analysis. Metabolic abnormalities were found in 90.5% patients, whereas there were no metabolic abnormalities in 19 (9.5%) patients. Forty patients (21.5%) only had one metabolic abnormality and 157 (78.5%) patients had multiple metabolic abnormalities. Hyperoxaluria was the most commonly observed metabolic abnormality and was found in 64.5% patients. Other significant metabolic abnormalities were hypercalciuria, Hypercalcemia, hypocitraturia and hyperuricemia. This study concludes that frequency of metabolic abnormalities is very high in patients with urolithiasis and hyperoxaluria, hypercalciuria and hypocitraturia are the most important metabolic abnormalities observed in these patients.

  16. Chemistry Misconceptions Associated with Understanding Calcium and Phosphate Homeostasis

    ERIC Educational Resources Information Center

    Cliff, William H.

    2009-01-01

    Successful learning of many aspects in physiology depends on a meaningful understanding of fundamental chemistry concepts. Two conceptual diagnostic questions measured student understanding of the chemical equilibrium underlying calcium and phosphate homeostasis. One question assessed the ability to predict the change in phosphate concentration…

  17. Abnormal Cervical Cancer Screening Test Results

    MedlinePlus

    ... FAQ187 GYNECOLOGIC PROBLEMS Abnormal Cervical Cancer Screening Test Results • What is cervical cancer screening? • What causes abnormal cervical cancer screening test results? • What is the difference between the terms cervical ...

  18. Tooth - abnormal shape

    MedlinePlus

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... The appearance of normal teeth varies, especially the molars. ... conditions. Specific diseases can affect tooth shape, tooth ...

  19. Influence of Amino Acids in Dairy Products on Glucose Homeostasis: The Clinical Evidence.

    PubMed

    Chartrand, Dominic; Da Silva, Marine S; Julien, Pierre; Rudkowska, Iwona

    2017-06-01

    Dairy products have been hypothesized to protect against type 2 diabetes because of their high content of whey proteins, rich in branched-chain amino acids (BCAAs) - leucine, isoleucine and valine - and lysine, which may decrease postprandial glucose responses and stimulate insulin secretion. Paradoxically, epidemiologic studies also show that higher levels of plasma BCAAs have been linked to insulin resistance and type 2 diabetes. Therefore, the objective was to review the recent clinical evidence concerning the intake of amino acids found in dairy proteins so as to determine their impact on glucose homeostasis in healthy persons and in those with prediabetes and type 2 diabetes. Clinical studies have reported that the major dairy amino acids, namely, leucine, isoleucine, glutamine, phenylalanine, proline and lysine, have beneficial effects on glucose homeostasis. Yet the reported doses of amino acids investigated are too elevated to be reached through adequate dairy product intake. The minor dairy amino acids, arginine and glycine, may improve glucose homeostasis by improving other risk factors for type 2 diabetes. Further, the combination of amino acids may also improve glucose-related outcomes, suggesting additive or synergistic effects. Nevertheless, additional long-term studies in individuals with prediabetes and type 2 diabetes are needed to ascertain the benefits for glucose homeostasis of amino acids found in dairy foods. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  20. Air pollution particles and iron homeostasis | Science ...

    EPA Pesticide Factsheets

    Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, functional groups at the surface of retained particle complex iron available in the cell. In response to a reduction in concentrations of requisite iron, a functional deficiency can result intracellularly. Superoxide production by the cell exposed to a particle increases ferrireduction which facilitates import of iron with the objective being the reversal of the metal deficiency. Failure to resolve the functional iron deficiency following cell exposure to particles activates kinases and transcription factors resulting in a release of inflammatory mediators and inflammation. Tissue injury is the end product of this disruption in iron homeostasis initiated by the particle exposure. Elevation of available iron to the cell precludes deficiency of the metal and either diminishes or eliminates biological effects.General Significance: Recognition of the pathway for biological effects after particle exposure to involve a functional deficiency of iron suggests novel therapies such as metal supplementation (e.g. inhaled and oral). In addition, the demonstration of a shared mechanism of biological effects allows understanding the common clinical, physiological, and pathological presentation fol

  1. Effect of non-Newtonian viscosity on the fluid-dynamic characteristics in stenotic vessels

    NASA Astrophysics Data System (ADS)

    Huh, Hyung Kyu; Ha, Hojin; Lee, Sang Joon

    2015-08-01

    Although blood is known to have shear-thinning and viscoelastic properties, the effects of such properties on the hemodynamic characteristics in various vascular environments are not fully understood yet. For a quantitative hemodynamic analysis, the refractive index of a transparent blood analogue needs to be matched with that of the flowing conduit in order to minimize the errors according to the distortion of the light. In this study, three refractive index-matched blood analogue fluids with different viscosities are prepared—one Newtonian and two non-Newtonian analogues—which correspond to healthy blood with 45 % hematocrit (i.e., normal non-Newtonian) and obese blood with higher viscosity (i.e., abnormal non-Newtonian). The effects of the non-Newtonian rheological properties of the blood analogues on the hemodynamic characteristics in the post-stenosis region of an axisymmetric stenosis model are experimentally investigated using particle image velocimetry velocity field measurement technique and pathline flow visualization. As a result, the centerline jet flow from the stenosis apex is suppressed by the shear-thinning feature of the blood analogues when the Reynolds number is smaller than 500. The lengths of the recirculation zone for abnormal and normal non-Newtonian blood analogues are 3.67 and 1.72 times shorter than that for the Newtonian analogue at Reynolds numbers smaller than 200. The Reynolds number of the transition from laminar to turbulent flow for all blood analogues increases as the shear-thinning feature increases, and the maximum wall shear stresses in non-Newtonian fluids are five times greater than those in Newtonian fluids. However, the shear-thinning effect on the hemodynamic characteristics is not significant at Reynolds numbers higher than 1000. The findings of this study on refractive index-matched non-Newtonian blood analogues can be utilized in other in vitro experiments, where non-Newtonian features dominantly affect the flow

  2. Molecular control of vertebrate iron homeostasis by iron regulatory proteins

    PubMed Central

    Wallander, Michelle L.; Leibold, Elizabeth A.; Eisenstein, Richard S.

    2008-01-01

    Both deficiencies and excesses of iron represent major public health problems throughout the world. Understanding the cellular and organismal processes controlling iron homeostasis is critical for identifying iron-related diseases and in advancing the clinical treatments for such disorders of iron metabolism. Iron regulatory proteins (IRPs) 1 and 2 are key regulators of vertebrate iron metabolism. These RNA binding proteins post-transcriptionally control the stability or translation of mRNAs encoding proteins involved in iron homeostasis thereby controlling the uptake, utilization, storage or export of iron. Recent evidence provides insight into how IRPs selectively control the translation or stability of target mRNAs, how IRP RNA binding activity is controlled by iron-dependent and iron-independent effectors, and the pathological consequences of dysregulation of the IRP system. PMID:16872694

  3. The Effect of Age in the Alteration in Fluid Balance of Rats in Response to Centrifugation

    NASA Technical Reports Server (NTRS)

    Fuller, Charles A.

    2000-01-01

    With an increase in gravity load induced by centrifugation or upon return to Earth following spaceflight, there is a period of adjustment in fluid balance in rats. With centrifugation there is a reduced fluid intake with maintenance of the rate of urine excretion. Following spaceflight there is an increase in urine output and maintenance of fluid intake. The initial period of acclimation to hypergravity is associated with a net loss of fluids. In the present study in response to centrifugation at 2.0 G this period of acclimation is present in mature rats for a longer period of time, about 24 hours. Following this initial response a period of over compensation has previously been reported. In the present study this was not observed. The net effect of these alterations in water intake and output in response to centrifugation for 14 days was slight increase in the percent total body water, with effective compensation seen in both young and mature rats. Older rats have been shown to have a reduced relative thirst and compensatory renal function in response to hypohydration, hyperosmolality and pharmacological stimuli. Responsiveness to these stimuli are delayed and/or attenuated in older animals. Similar findings were noted in the present study in the initial response to centrifugation. The older animal had a delayed return of fluid intake to control levels. The delay of one day did not appear to effect long-term fluid homeostasis, as there was difference in the response of percent total body water at the end of 14 days of centrifugation with both age groups having a slight but significant increase. This increase has been attributed to the increase in lean body mass induced by centrifugation.

  4. A Novel Oxidative Stress Mediator in Acute Appendicitis: Thiol/Disulphide Homeostasis

    PubMed Central

    Turan, Umit; Kuvvetli, Adnan; Kilavuz, Huseyin; Karakaya, Burak; Ozaltun, Pınar; Alısık, Murat; Erel, Ozcan

    2016-01-01

    Aim. To investigate the role of a novel oxidative stress marker, thiol/disulphide homeostasis, in patients diagnosed with acute appendicitis (AA). Methods. In this study, seventy-one (43 male and 28 female) patients diagnosed with AA and 71 (30 male and 41 female) healthy volunteers were included. Age, gender, body mass index (BMI), haemoglobin (Hb), white blood cell (WBC), c-reactive protein (CRP), and thiol/disulphide homeostasis parameters (native thiol, total thiol, disulphide, disulphide/native thiol, native thiol/total thiol, and disulphide/total thiol ratios) were compared between the groups. Thiol/disulphide homeostasis was determined by a newly developed method by Erel and Neselioglu. Results. The native thiol, total thiol, and the native thiol/total thiol ratio levels were statistically significantly decreased in the AA compared with the control group (p < 0.001). Disulphide level and the ratios of disulphide/native thiol and disulphide/total thiol were higher in the AA group than in the control group (p < 0.001). There was a negative correlation of CRP with native thiol, total thiol, and native thiol/total thiol ratio while there was a positive correlation of CRP with disulphide/native thiol and disulphide/total thiol in the AA group. In the stepwise regression model, risk factors as disulphide/native thiol (OR = 1.368; p = 0.018) and CRP (OR = 1.635; p = 0.003) were determined as predictors of perforated appendicitis compared to the nonperforated group. Conclusion. This is the first study examining the thiol/disulphide homeostasis as a diagnostic aid in AA and establishing thiol/disulphide homeostatis balance shifted towards the disulphide formation due to thiol oxidation. Further studies are needed to optimize the use of this novel oxidative stress marker in AA. PMID:27642237

  5. Thiol/disulfide homeostasis in pregnant women with obstructive sleep apnea syndrome.

    PubMed

    Üstündağ, Yasemin; Demirci, Hakan; Balık, Rifat; Erel, Ozcan; Özaydın, Fahri; Kücük, Bilgen; Ertaş, Dilber; Ustunyurt, Emin

    2017-11-27

    Repetitive episodes of hypoxia and reoxygenation during sleep in patients with obstructive sleep apnea syndrome (OSAS) resemble an ischemia-reperfusion injury. We aimed to test the hypothesis that oxidative stress occurs in pregnant women with OSAS. We also aimed to compare thiol/disulfide homeostasis with ischemia-modified albumin (IMA) and total antioxidant capacity (TAC) as markers of ischemia-reperfusion injury in pregnant women with and without OSAS and healthy control. This study included 29 pregnant women with OSAS, 30 women without OSAS in the third trimester applying for periodic examinations, and 30 healthy women. Serum IMA and TAC (using the ferric reducing power of plasma method) were measured. Serum thiol/disulfide homeostasis was determined by a novel automated method. The mean age of the pregnant women with OSAS was 31.0 ± 4.7 years with a mean gestational age of 36.5 ± 3.0 weeks. The mean age of pregnant women without OSAS was 29.8 ± 4.9 years with a mean gestational age of 36.9 ± 2.7 weeks. The mean age of the nonpregnant control group was 29.7 ± 6.4 years. Both native thiol (291 ± 29 μmol/L versus 314 ± 30 μmol/L; p = .018) and total thiol (325 ± 32 versus 350 ± 32, p = .025) levels were lower in pregnant women with OSAS compared to pregnant women without OSAS, respectively (p < .01). This is the first study demonstrating the thiol/disulfide homeostasis in pregnant women with OSAS. Native thiol and total thiol levels were lower in pregnant women with OSAS compared to those without OSAS. However, dynamic thiol/disulfide homeostasis parameters cannot provide valuable information to discriminate OSAS in pregnant women.

  6. Energy homeostasis and running wheel activity during pregnancy in the mouse.

    PubMed

    Ladyman, S R; Carter, K M; Grattan, D R

    2018-05-05

    Pregnancy and lactation are metabolically challenging states, where the mother must supply all the energy requirements for the developing fetus and growing pups respectively. The aim of the current study was to characterize many aspects of energy homeostasis before and during pregnancy in the mouse, and to examine the role of voluntary activity on changes in energy expenditure during pregnancy. In a secondary aim, we evaluate measures of energy homeostasis during pregnancy in mice that successfully reared their litter or in mice that went on to abandon their litter, to determine if an impairment in pregnancy-induced adaptation of energy homeostasis might underlie the abandonment of pups soon after birth. During pregnancy, food intake was increased, characterized by increased meal size and duration but not number of meals per day. The duration of time spent inactive, predicted to indicate sleep behaviour, was increased both early and late in pregnancy compared to pre-pregnancy levels. Increased x + y beam breaks, as a measure of activity increased during pregnancy and this reflected an increase in ambulatory behaviour in mid pregnancy and an increase in non-ambulatory movement in late pregnancy. Energy expenditure, as measured by indirect calorimetry, increased across pregnancy, likely due to the growth and development of fetal tissue. There was also a dramatic reduction in voluntary wheel running as soon as the mice became pregnant. Compared with successful pregnancies and lactations, pregnancies where pups were abandoned soon after birth were associated with reduced body weight gain and an increase in running wheel activity at the end of pregnancy, but no difference in food intake or energy expenditure. Overall, during pregnancy there are multiple adaptations to change energy homeostasis, resulting in partitioning of provisions of energy to the developing fetus and storing energy for future metabolic demands. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Brain iron homeostasis: from molecular mechanisms to clinical significance and therapeutic opportunities.

    PubMed

    Singh, Neena; Haldar, Swati; Tripathi, Ajai K; Horback, Katharine; Wong, Joseph; Sharma, Deepak; Beserra, Amber; Suda, Srinivas; Anbalagan, Charumathi; Dev, Som; Mukhopadhyay, Chinmay K; Singh, Ajay

    2014-03-10

    Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mis-metabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders.

  8. Global Identification of Genes Affecting Iron-Sulfur Cluster Biogenesis and Iron Homeostasis

    PubMed Central

    Hidese, Ryota; Kurihara, Tatsuo; Esaki, Nobuyoshi

    2014-01-01

    Iron-sulfur (Fe-S) clusters are ubiquitous cofactors that are crucial for many physiological processes in all organisms. In Escherichia coli, assembly of Fe-S clusters depends on the activity of the iron-sulfur cluster (ISC) assembly and sulfur mobilization (SUF) apparatus. However, the underlying molecular mechanisms and the mechanisms that control Fe-S cluster biogenesis and iron homeostasis are still poorly defined. In this study, we performed a global screen to identify the factors affecting Fe-S cluster biogenesis and iron homeostasis using the Keio collection, which is a library of 3,815 single-gene E. coli knockout mutants. The approach was based on radiolabeling of the cells with [2-14C]dihydrouracil, which entirely depends on the activity of an Fe-S enzyme, dihydropyrimidine dehydrogenase. We identified 49 genes affecting Fe-S cluster biogenesis and/or iron homeostasis, including 23 genes important only under microaerobic/anaerobic conditions. This study defines key proteins associated with Fe-S cluster biogenesis and iron homeostasis, which will aid further understanding of the cellular mechanisms that coordinate the processes. In addition, we applied the [2-14C]dihydrouracil-labeling method to analyze the role of amino acid residues of an Fe-S cluster assembly scaffold (IscU) as a model of the Fe-S cluster assembly apparatus. The analysis showed that Cys37, Cys63, His105, and Cys106 are essential for the function of IscU in vivo, demonstrating the potential of the method to investigate in vivo function of proteins involved in Fe-S cluster assembly. PMID:24415728

  9. What proportion of congenital abnormalities can be prevented?

    PubMed Central

    Czeizel, A E; Intôdy, Z; Modell, B

    1993-01-01

    OBJECTIVE--To estimate the proportion of preventable congenital abnormalities in Hungary. DESIGN--Analysis of available Hungarian data-bases and of the effectiveness of primary, secondary, and tertiary preventive methods. SETTING--Databases of ad hoc epidemiological studies and of the Hungarian congenital abnormality registry. MAIN OUTCOME MEASURES--Prevalence at birth and prevalence after prevention in 73 congenital abnormality types or groups. RESULTS--Preventive methods are available for 51 (70%) of the 73 congenital abnormality types or groups evaluated. The birth prevalence of all congenital abnormalities could be reduced from 65 to 26 per 1000; thus 39 per 1000 (60%) are preventable. Without congenital dislocation of the hip, which is unusually common in Hungary, the preventable proportion of congenital abnormalities is 52%. CONCLUSION--Many congenital abnormalities can be prevented, but as they do not represent a single pathological category there is no single strategy for their prevention. Images p502-a p503-a PMID:8448464

  10. Fluid Extravasation in Shoulder Arthroscopic Surgery: A Systematic Review

    PubMed Central

    Memon, Muzammil; Kay, Jeffrey; Gholami, Arian; Simunovic, Nicole; Ayeni, Olufemi R.

    2018-01-01

    Background: Arthroscopic surgery of the shoulder joint has become increasingly more common given its advantages over open surgery; however, one rare but potentially life-threatening complication is fluid extravasation into the surrounding tissues, causing edema, respiratory compromise, abnormal results on laboratory blood tests, and possibly death. Currently, no systematic review exists that summarizes the existing clinical research on this topic. Purpose: To perform a systematic review on fluid extravasation as a complication of shoulder arthroscopic surgery, specifically assessing clinical presentation, risk factors, management, and outcomes. Study Design: Systematic review; Level of evidence, 4. Methods: Two reviewers independently searched 3 databases (PubMed, Ovid [MEDLINE], and Embase) from database inception until July 1, 2017. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist guided the reporting and data abstraction. The methodological quality of these studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) checklist. The results are presented in a narrative summary fashion using descriptive statistics including ranges and agreement statistics. Results: A total of 26 studies (20 case reports, 4 case series, and 2 prospective comparative studies) encompassing 205 patients (mean age, 50.8 years [range, 15-83 years]) were included. The most common signs of fluid extravasation included chest wall swelling (n = 86) and neck swelling (n = 116). In 32 patients, observation alone was sufficient. Other patients required airway intubation (n = 16), diuretics (n = 7), steroids (n = 1), and percutaneous drainage of fluid (n = 1). Clinical edema resolved after 2 to 48 hours, and patients were discharged 1 to 20 days postoperatively. Serious complications included transfer to the intensive care unit (n = 14), anterior interosseous nerve palsy (n = 4), rhabdomyolysis (n = 1), and death (n = 1

  11. Bions: A Family of Biomimetic Mineralo-Organic Complexes Derived from Biological Fluids

    PubMed Central

    Martel, Jan; Young, John D.

    2013-01-01

    Mineralo-organic nanoparticles form spontaneously in human body fluids when the concentrations of calcium and phosphate ions exceed saturation. We have shown previously that these mineralo-organic nanoparticles possess biomimetic properties and can reproduce the whole phenomenology of the so-called nanobacteria—mineralized entities initially described as the smallest microorganisms on earth. Here, we examine the possibility that various charged elements and ions may form mineral nanoparticles with similar properties in biological fluids. Remarkably, all the elements tested, including sodium, magnesium, aluminum, calcium, manganese, iron, cobalt, nickel, copper, zinc, strontium, and barium form mineralo-organic particles with bacteria-like morphologies and other complex shapes following precipitation with phosphate in body fluids. Upon formation, these mineralo-organic particles, which we term bions, invariably accumulate carbonate apatite during incubation in biological fluids; yet, the particles also incorporate additional elements and thus reflect the ionic milieu in which they form. Bions initially harbor an amorphous mineral phase that gradually converts to crystals in culture. Our results show that serum produces a dual inhibition-seeding effect on bion formation. Using a comprehensive proteomic analysis, we identify a wide range of proteins that bind to these mineral particles during incubation in medium containing serum. The two main binding proteins identified, albumin and fetuin-A, act as both inhibitors and seeders of bions in culture. Notably, bions possess several biomimetic properties, including the possibility to increase in size and number and to be sub-cultured in fresh culture medium. Based on these results, we propose that bions represent biological, mineralo-organic particles that may form in the body under both physiological and pathological homeostasis conditions. These mineralo-organic particles may be part of a physiological cycle that

  12. Neural conduction abnormality in the brain stem and prevalence of the abnormality in late preterm infants with perinatal problems.

    PubMed

    Jiang, Ze Dong

    2013-08-01

    Neurodevelopment in late preterm infants has recently attracted considerable interest. The prevalence of brain stem conduction abnormality remains unknown. We examined maximum length sequence brain stem auditory evoked response in 163 infants, born at 33-36 weeks gestation, who had various perinatal problems. Compared with 49 normal term infants without problems, the late preterm infants showed a significant increase in III-V and I-V interpeak intervals at all 91-910/s clicks, particularly at 455 and 910/s (p < 0.01-0.001). The I-III interval was slightly increased, without statistically significant difference from the controls at any click rates. These results suggest that neural conduction along the, mainly more central or rostral part of, auditory brain stem is abnormal in late preterm infants with perinatal problems. Of the 163 late preterm infant, the number (and percentage rate) of infants with abnormal I-V interval at 91, 227, 455, and 910/s clicks was, respectively, 11 (6.5%), 17 (10.2%), 37 (22.3%), and 31 (18.7%). The number (and percentage rate) of infants with abnormal III-V interval at these rates was, respectively, 10 (6.0%), 17 (10.2%), 28 (16.9), and 36 (21.2%). Apparently, the abnormal rates were much higher at 455 and 910/s clicks than at lower rates 91 and 227/s. In total, 42 (25.8%) infants showed abnormal I-V and/or III-V intervals. Conduction in, mainly in the more central part, the brain stem is abnormal in late preterm infants with perinatal problems. The abnormality is more detectable at high- than at low-rate sensory stimulation. A quarter of late preterm infants with perinatal problems have brain stem conduction abnormality.

  13. Frequency of metabolic abnormalities in urinary stones patients

    PubMed Central

    Ahmad, Iftikhar; Pansota, Mudassar Saeed; Tariq, Muhammad; Tabassum, Shafqat Ali

    2013-01-01

    Objective: To determine the frequency of metabolic abnormalities in the serum and urine of patients with urinary stones disease. Methods: Two hundred patients with either multiple or recurrent urolithiasis diagnosed on ultrasonography and intravenous urography were included in this study. 24 hour urine sample were collected from each patient and sent for PH, specific gravity, Creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. In addition, blood sample of each patient was also sent for serum levels of urea, creatinine, uric acid, phosphate and calcium. Results: Mean age of patients was 38 ± 7.75 years with male to female ratio of 2:1. The main presenting complaint was lumber pain and 82.5% patients were found to have calcium oxalate stones on chemical analysis. Metabolic abnormalities were found in 90.5% patients, whereas there were no metabolic abnormalities in 19 (9.5%) patients. Forty patients (21.5%) only had one metabolic abnormality and 157 (78.5%) patients had multiple metabolic abnormalities. Hyperoxaluria was the most commonly observed metabolic abnormality and was found in 64.5% patients. Other significant metabolic abnormalities were hypercalciuria, Hypercalcemia, hypocitraturia and hyperuricemia. Conclusion: This study concludes that frequency of metabolic abnormalities is very high in patients with urolithiasis and hyperoxaluria, hypercalciuria and hypocitraturia are the most important metabolic abnormalities observed in these patients. PMID:24550954

  14. Integrating physiological regulation with stem cell and tissue homeostasis

    PubMed Central

    Nakada, Daisuke; Levi, Boaz P.; Morrison, Sean J.

    2015-01-01

    Summary Stem cells are uniquely able to self-renew, to undergo multilineage differentiation, and to persist throughout life in a number of tissues. Stem cells are regulated by a combination of shared and tissue-specific mechanisms and are distinguished from restricted progenitors by differences in transcriptional and epigenetic regulation. Emerging evidence suggests that other aspects of cellular physiology, including mitosis, signal transduction, and metabolic regulation also differ between stem cells and their progeny. These differences may allow stem cells to be regulated independently of differentiated cells in response to circadian rhythms, changes in metabolism, diet, exercise, mating, aging, infection, and disease. This allows stem cells to sustain homeostasis or to remodel relevant tissues in response to physiological change. Stem cells are therefore not only regulated by short-range signals that maintain homeostasis within their tissue of origin, but also by long-range signals that integrate stem cell function with systemic physiology. PMID:21609826

  15. Peripheral Serotonin: a New Player in Systemic Energy Homeostasis

    PubMed Central

    Namkung, Jun; Kim, Hail; Park, Sangkyu

    2015-01-01

    Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. An ancient neurotransmitter, serotonin is among those traditional pharmacological targets for anti-obesity treatment because it exhibits strong anorectic effect in the brain. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Here, we discuss the role of serotonin in the regulation of energy homeostasis and introduce peripheral serotonin as a possible target for anti-obesity treatment. PMID:26628041

  16. Lactate rescues neuronal sodium homeostasis during impaired energy metabolism.

    PubMed

    Karus, Claudia; Ziemens, Daniel; Rose, Christine R

    2015-01-01

    Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle.

  17. The nucleolus—guardian of cellular homeostasis and genome integrity.

    PubMed

    Grummt, Ingrid

    2013-12-01

    All organisms sense and respond to conditions that stress their homeostasis by downregulating the synthesis of rRNA and ribosome biogenesis, thus designating the nucleolus as the central hub in coordinating the cellular stress response. One of the most intriguing roles of the nucleolus, long regarded as a mere ribosome-producing factory, is its participation in monitoring cellular stress signals and transmitting them to the RNA polymerase I (Pol I) transcription machinery. As rRNA synthesis is a most energy-consuming process, switching off transcription of rRNA genes is an effective way of saving the energy required to maintain cellular homeostasis during acute stress. The Pol I transcription machinery is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production which, in turn, guides cell growth and proliferation. This review focuses on the mechanisms that link cell physiology to rDNA silencing, a prerequisite for nucleolar integrity and cell survival.

  18. The GARP complex is required for cellular sphingolipid homeostasis.

    PubMed

    Fröhlich, Florian; Petit, Constance; Kory, Nora; Christiano, Romain; Hannibal-Bach, Hans-Kristian; Graham, Morven; Liu, Xinran; Ejsing, Christer S; Farese, Robert V; Walther, Tobias C

    2015-09-10

    Sphingolipids are abundant membrane components and important signaling molecules in eukaryotic cells. Their levels and localization are tightly regulated. However, the mechanisms underlying this regulation remain largely unknown. In this study, we identify the Golgi-associated retrograde protein (GARP) complex, which functions in endosome-to-Golgi retrograde vesicular transport, as a critical player in sphingolipid homeostasis. GARP deficiency leads to accumulation of sphingolipid synthesis intermediates, changes in sterol distribution, and lysosomal dysfunction. A GARP complex mutation analogous to a VPS53 allele causing progressive cerebello-cerebral atrophy type 2 (PCCA2) in humans exhibits similar, albeit weaker, phenotypes in yeast, providing mechanistic insights into disease pathogenesis. Inhibition of the first step of de novo sphingolipid synthesis is sufficient to mitigate many of the phenotypes of GARP-deficient yeast or mammalian cells. Together, these data show that GARP is essential for cellular sphingolipid homeostasis and suggest a therapeutic strategy for the treatment of PCCA2.

  19. Activating Transcription Factor 3 Regulates Immune and Metabolic Homeostasis

    PubMed Central

    Rynes, Jan; Donohoe, Colin D.; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek

    2012-01-01

    Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins. PMID:22851689

  20. Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

    PubMed Central

    Karus, Claudia; Ziemens, Daniel; Rose, Christine R

    2015-01-01

    Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle. PMID:26039160

  1. Cold ischemia with selective anterograde in situ pulmonary perfusion preserves gas exchange and mitochondrial homeostasis and curbs inflammation in an experimental model of donation after cardiac death.

    PubMed

    Pottecher, Julien; Santelmo, Nicola; Noll, Eric; Charles, Anne-Laure; Benahmed, Malika; Canuet, Matthieu; Frossard, Nelly; Namer, Izzie J; Geny, Bernard; Massard, Gilbert; Diemunsch, Pierre

    2013-10-01

    The aim of this study was to assess the functional preservation of the lung graft with anterograde lung perfusion in a model of donation after cardiac death. Thirty minutes after cardiac arrest, in situ anterograde selective pulmonary cold perfusion was started in six swine. The alveolo-capillary membrane was challenged at 3, 6, and 8 h with measurements of the mean pulmonary arterial pressure (mPAP), the pulmonary vascular resistance (PVR), the PaO2 /FiO2 ratio, the transpulmonary oxygen output (tpVO2 ), and the transpulmonary CO2 clearance (tpCO2 ). Mitochondrial homeostasis was investigated by measuring maximal oxidative capacity (Vmax ) and the coupling of phosphorylation to oxidation (ACR, acceptor control ratio) in lung biopsies. Inflammation and induction of primary immune response were assessed by measurement of tumor necrosis factor alpha (TNFα), interleukine-6 (IL-6) and receptor for advanced glycation endproducts (RAGE) in bronchoalveolar lavage fluid. Data were compared using repeated measures Anova. Pulmonary hemodynamics (mPAP: P = 0.69; PVR: P = 0.46), oxygenation (PaO2 /FiO2 : P = 0.56; tpVO2 : P = 0.46), CO2 diffusion (tpCO2 : P = 0.24), mitochondrial homeostasis (Vmax : P = 0.42; ACR: P = 0.8), and RAGE concentrations (P = 0.24) did not significantly change up to 8 h after cardiac arrest. TNFα and IL-6 were undetectable. Unaffected pulmonary hemodynamics, sustained oxygen and carbon dioxide diffusion, preserved mitochondrial homeostasis, and lack of inflammation suggest a long-lasting functional preservation of the graft with selective anterograde in situ pulmonary perfusion. © 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.

  2. Natural history of echocardiographic abnormalities in mucopolysaccharidosis III.

    PubMed

    Wilhelm, Carolyn M; Truxal, Kristen V; McBride, Kim L; Kovalchin, John P; Flanigan, Kevin M

    2018-06-01

    Mucopolysaccharidosis (MPS) type III, Sanfilippo Syndrome, is an autosomal recessive lysosomal storage disorder. MPS I and II patients often develop cardiac involvement leading to early mortality, however there are limited data in MPS III. The objective of this study is to describe cardiac abnormalities in a large group of MPS III patients followed in a longitudinal natural history study designed to determine outcome measures for gene transfer trials. A single center study of MPS III patients who were enrolled in the Nationwide Children's Hospital natural history study in 2014. Two cardiologists reviewed all patient echocardiograms for anatomic, valvular, and functional abnormalities. Valve abnormalities were defined as abnormal morphology, trivial mitral regurgitation (MR) with abnormal morphology or at least mild MR, and any aortic regurgitation (AR). Abnormal left ventricular (LV) function was defined as ejection fraction < 50%. Group comparisons were assessed using two-sample t-tests or Wilcoxon rank sum tests for continuous variables and chi-square or Fisher's exact tests for categorical variables. Twenty-five patients, 15 Type A and 10 Type B MPS III, underwent 45 echocardiograms. Fifteen patients (60%) demonstrated an abnormal echocardiographic finding with age at first abnormal echocardiogram within the study being 6.8 ± 2.8 years. Left-sided valve abnormalities were common over time: 7 mitral valve thickening, 2 mitral valve prolapse, 16 MR (8 mild, 8 trivial), 3 aortic valve thickening, and 9 AR (7 mild, 2 trivial). Two patients had asymmetric LV septal hypertrophy. No valvular stenosis or ventricular function abnormalities were noted. Incidental findings included: mild aortic root dilation (2), bicommissural aortic valve (1), and mild tricuspid regurgitation (3). Individuals with Sanfilippo A and B demonstrate a natural history of cardiac involvement with valvular abnormalities most common. In short-term follow up, patients demonstrated only

  3. Behavioral Sleep-Wake Homeostasis and EEG Delta Power Are Decoupled By Chronic Sleep Restriction in the Rat

    PubMed Central

    Stephenson, Richard; Caron, Aimee M.; Famina, Svetlana

    2015-01-01

    Study Objectives: Chronic sleep restriction (CSR) is prevalent in society and is linked to adverse consequences that might be ameliorated by acclimation of homeostatic drive. This study was designed to test the hypothesis that the sleep-wake homeostat will acclimatize to CSR. DESIGN: A four-parameter model of proportional control was used to quantify sleep homeostasis with and without recourse to a sleep intensity function. Setting: Animal laboratory, rodent walking-wheel apparatus. Subjects: Male Sprague-Dawley rats. Interventions: Acute total sleep deprivation (TSD, 1 day × 18 or 24 h, N = 12), CSR (10 days × 18 h TSD, N = 6, or 5 days × 20 h TSD, N = 5). Measurements and Results: Behavioral rebounds were consistent with model predictions for proportional control of cumulative times in wake, nonrapid eye movement sleep (NREM) and rapid eye movement sleep (REM). Delta (Δ) energy homeostasis was secondary to behavioral homeostasis; a biphasic NREM Δ power rebound contributed to the dynamics (rapid response) but not to the magnitude of the rebound in Δ energy. REM behavioral homeostasis was little affected by CSR. NREM behavioral homeostasis was attenuated in proportion to cumulative NREM deficit, whereas the biphasic NREM Δ power rebound was only slightly suppressed, indicating decoupled regulatory mechanisms following CSR. Conclusions: We conclude that sleep homeostasis is achieved through behavioral regulation, that the nonrapid eye movement sleep behavioral homeostat is susceptible to attenuation during chronic sleep restriction and that the concept of sleep intensity is not essential in a model of sleep-wake regulation. Citation: Stephenson R, Caron AM, Famina S. Behavioral sleep-wake homeostasis and EEG delta power are decoupled by chronic sleep restriction in the rat. SLEEP 2015;38(5):685–697. PMID:25669184

  4. Ergonomics for enhancing detection of machine abnormalities.

    PubMed

    Illankoon, Prasanna; Abeysekera, John; Singh, Sarbjeet

    2016-10-17

    Detecting abnormal machine conditions is of great importance in an autonomous maintenance environment. Ergonomic aspects can be invaluable when detection of machine abnormalities using human senses is examined. This research outlines the ergonomic issues involved in detecting machine abnormalities and suggests how ergonomics would improve such detections. Cognitive Task Analysis was performed in a plant in Sri Lanka where Total Productive Maintenance is being implemented to identify sensory types that would be used to detect machine abnormalities and relevant Ergonomic characteristics. As the outcome of this research, a methodology comprising of an Ergonomic Gap Analysis Matrix for machine abnormality detection is presented.

  5. Sex chromosome abnormalities and psychiatric diseases

    PubMed Central

    Zhang, Xinzhu; Yang, Jian; Li, Yuhong; Ma, Xin; Li, Rena

    2017-01-01

    Excesses of sex chromosome abnormalities in patients with psychiatric diseases have recently been observed. It remains unclear whether sex chromosome abnormalities are related to sex differences in some psychiatric diseases. While studies showed evidence of susceptibility loci over many sex chromosomal regions related to various mental diseases, others demonstrated that the sex chromosome aneuploidies may be the key to exploring the pathogenesis of psychiatric disease. In this review, we will outline the current evidence on the interaction of sex chromosome abnormalities with schizophrenia, autism, ADHD and mood disorders. PMID:27992373

  6. Targeting Cellular Calcium Homeostasis to Prevent Cytokine-Mediated Beta Cell Death.

    PubMed

    Clark, Amy L; Kanekura, Kohsuke; Lavagnino, Zeno; Spears, Larry D; Abreu, Damien; Mahadevan, Jana; Yagi, Takuya; Semenkovich, Clay F; Piston, David W; Urano, Fumihiko

    2017-07-17

    Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets. These agents are also able to restore cytokine-mediated suppression of functional ER calcium release. In addition, sitagliptin preserves function of the ER calcium pump, sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA), and decreases levels of the pro-apoptotic protein thioredoxin-interacting protein (TXNIP). Supporting the role of TXNIP in cytokine-mediated cell death, knock down of TXNIP in INS1-E cells prevents cytokine-mediated beta cell death. Our findings demonstrate that modulation of dynamic cellular calcium homeostasis and TXNIP suppression present viable pharmacologic targets to prevent cytokine-mediated beta cell loss in diabetes.

  7. Transient abnormal Q waves during exercise electrocardiography

    PubMed Central

    Alameddine, F F; Zafari, A M

    2004-01-01

    Myocardial ischaemia during exercise electrocardiography is usually manifested by ST segment depression or elevation. Transient abnormal Q waves are rare, as Q waves indicate an old myocardial infarction. The case of a patient with exercise induced transient abnormal Q waves is reported. The potential mechanisms involved in the development of such an abnormality and its clinical implications are discussed. PMID:14676264

  8. Disruption of iron homeostasis in mesothelial cells following talc pleurodesis

    EPA Science Inventory

    The mechanism for biological effect following particle exposure is incompletely understood. One postulate proposed to explain biological effect after particles is an altered iron homeostasis in the host. The fibro-inflammatory properties of particles are exploited therapeutically...

  9. Immune status, antibiotic medication and pH are associated with changes in the stomach fluid microbiota.

    PubMed

    von Rosenvinge, Erik C; Song, Yang; White, James R; Maddox, Cynthia; Blanchard, Thomas; Fricke, W Florian

    2013-07-01

    The stomach acts as a barrier to ingested microbes, thereby influencing the microbial ecology of the entire gastrointestinal (GI) tract. The stomach microbiota and the role of human host and environmental factors, such as health status or medications, in shaping its composition remain largely unknown. We sought to characterize the bacterial and fungal microbiota in the stomach fluid in order to gain insights into the role of the stomach in GI homeostasis. Gastric fluid was collected from 25 patients undergoing clinically indicated upper endoscopy. DNA isolates were used for PCR amplification of bacterial 16S ribosomal RNA (rRNA) genes and fungal internal transcribed spacers (ITS). RNA isolates were used for 16S rRNA cDNA generation and subsequent PCR amplification. While all stomach fluid samples are dominated by the phyla Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Fusobacteria (>99% of sequence reads), the transcriptionally active microbiota shows significant reduction in Actinobacteria (34%) and increase in Campylobacter (444%) (P<0.003), specifically the oral commensal and suspected intestinal pathogen Campylobacter concisus. Bacterial but not fungal diversity is reduced by antibiotic treatment (28%; P<0.02), immunosuppression in transplant recipients and HIV/AIDS patients (42%; P<0.001) and gastric fluid pH >4 (70%; P<0.05). Immunosuppression correlates with decreased abundance of Prevotella (24%), Fusobacterium (2%) and Leptotrichia (6%) and increased abundance of Lactobacillus (3844%) (P<0.003). We have generated the first in-depth characterization of the human gastric fluid microbiota, using bacterial 16S rRNA gene and transcript, and fungal ITS amplicon sequencing and provide evidence for a significant impact of the host immune status on its composition with likely consequences for human health.

  10. Therapeutic Options for Controlling Fluids in the Visual System

    NASA Technical Reports Server (NTRS)

    Curry, Kristina M.; Wotring, Virginia E.

    2014-01-01

    Visual Impairment/Intracranial Pressure (VIIP) is a newly recognized risk at NASA. The VIIP project examines the effect of long-term exposure to microgravity on vision of crewmembers before and after they return to Earth. Diamox (acetazolamide) is a medication which is used to decrease intraocular pressure; however, it carries a 3% risk of kidney stones. Astronauts are at a higher risk of kidney stones during spaceflight and the use Diamox would only increase the risk; therefore alternative therapies were investigated. Histamine 2 (H2) antagonist acid blockers such as cimetidine, ranitidine, famotidine and nizatidine are typically used to relieve the symptoms of gastroesophageal reflux disease (GERD). H2 receptors have been found in the human visual system, which has led to research on the use of H2 antagonist blockers to control fluid production in the human eye. Another potential therapeutic strategy is targeted at aquaporins, which are water channels that help maintain fluid homeostasis. Aquaporin antagonists are also known to affect intracranial pressure which can in turn alter intraocular pressure. Studies on aquaporin antagonists suggest high potential for effective treatment. The primary objective of this investigation is to review existing research on alternate medications or therapy to significantly reduce intracranial and intraocular pressure. A literature review was conducted. Even though we do not have all the answers quite yet, a considerable amount of information was discovered, and findings were narrowed, which should allow for more conclusive answers to be found in the near future.

  11. Deletion of the Rab GAP Tbc1d1 modifies glucose, lipid, and energy homeostasis in mice.

    PubMed

    Hargett, Stefan R; Walker, Natalie N; Hussain, Syed S; Hoehn, Kyle L; Keller, Susanna R

    2015-08-01

    Tbc1d1 is a Rab GTPase-activating protein (GAP) implicated in regulating intracellular retention and cell surface localization of the glucose transporter GLUT4 and thus glucose uptake in a phosphorylation-dependent manner. Tbc1d1 is most abundant in skeletal muscle but is expressed at varying levels among different skeletal muscles. Previous studies with male Tbc1d1-deficient (Tbc1d1(-/-)) mice on standard and high-fat diets established a role for Tbc1d1 in glucose, lipid, and energy homeostasis. Here we describe similar, but also additional abnormalities in male and female Tbc1d1(-/-) mice. We corroborate that Tbc1d1 loss leads to skeletal muscle-specific and skeletal muscle type-dependent abnormalities in GLUT4 expression and glucose uptake in female and male mice. Using subcellular fractionation, we show that Tbc1d1 controls basal intracellular GLUT4 retention in large skeletal muscles. However, cell surface labeling of extensor digitorum longus muscle indicates that Tbc1d1 does not regulate basal GLUT4 cell surface exposure as previously suggested. Consistent with earlier observations, female and male Tbc1d1(-/-) mice demonstrate increased energy expenditure and skeletal muscle fatty acid oxidation. Interestingly, we observe sex-dependent differences in in vivo phenotypes. Female, but not male, Tbc1d1(-/-) mice have decreased body weight and impaired glucose and insulin tolerance, but only male Tbc1d1(-/-) mice show increased lipid clearance after oil gavage. We surmise that similar changes at the tissue level cause differences in whole-body metabolism between male and female Tbc1d1(-/-) mice and between male Tbc1d1(-/-) mice in different studies due to variations in body composition and nutrient handling. Copyright © 2015 the American Physiological Society.

  12. [Hysteroscopic polypectomy, treatment of abnormal uterine bleeding].

    PubMed

    de Los Rios, P José F; López, R Claudia; Cifuentes, P Carolina; Angulo, C Mónica; Palacios-Barahona, Arlex U

    2015-07-01

    To evaluate the effectiveness of the hysteroscopic polypectomy in terms of the decrease of the abnormal uterine bleeding. A cross-sectional and analytical study was done with patients to whom a hysteroscopic polypectomy was done for treating the abnormal uterine bleeding, between January 2009 and December 2013. The response to the treatment was evaluated via a survey given to the patients about the behavior of the abnormal uterine bleeding after the procedure and about overall satisfaction. The results were obtained after a hysteroscopic polypectomy done to 128 patients and were as follows. The average time from the polypectomy applied until the survey was 30.5 months, with a standard deviation of 18 months. 67.2% of the patients reported decreased abnormal uterine bleeding and the 32.8% reported a persistence of symptoms. On average 82.8% of the. patients were satisfied with the treatment. Bivariate and multivariate analysis showed no association between the variables studied and no improvement of abnormal uterine bleeding after surgery (polypectomy). There were no complications. Hysteroscopic polypectomy is a safe surgical treatment, which decreases on two of three patients the abnormal uterine bleeding in the presence of endometrial polyps, with an acceptable level of satisfaction.

  13. Iron Homeostasis in Yellowstone National Park Hot Spring Microbial Communities

    NASA Technical Reports Server (NTRS)

    Brown, I.; Tringe, S. G.; Franklin, H.; Bryant, D. A.; Klatt, C. G.; Sarkisova, S. A.; Guevara, M.

    2010-01-01

    It has been postulated that life may have originated on Earth, and possibly on Mars, in association with hydrothermal activity and high concentrations of ferrous iron. However, it is not clear how an iron-rich thermal hydrosphere could be hospitable to microbes, since reduced iron appears to stimulate oxidative stress in all domains of life and particularly in oxygenic phototrophs. Therefore, the study of microbial diversity in iron-depositing hot springs (IDHS) and the mechanisms of iron homeostasis and suppression of oxidative stress may help elucidate how Precambrian organisms could withstand the extremely high concentrations of reactive oxygen species (ROS) produced by interaction between environmental Fe(2+) and O2. Proteins and clusters of orthologous groups (COGs) involved in the maintenance of Fe homeostasis found in cyanobacteria (CB) inhabiting environments with high and low [Fe] were main target of this analysis. Preliminary results of the analysis suggest that the Chocolate Pots (CP) microbial community is heavily dominated by phototrophs from the cyanobacteria (CB), Chloroflexi and Chlorobi phyla, while the Mushroom Spring (MS) effluent channel harbors a more diverse community in which Chloroflexi are the dominant phototrophs. It is speculated that CB inhabiting IDHS have an increased tolerance to both high concentrations of Fe(2+) and ROS produced in the Fenton reaction. This hypothesis was explored via a comparative analysis of the diversity of proteins and COGs involved in Fe and redox homeostasis in the CP and MS microbiomes.

  14. [INDIVIDUAL EVALUATION OF LORETA ABNORMALITIES IN IDIOPATHIC GENERALIZED EPILEPSY].

    PubMed

    Clemens, Béla; Puskás, Szilvia; Besenyei, Mónika; Kondákor, István; Hollódy, Katalin; Fogarasi, Andrós; Bense, Katalin; Emri, Miklós; Opposits Gábor; Kovács, Noémi Zsuzsanna; Fekete, István

    2016-03-30

    Contemporary neuroimaging methods disclosed structural and functional cerebral abnormalities in idiopathic generalized epilepsies (IGEs). However, individual electrical (EEG) abnormalities have not been evaluated yet in IGE patients. IGE patients were investigated in the drug-free condition and after 3-6 month of antiepileptic treatment. To estimate the reproducibility of qEEG variables a retrospective recruited cohort of IGE patients was investigated. 19-channel resting state EEG activity was recorded. For each patient a total of 2 minutes EEG activity was analyzed by LORETA (Low Resolution Electromagnetic Tomography). Raw LORETA values were Z-transformed and projected to a MRI template. Z-values outside within the [+3Z] to [-3Z] range were labelled as statistically abnormal. 1. In drug-free condition, 41-50% of IGE patients showed abnormal LORETA values. 2. Abnormal LORETA findings showed great inter-individual variability. 3. Most abnormal LORETA-findings were symmetrical. 4. Most maximum Z-values were localized to frontal or temporal cortex. 5. Succesfull treatment was mostly coupled with disappearence of LORETA-abnormality, persistent seizures were accompanied by persistent LORETA abnormality. 1. LORETA abnormalities detected in the untreated condition reflect seizure-generating property of the cortex in IGE patients. 2. Maximum LORETA-Z abnormalities were topographically congruent with structural abnormalities reported by other research groups. 3. LORETA might help to investigate drug effects at the whole-brain level.

  15. A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice.

    PubMed

    Abdelhamed, Zakia; Vuong, Shawn M; Hill, Lauren; Shula, Crystal; Timms, Andrew; Beier, David; Campbell, Kenneth; Mangano, Francesco T; Stottmann, Rolf W; Goto, June

    2018-01-09

    Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 ( Ccdc39 ) is responsible for early postnatal hydrocephalus in the progressive hydrocephal us ( prh ) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia. The Ccdc39 prh/prh ependymal cells develop shorter cilia with disorganized microtubules lacking the axonemal inner arm dynein. Using high-speed video microscopy, we show that an orchestrated ependymal ciliary beating pattern controls unidirectional CSF flow on the ventricular surface, which generates bulk CSF flow in the developing brain. Collectively, our data provide the first evidence for involvement of Ccdc39 in hydrocephalus and suggest that the proper development of medial wall ependymal cilia is crucial for normal mouse brain development. © 2018. Published by The Company of Biologists Ltd.

  16. Abnormal maternal serum alpha fetoprotein and pregnancy outcome.

    PubMed

    Zarzour, S J; Gabert, H A; Diket, A L; St Amant, M; Miller, J M

    1998-01-01

    The objective was to assess the occurrence of miscarriages, low birth weight, and karyotype abnormalities found with low and elevated maternal serum alpha-fetoprotein (MSAFP) among women who had genetic amniocentesis performed. A retrospective study of 2,159 women who had MSAFP analysis prior to amniocentesis was conducted. Pregnancy outcomes were obtained from record review and physicians follow-up. Limits of MSAFP used in analysis were <0.5 adjusted multiples of the median (MOM) (lower levels) and >2.0 MOM (upper levels). Autosomal trisomy was found in 1.6% with low, 0.9% normal, and 0.6% with elevated MSAFP values. Sex chromosome abnormalities were present only in patients with normal MSAFP, [45X (n = 6), 47XXY (n = 2), 69XXX]. Of five open neural tube defects, four had elevated MSAFP and one had a normal value. Omphalocele was identified in four patients, two with normal and two with elevated MSAFP. Gastroschisis was found in one low and one elevated MSAFP. Amniotic fluid alpha-fetoprotein (AFAFP) values did not correlate with MSAFP values. Patients with low MSAFP levels had a greater prevalence of abnormal karyotype (19 of 249, prevalence = 0.076) than patients with an elevated MSAFP level (2 or 166, prevalence = 0.012 OR (odds ratio) = 0.20 (P value = 0.024) when unadjusted for maternal age, and OR = 0.09 (P value = 0.001) when adjusted for maternal age. Spontaneous abortion occurred more often in patients with elevated (4 of 166, or 4%) than normal or low (20 of 1948, or 1%) values of MSAFP (odds ratio 4.32, P = 0.020 when adjusted for maternal age). Birth weight below 2,500 g was present less frequently with low or normal MSAFP (136 of 1,760, or 7.7%) than in elevated MSAFP (21 of 144 or 14.6%) (odds ratio 2.04, P = 0.005, unadjusted; and odds ratio = 2.32, P = 0.003, adjusted for maternal age). Female fetuses were present more often with low MSAFP (136 of 249, or 55%) than elevated levels 43% (71 of 164, or 43%; P = 0.024). We conclude that patients

  17. Physiology and pathophysiology of pleural fluid turnover.

    PubMed

    Zocchi, L

    2002-12-01

    case of a primary abnormality of one ore more of the mechanisms of pleural liquid turnover, a pleural effusion ensues. The factors responsible for pleural effusion may be subdivided into three main categories: those changing transpleural pressure balance, those impairing lymphatic drainage, and those producing increases in mesothelial and capillary endothelial permeability. Except in the first case, pleural fluid protein concentration increases above normal: this feature underlies the classification of pleural effusions into transudative and exudative.

  18. Clozapine-induced EEG abnormalities and clinical response to clozapine.

    PubMed

    Risby, E D; Epstein, C M; Jewart, R D; Nguyen, B V; Morgan, W N; Risch, S C; Thrivikraman, K V; Lewine, R L

    1995-01-01

    The authors hypothesized that patients who develop gross EEG abnormalities during clozapine treatment would have a less favorable outcome than patients who did not develop abnormal EEGs. The clinical EEGs and the Brief Psychiatric Rating Scale (BPRS) scores of 12 patients with schizophrenia and 4 patients with schizoaffective disorder were compared before and during treatment with clozapine. Eight patients developed significant EEG abnormalities on clozapine; 1 showed worsening of an abnormal pre-clozapine EEG; none of these subjects had clinical seizures. BPRS scores improved significantly in the group of patients who developed abnormal EEGs but not in the group who did not. Findings are consistent with previous reports of a high incidence of clozapine-induced EEG abnormalities and a positive association between these abnormalities and clinical improvement.

  19. Physiology and role of irisin in glucose homeostasis

    PubMed Central

    Perakakis, Nikolaos; Triantafyllou, Georgios A.; Fernández-Real, José Manuel; Huh, Joo Young; Park, Kyung Hee; Seufert, Jochen; Mantzoros, Christos S.

    2018-01-01

    Irisin is a myokine that leads to increased energy expenditure by stimulating the ‘browning’ of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Consequently, several studies attempted to characterize the role of irisin in glucose regulation, but contradictory results have been reported, and even the existence of this hormone has been questioned. In this Review, we present the current knowledge on the physiology of irisin and its role in glucose homeostasis. We describe the mechanisms involved in the synthesis, secretion, circulation and regulation of irisin, and the controversies regarding the measurement of irisin. We also discuss the direct effects of irisin on glucose regulatory mechanisms in different organs, the indirect effects and interactions with other hormones, and the important open questions with regard to irisin in those organs. Finally, we present the results from animal interventional studies and from human clinical studies investigating the association of irisin with obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome. PMID:28211512

  20. Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

    PubMed Central

    Haldar, Swati; Tripathi, Ajai K.; Horback, Katharine; Wong, Joseph; Sharma, Deepak; Beserra, Amber; Suda, Srinivas; Anbalagan, Charumathi; Dev, Som; Mukhopadhyay, Chinmay K.; Singh, Ajay

    2014-01-01

    Abstract Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mis-metabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders. Antioxid. Redox Signal. 20, 1324–1363. PMID:23815406

  1. Numerically abnormal chromosome constitutions in humans

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  2. The PICALM Protein Plays a Key Role in Iron Homeostasis and Cell Proliferation

    PubMed Central

    Scotland, Paula B.; Heath, Jessica L.; Conway, Amanda E.; Porter, Natasha B.; Armstrong, Michael B.; Walker, Jennifer A.; Klebig, Mitchell L.; Lavau, Catherine P.; Wechsler, Daniel S.

    2012-01-01

    The ubiquitously expressed phosphatidylinositol binding clathrin assembly (PICALM) protein associates with the plasma membrane, binds clathrin, and plays a role in clathrin-mediated endocytosis. Alterations of the human PICALM gene are present in aggressive hematopoietic malignancies, and genome-wide association studies have recently linked the PICALM locus to late-onset Alzheimer's disease. Inactivating and hypomorphic Picalm mutations in mice cause different degrees of severity of anemia, abnormal iron metabolism, growth retardation and shortened lifespan. To understand PICALM’s function, we studied the consequences of PICALM overexpression and characterized PICALM-deficient cells derived from mutant fit1 mice. Our results identify a role for PICALM in transferrin receptor (TfR) internalization and demonstrate that the C-terminal PICALM residues are critical for its association with clathrin and for the inhibitory effect of PICALM overexpression on TfR internalization. Murine embryonic fibroblasts (MEFs) that are deficient in PICALM display several characteristics of iron deficiency (increased surface TfR expression, decreased intracellular iron levels, and reduced cellular proliferation), all of which are rescued by retroviral PICALM expression. The proliferation defect of cells that lack PICALM results, at least in part, from insufficient iron uptake, since it can be corrected by iron supplementation. Moreover, PICALM-deficient cells are particularly sensitive to iron chelation. Taken together, these data reveal that PICALM plays a critical role in iron homeostasis, and offer new perspectives into the pathogenesis of PICALM-associated diseases. PMID:22952941

  3. Practical homeostasis lighting control system using sensor agent robots for office space

    NASA Astrophysics Data System (ADS)

    Tokiwa, Momoko; Mita, Akira

    2014-03-01

    The comfortable space can be changed by season, age, physical condition and the like. However, the current systems are not able to resolve them absolutely. This research proposes the Homeostasis lighting control system based on the mechanism of biotic homeostasis for making the algorithms of apparatus control. Homeostasis are kept by the interaction of the three systems, endocrine system, immune system, and nervous system[1]. By the gradual reaction in the endocrine system, body's protective response in the immune system, and the electrical reaction in the nerve system, we can keep the environments against variable changes. The new lighting control system utilizes this mechanism. Firstly, we focused on legibility and comfort in the office space to construct the control model learning from the endocrine and immune systems. The mechanism of the endocrine system is used for ambient lights in the space is used considering circadian rhythm for comfort. For the legibility, the immune system is used to control considering devices near the human depending on the distance between the human. Simulations and the demonstration were conducted to show the feasibility. Finally, the nerve system was intruded to enhance the system.

  4. Using Correlative Properties of Neighboring Pixels to Enhance Contrast-to-Noise Ratio of Abnormal Hippocampus in Patients With Intractable Epilepsy and Mesial Temporal Sclerosis.

    PubMed

    Parsons, Matthew S; Sharma, Aseem; Hildebolt, Charles

    2018-06-12

    To test whether an image-processing algorithm can aid in visualization of mesial temporal sclerosis on magnetic resonance imaging by selectively increasing contrast-to-noise ratio (CNR) between abnormal hippocampus and normal brain. In this Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, baseline coronal fluid-attenuated inversion recovery images of 18 adults (10 females, eight males; mean age 41.2 years) with proven mesial temporal sclerosis were processed using a custom algorithm to produce corresponding enhanced images. Average (Hmean) and maximum (Hmax) CNR for abnormal hippocampus were calculated relative to normal ipsilateral white matter. CNR values for normal gray matter (GM) were similarly calculated using ipsilateral cingulate gyrus as the internal control. To evaluate effect of image processing on visual conspicuity of hippocampal signal alteration, a neuroradiologist masked to the side of hippocampal abnormality rated signal intensity (SI) of hippocampi on baseline and enhanced images using a five-point scale (definitely abnormal to definitely normal). Differences in Hmean, Hmax, GM, and SI ratings for abnormal hippocampi on baseline and enhanced images were assessed for statistical significance. Both Hmean and Hmax were significantly higher in enhanced images as compared to baseline images (p < 0.0001 for both). There was no significant difference in the GM between baseline and enhanced images (p = 0.9375). SI ratings showed a more confident identification of abnormality on enhanced images (p = 0.0001). Image-processing resulted in increased CNR of abnormal hippocampus without affecting the CNR of normal gray matter. This selective increase in conspicuity of abnormal hippocampus was associated with more confident identification of hippocampal signal alteration. Copyright © 2018 Academic Radiology. Published by Elsevier Inc. All rights reserved.

  5. Abnormal findings in peers during skills learning.

    PubMed

    Wearn, Andy; Nakatsuji, Miriam; Bhoopatkar, Harsh

    2017-02-01

    Peer physical examination (PPE), where students examine each other, is common in contemporary clinical skills learning. A range of benefits and risks have been explored in the literature. One persistent concern has been the identification and management of abnormal physical findings. Two previous studies have attempted to quantify the risk, one through the discussion of two exemplar cases and the other with a retrospective student survey. Here, we report the first prospective study of the number and type of abnormalities encountered as part of early clinical skills learning in a medical programme. We have a formal written consent process for PPE, which includes the management of abnormal findings through the completion of an event form. Our data come from cohorts undertaking years 2 and 3 of the programme between 2003 and 2014. One persistent concern (of PPE) has been the identification and management of abnormal physical findings RESULTS: Nineteen event forms were completed over this period. The incidence rates per year ranged from 0.23 to 1.05 per cent. Abnormal findings included raised blood pressure, heart murmur, abnormal bedside test values, and eye and skin conditions. The low event rate, along with a feasible process for dealing with this issue, goes some way to reassuring those with concerns. We acknowledge that some abnormalities may have been missed, and that some data may have been lost as a result of incorrect process; however, even the highest annual rate is low in absolute terms. We recommend a formal process for managing abnormalities. Ideally this would be part of an overall PPE written policy, communicated to students, enacted by tutors and approved by the local ethics committee. © 2016 John Wiley & Sons Ltd.

  6. Electrocardiogram abnormalities and coronary calcification in postmenopausal women.

    PubMed

    Sabour, Siamak; Grobbee, Diederick; Rutten, Annemarieke; Prokop, Mathias; Bartelink, Marie-Louise; van der Schouw, Yvonne; Bots, Michiel

    2010-01-01

    An electrocardiogram (ECG) can provide information on subclinical myocardial damage. The presence, and more importantly, the quantity of coronary artery calcification (CAC), relates well with the overall severity of the atherosclerotic process. A strong relation has been demonstrated between coronary calcium burden and the incidence of myocardial infarction, a relation independent of age. The aim of this study was to assess the relation of left ventricular hypertrophy (LVH) and ECG abnormalities with CAC. The study population comprised 566 postmenopausal women selected from a population-based cohort study. Information on LVH and repolarization abnormalities (T-axis and QRS-T angle) was obtained using electrocardiography. Modular ECG Analysis System (MEANS) was used to assess ECG abnormalities. The women underwent a multi detector-row computed tomography (MDCT) scan (Philips Mx 8000 IDT 16) to assess CAC. The Agatston score was used to quantify CAC; scores greater than zero were considered as the presence of coronary calcium. Logistic regression was used to assess the relation of ECG abnormality with coronary calcification. LVH was found in 2.7% (n = 15) of the women. The prevalence of T-axis abnormality was 6% (n = 34), whereas 8.5% (n = 48) had a QRS-T angle abnormality. CAC was found in 62% of the women. Compared to women with a normal T-axis, women with borderline or abnormal T-axes were 3.8 fold more likely to have CAC (95% CI: 1.4-10.2). Similarly, compared to women with a normal QRS-T angle, in women with borderline or abnormal QRS-T angle, CAC was 2.0 fold more likely to be present (95% CI: 1.0-4.1). Among women with ECG abnormalities reflecting subclinical ischemia, CAC is commonly found and may in part explain the increased coronary heart disease risk associated with these ECG abnormalities.

  7. Electrocardiogram Abnormalities and Coronary Calcification in Postmenopausal Women

    PubMed Central

    Sabour, Siamak; Grobbee, Diederick; Rutten, Annemarieke; Prokop, Mathias; Bartelink, Marie-Louise; van der Schouw, Yvonne; Bots, Michiel

    2010-01-01

    Background: An electrocardiogram (ECG) can provide information on subclinical myocardial damage. The presence, and more importantly, the quantity of coronary artery calcification (CAC), relates well with the overall severity of the atherosclerotic process. A strong relation has been demonstrated between coronary calcium burden and the incidence of myocardial infarction, a relation independent of age. The aim of this study was to assess the relation of left ventricular hypertrophy (LVH) and ECG abnormalities with CAC. Methods: The study population comprised 566 postmenopausal women selected from a population-based cohort study. Information on LVH and repolarization abnormalities (T-axis and QRS-T angle) was obtained using electrocardiography. Modular ECG Analysis System (MEANS) was used to assess ECG abnormalities. The women underwent a multi detector-row computed tomography (MDCT) scan (Philips Mx 8000 IDT 16) to assess CAC. The Agatston score was used to quantify CAC; scores greater than zero were considered as the presence of coronary calcium. Logistic regression was used to assess the relation of ECG abnormality with coronary calcification. Results: LVH was found in 2.7% (n = 15) of the women. The prevalence of T-axis abnormality was 6% (n = 34), whereas 8.5% (n = 48) had a QRS-T angle abnormality. CAC was found in 62% of the women. Compared to women with a normal T-axis, women with borderline or abnormal T-axes were 3.8 fold more likely to have CAC (95% CI: 1.4–10.2). Similarly, compared to women with a normal QRS-T angle, in women with borderline or abnormal QRS-T angle, CAC was 2.0 fold more likely to be present (95% CI: 1.0–4.1). Conclusion: Among women with ECG abnormalities reflecting subclinical ischemia, CAC is commonly found and may in part explain the increased coronary heart disease risk associated with these ECG abnormalities. PMID:23074563

  8. PPAR-γ Regulates Carnitine Homeostasis and Mitochondrial Function in a Lamb Model of Increased Pulmonary Blood Flow

    PubMed Central

    Rafikov, Ruslan; Kumar, Sanjiv; Hou, Yali; Oishi, Peter E.; Datar, Sanjeev A.; Raff, Gary; Fineman, Jeffrey R.; Black, Stephen M.

    2012-01-01

    Objective Carnitine homeostasis is disrupted in lambs with endothelial dysfunction secondary to increased pulmonary blood flow (Shunt). Our recent studies have also indicated that the disruption in carnitine homeostasis correlates with a decrease in PPAR-γ expression in Shunt lambs. Thus, this study was carried out to determine if there is a causal link between loss of PPAR-γ signaling and carnitine dysfunction, and whether the PPAR-γ agonist, rosiglitazone preserves carnitine homeostasis in Shunt lambs. Methods and Results siRNA-mediated PPAR-γ knockdown significantly reduced carnitine palmitoyltransferases 1 and 2 (CPT1 and 2) and carnitine acetyltransferase (CrAT) protein levels. This decrease in carnitine regulatory proteins resulted in a disruption in carnitine homeostasis and induced mitochondrial dysfunction, as determined by a reduction in cellular ATP levels. In turn, the decrease in cellular ATP attenuated NO signaling through a reduction in eNOS/Hsp90 interactions and enhanced eNOS uncoupling. In vivo, rosiglitazone treatment preserved carnitine homeostasis and attenuated the development of mitochondrial dysfunction in Shunt lambs maintaining ATP levels. This in turn preserved eNOS/Hsp90 interactions and NO signaling. Conclusion Our study indicates that PPAR-γ signaling plays an important role in maintaining mitochondrial function through the regulation of carnitine homeostasis both in vitro and in vivo. Further, it identifies a new mechanism by which PPAR-γ regulates NO signaling through Hsp90. Thus, PPAR-γ agonists may have therapeutic potential in preventing the endothelial dysfunction in children with increased pulmonary blood flow. PMID:22962578

  9. Fluid channeling system

    NASA Technical Reports Server (NTRS)

    Davis, Donald Y. (Inventor); Hitch, Bradley D. (Inventor)

    1994-01-01

    A fluid channeling system includes a fluid ejector, a heat exchanger, and a fluid pump disposed in series flow communication The ejector includes a primary inlet for receiving a primary fluid, and a secondary inlet for receiving a secondary fluid which is mixed with the primary fluid and discharged therefrom as ejector discharge. Heat is removed from the ejector discharge in the heat exchanger, and the heat exchanger discharge is compressed in the fluid pump and channeled to the ejector secondary inlet as the secondary fluid In an exemplary embodiment, the temperature of the primary fluid is greater than the maximum operating temperature of a fluid motor powering the fluid pump using a portion of the ejector discharge, with the secondary fluid being mixed with the primary fluid so that the ejector discharge temperature is equal to about the maximum operating temperature of the fluid motor.

  10. Regulation of Glucose Homeostasis by GLP-1

    PubMed Central

    Nadkarni, Prashant; Chepurny, Oleg G.; Holz, George G.

    2014-01-01

    Glucagon-like peptide-1(7–36)amide (GLP-1) is a secreted peptide that acts as a key determinant of blood glucose homeostasis by virtue of its abilities to slow gastric emptying, to enhance pancreatic insulin secretion, and to suppress pancreatic glucagon secretion. GLP-1 is secreted from L cells of the gastrointestinal mucosa in response to a meal, and the blood glucose-lowering action of GLP-1 is terminated due to its enzymatic degradation by dipeptidyl-peptidase-IV (DPP-IV). Released GLP-1 activates enteric and autonomic reflexes while also circulating as an incretin hormone to control endocrine pancreas function. The GLP-1 receptor (GLP-1R) is a G protein-coupled receptor that is activated directly or indirectly by blood glucose-lowering agents currently in use for the treatment of type 2 diabetes mellitus (T2DM). These therapeutic agents include GLP-1R agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, and langlenatide) and DPP-IV inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin). Investigational agents for use in the treatment of T2DM include GPR119 and GPR40 receptor agonists that stimulate the release of GLP-1 from L cells. Summarized here is the role of GLP-1 to control blood glucose homeo-stasis, with special emphasis on the advantages and limitations of GLP-1-based therapeutics. PMID:24373234

  11. Diuretics and disorders of calcium homeostasis.

    PubMed

    Grieff, Marvin; Bushinsky, David A

    2011-11-01

    Diuretics commonly are administered in disorders of sodium balance. Loop diuretics inhibit the Na-K-2Cl transporter and also increase calcium excretion. They are often used in the treatment of hypercalcemia. Thiazide diuretics block the thiazide-sensitive NaCl transporter in the distal convoluted tubule, and can decrease calcium excretion. They are often used in the treatment of nephrolithiasis. Carbonic anhydrase inhibitors decrease bicarbonate absorption and the resultant metabolic acidosis can increase calcium excretion. Their use can promote nephrocalcinosis and nephrolithiasis. This review will address the use of diuretics on disorders of calcium homeostasis. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. A comprehensive phylogeny of auxin homeostasis genes involved in adventitious root formation in carnation stem cuttings.

    PubMed

    Sánchez-García, Ana Belén; Ibáñez, Sergio; Cano, Antonio; Acosta, Manuel; Pérez-Pérez, José Manuel

    2018-01-01

    Understanding the functional basis of auxin homeostasis requires knowledge about auxin biosynthesis, auxin transport and auxin catabolism genes, which is not always directly available despite the recent whole-genome sequencing of many plant species. Through sequence homology searches and phylogenetic analyses on a selection of 11 plant species with high-quality genome annotation, we identified the putative gene homologs involved in auxin biosynthesis, auxin catabolism and auxin transport pathways in carnation (Dianthus caryophyllus L.). To deepen our knowledge of the regulatory events underlying auxin-mediated adventitious root formation in carnation stem cuttings, we used RNA-sequencing data to confirm the expression profiles of some auxin homeostasis genes during the rooting of two carnation cultivars with different rooting behaviors. We also confirmed the presence of several auxin-related metabolites in the stem cutting tissues. Our findings offer a comprehensive overview of auxin homeostasis genes in carnation and provide a solid foundation for further experiments investigating the role of auxin homeostasis in the regulation of adventitious root formation in carnation.

  13. A comprehensive phylogeny of auxin homeostasis genes involved in adventitious root formation in carnation stem cuttings

    PubMed Central

    Cano, Antonio; Acosta, Manuel

    2018-01-01

    Understanding the functional basis of auxin homeostasis requires knowledge about auxin biosynthesis, auxin transport and auxin catabolism genes, which is not always directly available despite the recent whole-genome sequencing of many plant species. Through sequence homology searches and phylogenetic analyses on a selection of 11 plant species with high-quality genome annotation, we identified the putative gene homologs involved in auxin biosynthesis, auxin catabolism and auxin transport pathways in carnation (Dianthus caryophyllus L.). To deepen our knowledge of the regulatory events underlying auxin-mediated adventitious root formation in carnation stem cuttings, we used RNA-sequencing data to confirm the expression profiles of some auxin homeostasis genes during the rooting of two carnation cultivars with different rooting behaviors. We also confirmed the presence of several auxin-related metabolites in the stem cutting tissues. Our findings offer a comprehensive overview of auxin homeostasis genes in carnation and provide a solid foundation for further experiments investigating the role of auxin homeostasis in the regulation of adventitious root formation in carnation. PMID:29709027

  14. Homeostasis of exercise hyperpnea and optimal sensorimotor integration: the internal model paradigm.

    PubMed

    Poon, Chi-Sang; Tin, Chung; Yu, Yunguo

    2007-10-15

    Homeostasis is a basic tenet of biomedicine and an open problem for many physiological control systems. Among them, none has been more extensively studied and intensely debated than the dilemma of exercise hyperpnea - a paradoxical homeostatic increase of respiratory ventilation that is geared to metabolic demands instead of the normal chemoreflex mechanism. Classical control theory has led to a plethora of "feedback/feedforward control" or "set point" hypotheses for homeostatic regulation, yet so far none of them has proved satisfactory in explaining exercise hyperpnea and its interactions with other respiratory inputs. Instead, the available evidence points to a far more sophisticated respiratory controller capable of integrating multiple afferent and efferent signals in adapting the ventilatory pattern toward optimality relative to conflicting homeostatic, energetic and other objectives. This optimality principle parsimoniously mimics exercise hyperpnea, chemoreflex and a host of characteristic respiratory responses to abnormal gas exchange or mechanical loading/unloading in health and in cardiopulmonary diseases - all without resorting to a feedforward "exercise stimulus". Rather, an emergent controller signal encoding the projected metabolic level is predicted by the principle as an exercise-induced 'mental percept' or 'internal model', presumably engendered by associative learning (operant conditioning or classical conditioning) which achieves optimality through continuous identification of, and adaptation to, the causal relationship between respiratory motor output and resultant chemical-mechanical afferent feedbacks. This internal model self-tuning adaptive control paradigm opens a new challenge and exciting opportunity for experimental and theoretical elucidations of the mechanisms of respiratory control - and of homeostatic regulation and sensorimotor integration in general.

  15. Classification of breast abnormalities using artificial neural network

    NASA Astrophysics Data System (ADS)

    Zaman, Nur Atiqah Kamarul; Rahman, Wan Eny Zarina Wan Abdul; Jumaat, Abdul Kadir; Yasiran, Siti Salmah

    2015-05-01

    Classification is the process of recognition, differentiation and categorizing objects into groups. Breast abnormalities are calcifications which are tumor markers that indicate the presence of cancer in the breast. The aims of this research are to classify the types of breast abnormalities using artificial neural network (ANN) classifier and to evaluate the accuracy performance using receiver operating characteristics (ROC) curve. The methods used in this research are ANN for breast abnormalities classifications and Canny edge detector as a feature extraction method. Previously the ANN classifier provides only the number of benign and malignant cases without providing information for specific cases. However in this research, the type of abnormality for each image can be obtained. The existing MIAS MiniMammographic database classified the mammogram images into three features only namely characteristic of background tissues, class of abnormality and radius of abnormality. However, in this research three other features are added-in. These three features are number of spots, area and shape of abnormalities. Lastly the performance of the ANN classifier is evaluated using ROC curve. It is found that ANN has an accuracy of 97.9% which is considered acceptable.

  16. Chronic Exposure to Type-I IFN under Lymphopenic Conditions Alters CD4 T Cell Homeostasis

    PubMed Central

    Le Saout, Cecile; Hasley, Rebecca B.; Imamichi, Hiromi; Tcheung, Lueng; Hu, Zonghui; Luckey, Megan A.; Park, Jung-Hyun; Durum, Scott K.; Smith, Mindy; Rupert, Adam W.; Sneller, Michael C.; Lane, H. Clifford; Catalfamo, Marta

    2014-01-01

    HIV infection and the associated chronic immune activation alter T cell homeostasis leading to CD4 T cell depletion and CD8 T cell expansion. The mechanisms behind these outcomes are not totally defined and only partially explained by the direct cytopathic effect of the virus. In this manuscript, we addressed the impact of lymphopenia and chronic exposure to IFN-α on T cell homeostasis. In a lymphopenic murine model, this interaction led to decreased CD4 counts and CD8 T cell expansion in association with an increase in the Signal Transducer and Activator of Transcription 1 (STAT1) levels resulting in enhanced CD4 T cell responsiveness to IFN-α. Thus, in the setting of HIV infection, chronic stimulation of this pathway could be detrimental for CD4 T cell homeostasis. PMID:24603698

  17. Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology.

    PubMed

    Guzel, Elif; Arlier, Sefa; Guzeloglu-Kayisli, Ozlem; Tabak, Mehmet Selcuk; Ekiz, Tugba; Semerci, Nihan; Larsen, Kellie; Schatz, Frederick; Lockwood, Charles Joseph; Kayisli, Umit Ali

    2017-04-08

    The endoplasmic reticulum (ER), comprises 60% of the total cell membrane and interacts directly or indirectly with several cell organelles i.e., Golgi bodies, mitochondria and proteasomes. The ER is usually associated with large numbers of attached ribosomes. During evolution, ER developed as the specific cellular site of synthesis, folding, modification and trafficking of secretory and cell-surface proteins. The ER is also the major intracellular calcium storage compartment that maintains cellular calcium homeostasis. During the production of functionally effective proteins, several ER-specific molecular steps sense quantity and quality of synthesized proteins as well as proper folding into their native structures. During this process, excess accumulation of unfolded/misfolded proteins in the ER lumen results in ER stress, the homeostatic coping mechanism that activates an ER-specific adaptation program, (the unfolded protein response; UPR) to increase ER-associated degradation of structurally and/or functionally defective proteins, thus sustaining ER homeostasis. Impaired ER homeostasis results in aberrant cellular responses, contributing to the pathogenesis of various diseases. Both female and male reproductive tissues undergo highly dynamic cellular, molecular and genetic changes such as oogenesis and spermatogenesis starting in prenatal life, mainly controlled by sex-steroids but also cytokines and growth factors throughout reproductive life. These reproductive changes require ER to provide extensive protein synthesis, folding, maturation and then their trafficking to appropriate cellular location as well as destroying unfolded/misfolded proteins via activating ER-associated degradation mediated proteasomes. Many studies have now shown roles for ER stress/UPR signaling cascades in the endometrial menstrual cycle, ovarian folliculogenesis and oocyte maturation, spermatogenesis, fertilization, pre-implantation embryo development and pregnancy and parturition

  18. Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology

    PubMed Central

    Guzel, Elif; Arlier, Sefa; Guzeloglu-Kayisli, Ozlem; Tabak, Mehmet Selcuk; Ekiz, Tugba; Semerci, Nihan; Larsen, Kellie; Schatz, Frederick; Lockwood, Charles Joseph; Kayisli, Umit Ali

    2017-01-01

    The endoplasmic reticulum (ER), comprises 60% of the total cell membrane and interacts directly or indirectly with several cell organelles i.e., Golgi bodies, mitochondria and proteasomes. The ER is usually associated with large numbers of attached ribosomes. During evolution, ER developed as the specific cellular site of synthesis, folding, modification and trafficking of secretory and cell-surface proteins. The ER is also the major intracellular calcium storage compartment that maintains cellular calcium homeostasis. During the production of functionally effective proteins, several ER-specific molecular steps sense quantity and quality of synthesized proteins as well as proper folding into their native structures. During this process, excess accumulation of unfolded/misfolded proteins in the ER lumen results in ER stress, the homeostatic coping mechanism that activates an ER-specific adaptation program, (the unfolded protein response; UPR) to increase ER-associated degradation of structurally and/or functionally defective proteins, thus sustaining ER homeostasis. Impaired ER homeostasis results in aberrant cellular responses, contributing to the pathogenesis of various diseases. Both female and male reproductive tissues undergo highly dynamic cellular, molecular and genetic changes such as oogenesis and spermatogenesis starting in prenatal life, mainly controlled by sex-steroids but also cytokines and growth factors throughout reproductive life. These reproductive changes require ER to provide extensive protein synthesis, folding, maturation and then their trafficking to appropriate cellular location as well as destroying unfolded/misfolded proteins via activating ER-associated degradation mediated proteasomes. Many studies have now shown roles for ER stress/UPR signaling cascades in the endometrial menstrual cycle, ovarian folliculogenesis and oocyte maturation, spermatogenesis, fertilization, pre-implantation embryo development and pregnancy and parturition

  19. Unique roles of estrogen-dependent Pten control in epithelial cell homeostasis of mouse vagina.

    PubMed

    Miyagawa, S; Sato, M; Sudo, T; Yamada, G; Iguchi, T

    2015-02-19

    Numerous studies support a role of phosphatase and tensin homolog deleted from chromosome 10 (Pten) as a tumor suppressor gene that controls epithelial cell homeostasis to prevent tumor formation. Mouse vaginal epithelium cyclically exhibits cell proliferation and differentiation in response to estrogen and provides a unique model for analyzing homeostasis of stratified squamous epithelia. We analyzed vaginal epithelium-specific Pten conditional knockout (CKO) mice to provide new insights into Pten/phosphoinositide-3-kinase (PI3K)/Akt function. The vaginal epithelium of ovariectomized (OVX) mice (control) was composed of 1-2 layers of cuboidal cells, whereas OVX CKO mice exhibited epithelial hyperplasia in the suprabasal cells with increased cell mass and mucin production. This is possibly due to misactivation of mammalian target of rapamycin and mitogen-activated protein kinase. Intriguingly, estrogen administration to OVX Pten CKO mice induced stratification and keratinized differentiation in the vaginal epithelium, as in estrogen-treated controls. We found that Pten is exclusively expressed in the suprabasal cells in the absence of estrogens, whereas estrogen administration induced Pten expression in the basal cells. This suggests that Pten acts to prevent excessive cell proliferation as in the case of other squamous tissues. Thus, Pten exhibits a dual role on the control of vaginal homeostasis, depending on whether estrogens are present or absent. Our results provide new insights into how Pten functions in tissue homeostasis.

  20. Abnormal Selective Attention Normalizes P3 Amplitudes in PDD

    ERIC Educational Resources Information Center

    Hoeksma, Marco R.; Kemner, Chantal; Kenemans, J. Leon; van Engeland, Herman

    2006-01-01

    This paper studied whether abnormal P3 amplitudes in PDD are a corollary of abnormalities in ERP components related to selective attention in visual and auditory tasks. Furthermore, this study sought to clarify possible age differences in such abnormalities. Children with PDD showed smaller P3 amplitudes than controls, but no abnormalities in…