Promoting bone health in children and adolescents following solid organ transplantation.
bisphosphonates; bone; calcium; magnesium; metabolic bone disease; phosphorous; physical activity; solid organ transplant; vitamin D
Solid organ transplantation in children and adolescents provides many benefits through improving critical organ function, including better growth, development, cardiovascular status, and quality of life. Unfortunately, bone status may be adversely affected even when overall status is improving, due to issues with pre-existing bone disease as well as medications and nutritional challenges inherent post-transplantation. For all children and adolescents, bone status entering adulthood is a critical determinant of bone health through adulthood. The overall health and bone status of transplant recipients benefits from attention to regular physical activity, good nutrition, adequate calcium, phosphorous, magnesium and vitamin D intake and avoidance/minimization of soda, extra sodium, and obesity. Many immunosuppressive agents, especially glucocorticoids, can adversely affect bone function and development. Minimizing exposure to "bone-toxic" medications is an important part of promoting bone health in children post-transplantation. Existing guidelines detail how regular monitoring of bone status and biochemical markers can help detect bone abnormalities early and facilitate valuable bone-directed interventions. Attention to calcium and vitamin D supplementation, as well as tapering and withdrawing glucocorticoids as early as possible after transplant, can provide best bone outcomes for these children. Dual-energy X-ray absorptiometry can be useful to detect abnormal bone mass and fracture risk in this population and newer bone assessment methods are being evaluated in children at risk for poor bone outcomes. Newer bone therapies being explored in adults with transplants, particularly bisphosphonates and the RANKL inhibitor denosumab, may offer promise for children with low bone mass post-transplantation.
Kusumi K; Shaikhkhalil A; Patel HP; Mahan John D
Pediatric Transplantation
2020
2020-12-19
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1111/petr.13940" target="_blank" rel="noreferrer noopener">10.1111/petr.13940</a>
Prolactin Stimulates Dopamine Release From The Rat Corpus Striatum In The Absence Of Extracellular Calcium
amphetamine; behavior; binding-sites; brain; calcium; cerebrospinal-fluid; corpus striatum; dopamine; hypothalamus; in-vitro; Neurosciences & Neurology; prolactin; rat
Prolactin (PRL) increased basal dopamine (DA) release and attenuated amphetamine (AMPH)-stimulated DA release in vitro from rat corpus striatum in a concentration-dependent manner with 10(-5) M PRL being the most effective. The effects of PRL on DA release were enhanced in the absence of extracellular calcium. PRL at 10(-5) M did not alter the DA post-superfusion content of the striatal tissue. These results indicate that the stimulatory effect of PRL on basal DA release does not require extra-cellular calcium and the inhibitory effect on AMPH-stimulated DA release is not due to depletion of DA stores.
Laping N J; Dluzen D E; Ramirez V D
Neuroscience Letters
1991
1991-12
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0304-3940(91)90494-e" target="_blank" rel="noreferrer noopener">10.1016/0304-3940(91)90494-e</a>
Different Mechanisms May Be Required For Maintenance Of Nimda Receptor-dependent And Independent Forms Of Long-term Potentiation
activation; area; ca1; calcium; calcium channels; calmodulin inhibitors; d-aspartate receptors; dentate gyrus; depression; glutamate; hippocampal slice; induction; Neurosciences & Neurology; protein kinase; protein-kinase-c; rat hippocampal slices
In hippocampal area CA1, long-term potentiation (LTP) is induced by tetanic stimulation protocols that activate N-methyl-D-aspartate (NMDA) receptors. In addition, some stimulation protocols can induce LTP during NMDA receptor blockade. An initial signal in both NMDA receptor-dependent and independent LTPs is increased intracellular Ca2+ concentration in postsynaptic neurons. It therefore seems possible that subsequent steps leading to expression and maintenance of potentiation are shared whether or not LTP is induced through NMDA receptor activation. We tested this hypothesis by applying a broad spectrum protein kinase inhibitor, previously shown to inhibit NMDA receptor-dependent LTP. In agreement with earlier reports, we found that H-7 inhibited NMDA receptor-dependent LTP when applied either during tetanic stimulation, or beginning 30 min following tetanic stimulation. In contrast, NMDA receptor-independent LTP was not inhibited by H-7 applied during or following tetanic stimulation. We also tested for mutual occlusion between NMDA receptor-dependent and independent LTPs. Although induction of NMDA receptor-independent LTP did not occlude later induction of NMDA receptor-dependent LTP, induction of NMDA receptor-dependent LTP did occlude NMDA receptor-independent LTP. While the kinase inhibitor experiment showed a clear difference between NMDA receptor-dependent and independent LTPs, the occlusion experiments suggest an interaction between the signalling pathways for the two LTPs. (C) 1995 Wiley-Liss, Inc.
Grover L M; Teyler T J
Synapse
1995
1995-02
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/syn.890190208" target="_blank" rel="noreferrer noopener">10.1002/syn.890190208</a>
Alpha-difluoromethylornithine Decreases Inhibitory Transmission In Hippocampal Slices Independently Of Its Inhibitory Effect On Ornithine Decarboxylase
alpha-difluoromethylornithine; aspartate; brain; ca1; calcium; gamma-aminobutyric acid (a); hippocampus; ischemia; Neurosciences & Neurology; ornithine decarboxylase; polyamines; putrescine; rat; release
Ferchmin P A; Discenna P; Borroni A M; Velez M M; Rivera E M; Teyler T J
Brain Research
1993
1993-01
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0006-8993(93)91699-s" target="_blank" rel="noreferrer noopener">10.1016/0006-8993(93)91699-s</a>
Exercise Training Decreases Store-operated Ca2+ Entry Associated With Metabolic Syndrome And Coronary Atherosclerosis
artery-disease; calcium; calcium channel; Cardiovascular System & Cardiology; cardiovascular-disease; channels; Coronary smooth muscle; diabetic dyslipidemia; endothelial-cells; hyperplasia; Intravascular ultrasound; neointimal; Orai1; ossabaw miniature swine; ossabaw miniature swine; porcine model; smooth-muscle; STIM1; Store-operated; Transient receptor potential 1 channel
Edwards J M; Neeb Z P; Alloosh M; Long X; Bratz I N; Peller C R; Byrd J P; Kumar S; Obukhov A G; Sturek M
Cardiovascular Research
2010
2010-02
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1093/cvr/cvp308" target="_blank" rel="noreferrer noopener">10.1093/cvr/cvp308</a>
Evaluation of bioreactor-cultivated bone by magnetic resonance microscopy and FTIR micro spectroscopy
bone; mineralization; collagen; Endocrinology & Metabolism; tissue; calcium; flow; water; articular-cartilage; mineral; bioreactor; calcification; magnetic resonance microscopy; microscopy; cell-cultures; FTIR; ir; microspectroscopic analysis; microspectroscopy
We present a three-dimensional mineralizing model based on a hollow fiber bioreactor (HFBR) inoculated with primary osteoblasts isolated from embryonic chick calvaria. Using non-invasive magnetic resonance microscopy (MRM), the growth and development of the mineralized tissue around the individual fibers were monitored over a period of 9 weeks. Spatial maps of the water proton MRM properties of the intact tissue, with 78 mu m resolution, were used to determine changes in tissue composition with development. Unique changes in the mineral and collagen content of the tissue were detected with high specificity by proton density (PD) and magnetization transfer ratio (MTR) maps, respectively. At the end of the growth period, the presence of a bone-like tissue was verified by histology and the formation of poorly crystalline apatite was verified by selected area electron diffraction and electron probe X-ray microanalysis. FTIR microspectroscopy confirmed the heterogeneous nature of the bone-like tissue formed. FTIR-derived phosphate maps confirmed that those locations with the lowest PD values contained the most mineral, and FTIR-derived collagen maps confirmed that bright pixels on NITR maps corresponded to regions of high collagen content. In conclusion, the spatial mapping of tissue constituents by FTIR micro spectroscopy corroborated the findings of non-invasive MRM measurements and supported the role of MRM in monitoring the bone formation process in vitro. (c) 2006 Elsevier Inc. All rights reserved.
Chesnick I E; Avallone F A; Leapman R D; Landis W J; Eidelman N; Potter K
Bone
2007
2007-04
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.bone.2006.10.020" target="_blank" rel="noreferrer noopener">10.1016/j.bone.2006.10.020</a>
Penitrem A as a Tool for Understanding the Role of Large Conductance Ca2+/Voltage-Sensitive K+ Channels in Vascular Function
metabolic syndrome; Pharmacology & Pharmacy; expression; calcium; smooth-muscle; coronary vasodilation; ca2+; activated potassium channel; beta-1 subunit; bkca channels; elevated blood-pressure; sparks
Large conductance, Ca2+/voltage-sensitive K+ channels (BK channels) are well characterized, but their physiological roles, often determined through pharmacological manipulation, are less clear. Iberiotoxin is considered the "gold standard" antagonist, but cost and membrane-impermeability limit its usefulness. Economical and membrane-permeable alternatives could facilitate the study of BK channels. Thus, we characterized the effect of penitrem A, a tremorigenic mycotoxin, on BK channels and demonstrate its utility for studying vascular function in vitro and in vivo. Whole-cell currents from human embryonic kidney 293 cells transfected with hSlo alpha or alpha + beta 1 were blocked >95% by penitrem A (IC50 6.4 versus 64.4 nM; p < 0.05). Furthermore, penitrem A inhibited BK channels in inside-out and cell-attached patches, whereas iberiotoxin could not. Inhibitory effects of penitrem A on whole-cell K+ currents were equivalent to iberiotoxin in canine coronary smooth muscle cells. As for specificity, penitrem A had no effect on native delayed rectifier K+ currents, cloned voltage-dependent Kv1.5 channels, or native ATP-dependent K-ATP current. Penitrem A enhanced the sensitivity to K+-induced contraction in canine coronary arteries by 23 +/- 5% (p < 0.05) and increased the blood pressure response to phenylephrine in anesthetized mice by 36 +/- 11% ( p < 0.05). Our data indicate that penitrem A is a useful tool for studying the role of BK channels in vascular function and is practical for cell and tissue (in vitro)
Asano S; Bratz I N; Berwick Z C; Fancher I S; Tune J D; Dick G M
Journal of Pharmacology and Experimental Therapeutics
2012
2012-08
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1124/jpet.111.191072" target="_blank" rel="noreferrer noopener">10.1124/jpet.111.191072</a>
CASE-REPORT - METOLAZONE-ASSOCIATED HYPERCALCEMIA AND ACUTE-PANCREATITIS
calcium; diuretics; General & Internal Medicine; hydrochlorothiazide; hypercalcemia; mechanism; metolazone; pancreatitis; parathyroid-hormone; serum; thiazide
Metolazone-induced acute pancreatitis and hypercalcemia are described in a 58-year-old woman with severe congestive cardiac failure. Her symptoms and laboratory abnormalities rapidly resolved upon discontinuation of metolazone. Both clinical and laboratory findings make other etiologies for the patient's pancreatitis extremely unlikely. The pathophysiology of thiazide-related hypercalcemia and pancreatitis is reviewed. To our knowledge, neither hypercalcemia nor the combination of acute pancreatitis with hypercalcemia has been reported previously in association with metolazone therapy, and the association of pancreatitis and metolazone has been noted previously only once.
Anderson P E; Ellis G G; Austin S M
American Journal of the Medical Sciences
1991
1991-10
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1097/00000441-199110000-00008" target="_blank" rel="noreferrer noopener">10.1097/00000441-199110000-00008</a>
Absence of TRPV4 Channels Improves Cardiac Function and Remodeling Following Myocardial Infarction and Transverse Aortic Constriction
calcium; Cardiovascular System & Cardiology; fibrosis; Hematology; Ion channels; Myocardial infarction; Remodeling
Adapala R K; Luther D J; Ohanyan V A; Luli J; Thoppil R; Cappelli H; Paruchuri S; Chilian W; Meszaros J G; Thodeti C
Circulation Research
2013
2013-12
Journal Article or Conference Abstract Publication
n/a
Skeletal survey of Cayo Santiago rhesus macaques: Osteoarthritis and articular plate excrescences
age; arthritis; calcium; calcium pryrophosphate deposition disease; Cayo Santiago; defleshed bones; dihydrate crystals; epidemiology; erosive arthritis; macaca-mulatta; monkeys macaca-mulatta; population analysis; pyrophosphate deposition disease; reproductive; rhesus macaques; rheumatoid-arthritis; Rheumatology; spondyloarthropathy; success
Objectives: This study was performed to complement studies on spondyloarthropathy in rhesus macaques by quantifying and characterizing another major form of arthritis and contrasting it with osteoarthritis. Methods: Skeletons of 269 macaques of known age and troop affiliation from the free-ranging Cayo Santiago colony (Caribbean Primate Research Center) were macroscopically surveyed for the presence of articular changes of osteoarthritis, articular plate excrescences, and calcifications that project back over the joint surface in all diarthrodial joints. Statistical tests were used to establish the independence of pathological conditions, age, gender, troop membership, and specific joint involvement. Results: Subchondral articular surface excrescences or calcific plate-like articular surface overgrowth were noted in 17% and osteoarthritis in 18% of Cayo Santiago macaques. Distribution of joint involvement and sex ratio (1:1) of the former condition were independent of either troop membership or the distribution of osteoarthritis. Conclusion: Three major forms of arthritis are common in rhesus macaques: osteoarthritis, spondyloarthropathy and a category that might be referred to as apical plate excrescences (APE). The latter is very different from spondyloarthropathy, rheumatoid arthritis, osteoarthritis, gout, and infectious arthritis. It is quite similar to what in the past has been referred to as the radiographic form of calcium pyrophosphate deposition disease (CPPD) in humans. A new name has not been offered for the identification/categorization of this phenomenon in dry bone. Its occurrence in rhesus macaques appears to present a natural model for characterization of genetic, immunologic, and environmental aspects of this phenomenon. The acronym APE is offered for consideration in naming this category of arthritis in skeletal material. Semin Arthritis Rheum 29:100-111. Copyright (C) 1999 by W.B. Saunders Company.
Rothschild B M; Hong N; Turnquist J E
Seminars in Arthritis and Rheumatism
1999
1999-10
Journal Article
<a href="http://doi.org/10.1016/s0049-0172(99)80041-9" target="_blank" rel="noreferrer noopener">10.1016/s0049-0172(99)80041-9</a>
EFFECTS OF MELATONIN ON WATER METABOLISM AND RENAL-FUNCTION IN MALE SYRIAN-HAMSTERS (MESOCRICETUS-AURATUS)
arginine vasopressin; calcium; drinking; Endocrinology & Metabolism; localization; melatonin; neurohypophysis; Neurosciences & Neurology; osmotic pressure; oxytocin; Physiology; pineal-gland; pinealectomized rats; plasma; potassium; radioimmunoassay; responsiveness; sodium; urine; water balance
The pineal indoleamine, melatonin, has been shown to influence many physiological systems within the mammalian body. Few studies, however, have examined the influence of melatonin on renal function. This study investigated the effects of melatonin on water metabolism and renal function. Young adult male Syrian hamsters were maintained on a long photoperiod (LD 14:10) in metabolic cages. The animals received daily (1700) injections of either control vehicle or 25 mug of melatonin for 85 consecutive days. Melatonin administration resulted in significant increases in water consumption and urine production. Water budgets were also significantly influenced by melatonin, as were urinary osmolality, urinary sodium, and potassium concentrations, but urinary calcium concentrations were essentially unaltered. When excretion rates for sodium, potassium, and calcium were calculated, no differences were observed between the vehicle control and melatonin-treated groups. Injections of melatonin also significantly decreased plasma antidiuretic hormone (ADH). These results demonstrate that afternoon injections of melatonin can alter renal function, which may involve direct (i.e., on ADH secretion and/or thirst mechanisms) or indirect (i.e., behavioral) effects.
Richardson B A; Studier E H; Stallone J N; Kennedy C M
Journal of Pineal Research
1992
1992-09
Journal Article
<a href="http://doi.org/10.1111/j.1600-079X.1992.tb00054.x" target="_blank" rel="noreferrer noopener">10.1111/j.1600-079X.1992.tb00054.x</a>
MEDIAL CALCIFICATION (WHITLOCKITE) IN THE AORTA
aorta; atheroma; calcium; Cardiovascular System & Cardiology; drinking water; elastin; matrix vesicles; whitlockite
Calcified deposits in the tunica media of the human aorta have been studied in 128 cases by light microscopy and by electron microscopy and analytical methods in selected samples. Although dissolved and not visible in routine histology with alum hematoxylin stains, such calcification can be clearly seen after methylene blue staining in the form of unstained refractile particles of 1-2 mum size. These are found between the elastic laminae chiefly in the inner two-thirds of the media and appear at about age 20. By X-ray diffraction supported by energy dispersive X-ray analysis, they have been identified as whitlockite (Ca,Mg)3(PO4)2. Statistical analysis shows a significant increase in numbers with age and significant differences in severity related to county of origin but no differences between sexes or races and no correlation with deaths related to cardiovascular diseases. Among various substructures of the aortic wall, no unique crystal precursor was identified. Possible etiologic factors and clinicopathologic significance are considered.
Reid J D; Andersen M E
Atherosclerosis
1993
1993-07
Journal Article
<a href="http://doi.org/10.1016/0021-9150(93)90118-e" target="_blank" rel="noreferrer noopener">10.1016/0021-9150(93)90118-e</a>
Cartilage calcification studied by proton nuclear magnetic resonance microscopy
bioreactor; bone; calcification; calcium; cartilage; chondrocyte; Endocrinology & Metabolism; expression; growth-plate; mineral phase; nuclear magnetic resonance microscopy; retinoic acid; tissue
A three-dimensional (3D) mineralizing culture system using hollow fiber bioreactors has been developed to study the early stages of endochondral ossification by proton nuclear magnetic resonance (NMR) microscopy. Chondrocytes harvested from the cephalic half of the sterna from 17-day-old chick embryos were terminally differentiated with 33 nM of retinoic acid for I week and mineralization was initiated by the addition of 1% beta-glycerophosphate to the culture medium. Histological sections taken after 6 weeks of development in culture confirmed calcification of the cartilage matrix formed in bioreactors. Calcium to phosphorus ratios (1.62-1.68) from X-ray microanalysis supported electron diffraction of thin tissue sections showing the presence of a poorly crystalline hydroxyapatite mineral phase in the cultures. After 4 weeks of culture, quantitative proton NMR images showed water proton magnetization transfer rate constants (km) were higher in premineralized cartilage compared with uncalcified cartilage, a result suggesting collagen enrichment of the matrix. Notably after 5 weeks mineral deposits formed in bioreactors principally in the collagen-enriched zones of the cartilage with increased km values. This caused marked reductions in water proton longitudinal (T-1) and transverse (T-2) relaxation times and water diffusion coefficients (D). These results support the hypothesis that mineralization proceeds in association with a collagen template. After 6 weeks of culture development, the water proton T2 values decreased by 13% and D increased by 7% in uncalcified areas, compared with the same regions of tissue examined 1 week earlier. These changes could be attributed to the formation of small mineral inclusions in the cartilage, possibly mediated by matrix vesicles, which may play an important role in cartilage calcification. In summary, NMR images acquired before and after the onset of mineralization of the same tissue provide unique insights into the matrix events leading to endochondral mineral formation.
Potter K; Leapman R D; Basser P J; Landis W J
Journal of Bone and Mineral Research
2002
2002-04
Journal Article
<a href="http://doi.org/10.1359/jbmr.2002.17.4.652" target="_blank" rel="noreferrer noopener">10.1359/jbmr.2002.17.4.652</a>
Knockdown of amyloid precursor protein normalizes cholinergic function in a cell line derived from the cerebral cortex of a trisomy 16 mouse: An animal model of Down syndrome
16 mice; abnormalities; acetylcholine; acetylcholine-release; alzheimers-disease; amyloid; antisense; beta-protein; calcium; cell line; Down syndrome; Neurosciences & Neurology; neurotoxicity; peptide; rat hippocampal slices; root ganglion neurons
We have generated immortal neuronal cell lines from normal and trisomy 16 (Ts16) mice, a model for Down syndrome (DS). Ts16 lines overexpress DS-related genes (App, amyloid precursor protein; Sod1, Cu/Zn superoxide dismutase) and show altered cholinergic function (reduced choline uptake, ChAT expression and fractional choline release after stimulation). As previous evidence has related amyloid to cholinergic dysfunction, we reduced APP expression using specific mRNA antisense sequences in our neuronal cell line named CTb, derived from Ts16 cerebral cortex, compared to a cell line derived from a normal animal, named CNh. After transfection, Western blot studies showed APP expression knockdown in CTb cells of 36% (24 hr), 40.4% (48 hr), and 50.2% (72 hr) compared to CNh. Under these reduced APP levels, we studied 3 H-choline uptake in CTb and CNh cells. CTb, as reported previously, expressed reduced choline uptake compared to CNh cells (75%, 90%, and 69% reduction at 1, 2, and 5 min incubation, respectively). At 72 hr of APP knockdown, choline uptake levels were essentially similar in both cell types. Further, fractional release of H-3-choline in response to glutamate, nicotine, and depolarization with KCI showed a progressive increase after APP knockdown, reaching values similar to those of CNh after 72 hr of transfection. The results suggest that APP overexpression in CTb cells contributes to impaired cholinergic function, and that gene knockdown in CTb cells is a relevant tool to study DS-related dysfunction. (c) 2006 Wiley-Liss, Inc.
Opazo P; Saud K; de Saint Pierre M; Cardenas A M; Allen D D; Segura-Aguilar J; Caviedes R; Caviedes P
Journal of Neuroscience Research
2006
2006-11
Journal Article
<a href="http://doi.org/10.1002/jnr.21035" target="_blank" rel="noreferrer noopener">10.1002/jnr.21035</a>