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TEKTRAN
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IRON DEPOSITION IN THE JOINTS OF CHILDREN WITH JUVENILE RHEUMATOID ARTHRITIS

   Author(s): 
          SHYPAILO ROMAN J
          ELLIS KENNETH J
          PEREZ MARIA
          ABRAMS STEVEN A
          
   Interpretive Summary: 
          We wanted to develop an accurate and noninvasive way of
          determining the amount of iron deposited in the joints of
          patients with juvenile rheumatoid arthritis. Children with JRA
          often develop excess iron in their joints, so doctors need a
          way of monitoring the iron level, particularly when prescribing
          iron supplements for the common problem of anemia. However, the
          only method currently available is to take a biopsy. We adapted
          a machine called a gamma counter to measure the iron in eight
          patients' joints after giving them an iron isotope by vein.
          Then we compared the results with the total amount of iron in
          their bodies, measured by a whole-body counter. We found that
          we had developed an accurate new way of measuring iron in these
          patients' joints. We also found that six of the eight subjects
          had excess uptake of the iron isotope in their joints. That
          provided a signal that a preponderance of JRA patients are
          prone to have this problem, and clinicians should take special
          care to monitor them for it. Moreover, this is the first time a
          noninvasive way of performing this measurement has been
          available.
          
   Keywords: 
          energy reproduction growth body composition women infants
          children water potassium bioelectrical impedance conductance
          bromide space lactating iron adipose tissue lipid motabolism
          beta-adrenergic receptor cell culture neutron activation
          nitrogen carbon calcium sodium chlorine phosphorus hormonal
          changes differentiation adipocyte hnrim021125
          
   Contact: 
          USDA/ARS CHILDREN'S NUTR
          1100 BATES ST.
          HOUSTON
          TX 77030
          FAX: (713)798-7130
          Email: kellis@bcm.tmc.edu
          
   Approved Date: 1999-01-07
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    TEKTRAN
    United States Department of Agriculture
    Agricultural Research Service
    
   Updated: 1999-01-16
   
   Arthritis Rheum 1999 Apr;42(4):799-806
   
Elevated parathyroid hormone 44-68 and osteoarticular changes in patients with
genetic hemochromatosis.

    Pawlotsky Y, Le Dantec P, Moirand R, Guggenbuhl P, Jouanolle AM, Catheline
    M, Meadeb J, Brissot P, Deugnier Y, Chales G
    
   Centre Hospitalier et Universitaire, Rennes, France.
   
   OBJECTIVE: To determine whether the osteoarticular changes associated
   with genetic hemochromatosis could be explained by metabolic
   parathyroid hormone (PTH) disorders. METHODS: The study involved 210
   patients with liver iron overload syndromes. Osteoarticular changes
   were numerically scored as the number of damaged joints. PTH 1-84 and
   44-68 were assayed. RESULTS: An increase in serum PTH 44-68 levels was
   found in one-third of untreated patients who had no calcium or PTH
   1-84 abnormalities. Serum PTH 44-68 levels correlated positively with
   serum ferritin levels. In multivariate analyses, the number of
   affected joints correlated positively with age, serum PTH 44-68
   levels, and serum ferritin levels. CONCLUSION: Liver iron overload
   syndromes, especially genetic hemochromatosis, are associated with
   elevated circulating levels of PTH fragments containing the 44-68
   region, which appears to play a role in osteoarticular changes. This
   increase seems to be a consequence of iron overload.
   
   PMID: 10211896, UI: 99226878
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   Free Radic Res 1999 May;30(5):395-405
   
Aggrecan degradation in chondrocytes is mediated by reactive oxygen species and
protected by antioxidants.

    Tiku ML, Gupta S, Deshmukh DR
    
   Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New
   Brunswick, NJ 08903-0019, USA.
   
   Reactive oxygen species (ROS) are implicated in aging of cartilage and
   in the pathogenesis of osteoarthritis. However, the biological role of
   chondrocytes-derived ROS has not been elucidated. An in-vitro model
   was developed to study the role of chondrocyte-derived ROS in
   cartilage matrix degradation. The primary articular chondrocytes were
   cultured and the aggrecan matrix was radiolabeled with 35-sulfate. The
   labeled aggrecan matrix was washed to remove unincorporated label and
   chondrocytes were returned to serum free balanced salt solution. The
   cell-monolayer-matrix sensitivity to oxidative damage due to either
   hydrogen peroxide or glucose oxidase was established by monitoring the
   release of labeled aggrecan into the medium. Lipopolysaccharide (LPS)
   treatment of chondrocyte-monolayer enhanced the release of labeled
   aggrecan. Catalase significantly prevented the release of labeled
   aggrecan in LPS-chondrocyte cultures, suggesting a role for
   chondrocyte-derived hydrogen peroxide in aggrecan degradation.
   Superoxide dismutase or boiled catalase had no such inhibitory effect.
   The effect of several antioxidants on LPS-chondrocyte-dependent
   aggrecan degradation was examined. Hydroxyl radical scavengers
   (mannitol and thiourea) significantly decreased aggrecan degradation.
   A spin trapping agent N-tert-butyl-phenylnitrone (but not its inactive
   analog tert-butyl-phenylcarbonate) significantly decreased aggrecan
   degradation. Butylated hydroxytoluene also inhibited aggrecan
   degradation, whereas the other lipophilic antioxidant tested, propyl
   gallate, had a marked dose-dependent inhibitory effect. These data
   indicate that general antioxidants, hydroxyl radical scavengers,
   antioxidant vitamins, iron chelating agents, lipophilic antioxidants,
   and spin trapping agents can influence chondrocyte-dependent aggrecan
   degradation. These studies support the role of a chondrocyte-dependent
   oxidative mechanism in aggrecan degradation and indicate that
   antioxidants can prevent matrix degradation and therefore may have a
   preventive or therapeutic value in arthritis. The enhancement of
   oxidative activity in chondrocytes and its damaging effect on matrix
   may be an important mechanism of matrix degradation in osteoarthritis.
   
   PMID: 10342332, UI: 99271760
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   Clin Orthop 1998 Apr;(349):108-15
   
Hemochromatosis of the foot and ankle. Report of three cases and review of the
literature.

    Bailey EJ, Gardner AB
    
   Emory University School of Medicine, Atlanta, GA 30322, USA.
   
   Genetic hemochromatosis is a disorder of iron metabolism that results
   in deposition of massive amounts of iron in the tissues. Arthropathy
   is one of numerous clinical manifestations associated with this
   disease. Characteristic radiographic features have been reported in
   the hand and wrist, and the hip; however, there is no mention in the
   literature of joint manifestations in the foot and ankle. In this
   report, the authors present three patients with hemochromatosis
   arthropathy of the foot and ankle. Two patients presented primarily
   with foot pain and were treated initially with orthoses. One of these
   patients went on to have to midfoot arthrodesis performed. The third
   patient presented with ankle joint symptoms, and was treated
   successfully with an ankle foot orthosis. The arthritis of
   hemochromatosis has classic radiographic findings. However, the
   arthritis of hemochromatosis may be difficult to differentiate from
   several other joint diseases. Characteristic features of this disease
   in the foot and ankle are discussed.
   
   Publication Types:
     * Review
     * Review literature
       
   PMID: 9584373, UI: 98245352
   
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   Title: Mechanism of exacerbation of rheumatoid synovitis by total-dose
   iron-dextran infusion: in-vivo demonstration of iron-promoted oxidant
   stress.
   
   Author(s): Winyard PG; Blake DR; Chirico S; Gutteridge JM; Lunec J
   
   Source: Lancet 1987 Jan 10;1(8524):69-72
   
   Abstract: The mechanism by which a synovial flare occurred in a
   patient with rheumatoid arthritis after intravenous infusion of
   iron-dextran was investigated. After the infusion, serum and
   synovial-fluid iron-binding capacity became saturated, giving rise to
   low-molecular-mass iron chelates with the capacity to cause oxidative
   damage ("bleomycin-iron"). At the same time lipid peroxidation and the
   concentration of oxidised ascorbic acid (dehydroascorbate) increased
   in both serum and synovial fluid, and red-cell glutathione fell. These
   changes corresponded closely to an exacerbation of rheumatoid
   synovitis. Hepatic function was transiently disturbed 7 days after the
   infusion, reflecting hepatic oxidant stress within the iron-loaded
   liver. Such changes provide clear evidence that iron-catalysed
   oxidative reactions influence the inflammatory process in human beings
   
   
   Major Indexes:
     * Arthritis, Rheumatoid [metabolism]
     * Iron-Dextran Complex [adverse effects]
     * Iron [metabolism]
     * Synovitis [metabolism]
       
   Minor Indexes:
     * Bleomycins [diagnostic use]
     * Glutathione [blood]
     * Infusions, Intravenous
     * Iron-Dextran Complex [administration & dosage]
     * Knee Joint [physiopathology]
     * Lipid Peroxides [metabolism]
     * Liver [metabolism]
     * Middle Age
       
   Reagent Names:
     * 0 (Bleomycins)
     * 0 (Lipid Peroxides)
     * 70-18-8 (Glutathione)
     * 7439-89-6 (Iron)
     * 9004-66-4 (Iron-Dextran Complex)
       

Subject: Arthritis

Since there are over a hundred forms of arthritis caused by many factors, 
some of which remain unknown, we have no cure for this painful and 
crippling disease.
Free radicals contribute to the pain, swelling and joint injury of 
arthritis. Serum iron accumulates in the membranes and fluids 
surrounding affected joints and interacts with oxygen to form 
free-radicals called superoxide anion radicals. These, in turn, damage 
red blood cells, causing them to leak their contents into the inflamed 
area, which then produces the most damaging of all the free-radicals 
known-- hydroxyl radicals - that destroy DNA and break down the 
protective fluid that normally lubricates joints. The less fluid, the 
more stiffness and pain. The free-radicals also interact with unsaturated 
fats in the body, producing even more free-radicals and more injury. 
During this process , lysozomes (little sacs that contain powerful 
protein-disolving enxymes) are destroyed, leaking their enzymes into the 
damaged area, which further increases the damage to joint membranes. 
Most physicians who specialize in the study and treatment of arthritis 
and related diseases will tell you that diet has little to do with 
causing arthritis or relieving its pain and stiffness.
High fat, high cholesterol diets that are low in natural antioxidants 
such as vitamin E, beta carotene, vitamin C, and antioxidant metals such 
as selenium and zinc contribute to the damage done by oxygen and other 
unavoidable free radical stimulants.
Rely on antioxidants to prevent excessive production of harmful free 
radicals. Antioxidants can reduce the damage from most traumatic injuries 
and minimize free radical destruction of joint tissues.


DG DISPATCH - INFLAMMATION: Oxidised LDL Linked To Disease
Activity In Rheumatoid Arthritis
http://www.pslgroup.com/dg/10de6e.htm

Oxidised low density lipoprotein may be involved in the pathogenesis of
rheumatoid arthritis and may serve as an additional marker of disease activity,
researchers report.


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