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Ginger (Zingiber officinale) and rheumatic
disorders.
Srivastava KC, Mustafa T
Department of Environmental Medicine, Odense University,
Denmark.
Med Hypotheses 1989 May;29(1):25-8
Oxygenation of arachidonic acid is increased in inflamed
tissues. In this condition products of two enzymic
pathways-the cyclooxygenase and the 5-lipoxygenase producing
respectively prostaglandins and leukotrienes--are elevated. Of
the cyclooxygenase products, PGE2 and of the lipoxygenase
products, LTB4 are the strongest candidates for mediating
inflammation. Non-steroidal anti-inflammatory drugs which
inhibit the cyclooxygenase, and corticosteroids are used to
treat such disorders. Both types of drugs produce adverse
side-effects on prolonged use. Ginger is reported in Ayurvedic
and Tibb systems of medicine to be useful in rheumatic
disorders. Seven patients suffering from such disorders
reported relief in pain and associated symptoms on ginger
administration.
Ginger (Zingiber officinale) in rheumatism and
musculoskeletal disorders.
Srivastava KC, Mustafa T
Department of Environmental Medicine, Odense University,
Denmark.
Med Hypotheses 1992 Dec;39(4):342-8
One of the features of inflammation is increased
oxygenation of arachidonic acid which is metabolized by two
enzymic pathways--the cyclooxygenase (CO) and the
5-lipoxygenase (5-LO)--leading to the production of
prostaglandins and leukotrienes respectively. Amongst the CO
products, PGE2 and amongst the 5-LO products, LTB4 are
considered important mediators of inflammation. More than 200
potential drugs ranging from non-steroidal anti-inflammatory
drugs, corticosteroids, gold salts, disease modifying
anti-rheumatic drugs, methotrexate, cyclosporine are being
tested. None of the drugs has been found safe; all are known
to produce from mild to serious side-effects. Ginger is
described in Ayurvedic and Tibb systems of medicine to be
useful in inflammation and rheumatism. In all 56 patients (28
with rheumatoid arthritis, 18 with osteoarthritis and 10 with
muscular discomfort) used powdered ginger against their
afflictions. Amongst the arthritis patients more than
three-quarters experienced, to varying degrees, relief in pain
and swelling. All the patients with muscular discomfort
experienced relief in pain. None of the patients reported
adverse effects during the period of ginger consumption which
ranged from 3 months to 2.5 years. It is suggested that at
least one of the mechanisms by which ginger shows its
ameliorative effects could be related to inhibition of
prostaglandin and leukotriene biosynthesis, i.e. it works as a
dual inhibitor of eicosanoid biosynthesis.
Suppressive effects of eugenol and ginger oil on
arthritic rats.
Sharma JN, Srivastava KC, Gan EK
Department of Pharmacology, School of Medical Sciences,
University of Science Malaysia, Kelantan.
Pharmacology 1994 Nov;49(5):314-8
This study examined the effect of eugenol and ginger oil on
severe chronic adjuvant arthritis in rats. Severe arthritis
was induced in the right knee and right paw of male
Sprague-Dawley rats by injecting 0.05 ml of a fine suspension
of dead Mycobacterium tuberculosis bacilli in liquid paraffin
(5 mg/ml). Eugenol (33 mg/kg) and ginger oil (33 mg/kg), given
orally for 26 days, caused a significant suppression of both
paw and joint swelling. These findings suggest that eugenol
and ginger oil have potent antiinflammatory and/or
antirheumatic properties.
Plant extracts from stinging nettle (Urtica
dioica), an antirheumatic remedy, inhibit the proinflammatory
transcription factor NF-kappaB.
Riehemann K, Behnke B, Schulze-Osthoff K
Department of Internal Medicine I, Medical Clinics,
University of Tubingen, Germany.
FEBS Lett 1999 Jan 8;442(1):89-94
Activation of transcription factor NF-kappaB is elevated in
several chronic inflammatory diseases and is responsible for
the enhanced expression of many proinflammatory gene products.
Extracts from leaves of stinging nettle (Urtica dioica) are
used as antiinflammatory remedies in rheumatoid arthritis.
Standardized preparations of these extracts (IDS23) suppress
cytokine production, but their mode of action remains unclear.
Here we demonstrate that treatment of different cells with
IDS23 potently inhibits NF-kappaB activation. An inhibitory
effect was observed in response to several stimuli, suggesting
that IDS23 suppressed a common NF-kappaB pathway. Inhibition
of NF-kappaB activation by IDS23 was not mediated by a direct
modification of DNA binding, but rather by preventing
degradation of its inhibitory subunit IkappaB-alpha. Our
results suggests that part of the antiinflammatory effect of
Urtica extract may be ascribed to its inhibitory effect on
NF-kappaB activation.
[Anti-inflammatory effect of Urtica dioica folia
extract in comparison to caffeic malic acid].
Obertreis B, Giller K, Teucher T, Behnke B, Schmitz H
Strathmann AG, Hamburg.
Arzneimittelforschung 1996 Jan;46(1):52-6
Urtica dioica extract is a traditionary used adjuvant
therapeutic in rheumatoid arthritis. The antiphlogistic
effects of the urtica dioica folia extract IDS 23 (Extractum
Urticae dioicae foliorum) and the main phenolic ingredient
caffeic malic acid were tested concerning the inhibitory
potential on biosynthesis of arachidonic acid metabolites in
vitro. The caffeic malic acid was isolated from Urtica folia
extract using gel exclusion- and high performance liquid
chromatography and identified by mass spectroscopy and nuclear
magnetic resonance. Concerning the 5-lipoxygenase products IDS
23 showed a partial inhibitory effect. The isolated phenolic
acid inhibited the synthesis of the leukotriene B4 in a
concentration dependent manner. The concentration for
halfmaximal inhibition (IC50) was 83 microns/ml in the used
assay. IDS 23 showed a strong concentration dependent
inhibition of the synthesis of cyclooxygenase derived
reactions. The IC50 were 92 micrograms/ml for IDS 23 and 38
micrograms/ml for the caffeic malic acid. Calculating the
content in IDS 23 the caffeic malic acid is a possible but not
the only active ingredient of the plant extract in the tested
assay systems. It is demonstrated that the phenolic component
showed a different enzymatic target compared with IDS 23. The
antiphlogistic effects observed in vitro may give an
explanation for the pharmacological and clinical effects of
IDS 23 in therapie of rheumatoid diseases.
The effect of aurotherapy on the level of
unsaturated fatty acids during the treatment of rheumatoid
arthritis patients
Virstiuk NH
Lik Sprava (Ukraine) Sep-Oct 1997, (5) p166-70,
Patients with rheumatic arthritis displayed alterations in
blood serum fatty acid spectrum such that polyunsaturated
fatty acids tended to be on the decrease, arachidonic acid in
particular, monounsaturated ones on the increase. Long-term
aurotherapy (for up to 1.5 yr) made for normalization of serum
content of unsaturated fatty acids, which observation was
accompanied by clinical-and-laboratory remission of rheumatic
arthritis. Crisanole effect got higher with incrementing
dosage of metallic gold. Results of studies made
pathogenetically validate the expediency of long-term
aurotherapy in patients with rheumatic arthritis.
Putative analgesic activity of repeated oral doses
of vitamin E in the treatment of rheumatoid arthritis. Results
of a prospective placebo controlled double blind trial.
Edmonds SE; Winyard PG; Guo R; Kidd B; Merry P;
Langrish-Smith A; Hansen C; Ramm S; Blake DR
Inflammation Research Group, St Bartholomew's School of
Medicine and Dentistry, London.
Ann Rheum Dis (England) Nov 1997, 56 (11)
p649-55
OBJECTIVE: Vitamin E, the most potent naturally occurring
lipid soluble antioxidant has been suggested to possess both
anti-inflammatory and analgesic activity in humans. This
double blind and randomised study used a broad spectrum of
clinical and laboratory parameters to investigate whether
there was any additional anti-inflammatory or analgesic
effects, or both, of orally administered alpha-tocopherol in
rheumatoid arthritis patients who were already receiving
anti-rheumatic drugs.
METHODS: Forty two patients were enrolled and treated with
alpha-tocopherol (n = 20) at a dose of 600 mg twice a day (2 x
2 capsules) or with placebo (n = 22) for 12 weeks. The
following parameters were measured: (1) Three clinical indices
of inflammation--the Ritchie articular index, the duration of
morning stiffness, and the number of swollen joints; (2) three
measures of pain--pain in the morning, pain in the evening,
and pain after chosen activity; (3) haematological and
biochemical measures of inflammatory activity; (4) assays for
the oxidative modification of proteins and lipids.
RESULTS: All laboratory measures of inflammatory activity
and oxidative modification were unchanged. Furthermore, the
clinical indices of inflammation were not influenced by the
treatment. However, the pain parameters were significantly
decreased after vitamin E treatment when compared with
placebo.
CONCLUSION: The results provide preliminary evidence that
vitamin E may exert a small but significant analgesic activity
independent of a peripheral anti-inflammatory effect, but
which complements standard anti-inflammatory treatment.
Inadequate calcium, folic acid, vitamin E, zinc,
and selenium intake in rheumatoid arthritis patients: results
of a dietary survey.
Stone J; Doube A; Dudson D; Wallace J
Department of Rheumatology, Waikato Hospital, Hamilton, New
Zealand.
Semin Arthritis Rheum (United States) Dec 1997, 27 (3)
p180-5
OBJECTIVES: To determine the adequacy of calcium, folic
acid, vitamin E, zinc, and selenium intake in patients with
rheumatoid arthritis (RA).
METHODS: We conducted an observational study on 48 patients
(13 men, 35 women; mean age, 64.5 years) with RA attending a
specialty clinic in New Zealand comparing their dietary intake
as measured by a 5-day dietary survey with recommended dietary
intake (RDI) guidelines. Information on disease activity,
functional ability, and drug therapy also was obtained.
RESULTS: The percentage of patients who achieved the RDI
was 23% for calcium, 46% for folic acid, 29% for vitamin E,
10% for zinc, and only 6% for selenium . Patients on
methotrexate had a significantly reduced intake of folic acid
as a percentage of RDI (P < .05) compared with those on
other therapies. In contrast, dietary intake of iron and
protein was largely adequate and unrelated to anemia.
CONCLUSIONS : Patients with RA should receive dietary
education or supplementation to bring their intake of calcium,
folic acid, vitamin E, zinc, and selenium up to the RDI.
Dietary n-3 fatty acids and therapy for rheumatoid
arthritis.
James MJ; Cleland LG
Rheumatology Unit, Royal Adelaide Hospital, Australia.
Semin Arthritis Rheum (United States) Oct 1997, 27 (2)
p85-97
OBJECTIVE: To examine the potential for dietary n-3 fats to
be component of therapy for rheumatoid arthritis (RA).
METHODS: Studies of encapsulated fish oil use in RA were
reviewed and critiqued, and possible biochemical mechanisms
for fish oil effects were examined. The potential for use of
n-3 fats was evaluated within a dietary framework rather than
a quasi-pharmaceutical framework.
RESULTS: There is consistent evidence from double-blind,
placebo-controlled clinical trials that dietary n-3 fats,
supplied as fish oil, can have beneficial effects in RA. The
beneficial effects appear modest, but their size and extent
may have been moderated by common trial design factors such as
high n-6 polyunsaturated fat diets and concurrent
antiinflammatory drug use. Mechanisms for the clinical effects
of n-3 fats in RA may involve their ability to suppress
production of inflammatory mediators, including n-6
eicosanoids and proinflammatory cytokines. Suppression of n-6
eicosanoid and cytokine production will be possible using
foodstuffs that are rich in n-3 fats and poor in n-6 fats.
CONCLUSIONS: There are many overlapping biochemical effects
of n-3 fatty acids and antiinflammatory pharmaceuticals that
could explain the clinical actions of n-3 fats in RA. They
suggest that there is the potential for complementarity
between drug therapy and dietary choices that increase intake
of n-3 fats and decrease intake of n-6 fats. In particular,
there is the potential for drug-sparing effects. Future
studies with n-3 fats in RA need to address the fat
composition of the background diet and the issue of concurrent
drug use. (83 Refs.)
[Selenium concentration in erythrocytes of patients
with rheumatoid arthritis . Clinical and laboratory chemistry
infection markers during administration of selenium]
Heinle K; Adam A; Gradl M; Wiseman M; Adam O
Rheumaeinheit der Ludwig-Maximilians-Universitat, Staatliche
Orthopadische Klinik, Munchen.
Med Klin (Germany) Sep 15 1997, 92 Suppl 3
p29-31
PATIENTS AND METHODS: Seventy patients with definitive
rheumatoid arthritis were matched to built 2 groups, which
were double-blind and randomized allocated to supplementation
with sodium-selenit 200 micrograms/d or placebo for 3 months,
each. Both groups were given fish oil fatty acids (30 mg/kg
body weight), DMARDS were continued throughout the study,
while variations in steroids or NSAD were admitted.
RESULTS: Selenium concentrations in erythrocytes of
patients with rheumatoid arthritis were 85.1 +/- 26
micrograms/l, and significantly lower than found in an average
German population (123 +/- 23 micrograms/l). During the
observation period of 3 months normal selenium concentrations
were not restored, despite supplementation higher than RDA. At
the end of the experimental period the selenium supplemented
group showed less tender or swollen joints, and morning
stiffness. Selen-supplemented patients needed less cortisone
and NSAD than controls. In accordance with clinical
improvement we found a decrease of laboratory indicators of
inflammation (C-reactive protein, alpha 2-globuline,
prostaglandin E2).
CONCLUSION: No side effects of supplementation with
selenium were noted, which can be considered as adjuvant
therapy in patients with rheumatoid arthritis.
Abnormalities in skeletal growth in children with
juvenile rheumatoid arthritis.
Cassidy JT; Hillman LS
Department of Child Health, University of Missouri Health
Sciences Center, Columbia, USA.
Rheum Dis Clin North Am (United States) Aug 1997, 23 (3)
p499-522
A review of the acquisition of peak skeletal mass in normal
children and studies that have been reported for children with
JRA lead to the following tentative conclusions:
(1) The appendicular skeleton is predominantly the overall
status of skeletal mineralization;
(2) a failure to develop adequate bone mineralization is
virtually universal in children with JRA and is characterized
by a failure of bone formation. A failure to undergo the
normal increase in bone mass during puberty is common in
children with JRA and markedly decreases their potential to
achieve an adequate peak skeletal mass;
(3) the onset of accelerated skeletal maturation with
puberty is a critical period of potential intervention in JRA.
Conversely, therapeutic interventions later during adolescence
offer less promise of reversal of inadequate bone
mineralization; and
(4) the most important therapeutic maneuver is likely to be
control of the inflammation process, although there is hope,
at present unsubstantiated, that supplemental dietary calcium
and vitamin D, and normalization of physical activity, many
lead to some "catch-up" mineralization. (145 Refs.)
Availability of iron and degree of inflammation
modifies the response to recombinant human erythropoietin when
treating anemia of chronic disease in patients with rheumatoid
arthritis.
Nordstrom D; Lindroth Y; Marsal L; Hafstrom I; Henrich C;
Rantapaa-Dahlqvist S; Engstrom-Laurent A; Fyhrquist F; Friman
C
Dept of Rheumatology, Helsinki University Central Hospital,
Finland.
dan.nordstrom@huch.fi
Rheumatol Int (Germany) 1997, 17 (2) p67-73
Forty-six patients with rheumatoid arthritis (RA) and
documented anemia of chronic disease (Hb < 100/110 g/l)
were randomized to receive either human recombinant
erythropoietin (r-HuEPO, n = 36, 300 U/kg body weight) or
placebo (n = 10) for 12 weeks in a multicenter study. An
adequate response was defined as elevation of Hb > or = 120
g/l. Relevant clinical and laboratory assessments were made to
evaluate efficacy and secure safety. A significant elevation
in Hb from week 10 onwards was noted in twenty-six patients
(five drop-outs) out of nine patients receiving placebo (one
drop-out) (12 +/- 1.2 g/l vs 4 +/- 0.5 g/l; Hb elevation from
95 g/l to 107 g/l vs 93 g/l to 97 g/l, P < 0.05). Only
14.6%, however, were considered responders according to preset
criteria. In the responders a lower initial CRP, a significant
reduction in ESR but not in CRP was seen compared to the
remaining r-HuEPO group. A significant elevation of energy
level was noted in the r-HuEPO group; otherwise, no
differences in clinical variables were seen. No serious
adverse effects were noted. When analyzing patients receiving
oral iron in combination with r-HuEPO and adding five
additional, openly selected patients receiving both adequate
iron supplementation and r-HuEPO, there was a significant
weekly elevation of Hb from week 8 onwards in favor of
combination therapy over the ones only receiving r-HuEPO (18
+/- 1.1 g/l vs 7 +/- 1.1 g/l, P < 0.05). The initial six
responders had now reached ten of whom seven belonged to the
combination therapy group. Response to r-HuEPO in RA patients
appears to be dependent on availability of iron and on the
degree of inflammation. If r-HuEPO treatment is considered,
iron deficiency should always be corrected and strenuous
efforts should have been made to control the disease
itself.
Serum concentrations of alpha tocopherol, beta
carotene, and retinol preceding the diagnosis of rheumatoid
arthritis and systemic lupus erythematosus.
Comstock GW; Burke AE; Hoffman SC; Helzlsouer KJ; Bendich A;
Masi AT; Norkus EP; Malamet RL; Gershwin ME
Dept. of Epidemiology, School of Hygiene and Public Health,
Johns Hopkins University, Baltimore, Maryland, USA.
Ann Rheum Dis (England) May 1997, 56 (5) p323-5,
OBJECTIVES: Because oxidative damage has been implicated in
the pathogenesis of rheumatoid arthritis and systemic lupus
erythematosus, this study was designed to see if serum
concentrations of alpha tocopherol, beta carotene, and
retinol, substances believed to be involved in the prevention
or repair of oxidative damage, might be lower among persons
who develop rheumatoid arthritis or systemic lupus
erythematosus than among those who do not.
METHODS: For this prospective case-control study, persons
with rheumatoid arthritis and systemic lupus erythematosus
that developed two to 15 years after donating blood for a
serum bank in 1974 were designated as cases. For each case,
four controls were selected from the serum bank donors,
matched for race, sex, and age. Stored serum samples from
cases and controls were assayed for alpha tocopherol, beta
carotene, and retinol.
RESULTS: Cases of both diseases had lower serum
concentrations of alpha tocopherol, beta carotene, and retinol
in 1974 than their matched controls. For rheumatoid arthritis,
the difference for beta carotene (-29%) was statistically
significant.
CONCLUSIONS: These findings support those of a previous
study that low antioxidant status is a risk factor for
rheumatoid arthritis. They suggest a similar association for
systemic lupus erythematosus.
Faecal microbial flora and disease activity in
rheumatoid arthritis during a vegan diet.
Peltonen R; Nenonen M; Helve T; Hanninen O; Toivanen P;
Eerola E
Department of Medicine, Turku University Central Hospital,
Finland.
Br J Rheumatol (England) Jan 1997, 36 (1) p64-8
To clarify the role of the faecal flora in the diet-induced
decrease of rheumatoid arthritis (RA) activity, 43 RA patients
were randomized into two groups: the test group to receive
living food, a form of uncooked vegan diet rich in
lactobacilli, and the control group to continue their ordinary
omnivorous diets. Based on clinical assessments before, during
and after the intervention period, a disease improvement index
was constructed for each patient. According to the index,
patients were assigned either to a group with a high
improvement index (HI) or to a group with a low improvement
index (LO). Stool samples collected from each patient before
the intervention and at 1 month were analysed by direct stool
sample gas-liquid chromatography of bacterial cellular fatty
acids . This method has proved to be a simple and sensitive
way to detect changes and differences in the faecal microbial
flora between individual stool samples or groups of them. A
significant, diet-induced change in the faecal flora (P =
0.001) was observed in the test group, but not in the control
group. Further, in the test group, a significant (P = 0.001)
difference was detected between the HI and LO categories at 1
month, but not in the pre-test samples. We conclude that a
vegan diet changes the faecal microbial flora in RA patients,
and changes in the faecal flora are associated with
improvement in RA activity.
Dietary therapy with Lactobacillus GG, bovine
colostrum or bovine immune colostrum in patients with juvenile
chronic arthritis: Evaluation of effect on gut defence
mechanisms
Malin M.; Verronen P.; Korhonen H.; Syvaoja E.-L.; Salminen
S.; Mykkanen H.; Arvilommi H.; Eerola E.; Isolauri E.
M. Malin, Medical School, Univ. of Tampere/Paediatrics Dept.,
Tampere University Hospital, Tampere Finland
Inflammopharmacology (Netherlands), 1997, 5/3
(219-236)
The effect of dietary therapy with a human Lactobacillus
strain GG (ATCC 53103), bovine colostrum, or bovine immune
colostrum with specific antibodies against anaerobic
intestinal bacteria on gut defence mechanisms were studied in
juvenile chronic arthritis. Thirty patients with juvenile
chronic arthritis were randomly allocated to receive a
freeze-dried powder of Lactobacillus GG, or bovine colostrum,
or bovine immune colostrum, for a two- week period.
Immunologic and non-immunologic gut defence mechanisms were
indirectly investigated in blood and faecal samples. In
patients receiving Lactobacillus GG, the median (interquartile
range) frequency of immunoglobulin-secreting cells, determined
by enzyme-linked immunospot assay, increased in the IgA class
from 1840 (690-2530) to 3480 (1030-13 170)/106 cells; p =
0.02. Likewise the median (interquartile range) frequency of
specific antibody-secreting cells against dietary antigens
increased during the Lactobacillus GG therapy in the IgM class
from 3.8 (1.4-5.0) to 11.2 (5.0-30.0)/106 cells; p=0.02. In
addition, Lactobacillus GG therapy decreased the median
(interquartile range) activity of faecal urease, which has
been associated with mucosal tissue damage, from 40.3
(21.7-54.3) to 28.6 (24.5-49.4) nmol min-1 (mg protein)-1; p =
0.10, while, in patients receiving bovine colostrum, faecal
urease activity increased (from 42.2 to 80.6; p = 0.04). All
findings were transient. We suggest that gut defence
mechanisms are disturbed in juvenile chronic arthritis and we
further suggest that orally administered Lactobacillus GG has
a potential to reinforce the mucosal barrier mechanisms in
juvenile chronic arthritis.
Inflammation and bone metabolism in rheumatoid
arthritis. Pathogenetic aspects and therapeutic options
Oelzner P.; Hein G.
Dr. P. Oelzner, Klinik fur Innere Medizin IV, Erlanger Allee
101, D-07740 Jena, Germany
Medizinische Klinik (Germany), 1997, 92/10
(607-614)
Background: Systemic osteoporosis is a common and
pathogenetically heterogenous complication in rheumatoid
arthritis. Various factors such as disease disease activity,
dosage and duration of glucocorticoid treatment and
immobilization are involved in pathogenesis of osteoporosis in
rheumatoid arthritis. Inflammation and bone metabolism:
Proinflammatory cytokines secreted by immunocompetent cells
have a role in the regulation of the activity of osteoblasts.
The effects of these proiinflammatory cytokines include the
inhibition of bone formation and an increase in bone
resorption. Interleukin-6 and nitric oxide induced in
osteoblasts by proinflammatory cytokines are likely to be
important mediators between these cytokines and the function
of osteoblasts and osteoclasts. Furthermore, disease activity
dependent changes in the secretion of glucocorticoids and in
vitamin D metabolism may be involved in the pathogenesis of
osteoporosis in this disease. Alterations of bone remodelling
associated with immobilization is an important factor of
systemic bone loss in the rheumatoid arthritis. Conclusion:
The inflammatory process in rheumatoid arthritis may cause
periarticular and systemic bone loss by various cytokine and
hormone mediated mechanisms. Concluding from these
pathogenetic mechanisms, bisphosphonates and active vitamin D
metabolites are likely to be effective therapeutic options in
osteoporosis associated with rheumatoid arthritis.
Serum-concentration of 25-hydroxy- vitamin D in
elderly people with rheumatoid arthritis
Falkenbach A.; Wigand R.; Stein J.; Kaltwasser J.P.
Dr. A. Falkenbach, Kranken- und Kuranstalt, Gasteiner
Heilstollen, A-5645 Bockstein Germany
Geriatrie Forschung (Germany), 1997, 7/3
(129-133)
Elderly people suffering from rheumatic diseases are at an
increased risk of vitamin D deficiency. Due to impaired
mobility they are less exposed to the sun. Additionally, the
capability of cutaneous vitamin D synthesis and renal
1alpha-hydroxylation decreases with age. The increased risk of
osteoporosis in vitamin D deficiency has been shown in various
studies. In rheumatoid arthritis immobilisation and cortison
treatment significantly contribute to the development of
osteoporosis. In these patients a lack of vitamin D should be
carefully avoided. In 21 ambulatory patients (8 male, 13
female; age, 60 to 75 years, mean 66.5 plus or minus 5.2
years) suffering from rheumatoid arthritis for 11.1 plus or
minus 10.6 years (range, 1 to 40 years) the serum
concentration of 25-hydroxyvitamin D (25(OH)D) was determined
by use of a commercially available RIA. In most patients the
serum concentration of 25(OH)D was surprisingly high. The
serum concentration of 25(OH)D ranged from 10.3 to 166 ng/ml
(mean 64.5 plus or minus 45.5 ng/ml). In 4 patients the
concentration was more than 100 ng/ml. The very high levels in
several patients with rheumatoid arthritis point at a
selfmedication (without prescription) by the patient. In 3
patients the measurement revealed a relative deficiency of
vitamin D, so that an additional supplementation (exposure to
UVB, oral vitamin D) should be adviced.
Vitamin E in activated arthrosis and rheumatoid
arthritis: What is the therapeutic value of
alpha-tocopherol?
Miehle W.
Dr. W. Miehle, Reha-Klinik Wendelstein, BfA - Rheumazentrum,
Kolbermoorer Str. 56, D-83043 Bad Aibling Germany
Fortschritte der Medizin (Germany), 1997, 115/26
(39-42)
Known and recognized mechanisms of action of
alpha-tocopherols are the grounds for the use of vitamin E in
activated arthrosis or rheumatoid arthritis. This is also
supported by the positive clinical results obtained in
double-blind studies. On this basis, a change in the
evaluation of these substances has taken place in recent
years. Initially characterized as 'unorthodox',
'unconventional' or 'additive' therapy, the term now applied
tends to be 'adjuvant accepted' therapy. The results of
double-blind studies and clinical empiricism support the
following hyperthesis: The pathogenetic substrate 'free oxygen
radicals' increases quantitatively from activated arthrosis to
(bland, mild) chronic polyarthritis. This could explain the
graded differentiated antioxidative (or hypothetically the
'central-analgesic') effects of alpha-tocopherols. While there
still is no causal treatment with the alpha-tocopherols - pain
alleviation and anti-inflammatory effect - are similar to
those achieved with non-steroidal antiinflammatory drugs, the
potency of which, however, is superior.
Concentration of selenium in erythrocytes of
patients with rheumatoid arthritis in relation to clinical and
laboratory signs of inflammation
Heinle K.; Adam A.; Gradl M.; Wiseman M.; Adam O.
Prof. O. Adam, Rheumaeinheit Universitat, Orthopadische
Klinik, Harlachingerstrasse 51, D-81547 Munchen Germany
Medizinische Klinik (Germany), 1997, 92/SUPPL. 3
(29-31)
Patients and Methods: Seventy patients with definitive
rheumatoid arthritis were matched to built 2 groups, which
were double-blind and randomized allocated to supplementation
with sodium-selenit 200 microg/d or placebo for 3 months,
each. Both groups were given fish oil fatty acids (30 mg/kg
body weight), DMARDS were continued throughout the study,
while variations in steroids or NSAD were admitted. Results:
Selenium concentrations in erythrocytes of patients with
rheumatoid arthritis were 85.1 plus or minus 26 microg/l, and
significantly lower than found in an average German population
(123 plus or minus 23 microg/l). During the observation period
of 3 months normal selenium concentrations were not restored,
despite supplementation higher than RDA. At the end of the
experimental period the selenium supplemented group showed
less tender or swollen joints, and morning stiffness.
Selen-supplemented patients needed less cortison and NSAD than
controls. In accordance with clinical improvement we found a
decrease of laboratory indicators of inflammation (C-reactive
protein, alpha2-globuline, prostaglandin E2). Conclusion: No
side effects of supplementation with selenium were noted,
which can be considered as adjuvant therapy in patients with
rheumatoid arthritis.
Methyl- vitamin B12 blocks the CD28 co-stimulatory
pathway in human T cells and its possible therapeutic
application for T cell-mediated diseases, including rheumatoid
arthritis
Nagafuchi H.; Suzuki N.; Takeno M.; Sakane T.
Japan
Japanese Journal of Rheumatology (Netherlands), 1997, 7/1
(35-45)
The effects of methyl-vitamin B12 have been examined on
human T cell activation induced by stimulation of T cell
receptor (TCR)-CD3 and an accessory molecule, CD28. When T
cells in the presence of 10% mitomycin-treated non-T cells
were stimulated with anti-CD3 mAb at the optimal
concentration, methyl-B12 did not inhibit T cell
proliferation. However, when T cells were stimulated with the
suboptimal concentration of anti-CD3 and anti-CD28 mAbs,
methyl-B12 exhibited potent inhibition of T cell
proliferation. Methyl-B12 did not affect cell surface
expression of the CD3 and CD28 molecules of T cells.
Methyl-B12 inhibited a 29 kDa protein tyrosine phosphorylation
that was specifically induced by anti-CD3 and anti-CD28 mAbs.
Similarly, T cell proliferation of patients with rheumatoid
arthritis (RA), which is representative of T cell-mediated
disease was inhibited by methyl-B12, when T cells were
stimulated by anti-CD3 and anti-CD28 mAbs. These results
suggest that methyl-B12 modulates lymphocyte function through
blockade of the CD28 signaling pathway and that methyl-B12 may
have T cell inhibitory activity that is applicable for
treating patients with RA.
Effects of cyclosporin on joint damage in
rheumatoid arthritis. The Italian Rheumatologists Study Group
on Rheumatoid Arthritis.
Ferraccioli GF; Bambara LM; Ferraris M; Perpignano G;
Cattaneo R; Porzio F; Accardo S; Mattara L; Zoppini A; Benucci
M; Ostuni PA; Pasero G
Rheumatic Disease Unit, Universit of Udine, Italy.
Clin Exp Rheumatol (Italy) May-Jun 1997, 15 Suppl 17
pS83-9
According to the most recent literature, few antirheumatic
drugs can claim disease-controlling properties over the
anatomical joint damage in rheumatoid arthritis (RA). A small
number of studies have favored one or another of the available
agents, in particular parenteral gold salts, sulphasalazine
and methotrexate, but the evidence regarding their efficacy is
not convincing when analysed using methodological criteria
known to be important in evaluating radiologic evidence of
joint damage. The radiologic results in long-standing RA
patients have shown that CsA may be of benefit in reducing
disease progression. Data from the second year of a clinical
trial designed to compare the disease-controlling,
anti-rheumatic properties of CsA with those of conventional
disease-modifying anti-rheumatic drugs (DMARDs) in early RA
support the hypothesis that CsA may be useful in delaying the
appearance of new joint erosion. (32 Refs.)
Management of rheumatoid arthritis: Rationale for
the use of colloidal metallic gold
Abraham G.E.; Himmel P.B.
Dr. G.E. Abraham, Optimox Corp., 2720 Monterey St., Torrance,
CA 90503 United States
Journal of Nutritional and Environmental Medicine (United
Kingdom), 1997, 7/4 (295-305)
Gold salts of monovalent gold (AU I) with a gold-sulfur
ligand (aurothiolates) are the only form of gold currently in
use for the management of rheumatoid arthritis (RA).
Aurothiolates have limited success and are associated with a
high incidence of side-effects. Metallic gold (AUo) is
non-toxic and used extensively in dentistry. Monoatomic
metallic gold is generated in vivo from AU I salts, during
oxidation to trivalent gold (AU III). Monoatomic gold tends to
form clusters of colloid particles. It is postulated that the
active ingredient in aurotherapy is AUo and the side-effects
are caused by AU III. To test this postulate, ten RA patients
with long-standing erosive bone disease not responding to
previous treatment were recruited from a private practice.
Clinical and laboratory evaluations were performed prior to
oral administration of 30 mg of colloidal AUo daily and
thereafter weekly for 4 weeks and monthly for an additional 5
months. There was no clinical or laboratory evidence of
toxicity in any of the patients. The effects of the colloidal
gold on the tenderness and swelling of joints were rapid and
dramatic, with a significant decrease in both parameters after
the first week, which persisted during the study period. The
mean scores for tenderness and swelling were, respectively,
for pre- and post-1 week 58.8 and 18.2 (p < 0.01) and 42.5
and 15.9 (p < 0.01). By 24 weeks of gold administration,
the mean scores were ten times lower than the pre-treatment
levels being, respectively, 5.4 and 3.3 for tenderness and
swelling. As a group, there was a significant improvement of
functional status by 24 weeks of gold therapy: three patients
were in clinical remission and one patient's status improved
from totally disabled to full-time work. Evaluated
individually, nine of the ten patients improved markedly after
24 weeks of colloidal gold at 30 mg/day. The cytokines
interleukin-6 (IL-6) and tumour necrosis factor alpha
(TFN-alpha), the immune complexes IgG and IgM, and rheumatoid
factor were significantly suppressed by the colloidal gold.
The results of this open trial in ten patients with
long-standing erosive RA not responding to previous treatment
support the postulate that colloidal gold is indeed the active
ingredient in aurothiolate therapy and that the side-effects
are mainly due to the AU III generated by oxidation of AU I.
Colloidal AUo could become an effective and safer alternative
to the aurothiolates in the management of RA patients.
Methotrexate in rheumatoid arthritis. Folate
supplementation should always be given
Morgan S.L.; Baggott J.E.; Alarcon G.S.
Dr. S.L. Morgan, Department of Medicine, Division of Clinical
Nutrition, UAB Station - Webb 256A, 1675 University Boulevard,
Birmingham, AL 35294-3360 USA
BioDrugs (New Zealand), 1997, 8/3 (164-175)
Methotrexate is now the disease-modifying antirheumatic
drug prescribed most frequently for the treatment of
rheumatoid arthritis. Methotrexate is an antifolate that
inhibits methylation reactions and reactions of amino acid,
purine and pyrimidine metabolism. Toxic manifestations of
methotrexate administration for rheumatoid arthritis (at
relatively low doses compared with those used in cancer
chemotherapy) include cytopenias, gastrointestinal
intolerance, liver disease, pulmonary injury, central nervous
system dysfunction, skin rashes and nodulosis. Delayed wound
healing and increased risk for infections with opportunistic
organisms also occur. Some of these toxic manifestations
respond to supplementation with folates (folic acid or folinic
acid (calcium folinate)). The folate status of patients has
been shown to be impaired after prolonged treatment with
methotrexate, and poor baseline folate status is an
independent risk factor for subsequent toxicity. Numerous
studies have now documented that folic acid, even in high
doses, and moderate doses of folinic acid are beneficial in
preventing methotrexate toxicity without affecting efficacy.
In this article we present-guidelines and rationale for
monitoring methotrexate therapy, and guidelines for folate
supplementation during methotrexate therapy for rheumatoid
arthritis. It is our recommendation that folic acid should be
empirically supplemented in all patients at the initiation of
methotrexate therapy. This regimen is associated with a high
benefit :risk ratio and is likely to be cost effective.
The influence of topical application of Oeparol (R)
(evening primrose oil) on skin neovascular response induced in
mice by leucocytes of rheumatoid arthritis patients
Sommer E.; Skopinska-Rozewska E.; Demkow U.; Balan B.;
Kleniewska D.; Barcz E.; Marczak M.
E. Sommer, Zaklad Immunologii, Instytut Gruzlicy i Chorob
Pluc, ul. Plocka 26, 01-138 Warszawa Poland
Reumatologia (Poland), 1997, 35/2 (166-170)
Aberrant neovascularisation occurs in several diseases such
as psoriasis, rheumatoid arthritis, and neoplasia, and plays
an important role in their pathogenesis. Antiangiogenic
therapy seems to be a valuable addition to classical
pharmacotherapy for diseases dependent on uncontrolled
neovascularisation. It is widely known that plant substances
may modulate functions of immune cells without several side
effects. In recent years there have been edited a lot of
reports on the beneficial effects of primrose extracts rich in
unsaturated fatty acids, and different mineral substances. The
aim of our study was to estimate the influence of primrose oil
(Oeparol (R) Agropharm) on angiogenic activity of human
leucocytes of 7 healthy blood donors, and leucocytes with
excess angiogenic activity from 5 rheumatoid arthritis
patients. Cells were grafted intradermally to immunosuppressed
Balb/c mice. On the day of implantation and on the following
2nd and 3rd day the primrose oil was applied on the sites of
injection. After 72 hours mice were sacrificed and new blood
vessels were counted. Primrose oil has decreased high
angiogenic activity of leucocytes of rheumatoid arthritis
patients, and has had no influence on healthy donor cells.
Periarthritis humeroscapularis: Alternative pain
treatment with magnet plasters
Bettermann A.A.
Chir. Klin., Univ. Krankenh. Eppendorf, 2000 Hamburg 20
Germany, West
Ther. GGW. (Germany, West), 1982, 121/8
(487-492)
Traditional methods of physical treatment of humeroscapular
periarthritis (IR heat application, packs and medicinal baths,
short wave and massage) have only a brief effect and
necessitate much equipment and personal assistance. Also, they
have to be combined with pharmaceutical treatment, application
of acetosal and corticosteroids, local injection of
corticosteroids and combination preparations with vitamin B12,
local anesthetics, etc., which impose physical and mental
stress. Apart from the risk of side effects, this form of
chronic treatment is very expensive. A trial is reported which
leads to the conclusion that the use of magnet plasters in
various forms of humeroscapular periarthritis constitutes real
therapeutic progress.
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