http://www.arthritis.org/resources/Arthritistoday/2006_archives/2006_09_10/Germ_
Warfare_p1.asp

Germ Warfare
Arthritis Today, SEPTEMBER-OCTOBER 2006
by Mary Anne Dunkin

Antibiotics for Arthritis

Antibiotics for Arthritis
New Insights -- Old Infections

Might antibiotics be useful for treating rheumatoid arthritis (RA), if
infections can be a trigger? Benefits have been shown, but not because
of the bacteria-fighting property of antibiotics. Instead, say experts,
some antibiotics may block cartilage-degrading enzymes called
metalloproteinases. Regardless of the specific mechanism, antibiotics
often are part of RA treatment plans.

In addition to broad-spectrum tetracycline antibiotics, including
tetracycline, minocycline and doxycycline, sulfa drugs are used. The
commonly prescribed disease-modifying anti-rheumatic drug sulfasalzine
(Azulfidine) - a combination of salicylate (the active ingredient in
aspirin) and a sulfa antibiotic - has been used for decades.

Use of antibiotics for RA started in the 1940s, when Thomas McPherson
Brown, MD, of the Rockefeller Institute in New York, began treating
arthritis patients with tetracycline after he and his colleagues
discovered an infectious microorganism in the joint fluid of RA
patients - a finding that has not been confirmed. Dr. Brown correctly
concluded that antibiotics helped RA, but he wrongly explained why the
treatment worked. For the next 50 years, the medical community largely
dismissed antibiotics for RA.

In 1995, however, results of a 48-week study sponsored by the National
Institutes of Health in Bethesda, Md., showed more than half of
patients taking minocycline had at least a 50-percent improvement in
the number of swollen joints and in joint tenderness. The minocycline
group also showed significant improvement in several laboratory
measures of disease activity, including blood tests such as erythrocyte
sedimentation (SED) rate, hematocrit, platelet count and rheumatoid
factor levels.

Studies are continuing, although recent results have been mixed. In a
study led by Jim O'Dell, MD, at the University of Nebraska Medical
Center in Omaha, patients taking the antibiotic doxycycline along with
methotrexate fared better than those taking methotrexate alone. But a
separate study, conducted at the University of Texas Health Science
Center in Houston, failed to show a benefit for minocycline in people
with scleroderma.

---------------------------------------------------------------------------------------

Promise of Tetracycline Antibiotic for Osteoarthritis

Article Date: 14 Jul 2005 - 0:00am (PST)

Study Shows Effectiveness of Doxycycline in Slowing Disease
Progression. A tetracycline antibiotic, doxycycline, has been
successfully used to treat a wide-range of bacterial infections. In
addition to its effects as an antibiotic, doxycycline has other actions
as a drug and, in laboratory studies with animals and with human
tissue, can inhibit the degradation of cartilage in a way that could be
useful for the treatment of osteoarthritis (OA). OA is a common form of
arthritis associated with pain and disability related to the breakdown
of cartilage, the tissue in the joint that absorbs shock and promotes
smooth movement.

On the strength of preclinical evidence, a team of rheumatologists
affiliated with six clinical research centers across the United States
conducted the first long-term clinical trial to determine the benefits
of doxycycline in the treatment of OA-particularly, OA of the knee.
Their findings, featured in the July 2005 issue of Arthritis &
Rheumatism ( http://www.interscience.wiley.com/journal/arthritis),
suggest that doxycycline may slow the progression of joint damage and
point to the need for further research into the drug's effect on the
signs and symptoms of this disease.

For the trial, the team recruited 431 overweight women between the ages
of 45 and 64 with moderately advanced OA in one knee. The subjects were
randomly assigned to receive either 100 milligrams of doxycycline or a
placebo twice a day for 30 months. At baseline, the 2 treatment groups
were roughly equal with respect to all demographic variables, body mass
index, and types of drugs taken for pain, as well as for the x-ray
severity of OA in the affected knee and the level of knee pain and
functional impairment. OA progression was assessed by measuring joint
space narrowing in the medial tibiofemoral compartment through X-rays
obtained at baseline, 16 months and 30 months. Severity of joint pain
was assessed every 6 months after a washout period of all nonsteroidal
anti-inflammatory drugs (NSAIDs) and analgesics.

71 percent of the subjects completed the treatment protocol.
Radiographs were obtained from 85 percent of all subjects at 30 months.
After 16 months of treatment, the mean loss of joint space width in the
diseased knee in the doxycycline group was 40 percent less than in the
placebo group. After 30 months, it was 33 percent less. Yet, despite
significantly slowing disease progression, d oxycycline did not reduce
the severity of joint pain. However, mean pain scores at baseline were
low in both treatment groups, leaving only limited opportunity to
demonstrate improvement in joint pain. On the other hand, the drug
significantly reduced the frequency with which subjects reported
increases in knee pain 20 percent or greater than the level of pain
they had at their previous semi-annual visit.

Notably, doxycycline seemed to have no effect on joint space narrowing
or pain in the relatively disease-free knee. In both knees in both
treatment groups, the rate of joint space narrowing was more than twice
as rapid in subjects who reported frequent increases in pain than in
those with a stable pain score. ?Joint pain may serve as an indicator
of synovitis that leads to cartilage destruction,? observes the study's
leading author, Kenneth D. Brandt, M.D.

Throughout the trial, fewer than 5 percent of all subjects reported
side effects. In general, doxycycline seemed to be well tolerated.
Subjects in the active treatment group experienced the unexpected side
benefits of fewer urinary tract and upper respiratory tract infections
than their placebo counterparts.

In conclusion, in this study, doxcycyline showed benefits in slowing
the rate of joint space narrowing in knees with established OA. Whether
this drug has any value in the early treatment and symptomatic
management of OA, however, will require further investigation.

Article : ?Effects of Doxycyline on Progression of Osteoarthritis:
Results of a Randomized, Placebo-Controlled, Double-Blind Trial,?
Kenneth D. Brandt, Steven A. Mazzuca, Barry P. Katz, Kathleen A. Lane,
Kenneth A. Buckwalter, David E. Yocum, Frederick Wolfe, Thomas J.
Schnitzer, Larry W. Moreland, Susan Manzi, John D. Bradley, Leena
Sharma, Chester V. Oddis, Steven T. Hugenberg, and Louis W. Heck,
Arthritis & Rheumatism , July 2005; 52:7; pp. 2015-2025. Article is
available via Wiley InterScience at
interscience.wiley.com/journal/arthritis.

http://www.rheumatology.org

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<<snip>>
iron chelation plays a prominent role in the tetracycline management of

African trypanosomosis
<<snip>>

Biokemistri
Nigerian Society for Experimental Biology
ISSN: 0795-8080
Vol. 16, No. 2, 2004, pp. 56-63
Bioline Code: bk04020
Full paper language: English
Document available free of charge

Biokemistri, Vol. 16, No. 2, 2004, pp. 56-63
Iron chelation excludes protein synthesis inhibition in the
tetracycline management of African trypanosomosis
Justine T. EKANEM, Titilayo O. JOHNSON, Iyabo S. ADENIRAN and Valeelat
OKEOLA
Abstract

Ribonucleotide reductase, an iron requiring enzyme necessary in the
production of deoxyribonucleotides required for replication in cell
division and proliferation is induced during the S phase of the cell
cycle. We have compared the trypanocidal properties of four antibiotics

that show bactericidal activities by destabilizing ribosome-mRNA
complex to inhibit protein synthesis. Tetracycline and oxytetracycline
that have iron chelating properties extended the lifespan of
trypanosome infected rats from 6 and 5 days of control to 15 and 12
days respectively while chloramphenicol and streptomycin that have no
iron chelating properties could not extend the lifespan of infected
rats. We confirm our earlier report that iron chelation plays a
prominent role in the tetracycline management of African
trypanosomosis.
Keywords
Tetracycline, iron chelation, T. brucei, growth inhibition

© Copyright 2004 - Nigerian Society for Experimental Biology

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