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Induction of ulcerative colitis in mouse by bx isolated from human UC

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Shit, why aint we heard of this? I havent scrutinized it yet.

========================

Gut. 2003 Jan;52(1):79-83. Related Articles, Links

Induction of experimental ulcerative colitis by Fusobacterium varium

isolated from colonic mucosa of patients with ulcerative colitis.

Ohkusa T, Okayasu I, Ogihara T, Morita K, Ogawa M, Sato N.

Department of Gastroenterology, Juntendo University, School of

Medicine, Tokyo, Japan.

BACKGROUND: Bacteria are implicated in certain forms of model chronic

colitis but the identity and role of bacteria in human ulcerative

colitis (UC) are uncertain. AIMS: To isolate pathogenic bacteria from

inflamed mucosa of patients with UC, to examine whether the bacteria

have a toxin to Vero cells, and to determine whether the toxin

induces UC-like lesions in animals. METHODS: Bacteria were isolated

from UC patients and supernatants from cultures were filtered and

tested for cytotoxicity to Vero cells. Bacterial cells producing the

cytotoxic supernatants were examined by polymerase chain reaction for

verotoxin genes. Culture supernatants of cytotoxic strains were

examined by high performance liquid chromatography for organic acid

concentrations. Mice were given enemas containing organic acid at the

mean concentration in the supernatants of cytotoxic strains to

ascertain whether colonic lesions appear in UC. RESULTS: Only

supernatants from cultures of Fusobacterium varium killed Vero cells.

Bacterial cells lacked verotoxin genes. Bacterial culture

supernatants contained high concentrations of n-butyric acid and the

mean concentration (32 mmol/l) was cytotoxic to Vero cells. Twenty

four hours after mice were given enemas containing either butyric

acid or F varium culture supernatants, colonic ulcers with crypt

abscesses, inflammatory cell infiltration, and apoptotic changes were

observed. CONCLUSIONS: Butyric acid in culture supernatants from

cultures of F varium caused UC-like lesions in mice. This study

indicates that F varium may be one of the elusive pathogenic factors

in UC.

PMID: 12477765 [PubMed - indexed for MEDLINE]

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> Shit, why aint we heard of this? I havent scrutinized it yet.

Its a free full text by the way. But I'm alot more interested in what

the group went on to do:

Ohkusa T et al

Effectiveness of antibiotic combination therapy in patients with

active ulcerative colitis: a randomized, controlled pilot trial with

long-term follow-up.

Scand J Gastroenterol. 2005 Nov;40(11):1334-42.

PMID: 16334443

" [Twenty consecutive chronic, active UC patients with F. varium

infection] were [randomized]. In the treatment group (n=10), patients

received an antibiotic combination consisting of amoxicillin 500 mg

t.i.d., tetracycline 500 mg t.i.d. and metronidazole 250 mg t.i.d.

for 2 weeks;

[Two WEEKS? Are you KIDDING ME???????]

in the control group (n=10), patients underwent colonoscopic

examination but were not given antibiotics. "

And then there was long term followup:

Before treatment At 3–5 months At 12–14 months

Symptom score

Antibiotics 3 (2–10) 3 (0–3) 2 (1–5)

No antibiotics 3 (2–9) 4 (2–8) 4 (3–8)

p-value* 0.113 0.022 0.004

These symptom scores are objectively calculated. Too bad the scale

doesnt seem to be real sensitive.

Its VERY interesting that improvement took so long to reach a maximum

after the termination of treatment.

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That's really wild!

- Kate

On Apr 16, 2006, at 2:38 AM, wrote:

> " [Twenty consecutive chronic, active UC patients with F. varium

> infection] were [randomized]. In the treatment group (n=10), patients

> received an antibiotic combination consisting of amoxicillin 500 mg

> t.i.d., tetracycline 500 mg t.i.d. and metronidazole 250 mg t.i.d.

> for 2 weeks;

>

> [Two WEEKS? Are you KIDDING ME???????]

>

> Before treatment At 3–5 months At 12–14 months

>

> Symptom score

> Antibiotics 3 (2–10) 3 (0–3) 2 (1–5)

> No antibiotics 3 (2–9) 4 (2–8) 4 (3–8)

> p-value* 0.113 0.022 0.004

>

> Its VERY interesting that improvement took so long to reach a maximum

> after the termination of treatment.

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> Before treatment At 3–5 months At 12–14 months

>

> Symptom score

> Antibiotics 3 (2–10) 3 (0–3) 2 (1–5)

> No antibiotics 3 (2–9) 4 (2–8) 4 (3–8)

> p-value* 0.113 0.022 0.004

[...]

> Its VERY interesting that improvement took so long to reach a

maximum

> after the termination of treatment.

Actually, nix that last comment. These data dont really show a delayed

apex of improvement at all.

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