Arthritis - The Cannabis Science

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The Cannabis Science
J Pharm Pharmacol. 2006 Mar;58(3):351-8.

Arthritis and Cannabinoids: HU-210 and Win-55, 212-2 Prevent IL-1Alpha-Induced Matrix Degradation in Bovine Articular Chondrocytes In-Vitro.
Mbvundula EC, Bunning RA, Rainsford KD.
Biomedical Research Centre, Sheffield Hallam University, Sheffield, S1 1WB, UK.

Cannabinoids have analgesic, immunomodulatory and anti-inflammatory properties and attenuate joint damage in animal models of arthritis. In this study the mechanisms of action of the synthetic cannabinoid agonists, HU-210 and Win-55,212-2, were studied to determine if they affected interleukin-1 alpha (IL-1alpha)-induced proteoglycan and collagen degradation in bovine nasal cartilage explant cultures and prostaglandin E2 (PGE2) production in primary cultures of bovine articular chondrocytes. The effects of the inactive enantiomer, Win-55,212-3, were compared with those of the active enantiomer, Win-55,212-2, to determine if the effects were cannabinoid (CB)-receptor mediated. The chondrocytes and explants were stimulated by IL-1alpha (100 U mL(-1) identical with 0.06 nM and 500 U mL(-1) identical with 0.3 nM, respectively). Proteoglycan breakdown was determined as sulfated glycosaminoglycan (sGAG) release using the dimethylmethylene blue assay. Collagen degradation was determined as hydroxyproline in the conditioned culture media and cartilage digests. PGE2 was determined by ELISA. Expression of cannabinoid receptors, CB1 and CB2; cyclooxygenase-1 and -2 (COX-1 and COX-2); inducible nitric oxide synthase (iNOS); as well as activation of nuclear factor-kappa B (NF-kappaB) in chondrocytes were studied using immunoblotting techniques and immunofluorescence.

The results showed that HU-210 and Win-55,212-2 (5-15 microM) significantly inhibited IL-1-alpha stimulated proteoglycan (P < 0.001) and collagen degradation (P < 0.001). Win-55,212-2 (5-10 microM) also significantly inhibited PGE2 production (P < 0.01). At 5 microM, Win-55,212-2 inhibited the expression of iNOS and COX-2 and activation of NF-kappaB. Chondrocytes appeared to constitutively express cannabinoid receptors CB1 and CB2. It is concluded that biologically stable synthetic cannabinoids protect cartilage matrix from degradation induced by cytokines and this effect is possibly CB-receptor mediated and involves effects on prostaglandin and nitric oxide metabolism. Cannabinoids could also be producing these effects via inhibition of NF-kappaB activation.
PMID: 16536902 [PubMed - indexed for MEDLINE]

[william morley]

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[vwxy336]

RUSTENBURG, South Africa (AFP) - Ricardo Clark admitted responsibility after his side's 2-1 defeat to Ghana in the last 16 of the World Cup on Saturday.

The United States midfielder was caught in possession after five minutes, allowing Kevin-Prince Boateng to run through and drive past Tim Howard to open the scoring.

With Ghana?s passing superb in the opening stages, and the USA in danger of being outplayed, Clark was booked for a crude foul on Boateng. His miserable night ended when he was withdrawn after 30 minutes for Maurice Edu
Clark was clearly disappointed, and US coach Bob Bradley made a point of hugging him on the touchline and explaining his decision.

"He just said he took me off because I had a yellow and if I got another one I?d get sent off," Clark explained. "It wasn?t the best performance from me. I had some good moments, but unfortunately one of my bad moments led to a goal on the counterattack. A player of my calibre and experience shouldn?t be making those mistakes."

The Eintracht Frankfurt midfielder received the ball on halfway, but seemed to stumble, gifting possession to Ghana?s Kwadwo Asamoah, who helped the ball on to Boateng.

"I kind of got the ball stuck in my feet," he said. "I think they played [the ball on] in the midfield. I got caught in my decision making, didn't react fast enough and the guy stole the ball. Unfortunately it led to the goal. I feel like I let my team down. I take full responsibility on the goal. I apologised for the goal (to the coach)."

Even a few minutes after the game, as Clark admitted culpability, it seemed it was an incident that he would play over and over in his mind, something that will haunt him. He admitted that what made it all the worse was that he hadn?t been able to stay on to try to rectify the mistake.

"Of course I wanted to stay on," he said. "But it's up to the coach."

The introduction of Edu seemed to tip the game in the USA's favour, particularly after the introduction of Benny Feilharber at half-time allowed Clint Dempsey to move into a more central position.

It was Dempsey who won a penalty after 61 minutes, beating John Mensah and then being tripped by Jonathan Mensah. Landon Donovan scored from the spot.

"I did think we'd win after the penalty-kick," Clark said."We were applying the pressure and could have had two or three goals but it didn't happen. Ghana are a good team. They wouldn't have made it this far if they were not."

Jonathan Mensah similarly thought the game was slipping away from Ghana when Donovan equalised. "When they came up 1-1, we had to make sure we weren't down, we had to fight to get another goal and we did," he said.

"When the game was over 90 minutes we knew we had to pick ourselves up and fight and that's what we did. We talked to each other in the group, got together and that was what gave us the spirit and strength."

Asamoah Gyan thumped the winner three minutes into extra time. Mensah insisted that his side don?t fear Uruguay, who stand between them and being the first African team to reach a World Cup semi-final.

"All the other African teams are out so the whole of Africa is looking at us. So we need to deliver.

"We're not worried about Uruguay. When we qualified to play the USA we weren't worried and we won, so we're going to do the same thing."

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