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Pro-Test: standing up for science
Pro-Test: Standing Up For Science
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Archives for: November 2008

30/11/08

Permalink 09:30:34 pm, by Tom, 233 words, 3992 views   English (UK)
Categories: Information

Discworld author calls for more funding of Alzheimer's research

The author Terry Pratchett, who is best known for writing the hugely inventive Discworld novels, has handed a petition to number 10 Downing street calling on the government to increase spending on research into the treatment of Alzheimer's disease. The petition has been signed by 20,000 people, including over 100 leading scientists, and
is backed by the Alzheimer's Research Trust, the UK's leading research charity for dementia.

The Alzheimer's Research Trust strongly supports high quality animal research, and currently funds several projects that involve the use of animals. That they do so is hardly a surprise since animal research has made a major contribution to the development of potential treatments for Alzheimer's disease, some of which we discussed recently on our science blog.

Pro-Test wishes Terry Pratchett and the Alzheimer's Research Trust every success on this campaign. Oxford University is an important centre for research into Alzheimer's disease, indeed the new biomedical sciences building for which we have campaigned will soon house some of this work, so we understand just how vital it is that it advances.

Interestingly the BBC report listed Tony Benn, a long time opponent of animal research, among those who have signed the petition. Could this be a sign that he is now willing to listen to the scientists working on Alzheimer's disease rather than his friends in the animal rights movement? Well one can only live in hope!

Regards

Paul Browne

20/11/08

Permalink 11:54:32 am, by Tom, 413 words, 3301 views   English (UK)
Categories: Information

Trachea Transplant Makes History

Many years of research have today culminated in what could arguably be deemed an historic medical event. Claudia Castillo, a Columbian woman aged 30 who now lives in Spain, has been pronounced 'in excellent health' five months after a significant tissue-engineering operation following irreparable damage from tuberculosis.

As a result of a long line of experiments using pigs, cows, dogs, rats and sheep during the 1990s, Spanish doctors were able to work with researchers in Bristol to decellularise a donor trachea from a 51-year-old woman and successfully implant it into Ms Castillo. Decellularisation is needed in order to ensure that the receiver's body does not reject the transplanted organ: however, this must not take place to such a degree that the integrity of the donor organ's structure is compromised negatively. Significantly, the donor trachea was repopulated with Ms Castillo's own stem cells, rather than xenogeneically- or allogeneically-produced cells being used, and unlike other transplant patients, Ms Castillo will not have to take immunosuppressants as part of her post-operative care (a positive, given how far immunosuppressants can leave patients vulnerable to infection), as her body recognises her own cells. The other option for Ms Castillo would have been to have a lung removed, which could potentially have shortened her life.

The findings of the research, published in The Lancet (1), describe how the decellularised donated trachea was rotated in a bioreactor with Ms Castillo's stem cells before transplantation. The donor trachea, after time in the bioreactor, looked identical to a normal trachea, and some time after the operation had taken place, the divisions between Ms Castillo's own trachea and the donated trachea could barely be seen.

Even in 2007 (2), researchers using animals were writing cautiously about their results and claiming that more research needed to be carried out. However, to be able to start clinical trials on humans within the next 5 years is perhaps in another league, paving the way for the future of transplantation in humans. Animal research in Europe over the past ten years showed extremely positive results in both pigs and dogs, and Ms Castillo is the first human in which the same techniques have been applied. The success of her treatment allows enormous progression both in terms of transplant development and in terms of the use of extra-cellular matrices.

Regards

Bianca Summons

(1) Macchiarini, P. et al., "Clinical Transplantation of a tissue-engineered airway", The Lancet, Online Publication 19th November 2008
(2) Badylak, S.F. et al., "The extra-cellular matrix as a biologic scaffold material", Biomaterials 28: 2007, 3587-3593

17/11/08

Permalink 03:28:54 pm, by Tom, 680 words, 1807 views   English (UK)
Categories: Information

Fighting hospital superbugs

In recent years the "hospital superbug" Clostridium difficile has gained notoriety as a major cause of illness and death among patients, and poses a particular danger to the elderly. C.diff is found naturally in the intestines of a minority of the human population and usually poses no threat, but when the bacterial population of the gut is disturbed, for example by treatment with antibiotics that kill a broad range of bacteria, it can quickly multiply, producing toxins that cause diarrhea and colitis. Rigorous cleaning can help prevent the spread of C.diff but it cannot prevent it entirely because many patients will be carrying the bacteria upon admission to hospital. As you'd expect treatment with antibiotics is the usual practice when C.diff infection is diagnosed, but here there is another problem; C.diff is resistant to most available antibiotics. Only two antibiotics, metronidazole and vancomycin are commonly used to treat it. This lack of antibiotic options is of grave concern since neither antibiotic is successful in clearing the infection in all patients, but the greatest worry for the medical community is that C.diff will evolve resistance to one or both of these antibiotics, a development that would drastically reduce treatment options.

The development of new drugs that can kill C.diff is a priority, so it was good to hear that a new antibiotic named OPT-80, developed by the San Diego based Optimer Pharmaceuticals, has performed well in a large clinical trial. In the Phase III trial OPT-80 was found to be as good at clearing C.diff infection as vancomycin and better at preventing a reoccurrence of the disease. It was also found in an earlier Phase II trial to be free from adverse reactions (1), due in part to the fact that it is very selective for C.diff, leaving other gut bacteria intact, and to the fact that it stays in the intestine, with almost none crossing into the bloodstream.

These properties were selected during early research when OPT-80, then named tiacumicin B, was identified by Abbott Laboratories during screening of antibiotics produced by the bacterium Dactylosporangium aurantiacum for any that could be medically useful (2). Tiacumicin B was found to have a strong and selective anti-bacterial activity against C.diff in vitro. Good activity in vitro does not necessarily predict whether an antibiotic will clear an infection in a living patient, toxicity, accumulation in the wrong organs, or a poor metabolic profile can all scupper a promising drug, so the scientists at Abbott turned to the hamster, an animal in which the full spectrum of symptoms including diarrhoea and colitis following C. difficile infection are seen. In hamsters tiacumicin B was found to be as effective as vancomycin in treating C.diff and to stay within the intestine when given orally, just as was later observed in human patients. These results, and later pre-clinical safety studies which showed it to be safe even at high doses when given orally to rats and monkeys, lead to tiacumicin B, by now renamed OPT-80, entering clinical trials in human patients where it appears to be performing well.

Turning to another, and it must be admitted sexier, field of research Mo over at the Neurophilosophy blog has written a nice account of research by Japanese scientists who are producing brain tissue from embryonic stem cells. This research may in time aid the development of stem cell treatments for diseases such as Alzheimers and ALS but in the short term it should help scientists to develop better in vitro models of brain development and function, to be used in basic research and the evaluation of new drugs. Good work, and a blog worth keeping an eye on!

Regards

Paul Browne

1) Louie T. et al. "Clinical outcomes, safety and pharmacokinetics of OPT-80 in a phase 2 trial of patients with Clostridium difficile infection." Antimicrobial Agents and Chemotherapy, Published Online Oct 2008, DOI:10.1128/AAC.01442-07.

2) Swanson R.N. et al. "In vitro and in vivo evaluation of tiacumicins B and C against Clostridium difficile." Antimicrobial Agents and Chemotherapy, Vol. 35(6), pages 1108-1111 (1991). PubMed Central: PMC284295.

12/11/08

Permalink 04:07:01 pm, by Tom, 363 words, 11774 views   English (UK)
Categories: News

No more threats, no more fear, animal research is finally here!

The Oxford Biomedical Facility is finally complete after five bumpy years. Despite violence, arson, threats, intimidation and harassment, Oxford University has pulled through with its new animal research facility. This lab is setting a new "Gold Standard" in animal welfare, one that will meet and exceed the standards set by the Home Office regulations. The past five years have also witnessed increased understanding of the need for well regulated animal research, and we are honoured to have played our part in enabling the students and residents of Oxford to show their support for the new biomedical facility

The life-saving research that can now go ahead in the lab will include work on cancer, stroke, heart disease, diabetes, HIV, muscular dystrophy, motor neurone disease, epilepsy, Parkinson’s and Alzheimer’s. The lab will be using state of the art equipment to help further the 3Rs - Refinement, Replacement and Reduction.

Here's what Oxford University has to say about the 3Rs:
"In terms of replacement, the facility has been designed so that in the long-term future the space can be used flexibly, including for non-animal research. In terms of reduction and refinement, the facility will bring expertise onto one site, allowing for best advice. Oxford’s Veterinary Services team, which exists to advise on the welfare and health of Oxford’s research animals, has expertise in the 3Rs and will be in the building with training rooms and other facilities that represent a huge improvement from the space they had before."

The lab will contain 98% rodents, mainly transgenic mice, with non-human primates accounting for less than 0.5% of the animals in the lab.

"With the support of the students, the scientists and the public, the completion of the Oxford Biomedical Facility is a victory for both science and reason. It is our family, our friends, and ourselves who stand to gain from the lifesaving medical research that has marked Oxford University as a world leader in biomedicine . This lab represents not just better facilities for scientists, but also better welfare conditions for the animals within, showing Oxford University's commitment to the principles of Refinement, Replacement and Reduction in animal research."
- James Burgess, Pro-Test.

Cheers

Tom

07/11/08

Permalink 11:26:06 pm, by Tom, 523 words, 1909 views   English (UK)
Categories: Information

A better, safer TB vaccine

There's an interesting report in "Infection and Immunity" this week about the development of a safer and more effective tuberculosis (TB) vaccine (1), something that is certainly needed as the rate of TB infection is rising in many countries.

A major problem for the current TB vaccine, the BCG vaccine first developed in the 1920's, is that it is a live attenuated tuberculosis bacterium and so cannot be given to individuals whose immune system is compromised since even a weakened bacteria can cause deadly disease if the immune system is not functioning properly. This is a serious problem, especially in countries such as South Africa where there are high rates of HIV infection and a growing problem of multi-drug resistant TB. The effectiveness of the BCG vaccine in preventing TB infection is also lower than ideal, though it is very effective at preventing tuberculosis meningitis,and a new vaccine that can confer better protection is highly desirable.

Scientists at UCLA have developed a vaccine, given the name rBCG(mbtB)30, that promises to be both more effective at preventing TB infection and safer than the existing vaccine. They did this by genetically altering an improved BCG strain called rBCG30 that they had previously developed so that it now lacked a scavenger protein needed to obtain iron from its environment. rBCG(mbtB)30 only undergoes a limited number of cell divisions after vaccination, a change that the UCLA team hoped would severely limit its potential to multiply and cause disease in immunocompromised individuals.
To verify that the new vaccine had not lost it's improved ability to protect against infection Marcus Horwitz and his colleagues turned to the guinea pig. The guinea pig is an animal in which TB infection closely resembles human disease clinically, immunologically, and pathologically, and which has played an important role in TB research for over a hundred years, both in the development of antibiotics to treat the disease and vaccines to prevent it. They found that the new vaccine gave greater protection than the current BCG vaccine, though it wasn't quite as good as their previous rBCG30 vaccine. To evaluate the potential of the new vaccine to cause disease in individuals with compromised immune systems they turned to another animal model, the severe combined immunodeficiency (SCID) mouse that completely lacks an immune system. In SCID mice rBCG(mbtB)30 was found to be safer than the existing BGC vaccine, with fewer animals developing lethal TB infections.

This vaccine is very promising and a significant advance in terms of both safety and effectiveness over existing TB vaccines, though it still has room for improvement so I would ideally like to see it developed further before it is tested in human clinical trials. Having said that it is without doubt a step in the right direction, showing that a TB vaccine can be made simultaneously more effective and safer for individuals with weakened immune systems.

Regards

Paul

1) Tullius M.V. et al. "A Replication-Limited Recombinant Mycobacterium bovis BCG vaccine against tuberculosis designed for human immunodeficiency virus-positive persons is safer and more efficacious than BCG." Infection and Immunity p. 5200-5214, Volume 76, No. 11, pages 5200-5214 (2008). DOI:10.1128/IAI.00434-08

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