KEEPING CALM

Benzodiazepines [e.g. Valium] are the most prescribed anxiolytics and are used by a broad population. However, benzodiazepines can cause unwanted side effects, including sedation, development of tolerance, and withdrawal symptoms after long-term administration. Rupprecht et al. (p. 490; published online 18 June) now find that a translocator protein (18-kD) ligand, XBD173, is a fast-acting anxiolytic agent, both in animals and humans, which lacks the unwanted side effects of benzodiazepines and provides a promising target for novel clinically effective anxiolytic drugs.

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Translocator Protein (18 kD) as Target for Anxiolytics Without Benzodiazepine-Like Side Effects

By Rainer Rupprecht et al

Abstract

Most antianxiety drugs (anxiolytics) work by modulating neurotransmitters in the brain. Benzodiazepines are fast and effective anxiolytic drugs; however, their long-term use is limited by the development of tolerance and withdrawal symptoms. Ligands of the translocator protein [18 kilodaltons (kD)] may promote the synthesis of endogenous neurosteroids, which also exert anxiolytic effects in animal models. Here, we found that the translocator protein (18 kD) ligand XBD173 enhanced -aminobutyric acid–mediated neurotransmission and counteracted induced panic attacks in rodents in the absence of sedation and tolerance development. XBD173 also exerted antipanic activity in humans and, in contrast to benzodiazepines, did not cause sedation or withdrawal symptoms. Thus, translocator protein (18 kD) ligands are promising candidates for fast-acting anxiolytic drugs with less severe side effects than benzodiazepines.

Science 24 July 2009: Vol. 325. no. 5939, pp. 490 - 493





Grow your own teeth: Breakthrough in the lab may spell the end of dentures -- one day

Scientists have made teeth from stem cells in a world first that could make dentures a thing of the past. They looked like normal teeth, were sensitive to pain and chewed food easily. While the experiments were on mice, they pave the way for people to 'grow their own teeth' as required. The technique could also be adapted to other organs, allowing hearts, lungs and kidneys to be grown inside the body to replace parts worn by age or damaged by disease.

The Japanese study focused on stem cells - 'master cells' with the ability to turn into other cell types. The researchers from the Tokyo University of Science identified two types of stem cell, which together contain all the instructions for a fully grown tooth. The cells were grown in the laboratory for five days until they formed a tiny tooth 'bud'. This was then transplanted deep into the jawbone of a mouse that had had a tooth removed. Five weeks later, the tip of the tooth broke through the gum. And after seven weeks, it was fully-grown, the journal Proceedings of the National Academy of Sciences reports.

The researchers, who repeated the experiment many times, also showed that the new, bioengineered teeth were fully-functional. Dr Kazuhisa Nakao said: 'Every bio- engineered tooth erupted through the gum and had every tooth component such as dentine, enamel, pulp, blood vessels, nerve fibres, crown and root.' Importantly, the rodent recipients had no trouble eating.

The cells used were take from mouse embryos, but the researchers believe it should be possible to make teeth from other types of cell as well. They are now looking for suitable cells in people. Possibilities include skin cells and cells from the pulp inside teeth. They also have to work out how to control the size of the bio-engineered teeth, as those grown in the experiments were slightly smaller than usual. The process would also have to be speeded up if it was to be used on people as human teeth take years to form.

However, the pioneering technology could one day allow those with teeth missing to fill the gaps in their smile without having to resort to false teeth, bridges or synthetic implants. Experts believe that using 'living' teeth rather than artificial ones would be better for oral health and may also provide a more natural 'bite'. Bio- engineered teeth are likely to cost around £2,000 each - a similar price to the implants used at the moment.

But Britain's 11 million denture wearers should not throw away their fixative creams and gels quite yet. The technology is still at a very early stage and the Japanese researchers believe it will not be widely used by dentists for at least 15 years. Despite this, British experts said it was an important landmark.

Professor Robin Lovell-Badge, a stem cell researcher at the National Institute for Medical Research in London, said the work was 'excellent' and highlighted the promise of using bio-engineering to make complex structures. But he cautioned that the researchers had yet to find cells suitable for use in people.

Professor Damien Walmsley, of the British Dental Association, said: 'If you lose a tooth at the moment, one of the options is a metal implant. If you could have a natural replacement, that would be good.' Natural-looking replacements-also have massive psychological benefits for self-conscious patients.

The technique of creating cell 'buds' could be applied more widely to grow other organs, such as hearts, kidneys and livers, inside the body. Lead researcher Professor Takashi Tsuji said: 'The ultimate goal of regenerative therapy is to develop fully-functioning bioengineered organs that can replace lost or damaged organs following disease, injury or ageing. 'Our study makes a substantial contribution to the development of bio- engineering technology for future organ replacement therapy.'

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