The Pharmaceutical Journal
Vol 280 No 7492 p287
8 March 2008

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Drug delivery by tattoo?

Colourful past of the humble carrot

Biological batteries

Wine mouthwash

Drug delivery by tattoo?

Tattooing is an ancient tradition used in a variety of cultures, including those in Asia, Africa and Australasia. The practice was filtered into the west by Captain James Cook, whose sailors incorporated the practice of “tattow” or “tatatow” as used by the Tahitians in the South Pacific.

Nowadays the tattoo has become a symbol of beauty, rebellion and self-expression.

In a new study by Martin Müller, German scientists suggest that tattooing can by used as a means of DNA drug delivery, which in the past has been subject to the challenges of poor cellular absorption.

In an article in Genetic Vaccines and Therapy for February 2008, the group reports that it has found tattooing to be an effective method for delivering DNA vaccines.

Using a coat protein from the human papillomavirus as a model for a DNA vaccine antigen, they compared delivery by tattooing with standard intramuscular injection into the skin of mice. Both methods were tested with and without molecular adjuvants that are often given to boost the immune response.

The tattoo method gave a stronger humoral and cellular response than intramuscular injection, even when adjuvants were included in the latter. When tested, the tattooed DNA vaccine produced at least 16 times higher antibody levels than the equivalent number of intramuscular injections with adjuvant. In addition, adjuvants enhanced the effect of intramuscular injection, but not of tattooing.

So how does it work? Tattooing is an invasive procedure using a vibrating needle to insert pigment, or in this case DNA, into the top layers of the skin. By breaking the skin’s barrier it provokes an immune response which is believed to increase the efficacy of this method.

The introduced genetic material can enter into the epidermal and dermal layers of the skin. The tattoo can be carried out over a large area of skin, thereby exposing more cells to the DNA.

In the age of great genetic discoveries, this method may provide a novel type of drug-delivery with great potential.

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Colourful past of the humble carrot

The carrot has been part of human diet for at least 5,000 years. Early studies show that the first carrots were white, purple, red, yellow, green and black — anything but orange. The vegetable’s orange colour came about in the 1500s, when patriotic Dutch growers cross-bred the red variety with a mutant yellow strain from North Africa. The resulting orange was subsequently adopted as the royal vegetable in honour of the House of Orange.

As well as for their colour, carrots are well known for their antioxidant activity. New work by Jay Morris, published in the January 2008 issue of Proceedings of the National Academy of Sciences, means that Peter Rabbit’s favourite food may soon have more to offer than beta-carotene.

Calcium is important for a variety of cellular functions. Perhaps most well known is its role in bones and teeth. Inadequate calcium uptake may play a role in osteoporosis. In the UK the recommended daily amount is 700mg, which is approximately equivalent to a pint of milk. Dairy foods, although popular, can be difficult for some people to digest in sufficiently high quantities and also for vegans for whom the alternatives are leafy vegetables and nuts.

Morris’s group has genetically engineered carrots to increase the levels of cellular plant calcium transporters. Subsequent tests show that their carrots contain twice as much calcium in the edible portion of the vegetable than normal varieties. To test whether these levels were bioavailable, the group labeled the carrots with isotopic calcium and fed them to mice and humans. Calcium incorporation into bones was then measured. In both mice and human studies, the calcium levels obtained were significantly higher (by 40 per cent) than from control carrots.

These findings suggest that fortifying vegetables with this mineral could have benefits for people seeking an alternative source of calcium, and is perhaps an extension into this vegetable’s tailored past.

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Biological batteries

Escherichia coli, often associated with food poisoning, may become a powerful player in the search for alternative energy sources.

Hydrogen is a renewable, clean and efficient gas. It is a key ingredient in fuel-cell technology, which has the potential to power everything from portable devices to cars and even entire power plants. It can be produced by a process known as “cracking water”, which separates the hydrogen from the oxygen. However, this is an expensive process, requiring vast amounts of energy.

E coli has three active hydrogenases, as well as a system for synthesising hydrogen from formate. By selectively deleting six specific genes in E coli’s DNA, Thomas Wood’s group (Microbial Biotechnology, January 2008) massively enhanced the bacteria’s naturally occurring glucose-conversion process. The result was a 141-fold increase in hydrogen production to create a bacterium that produces the largest amount of hydrogen to date.

Biological methods such as this are promising as they do not require a great deal of energy to produce and use sugar, an existing, easily available product. However, as yet, studies are in early stages and it will be some time before we see such biological batteries.

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Wine mouthwash

Moderate wine consumption has beneficial effects on human health. The antioxidant and antiradical properties, particularly of red wine, are attributed to the high polyphenol content. These are found in large amounts in pomace, the fermented seeds and skins that are discarded after grapes are pressed.

Wine has been shown to possess antimicrobial activity. Several strains of oral streptococci are capable of initiating the formation of dental plaque, which plays an important role in the development of caries and periodontal disease in humans.

A study by Olga Padilla-Zakour, published in the July 2007 issue of the Journal of Agricultural and Food Chemistry suggests that polyphenols from pomace may have antibacterial effects. The group obtained red wine grapes and pomace from wineries in New York state and prepared polyphenolic extracts from these.

When tested, all the extracts inhibited the bacterial enzymes glycosyltransferases, a process thought to help anchor bacteria onto the teeth and protect colonies. The bacteria were also shown to produce less acid when treated with the extracts. However, none of the extracts tested were bactericidal.

Naturally effective antimicrobial agents against oral pathogens could play an important role in preventing dental caries. It should be noted that it is the compounds in the wine, and not the wine itself that is beneficial. Swilling your mouth with Merlot is unlikely to have beneficial effects.