The Pharmaceutical Journal
Vol 279 No 7481 p658
8 December 2007

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Out with the frying pan, in with the frog

How the sea cucumber may help vision

Chicken feed

Footloose and fancy free?

Blood transfusion difficulties

Out with the frying pan, in with the frog

Antimicrobial peptides (AMPs) are cationic short proteins (with sequences of 15–30 amino acids) produced by all animals from insects, to frogs, to humans. These molecules are believed to have antibacterial, antiviral and antifungal effects and even some cytotoxic effects on cancer cells.

The major challenge with using AMPs as medicinal compounds is the fact that, given orally, they are susceptible to breakdown by proteases in the gastric tract, rendering them inactive.

At a recent meeting of the American Chemical Society in Boston, Neil Marsh from the University of Michigan, reported that using the theories of “non-stick”, his team have developed AMPs that are resistant to proteases.

Teflon technology involves fluorinating carbon polymers so that the surface becomes not only slippery, but also chemically inert. Adapting the same idea, the team used pexiganan, a synthetic analogue of an AMP isolated from the Xenopus laevis frog. They replaced certain residues in pexiganan with fluorinated alternatives, which resulted in a new peptide that the researchers named fluorogainin-1.

Preliminary in vitro studies have shown that not only is fluorogainin-1 resistant to the proteases trypsin and chymotrypsin, but also that it retains the same, if not more, antibacterial capabilities against certain bacteria. These results are extremely promising, and may pave the way for future developments of other drugs sensitive to similar degradation.

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How the sea cucumber may help vision

The cornea, a clear dome like structure, protects the contents of the eye as well as refracting light onto the retina. Though lacking blood vessels, it is densely innervated making it one of the most sensitive organs of the body. Disorders of the cornea can occur due to inflammation, trauma, infections and genetic conditions. These can, in some cases, cause visual impairment and blindness.

Where the damage is severe, one option is to replace the cornea. Keratoplasty, or corneal transplantation, can be carried out using donated corneal tissue. However, like many other transplantations, there is a shortage of donors.

Several attempts at creating a synthetic keratoprostheses have been made. These are often devised using plastic or biocompatible materials that would allow them to integrate into the surrounding tissue. This has not been without success. However, Garret Matthews of University of South Florida, recently reported that his team have produced completely natural, cornea-like structures.

These have been produced using collagen taken from the sea cucumber. Matthews’s group manipulated them using techniques such as centrifugation, into a film of aligned fibrils. These form a transparent surface of varying thickness and curvature that appear to have the same structure as the mammalian cornea.

As yet, these keratoprostheses have not been tested in humans.

The researchers claim that by using biologically derived collagen, these transplants should have minimal immunological impact and may provide a safe and cost-effective alternative to synthetic prostheses.

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Chicken feed

A new type of chicken feed has been developed by researchers at the University of Delaware. It contains phytase, an enzyme that increases phosphorus digestion.

Phosphorus is essential in chicken feed but is generally provided in a form that is difficult to digest. This results in high levels of water-soluble phosphorus in the litter, which can then leach into waterways causing algal blooms and detrimental effects to fish life.

One study (Poultry Science, October 2006) has shown that chickens fed phytase and 25-hydroxycholecalciferol supplements excreted the lowest levels of phosphorus compared with controls (fed a low phosphorus diet). These supplements had no undue effects on the birds’ health.

Combining phytase or 25-hydroxycholecalciferol with chicken feed significantly could reduce the phosphorus load to the environment.

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Footloose and fancy free?

Do spiders get caught in their own webs? The simple answer is yes. They are not immune to the stickiness of their silk; however they do take some precautions.

First, the spider weaves a number of “dry” silk strands around the outside of the web where she may sit. In a conventional orb web (that is the classical type with the spiral thread), the spokes that radiate from the centre of the web are also non-adherent and may provide a pathway for a spider to navigate across the web.

Secondly, in order to ensure minimal contact spiders seem to walk on the tips of their legs, with their head and body often raised high above the structure. Their feet are also believed to have special apparatus that helps them avoid becoming stuck. The mechanism by which this occurs is still debatable.

Spiders are also diligent groomers and frequently clean their legs by passing them through their jaws. As well as freeing them of debris, this action may also coat their feet with an oily substance that prevents them from getting stuck.

Blood transfusion difficulties

Blood transfusions are not always as successful as one might imagine. Studies show that recipients of transfusions do not always show the expected increase in delivery of oxygen to tissues and can result in an increase in ischaemic events.

As well as carrying oxygen, red blood cells, which consist of the metallo-protein haemoglobin, are also vehicles for nitric oxide (NO) transportation, forming S-nitrosohaemoglobin (SNO-Hb). NO is a potent vasodilator that works directly on vascular smooth muscle. This small molecule is highly reactive and susceptible to breakdown as soon as it is released.

Studies of banked blood show that the levels of SNO-Hb significantly decline during storage. A new study (Proceedings of the National Academy of Sciences, October 2007) hypothesised that this reduction of NO could the impair vasodilation and compromise blood flow.

Renitrosylation of banked blood during storage not only increased the SNO-Hb content, but also restored the vasodilatory activity of the blood. Increasing SNO-Hb levels in banked blood may improve transfusion efficacy.