Friday, 22 August 2008

St. John's Wort interferes with Voriconazole (Vfend) Dose

St. John's Wort is commonly used around the world to treat depression. There is some scientific evidence to support its use for mild to moderate depression but this remains controversial as there is also evidence that suggests it has no such effect. This herb is also known to increase the levels of cytochrome P450 enzymes and that can cause problems for other drugs.

Voriconazole (Vfend) is one of the newer antifungal drugs that is in use to treat aspergillosis. Its concentration in the blood is reduced by the action of cytochrome P450 enzymes, so an increase in the level of those enzymes will reduce the amount of voriconazole available to attack fungal growth:
In vitro studies have indicated that voriconazole is metabolized by the cytochrome P450 isoenzymes 2C19, 2C9, and 3A4. Because long-term use of St. John's Wort (a cytochrome P450 inducer) could lead to reduced voriconazole exposure, concomitant use of these drugs is contraindicated.
If a patient is prescribed voriconazole it is therefore best if they do not take this herbal medication. The FDA in the US have required that a warning is added to Voriconazole medication prescribing information

Caspofungin Acetate (Cancidas) Approved for Pediatric Indications

Caspofungin acetate (Cancidas) is the first of a new class of antifungal drugs (echinocandins). It works by interfering with the mechanism a fungus uses to build its cell wall which is quite different to all other antifungal drugs which mostly work by inhibiting cell membrane synthesis. This makes it particularly useful when other drugs have been tried and failed as it attacks a different target - there would be little point in using an antifungal which tried to 'hit' the same target when inhibiting that target molecule has already failed.

As with most drugs approval is often granted in stages as research confirms or denies the efficacy of that drug in different patient groups. Caspofungin has been approved for some time for adult patients that had been treated and failed with other antifungals, but this new approval now allows use in children from 3 months to 17 years of age for the following conditions:
invasive aspergillosis in patients refractory or intolerant of other therapies. It also may be used as empiric therapy for presumed fungus infection in patients with fever and neutropenia.
Caspofungin was found to be superior to established drugs in particular circumstances in children in two separate papers and was thus granted approval for the US by the FDA.

Tuesday, 12 August 2008

Aspergillus causing problems in outer space

A russian spacecraft launch
Russian scientists have been exploring the causes of corrosion inside spacecraft (translation of original article). An initial (somewhat alarming) observation that manned spacecraft suffered from corrosion more than unmanned spacecraft prompted further investigation.

The corrosion in question is of the aluminium alloys widely used in spacecraft because they are lightweight and highly resistant to corrosion - normal chemical corrosion. Biocorrosion is the term coined to cover corrosion caused by living organisms growing on the metal surface (biofilm). The organisms can secrete acids and other corrosive chemicals such as ammonia which cause the damage.

Aspergillus versicolor has (amongst others) been isolated from spacecraft even though growth conditions are harsh, and it has been found that the conditions of high humidity and ultrasonic irradiation found in a spacecraft allow these organisms to grow well. They grow readily on most surfaces of the spaceship and contribute to microscopic caverns appearing on and in equipment/work surfaces along with Penicillium expansum, Cladosporium cladosporioides and others.

Monday, 11 August 2008

Improving nutritional content of crops using aspergillus

phytase structure
In many parts of the world the diet is limited and deficient in the nutrients needed to maintain a healthy body. There are many difficulties in providing a complete diet - both for humans and for their food animals - but the one we are focusing on here is called phytate.
Phytate is sometimes referred to as an 'antinutrient' because it locks up phosphates and minerals into a form most animals cannot digest because they lack the enzyme needed to break up phytate , and that enzyme is called phytase.

One effect of this problem is that foodstuffs for some animals (birds & pigs) must be supplemented with phosphates in order to replace the phosphates locked up inside phytate - increasing the cost of producing meat.

There is an additional problem concerning the environment. Foodstuffs rich in phytate are corn and soybean which are routinely the staple diet of fowl and pigs. Combine the effect of supplementary phosphates (not all of which are absorbed) and all that unabsorbed phytate on the living quarters of commercially produced chickens, turkeys & other fowl along with pigs and you have a lot of phosphate pollution. Microbes produce an abundance of phytase so the phytate does not last long once on the floor! Should that rich phosphate soup make its way into river systems or onto land the result can be eutrophication - severe pollution.

Ruminants such as cows, horses, deer & sheep make their own phytase and thus do not need extra phosphates .

Phytase is made by many microbes including Aspergillus, and it is known that the addition of phytase to feeds can aid uptake of phosphates along with other important minerals such as calcium, magnesium and iron. This has now been taken a step further and instead of adding phytase purified from aspergillus (which would be expensive as well as having the potential to cause health problems for people allergic to aspergillus), the phytase gene has been extracted from aspergillus and inserted directly into the crop DNA. When expressed alongside another gene from soybean called ferritin the resultant transgenic crop has far higher nutritional value without the need for supplements.

The potential for this technology has several benefits including for the environment, food safety and for the improvement of the diet of humans and animals. Whether or not foods manipulated in this way will enter the foodchain is a topic for a different column!

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