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It is small, 0.6 mm to 2 cm in size, but can cause considerable damage. Each year, the brown spider ( Loxosceles sp ) hits about 7,000 people in Brazil – 7,441 in 2016, the latest available data from Sinan, Health.
Her venom can cause skin necrosis, kidney failure, and even the death of victims – six years old that year.
To reduce these problems, scientists at the Butantan Institute (IB) have developed an ointment whose curative effects have already been demonstrated in tests conducted on cell cultures and animals.
According to the IB researcher, Denise Tambourgi, main supervisor of the work, the developed ointment is based on tetracycline, a substance known and already used as an antibiotic. "However, we used a lower concentration than would be microbicidal," he says.
"That is, less than that required to be considered an antibiotic, but we use it in an baday capable of interfering with the activity of sphingomyelinase D, the main component of spider venom and intervening in the inflammatory process and destruction of tissue (necrosis) and other effects. "
In addition to a skin lesion – which occurs in 80% of cases and may take months to heal – the bite of Loxosceles can also cause systemic effects in 20% of other victims, such as haemolysis (alteration, dissolution or destruction). red blood cells), platelet aggregation (which causes clots to form in the blood vessels that make circulation difficult or impede circulation), inflammation and kidney failure that can lead to death.
The history of Denise's research that led to the creation of the ointment is long. She began to decipher the main components of the brown spider toxin in 1994. To do this, she and her team relied on genetic engineering.
As each Loxosceles produces very little venom – about 30 micrograms – it would be very difficult to get the amount needed for the studies. The researchers then inserted a gene from it into the Escherichia coli bacterium, creating a bioproduction of sphingomyelinase D, and produced it in a volume sufficient for research.
Denise and her team discovered throughout the work that brown spider venom can cause, in addition to known effects, secondary reactions, triggered primarily by the protein sphingomyelinase D.
The study has decrypted the mechanism of action of the venom released by the brown spider as well as the systemic and cutaneous form of the disease. "I often say that the poison gives only "the beginning" and that the protein modifies the cells, he explains. "Then there is a deregulation of the organism, which leads to the production of proteases. function is to break the chemical bonds of other proteins, which causes cell death and necrosis. "
In summary, the study coordinated by Denise has deciphered the mechanism of action of the venom released by the brown spider as well as the systemic and cutaneous form of the disease.
l & # Antidote for skin
The first tests, carried out on culture of human cutaneous cells, more specifically keratinocytes and fibroblasts, and on animals began to be carried out in 2005 and prolonged until August 2018. [19659016] "We did several experiments, applying the venom of the brown spider to crops," says Denise. As expected, the cells would die. Then we expose them to toxin and tetracycline at multiple doses at the same time. We then found that the venom was no longer able to kill the cells. "
The researchers then went on to the next stage of work, which was the test in the animal." Rabbits were chosen for their good model. for the study of cutaneous necrosis caused by Loxosceles toxin, "says Denise." The lesion of this animal is similar to that which is formed in humans. We injected the poison into the skin and after a few hours we started treating them with an ointment containing tetracycline and lanolin. The latter went into the composition as it is able to bring the drug into the deeper layers of the skin. "
The results are encouraging: In rabbits treated with tetracycline, the lesion regresses rapidly." The ointment has reduced the size of the lesion by about "
Tetracycline being a drug already tested for several infections and therefore used commercially, it is not necessary to go through the" In fact, we only make a new application for this substance, "says the researcher.
This phase began in October, a total of 240 patients will be treated, including 120 with ointment and 120 with placebo, in 61 hospitals in Santa Catarina, where most bites occur and in which Denise has several partnerships Clusive with the UFSC (Federal University of UFSC), along with doctors, nurses and pharmacy and health professionals. to date, 20 patients are already treated
Those who receive a placebo will not remain untreated.They will receive what is used today for the bite, namely the specific antivenom serum of the brown or nonspecific, against arachnid toxins in general. The bites can also be treated with medications called corticosteroids, better known as corticosteroids.
If the results of the clinical tests are as expected, the ointment can reach the pharmacies. But there is no time limit for that. Once approved during testing, it still has to be published for use in humans and marketed by the National Health Surveillance Agency (Anvisa). If and when this happens, your market could be bigger than Brazil's.
In addition to accidents with Loxosceles in South, Central and North America in recent years, cases of bites have also occurred in Europe, with cases reported in countries such as Spain, France, Portugal and Italy. the death.
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