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Year of Chemistry

Reinforcements for medicine

Substances and molecular analyses innovate in treatment and diagnoses

EYE OF SCIENCE / SCIENCE PHOTO LIBRARYSuperabsorbent polymer made from acrylic acid can be used in diapersEYE OF SCIENCE / SCIENCE PHOTO LIBRARY

In the midst of advances in equipment, drugs, techniques and procedures linked to medicine, the central protagonist usually remains hidden: chemistry. Although the subject merits much more discussion time, a fair amount was presented at the last set of talks of the International Year of Chemistry cycle in the session “Intelligent chemistry at the service of medicine,” coordinated by Leandro Helgueira, from the Institute of Chemistry of the University of São Paulo (IQ-USP). The topic brought together a panel on November 9, comprised almost exclusively of chemists: Luiz Henrique Catalani, from IQ-USP, Sidney Ribeiro, from the Chemistry Institute of the Paulista State University (Unesp) in Araraquara, Etelvino Bechara, from the Diadema campus of the Federal University of São Paulo (Unifesp), and Jerson Lima Silva, from the Federal University of Rio de Janeiro (UFRJ) – the only doctor in the group.

The chemistry of polymers, which is responsible for products like plastics, was the focus of Luiz Henrique Catalani, who showed just how old is the use of substances known as biomaterials that act along with biological systems in substituting some tissue, organ or function in the body. “Neolithic skeletons show that sutures were already known 32,000 years ago,” was the example he gave. And there’s a lot more. Two thousand years ago the Chinese, Aztecs and Romans already used gold for repairing teeth and George Washington, president of the United States between 1789 and 1797, used false teeth made from rhinoceros bone.

For prosthesis to be functional it is essential to think about the appropriate relationship between the host tissues and the biomaterial, a property known as biocompatibility. “The in vivo environment is not static;” Catalani recalled, “it’s a dynamic process.” In search of this good relationship, increasingly the chemical properties of the materials developed when in contact with biological tissue are being analyzed. Such is the case of the use of Teflon and polyester in ligaments, tendons and intervertebral discs.

A type of substance that his group has been developing in the Laboratory of Polymeric Biomaterials is electro-wiring. These are nanometric scale wires produced by injecting an electrical charge into a drop of polymer solution, which stretches the sticky substance. The possible application of these wires is to form meshes on the same scale as cells, like a framework into which they fit, thus serving as a substratum for tissue recuperation.

Another important focus of Catalani’s laboratory at USP is the hydrogel-based dressing. “The idea that a dressing must be dry is wrong,” he explained. The ideal thing is that it’s moist, light, non-abrasive and highly permeable, adhering to the healthy skin and not the wound. This is no small matter, and does not necessarily stop there: the substances that comprise the nanogels can have both a fungicide and bactericide effect, contributing even more to the healing of wounds.

Hydrogels are also the focus of the Laboratory of Photonic Materials, coordinated by Sidney Ribeiro in Araraquara. This is a material comprising 98% water and 2% cellulose, with a three-dimensional, nanometric structure produced by bacteria from sugar. Synthesis by means of microorganisms is an important alternative due to the ecological impact of cellulose mills in terms of pollution and land occupation, with their eucalyptus plantations. “The cellulose extracted from plants is eco-friendly material, provided you’re far away from the planted areas and the producing industry,” he joked.

SIDNEY RIBEIRO LABORATORY / UNESPFibroin sponge with cellulose fibers for regenerating bone (left) and a bacterial cellulose membraneSIDNEY RIBEIRO LABORATORY / UNESP

The group has been managing to produce membranes with thicknesses that can range from micrometers to centimeters. The result is a transparent material that has high mechanical resistance and that can be used as a substitute for the skin in dressings on wounds that are difficult to treat. The group is working also with second generation materials, enriched with substances that have medicinal properties, like nanoparticles of silver or propolis.

The protein, fibroin, the main component of silk, dominates another line of research being carried out by Ribeiro. Brazil is the world’s third largest producer of this thread that is extracted from the cocoon of the Bombyx mori caterpillar. From these cocoons it is possible to extract fibroin, which in the hands of the researchers gives rise to technological materials with applications that range from medicine to optoelectronics, like magnetic sponges and luminous transparent films.

The group from Unesp is concentrating on the use of luminous materials for imaging in medicine. Important elements for this are rare earth, which can lead to more effective luminous markers for diagnosis and therapy. Ribeiro also dreams about solar lights and photovoltaic cells. The first customer will be FAPESP, which is funding the study, he joked, looking up at the lighting in the auditorium.

Altered organism
Etelvino Bechara is a lighting specialist and a pioneer in the studies of how and why glow-worms emit light. His group at USP has also explained the stains left by dragon flies on the paintwork of automobiles: they lay their eggs on them, attracted by the light that is polarized by the resin, which their eyes confuse with the surface of a lake.

But it was a very different theme that the chemist, now a professor at Unifesp in Diadema, took to the audience at the cycle of talks: the damage caused in the organism by poisoning by lead, a common element in the paints used for painting walls, in car batteries and in plastic toys, to mention just a few of the countless examples. Some historical figures recorded as suffering from this type of poisoning were composer, Ludwig van Beethoven, exposed to high lead concentrations because he used to visit print shops to control the printing of his scores, as well as artists, Vincent van Gogh and Candido Portinari, who were affected by the paints they used in their paintings.

The effects spread, because lead substitutes calcium and zinc ions in essential proteins in the organism, making the enzymes involved in aerobic metabolism and nervous transmission inactive. The inhibition of reactions involved in biosynthesis of part of the hemoglobin also leads to greater production of aminolevulinic acid (ALA), with a structure very similar to gamma-aminobutyric acid (Gaba), an essential substance in synapses. The result can include serious neurological and psychiatric damage, like antisocial and delinquent behavior. The oxidative stress caused by lead poisoning also has a mutagenic effect on DNA and generates malfunctioning in the liver and kidneys. ALA also induces the release of iron stored by the ferritin protein, damaging cell respiration and leading to a loss of physical resistance.

leo ramosLuiz Henrique Catalani, Jerson Lima Silva, Sidney Ribeiro and Etelvino Becharaleo ramos

With regard to behavior, Bechara also relied on studies with teenagers who had been imprisoned because of their criminal activities. On measuring the levels of lead in the organism, researchers discovered as the metal built up in the body there was a four times greater chance of aggressive attitudes. In 2005, in his search to confirm these international results, he was one of the coordinators of a study that evaluated lead levels in young people in the then-Febem, today Fundação Casa [Home Foundation]. “The relationship was confirmed, but the results were not more damning, because the project was blocked for unjustified reasons,” he said.

The chemist has not yet given up: he is still studying the association between lead and antisocial behavior and intends establishing an exposure treatment and prevention center at Unifesp. Meanwhile, it is already known that treatment with chelates and antioxidants may help lessen the oxidative stress caused by lead poisoning, but much of the damage cannot be reversed.

But the harmful effects in the brain do not come merely from external factors, as Jerson Lima Silva showed. Alterations in normal protein structures in the organism may be behind neurodegenerative diseases and cancer. In the latter case, the agent is the protein p53, which is a protection factor against the formation of tumors. A mutation that causes an incorrect doubling and, therefore, affects its structure may lead to an imbalance in the functioning of the genes and, as a consequence, to the development of some types of cancer, as is being proved in several studies. A curious effect reported by the speaker is that the mutated cell seems to have an effect on others, which also start behaving incorrectly and proliferate in an uncontrolled manner as if it were an infectious process.

This infectious effect is also typical in diseases caused by prions, like spongiform encephalopathies, which were “popularized” by mad cow disease. In this case, it has already been shown that the relationship between the prion “an altered protein” and water molecules is essential for structural stability. “It seems that it’s hydration that controls protein conformational diseases,” said Lima Silva, who has also been trying to understand the action of genetic agents – DNA and RNA – in the creation of these anomalous proteins.

In harmony with the subject discussed earlier on the same day, he recalled one of the pioneers in the structural study of molecules was British woman, Rosalind Franklin, who was not duly recognized for the role she played in elucidating the structure of DNA. “Now we have very different and more detailed techniques, but there are still unresolved problems that delay the development of drugs,” he stated.