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Untold potential

Once considered a solution in search of a problem, lasers are playing an ever greater role in health care

Bright smile: in dentistry, lasers cut and mold teeth and also reduce infection

LÉO RAMOSBright smile: in dentistry, lasers cut and mold teeth and also reduce infectionLÉO RAMOS

In the 1960s, American physicist Arthur Schawlow’s playful demonstrations of the invention he helped create earned him the nickname “Laser Man.” In one of his favorite presentations, he used a laser gun to pop a Mickey Mouse-shaped balloon that had been placed inside a clear balloon. In the test, a red laser beam lasting half a millisecond passed through the wall of the outer balloon without damaging it, concentrating its energy instead on the dark wall of the inner balloon and popping it. This simple experiment—which Schawlow recounts in his book Lasers and their uses, published in 1983—illustrates the principle behind one of the first applications of the laser: its ophthalmological use in the prevention of retinal detachment. By penetrating a few layers of tissue without damaging them and then leaving tiny lesions on the retina—the thin layer of cells that absorb light at the back of the eye—the laser prompts scarring and thus forestalls detachment and possible vision loss.

Since the laser was first used in ophthalmology, many advances have been made in its application to health care. Physicists, engineers, and technical specialists have grown more skilled in producing this very pure-colored light, which has an extremely dense beam that can be emitted in either continuous waves or split-second pulses. They have devised a broad gamut of laser types, now employed in fields as diverse as cardiology, dermatology, dentistry, and physical therapy.

Today’s lasers can cut, peel, and destroy living tissue in the blink of an eye. The tool can also repair blood vessels or furnish cells with extra energy, helping them beat infection and regenerate. In step with progress abroad, Brazilian researchers have been testing and refining the use of lasers and LEDs (light-emitting diodes, which, like the laser, can control the color and power of light) to aid in the diagnosis and treatment of various health problems. Some of these applications are still experimental.

One of the most active groups in the field is based at the University of São Paulo (USP) in São Carlos. There, the team of physicist Vanderlei Bagnato and dentist Cristina Kurachi has been at work for a little over 10 years to develop a laser or LED therapy to identify and treat skin tumors. In partnership with doctors from Amaral Carvalho Hospital—a leading cancer center in Jaú, São Paulo—the researchers assisted in producing a Brazilian version of a cancer treatment method that relies on a photosensitizing agent made from aminolevulinic acid and a laser or LED, which aids in defining tumor edges and destroying diseased cells. Known as photodynamic therapy (PDT), the treatment uses light to turn on the aminolevulinic acid that has been absorbed by tumor cells and activate the production of toxic substances that kill cancer cells.

Test using green LEDs to eliminate fungi

EDUARDO CESARTest using green LEDs to eliminate fungiEDUARDO CESAR

Fighting skin cancer
In recent years, Bagnato and his collaborators have been testing the safety and efficacy of PDT in the fight against basal cell carcinoma, the most common and least aggressive form of skin cancer, which accounts for nearly 130,000 new cases a year in Brazil. Their broadest trial involved 297 people who were seen at 27 dermatology centers in Brazil. Physicians trained by dermatologist Ana Gabriela Salvio applied PDT to 366 carcinomas that had a maximum diameter of two centimeters and maximum thickness of two millimeters. The strategy eliminated the tumor lesion in at least 70% of the cases, according to their article published in Photodiagnosis and Photodynamics Therapy in 2014.

“The response is better when the lesion is diagnosed with the aid of ultraviolet light,” states Kurachi. If further studies prove that the treatment is effective, researchers plan to make it available through the country’s public health system. “It could become a useful tool in Brazil, where people sometimes wait up to a year before receiving treatment for a skin tumor,” says the scientist, who tries to use laser in the early detection of melanoma, the most aggressive and deadliest form of skin cancer.

The work of the São Carlos team goes beyond oncology. Researchers are currently testing other photosensitizing agents and specific colors of light to eliminate nail fungus and accelerate the healing of wounds that are hard to close, a common problem for diabetes sufferers. In collaboration with dentists from the states of São Paulo, Paraná, and Bahia, Bagnato and Kurachi are trying to tailor PDT to fight the bacteria and fungi that cause mouth infections (see Pesquisa FAPESP Issue nº 181).

Photodynamic therapy session to treat skin cancer

EDUARDO CESARPhotodynamic therapy session to treat skin cancerEDUARDO CESAR

At the USP School of Dentistry in São Paulo, dentist Carlos de Paula Eduardo and his team have been using lasers in studies to restore oral health for the past 25 years, a pioneer effort in Brazil. Eduardo founded the Special Laboratory for Laser Dentistry (Lelo) in 1990 after returning from an internship at Kyushu University in Japan. Since then, various aspects of the odontological use of high- and low-level lasers have been the subject of some 250 master’s theses and doctoral dissertations at Lelo, with topics ranging from surgical application (precision cutting of teeth and soft tissue) to the prevention of inflammation and infection to tissue recovery.

One of the group’s valuable contributions was demonstrating that low-level laser treatment soothes mucositis, an inflammation of the mucous membranes that line the mouth; it affects 40% of people who undergo chemotherapy and 90% of those who receive a bone marrow transplant to restore their immune system following leukemia treatment. Working with teams abroad, Eduardo and dentist Walter Niccoli Filho, of São Paulo State University (Unesp) in São José dos Campos, tested the effect of laser treatment on 70 people who had undergone a bone marrow transplant. Seven to thirteen applications were given from the first day of preparation for the transplant to the third day after the procedure. The red laser proved more efficacious than the infrared in reducing inflammation and both performed better than the placebo, although neither eliminated the mucositis.

Since they began their work with low-level lasers, Eduardo and his team have tested a range of application strategies in order to identify one that is effective in preventing the recurrence of labial herpes. Caused by a virus that lies dormant in the nerves and lymph nodes, this infection triggers outbreaks of painful sores, fever, and muscle aches during periods of stress, when the immune system is weak. Both the frequency and intensity of the infection were decreased through the application of red laser to the lips, according to the findings of a study by the Lelo group, which followed patients for three years. “It took us 15 years to arrive at this treatment protocol, which can now be adopted in clinical practice,” says Eduardo.

More energy and less fatigue
The same light that hastens the death of cells can also protect them. Nivaldo Parizotto, physical therapist and senior professor at the Federal University of São Carlos (UFSCar), has found that some laser and LED colors have a reinvigorating effect on muscles. In research conducted by Parizotto and his former doctoral student Cleber Ferraresi, in partnership with researchers from Harvard University, the application of red and infrared lights over the skin reduced fatigue and improved muscle performance. In experiments on mice, use of the lights doubled the ability to exert physical effort. Decreased fatigue was attributed to the cell’s increased ability to produce energy, which rose tenfold.

Although the mechanism is still not fully understood, the application of red and infrared light before intense exercise protects muscle cells from mechanical damage. In a more recent study, Parizotto and Ferraresi used an LED and laser device designed by Bagnato’s group and developed by a company from São Carlos to conduct phototherapy on a professional men’s volleyball team in São Bernardo, São Paulo.

From 40 to 60 minutes prior to games, the athletes received 20 to 60 seconds of therapy over their thighs, the musculature that suffers greatest stress during this sport. The light therapy reduced damage to muscle cells, especially at the intermediate and maximum doses (40 and 60 seconds). The researchers presented their findings in a paper published by Laser in Medical Science in May 2015, where they suggest that the light helps stabilize the membranes of cell muscles and prevent rupture. The same group had shown earlier that the application of infrared light in conjunction with exercise can have systemic effects: it boosts muscle performance, helps the cardiovascular system function better, and accelerates weight loss (see Pesquisa FAPESP Issue nº 187). “The use of light seems to help control the subclinical inflammation associated with obesity and enhance the ability to burn fat,” says Parizotto.

Physician Maria Cristina Chavantes, specialist in the clinical and surgical application of lasers and current president of the Brazilian Society for Laser Medicine and Surgery, has for some years been coordinating pilot clinical trials to assess the therapeutic potential of this tool in an array of situations. After training in Japan, Germany, and the United States, Chavantes started using high-level lasers in the late 1980s to remove tumors that had invaded the trachea and bronchial tubes of lung cancer sufferers, compromising their respiration; although the procedure did not remove the cancer, it made it easier for patients to breathe. During her time at Henry Ford Hospital, she also assisted James Ausman’s team in applying laser in neurosurgery. In the early 1990s, at the invitation of cardiac surgeon Adib Jatene (1929-2014), Chavantes set up a laser unit at USP’s Heart Institute (InCor), where the cardiologist Radi Macruz was the world pioneer in the use of lasers to remove fatty deposits (atheromas) from the lining of the aorta, in 1979.

At InCor, Chavantes helped surgeons Luís Alberto Dallan and Sérgio Almeida de Oliveira use a very high power laser to make small channels through the heart wall and partly restore the organ’s ability to pump blood. The procedure was carried out on people with serious heart disease for whom no alternative treatment had presented itself. Of the 40 patients who underwent surgery, 34 had fewer symptoms one year after surgery. Around 1996, Chavantes had her first contact with low-level lasers and began using the tool in other situations where no satisfactory treatment was available, such as the healing process after extensive operations, like cardiovascular surgery or spinal repair.

More recently, Chavantes and her team at Nove de Julho University have been testing how the anti-inflammatory action of low-level lasers might support healing after gastric bypass surgery, stimulate thyroid gland function, and treat a chronic inflammatory condition of the genital region known as lichen sclerosus. She is also evaluating the application of lasers over different areas of the body to help lower blood pressure in hypertensive pregnant women. Chavantes believes that because low-level lasers are safe, non-invasive, and painless, they hold great potential for clinical use in many areas of medicine, “especially in promoting healing and pain relief.” Not bad for a tool that shortly after its invention was deemed useless by some or—in the words of physicist Charles Townes, who together with Schawlow laid the theoretical foundations for laser emitters—was a solution in search of a problem.

Projects
1. CEPOF – Optics and Photonic Research Center (nº 2013/07276-1); Grant Mechanism Research, Innovation and Dissemination Centers (RIDC); Principal Investigator Vanderlei Salvador Bagnato (IFSC-USP); Investment R$24,240,400.00 (all FAPESP).
2. Use of low-level laser and light-emitting diode therapy to increase muscle performance: from in vitro and experimental studies to clinical applications (nº 2010/07194-7); Grant Mechanism Scholarship in Brazil – Doctorate; Principal Investigator Nivaldo Antonio Parizotto (UFSCar); Awardee Cleber Ferraresi; Investment R$111,006.00 (FAPESP).
3. Clinical trial of the effect of laser radiation (high- and/or low-level) on the treatment of post-radiation therapy oral mucositis (nº 2005/57578-8); Grant Mechanism Regular Research Grant; Principal Investigator Carlos de Paula Eduardo (FO-USP); Investment R$26,161.90 (FAPESP).
4. Evaluation of photodynamic therapy in the treatment of herpes labialis: an in vivo, randomized and blind study (nº 2013/12317-9); Grant Mechanism Scholarship in Brazil – Post-Doctorate; Principal Investigator Carlos de Paula Eduardo (FO-USP); Awardee Karen Muller Ramalho Eboli; Investment R$94,191.90 (FAPESP).
5. In vitro study on the use of low-level laser in cardiac muscle cell proliferation (biostimulation using gallium arsenide) (nº 2001/11865-5); Grant Mechanism Scholarship in Brazil – Master’s; Principal Investigator Maria Cristina Chavantes (Universidade do Vale do Paraíba); Awardee Ritchelli Ricci; Investment R$26,400.00 (FAPESP).

Scientific articles
RAMIREZ, D. P. et al. Experience and BCC subtypes as determinants of MAL-PDT response: preliminary results of a national Brazilian project. Photodiagnosis and Photodynamic Therapy. V. 11, p. 22-6, 2014.
SCHUBERT, M. M. et al. A phase III randomized double-blind placebo-controlled clinical trial to determine the efficacy of low-level laser therapy for the prevention of oral mucositis in patients undergoing hematopoietic cell transplantation. Supportive Care in Medicine. 2007.
FERRARESI, C. et al. Light-emitting diode therapy in exercise-trained mice increases muscle performance, cytochrome c oxidase activity, ATP and cell proliferation. Journal of Biophotonics. 2015.
FERRARESI, C. et al. Light-emitting diode therapy (LEDT) before matches prevents increase in creatine kinase with a light dose response in volleyball players. Lasers in Medical Science. 2015.

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