Adult Health in Focus
PUCRS to be home to first brain bank of cocaine / crack users in south of Brazil
One of the projects that is embraced by PUCRS-PrInt, an institutional project that was awarded grants in support of Capes’ Institutional Program of Internationalization, Biopsychosocial Aspects Associated with an Individual’s Health in Adult Life, brings together faculty from different areas in connection with researchers from 22 institutions in the following countries: South Africa, Belgium, Canada, China, Spain, USA, Finland, Italy, United Kingdom and Switzerland. One of such institutions is US-based Mayo Clinic, the world’s leading non-profit medical care provider.
Coordinated by Dr Tatiana Irigaray, the studies look at the aspects of health through two major tracks: clinical and experimental. In the clinical track, researchers aim to investigate health in a comprehensive way. The experimental track seeks to understand the impacts of early environment stress on adult behavior, routes to neurotoxicity and their possible connection with neurological and psychiatric disorders and mechanisms of bacterial resistance. As a result, the project’s researchers hope to design intervention and prevention practices.
Being embraced by the theme Health in Human Development, the initiative started this year, and is expected to be concluded in 2023. The project congregates researchers from the following Graduate Programs: Medicine and Health Sciences, Pediatrics and Child Health, Cellular and Molecular Biology, Psychology, Dentistry and Computer Science as well as Brain Institute researchers. In 2019 and 2020, funding has been alloted for 11 faculty missions abroad, 5 training programs, 8 doctoral research internships, 8 visiting professors in Brazil, 2 senior visiting professors from abroad and 6 postdoctoral fellows with experience abroad.
Brain Bank to advance new investigations
PUCRS is about to have the first brain bank of cocaine / crack users in the South of the country. “As a research complex, the University will do whatever it takes to validate in the investigation on neuropsychiatric diseases,” Prof. Rodrigo Grassi de Oliveira, coordinator of the study, says. The PUCRS PrInt will make it possible for the institution to strengthen its partnership with Consuelo Walss-Bass of the University of Texas, USA, who has developed a methodology for collecting and storing tissues to study brain disorders. The Texas-based researcher is scheduled to come in October to assist in the development of this structure, which will be part of PUCRS’ Biobank. She will also make her contribution to psychological autopsy. It is not enough to store the patient’s tissues, it is necessary to interview the family to know more about them, whether the patients suffered from mental disorders, for instance.
In cooperation with the US group, the research project led by Grassi de Oliveira aims to investigate whether the DNA alterations in the blood of cocaine users can be found in the brain. So far, the blood of 172 users and 125 healthy individuals has been studied. After the analysis of 850,000 DNA regions, in the group of 172 users, the group identified 34 genes with significant methylation, that is, alterations in the characteristics of cells. The most important of such alterations has been found is S100A8, which is involved in immune response. In the analysis of brains of 11 healthy individuals and 32 users of various types of drugs, conducted in the USA, a different gene was identified, but the immunological signaling pathway was that of the same S100A8 receptor.
In Grassi de Oliveira’s view, these findings change the perspective of the treatment. “We always think that cocaine influences the reward and pleasure systems. We now know that in addition to risky behavior, drug abuse makes them more susceptible to infections. “In actuality, this is no surprise, since HIV rates among crack users are at 20%, in contrast with rates among the general population, at 0.8%.
The Enigma of Pre-Eclampsia
The Chicago Lying-in Hospital recognized renowned obstetricians and hang plaques on its walls in tribute of such professionals. However, one of them is empty. It has been reserved for the scientist who finds out about how to treat pre-eclampsia, the gestational hypertension disorder that affects 3% of women and is the main cause of maternal and fetal mortality all over the world, making up a total of 23%. These findings took nephrologist Carlos Eduardo Poli de Figueiredo aback, as he photographed the front side of the building. His group in the Graduate Program in Medicine and Health Sciences has been investigating the mechanisms of this disorder for decades. The condition begins after the 20th week of pregnancy and may cause circulation problems and consequently, kidneys, lungs and heart problems.
In collaboration with the University of Nottingham and King’s College, both in England, and the Mayo Clinic, USA, the group has taken the initial steps. “These partnerships advance the exchange of information and contribute to staff development,” Poli says.
The thing about pre-eclampsia is the placenta, since it is often necessary to deliver the baby in order to save the mother’s life. “This is a difficult decision for the obstetrician, because it is only after the 34th week that the fetus is mature.” Pre-eclampsia is characterized by a dysfunction in the endothelium, the interior surface of veins that causes blood to circulate to the tissues. The researchers have identified an increased action of an enzyme called phosphodiesterase, in pre-eclampsia women. This enzyme prevents vessel dilation.
“Some drugs in the market will inhibit their action, such as sildenafil, Viagra, but there’s a long way to go until you get to conduct a clinical trial to test it on pregnant women.” If large-scale use is far-fetched, Poli says that studies can lead to the definition of markers that assist in the diagnosis. The following faculty members are participating in the project: Dr Bartira Pinheiro da Costa, Dr Ana Elizabeth Figueiredo, Dr Ivan Antonello and Dr Domingos D’Avila.
Challenging Alzheimer’s and Meningitis
Researchers at the Brain Institute are looking to find out about the role played by ureases in neurological disorders, such as Alzheimer’s and meningitis. Ureases are enzymes produced by bacteria that cause various types of diseases. This is the first step toward a larger goal: to identify molecules that inhibit these proteins and have a therapeutic effect against infections caused by microorganisms that affect the Central Nervous System (CNS).
Epidemiological studies have pointed that Helicobacter pylori infection had consequences on Alzheimer’s disease. These effects can lead to gastritis and gastric cancer. This pathogen produces large amounts of urease, which is critical to the bacterium’s survival, as it neutralizes stomach acid. Half of the world’s population is infected with H. pylori (75% do not show symptoms), and the percentage of patients with Alzheimer’s is much higher. The group led by Professor Célia Carlini has identified that urease loosens the bond between cells not only the epithelium (tissue that covers exposed surfaces and cavities), but also the endothelium (cell layer that covers the vessels). Once it is found in blood circulation, this mechanism could facilitate the circulation of urease into the CNS.
In insects, it has been shown that plant ureases affect the electrical communication between cells. The group now characterizes the neurotoxic effect in mammalian models, as they are studying, for example, what happens in the hippocampus (considered to be the home to memory) of mice treated with the proteins.
The second part of the research seeks to understand the relationship between meningitis in newborns and Proteus mirabilis, which causes infections in the urinary tract. It seeks to detect the presence of urease in the cerebrospinal fluid (one of the components of the nervous system) of infants hospitalized at São Lucas Hospital. The fluid has already been collected for diagnostic purposes and the identification of the bacteria. Then, follow-up studies of the cases are expected to be conducted. The idea is to assess whether patients with urease-positive CSF had the most severe cases of meningitis.
The study involves the following researchers: Two CNPq 1A (top level) research fellows – Dr Jaderson Costa da Costa and Dr Célia Carlini; Dr Magda Lahorgue Nunes and postdoctoral fellows Felipe Kalil and Augusto Uberti, as well as Master’s and PhD students. International partners at the Universities of Louvain (Belgium) and Shanghai (China) will contribute to the training of PUCRS personnel in electrophysiology methodologies. These methods will evaluate the electrical communication between the neurons and between neurons and muscles.