Topics:

• Basic optics, light phenomena, objective lenses and resolution.
• Wide field techniques; phase contrast, dark field and DIC.
• Fluorescence and confocal microscopy.
• 3D and live imaging.
• How to assemble figures for publications.
• Sample preparation.
• Practical sessions with microscopes.

The study that improves treatment for a type of schizophrenia, carried out by researchers from the Pasteur Institute de Montevideo, the Vilardebó Hospital and the Faculty of Chemistry (Udelar), won the National Grand Prize for Medicine awarded each year by the Academy of Medicine of Uruguay.

The award ceremony took place on Thursday, December 12 at 6:30 p.m. in the Executive Tower Auditorium.

About the study

The work, entitled ‘Study of the variables that affect the response to clozapine in patients at the Vilardebó Hospital’, analyzed the interaction in the organism of a drug used to treat a type of schizophrenia that affects around 10,000 people in the country.

In Uruguay, more than 30,000 people suffer from schizophrenia, and 30% do not respond to conventional antipsychotics. This type of schizophrenia is called resistant schizophrenia. For this group of patients there is clozapine, which controls the disease, but generates adverse effects. In order to understand the effect of this drug, the project motinored 108 adult men and women treated with clozapine at the Vilardebó Hospital for two years.

From genetic and metabolic analyses, the team observed that, in patients that
smoked, the drug is metabolized more rapidly, so doses should be higher. Meanwhile, overweight patients are associated with slower metabolization rates and increased adverse effects compared to non-overweight ones.

These findings led to personalized clozapine dosing, which not only improved treatment efficacy but also reduced adverse effects.

Different professionals from the Institute participated in the study: Magdalena Cárdenas, Clara Menéndez and José Badano, from the Human Molecular Genetics Laboratory; Valentina Blanco and Alfonso Cayota, from the Functional Genomics Laboratory; and Lucía Spangenberg, from the Bioinformatics Unit. The team also includes Ismael Olmos, Carina Ricciardi, Mauricio Mato, Natalia Guevara, Sabrina Acuña, Cecilia Maldonado, Marta Vázquez and Mauricio Toledo, from the Vilardebó Hospital and the Faculty of Chemistry.

The presence of coronavirus viral particles in red blood cells could facilitate the spread of the disease and be a pathway for systemic invasion throughout the body, beyond the respiratory system as previously believed.

This is one of the conclusions of a study carried out by researchers from the Institut Pasteur de Montevideo, the Faculty of Sciences (Udelar) and the University of Buenos Aires (UBA), published in the scientific journal Cell Death and Disease, part of the Nature group.

The finding suggests that hemoproteins (a type of protein present in red blood cells that, among other things, serve to transport oxygen to the blood) could facilitate viral dissemination. On that basis, the scientific team estimates that in patients with covid-19, the severity of the disease could be reduced through treatments that target hemoproteins. ‘Our findings propose a paradigm shift in the therapeutic approach, taking advantage of the virus-heme interaction as a strategic hinge for intervention’, the study indicates.

Understanding the mechanism

The research emerged to gain a better understanding of the mechanisms of coronavirus spread, which are still not fully understood. ‘The ability of the virus to navigate between cell and cell, tissue and tissue, and therefore cause organ failure in some cases, is still a question that is not fully understood’, said researcher Gonzalo Moratorio, who was part of the study.

The scientific team explored the effects the virus has on the body by combining clinical observations from autopsies of patients with covid-19 with data from infected mice. Specifically, a type of coronavirus that naturally infects mice was used to look for points of comparison with SARS-CoV-2 that affects humans. They arrived at the results thanks to the combination of several techniques and the collaboration of researchers from Uruguay, Argentina and Canada.

These findings help provide a more complete understanding of how the coronavirus acts and what potential treatments for patients might be. ‘Our findings propose a paradigm shift in therapeutic approaches, leveraging the virus-heme (virus and blood) interaction as a strategic hinge for intervention’, the study states.

The full study can be read here.

Researchers from the Institut Pasteur de Montevideo and the Feinstein Institutes for Medical Research (USA) have identified a key protein linked to vascular anomalies (such as arteriovenous malformations) characteristic of a rare genetic disease that affects around 800 people in Uruguay and so far has no cure.

As part of the study -published in the scientific journal Nature Cardiovascular Research-, the scientific team also tested two drugs that, in the medium term, could be used to treat the pathology.

This is Hereditary Hemorrhagic Telangiectasia (HHT), a disease that affects the blood vessels, and in extreme cases can be fatal. Sufferers develop certain arteriovenous malformations, which cause abundant bleeding from the nose and gastrointestinal tract, which, in the long term, can lead to anemia. Arteriovenous malformations (abnormal connections between arteries and veins) can affect the brain, liver and/or lungs and, depending on the organ affected, lead to complications that can be very serious and even fatal.

The arteriovenous malformations of HHT occur, among other things, because the cells of the blood vessels lose control and begin to multiply uncontrollably. The mechanism is similar to that which occurs in some types of cancer, when the cells lose control, proliferate uncontrollably and grow in size, forming a tumor.

In tests on mice, the research team found that, in the case of HHT, the CDK6 enzyme (a protein involved in the control of cell division) is responsible for this dysregulation.

During the tests they found that, in mice lacking the enzyme, they did not experience arteriovenous malformations and, therefore, did not develop the pathology.

Other studies have already evaluated the involvement of CDK6 in breast cancer, for example. Therefore, thinking of a future application in humans, the team looked for existing drugs that inhibit the action of the enzyme. In particular, they tested in mice with HHT two drugs used to treat oncology patients: Palbociclib and Ribociclib. In these tests, they observed that the HHT animals that received the medication reversed the arteriovenous malformations.

“In the medium term, drugs of this type could be used to treat HHT in humans. It is going to take several years of research and some punctual trials for patients to finally be able to use them as therapy,” said Santiago Ruiz, a researcher at the Laboratory of Metabolism and Aging Pathologies of the Institut Pasteur in Montevideo, who was part of the study.

“There is also the possibility that these drugs could be used in other diseases in which arteriovenous malformations occur whose development depends on CDK6 upregulation,” he added.

HHT in the world

Worldwide, the disease has a low prevalence (which is why it is classified as a “rare disease”) of one case per 5,000 people. Given the small number of cases, the general lack of knowledge makes diagnosis and treatment difficult. So far, HHT has no cure, and only palliative treatments are available.
Ruiz, in collaboration with other members of the Institute’s Laboratory of Metabolism and Aging Pathologies and physicians from the Pereira Rossell and Maciel Hospitals, have been studying the disease for several years.

The full study can be read here.