Annals of the Brazilian Academy of Sciences

AABC - Volume 87 (2 Suppl.) - August 2015

Hot Topics in Biomedical Sciences

I am very proud to introduce the Special Issue HOT TOPICS IN BIOMEDICAL SCIENCES that was just published by the Annals of the Brazilian Academy of Sciences (AABC). This volume was organized by two young researchers that are also on the Editorial Board of the AABC - YRAIMA CORDEIRO (Universidade Federal do Rio de Janeiro) and PATRÍCIA F. SCHUCK (Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina), and consists of 17 papers, including both original studies and review articles. From fungi that causes brain damage to new therapeutic strategies for neurodegenerative and psychiatric disorders, passing through articles that deal with serious problems as the resistance of families to vaccinated their children and different aspects of genetic disorders, this Special Issue has contributions in a variety of fields and will be of interest to scientists and students such as geneticists, pharmacologists, biochemists, and neuroscientists, just to name a few.

Now I would like to invite you to scroll through the text, click on the title of the article that interests you, and enjoy!

Alexander W. A. Kellner
Editor-in-Chief

1- Disaggregases, molecular chaperones that resolubilize protein aggregates

Authors: David Z. Mokry. Josielle Abrahão and Carlos H.I. Ramos

This review aims to describe the characteristics of disaggregases, chaperones involved in the dissolution of protein aggregates. Protein aggregates are usually harmful to the cell as they lack physiological function and are involved in several diseases such as Alzheimer, Parkinson and many cancers. Surprisingly, unlike yeast and plants, metazoans lack a bona fide cytosolic disaggregase. This is unexpected, since such mechanism would be an advantage against the deleterious actions of stress-induced and prion-like aggregates. This review also discusses the possibility that metazoans may have evolved multiple systems that degrade protein aggregates with weak activities but with specific cellular or tissue specific localizations.

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2- Fungal colonization of the brain: anatomopathological aspects of neurological cryptococcosis

Authors: Ana Caroline Colombo and Marcio L. Rodrigues

Patients whose immune systems are compromised are highly susceptible to infections by the fungus Cryptococcus neoformans. This fungus can invade the brain of these patients causing serious conditions that result in high mortality rates. The mechanisms by which C. neoformans cause damage to the brain are still obscure. In our manuscript, we discuss the interaction of host brain cells with C. neoformans and conclude that multiple efforts are necessary to improve the knowledge on how this fungus causes damage to the central nervous system.

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3- The re-emergency and persistence of vaccine preventable diseases

Authors: Rodrigo C.N. Borba, Vinícius M. Vidal and Lilian O. Moreira

Vaccines are still the most effective method to prevent deadly infectious diseases. Despite the enormous achievements of vaccination, the incidence of certain infectious diseases, such as measles, polio and pertussis, has increased dramatically. Here we will discuss some epidemiological aspects and possible arguments that may explain why ancient diseases such as, measles, polio, pertussis, diphtheria and tuberculosis are still a threat.

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4- From Gene Targeting to Genome Editing: Transgenic animals applications and beyond

Authors: Maurício Rocha-Martins, Gabriel R. Cavalheiro, Gabriel E. Matos-Rodrigues and Rodrigo A.P. Martins

A universal question in biology is how the genome translates into phenotypes, giving rise to the endless forms of nature. Genome editing technologies are powerful tools that allowed scientists to explore the relationship between an organism’s genome and its phenotype over the last thirty years. Here, we review and discuss the various methods to create genome targeted modifications and present a historical perspective of transgenic animal generation, including its applications from basic research to biotechnology. Moreover, we describe recent nuclease-guided genome editing methods that greatly improved transgenesis, such as ZFNs, TALENs and CRISPR/Cas. Finally, we present the paradigm shifts and discuss their limitations as well as possible future directions.

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5- Prevalence and Fluconazole susceptibility Profile of Candida spp. Clinical Isolates in a Brazilian Tertiary Hospital in Minas Gerais, Brazil

Authors: Athayde Neves-Junior, Ana Carolina Cartágenes-Pinto, Débora A.S. Rocha, Leandro F. Reis de Sá, Maria de Lourdes Junqueira and Antonio Ferreira-Pereira

Candidiasis has become an important concern for clinical practice and the development resistance to fluconazole presents a challenge for treating these opportunistic infections. The aim of this study was to evaluate some epidemiology features of Candida infections in a Brazilian Federal University Hospital. Our study highlights requirement for developing control measures for fungal infections, rational use of antifungal drugs and development of new molecules able to abrogate the active transport of antifungals. 

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6- The neurotoxic effects of vitamin A and retinoids

Authors: Marcos Roberto de Oliveira

Vitamin A and retinoids modulate several biological events in the mammalian cells, including cell differentiation, proliferation, survival, and death. Additionally, retinoids have been utilized in the clinical field to treat some diseases, as for instance dermatological disturbances, immunodeficiency, and cancer. On the other hand, retinoids elicit several detrimental effects that have been associated to cell death or proliferation in different experimental models. Neurotoxicity has been reported as a consequence of exceeding retinoids intake. In this review, it is discussed possible mechanisms by which retinoids affect neuronal cells negatively.

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7- New approaches to the treatment of orphan genetic disorders: Mitigating molecular pathologies using chemicals

Authors: Renata V. Velho, Fernanda Sperb-Ludwig and Ida V.D. Schwartz

With the advance and popularization of molecular techniques, the identification of genetic mutations that cause diseases has increased dramatically. Although it is necessary to identify mutations and provide diagnosis, it is also critical to develop specific therapeutic approaches based on this information. This review aims to highlight recent advances in mutation-targeted therapies with chemicals that mitigate mutational pathology at the molecular level, for disorders that, for the most part, have no effective treatment. Currently, there are several strategies being used to correct different types of mutations. These therapies and other approaches are reviewed in this paper.

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8- Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats

Authors: Brena P. Teodorak, Gabriela K. Ferreira, Giselli Scaini, Letícia B. Wessler, Alexandra S. Heylmann, Pedro Deroza, Samira S. Valvassori, Alexandra I. Zugno, João Quevedo and Emilio L. Streck

Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide, and is associated with neurotoxicity and cognition impairment. Thus, in this study we investigated the effects of acute administration of fenproporex on acetylcholinesterase activity, a regulatory enzyme which is involved in cholinergic synapses, in brain of young rats. Our results showed that fenproporex administration increases acetylcholinesterase activity in hippocampus and posterior cortex, suggesting that fenproporex exerts an effect in cholinergic system, and this imbalance in cholinergic homeostasis could be considered as an important pathophysiological mechanism underlying the brain damage observed in patients who use amphetamines as fenproporex.

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9- Antioxidant, analgesic and anti-inflammatory effects of lavender essential oil

Authors: Gabriela L. da Silva, Carolina Luft, Adroaldo Lunardelli, Robson H. Amaral, Denizar A. da Silva Melo, Márcio V.F. Donadio, Fernanda B. Nunes, Marcos S. de Azambuja, João C. Santana, Cristina M.B. Moraes, Ricardo O. Mello, Eduardo Cassel, Marcos Aurélio de Almeida Pereira and Jarbas R. de Oliveira

This work suggests the lavenTer interference in the inflammatory route. Besides  the lavender oil consistently inhibited spontaneous nociception and presented a similar effect as the tramadol. The results of this study reveal  analgesic and anti-inflammatory activities of the lavender oil.

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10- D-glyceric aciduria

Authors: Nádia W. Dimer, Patrícia F. Schuck, Emilio L. Streck and Gustavo C. Ferreira

D-glyceric aciduria is an inherited metabolic disease caused by a deficiency of glycerate 2-kinase activity, whose pathophysiological mechanisms remain unknown. The main clinical and neurological symptoms seen in affected patients include progressive encephalopathy, hypotonia, psychomotor and mental retardation, microcephaly, seizures, speech delay, metabolic acidosis, and even death. In this review we shall discuss these clinical and biochemical findings, as well as diagnosis and treatment of affected patients in order to raise awareness about this condition.

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11- Efficacy of topical 5% Acyclovir-1% Hydrocortisone Cream (ME-609) for Treatment of Herpes Labialis: a systematic review

Authors: Maria Inês da Rosa, Suéli L. Souza, Bruna F. de Farias, Patrícia D.S. Pires, Eduardo R. Dondossola and Maria Eduarda F. dos Reis

Herpes labialis  is a very frequent disease that affects millions of people. This systematic review and meta-analysis evaluated   the  efficacy of 5% acyclovir–1% hydrocortisone cream for treatment of patients with herpes simplex labialis. A meta-analysis of two included studies showed a RR = 0.77, (95% CI 0.70-0.86).This result suggests that an early episodic treatment with the combination of an antiviral and a steroid is beneficial for herpes simplex labialis treatment.

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12- Toxicological Evaluation of Anti-Scrapie Trimethoxychalcones and Oxadiazoles

Authors: Claudia P. Figueiredo, Natalia C. Ferreira, Giselle F. Passos, Robson da Costa, Fernanda S. Neves, Clarice S.C. Machado, Alessandra Mascarello, Louise D. Chiaradia-Delatorre, Patrícia D. Neuenfeldt, Ricardo J. Nunes and Yraima Cordeiro

Prion diseases are neurodegenerative disorders for which there is still no cure. Changes in the conformation of a cell-surface protein, the prion protein, generate the scrapie form, which is responsible for disease onset. Although several compounds are effective in vitro they fail in vivo probably due to poor pharmacokinetic profile. Here we evaluate the in vivo toxicity of heterocyclic organic compounds previously described to have anti-prion activity in prion-infected cells. We verified that the most promising compounds were safe to mice after oral and intraperitoneal administration, showing that they have potential application for the therapy against prion diseases.

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13- Mesenchymal Stem cells for the treatment of neurodegenerative and psychiatric disorders

Authors: Gabriela D. Colpo, Bruna M. Ascoli, Bianca Wollenhaupt-Aguiar, Bianca Pfaffenseller, Emily G. Silva, Elizabeth O. Cirne-Lima, João Quevedo, Flávio Kapczinski and Adriane R. Rosa

The main topic of this review is Mesenchymal stem cells (MSCs) for the treatment of neurodegenerative and psychiatric disorders.  MSCs are multipotent cells that have the capacity to differentiate into different cells lineages. MSCs have been identified in different tissues and they have the ability to migrate to injured sites. Further, MSCs can regulate the immune system with immunomodulatory and anti-inflammatory effects.  Therapies with MSCs have shown promising results in neurodegenerative and psychiatric disorders. However, despite the vast amount of research into MSCs in neurodegenerative diseases, the mechanisms of action of MSCs are still not completely clarified.

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14- Neutrotoxic effects of fructose administration in rat brain: implications for fructosemia

Authors: Ernesto A. Macongonde, Naithan L.F. Costa, Bruna K. Ferreira, Mairis S. Biella, Marisa J.S. Frederico, Marcos R. de Oliveira, Silvio Ávila Júnior, Fátima R.M.B. Silva, Gustavo C. Ferreira, Emilio L. Streck and Patrícia F. Schuck

Fructose accumulates in tissue and body fluids of patients affected by hereditary fructose intolerance (HFI), whose pathophysiology is still to be unravelled. Acute fructose administration decreases albumin levels and increases cholesterol levels in CSF of animals 12 h after the administration. In addition, anaerobic glycolysis is upgraded, as evidenced by the increased serum lactate levels. Furthermore, malate dehydrogenase activity increases in cerebral cortex from treated group 24 h after the administration of this carbohydrate. These findings indicate a possible role of fructose on brain alterations found in HFI.

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15- Alzheimer`s Disease associated with Psychiatric Comorbidities

Authors: Michelle L. Garcez, Ana Carolina B. Falchetti, Francielle Mina and Josiane Budni

Alzheimer's disease (AD) is the most common cause of dementia and has become a severe public health issue. It is estimated that globally, 35.6% of people have some form of dementia. In addition, it is common to find the presence of neuropsychiatric comorbidities such as depression, schizophrenia and bipolar disorder during the course or development of AD. These disorders can become severe enough to interfere with the patients daily functioning, and can worsen the course of the disease. However, little is known about the causal relationship between psychiatric comorbidities and AD, or the reasons for the predisposition of some individuals to such disorders.

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16- Effects of omega-3 supplementation on interleukin and neurotrophin levels in an animal model of schizophrenia

Authors: Alexandra I. Zugno, Lara Canever, Helder Chipindo, Gustavo Mastella, Alexandra S. Heylmann, Mariana B. Oliveira, Amanda V. Steckert, Adalberto A. Castro, Felipe Dal Pizzol, João Quevedo and Clarissa S. Gama

New studies suggest that polyunsaturated fatty acids, such as omega-3, may reduce the symptoms of schizophrenia. The findings of the present article suggest that the similarity of IL-1β and IL6 levels in our experimental groups are due to the mechanism of action of ketamine on the immune system. More studies have to be carried out to explain this pathology. In conclusion, we could suggest a prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia.

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17- Effects of primaquine and chloroquine on oxidative stress parameters in rats

Authors: Francianne Giovanella, Gabriela K. Ferreira, Samira D.T. de Prá, Milena Carvalho-Silva, Lara M. Gomes, Giselli Scaini, Renata C. Gonçalves, Monique Michels, Letícia S. Galant, Luiza M. Longaretti, Ana Luiza Dajori, Vanessa M. Andrade, Felipe Dal-Pizzol, Emilio L. Streck and Renan P. de Souza

Primaquine and chloroquine are used not only for the treatment of malaria but also for the prevention and prophylaxis, as well as for treatment of other diseases, and are associated with oxidative stress. Thus, in this study we investigated the effects of these drugs on oxidative stress and DNA damage in brain, liver and kidney of rats. Our results demonstrated that primaquine and chloroquine causes DNA damage. However, these drugs have showed different results in oxidative stress markers. In conclusion, the results of our present studies show that prolonged treatment with antimalarial can adversely affect the DNA.

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