O FARMACÊUTICO NA ONCOLOGIA: USO DE NOVAS TECNOLOGIAS NO ACOMPANHAMENTO FARMACOTERAPÊUTICO

The clinical oncologist pharmacist has an important paper on the pharmacotherapeutic management of patients in chemotherapy. Currently, methods are used by this professional to facilitate the use of Pharmacotherapeutic Monitoring in Oncology, like the Dáder Method. Artificial Intelligence emerged as a new tool to assist clinical oncologist pharmacists and optimize their assignments. Also, the performance of this professional in oncological pharmacist care on a multidisciplinary team has also brought benefits to patients in many different hospitals. Finally, platforms like Medscape and Drugs.com are addressed to verify drug interactions.El farmacéutico oncológico clínico tiene un papel importante en el manejo farmacoterapéutico de pacientes en quimioterapia. Actualmente, este profesional utiliza algunos métodos para facilitar el uso del monitorización farmacoterapêutica en oncología, como el Método Dáder, utilizado en  diversos hospitales en todo  el mundo. La Inteligencia Artificial surge como una nueva herramienta para ayudar a los farmacéuticos oncológicos clínicos y optimizar sus atribuciones. Además, la actuación de este profesional en el cuidado farmacéutico oncológico en un equipo multidisciplinario ha traído beneficios para los pacientes en diferentes hospitales. Por último, plataformas como Medscape y Drugs.com se abordan para la verificación de interacciones medicamentosas.O farmacêutico oncológico clínico tem um importante papel no manejo farmacoterapêutico de pacientes que realizam quimioterapia. Atualmente, este profissional faz uso de alguns métodos para facilitar o emprego do Acompanhamento Farmacoterapêutico em Oncologia, como o Método Dáder. A Inteligência Artificial surge como uma nova ferramenta para auxiliar os farmacêuticos oncológicos clínicos e otimizar suas atribuições. Também, a atuação deste profissional no cuidado farmacêutico oncológico em uma equipe uma multidisciplinar trouxe benefícios para os pacientes em diferentes hospitais. Por fim, plataformas como o Medscape e o Drugs.com são abordadas para verificação de interações medicamentosas.O farmacêutico oncológico clínico tem um importante papel no manejo farmacoterapêutico de pacientes que realizam quimioterapia. Atualmente, este profissional faz uso de alguns métodos para facilitar o emprego do Acompanhamento Farmacoterapêutico em Oncologia, como o Método Dáder. A Inteligência Artificial surge como uma nova ferramenta para auxiliar os farmacêuticos oncológicos clínicos e otimizar suas atribuições. Também, a atuação deste profissional no cuidado farmacêutico oncológico em uma equipe uma multidisciplinar trouxe benefícios para os pacientes em diferentes hospitais. Por fim, plataformas como o Medscape e o Drugs.com são abordadas para verificação de interações medicamentosas

ANÁLISE IN SILICO DO PROCESSO DE REGENERAÇÃO CELULAR ATRAVÉS DA INTERAÇÃO PIWI/PIRNA EM MUS MUSCULUS

Cell and tissue regeneration, much discussed in various areas of medicine and biology, still has gaps in its processes and functioning. In the last decade, the role of epigenetics in this function has been elucidated, with emphasis on non-coding RNAs, including piRNAs (PIWI-interacting RNAs), previously known for their role in germ cells and in controlling transposable elements. Recent studies have demonstrated piRNA functions in somatic tissue cells, such as the nervous system, and research in small rodents, especially Mus musculus, has indicated an important link between the expression of this pathway and the correct functioning of the regeneration process. As it is a relevant challenge for regenerative medicine to understand these processes, through the robust studies described here and using Bioinformatics tools, protein-protein interaction networks (PPIN) were built to identify target proteins for therapeutic treatments based on the functioning of the PIWI/piRNA gene pathway in Mus musculus. By analyzing these networks, we were able to identify relevant proteins, as well as their interactions, for the regenerative process in mammals and, with these results, in the future we will be able to develop in vivo tests based on the data obtained in silico, thus saving time and financial investment.La regeneración celular y tisular, muy discutida en diversos ámbitos de la medicina y la biología, aún presenta lagunas en cuanto a sus procesos y funcionamiento. En la última década se ha dilucidado el papel de la epigenética en esta función, con énfasis en los ARN no codificantes, entre ellos los piARN (ARN que interactúan con PIWI), antes conocidos por su papel en las células germinales y en el control de los elementos transponibles. Estudios recientes han demostrado las funciones de los piRNAs en células de tejidos somáticos, como el sistema nervioso, y la investigación en pequeños roedores, especialmente Mus musculus, ha indicado un importante vínculo entre la expresión de esta vía y el correcto funcionamiento del proceso de regeneración. Dado que entender estos procesos es un reto relevante para la medicina regenerativa, a través de los robustos estudios aquí descritos y utilizando herramientas de Bioinformática, se construyeron redes de interacción proteína-proteína (PPIN) para identificar proteínas diana para tratamientos terapéuticos basados en el funcionamiento de la vía génica PIWI/piRNA en Mus musculus. Mediante el análisis de estas redes, pudimos identificar proteínas relevantes, así como sus interacciones, para el proceso regenerativo en mamíferos y, con estos resultados, en el futuro podremos desarrollar ensayos in vivo basados en los datos obtenidos in silico, ahorrando así tiempo e inversión económica.A regeneração celular e tecidual, muito abordada em diversas áreas da medicina e da biologia, ainda permanece com lacunas sobre seus processos e funcionamento. Na última década, elucidou-se o papel da epigenética na referida função, dando-se ênfase para RNAs não codificantes, e entre eles, os piRNAs (PIWI-interacting RNAs), antes conhecidos por sua atuação em células germinativas e no controle de elementos transponíveis. Estudos recentes demonstraram funções dos piRNA em células de tecidos somáticos, como o nervoso, e pesquisas com pequenos roedores, especialmente em Mus musculus, apontaram uma importante ligação entre a expressão dessa via e o correto funcionamento do processo de regeneração. Por ser um desafio relevante para a medicina regenerativa entender esses processos, através de estudos robustos aqui descritos e utilizando ferramentas de Bioinformática, construiu-se redes de interação proteína-proteína (PPIN) para identificar proteínas-alvo para tratamentos terapêuticos com base no funcionamento da via do gene PIWI/piRNA em Mus musculus. A partir da análise dessas redes, conseguimos identificar proteínas relevantes, assim como suas interações, para o processo regenerativo em mamíferos e, com esses resultados, futuramente, poder-se-á desenvolver testes in vivo com base nos dados obtidos in silico, economizando, assim, tempo e investimentos financeiros.A regeneração celular e tecidual, muito abordada em diversas áreas da medicina e da biologia, ainda permanece com lacunas sobre seus processos e funcionamento. Na última década, elucidou-se o papel da epigenética na referida função, dando-se ênfase para RNAs não codificantes, e entre eles, os piRNAs (PIWI-interacting RNAs), antes conhecidos por sua atuação em células germinativas e no controle de elementos transponíveis. Estudos recentes demonstraram funções dos piRNA em células de tecidos somáticos, como o nervoso, e pesquisas com pequenos roedores, especialmente em Mus musculus, apontaram uma importante ligação entre a expressão dessa via e o correto funcionamento do processo de regeneração. Por ser um desafio relevante para a medicina regenerativa entender esses processos, através de estudos robustos aqui descritos e utilizando ferramentas de Bioinformática, construiu-se redes de interação proteína-proteína (PPIN) para identificar proteínas-alvo para tratamentos terapêuticos com base no funcionamento da via do gene PIWI/piRNA em Mus musculus. A partir da análise dessas redes, conseguimos identificar proteínas relevantes, assim como suas interações, para o processo regenerativo em mamíferos e, com esses resultados, futuramente, poder-se-á desenvolver testes in vivo com base nos dados obtidos in silico, economizando, assim, tempo e investimentos financeiros

Computational biology helps understand how polyploid giant cancer cells drive tumor success

Precision and organization govern the cell cycle, ensuring normal proliferation. However, some cells may undergo abnormal cell divisions (neosis) or variations of mitotic cycles (endopolyploidy). Consequently, the formation of polyploid giant cancer cells (PGCCs), critical for tumor survival, resistance, and immortalization, can occur. Newly formed cells end up accessing numerous multicellular and unicellular programs that enable metastasis, drug resistance, tumor recurrence, and self-renewal or diverse clone formation. An integrative literature review was carried out, searching articles in several sites, including: PUBMED, NCBI-PMC, and Google Academic, published in English, indexed in referenced databases and without a publication time filter, but prioritizing articles from the last 3 years, to answer the following questions: (i) “What is the current knowledge about polyploidy in tumors?”; (ii) “What are the applications of computational studies for the understanding of cancer polyploidy?”; and (iii) “How do PGCCs contribute to tumorigenesis?

Continent-wide decoupling of Y-chromosomal genetic variation from language and geography in native South Americans

Numerous studies of human populations in Europe and Asia have revealed a concordance between their extant genetic structure and the prevailing regional pattern of geography and language. For native South Americans, however, such evidence has been lacking so far. Therefore, we examined the relationship between Y-chromosomal genotype on the one hand, and male geographic origin and linguistic affiliation on the other, in the largest study of South American natives to date in terms of sampled individuals and populations. A total of 1,011 individuals, representing 50 tribal populations from 81 settlements, were genotyped for up to 17 short tandem repeat (STR) markers and 16 single nucleotide polymorphisms (Y-SNPs), the latter resolving phylogenetic lineages Q and C. Virtually no structure became apparent for the extant Y-chromosomal genetic variation of South American males that could sensibly be related to their inter-tribal geographic and linguistic relationships. This continent-wide decoupling is consistent with a rapid peopling of the continent followed by long periods of isolation in small groups. Furthermore, for the first time, we identified a distinct geographical cluster of Y-SNP lineages C-M217 (C3*) in South America. Such haplotypes are virtually absent from North and Central America, but occur at high frequency in Asia. Together with the locally confined Y-STR autocorrelation observed in our study as a whole, the available data therefore suggest a late introduction of C3* into South America no more than 6,000 years ago, perhaps via coastal or trans-Pacific routes. Extensive simulations revealed that the observed lack of haplogroup C3* among extant North and Central American natives is only compatible with low levels of migration between the ancestor populations of C3* carriers and non-carriers. In summary, our data highlight the fact that a pronounced correlation between genetic and geographic/cultural structure can only be expected under very specific conditions, most of which are likely not to have been met by the ancestors of native South Americans

DNA typing from vaginal smear slides in suspected rape cases

In an investigation of suspected rape, proof of sexual assault with penetration is required. In view of this, detailed descriptions of the genitalia, the thighs and pubic region are made within the forensic medical service. In addition, vaginal swabs are taken from the rape victim and some of the biological material collected is then transferred to glass slides. In this report, we describe two rape cases solved using DNA typing from cells recovered from vaginal smear slides. In 1999, two young women informed the Rio de Janeiro Police Department that they had been victims of sexual assaults. A suspect was arrested and the victims identified him as the offender. The suspect maintained that he was innocent. In order to elucidate these crimes, vaginal smear slides were sent to the DNA Diagnostic Laboratory for DNA analysis three months after the crimes, as unique forensic evidence. To get enough epithelial and sperm cells to perform DNA analysis, we used protocols modified from the previously standard protocols used for DNA extraction from biological material fixed on glass slides. The quantity of cells was sufficient to perform human DNA typing using nine short tandem repeat (STR) loci. It was 3.3 billion times more probable that it was the examined suspect who had left sperm cells in the victims, rather than any other individual in the population of Rio de Janeiro

Identification of a criminal by DNA typing in a rape case in Rio de Janeiro, Brazil

CONTEXT: Human DNA identification is a powerful tool for paternity cases as well as for criminal investigation, in which biological evidence is typed after collection from crime scenes and for the identification of human remains. OBJECTIVE: Identification of a criminal in a rape case with 4 suspects using STR and VNTR DNA analysis. TYPE OF STUDY: Forensic DNA analysis. SETTING: DNA Diagnostic Laboratory, Universidade Estadual do Rio de Janeiro, Brazil. PARTICIPANTS: Blood from 4 suspects and the victim, and skin from the fetus. PROCEDURES: Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: Three of the suspects were excluded and one of them was identified as the biological father of the fetus after typing with CTT and FFv Multiplexes. Complementary DNA typing at 3 VNTR loci was also carried out. CONCLUSIONS: After typing four suspects using 6 STR loci, one of them was identified as the biological father of the fetus. In order to significantly enhance the Combined Paternity Index (PI), complementary DNA typing in 3 VNTR loci was carried out. The included suspect was found to be the biological father with a PI of 412,860 (Probability of Paternity: 99.9997%)

Allele frequencies data and statistic parameters for 16 STR loci—D19S433, D2S1338, CSF1PO, D16S539, D7S820, D21S11, D18S51, D13S317, D5S818, FGA, Penta E, TH01, vWA, D8S1179, TPOX, D3S1358—in the Rio de Janeiro population, Brazil

Allele frequencies for 16 short tandem repeats (STR) loci were determined with a sample of 230–300 unrelated individuals from the population of Rio de Janeiro, Brazil. The loci are the most commonly used in forensic and paternity testing, being analysed by the Identifiler (Applied Biosystems) and PowerPlex 2.1 (Promega) commercial kits. It was proved that Penta E and D18S51 are the most polymorphic loci

Association of NOD2 and IFNG single nucleotide polymorphisms with leprosy in the Amazon ethnic admixed population.

Leprosy is a chronic infectious disease, caused by Mycobacterium leprae, which affects skin and peripheral nerves. Polymorphisms in genes associated with autophagy, metabolism, innate and adaptive immunity confer susceptibility to leprosy. However, these associations need to be confirmed through independent replication studies in different ethnicities. The population from Amazon state (northern Brazil) is admixed and it contains the highest proportion of Native American genetic ancestry in Brazil. We conducted a case-control study for leprosy in which we tested fourteen previously associated SNPs in key immune response regulating genes: TLR1 (rs4833095), NOD2 (rs751271, rs8057341), TNF (rs1800629), IL10 (rs1800871), CCDC122/LACC1 (rs4942254), PACRG/PRKN (rs9356058, rs1040079), IFNG (rs2430561), IL6 (rs2069845), LRRK2 (rs7298930, rs3761863), IL23R (rs76418789) and TYK2 (rs55882956). Genotyping was carried out by allelic discrimination in 967 controls and 412 leprosy patients. Association with susceptibility was assessed by logistic regression analyses adjusted for the following covariates: gender, age and ancestry. Genetic ancestry was similar in case and control groups. Statistically significant results were only found for IFNG and NOD2. The rs8057341 polymorphism within NOD2 was identified as significant for the AA genotype (OR = 0.56; 95% CI, 0.37-0.84; P = 0.005) and borderline for the A allele (OR = 0.76; 95% CI, 0.58-1.00; P = 0.053) and carrier (OR = 0.76; 95% CI, 0.58-1.00; P = 0.051). The rs2430561 SNP in IFNG was associated with disease susceptibility for the AT genotype (OR = 1.40; 95% CI, 1.06-1.85; P = 0.018) and carrier (OR = 1.44; 95% CI, 1.10-1.88; P = 0.008). We confirmed that NOD2 and IFNG are major players in immunity against M.leprae in the Amazon ethnic admixed population