Cristóvão Luís Pitangueira Mangueira

Hospital Israelita Albert Einstein

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Paulo Luiz Carvalho Francescantônio

Pontifícia Universidade Católica de Goiás

Wilson de Melo Cruvinel

Pontifícia Universidade Católica de Goiás

Alessandra Dellavance

Fleury S.A. (Brazil)

Carlos David Araújo Bichara

Universidade Federal do Pará

Luís Eduardo Coelho Andrade

Fleury S.A. (Brazil)

Wilton Silva dos Santos

Universidade Federal de Santa Maria

Carlos Alberto von Mühlen

Hospital Moinhos de Vento

Suzane Pretti Figueiredo Neves

Universidade Federal de Minas Gerais

Jozélia Rêgo

Universidade Federal de Goiás

Flávia Ikeda e Araújo

Universidade Católica de Brasília

Cooperative Institutions

Hospital Israelita Albert Einstein

218

Universidade de São Paulo

149

Universidade Federal de São Paulo

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Hospital São Paulo

Hospital Universitário da Universidade de São Paulo

Fundação de Apoio à Universidade Federal de São Paulo

Universidade Estadual de Campinas (UNICAMP)

Universidade Federal de Minas Gerais

Universidade Brasil

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Personalized medicine and the clinical laboratory

Einstein (São Paulo) (2014)

João Renato Rebello Pinho Roberta Sitnik Cristóvão Luís Pitangueira Mangueira

Personalized medicine is the use of biomarkers, most of them molecular markers, for detection of specific genetic traits to guide various approaches for preventing and treating different conditions. The identification of several genes related to heredity, oncology and infectious diseases lead to the detection of genetic polymorphisms that are involved not only in different clinical progression of these diseases but also in variations in treatment response. Currently, it is possible to detect these polymorphisms using several methodologies: detection of single nucleotide polymorphisms using polymerase chain reaction methods; nucleic acid microarray detection; and nucleic acid sequencing with automatized DNA sequencers using Sanger-derived methods and new generation sequencing. Personalized medicine assays are directed towards detecting genetic variations that alter interactions of drugs with targets or the metabolic pathways of drugs (upstream and downstream) and can be utilized for the selection of drug formulations and detect different immunogenicities of the drug. Personalized medicine applications have already been described in different areas of Medicine and allow specific treatment approaches to be applied to each patient and pathology according to the results of these assays. The application of such a protocol demands an increasing interaction between the clinical laboratory and the clinical staff. For its implementation, a coordinated team composed of basic researchers and physicians highly specialized in their areas supported by a highly specialized team of clinical analysts particularly trained in molecular biology assays is necessary.

Personalized Medicine

Sanger sequencing

Molecular diagnostics

Pharmacogenomics

Identification

10.1590/s1679-45082014rw2859

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Citations (7)

A PCSK9 e sua relevância clínica com os novos alvos terapêuticos contra a dislipidemia PCSK9 and its clinical importance with the new therapeutic targets against dyslipidemia

Carlos Eduardo Santos Ferreira Francisco Antônio Helfenstein Fonseca Cristóvão Luís Pitangueira Mangueira

ABSTRACT This is a remarkable progress; since the finding of statins, there was no new way of reducing, significantly, cholesterol and LDL fraction. It is also clear that this decrease, by statins, is related to future cardiovascular lesions, being useful in its primary and secondary prophylaxis. The authors presented studies on research to promote the falling of blood cholesterol by means of antibodies, which inhibit the pro-protein PCSK9, as well as agents that act performing the RNA interference. We had two advantages immediately: for patients with myopathy associated with statins, and the fact of being injected every 15 days, that may contribute to better treatment adherence. Keywords: Dyslipidemias; Lipoproteins; Cholesterol, LDL INTRODUCAO A pro-proteina convertase subtilisina/Kexin tipo 9, tam-bem conhecida como PCSK9, e uma enzima que, nos seres humanos, e codificada pelo gene PCSK9 (1) com ortologos encontrados em praticamentes todas as es-pecies. Esse gene codifica uma pro-proteina convertase pertencente a subfamilia proteinase K da familia subti-lase secretora. A proteina codificada e sintetizada como um zimogenio soluvel, que sofre processamento auto-catalitico intramolecular no reticulo endoplasmatico. Essa proteina tem um papel fundamental na regulacao da homeostase do colesterol. A PCSK9 liga-se ao fator de crescimento epidermico de repeticao do dominio A (EGF-A), do receptor de lipoproteina de baixa densi-dade (R-LDL), induzindo a degradacao desse receptor. Esses niveis reduzidos de R-LDL resultam em dimi-nuicao do metabolismo das lipoproteinas de baixa den-sidade (LDL-colesterol – LDL-c), o que poderia levar a hipercolesterolemia

PCSK9

Alirocumab

Dyslipidemia

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Development and validation of a liquid chromatography-mass spectrometry (LC-MS/MS) method for amikacin and polymyxin B monitoring

Clinica Chimica Acta (2019)

Priscilla Bento Matos Cruz Derogis Marcelo C. Batista Lívia Rentas Sanches Adriana Caschera Leme Faulhaber Cristóvão Luís Pitangueira Mangueira

Isotope dilution

Bioanalysis

Deoxyribonucleosides

10.1016/j.cca.2019.03.1591

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Citations (3)

Fabricantes profissionais de cerâmica aln de alto desempenhoBrazilian Guidelines for autoantibodies on HEp-2 cells

Paulo Luiz Carvalho Francescantônio Wilson de Melo Cruvinel Alessandra Dellavance Luís Eduardo Coelho Andrade Ben Hur Taliberti

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Prateleiras para prateleiras móveis manuais para arquivos móveis Prateleiras arquivo compacto Biblioteca do EscritórioBrazilian Guidelines for autoantibodies on HEp-2 cells

Paulo Luiz Carvalho Francescantônio Wilson de Melo Cruvinel Alessandra Dellavance Luís Eduardo Coelho Andrade Ben Hur Taliberti

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A Novel Assay for the Identification of NOTCH1 PEST Domain Mutations in Chronic Lymphocytic Leukemia

BioMed Research International (2016)

Paulo Vidal Campregher Roberta Cardoso Petroni Nair Hideko Muto Roberta Sitnik Flavia Pereira de Carvalho

Aims. To develop a fast and robust DNA-based assay to detect insertions and deletions mutations in exon 34 that encodes the PEST domain of NOTCH1 in order to evaluate patients with chronic lymphocytic leukemia (CLL). Methods. We designed a multiplexed allele-specific polymerase chain reaction (PCR) combined with a fragment analysis assay to detect specifically the mutation c.7544_7545delCT and possibly other insertions and deletions in exon 34 of NOTCH1. Results. We evaluated our assay in peripheral blood samples from two cohorts of patients with CLL. The frequency of NOTCH1 mutations was 8.4% in the first cohort of 71 unselected CLL patients. We then evaluated a second cohort of 26 CLL patients with known cytogenetic abnormalities that were enriched for patients with trisomy 12. NOTCH1 mutations were detected in 43.7% of the patients with trisomy 12. Conclusions. We have developed a fast and robust assay combining allele-specific PCR and fragment analysis able to detect NOTCH1 PEST domain insertions and deletions.

Trisomy

10.1155/2016/4247908

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Citations (4)

STORMS checklist: Dysbiosis of the enteric microbiota due to Crohn's disease treatment associated with MAIT cell activation

Zenodo (CERN European Organization for Nuclear Research) (2022)

Lucas Pires Garcia Oliveira Angélica Cruz-Lebrón Ana Eduarda Zulim de Carvalho Reginaldo Keller Fernandes Leticia D'Argenio-Garcia

STORMS checklist initiative to standardize reporting of human microbiome research, regarding submission to peer-reviewed journal.

Dysbiosis

10.5281/zenodo.6998799

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Antinucleosome Antibodies in Patients with Juvenile Systemic Lupus Erythematosus

Lupus (2006)

LMA Campos MHB Kiss MA Scheinberg Cristóvão Luís Pitangueira Mangueira CA Silva

Our objective was to evaluate the frequency of antinucleosome antibodies (anti-Ncs) in juvenile systemic lupus erythematosus (JSLE) comparing it to that observed for anti-DNA and to correlate the presence of these antibodies with clinical manifestations and disease activity. Anti-Ncs and anti-DNA were detected by ELISA in 74 patients with JSLE and 64 normal controls. Clinical records were reviewed. Disease activity was assessed by SLEDAI score. Anti-Ncs and anti-DNA showed sensitivity of 52.7% and 54% and specificity of 98.4% and 95.3%, respectively. Disagreement between the two assays was found in 25.7% of the cases: isolated positive Anti-Ncs in nine cases (12.2%) and isolated positive anti-DNA in 10 cases (13.5%). Agreement was found in 74.3%: both positive antibodies in 30 cases and both negative in 25. The presence of anti-Ncs was significantly associated with malar erythema, hemolytic anemia, anti-DNA and low complement levels, but not with renal manifestations. The presence of anti-Ncs was associated with a higher SLEDAI median (P < 0.001) and its titers correlated with the SLEDAI score (r = 0.504; P < 0.001). The frequency, sensitivity and specificity values were similar between anti-Ncs and anti-DNA antibodies in patients with JSLE. Nevertheless, the discordance of 25.7% between the two assays suggests that both antibodies may have a complementary diagnostic role. The association and correlation between anti-Ncs and several disease activity parameters demonstrated its usufulness in the follow-up of these patients.

10.1191/0961203306lu2317oa

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Citations (35)

REFERENCE INTERVAL OF TSH AND FREE T4 FOR KIDS AND TEENAGERS FROM SÃO PAULO

Sao Paulo Medical Journal (2022)

Gabriela Chiuffa Tunes Tatiana Ferreira de Almeida MC Batista Cristóvão Luís Pitangueira Mangueira

Objective: According to de literature free thyroxine (Free T4) and thyrotropin (TSH) reference interval are age, population, and instrument dependent. Our aim was to define age partitioning and reference intervals for kids and teenagers of our population. Method: We collected retrospective free thyroxine (Free T4) and thyrotropin (TSH) results of 11649 individuals with age between > 1 month and < 19 years from electronic health records. Also, we filtered from our cohort individuals with multiple records, deaths, or any of the CID-10. Conclusion: For TSH we found four age segments (> 1 month and < 1 year, ≥ 1 and < 5 years, ≥ 5 and < 10 years and ≥ 10) while for free-T4 we found five age segments (> 1 month and < 1 year, ≥ 1 and < 2.5 years, ≥ 2.5 and < 9 years, ≥ 9 and < 13 years and ≥ 13). Comparing the statistics approaches, we noted that the lower and upper limit was very similar for Free T. References: 1. Kapelari K et al. Pediatric reference intervals for thyroid hormone levels from birth to adulthood: a retrospective study. BMC Endocrine Dis. 2008; 8(1): 1-10. 2. Yang Q et al. An automated and objective method for age partitioning of reference intervals based on continuous centile curves. Pathology. 2016; 48(6): 581-85.

10.5327/1516-3180.140s1.6296

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Contents Vol. 118, 2011

Nephron Clinical Practice (2011)

Sérgio Gardano Elias Bucharles Sílvio Henrique Barberato Andréa Emília Marques Stinghen B. Gruber Henrique Meister

10.1159/000330662

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