Abstract Background Cardiovascular diseases (CVDs) are relevant to the management of breast cancer treatment since a substantial number of patients develop these complications after chemotherapy. Objective This study aims to evaluate new cardiovascular biomarkers, namely CXCL-16 (C-X-C motif ligand 16), FABP3 (fatty acid binding protein 3), FABP4 (fatty acid binding protein 4), LIGHT (tumor necrosis factor superfamily member 14/TNFS14), GDF-15 (Growth/differentiation factor 15), sCD4 (soluble form of CD14), and ucMGP (uncarboxylated Matrix Gla-Protein) in breast cancer patients treated with doxorubicin (DOXO). Methods This case-control study was conducted in an oncology clinic that included 34 women diagnosed with breast cancer and chemotherapy with DOXO and 34 control women without cancer and CVD. The markers were determined immediately after the last cycle of chemotherapy. The statistical significance level adopted was 5%. Results The breast cancer group presented higher levels of GDF-15 (p<0.001), while control subjects had higher levels of FABP3 (p=0.038), FABP4 (p=0003), sCD14, and ucMGP (p<0.001 for both). Positive correlations were observed between FABPs and BMI in the cancer group. Conclusion GDF15 is an emerging biomarker with potential clinical applicability in this scenario. FABPs are proteins related to adiposity, which are potentially involved in breast cancer biology. sCD14 and ucMGP engage in inflammatory and vascular calcification. The evaluation of these novel cardiovascular biomarkers could be useful in the management of breast cancer chemotherapy with DOXO. CVDs (CVDs CXCL16 CXCL 16 CXCL-1 CXC C X 16, , 16) FABP fatty 3, 3 3) 4, 4 4) tumor 14/TNFS14, 14TNFS14 TNFS 14/TNFS14 14 TNFS14 14/TNFS14) GDF 15 GDF-1 Growth/differentiation Growthdifferentiation Growth differentiation 15, 15) sCD soluble CD14, CD14 CD CD14) uncarboxylated GlaProtein Gla Protein Gla-Protein . (DOXO) casecontrol case CVD 5 5% p<0.001, p0001 p p<0.001 0 001 (p<0.001) p=0.038, p0038 p=0.038 038 (p=0.038) p=0003, p0003 p=0003 0003 (p=0003) (p<0.00 both. both both) GDF1 scenario adiposity biology sCD1 calcification CXCL1 1 CXCL- 14TNFS1 14/TNFS1 TNFS1 GDF- CD1 (DOXO p000 p<0.00 00 p003 p=0.03 03 (p=0.038 p=000 000 (p=0003 (p<0.0 14TNFS 14/TNFS p00 p<0.0 p=0.0 (p=0.03 p=00 (p=000 (p<0. p0 p<0. p=0. (p=0.0 p=0 (p=00 (p<0 p<0 (p=0. p= (p=0 (p< p< (p= (p

Resumo Fundamento As doenças cardiovasculares (DCV) são relevantes para o manejo do tratamento do câncer de mama, uma vez que um número significativo de pacientes desenvolve essas complicações após a quimioterapia. Objetivo Este estudo teve como objetivo avaliar novos biomarcadores cardiovasculares, sendo eles CXCL-16 (ligante de motivo C-X-C 16), FABP3 (proteína de ligação a ácidos graxos 3), FABP4 (proteína de ligação a ácidos graxos 4), LIGHT (membro da superfamília do fator de necrose tumoral 14/TNFS14), GDF-15 (fator de crescimento/diferenciação 15) , sCD4 (forma solúvel de CD14) e ucMGP (matriz Gla-proteína não carboxilada) em pacientes com câncer de mama tratadas com doxorrubicina (DOXO). Métodos Este estudo de caso-controle foi realizado em uma clínica oncológica, incluindo 34 mulheres com diagnóstico de câncer de mama tratadas com quimioterapia com DOXO e 34 mulheres controle, sem câncer ou DCV. Os marcadores foram determinados imediatamente após o último ciclo de quimioterapia. O nível de significância estatística adotado foi de 5%. Resultados O grupo com câncer de mama apresentou níveis mais elevados de GDF-15 (p<0,001), enquanto os indivíduos controle apresentaram níveis mais elevados de FABP3 (p=0,038), FABP4 (p=0003), sCD14 e ucMGP (p<0,001 para ambos). Correlações positivas foram observadas entre FABPs e IMC no grupo com câncer. Conclusão GDF15 é um biomarcador emergente com potencial aplicabilidade clínica neste cenário. FABPs são proteínas relacionadas à adiposidade, potencialmente envolvidas na biologia do câncer de mama. sCD14 e ucMGP estão envolvidos na calcificação inflamatória e vascular. Acima de tudo, a avaliação destes novos biomarcadores cardiovasculares pode ser útil no tratamento da quimioterapia do câncer de mama com DOXO. DCV (DCV CXCL16 CXCL 16 CXCL-1 ligante CXC C X 16, 16) FABP proteína 3, 3 3) 4, 4 4) membro 14/TNFS14, 14TNFS14 TNFS 14/TNFS14 14 TNFS14 14/TNFS14) GDF 15 GDF-1 crescimentodiferenciação crescimento diferenciação sCD forma CD14 CD matriz Glaproteína Gla carboxilada . (DOXO) casocontrole caso oncológica 5 5% p<0,001, p0001 p p<0,001 0 001 (p<0,001) p=0,038, p0038 p=0,038 038 (p=0,038) p=0003, p0003 p=0003 0003 (p=0003) sCD1 (p<0,00 ambos. ambos ambos) GDF1 cenário adiposidade vascular tudo CXCL1 1 CXCL- 14TNFS1 14/TNFS1 TNFS1 GDF- CD1 (DOXO p000 p<0,00 00 p003 p=0,03 03 (p=0,038 p=000 000 (p=0003 (p<0,0 14TNFS 14/TNFS p00 p<0,0 p=0,0 (p=0,03 p=00 (p=000 (p<0, p0 p<0, p=0, (p=0,0 p=0 (p=00 (p<0 p<0 (p=0, p= (p=0 (p< p< (p= (p

RESUMO Objetivo: O objetivo deste estudo foi caracterizar o perfil lipídico convencional, os níveis de LDL-ox e o polimorfismo da ApoE em pacientes com doença de Alzheimer (DA) e em indivíduos idosos sem comprometimento cognitivo. Métodos: Foram selecionados oitenta indivíduos idosos. Os níveis de LDL-ox foram determinados usando o kit ELISA e a investigação do polimorfismo do gene da ApoE por PCR-RFLP. Resultados: Níveis significativamente reduzidos de LDL-ox foram observados em pacientes com DA comparado ao grupo controle. Uma maior frequência do alelo ε4 da ApoE foi observada nos pacientes com DA em relação aos controles. Nenhuma diferença foi observada para os níveis de colesterol total, HDL-C e LDL-C entre os dois grupos, enquanto níveis de triglicérides foram mais altos em controles comparados aos pacientes com DA. Conclusão: Os dados analisados em conjunto não revelaram diferenças significativas no perfil lipídico, incluindo os níveis de LDL-ox. No entanto, não se pode excluir a importância de alterações lipídicas na gênese da doença. Não obstante, o alelo ε4 da ApoE foi signicativamente mais frequente nos pacientes com demência de Alzheimer em concordância com achados prévios da literatura, mas esse componente genético não interferiu nos níveis de LDL-ox.

ABSTRACT Objective: The objective of this study was to characterize the conventional lipid profile, oxLDL levels and ApoE polymorphism in patients with Alzheimer's disease (AD) and in elderly individuals without cognitive impairment. Methods: Eighty elderly individuals were selected and the levels of oxLDL were determined using the ELISA kit, and ApoE gene polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism. Results: Significantly reduced levels of oxLDL were observed in patients with AD compared to the control group. A higher frequency of the ApoE ε4 allele was observed in patients with AD compared to controls. No difference was observed for total cholesterol, HDL-C, and LDL-C levels between the two groups, while triglyceride levels were higher in controls compared with patients with AD. Conclusion: The data analyzed together did not reveal significant differences in lipid profiles, including oxLDL levels. However, the importance of lipid changes in the genesis of the disease cannot be ruled out. Nevertheless, the ApoE ε4 allele was significantly more frequent in patients with Alzheimer's dementia in agreement with previous findings in the literature, but this genetic component did not change the levels of oxLDL.

ABSTRACT Objective This study aimed to evaluate the association between different renal biomarkers with D-Dimer levels in diabetes mellitus (DM1) patients group classified as: low D-Dimer levels (< 318 ng/mL), which included first and second D-Dimer tertiles, and high D-Dimer levels (≥ 318 ng/mL), which included third D-Dimer tertile. Materials and methods D-Dimer and cystatin C were measured by ELISA. Creatinine and urea were determined by enzymatic method. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI equation. Albuminuria was assessed by immunoturbidimetry. Presence of renal disease was evaluated using each renal biomarker: creatinine, urea, cystatin C, eGFR and albuminuria. Bivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels and odds ratio was calculated. After, multivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels (after adjusting for sex and age) and odds ratio was calculated. Results Cystatin C presented a better association [OR of 9.8 (3.8–25.5)] with high D-Dimer levels than albuminuria, creatinine, eGFR and urea [OR of 5.3 (2.2–12.9), 8.4 (2.5–25.4), 9.1 (2.6–31.4) and 3.5 (1.4–8.4), respectively] after adjusting for sex and age. All biomarkers showed a good association with D-Dimer levels, and consequently, with hypercoagulability status, and cystatin C showed the best association among them. Conclusion Therefore, cystatin C might be useful to detect patients with incipient diabetic kidney disease that present an increased risk of cardiovascular disease, contributing to an early adoption of reno and cardioprotective therapies.

ABSTRACT Objective This study aimed to investigate the association of plasma TNF-α, IL-6, and lL-10 levels and cytokine gene polymorphisms [TNF-α (-308 G→A), IL-6 (-174 C→G) and IL-10 (-1082 A→G, -819 T→C and -592 A→C)] in type 2 diabetes mellitus (T2DM) and obese patients. Subjects and methods One hundred and two T2DM patients and 62 controls were included in this study. Cytokine plasma levels were measured by the Cytometric Bead Array method. Genotyping was carried out by the polymerase chain reaction. Results IL-6 levels were significantly different between T2DM patients and controls. Interestingly, IL-6 levels were higher in T2DM patients with BMI > 30 kg/m2 compared with other patients and obese controls. The genotype and allele frequencies were similar between patients and controls. In the T2DM group, the SNP IL-10 -819 T/C showed a difference between the cytokine level and genotypes: IL-10 level in the TT genotype was significantly higher when compared to CC genotype. Conclusions These results suggest an association between IL-6 levels and obesity, and IL-10 levels and the SNP -819 T/C in T2DM. Knowledge of these variants in T2DM might contribute to a better understanding of the role of inflammation in the etiology and progression of this disease.

RESUMO A doença de Alzheimer (DA) é a forma mais comum de demência. Nos últimos 15 anos, uma nova teoria propõe um mecanismo autoimmune como o gatilho para a DA. Associações entre DA e biomarcadores inflamatórios têm sido registradas, contudo com resultados controversos. A interleucina-10 (IL-10), um mediador anti-inflamatório, tem sido apontada como uma das principais citocinas associadas com a ocorrência de DA. Além disso, os tratamentos que aumentam os níveis de IL-10 podem ser uma terapia potencial para DA, uma vez que esta citocina atua sobre a redução de substância amiloide e de moléculas pró-inflamatórias. Baseando-se em literaturas atuais, este estudo revisa evidências relacionadas com o papel da IL-10 e seus polimorfismos no contexto da DA, o qual se mostrou ser de fundamental importância para atenuar a neuroinflamação, a disfunção cognitiva e a neurodegeneração.

ABSTRACT Alzheimer’s disease (AD) is the most common form of dementia. In the last 15 years, a new theory has proposed the autoimmune mechanism as a trigger for AD. Studies on the association between AD and inflammatory biomarkers have yielded controversial results. Interleukin-10 (IL-10), an anti-inflammatory mediator, has been pointed out as one of the main cytokines associated with the occurrence of AD. Moreover, treatment that increases IL-10 levels could be a potential therapy for AD, since this cytokine acts on amyloid and pro-inflammatory molecule reduction. Based on the current literature, this study reviews evidence regarding the role of IL-10 polymorphisms in the context of AD, which has been shown to be of paramount importance for attenuating neuroinflammation, cognitive dysfunction and neurodegeneration.

RESUMO Neste estudo prospectivo foi avaliada a influência do polimorfismo -351A/G XbaI do gene do receptor de estrogênio alfa (ESR-1) sobre o desempenho cognitivo global em idosos muito idosos (≥ 75 anos) saudáveis durante um ano. Métodos Os indivíduos foram divididos em dois grupos de acordo com a presença ou ausência de declínio cognitivo. Dados cognitivos foram relacionados à informação genética. Resultados O genótipo XbaI -351 AA foi mais comum entre indivíduos que apresentaram declínio cognitivo, enquanto carreadores do alelo -351G demonstraram estabilidade ou melhora cognitiva. Conclusão Estes resultados sugerem que ESR-1 poderia estar associado ao declínio cognitivo em curto prazo em idosos saudáveis, possivelmente por meio de propriedades neuroprotetoras do estrogênio, mesmo em cérebros idosos saudáveis.

ABSTRACT This prospective study aimed to evaluate the influence of the -351A/G XbaI polymorphism in the estrogen receptor-alpha (ESR-1) gene on global cognitive scores of a community sample of healthy oldest-old individuals within one year of follow up. Methods The individuals were categorized in two groups according to the presence or absence of cognitive decline. Cognitive data were related to genetic information. Results The XbaI -351 AA genotype was more common among cognitive decliners, while -351G allele carriers showed cognitive stability or improvement. Conclusion These results suggest that ESR-1 could be associated with one-year cognitive decline in healthy oldest-old individuals, since the estrogen pathway may be involved with neuroprotection, even in healthy brain aging.

ABSTRACT Objective Several formulas based in different biomarkers may be used to estimate glomerular filtration rate (GRF). However, all of them have some limitations, and it is very important to evaluate their performances in different groups of patients. Therefore, we compared GFR, as estimated by creatinine-based and cystatin C-based equations, according to albuminuria, in type 1 diabetes (T1DM), in an observational case-control study. Subjects and methods T1DM patients were classified according to albuminuria: normoalbuminuric (n = 63), microalbuminuric (n = 30), macroalbuminuric (n = 32). GFR was calculated using creatinine-based and cystatin C-based (aMDRD, CKD-EPIcr, CKD-EPIcys, MacIsaac, Tan and CKD-EPIcrcys) equations. Spearman Correlation was used to evaluate the correlation of GFR estimated by the formulas with albuminuria. ROC curves were constructed to compare AUCs of GFR estimated by equations, in reference to macroalbuminuria. Sensibility, specificity and accuracy were calculated for a cut-off < 60 mL/min/1.73 m2. Results GFR estimated by creatinine-based and cystatin C-based equations significantly differed among normoalbuminuric, microalbuminuric and macroalbuminuric patients. Spearman correlation and AUCs of GFR estimated by creatinine-based and cystatin C-based formulas were very similar to each other, though cystatin C-based equations presented better correlation with albuminuria and higher AUCs than the creatinine-based ones, and the best accuracy to detect macroalbuminuric patients. Conclusion Although GFR estimated by all creatinine-based and cystatin C-based equations permitted the differentiation between T1DM patients, according to albuminuria, cystatin C-based equations presented best accuracy to detect macroalbuminuria in T1DM patients and should be considered in the clinical routine in order to increase the possibility of early diagnostic of chronic renal disease.

Resistance to recombinant human erythropoietin is a common condition in dialyzed patients with chronic kidney disease and is associated with more hospitalizations, increased mortality and frequent blood transfusions. The main cause of hyporesponsiveness to recombinant human erythropoietin in these patients is iron deficiency. However, a high proportion of patients does not respond to treatment, even to the use of intravenous iron, which indicates the presence of other important causes of resistance. In addition to the iron deficiency, the most common causes of resistance include inflammation, infection, malnutrition, inadequate dialysis, and hyperparathyroidism, although other factors may be associated. In the presence of adequate iron stores, other causes should be investigated and treated appropriately.

O diagnóstico diferencial das anemias microcíticas é clinicamente importante. Na tentativa de tornar esse diagnóstico menos oneroso e mais eficiente, o uso de parâmetros dos contadores automáticos tem sido sugerido. O objetivo deste estudo foi avaliar a eficiência diagnóstica de alguns parâmetros do hemograma na diferenciação das anemias microcíticas. Foram comparados os parâmetros hematológicos de 395 pacientes portadores de anemia ferropriva, anemia de doença crônica ou talassemia menor. O número de hemácias apresentou os maiores valores combinados de sensibilidade e especificidade na diferenciação dessas anemias. Em conclusão, a contagem de hemácias pode ser útil no diagnóstico diferencial de anemias microcíticas.

Differential diagnosis of microcytic anemia is clinically important. In an attempt to make this diagnosis more cost-effective, the use of some parameters obtained from automated blood count analyzers has been suggested. The objective of this study was to evaluate the efficiency of blood count parameters in differentiating microcytic anemias. Blood parameters were compared in 395 patients with iron deficiency anemia, chronic disease anemia or thalassemia minor. The number of red blood cells showed the highest combined sensitivity and specificity in differentiating these anemias. Hence, blood counts may be a useful tool in the differential diagnosis of microcytic anemias.

INTRODUÇÃO: Evidências sugerem que a giardíase é uma doença zoonótica. O presente trabalho tem como objetivo avaliar a identidade genética da Giardia duodenalis isolada de fezes humanas e de cães de Belo Horizonte. MÉTODOS: Amostras de fezes humanas e de cães foram cultivadas para isolamento de G. duodenalis. Para determinação do genótipo dos isolados, foram usados oligonuclotídeos que amplificam regiões específicas do gene para rRNA. RESULTADOS: Dois isolados de G. duodenalis foram obtidos, os quais apresentaram o genótipo do sub-grupo A. CONCLUSÕES: Estes dados sugerem que a transmissão da giardíase segue um padrão zoonótico.

INTRODUCTION: Evidence suggests that giardiasis is a zoonotic disease. The present work aimed to evaluate the genetic identity of Giardia duodenalis isolated from human and dog fecal samples from Belo Horizonte. METHODS: Human and dog fecal samples were cultured for isolation of G. duodenalis. To determine the genotype of the isolates, primers that amplify a specific region in rRNA of the protozoan were used. RESULTS: Two G. duodenalis isolates were obtained, which belong to the subgroup A genotype. CONCLUSIONS: These findings suggest that the transmission of giardiasis follows a zoonotic pattern.

INTRODUÇÃO: O diabetes melito tipo 1 (T1ADM) é uma doença multifatorial em que os aspectos genéticos e ambientais são importantes para o seu desenvolvimento. A associação das variações genéticas com a doença tem sido demonstrada em vários trabalhos, no entanto, o papel de alguns locos gênicos não foi ainda completamente elucidado. OBJETIVOS: Comparar a frequência de alelos do HLA e polimorfismos nos genes CTLA-4 e insulina em brasileiros com T1ADM e indivíduos sem a doença, além de identificar marcadores gênicos que sejam capazes de discriminar indivíduos diabéticos e não diabéticos. MÉTODOS: A presença dos alelos de HLA DQB1, DQA1 e DRB1, bem como dos polimorfismos -2221 MspI no gene da insulina e 49 A/G no gene CTLA-4, foram identificados por meio da técnica Time-resolved fluorometer, após hibridização com sondas marcadas com Eu (III)/Sm (III) e Tb (III). RESULTADOS: Os alelos DQB1*0302 e DQA1*03 foram identificados como sendo de predisposição ao T1ADM, e o alelo DQB1*0301 mostrou um efeito protetor à doença. Analisando somente o marcador DQA1, este mostrou ser capaz de diferenciar 71,13% dos indivíduos entre diabéticos e não diabéticos, cujo valor aumentou para 82,47% quando adicionado o marcador DQB1. A frequência dos polimorfismos nos genes da insulina e CTLA-4 não mostrou diferença significativa entre os dois grupos estudados. CONCLUSÕES: Os marcadores genéticos que melhor caracterizaram e discriminaram diabéticos e não diabéticos foram os alelos de HLA DQA1 e DQB1.

INTRODUCTION:Type 1A diabetes mellitus (T1ADM) is a multifactorial disease in which genetic and environmental aspects are important to its development. The association of genetic variations with disease has been demonstrated in several studies; however, the role of some gene loci has not yet been fully elucidated. OBJECTIVE:To compare the frequency of HLA alleles and polymorphism in CTLA-4 and insulin genes in Brazilians with T1ADM and individuals without the disease, as well as to identify genetic markers that are able to discriminate between diabetic and non-diabetic individuals. METHODS: The presence of HLA DQB1, DQA1 and DRB1 alleles, as well as the -2221 MspI polymorphism in the insulin gene and 49 A/G in the CTLA-4 gene were identified by the "Time-resolved fluorometer" technique after hybridization with probes labeled with Eu (III) / Sm (III) and Tb (III). RESULTS: The DQB1 *0302 and DQA1 *03 alleles were identified as predisposed to T1ADM, and the DQB1 *0301 allele presented a protective effect against the disease.The DQA1 label proved to be able to differentiate between 71.13% of the diabetic and non-diabetic individuals.This value increased to 82.47% when the DQB1 label was added. No significant difference in the frequency of polymorphisms in the insulin and CTLA-4 genes was observed between the two groups. CONCLUSIONS: The genetic markers that best characterized and discriminated diabetic and non-diabetic individuals were the HLA DQA1 and DQB1.alleles.