In vitro results with minimal blood toxicity of a combretastatin A4 analogue.

Cancer is a disease caused by uncontrolled cell growth that is responsible for several deaths worldwide. Breast cancer is the most common type of cancer among women and is the leading cause of death. Chemotherapy is the most commonly used treatment for cancer; however, it often causes various side effects in patients. In this study, we evaluate the antineoplastic activity of a parent compound based on a combretastatin A4 analogue. We test the compound at 0.01 mg mL- 1, 0.1 mg mL- 1, 1.0 mg mL- 1, 10.0 mg mL- 1, 100.0 mg mL- 1, and 1,000.0 mg mL- 1. To assess molecular antineoplastic activity, we conduct in vitro tests to determine the viability of Ehrlich cells and the blood mononuclear fraction. We also analyze the cytotoxic behavior of the compound in the blood and blood smear. The results show that the molecule has a promising antineoplastic effect and crucial anticarcinogenic action. The toxicity of blood cells does not show statistically significant changes.

Determination of vitamin D in tears of healthy individuals by the electrochemiluminescence method.

BACKGROUND: Vitamin D is a fat-soluble steroid hormone which can be converted into various forms and is of extreme physiological importance to our body. However, its functions and local metabolic pathways in some organs, such as the eye, have not yet been well studied. We aimed to verify the correlation between vitamin D levels in blood and tear fluid and the possibility of using tear fluid as a biological material for monitoring eye disorders in the future. METHODS: The electrochemiluminescence method was used to examine blood and tear samples collected with Schirmer test strips from 21 individuals without ocular disease. RESULTS: At the 95% confidence interval, mean tear fluid vitamin D = 37.8 ± 3.6 ng/mL, which is higher than the serum level, with a mean of 30.3 ± 7.7 ng/mL; Lin's concordance correlation coefficient = -0.018 (-0.174; 0.139), Pearson's coefficient = -0.070, and the Bland-Altman coefficient = -11.12 (-30.40; 8.16). Results were obtained using the program Stata version 11.0. CONCLUSION: It is possible to determine vitamin D levels in tear fluid using the electrochemiluminescence method, and as the results do not correlate with blood, there is possibility of using tear fluid as a biological matrix for detection of vitamin D, which may increase the possibilities of new studies in eye disorders.

Systemic chemotherapy interferes in homocysteine metabolism in breast cancer patients.

BACKGROUND: Hyperhomocysteinemia in breast cancer (BC) patients can be a risk factor for thromboembolic events. This study aimed to evaluate homocysteine and its cofators (folic acid and vitamin B12) concentrations and platelet count at diagnosis of BC, 3 and 6 months after the beginning of chemotherapy treatment and to correlate them with clinical data. METHODS: Thirty-five BC patients were included; blood samples were obtained by venipuncture. Plasmatic Hcy and cofactors concentrations were measured by competitive chemiluminescent enzyme immunoassay method. Platelet count was done using an automated analyzer. Statistical analysis was performed using the software SPSS. RESULTS: During chemotherapy, homocysteine (P = 0.032) and vitamin B12 (P < 0.001) concentrations increased, while folate and platelets decreased (P < 0.001). Among the clinical data, the menopausal status showed significant positive correlation (P = 0.022) with homocysteine concentration increase. CONCLUSIONS: Evaluation of homocysteine concentrations during chemotherapy is extremely important because their levels increase during chemotherapy treatment, thus increasing the risk of thromboembolism development.

Circulating tumor cell detection during chemotherapy in patients with breast cancer is not associated with plasma homocysteine levels.

Breast cancer remains the second most frequent type of cancer in the world and the first among women, and systemic chemotherapy is an adjuvant therapeutic modality that improves survival in a great part of patients. Women with breast cancer, however, frequently show a higher risk of thromboembolism, an event associated to hyperhomocysteinemia and the presence of circulating tumor cells (CTC). Our aim is to correlate the presence of CTCs, detected by the analysis of CK19 and c-erbB2 gene expressions, and the homocysteine plasma levels in the peripheral blood in patients with breast cancer undergoing chemotherapy. Epithelial marker expression (CK19 and c-erbB2) and homocysteine levels were analyzed in a mononuclear fraction of the peripheral blood and plasma, respectively, obtained from 35 patients diagnosed with breast cancer at diagnosis and throughout chemotherapy treatment. No significant relation between the CK19 and c-erbB2 expressions and hyperhomocysteinemia was observed at any moment of the evaluation throughout the chemotherapy treatment (3 and 6 months after the onset). Among clinical data, only menopausal status showed a statistically significant correlation with homocysteine concentration. Although differences in the expressions of the analyzed epithelial markers were detected at 3 and 6 months of chemotherapy treatment, no relation between plasma homocysteine variations and the CK19 and c-erbB2 gene expressions was found in patients under chemotherapy treatment at any moment of the evaluation, suggesting that chemotherapy affects the expressions of the studied genes independently.

Hematological and hepatic effects of vascular epidermal growth factor (VEGF) used to stimulate hair growth in an animal model.

BACKGROUND: Alopecia areata is the hair loss usually reversible, in sharply defined areas. The treatment of alopecia using growth factors shows interesting activity in promoting hair growth. In this concept, VEGF (vascular endothelial growth factor) is a marker of angiogenesis, stimulating hair growth by facilitating the supply of nutrients to the hair follicle, increasing follicular diameter. The aim of this study was the evaluation of a topical gel enriched with VEGF liposomes on the hair growth stimulation and its toxicological aspects. METHODS: Mesocricetus auratus were randomly divided into three groups. Control group was treated with Aristoflex® gel, 1% group with the same gel but added 1% VEGF and 3% group with 3% VEGF. Biochemical, hematological and histological analyses were done. RESULTS: At the end of the experiment (15th day of VEGF treatment) efficacy was determined macroscopically by hair density dermatoscopy analysis, and microscopically by hair diameter analysis. They both demonstrated that hair of the VEGF group increased faster and thicker than control. On the other hand, biochemical and hematological results had shown that VEGF was not 100% inert. CONCLUSIONS: VEGF increased hair follicle area, but more studies are necessary to confirm its toxicity.

Survivin expression as a prognostic marker for breast cancer.

OBJECTIVE: Due to the speed of development observed in breast cancer, several studies aimed at discovering new biomarkers have been carried out in order to arrive at an early diagnosis. As survivin plays a fundamental role in the evasion of apoptosis in tumor cells, the aim of this study was to verify the expression profile of the survivin gene in paraffin-embedded breast tumor samples and associate it with the clinical characteristics of the patients. METHODS: This is a cross-sectional study, for which 100 tumor samples were obtained from cancer patients treated throughout the year 2019 at Instituto de Mama do Cariri (Juazeiro do Norte, in the state of Ceará). This study included women over 30 years old who had confirmed breast cancer through anatomopathological examination but excluded those with non-neoplastic breast comorbidities, other neoplasms, or chronic diseases. Survivin gene expression was assessed by quantitative polymerase chain reaction. RESULTS: The expression of survivin is associated with the lack of expression of estrogen (p=0.027) and progesterone (p>0.0005) receptors. It means that survivin expression is higher in patients in which labeling was absent for estrogen receptor and progesterone receptor. CONCLUSION: Our data reinforce that survivin expression is higher in estrogen receptor-patients, thus representing an additional prognostic tool.

Use of Saliva to Assess the Adherence to Treatment with Oral Hypoglycemic Agents in Patients with Type 2 Diabetes.

BACKGROUND: The diagnosis of Type 2 Diabetes Mellitus (T2DM) is made by demonstrating the hypoglycemic condition, which involves the determination of plasma glucose, and the follow-up of hypoglycemic treatment is performed by assessing the glycated hemoglobin (HbA1c) concentration. AIM: The aim of this study was to evaluate the saliva as an alternative sample in assessing the adherence to treatment with oral hypoglycemic agents in patients with Type 2 Diabetes. METHODS: We selected 68 patients with T2DM, who were subjected to venous blood and saliva collection, in addition to answering a standardized questionnaire on adherence to hypoglycemic treatment. Laboratory tests performed on saliva, whole blood, serum or plasma included assessment of glycemia, urea, creatinine, uric acid, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, and glycated hemoglobin. RESULTS: It was concluded that 82% of the patients adhered to hypoglycemic treatment based on glycated hemoglobin concentration (cut-off value of 7.0%). Comparing the groups that adhered to hypoglycemic treatment and those that did not adhere, statistical differences (P<0.05) were observed in the glucose, HDL-cholesterol, triglycerides, and insulin use (insulin therapy) parameters. Plasma glucose and urea serum concentration showed positive correlations when compared to saliva samples. Regarding the questionnaire, it was found that 35% of the patients presented positive screening for belief barriers and 83% positive score for recall barriers, and the positive screening correlated with glycated hemoglobin. CONCLUSION: Data have shown that it is possible to use saliva as an alternative sample to the laboratory assessment of hypoglycemic treatment adherence in T2DM patients.

COVID-19 compromises iron homeostasis: Transferrin as a target of investigation.

IMPORTANCE: Since the beginning of the COVID-19 pandemic, numerous metabolic alterations have been observed in individuals with this disease. It is known that SARS-CoV-2 can mimic the action of hepcidin, altering intracellular iron metabolism, but gaps remain in the understanding of possible outcomes in other pathways involved in the iron cycle. OBJECTIVE: To profile iron, ferritin and hepcidin levels and transferrin receptor gene expression in patients diagnosed with COVID-19 between June 2020 and September 2020. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study that evaluated iron metabolism markers in 427 participants, 218 with COVID-19 and 209 without the disease. EXPOSURES: The primary exposure was positive diagnose to COVID-19 in general population of Santo André and São Bernardo cities. The positive and negative diagnose were determinate through RT-qPCR. MAIN OUTCOMES AND MEASURES: Devido a evidências de alterações do ciclo do ferro em pacientes diagnosticados com COVID-19 e devido a corregulação entre hepcidina e receptor de transferrina, uma análise da expressão gênica deste último, poderia trazer insights sobre o estado de ferro celular. A hipótese foi confirmada, mostrando aumento da expressão de receptor de transferrina concomitante com redução do nível de hepcidina circulante. RESULTS: Serum iron presented lower values in individuals diagnosed with COVID-19, whereas serum ferritin presented much higher values in infected patients. Elderly subjects had lower serum iron levels and higher ferritin levels, and men with COVID-19 had higher ferritin values than women. Serum hepcidin was lower in the COVID-19 patient group and transferrin receptor gene expression was higher in the infected patient group compared to controls. CONCLUSIONS AND RELEVANCE: COVID-19 causes changes in several iron cycle pathways, with iron and ferritin levels being markers that reflect the state and evolution of infection, as well as the prognosis of the disease. The increased expression of the transferrin receptor gene suggests increased iron internalization and the mimicry of hepcidin action by SARS-CoV-2, reduces iron export via ferroportin, which would explain the low circulating levels of iron by intracellular trapping.

Quantification of Vitamin D at Different Levels of Clinical Worsening of COVID-19.

INTRODUCTION AND AIM: Vitamin D is the name given to a group of lipid-soluble steroidal substances of physiological importance in the body, especially in bone metabolism. The active form of vitamin D is believed to have immunomodulatory effects on immune system cells, especially T lymphocytes, as well as on the production and action of several cytokines and on the expression of potent antimicrobial peptides in epithelial cells that line the respiratory tract, playing an important role in protecting the lung from infections. The aim of this study was to assess vitamin D levels in patients with COVID-19 in healthcare service and to verify that these levels are adequate to protect the progression of this infection. METHODS: The aim of this observational study was to evaluate the serum concentration of vitamin D in 300 patients suspected of being infected with COVID-19, treated at Basic Health Units (BHUs) and at the Hospital Complex in the municipality of São Bernardo do Campo. RESULTS: 294 patients were included, 195 (66%) of which tested positive for COVID-19 and 99 (34%) negative for COVID-19. Among the patients in the positive group, 163 patients were in the mild group (84%); 22 patients in the moderate group (11%); 8 patients in the severe group (4%), and 2 patients in the deceased group (1%). CONCLUSION: For the patients in this study, no association was observed for the protective factor of vitamin D against COVID-19 infection, and its role in controlling the clinical staging of the disease was not verified.

NGAL and SMAD1 gene expression in the early detection of diabetic nephropathy by liquid biopsy.

INTRODUCTION: Diabetic nephropathy (DN) is a disease that progresses with the slow and progressive decline of the glomerular filtration rate (GFR); the installation of this pathology is silent and one of the major causes of death in patients with diabetes. AIMS: To identify new molecular biomarkers for early identification of the onset of DN in patients with type II diabetes mellitus (DM2). We studied the expression profile of the genes; suppressor of mothers against decapentaplegic type 1 (SMAD1), neutrophil gelatinase-associated lipocalin (NGAL) and type IV collagen (COLIV1A) in peripheral blood and urine sediment samples. METHODS: Ninety volunteers, 51 with DM2 and 39 healthy, were recruited from the Faculdade de Medicina do ABC outpatient clinic. We conducted an interview and collected anthropometric data, as well as blood and urine samples for biochemical evaluation and real-time PCR amplification of the genes of interest. RESULTS: Gene expression data: peripheral blood NGAL (DM2 0.09758±0.1914 vs CTL 0.02293±0.04578), SMAD1 (blood: DM2 0.01102±0.04059* vs CTL 0.0001317±0.0003609; urine: DM2 0.7195±2.344* vs CTL 0.09812±0.4755), there was no significant expression of COLIV1A. These genes demonstrated good sensitivity and specificity in the receiving operating characteristic curve evaluation. CONCLUSION: Our data suggest the potential use of NGAL and SMAD1 gene expression in peripheral blood and urine samples as early biomarkers of DN.

Irisin and troponin I expression in dialysis patients submitted to remote ischemic preconditioning: a pilot study.

BACKGROUND: Renal replacement therapy continues to be related to high hospitalization rates and poor quality of life. All-cause morbidity and mortality in renal replacement therapy in greater than 20% per year, being 44 times greater when diabetes is present, and over 10 times that of the general population. Regardless of treatment, the 5-year survival is 40%, surpassing many types of cancers. Irisin is a hormone that converts white adipose tissue into beige adipose tissue, aggregating positive effects like fat mass control, glucose tolerance, insulin resistance, prevention of muscle loss, and reduction in systemic inflammation. OBJECTIVES: To determine the serum levels of troponin I in hemodialysis patients submitted to remote ischemic preconditioning (RIPC) associated with irisin expression. METHODS: This was a prospective, randomized, double-blind clinical trial with patients with chronic kidney disease submitted to hemodialysis for a 6-month period. Troponin I, IL-6, urea, TNF-α, and creatinine levels were determined from blood samples. The expressions of irisin, thioredoxin, Nf-kb, GPX4, selenoprotein and GADPH were also evaluated by RT-PCR. RESULTS: Samples from 14 hypertensive patients were analyzed, 9 (64.3%) of whom were type 2 diabetics, aged 44-64 years, and 50% of each sex. The difference between pre- and post-intervention levels of troponin I was not significant. No differences were verified between the RIPC and control groups, except for IL-6, although a significant correlation was observed between irisin and troponin I. CONCLUSION: Remote ischemic preconditioning did not modify irisin or troponin I expression, independent of the time of collection.

Salivary uric acid is a predictive marker of body fat percentage in adolescents.

As saliva showed to be a noninvasive source of markers useful to monitor clinical status, the hypothesis tested was that saliva may provide reliable markers able to predict the body fat accumulation in young subjects. The salivary characteristics of 248 adolescent scholars (119 girls; 14-17 years) of flow rate, pH, phosphorus, urea, and calcium concentrations were assessed in stimulated saliva (colorimetric automated technique). The concentrations of cholesterol, 7-ketocholesterol, 25-hydroxyvitamin D2 and D3, and uric acid (UA) were measured with high-performance liquid chromatography in saliva collected at home (12-hour fast). Physical examination included height, weight, and body fat percentage (%BF) measured using bioelectric impedance to classify groups in below/above the %BF cutoff. Data were evaluated using 2-way analysis of variance and multiple linear regression. No significant difference was found in the levels of 25-hydroxyvitamin D2 and D3, cholesterol, 7-ketocholesterol, phosphorus, calcium, and urea between groups above and below %BF cutoff, and the variation in salivary flow was small. Significant sex and group effects were observed for salivary UA, which was increased in adolecents with higher %BF and in males (compared to females), without sex group interaction (power = 99.8%). Sex showed a significant effect on salivary urea, with lower levels in females. A predictive model was obtained, with salivary UA and sex explaining the variation of %BF (P < .001; power = 84%). Salivary UA showed to be an important marker of body fat accumulation in adolescents, demonstrating the clinical relevance of saliva to detect early changes and to monitor the nutritional status using a noninvasive and accurate method.

In vitro and in vivo persistence of IncN plasmids carrying qnr genes in uropathogenic Escherichia coli isolates.

OBJECTIVES: This study aimed to evaluate the persistence of the plasmid-mediated quinolone resistance (PMQR) among uropathogenic Escherichia coli strains grown under or without exposure to subinhibitory concentrations of ciprofloxacin. Based on that, we evaluated the possible spontaneous loss or maintenance of PMQR and the possible appearance of compensatory mutations in gyrA and parC genes. METHODS: Three uropathogenic E. coli strains harbouring chromosomal mutations in the gyrA and/or parC genes coupled with qnrS1 or qnrB2 determinants carried by distinct plasmid sizes and incompatibility N groups (IncN/ST1, IncN/ST5) were evaluated using in vitro and in vivo assays. RESULTS: PMQRs remained stable in all strains throughout the generations evaluated, independently of exposure to ciprofloxacin in both in vivo and in vitro assays. Analysis of gyrA and parC genes after in vivo and in vitro assays revealed that no changes occurred in quinolone-resistance determining regions (QRDR). CONCLUSION: We demonstrated that IncN plasmids were persistent over 14 days in E. coli clinical strains independently of exposure to ciprofloxacin, as well as previous mutations in QRDR.

The role of Survivin as a biomarker and potential prognostic factor for breast cancer.

Breast cancer (BC) is one of the primary health problems worldwide. As the most common cancer in women in the world and in Brasil, behind only non-melanoma skin cancer, this neoplasm corresponds to approximately 28% of new cases per year in the country. BC also affects men, although the incidence corresponds to only 1% of total cases. Currently, most of the chemotherapeutic agents used in BC treatment are extremely toxic and cause long-term side effects. There is also a need to obtain earlier diagnoses, more accurate prognoses and make new therapies available that are more selective and effective in order to improve the current scenario. Therefore, this work sought to evaluate the importance of the biomarker survivin (Sur) in relation to BC, through the detailing of the role of Sur as a biomarker, the correlation between this protein and the prognosis of BC patients, and a summary of therapeutic strategies that target Sur for the development of new anticancer therapies.

Survivin expression as a prognostic marker for breast cancer

SUMMARY OBJECTIVE: Due to the speed of development observed in breast cancer, several studies aimed at discovering new biomarkers have been carried out in order to arrive at an early diagnosis. As survivin plays a fundamental role in the evasion of apoptosis in tumor cells, the aim of this study was to verify the expression profile of the survivin gene in paraffin-embedded breast tumor samples and associate it with the clinical characteristics of the patients. METHODS: This is a cross-sectional study, for which 100 tumor samples were obtained from cancer patients treated throughout the year 2019 at Instituto de Mama do Cariri (Juazeiro do Norte, in the state of Ceará). This study included women over 30 years old who had confirmed breast cancer through anatomopathological examination but excluded those with non-neoplastic breast comorbidities, other neoplasms, or chronic diseases. Survivin gene expression was assessed by quantitative polymerase chain reaction. RESULTS: The expression of survivin is associated with the lack of expression of estrogen (p=0.027) and progesterone (p>0.0005) receptors. It means that survivin expression is higher in patients in which labeling was absent for estrogen receptor and progesterone receptor. CONCLUSION: Our data reinforce that survivin expression is higher in estrogen receptor-patients, thus representing an additional prognostic tool.

Lung cancer biomarkers. A literature review / Biomarcadores de câncer de pulmão. Uma revisão de literatura

ABSTRACT Lung cancer is the first in terms of incidence and mortality, being responsible worldwide for about 1.8 million deaths. In Brazil 31,270 new cases were diagnosed in 2018, 18,740 in men and 12,350 in women. One of the main challenges about lung cancer is performing an early diagnosis, in most cases the disease is detected in the late stages, which implies in poor prognoses. Tumor biomarkers are hugely relevant in early diagnosis, understanding of carcinogenesis, prognostic determination and therapeutic choice. The present paper reviews non-small cell lung cancer biomarkers described in the literature and their diagnostic, prognostic and therapeutic applications, intervention and therapeutic control for individualized therapy. Although there is still a vast universe to be explored, studies reveal a promising future for lung cancer treatment with increasingly personalized and assertive therapies that increase the chances of progression-free survival.

RESUMO O câncer de pulmão é o primeiro em incidência e mortalidade, sendo responsável mundialmente por cerca de 1,8 milhão de mortes. No Brasil, 31.270 casos novos foram diagnosticados em 2018, sendo 18.740 em homens e 12.350 em mulheres. Um dos principais desafios do câncer de pulmão é o diagnóstico precoce, na maioria das vezes a doença é detectada em fases tardias, o que implica em mau prognóstico. Os biomarcadores tumorais são extremamente relevantes no diagnóstico precoce, compreensão da carcinogênese, determinação do prognóstico e escolha terapêutica. O presente trabalho revisa biomarcadores de câncer de pulmão de células não pequenas descritos na literatura e suas aplicações diagnósticas, prognósticas e terapêuticas, intervenção e controle terapêutico para terapia individualizada. Embora ainda exista um vasto universo a ser explorado, estudos revelam um futuro promissor para o tratamento do câncer de pulmão com terapias cada vez mais personalizadas e assertivas que aumentam as chances de sobrevida livre de progressão.

Urinary beta-trace protein gene expression analysis in type 2 diabetes mellitus patients.

OBJECTIVE: To evaluate the gene expression of beta-trace protein in urine of diabetic patients, with no reduction in glomerular filtration rate, which was defined as below 60mL/min/1.73m2. METHODS: Type 2 diabetes mellitus patients were recruited, and a group of non-diabetic individuals served as control. Beta-trace protein gene expression was analyzed by quantitative PCR. Blood samples were collected to establish glucose levels and baseline kidney function. Accuracy was analyzed using ROC curves. RESULTS: Ninety type 2 diabetes mellitus patients and 20 non-diabetic individuals were recruited. The area under the curve was 0.601, sensitivity of 20% and specificity of 89.47%. Among diabetic participants, 18% showed an expression above the cutoff point. CONCLUSION: These results of accuracy of beta-trace protein gene expression in urine of diabetic patients are promising, although they did not achieve a higher area under the curve level.

Impact of Selenium Supplementation in Neutropenia and Immunoglobulin Production in Childhood Cancer Patients.

Essential to human health, selenium (Se) has enzymatic functions of fundamental importance to human biology due to its effects on DNA damage repair, its antioxidant properties, and cancer prevention. The best studied relationships between Se and the immune system is its role in the functions of neutrophils and of lymphocytes. Despite these observations, it is not yet clear by which mechanism Se is able to modify the immune status. This was a double-blind, crossover study: Group 1 received Se and Group 2 received placebo (30 days). After this, Group 1 received placebo and Group 2 received Se (30 days). Every 30 days, blood samples were collected for white blood cell count, red blood cell count, and Ig level measurement (IgA, IgG, IgE, IgM). Of the 36 patients, 17 were suffering from leukemia/lymphomas (LL) and 19 from solid tumors (ST). In the ST group's leukogram, a significant increase in neutrophils was observed after Se usage (P = .0192). During the analyzed period, Se minimized the triggering of neutropenia cases in both groups. IgA and IgG levels in ST patients were significantly higher than those identified in LL patients after Se usage (P = .0051 and P = .0055). For IgA, a significant increase in its production, after Se usage, was observed in the ST group when compared to the LL (P = .0011). The same did not occur to the IgM and IgE immunoglobulins. In our study, the supplementation with Se reduced the neutropenic cases (LL and ST patients) and reduced IgG and IgA levels in LL and increased in ST group.

Predictive Potential of Twenty-Two Biochemical Biomarkers for Coronary Artery Disease in Type 2 Diabetes Mellitus.

We investigated the potential of a panel of 22 biomarkers to predict the presence of coronary artery disease (CAD) in type 2 diabetes mellitus (DM2) patients. The study enrolled 96 DM2 patients with (n = 75) and without (n = 21) evidence of CAD. We assessed a biochemical profile that included 22 biomarkers: total cholesterol, LDL, HDL, LDL/HDL, triglycerides, glucose, glycated hemoglobin, fructosamine, homocysteine, cysteine, methionine, reduced glutathione, oxidized glutathione, reduced glutathione/oxidized glutathione, L-arginine, asymmetric dimethyl-L-arginine, symmetric dimethyl-L-arginine, asymmetric dimethyl-L-arginine/L-arginine, nitrate plus nitrite, S-nitrosothiols, nitrotyrosine, and n-acetyl-ß-glucosaminidase. Prediction models were built using logistic regression models. We found that eight biomarkers (methionine, nitratate plus nitrite, n-acetyl-ß-glucosaminidase, BMI, LDL, HDL, reduced glutathione, and L-arginine/asymmetric dimethyl-L-arginine) along with gender and BMI were significantly associated with the odds of CAD in DM2. These preliminary findings support the notion that emerging biochemical markers might be used for CAD prediction in patients with DM2. Our findings warrant further investigation with large, well-designed studies.

Irisin and troponin I expression in dialysis patients submitted to remote ischemic preconditioning: a pilot study / Expressão de irisina e troponina I em pacientes em diálise submetidos a pré-condicionamento isquêmico remoto: um estudo piloto

ABSTRACT Background: Renal replacement therapy continues to be related to high hospitalization rates and poor quality of life. All-cause morbidity and mortality in renal replacement therapy in greater than 20% per year, being 44 times greater when diabetes is present, and over 10 times that of the general population. Regardless of treatment, the 5-year survival is 40%, surpassing many types of cancers. Irisin is a hormone that converts white adipose tissue into beige adipose tissue, aggregating positive effects like fat mass control, glucose tolerance, insulin resistance, prevention of muscle loss, and reduction in systemic inflammation. Objectives: To determine the serum levels of troponin I in hemodialysis patients submitted to remote ischemic preconditioning (RIPC) associated with irisin expression. Methods: This was a prospective, randomized, double-blind clinical trial with patients with chronic kidney disease submitted to hemodialysis for a 6-month period. Troponin I, IL-6, urea, TNF-α, and creatinine levels were determined from blood samples. The expressions of irisin, thioredoxin, Nf-kb, GPX4, selenoprotein and GADPH were also evaluated by RT-PCR. Results: Samples from 14 hypertensive patients were analyzed, 9 (64.3%) of whom were type 2 diabetics, aged 44-64 years, and 50% of each sex. The difference between pre- and post-intervention levels of troponin I was not significant. No differences were verified between the RIPC and control groups, except for IL-6, although a significant correlation was observed between irisin and troponin I. Conclusion: Remote ischemic preconditioning did not modify irisin or troponin I expression, independent of the time of collection.

RESUMO Introdução: A terapia de substituição renal continua associada a altas taxas de hospitalização e baixa qualidade de vida. A morbimortalidade por todas as causas na terapia de substituição renal é superior a 20% ao ano, sendo 44 vezes maior quando a diabetes está presente e mais de 10 vezes a da população em geral. Independentemente do tratamento, a sobrevida em 5 anos é de 40%, superando muitos tipos de câncer. A irisina é um hormônio que converte tecido adiposo branco em tecido adiposo bege, agregando efeitos positivos como o controle de massa gorda, tolerância à glicose, resistência à insulina, prevenção de perda muscular e redução da inflamação sistêmica. Objetivos: Determinar os níveis séricos de troponina I em pacientes em hemodiálise submetidos ao pré-condicionamento isquêmico remoto (PCIR) associado à expressão da irisina. Métodos: Estudo clínico prospectivo, randomizado, duplo-cego, com pacientes com doença renal crônica submetidos à hemodiálise por um período de 6 meses. Os níveis de troponina I, IL-6, uréia, TNF-α e creatinina foram determinados a partir de amostras de sangue. As expressões de irisina, tioredoxina, Nf-kb, GPX4, selenoproteína e GADPH foram também avaliadas por RT-PCR. Resultados: Foram analisadas amostras de 14 pacientes hipertensos, 9 (64,3%) dos quais eram diabéticos tipo 2, com idades entre 44 e 64 anos e 50% de cada gênero. A diferença entre os níveis pré e pós-intervenção de troponina I não foi significativa. Não houve diferenças entre os grupos PCIR e controle, exceto pela IL-6, embora tenha sido observada correlação significativa entre irisina e troponina I. Conclusão: O pré-condicionamento isquêmico remoto não modificou a expressão de irisina ou troponina I, independentemente do tempo de coleta.