Karina Braga Gomes Borges

Hemostatic changes in patients with end stage renal disease undergoing hemodialysis

Patients undergoing hemodialysis may show both thrombotic complications and bleeding abnormalities. Hemostatic changes in patients on hemodialysis may result from alterations in vessel wall integrity and platelet function, and reduced blood flow in the native arteriovenous fistula. Vascular complications represent 20-25% of all hospitalizations of patients on hemodialysis. Literature survey revealed that changes in the hemostatic system may play a major role in vascular complications observed in these patients. Thus, it is essential to investigate hemostatic alterations in patients on hemodialysis so that adequate regimes for anticoagulant therapy could be implemented. In this review we discuss hemostatic abnormalities in end stage renal disease patients undergoing hemodialysis.

Effect of acetylsalicylic acid on platelet activation and oxidative profile in a set of Brazilian patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (DM2) is a metabolic disorder associated with hyperactivation of platelets, increased formation of platelet microparticles (PMPs) and oxidative stress that are related to cardiovascular complications. Acetylsalicylic acid (ASA) is an antiplatelet agent used in the prevention of atherothrombosis. The aim of this study was to evaluate the effect of ASA by means of platelet activation and oxidative profile. We collected blood samples of 81 patients with DM2 before and during ASA treatment. These samples were analyzed to determine the levels of 2,3-dinor thromboxane-B2 (2,3-dinor-TXB2), PMPs, thiobarbituric acid reactive species (TBARS) and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT). Moreover, the relationship between the levels of 2,3-dinor-TXB2 with some clinical and laboratory variables such as glycated hemoglobin, platelet count, D dimer, low-density lipoprotein cholesterol and glycoprotein IIb/IIIa and cyclooxygenase-1 polymorphisms was evaluated. ASA intake did not change the levels of PMP, TBARS and MTT. Although a significant decrease in the levels of 2,3 dinorTXB2 (P < 0.001) in patients under ASA has been observed, an equal and satisfactory response to this drug was not found. However, the presence of PIA2 allele in GPIIIa gene may be associated with a better response to ASA intake in these patients, whereas other clinical and laboratory variables showed no association with this drug use. These findings are consistent with previous reports in the literature that patients with DM2 do not benefit in an equal way from the use of ASA for primary prevention of atherothrombotic events.

A new index to discriminate between iron deficiency anemia and thalassemia trait

Background The most common microcytic and hypochromic anemias are iron deficiency anemia and thalassemia trait. Several indices to discriminate iron deficiency anemia from thalassemia trait have been proposed as simple diagnostic tools. However, some of the best discriminative indices use parameters in the formulas that are only measured in modern counters and are not always available in small laboratories. The development of an index with good diagnostic accuracy based only on parameters derived from the blood cell count obtained using simple counters would be useful in the clinical routine. Thus, the aim of this study was to develop and validate a discriminative index to differentiate iron deficiency anemia from thalassemia trait. Methods To develop and to validate the new formula, blood count data from 106 (thalassemia trait: 23 and iron deficiency: 83) and 185 patients (thalassemia trait: 30 and iron deficiency: 155) were used, respectively. Iron deficiency, β-thalassemia trait and α-thalassemia trait were confirmed by gold standard tests (low serum ferritin for iron deficiency anemia, HbA2 > 3.5% for β-thalassemia trait and using molecular biology for the α-thalassemia trait). Results The sensitivity, specificity, efficiency, Youdens Index, area under receiver operating characteristic curve and Kappa coefficient of the new formula, called the Matos & Carvalho Index were 99.3%, 76.7%, 95.7%, 76.0, 0.95 and 0.83, respectively. Conclusion The performance of this index was excellent with the advantage of being solely dependent on the mean corpuscular hemoglobin concentration and red blood cell count obtained from simple automatic counters and thus may be of great value in underdeveloped and developing countries.

Comparison of discriminative indices for iron deficiency anemia and β thalassemia trait in a Brazilian population

Abstract To discriminate iron deficiency anemia (IDA) from β thalassemia trait (βTT), several indices obtained from modern blood count analyzers have been reported. Discrimination power of seven indices to differentiate between IDA and βTT, such as Green and King Index (GKI), RDW Index (RDWI), Srivastava Index (SRI), Mentzer Index (MI), Shine and Lal Index (SLI), Ehsani Index (EI), and Sirdah Index (SI), were evaluated. These indices were applied on 47 patients with βTT and on 289 patients with IDA, as confirmed by gold standard tests. Sensitivity, specificity, positive and negative predictive values, efficiency, area under receiver-operating characteristics curve (AUC), and Youdens Index (YI) were calculated. GKI and RDWI showed the highest reliability, as they had the largest AUCs (0.919, 0.912, respectively) and Youdens Index (70.4, 74.6, respectively). Conversely, SLI presented a less satisfactory performance (AUC = 0.786 and YI = 6.6). Data taken together suggest the superiority of GKI and RDWI to discriminate between IDA and βTT.

RDW as differential parameter between microcytic anemias in "pure" and concomitant forms

Introduction: Iron deficiency anemia and thalassemia minor are microcytic and hypochromic types of anemia commonly found in our environment. The correct differentiation between them is of great clinical importance, although it is often hampered by the coexistence of diseases that may alter the results of standard tests for their discrimination, in addition to the significant costs of such tests. Objective: The objective of this study was to investigate the discriminatory power of red cell distribution width (RDW) between iron deficiency anemia and thalassemia minor. Method: Blood parameters were compared in 227 patients with iron deficiency anemia and/or thalassemia minor after diagnosis confirmed by molecular biology and HbA2 measurement for alpha thalassemia and beta thalassemia trait respectively. The frequency of alpha thalassemia trait in a population from two public hospitals of Minas Gerais was also determined. Result and conclusion: RDW was able to differentiate iron deficiency anemia from thalassemia trait, what indicates that this blood count parameter is a useful tool since concomitant disorders are excluded. In addition, a high frequency of the -α 3.7 mutation was observed in the study population (20.3%), justifying its investigation when another cause for microcytic anemia is absent.

Toxicological study of a new doxorubicin-loaded pH-sensitive liposome: A preclinical approach

&NA; Doxorubicin (DOX) is widely used in cancer treatment, however, the use of this drug is often limited due to its cardiotoxic side effects. In order to avoid these adverse effects, the encapsulation of DOX into nanosystems has been used in the last decades. In this context, pH‐sensitive liposomes have been shown promising for delivering cytotoxic agents into tumor cells, however, the lack of information about in vivo toxicity of this nanocarrier has impaired translational studies. Therefore, the aim of this work was to investigate the acute toxicity and cardiotoxicity of DOX‐loading pH‐sensitive liposomes (SpHL‐DOX). To achieve this, female BALB/c mice, after intravenous administration, were monitored by means of clinical, laboratory, histopathological and electrocardiographic (ECG) analyses. Results indicate that SpHL was able to prevent renal toxicity and the hepatic injury was less extensive than free DOX. In addition, lower body weight loss was associated with less ECG QT interval prolongation to animals receiving SpHL‐DOX (14.6 ± 5.2%) compared to animals receiving free DOX (35.7 ± 4.0%) or non‐pH‐sensitive liposomes (nSpHL‐DOX) (47.0 ± 9.8%). These results corroborate with SpHL‐DOX biodistribution studies published by our group. In conclusion, the SpHL‐DOX showed less toxic effects on mice compared to free DOX or nSpHL‐DOX indicating that SpHL‐DOX is a promising strategy to reduce the serious cardiotoxic effects of DOX. HighlightsDOX‐encapsulated liposomes prevent renal toxicity in miceFree DOX leading to more extensive hepatic injury than SpHL‐DOXElectrocardiographic parameters were much less affected by SpHL‐DOX than other groupsSpHL prove to be a promising strategy to overcome limitations of clinical use of DOX

EVALUATION OF PLATELET P-SELECTIN IN PATIENTS WITH ALZHEIMER'S DISEASE AND FRONTOTEMPORAL DEMENTIA

Background: Alcadeina (Alca) is a member of alcadein family composed of Alca, Alcb and Alcg, which is largely expressed in brain neuron and prone to form a tripartite complex with APP mediated by cytoplasmic neural-specific adaptor protein X11like (X11L). p3-Alca is generated from Alca by cleavage of aand g-secretases, and secreted into cerebrospinal fluid (CSF) and then into blood as does Ab from APP. The p3-Alca35 exists in CSF as a major species, as like as Ab40, while p3-Alca38 is minor as like as Ab42. p3-Alca is non-aggregatable so easily detected in CSF and plasma by sELISA (Hata 2009). To establish an effective AD diagnosis, we verified p3-Alca38/35, a ratio of p3-Alca38 to p3-Alca35. Methods: Previously, we showed the plasma level of p3-Alca35 using sELISAwith p3-Alca35 specific antibody (Omori 2014). To measure p3-Alca38/35 level, we tried to prepare new antibody raised to p3-Alca38 with higher affinity. Using cell surface display method, p3-Alca38 chimeric protein was expressed on cell surface and the cells were immunized. Several clones generating antibody specifically react to p3Alca38 were isolated, and we developed new sELISA system to quantify p3-Alca38 with higher sensitivity. Results:We first characterized the new sELISA systems to quantify p3-Alca38. With a combination of sELISA to quantify p3-Alca35, both p3-Alca35 and p3-Alca38 in body fluid were quantified. The levels p3Alca38/35 ratio in MCI and AD subjects showed a tendency increasing along with cognitive impairment degree compared to non-demented controls. The p3-Alca38/35 ratio significantly increased along with the increase of Ab42/40 ratio in vitro, while in vivo, the significant increase of p3-Alca38/35 correlated with the significant decrease of Ab42/40. Conclusions:Our study suggested that p3-Alca38/35 can be an effective biomarker of AD not only in CSF but also in plasma, which indicates a qualitative change of g-secretase activity. Further studies with samples from various cohorts (for example, with chronologically chasing and taking samples) will be performed to confirm the efficiency of p3-Alca38/35 as a biomarker to find prodromal and/or early stage MCI/AD subjects who shows an altered/attenuated g-secretase activity.

Features associated with cognitive impairment and dementia in a community-based sample of illiterate elderly aged 75+ years: The Pietà study

A higher level of educational attainment constitutes a protective factor against cognitive decline in the elderly. Nevertheless, the elements underpinning this association are yet not fully understood. Objective The primary aim of this study was to compare cognitively impaired illiterate elderly subjects with cognitively preserved counterparts, according to demographics, comorbidities, lifetime habits and APOE genotype. Methods This is a cross-sectional analysis of the illiterate subset of participants (n=174) from the Pietà study, a community-based survey of successful brain aging conducted in Caeté (MG), Brazil. Subjects were categorized into three diagnostic groups: cognitively normal (CN), cognitive impairment no-dementia (CIND) and dementia. The groups were then compared according to selected variables. Results Subjects with dementia were older and had an increased prevalence of reported stroke or transient ischemic attack. The three groups did not differ in relation to demographics, prevalence of comorbidities, socioeconomic level, previous occupation profile and APOE-ε4 allele frequency. Qualitatively evaluated lifetime habits, such as alcohol consumption, smoking and physical activity engagement were also similar across groups. Conclusion No associations were found between cognitive impairment/dementia and the variables evaluated in this community-based sample of illiterate elderly.

Regulatory and Pro-Inflammatory Cytokines in Brazilian Living-Related Renal Transplant Recipients According to Creatinine Plasma Levels

The maintenance of stable graft function in renal transplanted recipients (RTR) is a challenge for healthcare staff. The ideal biomarkers must have significant predictive values to monitor the intricate renal function response triggered after renal transplantation. The main purpose in this study was to evaluate the regulatory and pro‐inflammatory cytokines as biomarkers of allograft function in living‐related renal transplant patients.

Response to the assessment of the Matos & Carvalho index by Hoffmann and Urrechaga

Hoffmann and Urrechaga evaluated the Matos & Carvalho Index (MCI),1 however they performed their analyses characterizing the population differently from that used by us. In Matos et al.,2 anemia was characterized as hemoglobin (Hb) <12 g/dL for women and <13 g/dL for men.3 Conversely, Hoffmann and Urrechaga characterized anemia using the value of Hb <13 g/dL, independent of the sex of the patients, which is not recommended by the World Health Organization.3 In addition, the characterization of iron deficiency anemia (IDA) performed in our study was based on the ferritin level according to the gender, that is, <6 ng/mL for women and <28 ng/mL for men. Hoffmann and Urrechaga characterized IDA using ferritin <15 g/L regardless of gender. This variation in the definition of cases of anemia, particularly IDA, may affect the results, since in the study conducted by Hoffmann and Urrechaga, false positive women with Hb values greater than 12 g/dL and less than 13 g/dL were included in the study. Moreover, women with IDA and ferritin levels >6 and <15 ng/mL (false positive) and true positive men with ferritin levels >15 and <28 ng/mL were excluded. It is important to highlight that different criteria in the sample selection may interfere with the results of sensitivity, specificity and area under the curve. Following the above, some other aspects deserve clarification: Firstly, in Brazil, some studies have already been carried out to determine the frequency of the 3.7 kb deletion, the main mutation causing -thalassemia, with frequencies between 20% and 25% being found in the population studied.4,5 Despite this high frequency, the correct diagnosis of this disorder depends on molecular tests that are not accessible to a large proportion of the Brazilian population. Although used in many clinical laboratories, the hemoglobin (Hb) H test shows low sensitivity. The prevalence of the -thalassemia trait in Brazil is certainly lower than that observed in Mediterranean countries.