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Introduction: Neurogenic bladder was first confirmed as a urological sequela of Congenital Zika Syndrome (CZS) in 2018. Further clinical-epidemiological evidence also confirmed neurogenic bowel dysfunction and cryptorchidism. To strengthen the care for these children, the Congenital Zika Virus Bladder and Bowel Sequelae Network (RASZ in Brazilian) was created, including six integrated centers in Brazil. This article represents the initial outcome of the efforts by RASZ., Objective: To evaluate the prevalence of bladder and bowel dysfunction, cryptorchidism and other urological sequelae related to CZS in cohorts attended in six Brazilian states., Study Design: Observational, prospective, multicenter study including children with CZS assisted in one of six RASZ collaborative centers between June 2016 and February 2023. Data were collected from patient's first assessment using the same protocols for urological and bowel evaluation. Categorical variables were analyzed by frequency of occurrence and numerical variables by mean, median, and standard deviation. The study was approved by the Research Ethics Committees of each center, all parents/caregivers provided written informed consent., Results: The study included 414 children aged 2 months to 7 years (mean 2.77 years, SD 1.73), 227 (54.8 %) were male and 140 (33,8 %) referred urological and bowel symptoms on arrival. Prevalence of both urological and bowel sequelae was 66.7 %, 51 % of children aged 4 years and older had urinary incontinence (UI). UTI was confirmed in 23.4 % (two presented toxemia) and among males, 18.1 % had cryptorchidism. Renal ultrasonography, performed in 186 children, was abnormal in 25 (13.4 %), 7 had hydronephrosis. Among the 287 children who performed urodynamics, 283 (98.6 %) were altered: 232 had a lower bladder capacity, 144 a maximum bladder pressure of ≥40 cm H2O, and 127 did not satisfactorily empty their bladder., Discussion: A higher prevalence of NLUTD, neurogenic bowel and cryptorchidism was confirmed in children with CZS. Early diagnosis and appropriate treatment, including a multidisciplinary approach, may reduce the risk of UTIs, UI and kidney damage. A limitation of the study was the inability of children to complete the protocol, specifically urodynamic evaluation, and ultrasonography. In both exams, the percentage of abnormal cases was higher than that expected in the normal population., Conclusion: A 66,7 % prevalence of combined urological sequelae and bladder-bowel dysfunction related to CZS was confirmed in patients evaluated in six Brazilian cohorts. The most frequent changes were related to NLUTD, neurogenic bowel, and cryptorchidism. Prevalence may be underestimated due to access restrictions to diagnostic tests., Competing Interests: Conflict of interest None., (Copyright © 2023 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

The economic burden of chronic wounds, the complexity of the process of tissue repair and the possibility of resistant bacterial infections, have triggered a significant research interest in the application of natural alternative therapies for wound healing. Biomolecules are intrinsically multi-active, as they affect multiple mechanisms involved in tissue repair phenomenon, including immunomodulatory, anti-inflammatory, cell proliferation, extra cellular matrix remodeling and angiogenesis. Chitosan features a unique combination of attributes, including intrinsic hemostatic, antimicrobial, and immunomodulatory properties, that make it an exceptional candidate for wound management, in the development of wound dressings and scaffolds. In this study, we produced nanoemulsions (NE) loaded with SFO, characterized them, and evaluated their tissue repairing properties. Dynamic light scattering (DLS) analysis confirmed the formation of a nanoemulsion with a droplet size of 21.12 ± 2.31 nm and a polydispersity index (PdI) of 0.159, indicating good stability for up to 90 days. To investigate the potential wound healing effects, SFO-loaded NE were applied on male C57BL/6 mice for seven consecutive days, producing a significantly higher wound closure efficiency (p < 0.05) for the group treated with SFO-loaded NE compared to the control group treated with the saline solution. This finding indicates that the SFO-loaded NE exhibits therapeutic properties that effectively promote wound healing in this experimental model. Then, SFO-loaded NE were incorporated into chitosan:polyvinyl alcohol (PVA)-based films. The inclusion of NE into the polymer matrix resulted in increased lipophilicity reflected by the contact angle results, while decreasing moisture absorption, water solubility, and crystallinity. Moreover, FTIR analysis confirmed the formation of new bonds between SFO-NE and the film matrix, which also impacted on porosity properties. Thermal analysis indicated a decrease in the glass transition temperature of the films due to the presence of SFO-NE, suggesting a plasticizing role of NE, confirmed by XRD results, that showed a decrease in the crystallinity of the blend films upon the addition of SFO-NE. AFM images showed no evidence of NE droplet aggregation in the Chitosan:PVA film matrix. Moisture absorption and water content decreased upon incorporation of SFO-loaded NE. Although the inclusion of NE increased hydrophobicity and water contact angle, the values remained within an acceptable range for wound healing applications. Overall, our results emphasize the significant tissue repairing properties of SFO-loaded NE and the potential of Chitosan:PVA films containing nanoencapsulated SFO as effective formulations for wound healing with notable tissue repairing properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chagas Disease (CD) is a neglected illness whose immunopathological mechanisms have not yet been plainly elucidated. The asymptomatic (indeterminate) form of CD is a long-term condition and approximately 20% to 35% of the individuals with this form evolve into one of the three chronic symptomatic clinical forms of CD, namely: cardiac, digestive or cardio-digestive (mixed). A variant of blood monocytes characterized by low expression of the HLA-DR antigen (CD14 + /HLA-DR low/‒ ) constitutes a subtype of myeloid-derived suppressor cells (MDSCs) whose main function is to regulate exacerbated inflammatory processes. The development of the symptomatic forms of CD can be related to the interaction between the host's immune system and the CD14 + /HLA-DR low/‒ immunosuppressive monocytes. Here, we evaluated, by flow cytometry, the absolute number and the HLA-DR antigenic density of this population of MDSCs in 57 patients with the diagnosis of CD: 34 with the symptomatic clinical forms (26 cardiac and 8 mixed) and 23 with the asymptomatic (indeterminate) form. The asymptomatic form exhibited a greater number of CD14 + /HLA-DR low/‒ monocytes and, accordingly, a low HLA-DR antigenic density, when compared to the symptomatic forms. It is possible to speculate that the predominance of CD14 + /HLA-DR low/- monocytes in the patients with the asymptomatic (indeterminate) form might have been a factor that could delay or even prevent the evolution of the asymptomatic form to the symptomatic forms of Chagas Disease., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Children with Congenital Zika Syndrome (CZS) present structural cortical changes that may compromise the integrity of their connections with urinary and digestive systems, causing bowel and bladder dysfunctions., Objective: To evaluate bladder and bowel dysfunction (BBD) in children with CZS., Study Design: This is an observational cross-sectional study of a series of CZS cases. Urinary tracts were investigated using a bladder function protocol consisting of clinical history, detailed physical examination, laboratory tests, ultrasound of the lower and upper urinary tracts, and urodynamic evaluation. The bowel function protocol expanded anamnesis with questions related to signs and symptoms of functional disorders, Bristol scale, and ultrasound of the rectal ampoule., Results: Forty children with CZS, aged between one and five years were included. The majority (80%) had bladder and bowel dysfunction (BBD), 12.5% had bladder dysfunction only, and 7.5% only bowel dysfunction. A reduced bladder capacity was confirmed in 36 patients (90%), while 15 (40%) presented postvoid residual greater than 20% of their cystometric capacity. Thirty-five patients (87.5%) presented four signs/symptoms of functional bowel disorders and the rectal ampoule ultrasound was >2.9 cm in 21 (52.5%). Moreover, 19 (47.5%) presented urinary tract infection, while 5 (12.5%) developed pyelonephritis and required hospitalization. Renal ultrasound showed nephrolithiasis in three (7.5%), one (2.5%) presented horseshoe kidney, and a duplicated collecting system was found in three patients. Cryptorchidism was presented in eight (34%)., Discussion: Our study confirmed the presence of BBD in 80% of the children with CZS studied in this series. This is the first time that bowel dysfunction is confirmed in the settings of CZS. This recognition will facilitate early identification and appropriate therapies in an attempt to reduce complications. One limitation of the study is the absence of a control group. Due to the new aspects of CZS, it has been difficult to find a suitable group of patients with neurological disorders to compare and performing urodynamic studies in children without neurological or non-neurological voiding dysfunction is unethical. Appropriate control groups for future studies may be children with microcephaly due to other causes or older children with CZS who were not yet investigated or treated. Another limitation is the lack of a standard quantitative evaluation of bowel dysfunction in children with neurological disorders., Conclusion: Bladder and bowel dysfunction was confirmed in 80% of the children with CZS. This is a new Zika virus-associated neuromuscular disorder that needs to be further investigated., Competing Interests: Conflict of interest The authors have no conflicts of interest, and the sponsors contributed only with financial support., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Esthetic improvement is a key motivator in undergoing orthodontic treatment. This study aims to quantify the contribution of the smile and other facial components to the overall esthetics of attractiveness., Methods: The attractiveness of 60 subjects (30 men, 30 women), aged 18-35 years, before orthodontic treatment, was retrospectively evaluated by 8 laypersons using the Visual Analog Scale. Pearson and stepwise correlations were calculated between the attractiveness of the smiling face and the attractiveness of facial components; namely the smile, nose, eyes, hair, chin, eyebrows, and skin., Results: A strong correlation between the face and smile attractiveness was found (r = 0.71) for the whole sample. No significant correlations were found between attractiveness and the other facial components. When divided by gender, the smile (r = 0.70) and the eyes (r = 0.51) correlated with the attractiveness of the smiling face for men. For women, the face registered a significant correlation with the smile (r = 0.83) and the skin (r = 0.37)., Conclusions: In general, smile attractiveness was strongly correlated with the attractiveness of the smiling face, which is the only significant component. For men, the smile was responsible for 49% of the variation in the attractiveness of the smiling face, the eyes for 22%, and the hair for 6%. For women, 69% of the variation in facial attractiveness could be attributed to smile., (Copyright © 2019 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Biocompatible scaffolds have been used to promote cellular growth and proliferation in order to develop grafts, prostheses, artificial skins and cartilage. Electrospinning is widely studied as a method capable of producing nanofibers which enables cell attachment and proliferation, generating a functional scaffold that is suitable for many types of organs or tissues. In this study, electrospinning was used to obtain core-shell and monolithic fibers from the biocompatible poly (lactic acid) and poly (vinyl alcohol) polymers. The main purpose of this work is to produce core-shell nanofiber based scaffolds that works as a sustained delivery vehicle for BMP-2 protein, allowing those fibers to be used in the recovery of alveolar bone tissue without further bone surgery. Then, polymer nanofibers were manufactured by optimizing process parameters of coaxial electrospinning with emphasis on the most relevant ones: voltage, internal and external flows in an attempt to correlate fibers properties with protein releasing abilities. All nanofibers were characterized according to its morphology, thermal behaviour, crystallinity and release profile. For the release tests, bovine albumin was added into internal fiber for future periodontal restorage application. Obtained results demonstrate that fibers were formed with diameters up to 250 nm. According to electronic microscopy images, one could observe surface of nanofibers, thickness and core-shell morphology confirmed. X-ray diffraction analysis and contact angle tests showed fibers with low crystal degree and low hydrophobicity. Nanofibers structure affected in vitro release model tests and consequently the cellular assays., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: This study aimed to evaluate the influence of fetal hemoglobin (Hb F) on hemolysis biomarkers in sickle cell anemia patients., Methods: Fifty adult sickle cell anemia patients were included in the study. All patients were taking hydroxyurea for at least six months and were followed at the outpatient clinic of a hospital in Fortaleza, Ceará, Brazil. The control group consisted of 20 hemoglobin AA individuals. The reticulocyte count was performed by an automated methodology, lactate dehydrogenase and uric acid were measured by spectrophotometry and arginase I by enzyme-linked immunosorbent assay (ELISA). The presence of Hb S was detected by high-performance liquid chromatography. The level of significance was set for a p-value <0.05., Results: A significant increase was observed in the reticulocyte count and lactate dehydrogenase, uric acid and arginase I levels in sickle cell anemia patients compared to the control group (p-value <0.05). Patients having Hb F levels greater than 10% showed a significant decrease in the reticulocyte count, arginase I and lactate dehydrogenase. A significant decrease was observed in arginase I levels in patients taking hydroxyurea at a dose greater than 20mg/kg/day., Conclusion: The results of this study show that sickle cell anemia patients have increases in the hemolysis biomarkers, lactate dehydrogenase, reticulocyte count, arginase I, uric acid and increases in Hb F can reduce the reticulocyte count and arginase I and lactate dehydrogenase levels., (Copyright © 2015 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.)

Background: At the time of diagnosis, more than 50% of patients with myelodysplastic syndrome have a normal karyotype and are classified as having a favorable prognosis. However, these patients often show very variable clinical outcomes. Furthermore, current diagnostic tools lack the ability to look at genetic factors beyond karyotyping in order to determine the cause of this variability., Objective: To evaluate the impact of p53 protein expression at diagnosis in patients with low-risk myelodysplastic syndrome., Methods: This study enrolled 38 patients diagnosed with low-risk myelodysplastic syndrome. Clinical data were collected by reviewing medical records, and immunohistochemical p53 staining was performed on bone marrow biopsies., Results: Of the 38 participants, 13 (34.21%) showed p53 expression in their bone marrow. At diagnosis, this group of patients also presented clinical features characteristic of a poor prognosis more often than patients who did not express p53. Furthermore, patients expressing p53 had a shorter median survival time compared to those without p53 expression., Conclusion: This study shows that the expression of p53 at diagnosis is a useful indicator of distinct clinical characteristics and laboratory profiles found in low-risk myelodysplastic syndrome patients. These data indicate that the immunohistochemical analysis of p53 may be a prognostic tool for myelodysplastic syndrome and should be used as an auxiliary test to help determine the best therapeutic choice., (Copyright © 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.)

Background: Sickle cell anemia is a chronic inflammatory disease characterized by an increased production of proinflammatory cytokines including tumor necrosis factor-alpha. Hydroxyurea, by decreasing the polymerization of hemoglobin, reduces inflammatory states. The effect of the genetic polymorphisms of sickle cell patients on tumor necrosis factor-alpha levels remains unknown., Objective: The aim of this study was to investigate the association of tumor necrosis factor-alpha levels with β-globin haplotypes and the use of hydroxyurea., Methods: A cross-sectional study was performed of 67 patients with sickle cell anemia diagnosed at steady-state in a referral hospital in Fortaleza, Ceará, Brazil. A group of 26 healthy individuals was used as control. βS-haplotype analysis was performed by restriction fragment length polymorphism-polymerase chain reaction. The tumor necrosis factor-alpha levels were measured by the enzyme-linked immunosorbent assay test. Laboratory data (complete blood count and fetal hemoglobin) and information regarding the use of hydroxyurea were obtained from medical records. Statistical analysis was performed using R software with the Kruskal-Wallis and Mann-Whitney tests. Statistical significance was established for p-values < 0.05 for all analyses., Results: The mean age of the participants was 35.48 years. Patients with sickle cell anemia had significantly higher tumor necrosis factor-alpha levels than controls (p-values < 0.0001). Tumor necrosis factor-alpha levels were lower in sickle cell anemia patients who were receiving hydroxyurea treatment than those who were not (p-value = 0.1249). Sickle cell anemia patients with Bantu/n genotype had significantly higher levels than patients with the Bantu/Benin genotype (p-value = 0.0021)., Conclusion: In summary, βS-globin haplotypes, but not hydroxyurea therapy, have a role in modulating tumor necrosis factor-alpha levels in sickle cell anemia adults at steady-state. Many previous studies have investigated prognosis and inflammatory states in sickle cell anemia patients, but the discovery that tumor necrosis factor-alpha levels vary according to the genetic polymorphism of the patient is a new finding.

Objective: To investigate the association between kidney dysfunction and haplotypes in sickle cell disease., Methods: A cohort of 84 sickle cell disease patients, treated in a public health service in Fortaleza, Brazil, was studied. Hemoglobin S haplotypes were obtained from 57 patients as they had recently received blood transfusions with 18 of them agreeing to undertake urinary concentrating ability and acidification tests. The glomerular filtration rate was estimated using the Modification of Diet in Renal Disease Study equation. Urinary concentration was evaluated utilizing the urinary and serum osmolality ratio (U/Posm) after 12 hours of water deprivation. Urinary acidification was evaluated by measuring the urinary pH before and after the administration of oral CaCl2. The analysis of the haplotypes of the beta S gene cluster was carried out by polymerase chain reaction-restriction fragment length polymorphism. The analysis of variance (ANOVA) test was used for multiple comparisons of means and the Newman-Keuls test was used to identify which groups were significantly different., Results: The mean age of the patients was 33 ± 13 years with 64.2% being females. The glomerular filtration rate was normal in 25 cases (30%) and a rate > 120 mL/min was seen in 52 cases (62%). Urinary concentration deficit was found in all patients who underwent the test and urinary acidification in 22%. There was no significant difference when comparing patients with the Bantu/Bantu and Benin/Benin haplotypes. On comparing patients with the Central African Republic-haplotype however, a higher number had glomerular filtration rates between 60 and 120 mL/min., Conclusion: There was no significant difference among sickle cell disease patients regarding the haplotypes and kidney dysfunction.

Objective: The aim of this study was to evaluate the impact of iron overload on the profile of interleukin-10 levels, biochemical parameters and oxidative stress in sickle cell anemia patients., Methods: A cross-sectional study was performed of 30 patients with molecular diagnosis of sickle cell anemia. Patients were stratified into two groups, according to the presence of iron overload: Iron overload (n = 15) and Non-iron overload (n = 15). Biochemical analyses were performed utilizing the Wiener CM 200 automatic analyzer. The interleukin-10 level was measured by capture ELISA using the BD OptEIAT commercial kit. Oxidative stress parameters were determined by spectrophotometry. Statistical analysis was performed using GraphPad Prism software (version 5.0) and statistical significance was established for p-values < 0.05 in all analyses., Results: Biochemical analysis revealed significant elevations in the levels of uric acid, triglycerides, very low-density lipoprotein (VLDL), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea and creatinine in the Iron overload Group compared to the Non-iron overload Group and significant decreases in the high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Ferritin levels correlated positively with uric acid concentrations (p-value < 0.05). The Iron overload Group showed lower interleukin-10 levels and catalase activity and higher nitrite and malondialdehyde levels compared with the Non-iron overload Group., Conclusion: The results of this study are important to develop further consistent studies that evaluate the effect of iron overload on the inflammatory profile and oxidative stress of patients with sickle cell anemia.

Hydroxyurea (HU) is the primary pharmacologic agent for preventing the complications and improving the quality of life of sickle cell anemia (SCA) patients. Although HU has been associated with an increased risk of leukemia in some patients with myeloproliferative disorders, the mutagenic and carcinogenic potential of HU has not been established. This study used the alkaline comet assay to investigate DNA damage in peripheral blood leukocytes from 41 individuals with SCA treated with HU (SCAHU) and from 26 normal individuals. The presence of HbS and the analysis of the haplotypes of the beta S gene cluster were done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The damage index (DI) in the SCAHU group was significantly higher than in controls (p<0.001). Neither gender nor age was associated with DNA damage in controls or SCAHU individuals. Among the SCAHU individuals, DI was significantly influenced by length of HU treatment (p=0.0039) and BMI (p=0.001). Individuals with length of HU treatment≥20 months and BMI≤20kg/m(2) had a significantly greater DI than those with length of HU treatment<20 months and BMI>20kg/m(2). No significant influence of mean HU dose was observed on DI (p=0.950). However, individuals who received a mean HU dose≥20mg/kg showed a higher DI than those who received less. Furthermore, an association was observed between DI damage and HBB*S gene haplotypes. DI values for the Bantu/Bantu haplotype was greater when compared to the Benin/Benin haplotype; and the Bantu/Benin haplotype had a DI lower than the Bantu/Bantu haplotype and greater than the Benin/Benin haplotype. Our results show that DNA damage in sickle cell anemia is associated not only with treatment with HU but also with genotype., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Aim: The objective of this study was to correlate laboratory tests during the evolution of dengue fever, comparing frequencies between the different clinical forms in order to use test results to predict the severity of the disease., Methods: This is an observational, descriptive and retrospective study of 154 patients with clinical and serological diagnoses of dengue fever who, in the period from January to May 2008, were admitted in a tertiary state hospital in the city of Fortaleza that is a referral center for infectious diseases. The patients were allocated to two groups according to age: under 15 years old (n = 66) and 15 years or older (n = 88). The tests analyzed were blood count, platelet count, and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations., Results: Thrombocytopenia and elevated transaminases were observed in patients with classic dengue fever. The main laboratory abnormalities found in dengue hemorrhagic fever were thrombocytopenia, hemoconcentration and elevated transaminases, similar to severe dengue with the exception of hemoconcentration. Most laboratory abnormalities started on the 3rd day but were more evident on the 5th day with restoration of values by the 11(th) day; this was more prominent in under 15-year-olds and with the more severe clinical forms., Conclusion: These results are relevant in assessing the disease because they can be used as markers for more severe forms and can help by enabling the adaptation of the therapeutic conduct to the needs of individual patients.

Background: Sickle cell disease is a hemoglobinopathy characterized by hemolytic anemia, increased susceptibility to infections and recurrent vaso-occlusive crises that reduces the quality of life of sufferers., Objective: To evaluate the correlation of the levels of lactate dehydrogenase, malonaldehyde and nitrite to fetal hemoglobin in patients with sickle cell disease not under treatment with hydroxyurea in outpatients at a university hospital in Fortaleza, Ceará, Brazil., Methods: Forty-four patients diagnosed with sickle cell disease were enrolled at baseline. Diagnosis was confirmed by evaluating the beta globin gene using polymerase chain reaction-restriction fragment length polymorphism. The concentration of fetal hemoglobin was obtained by high-performance liquid chromatography. Serum levels of nitrite, malonaldehyde and lactate dehydrogenase were measured by biochemical methods., Results: Significantly higher levels of lactate dehydrogenase, nitrite and malonaldehyde were observed in patients with sickle cell disease compared to a control group. The study of the correlation between fetal hemoglobin levels and these variables showed a negative correlation with nitrite levels. No correlation was found between fetal hemoglobin and malonaldehyde or lactate dehydrogenase. When the study population was stratified according to fetal hemoglobin levels, a decrease in the levels of nitrite was observed with higher levels of fetal hemoglobin (p-value = 0.0415)., Conclusion: The results show that, similar to fetal hemoglobin levels, the concentration of nitrite can predict the clinical course of the disease, but should not be used alone as a modulator of prognosis in patients with sickle cell disease.

Background: Chronic myeloid leukemia is a neoplasm characterized by clonal expansion of hematopoietic progenitor cells resulting from the (9:22)(q34,11) translocation. The tyrosine kinase abl fusion protein,the initial leukemogenic event in chronic myeloid leukemia, is constitutively activated thus inducing the production of reactive oxygen species. Of particular relevance is the fact that an increase in reactive oxygen species can facilitate genomic instability and may contribute to disease progression., Objective: To evaluate oxidative stress by determining the levels of malondialdehyde and nitrite in chronic myeloid leukemia patients under treatment with 1st and 2nd generation tyrosine kinase inhibitors monitored at a referral hospital in Fortaleza, Ceará., Methods: A cross-sectional study was performed of 64 male and female adults. Patients were stratified according to treatment. The levels of malondialdehyde and nitrite were determined by spectrophotometry. Statistical differences between groups were observed using the Student t-test and Fisher's exact test. The results are expressed as mean ± standard error of mean. The significance level was set for a p-value < 0.05 in all analyses., Results: The results show significantly higher mean concentrations of nitrite and malondialdehyde in chronic myeloid leukemia patients using second-generation tyrosine kinase inhibitors compared to patients on imatinib., Conclusion: It follows that chronic myeloid leukemia patients present higher oxidative activity and that the increases in oxidative damage markers can indicate resistance to 1st generation tyrosine kinase inhibitors.

Background: Sickle cell anemia is a hemoglobinopathy caused by a mutation that results in the production of an abnormal hemoglobin molecule, hemoglobin S (Hb S). This is responsible for profound physiological changes, such as the sickling of red blood cells. Several studies have shown that hydroxyurea protects against vaso-occlusive crises., Objective: The aim of this study was to evaluate the oxidative stress associated with biochemical parameters in patients with sickle cell anemia treated with hydroxyurea., Methods: The study was conducted with 20 male and 25 female patients at the Hospital Universitário Walter Cantídio. The patients were divided into two groups: a study group (n = 12), patients with sickle cell anemia who were receiving hydroxyurea and a control group (n = 33) of sickle cell anemia patients not submitted to hydroxyurea treatment. The biochemical parameters analyzed were ferritin, transferrin, and serum iron. Glutathione was measured in its reduced form to analyze the oxidative state., Results: The results showed insignificant increases in the levels of serum iron, transferrin and ferritin in patients treated with hydroxyurea when compared with those who did not take the medication. However, the glutathione levels were significantly higher in patients taking hydroxyurea than in controls., Conclusions: These results indicate that hydroxyurea possibly acts as an antioxidant by increasing glutathione levels.

The voltage-dependent anion channel (VDAC) is the most abundant protein in the mitochondrial outer membrane (MOM). Due to its localization, VDAC is involved in a wide range of processes, such as passage of ATP out of mitochondria, and particularly plays a central role in apoptosis. Importantly, the assembly of VDAC provides interaction with a wide range of proteins, some implying oligomerization. However, many questions remain as to the VDAC structure, its supramolecular assembly, packing density, and oligomerization in the MOM is unknown. Here we report the so far highest resolution view of VDAC and its native supramolecular assembly. We have studied yeast MOM by high-resolution atomic force microscopy (AFM) in physiological buffer and found VDAC in two distinct types of membrane domains. We found regions where VDAC was packed at high density (approximately 80%), rendering the membrane a voltage-dependent molecular sieve. In other domains, VDAC has a low surface density (approximately 20%) and the pore assembly ranges from single molecules to groups of up to 20. We assume that these groups are mobile in the lipid bilayer and allow association and dissociation with the large assemblies. VDAC has no preferred oligomeric state and no long-range order was observed in densely packed domains. High-resolution topographs show an eye-shaped VDAC with 3.8 nm x 2.7 nm pore dimensions. Based on the observed VDAC structure and the pair correlation function (PCF) analysis of the domain architectures, we propose a simple model that could explain the phase behavior of VDAC, and illustrates the sensitivity of the molecular organization to conditions in the cell, and the possibility for modulation of its assembly. The implication of VDAC in cytochrome c release from the mitochondria during cell apoptosis has made it a target in cancer research.

The structural analysis of the individual components of the photosynthetic apparatus of Rhodopseudomonas palustris, or those of related species, is almost complete. To shed light on the assembly and organization of this machinery, we have studied native membranes of Rps.palustris grown under different light conditions using atomic force microscopy (AFM). The organization of the complexes in the membranes is different from any previously observed: with areas of crystalline core-complexes, crystalline peripheral antennae, mixed domains, and apparently pure lipid membranes devoid of protein. Examination of antennae structure shows that chromatic adaptation is associated with modifications in absorption and size of the peripheral light harvesting complexes (LH2) as light intensity is reduced. The core-complex is observed to contain a reaction centre (RC) surrounded by an elliptical assembly of 15 LH1 subunits and a "gap" attributed to the W-subunit. The localization of the W-subunit is not restricted to the periapsis of the core-complex but randomly located with respect to the RC imposed axis.