Identification of the first large deletion in the CLDN16 gene in a patient with FHHNC and late-onset of chronic kidney disease: case report.

BACKGROUND: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare autosomal recessive renal disease characterized by tubular disorders at the thick ascending limb of Henle's loop. It is caused by mutations in the tight junction structural proteins claudin-16 or claudin-19, which are encoded by the CLDN16 and CLDN19 genes, respectively. Patients exhibit excessive wasting of calcium and magnesium, nephrocalcinosis, chronic kidney disease, and early progression to end-stage renal failure during infancy. CASE PRESENTATION: We here report the phenotype and molecular analysis of a female Brazilian patient with a novel large homozygous deletion in the CLDN16 gene. The proband, born from consanguineous parents, presented the first symptoms at age 20. Clinical examination revealed hypocalcemia, hypomagnesemia, nephrocalcinosis, mild myopia, high serum levels of uric acid and intact parathyroid hormone, and moderate chronic kidney disease (stage 3). She and her mother were subjected to CLDN16 and CLDN19 mutational analysis. In addition, the multiplex ligation-dependent probe amplification method was used to confirm a CLDN16 multi-exon deletion. Direct sequencing revealed a normal CLDN19 sequence and suggested a large deletion in the CLDN16 gene. Multiplex ligation-dependent probe amplification showed a homozygous CLDN16 multi-exon deletion (E2_E5del). The patient initiated conventional treatment for familial hypomagnesemia with hypercalciuria and nephrocalcinosis and progressed to end-stage kidney disease after five years. CONCLUSIONS: This study provides the first report of a large homozygous deletion in the CLDN16 gene causing familial hypomagnesemia with hypercalciuria and nephrocalcinosis with late onset of the first symptoms. This description expands the phenotypic and genotypic characterization of the disease. The late-onset chronic kidney disease in the presence of a homozygous deletion in the CLDN16 gene reinforces the great variability of genotype-phenotype manifestation in patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis.

Steroid-induced ocular hypertensive response in children and adolescents with acute lymphoblastic leukemia and non-Hodgkin lymphoma.

The aim of this study was to evaluate intraocular pressure (IOP) associated with use of glucocorticoids in children and adolescents treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma. We carried out a prospective descriptive study with measurement of IOP before treatment (D0), 8th (D8), 14th (D14), and 28 h days (D28) of treatment. We examined 12 patients, with two cases of ocular hypertension, and it was found a statistically significant difference between the means of IOP between D0 versus D8 and D0 versus D14 (P = 0.013). The possibility of silent ocular hypertension with irreversible blindness indicates the need of IOP verification.

Exploring N-acylhydrazone derivatives against clinical resistant bacterial strains.

Bacterial multiresistance is a health problem worldwide that demands new antimicrobials for treating bacterial-related infections. In this study, we evaluated the antimicrobial activity and the theoretical toxicology profile of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazide derivatives against gram-positive and gram-negative bacteria clinical strains. On that purpose we determined the minimum inhibitory (MIC) and bactericidal (MBC) concentrations, the in vitro cytotoxicity, and in silico risk profiles, also comparing with antimicrobial agents of clinical use. Among the 16 derivatives analyzed, four nitrofurans (N-H-FUR-NO(2), N-Br-FUR-NO(2), N-F-FUR-NO(2), N-Cl-FUR-NO(2)) showed promising MIC and MBC values (MIC = MBC = 1-16 µg/mL). The experimental data revealed the potential of these derivatives, which were comparable to the current antimicrobials with similar bactericidal and bacteriostatic profiles. Therefore, these molecules may be feasible options to be explored for treating infections caused by multiresistant strains. Our in vitro and in silico toxicity reinforced these results as these derivatives presented low cytotoxicity against human macrophages and low theoretical risk profile for irritant and reproductive effects compared to the current antimicrobials (e.g., vancomycin and ciprofloxacin). The molecular modeling analysis also revealed positive values for their theoretical druglikeness and drugscore. The presence of a 5-nitro-2-furfur-2-yl group seems to be essential for the antimicrobial activity, which pointed these acylhydrazone derivatives as promising for designing more potent and safer compounds.

Simultaneous Treatment of Both Sides of the Polymer with a Conical-Shaped Atmospheric Pressure Plasma Jet.

A conical-shaped atmospheric pressure plasma jet (CS-APPJ) was developed to overcome a standard limitation of APPJs, which is their small treatment area. The CS-APPJs increase the treatment area but use the same gas flow. In the present work, polypropylene samples were treated by CS-APPJ and characterized by scanning electron microscope (SEM), the contact angle, Fourier-transformed infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). It was observed that the treatment co-occurs on the face directly in contact with the plasma and on the opposite face (OF) of the samples, i.e., no contact. However, the treatment changed the chemical composition on each side; the OF is rougher than the direct contact face (DCF), probably due to the oxygen groups in excess at the DCF and nitrogen in quantity at the OF. Although simultaneous treatment of both sides of the sample occurs for most atmospheric plasma treatments, this phenomenon is not explored in the literature.

Different Radial Modification Profiles Observed on APPJ-Treated Polypropylene Surfaces according to the Distance between Plasma Outlet and Target.

The plasma jet transfer technique relies on a conductive wire at floating potential, which, upon entering in contact with a primary discharge, is capable of igniting a small plasma plume at the distal end of a long flexible plastic tube. In this work, two different long tube configurations were employed for the surface modification of polypropylene (PP) samples using argon as the working gas. One of the jet configurations has a thin copper (Cu) wire, which was installed inside the long tube. In the other configuration, the floating electrode is a metallic mesh placed between two plastic tubes in a coaxial arrangement. In the first case, the tip of the Cu wire is in direct contact with the working gas at the plasma outlet, whereas, in the second, the inner plastic tube provides an additional dielectric barrier that prevents the conductor from being in contact with the gas. Water contact angle (WCA) measurements on treated PP samples revealed that different surface modification radial profiles are formed when the distance (d) between the plasma outlet and target is changed. Moreover, it was found that the highest WCA reduction does not always occur at the point where the plasma impinges the surface of the material, especially when the d value is small. Through X-ray photoelectron spectroscopy (XPS) analysis, it was confirmed that the WCA values are directly linked to the oxygen-functional groups formed on the PP surfaces after the plasma treatment. An analysis of the WCA measurements along the surface, as well as their temporal evolution, together with the XPS data, suggest that, when the treatment is performed at small d values, the plasma jet removes some functional groups at the point where the plasma hits the surface, thus leading to peculiar WCA profiles.

Fovea-threatening and fovea-involving peripheral Coats disease: effects of posture and intervention.

BACKGROUND: We believe that our experience with patients presenting with Coats disease and macular sparing should be shared with our colleagues. We would like to show the effect of posture and prompt intervention in cases with fovea-threatening and/or fovea-involving peripheral Coats disease (FTPCD). This association has been poorly debated in our specialty and literature. We call the attention for the unexpexted scenario of observing the lost of the fovea during some types of traditional and prompt interventional treatments of these cases with previous 20/20 vision (something that we have been studying and observing for many years). In order to publish our best representative cases, we have chosen 8 Brazilian patients (age range, 7-62 years; 5 male) with FTPCD. All patients underwent multimodal imaging and different treatments (observation, sleep-posture repositioning, laser, intraocular steroids, and/or anti-vascular endothelial growth factor therapy). All patients, initially, informed to adopt a sleeping lateral-down position, favoring exudation shifting to the fovea pre-treatment. Most promptly-treated patients in this way (n = 4), developed subretinal fluid and exudates in the macula and some had irreversible central visual loss (n = 3). Patients with recent fovea-involving exudation who changed postural sleep position (to protect the foveal area) before and during treatment fared better, with some preserved central vision and an intact fovea (n = 5). The fundus status was correlated with the gravitational effects of posture before and after treatment. Despite prepared as an observational/interventional study, with a small number of cases, the most difficult part is documenting the sleep position of these patients and its influence in the outcomes as there is not good way to prove how well or poorly the positioning occurred in our cases. Finally, we also intended to call the attention to the fact that Coats disease must be studied in all its clinical stage variants and not only seen as a potential blinding and incurable ocular disease. CASE PRESENTATION: This study is a retrospective and/or interventional analysis of eight cases with a less severe clinical variant of classic Coats disease that we refer to as fovea-threatening and fovea-involving peripheral Coats disease (FTPCD). All cases were unilateral with no systemic disease or family history of Coats disease. The bilateral anterior segment and intraocular pressure were normal in all patients. The characteristics of all patients are shown in the Table. CONCLUSION: The funduscopic features of FTPCD are fundamental to disease understanding and optimal management. Habitual posturing may affect the fundus morphologic features of retinal exudation as observed in all current patients with exudative peripheral Coats disease. When sleep habitual posture is not observed in patients with FTPCD, the effects of prompt invasive treatments can cause rapid visual loss because of foveal subretinal pooling of exudates post-treatment. Initial vigilant adjusting of the habitual sleep posture for several patients with FTPCD, before the indication of traditional invasive treatments (laser and/or pharmacologic medications) can result in improved vision and fundoscopic morphologic features.

Identification of nor-ß-lapachone derivatives as potential antibacterial compounds against Enterococcus faecalis clinical strain.

A broad-spectrum antibiotic therapy has led to medical complications and emergence of multiresistant bacteria including Enterococcus faecalis. In this study, we designed, synthesized, and evaluated the antibacterial activity of 13 nor-ß-lapachone derivatives against a drug resistant E. faecalis strain. Two triazole substituted compounds (1e = 8 µg/ml and 1c = 16 µg/ml) and the non-substituted derivative (1a = 8 µg/ml) were promising compared to chloramphenicol (12 µg/ml), an antibiotic currently available in the market. We also performed a structure-activity relationship analysis using a molecular modeling approach that pointed the low HOMO energy values; HOMO density concentrated on the nor-ß-lapachone ring, lipophilicity, solubility and number HBA as important stereoelectronic features for the antibacterial profile. In addition the triazole compounds presented low theoretical toxicity profile, and drug-score higher than commercial antibiotics also fulfilling the Lipinski "Rule of Five", which pointed them as promising candidates for further studies in infections caused by multiresistant E. faecalis hospital strains.

Optical Coherence Tomography Angiography Findings in Diffuse Unilateral Subacute Neuroretinitis.

BACKGROUND AND OBJECTIVE: To report a unique case series of diffuse unilateral subacute neuroretinitis (DUSN) patients imaged with optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: In this retrospective case series, multimodal imaging was performed in four patients with DUSN at the time of patient visit. The study patients underwent standard clinical treatment for DUSN. RESULTS: The clinical findings were consistent with the diagnosis of DUSN. Cross-sectional OCT showed disruption of outer retinal layers in the foveal area and an irregular structure of the outer plexiform layer. En face OCT revealed hyperreflective spots and a large hyperreflective lesion in the foveal area correspondent to the outer retina disruption seen on cross-sectional OCT. OCTA demonstrated decreased vascular perfusion in both the superficial and deep retinal capillary plexuses along with choriocapillaris preservation. CONCLUSION: OCTA may provide a more detailed assessment of the retinal microvascular changes, allowing a more precise anatomical-functional correlation in DUSN. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:76-83.].

Antibacterial profile against drug-resistant Staphylococcus epidermidis clinical strain and structure-activity relationship studies of 1H-pyrazolo[3,4-b]pyridine and thieno[2,3-b]pyridine derivatives.

Antibacterial resistance is a complex problem that contributes to health and economic losses worldwide. The Staphylococcus epidermidis is an important nosocomial pathogen that affects immunocompromised patients or those with indwelling devices. Currently, there are several resistant strains including S. epidermidis that became an important medical issue mainly in hospital environment. In this work, we report the biological and theoretical evaluations of a 4-(arylamino)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acids series (1, 1a-m) and the comparison with a new isosteric ring nucleus series, 4-(arylamino)thieno[2,3-b]pyridine-5-carboxylic acids derivatives (2, 2a-m). Our results revealed the 1H-pyrazolo[3,4-b]pyridine derivatives significant antibacterial activity against a drug-resistant S. epidermidis clinical strain in contrast to the thieno[2,3-b]pyridine series. The minimal inhibitory concentration (MIC) of the most active derivatives (1a, 1c, 1e, and 1f) against S. epidermidis was similar to that of oxacillin and twofold better than chloramphenicol. Interestingly, the position of the functional groups has a great impact on the activity as observed in our structure-activity relationship (SAR) study. The SAR of 1H-pyrazolo[3,4-b]pyridine derivatives shows that the highest inhibitory activity is observed when the meta position is occupied by electronegative substituents. The molecular modeling analysis of frontier molecular orbitals revealed that the LUMO density is less intense in meta than in ortho and para positions for both series (1 and 2), whereas HOMO density is overconcentrated in 1H-pyrazolo[3,4-b]pyridine ring nucleus compared to the thieno[2,3-b]pyridine system. The most active derivatives of series 1 were submitted to in silico ADMET screening, which confirmed these compounds as potential antibacterial candidates.

[Comparison of scanning laser polarimetry, optical coherence tomography 1 and Stratus optical coherence tomography for the detection of axonal loss in band atrophy of the optic nerve]. / Comparação entre o polarímetro de varredura a laser, a tomografia de coerência óptica 1 e o Stratus-oct na detecção da perda axonal da atrofia em banda do nervo óptico.

PURPOSE: To compare the abilitiy of scanning laser polarimetry (GDx), optical coherence tomography (OCT) 1 and Stratus- optical coherence tomography to discriminate between healthy eyes and eyes with band atrophy of the optic nerve and temporal hemianopsia. METHODS: Twenty-three eyes with band atrophy of the optic nerve and 23 eyes from healthy subjects were included in this observational prospective case-control study. All eyes underwent retinal nerve fiber layer (RNFL) thickness analysis using GDx, optical coherence tomography-1 and Stratus-optical coherence tomography. Mean values obtained with each equipment were compared between band atrophy and normal eyes. Receiver operating characteristic (ROC) curves and sensitivities at fixed specificities (80% e 95%) were calculated for each parameter calculated with each equipment and compared. RESULTS: When compared with healthy subjects, the parameters corresponding to the global average as well as each of the four quadrant retinal nerve fiber layer thickness in eyes with band atrophy were significantly smaller (p<0.05), than in normal eyes, with the exception of GDx's temporal thickness parameter. Comparison of the areas under ROC curves (AUCs) of the parameters from the three equipments revealed significantly greater values for the Stratus-OCT when compared to the OCT-1 in the global average and in the temporal quadrant thickness measurement. Stratus-OCT was significantly more sensitive than GDx in the global average as well as in the temporal, nasal and inferior quadrant. OCT-1 was superior to GDx only in the temporal quadrant. All three equipments revealed a similar ability to identify retinal nerve fiber layer reduction in the superior quadrant. CONCLUSIONS: The Stratus OCT showed the best ability to discriminate between eyes with band atrophy of the optic nerve and healthy eyes although all three equipments were able do identify most of the abnormal eyes. OCT-1 was inferior to Stratus-OCT and superior do GDx in the temporal quadrant. Although GDx was able identify some abnormality in most studied eyes, the equipment showed poor sensitivity in the detection of axonal loss in the nasal and temporal aspect of the optic disc and should be used with caution in neuro-ophthalmic diseases that cause retinal nerve fiber layer loss in those areas of the optic disc.

Retinal nerve fiber layer loss documented by Stratus OCT in patients with pituitary adenoma: case report.

PURPOSE: To report abnormalities of retinal nerve fiber layer (RNFL) thickness using optical coherence tomography (Stratus OCT) in patients with pituitary adenoma. METHODS: Two patients with long-standing bitemporal visual field defects and optic nerve band atrophy were submitted to optical coherence tomography examination (Stratus OCT). RESULTS: Both patients with band atrophy revealed diffuse loss of the retinal nerve fiber layer on Stratus OCT, with severe reduction in the nasal and temporal areas of the optic disc. Retinal nerve fiber layer loss correlated well with visual field loss and with previous histological studies of band atrophy of the optic nerve. CONCLUSIONS: Stratus optical coherence tomography can provide useful information in the diagnosis of band atrophy from chiasmal lesions such as pituitary adenomas.

Conjunctival hyperemia associated with bimatoprost use: a histopathologic study.

PURPOSE: To evaluate histopathologic signs of conjunctival inflammation in patients with conjunctival hyperemia induced by bimatoprost treatment. DESIGN: Prospective interventional study. METHODS: The study included 15 eyes of 15 patients scheduled for cataract surgery. Patients in the treatment group (n = 9) exhibited trace to moderate conjunctival hyperemia when treated with bimatoprost 0.03% every day for 15 to 30 days before surgery. The control group (n = 6) included untreated patients with no ocular disease other than cataract. Conjunctival biopsies were obtained for histologic evaluation with light microscopy. RESULTS: Vascular congestion was observed in biopsies from 7 patients (78%) in the bimatoprost group and 5 patients (83%) in the control group. Signs of inflammation were found in biopsies from 2 patients (22%) in the bimatoprost group and 2 patients (33%) in the control group. CONCLUSIONS: Histopathologic signs of inflammation were no more frequent in conjunctival specimens from bimatoprost-treated patients with trace to moderate hyperemia than in those from untreated control subjects.

Intraocular pressure fluctuations in medical versus surgically treated glaucomatous patients.

The purpose of this study was to compare the IOP fluctuations in the daytime tension curves of glaucoma patients under ocular hypotensive therapy with those of patients previously submitted to trabeculectomy. We also evaluated the IOP peaks and fluctuations for the same patients in response to the water-drinking test (WDT). The study included 30 primary open-angle glaucoma (POAG) patients using ocular hypotensive medications and with no history of previous intraocular surgery (medical group), and 30 POAG patients previously submitted to one or more trabeculectomies though taking no medication at the time of the study (surgical group). All patients were submitted to a diurnal tension curve--DTC (8:30-17:00/3-hour intervals) followed by the WDT. The IOP peak and IOP fluctuation during the diurnal tension curve were significantly greater in the medical group than in the surgical group. The same was observed following the WDT. From an overall baseline IOP of 10.6 mmHg, the mean IOP change following the WDT was 13% in the surgical group and 40% in the medical group. Patients submitted to trabeculectomy have less TOP fluctuations during the diurnal tension curve and following a water-drinking provocative test. This effect could represent an additional benefit of surgery in controlling the intraocular pressure of glaucomatous patients.

Dilemas da visualidade jornalística das violências contra pessoas LGBTQ+ e contra mulheres heterossexuais no Brasil / Dilemmas of journalistic visibility of violence against LGBTQ+ people and against heterosexual women in Brazil / Dilemas de la visualidad periodística de las violencias contra personas LGBTQ+ y contra mujeres heterosexuales en Brasil

Nos textos jornalísticos, chama a atenção a diferença entre as imagens de casos de violência contra a mulher cisgênero e heterossexual e as contra pessoas LGBTQ+. Tratando-se das pessoas LGBTQ+, as imagens costumam ser brutais, com exposição de sangue e de corpos feridos por armas diversas. Já a cobertura de casos de violência contra a mulher cis e heterossexual é diametralmente oposta: as imagens tendem a ser pouco contundentes, muitas vezes mostrando paisagens de lugares onde ocorreram os crimes, em alguns casos mostrando os rostos de agressores e vítimas, nunca cenas de sangue ou corpos com marcas de agressão. Neste artigo, tomamos a instabilidade textual como ponto de partida para refletirmos sobre o contraste entre os modos de tratamento jornalístico conferidos no Brasil a essas duas violências e o que impacta no entendimento acerca das relações que conformam a visualidade e a cultura visual.

In Brazilian journalistic texts, the difference between the images of cases of violence against cis and heterosexual women and those against LGBTQ+ people are astonishing. In the case of LGBTQ+ people, the images are usually brutal, with exposure of blood and bodies injured by various weapons. The coverage of cases of violence against cis and heterosexual women is the opposite: the images tend to be inconclusive, often showing landscapes of places where crimes occurred, sometimes showing the faces of perpetrators and victims and never scenes of blood or bodies with marks of aggression. In this article, we take the textual instability as a starting point to reflect on the contrast between the ways of journalistic treatment in Brazil conferred to these two violences and what impacts on the understanding about the relations that conform the visuality and the visual culture.

En los textos periodísticos, llama la atención la diferencia entre las imágenes de casos de violencia contra la mujer cis heterosexual y las contra personas LGBTQ+. Tratándose de las personas LGBTQ+, las imágenes suelen ser brutales, con exposición de sangre y de cuerpos heridos por armas diversas. La cobertura de casos de violencia contra la mujer cis heterosexual es diametralmente opuesta: las imágenes tienden a ser poco contundentes, muchas veces mostrando paisajes de lugares donde ocurrieron los crímenes, en algunos momentos mostrando los rostros de agresores y víctimas y nunca escenas de sangre o cuerpos con marcas de agresión. En este artículo tomamos la inestabilidad textual como punto de partida para reflexionar sobre el contraste entre los modos de tratamiento periodístico en Brasil conferidos a esas dos violencias y lo que impacta en el entendimiento acerca de las relaciones que conforman la visualidad y la cultura visual.

Análise da Resiliência entre Pessoas que Vivem com HIV/AIDS: Um Estudo Psicossocial / Analysis of Resilience among People Living with HIV/AIDS: A Psychosocial Study

RESUMO A presente investigação teve como objetivo principal estudar os processos psicossociais da resiliência entre as pessoas que convivem com o HIV. Trata-se de uma pesquisa transversal com dados qualitativos que foi realizada com 44 pessoas em acompanhamento no Centro de Testagem e Aconselhamento de Parnaíba- Piauí. Os resultados mostraram alguns fatores de risco e, também, de proteção, tais como preconceito e exclusão, dificuldades de iniciar o tratamento antirretroviral, complicações do uso dos medicamentos e importância do apoio social para que haja diminuição dos fatores de risco e melhor predisposição ao desenvolvimento da resiliência. Foi concluído que fatores psicossociais podem predispor os indivíduos ao maior desenvolvimento do processo de resiliência.

ABSTRACT The main objective of the present research was to study the psychosocial processes of resilience among people living with HIV. It is a cross-sectionalresearch with qualitative data that was carried out with 44 people in treatment at the Testing and Counseling Center of Parnaíba-Piauí. The results showed some risk and protection factors, such as prejudice and exclusion, difficulties in initiating antiretroviral treatment, complications in using prescribed drugs, and the relevance of social support to reduce risk factors and promote better predisposition to development. of resilience. It was concluded that psychosocial factors may predispose individuals to a greater development of the resilience process.

Synthesis using microwave irradiation and antibacterial evaluation of new N,O-acetals and N,S-acetals derived from 2-amino-1,4-naphthoquinones.

This paper describes a novel series of N,O-acetals and N,S-acetals (7a-o) derived from 2-amino-1,4-naphthoquinones that were synthesized and evaluated as potential antimicrobial agents. These compounds were obtained in good yields using microwave irradiation, and several of them showed promising antibacterial profiles. Three of our biologically active 2-amino-1,4-naphthoquinone N,O-acetals and N,S-acetals tested against hospital bacterial strains were identified as potential lead compounds. Characterization of all compounds was performed using one-dimensional NMR techniques ((1)H, (13)C-APT), IR spectra, elemental analyses and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS).

[Retinal impairment in young individuals with sickle cell anemia (hemoglobin SS disease) in university hospital in Northeastern of Brazil]. / Alterações retinianas em jovens portadores de anemia falciforme (hemoglobinopatias) em hospital universitário no nordeste do Brasil.

PURPOSES: To describe and categorize retinal vascular changes in patients with sickle cell anemia, as well as to compare diagnostic methods (indirect ophthalmoscopy and fluorescein angiography). METHODS: Patients with sickle cell anemia over the age of seven were examined. Complete ophthalmologic examination with indirect ophthalmoscopy and angiography was performed in each patient. The fundoscopy results were grouped in 3 classes: normal; non-proliferative retinopathy, which includes vascular tortuosity, black sunburst, salmon-patch and peripheral closure/anastomoses; and proliferative retinopathy, related to neovascular proliferation. Angiography results were classified according to Goldberg classifications from stage I to V. RESULTS: Retinopathy related to sickle cell anemia was seen in 62.3% (38/61) of the eyes checked. Neovascularization was observed in one eye. The frequency of bilateral changes in angiography was high. Non-proliferative retinopathy was more common, especially vascular tortuosities (17/61), followed by arteriovenous anastomoses in the retinal periphery (15/61) and arterial occlusions (5/61). The mean age of retinopathy group was 14.4 years old, significantly lower than the mean age of non-retinopathy group, which was 17.4. The result was normal in 16.4% (10/61) of the eyes in the fundoscopy exam, while angiography showed alterations. CONCLUSIONS: All the results pointed to the conclusion that the non-proliferative retinal vascular changes are frequent and precocious in patients with sickle cell anemia (SS genotype). Fluorescein angiography is more sensitive in the diagnosis of retinopathy when compared to indirect ophthalmoscopy.

Avaliação do eletrocardiograma de pacientes com leishmaniose tegumentar americana tratados com antimonial pentavalente (glucantime) / Electrocardiographic assessment of patients with american cutaneous leihmaniasis treated with pentavalent antimonial (glucantime)

Os antimoniais pentavalentes (Antimoniato de N-metilglumina – Glucantime®) são fármacosde primeira escolha no tratamento da leishmaniose tegumentar americana (LTA). Apresentama cardiotoxicidade como importante efeito adverso e é evidenciada por alterações noeletrocardiograma de repouso (ECG). O alargamento do intervalo QT corrigido (QTc) é a principale potencialmente mais grave delas. O presente estudo teve como objetivo avaliar as alteraçõesno ECG e sua frequência nos pacientes com LTA tratados com Glucantime® no Serviço deDermatologia de nossa instituição. Para isso, um cardiologista avaliou os ECGs de 15 pacientes entre 18 e 59 anos de idade diagnosticados com LTA. Os exames foram realizados imediatamenteantes, no 7º, 14º e 21º dias do tratamento. Desses pacientes, cinco (33 por cento) desenvolveram algumdistúrbio no eletrocardiograma, cuja frequência foi diretamente proporcional ao tempo de uso dofármaco. Bradicardia sinusal nova foi o mais comum (5/15 pacientes), seguida por alargamento dointervalo QTc (2/15 pacientes, os quais também apresentaram bradicardia). Não houve registro decomplicações graves e nenhum paciente desenvolveu sintomatologia cardiovascular. Em apenasum caso foi necessária a interrupção do tratamento. A frequência de alterações no ECG observada écompatível com a relatada por estudos anteriores sobre o tema. Concluímos que a cardiotoxicidadedos antimoniais pentavalentes se manifestou de forma insidiosa, cumulativa, em proporçãocompatível com os relatos da literatura e sem repercussões clínicas.

The pentavalent antimonial compounds (Meglumine Antimoniate – Glucantime®) are thecornerstone for the treatment of American Cutaneous Leishmaniasis (ACL). Cardiotoxicity is theirprincipal adverse effect, which becomes evident as abnormalities in the resting Electrocardiogram(ECG), the prolongation of the corrected QT interval (QTc) being the most important and potentiallyhazardous of them. The purpose of this study was to evaluate the disturbances on ECG and theirfrequency in patients diagnosed with ACL and treated with Glucantime® at our Institution. Fifteenpatients between 18 and 59 years had their ECGs assessed by a senior cardiologist. The tests wereperformed prior to treatment, as well as on its 7th, 14th and 21st day. Five patients (33 percent) developed anabnormality not previously observed, and frequency correlated with the duration of the treatment.The most common was sinus bradycardia (5 of 15 patients), followed by prolongation of the QTcinterval (2 of 15 patients; both also had sinus bradycardia). No major cardiovascular symptomsor complications were reported. Only one patient had to interrupt the treatment. This proportionof ECG disturbances is consistent with previous studies on the subject. We conclude that thecardiotoxicity of the pentavalent antimonial drugs occurred insidiously in a percentage of patientscompatible with the literature, and was not associated with major clinical complications.

Identification of a potential lead structure for designing new antimicrobials to treat infections caused by Staphylococcus epidermidis-resistant strains.

Bacterial infections are a significant cause of morbidity and mortality among critically ill patients. The increase of antibiotic resistance in bacteria from human microbiota-such as Staphylococcus epidermidis, an important nosocomial pathogen that affects immunocompromised patients or those with indwelling devices-increased the desire for new antibiotics. In this study we designed, synthesized, and determined the antimicrobial activity of 27 thieno[2,3-b]pyridines (1, 2, 2a-2m, 3, 3a-3m) derivatives against a drug-resistant clinical S. epidermidis strain. In addition, we performed a structure-activity relationship analysis using a molecular modeling approach, and discuss the drug absorption, distribution, metabolism, excretion, and toxicity profile and Lipinski's "rule of five," which are tools to assess the relationship between structures and drug-like properties of active compounds. Our results showed that compound 3b (5-(1H-tetrazol-5-yl)-4-(3;-methylphenylamino)thieno[2,3-b]pyridine) was as active as oxacillin and chloramphenicol but with lower theoretical toxicity risks and a better drug likeness and drug score potential than chloramphenicol. All molecular modeling and biological results reinforced the promising profile of 3b for further experimental investigation and development of new antibacterial drugs.