DODAB vesicles containing lysophosphatidylcholines: The relevance of acyl chain saturation on the membrane structure and thermal properties.

The saturated LPC18:0 and unsaturated LPC18:1 lysophosphatidylcholines have important roles in inflammation and immunity and are interesting targets for immunotherapy. The synthetic cationic lipid DODAB has been successfully employed in delivery systems, and would be a suitable carrier for those lysophosphatidylcholines. Here, assemblies of DODAB and LPC18:0 or LPC18:1 were characterized by Differential Scanning Calorimetry (DSC) and Electron Paramagnetic Resonance (EPR) spectroscopy. LPC18:0 increased the DODAB gel-fluid transition enthalpy and rigidified both phases. In contrast, LPC18:1 caused a decrease in the DODAB gel-fluid transition temperature and cooperativity, associated with two populations with distinct rigidities in the gel phase. In the fluid phase, LPC18:1 increased the surface order but, differently from LPC18:0, did not affect viscosity at the membrane core. The impact of the different acyl chains of LPC18:0 and 18:1 on structure and thermotropic behavior should be considered when developing applications using mixed DODAB membranes.

Thermotropic Behavior and Structural Organization of C24:1 Sulfatide Dispersions and Its Mixtures with Cationic Bilayers.

C24:1 sulfatide (SF) is an endogenous activator of type II NKT cells. The thermotropic behavior and structure of SF dispersions and its mixtures (4.8-16.6 mol %) with cationic dioctadecyldimethylammonium bromide (DODAB) bilayers were investigated by differential scanning calorimetry and electron paramagnetic resonance spectroscopy. The non-interdigitated lamellar structures formed by pure SF display broad thermal events around 27.5 °C when heated and cooled. These events disappear upon mixing with DODAB, showing complete lipid miscibility. SF decreases the DODAB gel-phase packing, with a consequent decrease in phase-transition temperatures and cooperativity upon heating. In contrast, SF increases the rigidity of the DODAB fluid phase, resulting in a smaller decrease in transition temperatures upon cooling. The hysteresis between heating and cooling decreased as the SF molar fraction increased. These effects on DODAB are similar to the ones described for other glycolipids, such as αGalCer and ßGlcCer. This might be due to the orientation of the rigid and planar amide bond that connects their sphingoid bases and acyl chains, which result in a V-shaped conformation of the glycolipid molecules. The current results may be important to plan and develop new immunotherapeutic tools based on SF.

Assessment of the strength and electrical activity of the pelvic floor muscles of male-to-female transgender patients submitted to gender-affirming surgery: A case series.

AIMS: To assess the strength and electrical activity of the pelvic floor muscles (PFMs) of male-to-female transgender individuals submitted to gender-affirming surgery (GAS). METHODS: A case series study was conducted from October 2016 to August 2018. Transgender women, who were scheduled for GAS, participated in the study. The volunteers were submitted to a clinical evaluation of the PFM followed by digital palpation (PERFECT method) and electromyography in the preoperative, 15, and 30 days after GAS. They responded to the International Consultation on Incontinence Questionnaire-Urinary Incontinence (UI)-Short Form to evaluate the effect of UI on quality of life and to questions related to the urinary, anorectal, and sexual symptoms. Fifteen days after the GAS, patients were instructed to perform perineal exercises at home, twice a day. RESULTS: The study sample consisted of 15 transgender women with an average age of 30.6 (SD = 6.7) years. There was a decline in median strength and sustained muscle contraction duration (PERFECT), in the electrical muscle activity (RMSmean and RMSmax) between pre-GAS and 15 days after GAS (p < 0.05). However, there was an increase in these parameters between 15 and 30 days after GAS (p < 0.05). Moreover, six patients exhibited pre-GAS UI, which continued after surgery, with a worsening of urgency symptoms and improvement in nocturia and postmicturition leakage. CONCLUSION: Strength, sustained muscle contraction duration, and PFM electrical activity may decline 15 days after GAS, returning to pre-GAS values in the first month after surgery.

A Gadolinium Metal-Organic Framework Film as a Converter Layer for Neutron Detection.

Metal-organic frameworks (MOFs) are known for their versatility in terms of their crystalline structure, porosity, resistance to temperature, radiation damage, and luminescence among others. Gadolinium (Gd) is one of the elements with the highest reported cross-section for low energy neutron capture, producing internal conversion electrons and γ rays as a result of the neutron absorption. The development of Gd-BTC films (BTC=1,3,5-benzenetricarboxylate) is shown that were deposited on Si and Al substrates by airbrushing, and characterized by profilometry, Raman, EDX and X-ray diffraction. Radiation damage, thermal decomposition and neutron absorption of these films were studied as well. Gd-BTC films were attached to CMOS devices (Complementary Metal-Oxide-Semiconductor), which are sensible to the internal conversion electrons, in order to build a neutron detector. The devices Gd-BTC/CMOS could selectively detect neutrons in the presence of γ rays with a thermal neutron detection efficiency of 3.3±0.1 %, a signal to noise ratio of 6 : 1, and were suitable to obtain images.

Supramolecular organization of α-galactosylceramide in pure dispersions and in cationic DODAB bilayers.

α-galactosylceramide (α-GalCer; KRN7000) strongly stimulates NKT cells. The structures of α-GalCer assemblies and of cationic DODAB bilayers containing α-GalCer were investigated by differential scanning calorimetry (DSC) and electron spin resonance (ESR) spectroscopy. Assemblies of α-GalCer have a very tightly packed gel phase, causing spin labels to cluster and display spin exchange interactions. An endothermic phase transition is observed by DSC, leading to a fluid phase. This phase transition peak disappears upon mixing with DODAB, showing that up to 9 mol% α-GalCer is miscible with the cationic lipid. ESR spectra show that α-GalCer decreases DODAB gel phase packing, resulting in a decrease of gel-fluid transition temperature and cooperativity in DSC thermograms of mixed bilayers. In contrast, α-GalCer increases the rigidity of the fluid phase. These effects are probably due to the conformation of the rigid amide bond that connects the phytosphingosine base of α-GalCer to its long and saturated acyl chain. Possibly, α-GalCer adopts a V-shaped conformation because of the perpendicular orientation of the amide bond towards the axes of the hydrocarbon chains. Apparently, the effect of the amide bond configuration is a key structural feature for the interaction between ceramide-based glycolipids and DODAB molecules, since we have previously reported a similar decrease of gel phase packing and increase in fluid phase rigidity for DODAB bilayers containing C24:1ß-glucosylceramide. Since the structure of delivery systems is critical to the biological activity of α-GalCer, this work certainly contributes to the planning and development of novel immunotherapeutic tools.

Serial Interval Distribution of SARS-CoV-2 Infection in Brazil

Using 65 transmission pairs of SARS-CoV-2 reported to the Brazilian Ministry of Health we estimate the mean and standard deviation for the serial interval to be 2.97 and 3.29 days respectively. We also present a model for the serial interval probability distribution using only two parameters.

Expected impact of COVID-19 outbreak in a major metropolitan area in Brazil

In January 2020 China reported to the World Health Organization an outbreak of pneumonia of undetermined origin in the city of Wuhan, Hubei. In January 30, 2020, the World Health Organization declared the outbreak of COVID-19 as a Public Health Emergency of International Interest (PHEI). ObjectivesThe aim of this study is to assess the impact of a COVID-19 epidemic in the metropolitan region of Sao Paulo, Brazil. MethodsWe used a generalized SEIR (Susceptibles, Exposed, Infectious, Recovered) model, with additional Hospitalized variables (SEIHR model) and age-stratified structure to analyze the expected time evolution during the onset of the epidemic in the metropolitan area of Sao Paulo. The model allows to determine the evolution of the number of cases, the number of patients admitted to hospitals and deaths caused by COVID-19. In order to investigate the sensibility of our results with respect to parameter estimation errors we performed Monte Carlo analysis with 100 000 simulations by sampling parameter values from an uniform distribution in the confidence interval. ResultsWe estimate 1 368 (IQR: 880, 2 407) cases, 301 (22%) in older people ([≥]60 years), 81 (50, 143) hospitalizations, and 14 (9, 26) deaths in the first 30 days, and 38 583 (IQR: 16 698, 113, 163) cases, 8 427 (21.8%) in older people ([≥]60 years), 2181 (914, 6392) hospitalizations, and 397(166, 1205) deaths in the first 60 days. LimitationsWe supposed a constant transmission probability Pc among different age-groups, and that every severe and critic case will be hospitalized, as well as that the detection capacity in all the primary healthcare services does not change during the outbreak. ConclusionSupposing the reported parameters in the literature apply in the city of Sao Paulo, our study shows that it is expected that the impact of a COVID-19 outbreak will be important, requiring special planning from the authorities. This is the first study for a major metropolitan center in the south hemisphere, and we believe it can provide policy makers with a prognosis of the burden of the pandemic not only in Brazil, but also in other tropical zones, allowing to estimate total cases, hospitalization and deaths, in support to the management of the public health emergence caused by COVID-19.

Structural characterization of cationic DODAB bilayers containing C24:1 ß-glucosylceramide.

The effect of 5 mol%, 9 mol%, and 16 mol% of C24:1 ß-glucosylceramide (ßGlcCer) on the structure of cationic DODAB bilayers was investigated by means of differential scanning calorimetry (DSC), electron spin resonance (ESR) spectroscopy and fluorescence microscopy. ßGlcCer is completely miscible with DODAB at all fractions tested, since no domains were observed in fluorescence microscopy or ESR spectra. The latter showed that ßGlcCer destabilized the gel phase of DODAB bilayers by decreasing the gel phase packing. As a consequence, ßGlcCer induced a decrease in the phase transition temperature and cooperativity of DODAB bilayers, as seen in DSC thermograms. ESR spectra also showed that ßGlcCer induced an increase in DODAB fluid phase order and/or rigidity. Despite their different structures, a similar effect of loosening the gel phase packing and turning the fluid phase more rigid/organized has also been observed when low molar fractions of cholesterol were incorporated in DODAB bilayers. The structural characterization of mixed membranes made of cationic lipids and glucosylceramides may be important for developing novel immunotherapeutic tools such as vaccine adjuvants.

Case Report: An Acute Chikungunya Infection and a Recent Secondary Dengue Infection in a Peripartum Case in Ecuador.

Dengue virus (DENV) and chikungunya virus (CHIKV) are transmitted by the same mosquito vectors and now co-circulate in many parts of the world; however, coinfections and serial infections are not often diagnosed or reported. A 38-week pregnant woman was admitted to the hospital with a diagnosis of suspected DENV and CHIKV in southern coastal Ecuador. The pregnancy was complicated by mild polyhydramnios and fetal tachycardia, and a healthy newborn was born. The patient was positive for a recent secondary DENV infection (Immunoglobulin M and Immunoglobulin G positive) and an acute CHIKV infection (real-time reverse transcriptase polymerase chain reaction positive) (Asian genotype). The newborn was not tested for either virus. This case resulted in a benign clinical course with a favorable pregnancy outcome.

Structural insights on biologically relevant cationic membranes by ESR spectroscopy.

Cationic bilayers have been used as models to study membrane fusion, templates for polymerization and deposition of materials, carriers of nucleic acids and hydrophobic drugs, microbicidal agents and vaccine adjuvants. The versatility of these membranes depends on their structure. Electron spin resonance (ESR) spectroscopy is a powerful technique that employs hydrophobic spin labels to probe membrane structure and packing. The focus of this review is the extensive structural characterization of cationic membranes prepared with dioctadecyldimethylammonium bromide or diC14-amidine to illustrate how ESR spectroscopy can provide important structural information on bilayer thermotropic behavior, gel and fluid phases, phase coexistence, presence of bilayer interdigitation, membrane fusion and interactions with other biologically relevant molecules.

Bacterial spores as particulate carriers for gene gun delivery of plasmid DNA.

Bacillus subtilis spores represent a suitable platform for the adsorption of proteins, enzymes and viral particles at physiological conditions. In the present work, we demonstrate that purified spores can also adsorb DNA on their surface after treatment with cationic molecules. In addition, we demonstrate that DNA-coated B. subtilis spores can be used as particulate carriers and act as an alternative to gold microparticles for the biolistic (gene gun) administration of plasmid DNA in mice. Gene gun delivery of spores pre-treated with DODAB (dioctadecyldimethylammonium bromide) allowed efficient plasmid DNA absorption and induced protein expression levels similar to those obtained with gold microparticles. More importantly, we demonstrated that a DNA vaccine adsorbed on spores can be loaded into biolistic cartridges and efficiently delivered into mice, which induced specific cellular and antibody responses. Altogether, these data indicate that B. subtilis spores represent a simple and low cost alternative for the in vivo delivery of DNA vaccines by the gene gun technology.

Genetic characterization of native and invasive Plagioscion squamosissimus (Perciformes, Sciaenidae) populations in Brazilian hydrographic basins.

The genetic diversity of invasive and native populations of Plagioscion squamosissimus (Heckel, 1840) from the Paraná, Parnaiba and Araguaia-Tocantins river basins was assessed by using Random Amplified Polymorphic DNA (RAPD) markers. Genetic data confirmed the hypothesis of low genetic variability within and among P. squamosissimus populations introduced in the upper Paraná River basin, and indicated that they likely originated from a common ancestor. Moreover, the data demonstrated that, in agreement with available historical records, the P. squamosissimus populations established in the Paraná River basin were derived from a population native to the Parnaíba River basin. The genetic data presented here are of potential future application for the management of the invasive P. squamosissimus populations and for the preservation of the genetic legacy of native fish.

The effect of an oligonucleotide on the structure of cationic DODAB vesicles.

The effect of a small single-stranded oligonucleotide (ODN) on the structure of cationic DODAB vesicles was investigated by means of differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS) and electron spin resonance (ESR) spectroscopy. ODN adsorption induced coalescence of vesicles and formation of multilamellar structures with close contact between lamellae. It also increased the phase transition temperature by 10 °C but decreased transition cooperativity. The ODN rigidified and stabilized the gel phase. In the fluid phase, a simultaneous decrease of ordering close to the bilayer surface and increase in bilayer core rigidity was observed in the presence of the ODN. These effects may be due not only to electrostatic shielding of DODAB head groups but also to superficial dehydration of the bilayers. The data suggest that oligonucleotides may induce the formation of a multilamellar poorly hydrated coagel-like phase below phase transition. These effects should be taken into account when planning ODN delivery employing cationic bilayer carriers.

Structural characterization of novel cationic diC16-amidine bilayers: Evidence for partial interdigitation.

In this work, the bilayer structure of novel cationic lipid diC16-amidine was compared to the one of zwitterionic dipalmitoyl phosphatidylcholine ( DPPC), which shares the same hydrophobic domain. Differential scanning calorimetry shows that DPPC and diC16-am idine bilayers have similar phase transition temperatures, but diC16-a midine membranes display a less cooperative phase transition and an absence of pretransition. Both bilayers were analyzed from surface to core, using 5-, 7-, 10-, 12-, 14-, and 16-PCSL spin labels. As expected, electron spin resonance (ESR) spectra show that the gel phase of DPPC presents a flexibility gradient toward the core. In contrast, this gradient exists in the gel phase of diC16-amidine bilayers but only down to the 12th lipid tail carbon. The 14th and 16th carbons of the cationic lipid are in a very rigid environment, similar to the one observed at the bilayer surface. These data suggest that diC16-amidine molecules are organized in a partially interdigitated gel phase. ESR spectroscopy also shows that the lamellar fluid phase of diC16-amidine is more rigid than the one of DPPC. Fluorescence resonance energy transfer assays reveal that diC16-amidine displays a more efficient fusogenic activity in the gel phase than in the fluid one, suggesting that the partial interdigitation of the gel phase is important for the fusion process to occur. Since the gel- fl uid transition temperature is 42 ·c. diC16-amid ine is fusogenic at the physiological temperature and is therefore a promising lipid for delivery applications without the need of helper lipids.

Acute coronary syndrome in the young: clinical characteristics, risk factors and prognosis.

BACKGROUND: To describe the characteristics of patients ≤40 years of age hospitalized for acute coronary syndrome, analyze the risk factors and identify the variables associated with prognosis. METHODS: Case series of patients admitted between 2003 and 2012 inclusive in a tertiary hospital (123 consecutive cases admitted between 2003 and 2012), and case-control study (369 controls selected from the general population matched for sex and age with cases, at a ratio of 3:1). OUTCOME VARIABLES: Mortality, likelihood of survival without readmission for heart-related problems, extent of coronary disease as determined by coronary angiography and cardiovascular risk factors. RESULTS: Mean age was 35.4±4.8 years and 83.7% of the participants were men. Myocardial infarction with abnormal Q wave (48%) and single-vessel involvement (44.7%) predominated. Intrahospital mortality was 1.6%. For the 108 patients eventually included in the follow-up, likelihood of readmission-free survival after 60 months was 69.3±4.8%. In the case group 36% of the patients admitted to using cocaine. Compared to controls, the prevalence in patients was higher for smoking (74.8 vs 33.1%, p<0001), diabetes (14.6% vs 5.1%, p=0.001), low HDL-cholesterol (82.9 vs 34.1%, p<0.001) and obesity (30.0 vs 20.3%, p=0.029). Decreased left ventricular ejection fraction (odds ratio=2.2, p=0.033) and smoking (odds ratio=7.8, p=0.045) were associated with readmission for coronary syndrome. CONCLUSION: Acute coronary syndrome in people younger than 40 years is associated with diabetes and unhealthy lifestyle: smoking, sedentary behavior (low HDL-cholesterol), cocaine use and obesity. The readmission rate is high, and readmission is associated with smoking and decreased ejection fraction.

Implicación de las moléculas HLA de clase I en el escape inmunitario de tumores urológicos / Involvement of HLA Class I Molecules in the Immune Escape of Urologic Tumors

Contexto y objetivo: Analizar la influencia de las distintas alteraciones de las moléculas del antígeno leucocitario humano de clase i (HLA I ) en la promoción del cáncer renal, vesical y prostático. También estudiaremos la correlación entre la expresión de estas moléculas y la progresión de la enfermedad neoplásica, además de la respuesta al tratamiento. Adquisición de evidencias: Se ha podido constatar, experimentalmente, que el sistema inmunitario puede reconocer y destruir células tumorales. Mediante el análisis de la expresión de las moléculas HLA I, en la superficie de células tumorales, hemos podido estudiar este mecanismo de escape tumoral frente al sistema inmunitario. Síntesis de evidencias: Una alteración o daño irreversible en las moléculas HLA de clase i es utilizado por las células cancerígenas como mecanismo de escape frente al sistema inmunitario. La función de estas moléculas es reconocer péptidos endógenos y presentarlos a los linfocitos T del sistema inmunitario. Existe una clara relación entre alteraciones reversibles de HLA I y el éxito de la terapia, mientras que las lesiones irreversibles implican una falta de respuesta al tratamiento. La activación del sistema inmunitario puede revertir la expresión de moléculas HLA I en aquellos tumores con lesiones reversibles, mientras que los tumores con lesiones irreversibles no responden a dicha activación. Determinar el tipo de alteración HLA I en los tumores es de vital importancia a la hora de elegir el tipo de tratamiento a seguir buscando el éxito terapéutico. Aquellos tumores con lesiones reversibles pueden ser tratados con inmunoterapias clásicas, sin embargo, los tumores con alteraciones irreversibles deberían seguir protocolos alternativos, como el uso de vectores virales que trasporten los genes HLA dañados para conseguir la reexpresión de la proteína. Conclusión: A partir de los estudios realizados, en tumores urológicos, podemos concluir que las moléculas HLA de clase i tienen un papel fundamental en el escape de estos tumores frente al sistema inmunitario

Context and objective: To analyze the influence of different alterations in human leukocyte antigen class I molecules (HLA I) in renal cell carcinoma, as well as in bladder and prostate cancer. We also study the correlation between HLA I expression and the progression of the disease and the response after immunotherapy protocols. Evidences acquisition: It has been shown, experimentally, that the immune system can recognize and kill neoplastic cells. By analyzing the expression of HLA I molecules on the surface of cancer cells, we were able to study the tumor escape mechanisms against the immune system. Evidences synthesis: Alteration or irreversible damage in HLA I molecules is used by the neoplastic cells to escape the immune system. The function of these molecules is to recognize endogenous peptides and present them to T cells of the immune system. There is a clear relationship between HLA I reversible alterations and success of therapy. Irreversible lesions also imply a lack of response to treatment. The immune system activation can reverse HLA I molecules expression in tumors with reversible lesions, whereas tumors with irreversible ones do not respond to such activation. Determine the type of altered HLA I molecules in tumors is of paramount importance when choosing the type of treatment to keep looking for therapeutic success. Those tumors with reversible lesions can be treated with traditional immunotherapy; however, tumour with irreversible alterations should follow alternative protocols, such as the use of viral vectors carrying the HLA genes to achieve damaged re-expression of the protein. Conclusion: From studies in urologic tumors, we can conclude that the HLA I molecules play a key role in these tumors escape to the immune system

Síndrome de Evans Fisher asociado con esclerodermia / Fisher Evans syndrome associated with scleroderma

El síndrome de Evans Fisher, descrito por primera vez en 1951, es un desorden autoinmune caracterizado por la presencia simultánea o secuencial de anemia hemolítica, trombocitopenia inmune y, en ocasiones, neutropenia inmune; con una prueba de antiglobulina directa positiva. Puede ser de causa primaria o secundaria a otras condiciones, como el lupus eritematoso sistémico, los síndromes linfoproliferativos o inmunodeficiencias primarias. Es muy rara su asociación con la esclerodermia. Con el término esclerodermia, que en sentido literal significa piel dura, se designa un grupo de enfermedades y síndromes que tienen como característica común la induración y el engrosamiento cutáneos. Se caracteriza por la presencia de un depósito excesivo de los componentes del tejido conjuntivo, expresado en forma de fibrosis hística, y por alteraciones estructurales del lecho vascular. Con un cuadro clínico muy amplio, afecta fundamentalmente la piel y ciertos órganos internos, como tubo digestivo, pulmón, corazón y riñón. Se presenta una paciente femenina de 75 años de edad, piel negra, con antecedentes de hipertensión arterial, diabetes mellitus tipo 2, cardiopatía isquémica y esclerodermia, esta última diagnosticada seis meses antes de su ingreso. Acudió por decaimiento marcado, palidez cutáneo-mucosa intensa y petequias generalizadas. En los estudios realizados se detectó anemia y trombocitopenia severas, reticulocitosis, prueba de antiglobulina directa positiva e hipercelularidad medular con hiperplasia severa de los sistemas megacariopoyético y eritropoyético. Se diagnosticó un síndrome de Evans Fisher y se trató con esteroides e inmunomoduladores; se logró la mejoría clínica y la remisión hematológica

The Evans syndrome, first described in 1951, is an autoimmune disorder characterized by the simultaneous or sequential development of hemolytic anemia and immune thrombocytopenia or immune neutropenia. It may be of primary origin or secondary to other diseases or conditions such as systemic lupus erythematosus, lymphoproliferative disorders or primary immunodeficiencies. Its association with scleroderma is considered very rare. The word scleroderma, which literally means hard skin, designates a group of diseases and syndromes of common feature in induration and thickening the skin. It is characterized by the presence of excessive deposition of connective tissue components, expressed as histic fibrosis, and structural alterations of the vascular bed. With a broad clinical view, it primarily affects the skin and certain internal organs such as gastrointestinal tract, lung, heart and kidney. We present a 75 year-old female, black skin, with a history of hypertension, type 2 diabetes, ischemic heart disease and scleroderma, the latter diagnosed six months before admission. The patient referred marked weakness, pale skin and generalized petechiae. The complete blood count detected severe anemia, thrombocytopenia and reticulocytosis. Other studies showed positive direct Coombs test and severe hypercellularity. Evans Fisher syndrome was diagnosed and treated with steroids and immunomodulators; clinical improvement and hematologic remission was achieved

Síndrome de Evans Fisher asociado con esclerodermia / Fisher Evans syndrome associated with scleroderma

El síndrome de Evans Fisher, descrito por primera vez en 1951, es un desorden autoinmune caracterizado por la presencia simultánea o secuencial de anemia hemolítica, trombocitopenia inmune y, en ocasiones, neutropenia inmune; con una prueba de antiglobulina directa positiva. Puede ser de causa primaria o secundaria a otras condiciones, como el lupus eritematoso sistémico, los síndromes linfoproliferativos o inmunodeficiencias primarias. Es muy rara su asociación con la esclerodermia. Con el término esclerodermia, que en sentido literal significa piel dura, se designa un grupo de enfermedades y síndromes que tienen como característica común la induración y el engrosamiento cutáneos. Se caracteriza por la presencia de un depósito excesivo de los componentes del tejido conjuntivo, expresado en forma de fibrosis hística, y por alteraciones estructurales del lecho vascular. Con un cuadro clínico muy amplio, afecta fundamentalmente la piel y ciertos órganos internos, como tubo digestivo, pulmón, corazón y riñón. Se presenta una paciente femenina de 75 años de edad, piel negra, con antecedentes de hipertensión arterial, diabetes mellitus tipo 2, cardiopatía isquémica y esclerodermia, esta última diagnosticada seis meses antes de su ingreso. Acudió por decaimiento marcado, palidez cutáneo-mucosa intensa y petequias generalizadas. En los estudios realizados se detectó anemia y trombocitopenia severas, reticulocitosis, prueba de antiglobulina directa positiva e hipercelularidad medular con hiperplasia severa de los sistemas megacariopoyético y eritropoyético. Se diagnosticó un síndrome de Evans Fisher y se trató con esteroides e inmunomoduladores; se logró la mejoría clínica y la remisión hematológica(AU)

The Evans syndrome, first described in 1951, is an autoimmune disorder characterized by the simultaneous or sequential development of hemolytic anemia and immune thrombocytopenia or immune neutropenia. It may be of primary origin or secondary to other diseases or conditions such as systemic lupus erythematosus, lymphoproliferative disorders or primary immunodeficiencies. Its association with scleroderma is considered very rare. The word scleroderma, which literally means hard skin, designates a group of diseases and syndromes of common feature in induration and thickening the skin. It is characterized by the presence of excessive deposition of connective tissue components, expressed as histic fibrosis, and structural alterations of the vascular bed. With a broad clinical view, it primarily affects the skin and certain internal organs such as gastrointestinal tract, lung, heart and kidney. We present a 75 year-old female, black skin, with a history of hypertension, type 2 diabetes, ischemic heart disease and scleroderma, the latter diagnosed six months before admission. The patient referred marked weakness, pale skin and generalized petechiae. The complete blood count detected severe anemia, thrombocytopenia and reticulocytosis. Other studies showed positive direct Coombs test and severe hypercellularity. Evans Fisher syndrome was diagnosed and treated with steroids and immunomodulators; clinical improvement and hematologic remission was achieved(AU)