Sevoflurane anesthetic preconditioning protects the lung endothelial glycocalyx from ischemia reperfusion injury in an experimental lung autotransplant model.

PURPOSE: The glycocalyx is a glycoprotein-polysaccaride layer covering the endothelium luminal surface, and plays a key regulatory role in several endothelial functions. Lung ischemia reperfusion (IR) is a clinical entity that occurs in everyday thoracic surgery and causes glycocalix destruction and a florid local and systemic immune response. Moreover, sevoflurane is able to modulate the inflammatory response triggered by IR lung injury. In this study, we evaluated the protective effects of sevoflurane on the pulmonary endothelial glycocalyx in an in-vivo lung autotransplant model in pigs. METHODS: Sixteen Large White pigs underwent pneumonectomy plus lung autotransplant. They were divided into two groups depending on the hypnotic agent received (propofol or anesthetic preconditioning with sevoflurane). Glycocalyx components (syndecan-1 and heparan sulphate), cathepsin B, chemokines (MCP-1, MIP-1, and MIP-2) and adhesion molecules (VCAM and ICAM-1) were measured at four different timepoints using porcine-specific enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: There were no differences between groups in weight or in surgical and one-lung ventilation time. Greater glycocalyx destruction and higher chemokine and adhesion molecule expression were observed in the group that did not receive sevoflurane. Heparan sulphate and serum syndecan levels were higher in the propofol group (P < 0.0001) after reperfusion, as was cathepsin B activity (P < 0.015). MCP-1, MIP-1, MIP-2, VCAM, and ICAM-1 levels were also higher in the propofol group (P < 0.006). CONCLUSION: Sevoflurane preconditioning protects pulmonary glycocalyx and reduces expression of leukocyte chemokines in an in-vivo model of pulmonary IR.

[Profile of women with breast disease wich does self-exploration. Which are the factors associated with this practice?]. / Mujer con patología mamaria.

BACKGROUND/AIMS: In recent decades the fight against breast cancer has focused primarily on the treatment and secondary prevention (early detection mainly). In the case of breast self-examination, althought it has not been prove to reduce mortality, it is important in cases detected by women themselves (it is estimated 90% of total), mainly in the interval cancers. OBJECTIVES: To identify within women with breast cancer, how many do self-examination and identify associated factors. Describe the clinical and pathological features of cancers in women who do perform self-examination. METHODOLOGY: In women diagnosed with breast cancer during 2007 in a hospital in the province of Cadiz, Spain, is reconstructed in retrospect the story related the cancer process: symptoms, psychosocial factors that determine the contact with the health system, preventive practices (self-examination, mammography screening). A description of the pathological tumor: presenting symptom, tumor size, node negative, grade of differentiation. RESULTS: We studied 149 women with breast cancer, from whom 52% did self-exploration. Women who performed self-examination were younger (54.78 years) against the women who did not (65.63 years), married (66.2%), active workers and have a higher educational level. The assessment of the first symptoms in these women as "important" is positively correlated with those women who practice self-examination. For other preventive practices, women who does self-examination are also the most actives in early detection programs (74.4% against 29.5% which didn't do self-examination). For the pathologic characteristics of tumor in women who did self-examination: the tumor size was 2.5 cm, 50.7/are well differentiated, and 59.1% of cases the nodes are negative. CONCLUSIONS: Women who does self-examination are younger, have higher educational level, are married, are active workers and are often involved in other preventive practices. On them, the tumors diagnosed have a smaller size, are diagnosed at earlier stages and usually present better degree of differentiation.

No evidence of association between inherited thrombophilia and increased risk of liver fibrosis.

BACKGROUND: Preliminary evidence suggests that inherited hypercoagulable disorders can lead to an increased risk of significant liver fibrosis. OBJECTIVE: We aimed to investigate the prevalence of significant fibrosis in patients with inherited thrombophilia, assessed by using liver stiffness (LS), and to compare this prevalence to that found in a large population-based cohort from the same region. METHODS: This was a single-center, cross-sectional study. A complete laboratory analysis for liver disease, LS by transient elastography and an abdominal ultrasound were performed in patients with inherited thrombophilia diagnosed between May 2013-February 2017. These patients were propensity score matched (ratio 1:4) with a population-based cohort from the same region (PREVHEP-ETHON study; NCT02749864; N = 5988). RESULTS: Of 241 patients with inherited thrombophilia, eight patients (3.3%) had significant fibrosis (LS ≥8 kPa). All of them had risk factors for liver disease and met diagnostic criteria for different liver diseases. After matching 221 patients with thrombophilia with 884 patients of the PREVHEP-ETHON cohort, the prevalence of significant fibrosis was similar between both cohorts (1.8% vs. 3.6%, p = 0.488). Multivariate analysis showed that age and liver disease risk factors, but not belonging to the thrombophilia cohort, were associated with the presence of significant fibrosis. The magnitude of the increased risk of significant fibrosis in patients with risk factors for liver disease was also similar in both cohorts. CONCLUSIONS: Our findings do not provide evidence supporting an association between inherited thrombophilia and an increased risk of significant liver fibrosis, independent of the presence of liver-related causes of fibrosis.

Portal Vein Thrombosis in the Setting of Cirrhosis: A Comprehensive Review.

Portal vein thrombosis constitutes the most common thrombotic event in patients with cirrhosis, with increased rates in the setting of advanced liver disease. Despite being a well-known complication of cirrhosis, the contribution of portal vein thrombosis to hepatic decompensation and overall mortality is still a matter of debate. The incorporation of direct oral anticoagulants and new radiological techniques for portal vein recanalization have expanded our therapeutic arsenal. However, the lack of large prospective observational studies and randomized trials explain the heterogenous diagnostic and therapeutic recommendations of current guidelines. This article seeks to make a comprehensive review of the pathophysiology, clinical features, diagnosis, and treatment of portal vein thrombosis in patients with cirrhosis.

[The impact of COVID-19 on urology restructuring and organization.] / Impacto de la COVID-19 sobre la reestructuración y organización en urología.

Desde que el 31 de diciembre de 2019, se informó el primer caso de neumonía de etiología desconocida en la ciudad de Wuhan (China), la humanidad desconocía cómo iba a cambiar la vida tal cual la conocíamos y los profundos cambios que se iban a suscitar. La Organización Mundial de la Salud (OMS) el 12 de enero de 2020 reporta una nueva cepa de coronavirus que causaba el Síndrome Respiratorio Agudo Severo CoronaVirus 2 (SARS-CoV-2) (1) caracterizado por un cuadro clínico que variaba desde el portador asintomático hasta casos mortales de neumonía, insuficiencia respiratoria y fallo multiorgánico...

Desde que el 31 de diciembre de 2019, se informó el primer caso de neumonía de etiología desconocida en la ciudad de Wuhan (China), la humanidad desconocía cómo iba a cambiar la vida tal cual la conocíamos y los profundos cambios que se iban a suscitar. La Organización Mundial de la Salud (OMS) el 12 de enero de 2020 reporta una nueva cepa de coronavirus que causaba el Síndrome Respiratorio Agudo Severo CoronaVirus 2 (SARS-CoV-2) (1)caracterizado por un cuadro clínico que variaba desde el portador asintomático hasta casos mortales de neumonía, insuficiencia respiratoria y fallo multiorgánico...

Synthesis, biological, and photophysical studies of molecular rotor-based fluorescent inhibitors of the trypanosome alternative oxidase.

We have recently reported on the development and trypanocidal activity of a class of inhibitors of Trypanosome Alternative Oxidase (TAO) that are targeted to the mitochondrial matrix by coupling to lipophilic cations via C14 linkers to enable optimal interaction with the enzyme's active site. This strategy resulted in a much-enhanced anti-parasite effect, which we ascribed to the greater accumulation of the compound at the location of the target protein, i.e. the mitochondrion, but to date this localization has not been formally established. We therefore synthesized a series of fluorescent analogues to visualize accumulation and distribution within the cell. The fluorophore chosen, julolidine, has the remarkable extra feature of being able to function as a viscosity sensor and might thus additionally act as a probe of the cellular glycerol that is expected to be produced when TAO is inhibited. Two series of fluorescent inhibitor conjugates incorporating a cationic julolidine-based viscosity sensor were synthesized and their photophysical and biological properties were studied. These probes display a red emission, with a high signal-to-noise ratio (SNR), using both single- and two-photon excitation. Upon incubation with T. brucei and mammalian cells, the fluorescent inhibitors 1a and 2a were taken up selectively in the mitochondria as shown by live-cell imaging. Efficient partition of 1a in functional isolated (rat liver) mitochondria was estimated to 66 ± 20% of the total. The compounds inhibited recombinant TAO enzyme in the submicromolar (1a, 2c, 2d) to low nanomolar range (2a) and were effective against WT and multidrug-resistant trypanosome strains (B48, AQP1-3 KO) in the submicromolar range. Good selectivity (SI > 29) over mammalian HEK cells was observed. However, no viscosity-related shift could be detected, presumably because the glycerol was produced cytosolically, and released through aquaglyceroporins, whereas the probe was located, virtually exclusively, in the trypanosome's mitochondrion.

Surgical management of complicated inflammatory glaucoma.

Case report: We report a case of a 26-year-old woman with a previous history of complicated ulcerative colitis, as well as multiple episodes of recurrent anterior uveitis in control with adalimumab and methotrexate, who develops ocular hypertension refractory to topical treatment. The implant of an EXPRESS® is proposed, but in the immediate post-operative period, the implant causes atalamia and does not achieve the correct control of intraocular pressure. A XEN® stent was implanted. Due to failure, it was decided to remove the stent and to release a subconjunctival fibrosis that had formed at the subconjunctival portion of the XEN®, in association with coating by an Ologen® collagen matrix, which led to an improvement of the results. Conclusions: The surgical management of inflammatory glaucoma is complex in young patients with a scar component. The new minimally invasive techniques are effective in cases refractory to topical treatment, whose characteristics prevent the use of conventional ones.

Conjugates of 2,4-Dihydroxybenzoate and Salicylhydroxamate and Lipocations Display Potent Antiparasite Effects by Efficiently Targeting the Trypanosoma brucei and Trypanosoma congolense Mitochondrion.

We investigated a chemical strategy to boost the trypanocidal activity of 2,4-dihydroxybenzoic acid (2,4-DHBA)- and salicylhydroxamic acid (SHAM)-based trypanocides with triphenylphosphonium and quinolinium lipophilic cations (LC). Three series of LC conjugates were synthesized that were active in the submicromolar (5a-d and 10d-f) to low nanomolar (6a-f) range against wild-type and multidrug resistant strains of African trypanosomes (Trypanosoma brucei brucei and T. congolense). This represented an improvement in trypanocidal potency of at least 200-fold, and up to >10 000-fold, compared with that of non-LC-coupled parent compounds 2,4-DHBA and SHAM. Selectivity over human cells was >500 and reached >23 000 for 6e. Mechanistic studies showed that 6e did not inhibit the cell cycle but affected parasite respiration in a dose-dependent manner. Inhibition of trypanosome alternative oxidase and the mitochondrial membrane potential was also studied for selected compounds. We conclude that effective mitochondrial targeting greatly potentiated the activity of these series of compounds.

Fournier's gangrene: a radiologic emergency.

Fournier's gangrene (FG) is a life-threatening, necrotizing infection involving the soft tissues of the scrotal area. Because of potential severe complications, it is important to diagnose the disease as early as possible. We present the CT findings of FG in a young male that came to the Emergency Department for genital pain and tenderness.

Bloqueo radicular lumbar selectivo guiado por TAC Alternativa para diagnòstico y tratamiento de radiculopatìas originadas por hernias discales y/o artrosis facetarias / Selective lumbar radicular lock replacement for CT-guided diagnosis and treatment of radiculopathy caused by herniated discs and / or facet arthrosis

El presente estudio muestra experiencia en la realización de bloqueos facetarios periarticulares y radiculares lumbares guiados Por Toomografía Axial Computada (TAC), en pacientes con dolor lumbar, o lumbociático provocado por estenosis foraminales de diversas causas, especialmente las secundarias a hernias discales foraminales sin manifestaciones de déficit motor y artrosis facetarias, en estos casos, la causa del dolor se supone se debe ala isquemia que afecta directamente las raíces nerviosas y produce sìntomas. Se realizó la evaluaciòn de 55 pacientes a los que se les efectuó este procedimiento entre los años 2007-2010 con diagnóstico de radiculopatía lumbar provocados por estenosis foraminales secundarias a hernias discales foraminales sin manifestaciones de deficít motor y artrosis facetarias y que no mejorarón con tratamiento médico - kinésico en 4 a 6 semana. 40 Hombres y 15 mujeres con edades entre 35 y 84 años. se realizaron 45 bloqueos de raíces nerviosas, a 10 pacientes se le realizó en dos espacios simultáneo en forma homolateral, y 10 facetarios periarticulares, 8 en forma bilateral. el 90% de los pacientes y refirió mejoría inmediata después del procedimiento, con resultados variables a largo plazo. la duración de la mejoría del dolor fue variable y osciló en un rango de 15 días hasta en forma permanente en el 80% de los casos. Los procedimientos en su mayoría se realizaron con internación de 24 horas. No se presentaron complicaciones técnicas ni posteriores a la inyección. En nuestra experiencia los mejores resultados se encuentran en el dolor radicular con el diagnóstico de hernia discal foraminal. Se concluye con los bloqueos facetarios y radiculares constituyen un método diagnóstico y terapéutico que puede realizarse con mucha precisión y seguridad utilizando la ayuda de imágenes diagnósticas, especialmente la TAC siendo útiles para la localización del origen del dolor y para decidir un eventual tratamiento definitivo...

SUMMARY: The following study shows our experience doing TAC-guided lumbar facet periarticular and radicular blockades in patients with lumbar or lumbociatic pain caused by foraminal stenosis due to different causes, specially those secondary to foraminal disc herniantions without motor impairment and facetary arthrosis (in these cases, the cause of the pain is supposed to be due to ischemia affecting the nerve roots which causes the symptoms). We evaluated patients to whom the procedure was performed between 2007 and 2010, with diagnosis of lumbar radiculopathy caused by foraminal stenosis secondary to foraminal disc herniations without evidence of motor impairment and facetary arthrosis, whichdidn' t improve with kinesic medical treatment in 4 to 6 weeks. 55 patients were incluided, 40 men and 15 women, between 35 and 84 years. 45 nerve root blockades, in 10 patients it was done homolaterally in two space simultaneously, and 10 periarticular facetary blockades were performed, 8 bilateral, 90% of the patients refered immediate improvement of the symptoms after the procedure, with variable long-term results. The duration of the pain relief was variable and ranged from 15 days to permanent in 80% of the cases. In most of the cases the procedure was done with 24-hour hospital stay. There were no complications, neither technical nor following the injections. In our experience the best results are achieved in the treatment of radicular pain with the diagnosis of foraminal disc herniation. In conclusion, facetary and radicular blockades represent highly precise and safe, both therapeutic and diagnostic methods, that could be used with the aid of diagnostic images, specially TAC, to localize the origin of the pain as well as to decide an eventual definitive treatment.