Erythrocytes as Carriers for Recombinant Human Erythropoietin

Purpose. The aim of this work was to encapsulate recombinant human erythropoietin (rHuEpo) in human and mouse red blood cells (RBCs) to improve the stability of encapsulated rHuEpo. Methods. The encapsulation of rHuEpo was achieved by an hypotonic dialysis-isotonic resealing procedure. A radioimmunoassay method was used for the estimation of rHuEpo. The hypoosmotic resistance of carrier erytrhocytes was studied by osmotic fragility measurements. Cell morphology was observed under scanning electron microscopy. Encapsulated rHuEpo was identified by an immunogold labeling assay. Results. Encapsulation yields were 22% for human RBCs and 14% for mouse RBCs. Cell recovery was around 70%. Carrier-RBCs exhibited a tendency to spherocytic morphology, and showed the typical higher hypoosmotic resistance than normal RBCs. The presence of rHuEpo inside carrier RBCs was identified. The stability of encapsulated rHuEpo seems to be related to the experimental conditions used during the encapsulation procedure. An increase with time of released rHuEpo was observed in carrier-RBC suspensions. Conclusions. The encapsulation of rHuEpo in RBCs has been achieved for the first time. These carrier RBC-preparations may serve as an alternative sustained cell delivery system for the in vivo administration of rHuEpo.     

Dihydrocucurbitacin B, isolated from Cayaponia tayuya, reduces damage in adjuvant-induced arthritis

23,24-Dihydrocucurbitacin B, from the anti-rheumatic plant Cayaponia tayuya, was tested on arthritis induced by adjuvant to corroborate the anti-inflammatory properties of this plant. Arthritis was induced in Lewis rats; the resulting arthritic rats were then treated with dihydrocucurbitacin B (1 mg/kg orally, daily, 1 week). The effect of dihydrocucurbitacin B on the synthesis, release, and activity of pro-inflammatory enzymes (elastase, cyclooxygenase-2, and nitric oxide synthase-2) as well as its effect on different mediators (tumor necrosis factor-alpha and interleukin-1beta) were determined. Dihydrocucurbitacin B modified the evolution of the clinical symptoms, reducing the swelling and bone and tissue damage along with the development of the disease, modifying the cell infiltration and the expression of both nitric oxide synthase-2 and cyclooxygenase-2. In addition, it decreased the tumor necrosis factor-alpha and interleukin-1beta production in lymphocytes, but did not modify it in macrophages.     

Modulation of protein tyrosine nitration and inflammatory mediators by isoprenylhydroquinone glucoside.

The nitration of tyrosine caused by peroxynitrite and other reactive nitrogen species is clearly detrimental for some physiological processes; however, its signalling role is still open to controversy. Among the natural phenolics known for their ability to oppose free tyrosine nitration, isoprenylhydroquinone glucoside is investigated due to its unusual structure, which contains a simple hydroxybenzene alkylated by a hemiterpenoid moiety. This hydroquinone was shown to be an effective inhibitor of peroxynitrite-induced protein tyrosine nitration in 3T3 fibroblasts. When tested on bovine seroalbumin nitration, however, the potency was reduced by half and the effect was almost abolished in the presence of bicarbonate. In contrast, addition of this anion had no effect on the nitrite/hydrogen peroxide/hemin system. Isoprenylhydroquinone glucoside was also active in the microM range on intra- and extracellular protein-bound tyrosine nitration by phorbol 12-myristate 13-acetate-stimulated neutrophils. The effects on nitric oxide synthase expression, interleukin-1beta and tumor necrosis factor-alpha production by lipopolysaccharide-stimulated macrophages were quite moderate. Thus, isoprenylhydroquinone glucoside is an inhibitor of protein nitration in situ, but lacks effect on the generation of either nitric oxide or inflammatory cytokines.     

Dental impactions related to pseudoxanthoma elasticum

Pseudoxanthoma elasticum is a rare genetic disorder causing degeneration and calcification of elastic fibers, leading to injuries in the skin, retina, and cardiovascular system. This report describes a case of a 30-year-old woman whose diagnosis of pseudoxanthoma elasticum was confirmed after a skin biopsy. The patient presented at the Clinical Management Unit of the Department of Oral and Maxillofacial Surgery, Virgen del Rocio Hospital (Seville, Spain) with pain related to a semi-erupted lower first molar. Radiologic examination disclosed multiple dental impactions. Cases of oligodontia, amelogenesis imperfecta, and mucosal lesions related to pseudoxanthoma elasticum were found in the current literature, but there were no reports of multiple dental impactions.     

Automatic detection of the intima-media thickness in ultrasound images of the common carotid artery using neural networks

Atherosclerosis is the leading underlying pathologic process that results in cardiovascular diseases, which represents the main cause of death and disability in the world. The atherosclerotic process is a complex degenerative condition mainly affecting the medium- and large-size arteries, which begins in childhood and may remain unnoticed during decades. The intima-media thickness (IMT) of the common carotid artery (CCA) has emerged as one of the most powerful tool for the evaluation of preclinical atherosclerosis. IMT is measured by means of B-mode ultrasound images, which is a non-invasive and relatively low-cost technique. This paper proposes an effective image segmentation method for the IMT measurement in an automatic way. With this purpose, segmentation is posed as a pattern recognition problem, and a combination of artificial neural networks has been trained to solve this task. In particular, multi-layer perceptrons trained under the scaled conjugate gradient algorithm have been used. The suggested approach is tested on a set of 60 longitudinal ultrasound images of the CCA by comparing the automatic segmentation with four manual tracings. Moreover, the intra- and inter-observer errors have also been assessed. Despite of the simplicity of our approach, several quantitative statistical evaluations have shown its accuracy and robustness.     

Evolución en el diagnóstico,el tratamiento y la mortalidad del síndrome aórtico agudo en los últimos 20 años

Introduction and objectivesMortality is high in acute aortic syndrome (AAS), which therefore requires early treatment. This study aimed to analyze changes in the diagnosis and treatment of AAS over 20 years at our center.MethodsFrom 1999 to 2018, 451 patients diagnosed with AAS (336 men; mean age, 60.9 ± 12.4 years) were prospectively included (270 type A and 181 type B). Clinical variables, diagnosis, treatment, and in-hospital complications were analyzed.ResultsThe use of computed tomography (CT) as the first-line diagnostic technique increased from 62.8% to 94.2% (P < .001). Surgical treatment of type A AAS rose from 67.4% to 82.5% (P = .09). Mortality from type A AAS decreased significantly from 53.1% to 26.3% (P < .001) as a result of the fall in mortality from surgical treatment (from 45.4% to 17.0%; P < .001). The use of medical treatment alone for type B AAS decreased from 91.8% to 61.7% (P < .001) due to the greater use of endovascular treatment. Mortality from type B AAS showed no significant reduction (16.2% to 10.6%; P = .15).ConclusionsThe diagnosis and treatment of AAS has changed substantially in the last 2 decades. CT has become the first-line diagnostic technique for AAS. In type A AAS, mortality has fallen significantly due to improvements in the results of surgical treatment. In type B AAS, the use of medical treatment alone has decreased due to the expansion of endovascular treatment, although in-hospital mortality has not decreased significantly.