Resultados clínicos de artroplastia total de cadera asistida por brazo robótico en España: estudio preliminar / Clinical results of total hip arthroplasty assisted by robotic arm in Spain: Preliminary study

Objetivos: Resultados clínicos, radiológicos y funcionales de la primera serie española de pacientes intervenidos de artroplastia total de cadera (ATC) asistida mediante brazo robótico Mako® (Stryker) del Hospital Clínico San Carlos (HCSC) de Madrid. Material y métodos: Estudio descriptivo prospectivo que analiza los primeros 25 pacientes intervenidos de ATC asistida por robot (ATCaR) en el HCSC, con un seguimiento mínimo de 4meses. Se evaluaron la demografía, los estudios de imagen (procesamiento Mako®, Rx y TAC), los parámetros clínicos, la funcionalidad (Harris modificada) y las complicaciones asociadas. Resultados: La edad media fue 67,2años (min 47, max 88), siendo el 56% varones. El 88% corresponden a coxartrosis primaria, el 4% postraumática, el 4% secundaria a NAV y el 4% secundaria a choque femoroacetabular. El tiempo medio de cirugía fue de 116,9minutos (min 92, max 150). La media de las cinco primeras intervenciones fue 122,6minutos, y la de las cinco últimas, de 108,2minutos. Como complicaciones intraoperatorias se cuantificaron 4 pérdidas de marcadores intraoperatorios. El tiempo de ingreso medio fue 4,4días (min 3, max 7), con una disminución de hemoglobina posquirúrgica media de 3,08±1,08g/dl, requiriendo transfusión en el 12% de los casos. Se registran tres complicaciones médicas durante el ingreso, destacando un síndrome confusional con caída y fractura periprotésica AG1 no desplazada. El análisis del posicionamiento de los implantes registrados con sistema Mako® fueron 40,55±1,53 grados de inclinación y 12,2±3,6 grados de anteversión acetabular. El estudio de imagen posquirúrgico realizado a los pacientes, en concordancia con Mako®, muestra valores de inclinación acetabular de 41,2±1,7 en Rx y versión acetabular de 16±4,6 en TAC. La discrepancia de longitud de cadera varía de valores preoperatorios de −3,91mm (DE: 3,9; min −12, max 3) a 1,29mm (DE: 1,96) tras la cirugía registrados con Mako...(AU)

Objectives: Clinical, radiological and functional results of the first Spanish series of patients undergoing total hip arthroplasty assisted by Mako® (Stryker) robotic arm at the Hospital Clínico San Carlos (HCSC) in Madrid. Material and methods: Prospective and descriptive study analyzing the first 25 patients who underwent robotic-assisted THA at the HCSC, with a minimum follow-up of 4months. Demographics, imaging studies (Mako® processing, Rx and CT), clinical parameters, functionality (modified Harris) and associated complications were evaluated. Results: Average age was 67.2years (min 47, max 88), being 56% male population sample. 88% involves primary coxarthrosis, 4% post-traumatic coxarthrosis, 4% secondary avascular necrosis and 4% secondary femoroacetabular impingement. Average surgery time was 116.9min (min 92, max 150). The average time of the first five surgeries was 122.6min, and, regarding the last five interventions, it was 108.2min. Found medical intraoperative complications were four intraoperative markers loss. Average admission time was 4.4days (min 3, max 7), with an average postoperative hemoglobin decrease of 3.08±1.08g/dL, requiring a transfusion in 12% of the cases. Three medical complications have been registered in the meantime of the admission, with a relevant case of a confusional syndrome and a fall, which resulted in a non-displaced AG1 periprosthetic fracture. The analysis of the positioning of registered implants with Mako® system shows 40.55±1.53 acetabular inclination degrees and 12.2±3.6 acetabular anteversion degrees. The postoperative image study carried out on patients, are consistent with Mako® s results, as it shows an acetabular inclination of 41.2±1.7 in Rx, as well as acetabular anteversion of 16±4.6 in CT. Hip length variance ranges depending on preoperative values of 3.91mm (SD: 3.9; min −12, max 3) to 1.29mm (SD: 1.96) after surgery registered with...(AU)

[Translated article] Clinical results of total hip arthroplasty assisted by robotic arm in Spain: Preliminary study / Resultados clínicos de la artroplastia total de cadera asistida por brazo robótico en España: estudio preliminar

Objetivos: Resultados clínicos, radiológicos y funcionales de la primera serie española de pacientes intervenidos de artroplastia total de cadera (ATC) asistida mediante brazo robótico Mako® (Stryker) del Hospital Clínico San Carlos (HCSC) de Madrid. Material y métodos: Estudio descriptivo prospectivo que analiza los primeros 25 pacientes intervenidos de ATC asistida por robot (ATCaR) en el HCSC, con un seguimiento mínimo de 4meses. Se evaluaron la demografía, los estudios de imagen (procesamiento Mako®, Rx y TAC), los parámetros clínicos, la funcionalidad (Harris modificada) y las complicaciones asociadas. Resultados: La edad media fue 67,2años (min 47, max 88), siendo el 56% varones. El 88% corresponden a coxartrosis primaria, el 4% postraumática, el 4% secundaria a NAV y el 4% secundaria a choque femoroacetabular. El tiempo medio de cirugía fue de 116,9minutos (min 92, max 150). La media de las cinco primeras intervenciones fue 122,6minutos, y la de las cinco últimas, de 108,2minutos. Como complicaciones intraoperatorias se cuantificaron 4 pérdidas de marcadores intraoperatorios. El tiempo de ingreso medio fue 4,4días (min 3, max 7), con una disminución de hemoglobina posquirúrgica media de 3,08±1,08g/dl, requiriendo transfusión en el 12% de los casos. Se registran tres complicaciones médicas durante el ingreso, destacando un síndrome confusional con caída y fractura periprotésica AG1 no desplazada. El análisis del posicionamiento de los implantes registrados con sistema Mako® fueron 40,55±1,53 grados de inclinación y 12,2±3,6 grados de anteversión acetabular. El estudio de imagen posquirúrgico realizado a los pacientes, en concordancia con Mako®, muestra valores de inclinación acetabular de 41,2±1,7 en Rx y versión acetabular de 16±4,6 en TAC. La discrepancia de longitud de cadera varía de valores preoperatorios de −3,91mm (DE: 3,9; min −12, max 3) a 1,29mm (DE: 1,96) tras la cirugía registrados con Mako...(AU)

Objectives: Clinical, radiological and functional results of the first Spanish series of patients undergoing total hip arthroplasty assisted by Mako® (Stryker) robotic arm at the Hospital Clínico San Carlos (HCSC) in Madrid. Material and methods: Prospective and descriptive study analyzing the first 25 patients who underwent robotic-assisted THA at the HCSC, with a minimum follow-up of 4months. Demographics, imaging studies (Mako® processing, Rx and CT), clinical parameters, functionality (modified Harris) and associated complications were evaluated. Results: Average age was 67.2years (min 47, max 88), being 56% male population sample. 88% involves primary coxarthrosis, 4% post-traumatic coxarthrosis, 4% secondary avascular necrosis and 4% secondary femoroacetabular impingement. Average surgery time was 116.9min (min 92, max 150). The average time of the first five surgeries was 122.6min, and, regarding the last five interventions, it was 108.2min. Found medical intraoperative complications were four intraoperative markers loss. Average admission time was 4.4days (min 3, max 7), with an average postoperative hemoglobin decrease of 3.08±1.08g/dL, requiring a transfusion in 12% of the cases. Three medical complications have been registered in the meantime of the admission, with a relevant case of a confusional syndrome and a fall, which resulted in a non-displaced AG1 periprosthetic fracture. The analysis of the positioning of registered implants with Mako® system shows 40.55±1.53 acetabular inclination degrees and 12.2±3.6 acetabular anteversion degrees. The postoperative image study carried out on patients, are consistent with Mako® s results, as it shows an acetabular inclination of 41.2±1.7 in Rx, as well as acetabular anteversion of 16±4.6 in CT. Hip length variance ranges depending on preoperative values of 3.91mm (SD: 3.9; min −12, max 3) to 1.29mm (SD: 1.96) after surgery registered with...(AU)

[Translated article] Validation of the Spanish version of the modified Harris score / Validación de la versión española de la escala de Harris modificada

Objetivos: Resultados clínicos, radiológicos y funcionales de la primera serie española de pacientes intervenidos de artroplastia total de cadera (ATC) asistida mediante brazo robótico Mako® (Stryker) del Hospital Clínico San Carlos (HCSC) de Madrid. Material y métodos: Estudio descriptivo prospectivo que analiza los primeros 25 pacientes intervenidos de ATC asistida por robot (ATCaR) en el HCSC, con un seguimiento mínimo de 4meses. Se evaluaron la demografía, los estudios de imagen (procesamiento Mako®, Rx y TAC), los parámetros clínicos, la funcionalidad (Harris modificada) y las complicaciones asociadas. Resultados: La edad media fue 67,2años (min 47, max 88), siendo el 56% varones. El 88% corresponden a coxartrosis primaria, el 4% postraumática, el 4% secundaria a NAV y el 4% secundaria a choque femoroacetabular. El tiempo medio de cirugía fue de 116,9minutos (min 92, max 150). La media de las cinco primeras intervenciones fue 122,6minutos, y la de las cinco últimas, de 108,2minutos. Como complicaciones intraoperatorias se cuantificaron 4 pérdidas de marcadores intraoperatorios. El tiempo de ingreso medio fue 4,4días (min 3, max 7), con una disminución de hemoglobina posquirúrgica media de 3,08±1,08g/dl, requiriendo transfusión en el 12% de los casos. Se registran tres complicaciones médicas durante el ingreso, destacando un síndrome confusional con caída y fractura periprotésica AG1 no desplazada. El análisis del posicionamiento de los implantes registrados con sistema Mako® fueron 40,55±1,53 grados de inclinación y 12,2±3,6 grados de anteversión acetabular. El estudio de imagen posquirúrgico realizado a los pacientes, en concordancia con Mako®, muestra valores de inclinación acetabular de 41,2±1,7 en Rx y versión acetabular de 16±4,6 en TAC. La discrepancia de longitud de cadera varía de valores preoperatorios de −3,91mm (DE: 3,9; min −12, max 3) a 1,29mm (DE: 1,96) tras la cirugía registrados con Mako...(AU)

Objectives: Clinical, radiological and functional results of the first Spanish series of patients undergoing total hip arthroplasty assisted by Mako® (Stryker) robotic arm at the Hospital Clínico San Carlos (HCSC) in Madrid. Material and methods: Prospective and descriptive study analyzing the first 25 patients who underwent robotic-assisted THA at the HCSC, with a minimum follow-up of 4months. Demographics, imaging studies (Mako® processing, Rx and CT), clinical parameters, functionality (modified Harris) and associated complications were evaluated. Results: Average age was 67.2years (min 47, max 88), being 56% male population sample. 88% involves primary coxarthrosis, 4% post-traumatic coxarthrosis, 4% secondary avascular necrosis and 4% secondary femoroacetabular impingement. Average surgery time was 116.9min (min 92, max 150). The average time of the first five surgeries was 122.6min, and, regarding the last five interventions, it was 108.2min. Found medical intraoperative complications were four intraoperative markers loss. Average admission time was 4.4days (min 3, max 7), with an average postoperative hemoglobin decrease of 3.08±1.08g/dL, requiring a transfusion in 12% of the cases. Three medical complications have been registered in the meantime of the admission, with a relevant case of a confusional syndrome and a fall, which resulted in a non-displaced AG1 periprosthetic fracture. The analysis of the positioning of registered implants with Mako® system shows 40.55±1.53 acetabular inclination degrees and 12.2±3.6 acetabular anteversion degrees. The postoperative image study carried out on patients, are consistent with Mako® s results, as it shows an acetabular inclination of 41.2±1.7 in Rx, as well as acetabular anteversion of 16±4.6 in CT. Hip length variance ranges depending on preoperative values of 3.91mm (SD: 3.9; min −12, max 3) to 1.29mm (SD: 1.96) after surgery registered with...(AU)

Clinical results of total hip arthroplasty assisted by robotic arm in Spain: Preliminary study. / Resultados clínicos de artroplastia total de cadera asistida por brazo robótico en España: estudio preliminar.

OBJECTIVES: Clinical, radiological and functional results of the first Spanish series of patients undergoing total hip arthroplasty assisted by Mako® (Stryker) robotic arm at the Hospital Clínico San Carlos (HCSC) in Madrid. MATERIAL AND METHODS: Prospective and descriptive study analyzing the first 25 patients who underwent robotic-assisted THA at the HCSC, with a minimum follow-up of 4months. Demographics, imaging studies (Mako® processing, Rx and CT), clinical parameters, functionality (modified Harris) and associated complications were evaluated. RESULTS: Average age was 67.2years (min 47, max 88), being 56% male population sample. 88% involves primary coxarthrosis, 4% post-traumatic coxarthrosis, 4% secondary avascular necrosis and 4% secondary femoroacetabular impingement. Average surgery time was 116.9min (min 92, max 150). The average time of the first five surgeries was 122.6min, and, regarding the last five interventions, it was 108.2min. Found medical intraoperative complications were four intraoperative markers loss. Average admission time was 4.4days (min 3, max 7), with an average postoperative hemoglobin decrease of 3.08±1.08g/dL, requiring a transfusion in 12% of the cases. Three medical complications have been registered in the meantime of the admission, with a relevant case of a confusional syndrome and a fall, which resulted in a non-displaced AG1 periprosthetic fracture. The analysis of the positioning of registered implants with Mako® system shows 40.55±1.53 acetabular inclination degrees and 12.2±3.6 acetabular anteversion degrees. The postoperative image study carried out on patients, are consistent with Mako® s results, as it shows an acetabular inclination of 41.2±1.7 in Rx, as well as acetabular anteversion of 16±4.6 in CT. Hip length variance ranges depending on preoperative values of 3.91mm (SD: 3.9; min -12, max 3) to 1.29mm (SD: 1.96) after surgery registered with Mako®, with an increase of an average hip length of 5.64mm (SD: 3.35). Rx simple study results show a postoperative difference between both hips of 0.5±3.08mm, which is consistent with Mako® results. Native femoral offset was stable after surgery with a showing difference both pre and post operative of the intervened hip of 0.1mm (SD: 3.7), registered with Mako®. Preoperatory modified Harris punctuation was 41.6±13.3, improving to postoperative values of 74.6±9.7 after four months since the surgery. No complications were registered in immediate postoperative (4month). CONCLUSIONS: Total hip arthroplasty robot-assisted achieves an adequate precision and repeatability of the implant positioning and the postoperative hip dysmetry without showing an increase of associated complications to the technique applied. Surgery time, complications and functional results in a short-time period are similar to conventional techniques applied to great series previously published.

[Translated article] Clinical results of total hip arthroplasty assisted by robotic arm in Spain: Preliminary study.

OBJECTIVES: Clinical, radiological and functional results of the first Spanish series of patients undergoing total hip arthroplasty assisted by Mako® (Stryker) robotic arm at the Hospital Clínico San Carlos (HCSC) in Madrid. MATERIAL AND METHODS: Prospective and descriptive study analyzing the first 25 patients who underwent robotic-assisted THA at the HCSC, with a minimum follow-up of 4 months. Demographics, imaging studies (Mako® processing, Rx and CT), clinical parameters, functionality (modified Harris) and associated complications were evaluated. RESULTS: Average age was 67.2 years (min 47, max 88), being 56% male population sample. 88% involves primary coxarthrosis, 4% post-traumatic coxarthrosis, 4% secondary avascular necrosis and 4% secondary femoroacetabular impingement. Average surgery time was 116.9min (min 92, max 150). The average time of the first five surgeries was 122.6min, and, regarding the last five interventions, it was 108.2min. Found medical intraoperative complications were four intraoperative markers loss. Average admission time was 4.4days (min 3, max 7), with an average postoperative haemoglobin decrease of 3.08±1.08g/dl, requiring a transfusion in 12% of the cases. Three medical complications have been registered in the meantime of the admission, with a relevant case of a confusional syndrome and a fall, which resulted in a non-displaced AG1 periprosthetic fracture. The analysis of the positioning of registered implants with Mako® system shows 40.55±1.53 acetabular inclination degrees and 12.2±3.6 acetabular anteversion degrees. The postoperative image study carried out on patients, are consistent with Mako® results, as it shows an acetabular inclination of 41.2±1.7 in Rx, as well as acetabular anteversion of 16±4.6 in CT. Hip length variance ranges depending on preoperative values of 3.91mm (SD: 3.9; min -12, max 3) to 1.29mm (SD: 1.96) after surgery registered with Mako®, with an increase of an average hip length of 5.64mm (SD: 3.35). Rx simple study results show a postoperative difference between both hips of 0.5±3.08mm, which is consistent with Mako® results. Native femoral offset was stable after surgery with a showing difference both pre and post operative of the intervened hip of 0.1mm (SD: 3.7), registered with Mako®. Preoperatory modified Harris punctuation was 41.6±13.3, improving to postoperative values of 74.6±9.7 after four months since the surgery. No complications were registered in immediate postoperative (4 months). CONCLUSIONS: Total hip arthroplasty robot-assisted achieves an adequate precision and repeatability of the implant positioning and the postoperative hip dysmetry without showing an increase of associated complications to the technique applied. Surgery time, complications and functional results in a short-time period are similar to conventional techniques applied to great series previously published.

Ruling out Color Transparency in Quasielastic

Quasielastic ^{12}C(e,e^{'}p) scattering was measured at spacelike 4-momentum transfer squared Q^{2}=8, 9.4, 11.4, and 14.2 (GeV/c)^{2}, the highest ever achieved to date. Nuclear transparency for this reaction was extracted by comparing the measured yield to that expected from a plane-wave impulse approximation calculation without any final state interactions. The measured transparency was consistent with no Q^{2} dependence, up to proton momenta of 8.5 GeV/c, ruling out the quantum chromodynamics effect of color transparency at the measured Q^{2} scales in exclusive (e,e^{'}p) reactions. These results impose strict constraints on models of color transparency for protons.

Probing the Deuteron at Very Large Internal Momenta.

We measure ^{2}H(e,e^{'}p)n cross sections at 4-momentum transfers of Q^{2}=4.5±0.5 (GeV/c)^{2} over a range of neutron recoil momenta p_{r}, reaching up to ∼1.0 GeV/c. We obtain data at fixed neutron recoil angles θ_{nq}=35°, 45°, and 75° with respect to the 3-momentum transfer q[over →]. The new data agree well with previous data, which reached p_{r}∼500 MeV/c. At θ_{nq}=35° and 45°, final state interactions, meson exchange currents, and isobar currents are suppressed and the plane wave impulse approximation provides the dominant cross section contribution. We compare the new data to recent theoretical calculations, where we observe a significant discrepancy for recoil momenta p_{r}>700 MeV/c.

Capillary electrophoresis and mutational images of hemoglobin sendagi [Β42 (CD1) PHE → VAL; HBB: C.127T→G].

We report two cases of hemoglobin Sendagi in a Romanian family residing in Spain: a four-year-old boy and his mother, who had been previously diagnosed with another type of congenital hemolytic anemia and had undergone splenectomy in her country during childhood. The unstable hemoglobin variant, hemoglobin Sendagi, is characterized by decreased oxygen affinity caused by replacement of one of the critical amino acid residues, phenylalanine beta 42 (CD1) of the beta-chain, with valine in the heme pocket, resulting in methemoglobin formation. As a result of migratory movements in Europe, new disease-causing hemoglobin variants are emerging in our country. Here, capillary electrophoresis enabled the identification of the variant and a molecular study was used to establish an accurate diagnosis.

Tension subcutaneous haematomas associated with anticoagulants in the elderly: Do they have earlier morbidity and mortality than hip fractures? / Hematomas subcutáneos a tensión por anticoagulantes en ancianos: ¿más morbimortalidad precoz que las fracturas de cadera?

INTRODUCTION: Complications related to anticoagulant therapy have been widely described, although tension haematomas in the extremities are frequently undervalued, and commonly considered banal pathologies. MATERIAL AND METHOD: Retrospective descriptive study between 2014 and 2017, including patients with limb haematomas after minimal trauma related with anticoagulant therapy, and surgically treated by Traumatology. RESULTS: 32 cases were eventually included, 81% were women, average age of 83.56 years, and a mean aCCI of 5.97. Anatomical location of haematomas was 65.6% in leg/foot, 15.6% in thigh/buttock, and 18.8% in the upper limb. Seventy-eight point thirteen percent received acenocoumarol, 15.63% LMWH, and 3.13% NOACs. Of the cases, 59.38% were due to AF, 15.63% to valvular heart disease/valve prosthesis, and 12.5% to PE/DVT. The mean time from diagnosis to surgical drainage was 2.66 days, mainly as a result of alterations in coagulation parameters. Forty-six point eighty-eight percent were reoperated for new drainage, cure or skin defect coverage, and 3 patients required embolisation. Of the patients, 78% needed consultation with other specialties. The average length of stay was 22.34 days, and the in-hospital mortality rate was 9.38%. CONCLUSION: Tension haematomas in the extremities associated with anticoagulants occur in patients with multiple comorbidities that make them vulnerable. Surgical drainage is usually delayed by numerous factors which lead to skin defects that require further surgical operations, and prolonged hospital stays that are associated with medical complications. In our study, the average length of stay and in-hospital mortality rate were higher than those for hip fractures, so we should not underestimate this pathology.

Liver stiffness and aspartate aminotransferase levels predict the risk for liver fibrosis progression in hepatitis C virus/HIV-coinfected patients.

OBJECTIVES: The aim of the study was to investigate liver fibrosis outcome and the risk factors associated with liver fibrosis progression in hepatitis C virus (HCV)/HIV-coinfected patients. METHODS: We prospectively obtained liver stiffness measurements by transient elastography in a cohort of 154 HCV/HIV-coinfected patients, mostly Caucasian men on suppressive antiretroviral treatment, with the aim of determining the risk for liver stiffness measurement (LSM) increase and to identify the predictive factors for liver fibrosis progression. To evaluate LSM trends over time, a linear mixed regression model with LSM level as the outcome and duration of follow-up in years as the main covariate was fitted. RESULTS: After a median follow-up time of 40 months, the median increase in LSM was 1.05 kPa/year [95% confidence interval (CI) 0.72-1.38 kPa/year]. Fibrosis stage progression was seen in 47% of patients, and 17% progressed to cirrhosis. Aspartate aminotransferase (AST) levels and liver fibrosis stage at baseline were identified as independent predictors of LSM change. Patients with F3 (LSM 9.6-14.5 kPa) or AST levels ≥ 64 IU/L at baseline were at higher risk for accelerated LSM increase (ranging from 1.45 to 2.61 kPa/year), whereas LSM change was very slow among patients with both F0-F1 (LSM ≤ 7.5 kPa) and AST levels ≤ 64 IU/L at baseline (0.34 to 0.58 kPa/year). An intermediate risk for LSM increase (from 0.78 to 1.03 kPa/year) was seen in patients with F2 (LSM 7.6-9.5 kPa) and AST baseline levels ≤ 64 IU/L. CONCLUSIONS: AST levels and liver stiffness at baseline allow stratification of the risk for fibrosis progression and might be clinically useful to guide HCV treatment decisions in HIV-infected patients.

Ivermectin in human medicine, an overview of the current status of its clinical applications.

Ivermectin is a broad spectrum antiparasitic veterinary drug introduced in human medicine in 1987. It is considered the drug of choice in onchocerciasis and strongyloidiasis infections, and remains as a therapeutic option for mass treatment in lymphatic filariasis, for which it has widely proved its efficacy. While research continued for human use, new therapeutic targets for ivermectin have emerged. It is currently the better therapeutic option in the treatment of gnathostomiasis and crusted scabies, and could be an alternative option in ascariasis and Mansonella infections. Although these uses are already included in clinical guidelines, more trials are needed to increase their grade of evidence and to obtain their official approval. Concerning other minor uses such as the treatment of enterobiasis or against Trichuris trichiura, more research is still needed in order to test the real activity of ivermectin. The use of ivermectin in human medicine has shown an outstanding low rate of adverse reactions, with the exception of treatment of loiasis and onchocerciasis, where the death of a high microfilarial load may cause severe encephalopathy. However special attention must be paid to the emergence of the first documented cases of resistance in treatment of scabies.

Hb Extremadura [ß64(E8)Gly→Ser;ß133(H11)Val→Leu]: a new molecular analysis.

Unstable hemoglobin (Hb) variants account for 9.5% of structural hemoglobinopathies. The majority of these unstable variants are the result of gene point mutations resulting in the substitution of a single amino acid by another. The presence of two mutations in the same allele is infrequent: of the 781 variants of the ß-globin cluster described, only 32 are due to two point mutations (4.1%). Hb Extremadura is a structural variant that is included within the so-called unstable Hb anomalies. It was first described in 1989, employing the most up-to-date techniques available at that time, reversed phase high performance liquid chromatography (HPLC) to separate the abnormal chain (ß(X)) digesting it with trypsin and analysis of the fragments with an automatic analyzer.

Caveolins in glial cell model systems: from detection to significance.

Glial cells prevail in number and in diversity of cellular phenotypes in the nervous system. They have also gained prominence due to their multiple physiological and pathophysiological roles. Our current knowledge of the asymmetry and heterogeneity of the plasma membrane demands an in depth analysis of the diverse array of membrane microdomains postulated to exist in the context of glial cells. This review focuses and analyzes the studies reported to date on the detection of caveolae membrane rafts and the caveolin family members in glial cell model systems, the conditions leading to changes in their level of expression, and their functional and clinical significance. Outstanding in this work emerge the ubiquitous expression of caveolins, including the typically regarded 'muscle-specific' cav3, in diverse glial cell model systems, their participation in reactive astrogliosis, cancer, and their key relevance to calcium signaling. The knowledge obtained to date demands incorporation of the caveolins and caveolae membrane rafts in our current models on the role of glial cells in heath and neurological disease.

Endocytosis mechanism of P2Y2 nucleotide receptor tagged with green fluorescent protein: clathrin and actin cytoskeleton dependence.

Extracellular nucleotides exert a large number of physiological effects through activation of P2Y receptors. We expressed rat P2Y2 (rP2Y2) receptor, tagged with green fluorescent protein (GFP) in HEK-293 cells and visualized receptor translocation in live cells by confocal microscopy. Functional receptor expression was confirmed by determining [Ca2+]i responses. Agonist stimulation caused a time-dependent translocation of the receptor from the plasma membrane to the cytoplasm. Rearrangement of the actin cytoskeleton was observed during agonist-mediated rP2Y2-GFP receptor internalization. Colocalization of the internalized receptor with early endosomes, clathrin and lysosomes was detected by confocal microscopy. The inhibition of receptor endocytosis by either high-density medium or chlorpromazine in the presence of UTP indicates that the receptor was internalized by the clathrin-mediated pathway. The caveolin-mediated pathway was not involved. Targeting of the receptor from endosomes to lysosomes seems to involve the proteasome pathway, because proteasomal inhibition increased receptor recycling back to the plasma membrane.

Prostaglandin E2 production in astrocytes: regulation by cytokines, extracellular ATP, and oxidative agents.

Upregulation and activation of phospholipases A2 (PLA2) and cyclooxygenases (COX) leading to prostaglandin E2(PGE2) production have been implicated in a number of neurodegenerative diseases. In this study, we investigated PGE2 production in primary rat astrocytes in response to agents that activate PLA2 including pro-inflammatory cytokines (IL-1beta, TNFalpha and IFNgamma), the P2 nucleotide receptor agonist ATP, and oxidants (H2O2 and menadione). Exposure of astrocytes to cytokines resulted in a time-dependent increase in PGE2 production that was marked by increased expression of secretory sPLA2 and COX-2, but not COX-1 and cytosolic cPLA2. Although astrocytes responded to ATP or phorbol ester (PMA) with increased cPLA2 phosphorylation and arachidonic acid release, ATP or PMA only caused a small increase in levels of PGE2. However, when astrocytes were first treated with cytokines, further exposure to ATP or PMA, but not H2O2 or menadione, markedly increased PGE2 production. These results suggest that ATP release during neuronal excitation or injury can enhance the inflammatory effects of cytokines on PGE2 production and may contribute to chronic inflammation seen in Alzheimer's disease.

Two new mutations in cis on (G)gamma chain of fetal hemoglobin: Hb F-Madrid [G gamma 50(D1)Ser-->Cys] and [G gamma 75(E19)Ile-->Thr].

We describe a new structural hemoglobin variant of (G)gamma with two amino acid replacements in cis found in the umbilical cord blood of a neonate in Madrid, Spain. The substitutions were identified on exon 2 of the (G)gamma globin gene, at codon 50 (T CT-->T GT) and at codon 75 (A TA-->A CA). We have named it Hb F-Madrid. The father of the propositus was the carrier of the same (G)gamma chain variant and, moreover, molecular study of alpha genes revealed the loss of an alpha gene (-alpha(3.7)/alpha alpha) both in the propositus and his mother.

[HFE gene mutations, hepatic iron content, and histological severity in hepatitis C virus-induced chronic hepatitis].

OBJECTIVE: To study whether any relationship exists between the C282Y and H63D mutations of the HFE gene, iron liver content, and the severity of histological damage in patients with hepatitis C virus (HCV)-induced chronic hepatitis. MATERIAL AND METHODS: In 72 patients diagnosed with HCV-chronic infection, naïve for antiviral therapy, and undergoing liver biopsy, the Knodell index was established, a morphometric evaluation of hepatic hemosiderin deposits was performed by using a semiautomatic method of image analysis, and mutations of the HFE gene were identified through a polymerase chain reaction on leukocyte genomic DNA by using specific restriction enzymes. The control group for the distribution of HFE genetic variants was composed of 181 healthy individuals with the same ethnic and geographical (white Spaniards) origin. RESULTS: (Cases/controls): 1. Genotype distribution: a) mutation C282Y: no homozygotes, 6/23 heterozygotes, 66/158 without the mutation (not significant, n.s.); b) mutation H63D: 2/5 homozygotes, 26/52 heterozygotes, 44/124 without the mutation (n.s.). compound heterozygotes 2/6. 2. Allele frequencies: a) mutation C282Y: 0.042/0.064 (n.s.); b) mutation H63D: 0.208/0.171 (n.s.). Four C282Y heterozygous patients had stainable liver iron (p=0.015 vs patients without mutations). Sixty-six patients were not carriers of the C282Y mutation; among them, 26.9% of 26 carriers and 15% of 40 non-carriers of the H63D mutation had liver stainable iron (n.s.). Knodell index score, gender, age at diagnosis, mode of transmission, and serum and liver iron values were not related to the HFE genotype. CONCLUSIONS: our results suggest that the C282Y mutation, but not the H63D mutation, of the HFE gene is frequently associated with stainable iron in the liver in HCV-related chronic hepatitis. The HFE genotype is not related to the histological severity of the disease.

Characterization of a new hemoglobin variant: Hb Badalona (beta31[B13]Leu-->Val).

Hemoglobin (Hb) Badalona was identified in a 35-year-old Spanish female and two other family members. All affected subjects presented erythrocytosis and increased oxygen affinity (P(50): 21 mmHg). Hemoglobinopathy was not detected with electrophoretic methods. It was, however, separated and quantified by cation exchange and reverse-phase high-performance liquid chromatography. Hb Badalona accounted for 35% of the total Hb. No significant clinical symptoms were found to be related to this hemoglobinopathy. This is the first case of a Leu-->Val replacement at position beta31(B13) reported in the world literature.