Inhibitory effect of biofilm-forming Lactobacillus kunkeei strains against virulent Pseudomonas aeruginosa in vitro and in honeycomb moth (Galleria mellonella) infection model.

Biofilms correspond to complex communities of microorganisms embedded in an extracellular polymeric matrix. Biofilm lifestyle predominates in Pseudomonas aeruginosa, an opportunistic Gram negative pathogen responsible for a wide spectrum of infections in humans, plants and animals. In this context, anti-biofilm can be considered a key strategy to control P. aeruginosa infections, thereby more research in the field is required. On the other hand, Lactobacillus species have been described as beneficial due to their anti-biofilm properties and their consequent effect against a wide spectrum of pathogens. In fact, biofilm-forming Lactobacilli seem to be more efficient than their planktonic counterpart to antagonise pathogenic bacteria. In this work, we demonstrated that Lactobacillus kunkeei, a novel Lactobacillus species isolated from honeybee guts, can form biofilms in vitro. In addition, the L. kunkeei biofilm can, in turn, inhibit the formation of P. aeruginosa biofilms. Finally, we found that L. kunkeei strains attenuate infection of P. aeruginosa in the Galleria mellonella model, presumably by affecting P. aeruginosa biofilm formation and/or their stability. Since L. kunkeei presents characteristics of a probiotic, this work provides evidence arguing that the use of this Lactobacillus species in both animals (including insects) and humans could contribute to impair P. aeruginosa biofilm formation.

Five cases of acrometastasis to the hand from a carcinoma and review of the literature.

Metastases in the hand bones are a rare form of cancer presentation. Their appearance as a sign of carcinoma is even rarer and is associated with a poor prognosis. While amputation is recommended in cases of isolated metastases in patients with at least a few months of survival, radiation therapy may be useful for treating pain and partially restoring function. We conducted a retrospective review of 5 consecutive patients (2 male, 3 female; mean age of 46 years) presenting with metastases in the hand bones who had lung (n=2), skin, uterus and kidney cancers. Conservative treatment was performed in three cases, transmetacarpal amputation in one case and distal phalanx amputation in one case. All patients died within a few months of the diagnosis (mean: 5.2months). Because acrometastases generally are related to widespread disease, the prognosis of patients with acrometastases is poor. These cases illustrate the rapid progression of the disease when acrometastases in the hand are present.

Decatropis bicolor (Zucc.) Radlk essential oil induces apoptosis of the MDA-MB-231 breast cancer cell line.

BACKGROUND: Decatropis bicolor (Zucc.)Radlk is a plant that has been traditionally used for the treatment of breast cancer in some communities of Mexico. So, the aim of this study was to determine the cytotoxic and apoptotic effect of the essential oil of Decatropis bicolor against breast cancer cell line, MDA-MB-231. METHODS: The essential oil obtained from hydrodestillation of leaves of Decatropis bicolor was studied for its biological activity against breast cancer cells MDA-MB-231 by MTT assay, Hematoxylin-eosin stain, Annexin V-FITC, TUNEL and western blot assays and for its chemical composition by GC-MS. RESULTS: The results showed a relevant cytotoxic effect of the essential oil towards MDA-MB-231 cells in a dose- and time- dependent manner, with an IC50 of 53.81 ± 1.691 µg/ml but not in the epithelial mammary cell line MCF10A (207.51 ± 3.26 µg/ml). Morphological examination displayed apoptotic characteristics in the treated cells like cell size reduction, membrane blebbing and apoptotic bodies. In addition, the apoptotic rate significantly increased as well as DNA fragmentation and western blot analysis revealed that the essential oil induced apoptosis in the MDA-MB-231 cells via intrinsic pathways due to the activation of Bax, caspases 9 and 3. Phytochemical analysis of the Decatropis bicolor essential oil showed the presence of twenty-three compounds. Major components of the oil were 1,5-cyclooctadiene,3-(methyl-2)propenyl (18.38 %), ß-terpineol (8.16 %) and 1-(3-methyl-cyclopent-2-enyl)-cyclohexene (6.12 %). CONCLUSIONS: This study suggests that essential oil of Decatropis bicolor has a potential cytotoxic and antitumoral effect against breast cancer cells, with the presence of potential bioactive compounds. Our results contribute to the validation of the anticancer activity of the plant in Mexican traditional medicine.

Profilin sensitisation in a Mediterranean population

BACKGROUND: Sensitisation to pan-allergens has become an interesting tool for the study of the allergenic profile of different populations. Profilins are one of the most common pan-allergens to be studied because they are responsible for a large number of sensitisations and are clearly related to cross-reactivity and co-sensitisation. OBJECTIVES: The objective of this study was to investigate the profile of sensitisation to profilins and to correlate it with sensitisation to foods and pollens. METHODS: Six hundred and fifty-four consecutive patients were skin-prick tested with a battery of common allergens including pollens, epithelia, mites and moulds and profilin and divided into three groups depending on their sensitisation profile (non-atopic, atopic with pollinosis and atopic without pollinosis). Patients with symptoms were challenged and diagnosed with the offending food extracts. Profilin sensitisation was identified and analysed in detail. RESULTS: According to the classification of the population, the prevalence of profilin sensitisation was estimated at 2.9% in patients suffering respiratory allergy, 4.2% in atopic patients, and 5.9% in pollen-sensitised individuals. Positive association was observed between pollen (except Cupressus and olive) and profilin but not with moulds, mites or epithelia. With respect to foods, positive association was only observed between profilin and melon sensitisation. Lastly, in terms of symptoms, positive association was only observed between profilin sensitisation and OAS. CONCLUSION: Profilin sensitisation seems to be a marker of pollen-related poly-sensitisation in our area. Pan-allergen diagnosis seems to be an essential tool for developing and improving selection of the correct treatment for allergic patients

No disponible

Profilin sensitisation in a Mediterranean population.

BACKGROUND: Sensitisation to pan-allergens has become an interesting tool for the study of the allergenic profile of different populations. Profilins are one of the most common pan-allergens to be studied because they are responsible for a large number of sensitisations and are clearly related to cross-reactivity and co-sensitisation. OBJECTIVES: The objective of this study was to investigate the profile of sensitisation to profilins and to correlate it with sensitisation to foods and pollens. METHODS: Six hundred and fifty-four consecutive patients were skin-prick tested with a battery of common allergens including pollens, epithelia, mites and moulds and profilin and divided into three groups depending on their sensitisation profile (non-atopic, atopic with pollinosis and atopic without pollinosis). Patients with symptoms were challenged and diagnosed with the offending food extracts. Profilin sensitisation was identified and analysed in detail. RESULTS: According to the classification of the population, the prevalence of profilin sensitisation was estimated at 2.9% in patients suffering respiratory allergy, 4.2% in atopic patients, and 5.9% in pollen-sensitised individuals. Positive association was observed between pollen (except Cupressus and olive) and profilin but not with moulds, mites or epithelia. With respect to foods, positive association was only observed between profilin and melon sensitisation. Lastly, in terms of symptoms, positive association was only observed between profilin sensitisation and OAS. CONCLUSION: Profilin sensitisation seems to be a marker of pollen-related poly-sensitisation in our area. Pan-allergen diagnosis seems to be an essential tool for developing and improving selection of the correct treatment for allergic patients.

Diferencias en riesgos psicosociales y estrés laboral percibido en los cuerpos de policía local atendiendo al género y la antigüedad / No disponible

Diversas investigaciones han mostrado que la función policial está sometida a un alto nivel de estrés. El principal objetivo de este estudio es valorar, dentro del colectivo de las policías locales, diferencias en riesgo y percepción de estrés laboral, dependiendo del género y años de antigüedad. Hemos tomado una muestra de 394 policías varones y 45 mujeres. Los resultados informan que no se dan diferencias significativas entre hombres y mujeres policías ni en riesgo ni en estrés laboral; por otro lado, y dentro de la variable años de antigüedad, no aparecen diferencias significativas en riesgo de estrés psicosocial, pero sí en percepción de estrés laboral, entre los grupos de 6 a 15 años de antigüedad, cuando son comparados con los policías que llevan más de 15 años en el Cuerpo Policial, siendo el primer grupo el que más percepción de estrés presenta (AU)

Research has shown the relationship between stress and the police. The main aim of this study is checking, within the community of the local police differences in risk and perception of job stress, depending on gender and years of work. We took a sample of 394 policemen and 45 policewomen. Results indicate that there are no significant differences between men and women in police, neither in risk nor work stress; on the other hand, and within the variable of years of age, no significant differences appear in risk of psychosocial stress, but in perception of work stress in groups from 6 to 15 years of work, when compared to the cops who have worked more than15 years in the police force, the first group having more perceived stress (AU)

Differential expression of CD30 on CD3 T lymphocytes in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune systemic disease caused as a result of an imbalance of Th1-/Th2-type cytokines. The soluble form of CD30 (CD30s) released from peripheral blood cells has been described as a marker of active disease in Th2-type immune response as in SLE. However, the expression of CD30 on CD3 T lymphocytes from patients with SLE has not been studied yet. Therefore, we have addressed our study to attempt this issue, studying CD30 expression by flow cytometry on CD3 T lymphocytes and CD4/CD8 subsets in samples from SLE patients mainly with lupus nephritis. In parallel, we have determined the production of the cytokines IL-4 (Th2), IFNγ (Th1), IL-10 and TGFß by intracellular staining. Differences between positive CD30 T cells in healthy controls and patients with SLE were found, with a higher percentage of CD30-expressing T cells in patients with SLE (P = 0.001). In contrast to healthy controls, CD30 was mainly expressed on CD8 T cells from patients with SLE. The intracellular cytokine staining showed that TGFß is the main cytokine expressed in CD3 T cells from patients with SLE. In addition to this, we have found a positive correlation between CD30-expressing T cells and IL-4, IFNγ, and immunosuppressive cytokines (IL-10 and TGFß) (P < 0.05). These results suggest that CD30 could play a role in the pathogenesis of SLE and its expression on CD3 T lymphocytes is not restricted only to Th2-type response.

Mycophenolate as induction therapy in lupus nephritis with renal function impairment.

BACKGROUND: Mycophenolate (MF) is effective as induction therapy for lupus nephritis (LN) in patients with normal renal function; however, little is known about its role in patients with impaired renal failure. The purpose of this study was to evaluate the response to MF in LN and its association with baseline renal function. METHODS: Data were obtained for 90 patients from 12 Spanish renal units who were receiving MF as induction therapy for LN. Patients were classified into 2 groups: group 1 (estimated glomerular filtration rate [eGFR] ≥60 ml/min/1.73 m(2)) and group 2 (eGFR <60 ml/min/ 1.73 m(2)). The primary outcome measure was the percentage of patients who achieved any response and its relationship with initial eGFR. The secondary outcome measures were the percentage of patients who achieved a complete response (CR) or partial response (PR) and the appearance of relapses during treatment and side effects. RESULTS: At initiation of MF treatment, there were no differences in the main parameters between group 1 (n = 63; eGFR 87 ± 23 ml/min/ 1.73 m(2)) and group 2 (n = 27; eGFR 44 ± 12 ml/min/1.73 m(2)). Exposure to prednisone and MF was similar. The percentages of patients who achieved a response in groups 1 and 2 were, respectively, 69.2 and 43.8% at 6 months and 81.3 and 73.7% at 12 months. CR was more frequent in group 1, whereas PR was similar in both groups. Four patients relapsed and side effects were unremarkable. CONCLUSIONS: MF is effective and safe as induction therapy for LN, and response is even achieved in patients with baseline renal impairment.

[Comorbidity, anemia and response to erythropoiesis stimulating agents in chronic hemodialysis]. / Relación entre comorbilidad, anemia y respuesta a derivados eritropoyéticos en pacientes incluidos en programa de hemodiálisis periódicas.

INTRODUCTION: Patients treated with haemodialysis have a high prevalence of co-morbidity that induces a elevate mortality risk. On the other hand, these patients have anaemia whose treatment is based in erythropoiesis stimulating agents. To date there are not enough studies to determine if co-morbidity alters erythropoietin response and the relationship between co-morbidity, response to treatment of anaemia and resistance to erythropoiesis-stimulating agents. OBJECTIVES: We have the following objectives: i) to study the prevalence of associated diseases in patients treated with haemodialysis in our Hospital Unit and to evaluate the co-morbidity Charlson Index, ii) to know the degree of anaemia control, dose and response to erythropoiesis-stimulating agents, and iii) to determine the relationship with co-morbidity and anaemia treatment. PATIENTS AND METHODS: We designed a retrospective study in stable haemodialysis treated patients. We calculated the Charlson co-morbidity index adjusted to age and we analysed levels of haemoglobin in the 6 months before study, dose of erythropoiesis-stimulating agents and its resistance index defined as doses of erythropoiesis-stimulating agents/weight (kg)/week/haemoglobin (g/dL). The different variables included in Charlson index were considered as independent variables and the index to repose to erythropoiesis-stimulating agents as a dependent variable, using bivariant and multivariate statistical analysis. RESULTS: We included 58 patients (31 males and 27 females), median age of 69.5 years (range 24-88), mean haemodialysis 83.7 months. Mean Charlson index was 7.4 +/- 2.8 (range 2-13). Comorbidity-age Charlson index was 2 in 3.4% of patients; 10.3% had 3 or 4 points; 43.2% between 5 and 7 and 43,1% 8 or more. Mean haemoglobin levels was 11,7+/-1,2 g/dL. Mean erythropoiesis-stimulating agents dose was 163.7+/-114.5 IU/kg/week and resistance index 14.1+/-9.7. Most of patients (57%) had a IRE value higher than 10. Fourteen patients (24%) had haemoglobin less than 11 g/dL, and 3 of them (5.1%) received erythropoiesis-stimulating agents more than 300 IU/kg/week. Nine subjects (15.5%) was treated with high dose of erythropoiesis-stimulating agents (>300 IU/kg/week): 3 of them had Hb>or=11 g/dL and 6 had Hb<11 g/dL. We did not found that the intensity of Charlson index is related with the degree of anaemia control or response to erythropoiesis-stimulating agents. CONCLUSIONS: Although the co-morbidity index is high and the response to erythropoiesis-stimulating agents is inadequate. In our study there is not relationship between these conditions.

Relación entre comorbilidad, anemia y respuesta a derivados eritropoyéticos en pacientes incluidos en programa de hemodiálisis periódicas / The relationship between comorbidity, anemia and response to erythropoiesis-stimulating agents in chronic hemodialysis

Introducción: Los pacientes en hemodiálisis presentan un elevado número de patologías asociadas. Por otro lado, la mayoría reciben derivados eritropoyéticos como tratamiento de la anemia. No hay estudios que indiquen si el grado de comorbilidad influye en la respuesta a los derivados eritropoyéticos. Objetivos: Estudiar la comorbilidad de los pacientes de una unidad de hemodiálisis hospitalaria, cuantificarla mediante el índice de comorbilidad de Charlson, conocer el control de anemia, la respuesta a derivados eritropoyéticos y, finalmente, evaluar la relación entre comorbilidad y control y tratamiento de la anemia. Pacientes y métodos: Realizamos un estudio retrospectivo. Incluimos 58 pacientes en hemodiálisis del Hospital General de Ciudad Real. Recogimos datos de la historia clínica para calcular el índice de comorbilidad de Charlson. Analizamos las cifras de hemoglobina y las dosis de derivados eritropoyéticos en los seis meses previos y calculamos el índice de resistencia a derivados eritropoyéticos. Las distintas entidades incluidas en el índice de comorbilidad y el propio índice de comorbilidad se consideraron variables independientes y el índice de resistencia a derivados eritropoyéticos como variable dependiente, mediante análisis uni y multivariante. Resultados: Edad media 69,5años; 53,4% varones; tiempo medio en hemdiálisis 83,7meses. El índice de Charlson medio fue 5,2 ± 2,4 (2-11) y el ajustado a la edad 7,4 ± 2,8 (2-13). La hemoglobina media fue 11,7 ± 1,2 g/dL. El 24,1% presentaban hemoglobina inferior a 11 g/dL. La media del índice de resistencia a derivados eritropoyéticos fue 14,1 ± 9,7. No observamos que los valores del índice de Charlson se relacionaran con el grado de anemia ni con la resistencia a derivados eritropoyéticos. Conclusiones: En nuestra muestra existe una elevada comorbilidad asociada y un porcentaje importante de pacientes con anemia no controlada. No hemos encontrado relación entre la comorbilidad y el control de la anemia ni el grado de respuesta a derivados eritropoyéticos (AU)

Introduction: Patients treated with haemodialysis have a highprevalence of co-morbidity that induces a elevate mortality risk. On the other hand, these patients have anaemia whose treatment is based in eritropoyesis stimulating agents. To date there are not enough studies to determine if co-morbidity alters erythropoietin response and the relationship between co-morbidity, response to treatment of anaemia and resistance to erythropoiesis-stimulating agents. Objectives: We have the following Objectives: i) to study the prevalence of associated diseases in patients treated with haemodialysis in our Hospital Unit and to evaluate the co-morbidity Charlson Index; ii) to know the degree of anaemia control, dose and response to erythropoiesis-stimulating agents, and iii) to determine the relationship with comorbidity and anaemia treatment. Patients and methods: We designed a retrospective study in stable haemodialysis treated patients. We calculated the Charlson co-morbidity index adjusted to age and we analysed levels of haemoglobin in the 6months before study, dose of erythropoiesis-stimulating agents and its resistance index defined as doses of erythropoiesis-stimulating agents/weight (kg)/week/haemoglobin (g/dL). The different variables included in Charlson index were considered as independent variables and the index to repose to erythropoiesisstimulating agents as a dependent variable, using bivariant and multivariate statistical analysis. Results: We included 58 patients(31 males and 27 females), median age of 69.5 years (range 24-88), mean haemodialysis 83,7 months. Mean Charlson index was 7.4 ± 2.8 (range 2-13). Comorbidity-age Charlson index was 2 in 3.4% of patients; 10.3% had 3 or 4 points; 43.2% between 5 and 7 and 43.1% 8 or more. Mean haemoglobin levels was 11.7±1.2 g/dL. Mean erythropoiesis-stimulating agents dose was 163.7 ± 114.5 IU/kg/week and resistance index 14.1 ± 9.7. Most of patients (57%) had a IRE value higher than 10. Forteen patients (24%) had haemoglobin less than 11 g/dL, and 3 of them (5.1%) received erythropoiesis-stimulating agents more than 300 IU/kg/week. Nine subjects (15.5%) was treated with high dose of erythropoiesis-stimulating agents (> 300 IU/kg/week): 3 of them had Hb ≥ 11 g/dL and 6 had Hb < 11 g/dL. We did not found that the intensity of Charlson index is related with the degree of anaemia control or response to erythropoiesis-stimulating agents. Conclusions: Althought in our study the comorbidity index is high and the response to erythropoiesis-stimulating agents is inadequate, there is not relationship between these conditions (AU)

[Factors which influence phosphorus removal in hemodialysis]. / Factores en la eliminación de fósforo en hemodialisis.

BACKGROUND: The sustained elevation of phosphorous among patients with end-stage renal failure is associated with elevated mortality rates. Phosphate binding agents are usually necessary to control serum phosphate levels. Phosphate removal during dialysis is limited largely due to the intracellular location of most inorganic phosphorous. The membrane surface, the frequency and the duration of therapy have proved to be very important factors in the serum phosphate control. THE AIM of our work is to investigate the influence on phosphate removal of factors that normally participate in the haemodialysis session: Plasma phosphate level (Php), treatment duration, membrane surface, high or low-flux membranes, the vascular access, dialysate flux , the volume of blood passing through the dialyzer (L) in each dialysis session and the blood flow during the first hour of dialysis. On 16 patients, we also had the possibility of comparing phosphate removal with 1.8 m(2) high-flux haemodialysis, 1.8 m(2) on-line hemodiafiltration and the on-line technique with the new Helixone dialyzer Fresenius Fx100. METHODS: 108 haemodialysis patients, 62% men, 38% women aged 21-82 years (61+/-14;mean+/-sem),) were selected for the study. Mean treatment time 4.14+/-0.41 hours (range 3.5-5 hours). The vascular access was an arterio-venous fistula in eighty five (78%) and a double lumen tunnelled catheter 23 (22%). Patients were studied under their normal every day conditions. High-flux membrane was used by 31 (30%) patients and low-flux membrane by 77 (70%). Membrane surface was: 1.7 m2:17 (16%); 1.8 m2:77 (71%); 2,1 m2:14 (13%). Dialysate flux was: 500 ml/min. 55 patients; 700 ml/min: 53 patients. In 16 out of 108 patients we had the possibility of using on-line hemodiafiltration with ultrapure bicarbonate-buffered dialysate. Phosphate mass removal (MPO4) was calculated using the formula:MPO4=0.1 t-17+50 Cds 60+11Cb 60 (1), where t is treatment time in minutes, Cds60 and Cb60 are phosphate concentrations in dialysate and plasma measured at 60 min from the beginning of hemodialysis in mg/dl, and MPO4 is the estimated phosphate removed in mg/treatment. RESULTS: We found a good correlation between phosphate removal and serum phosphate levels (p=0.01), but not with the membrane surface or treatment duration. Phosphate removal was 640+/-180 mg/session with low-flux membrane and 700+/-170 mg/session with high-flux membrane (p=0.280). The MPO4 was 720+/-190 mg/treatment in patients with a AV fistula and 620+/-180 in patients with a tunnelled catheter (p=0.023). We found a good correlation between phosphate removal and the volume of blood (L) that passed the dialyzer in each session (r=0.001) but we did not find a correlation between phosphate removal and KT/Vurea, the dialysate flux or the ultra filtration. On-line technique did not increased the MPO4(733+/-280 mg, p=0.383). The on-line technique with the new dialyzer (Fresenius Fx100), increased the phosphate removal to 759+/-199 mg/session (p=0.057). CONCLUSION: Phosphate removal during dialysis is influenced by Plasma phosphate levels, the volume of blood that passed the dialyzer and the vascular access. Uniformity on time and membrane surface could explain the abs cense of influence in our case. The ultra filtration, dialysate flux, membrane permeability or on-line hemodiafiltration does not influence the phosphate removal. The new membrane helixone with 2,1 m2 (Fresenius Fx100) increases phosphate removal probably because the membrane surface is higher.

Factores en la eliminación de fósforo en hemodiálisis / Factors which influence phosphorus removal in hemodialysis

La elevación de los niveles plasmáticos de fósforo se asocia a tasas elevadas de mortalidad en los pacientes en diálisis. La eliminación de fósforo con la hemodiálisis es limitada, debido a la localización intracelular del mismo. La superficie de la membrana del dializador, el tiempo y la frecuencia de la diálisis influyen claramente en su eliminación. El objetivo de este trabajo es analizar la influencia en la eliminación de fósforo de los factores relacionados con la sesión de hemodiálisis: El fósforo plasmático (Pp), la duración de la sesión, la superficie del dializador, la permeabilidad de la membrana, la naturaleza del acceso vascular, el flujo de sangre en la primera hora, el volumen de sangre depurado (L), la ultra filtración, el KT/V de urea y la técnica de hemodiafiltración on-line. Métodos: Se seleccionaron 108 pacientes en hemodiálisis. El 78% disponía de FAVI y 22% de catéter tunelizado. La membrana del dializador fue de polisulfona de alta permeabilidad en 31 (30%) y de permeabilidad media en 77 (70%). La superficie del dializador fue: 1,7 m2: 17 (16%); 1,8 m2: 77 (71%); 2,1 m2: 14 (13%). Flujo del líquido de diálisis: 500 ml/min: 55 pacientes; 700 ml/min: 53 pacientes. Duración de la sesión: 4,14 ± 0,41 (Rango 3,5-5 horas). El 85% se dializaban entre 4 y 5 horas. Se realizó un corte transversal en el que se determinó la eliminación de fósforo en una sesión de mitad de semana simultáneamente a la realización del KT/V de urea (Bicompartimental). En la misma sesión se determinó la eliminación de fósforo (MPO4), utilizando la fórmula: MPO4 = 0,1 t-17 + 50 Cds 60 + 11 Cb 60 (1). Se analizó su relación con los parámetros señalados anteriormente. En un segundo tiempo, a 63 pacientes se les modificó únicamente la permeabilidad del dializador cambiando los de alta a media permeabilidad y viceversa de modo que cada uno era su propio control. La MPO4 se calculó y comparó en ambas situaciones. En 16 pacientes en los que tuvimos tecnología para realizar hemodiafiltración on-line, se comparó la eliminación de fósforo con hemodiálisis de alto flujo, hemodialiltración on-line con la misma membrana y hemodiafiltración on-line con la membrana Helixona de 2,1 m2 de superficie. Resultados: La eliminación de fósforo (MPO4) guarda una buena correlación con los niveles plasmáticos del mismo (p = 0,01) , con los litros de sangre depurados (p = 0,01) y con la existencia de una fistula (p = 0,05), pero no observamos relación con la duración de la sesión, con el flujo del líquido de diálisis, con el KT/V de urea ni con la ultra filtración o la superficie de la membrana del dializador en nuestro caso. Fue de 700 ± 170 mg / sesión con membrana de alta permeabilidad y de 640 ± 180 mg / sesión con membrana de media permeabilidad (p = 0,280). Al modificar la permeabilidad de la membrana siendo el paciente su propio control, tampoco hubo diferencias en la eliminación. La MPO4 es de 720 ± 190 mg/ tratamiento en los pacientes que disponen de una FAVI y de 620 ± 180 mg /tratamiento en los pacientes que disponen de un catéter (p = 0,023). Las diferencias en los pacientes con FAVI o catéter se deben fundamentalmente al flujo de sangre tanto en la 1ª hora de diálisis como al total de litros depurados (p = 0,001). Sin embargo al realizar un analisis multivariante, son los niveles de fósforo plasmático y los litros de sangre depurada los que predicen la eliminación de fósforo. En los pacientes en que se pudo realizar hemofiltración on-line, la eliminación de fósforo fue de 725 ± 202 mg/sesión de HD de alto flujo, 733 ± 280 mg/ sesión de hemodiafiltración con reposición de 18L postdilución (p = 0,383) y de 759 ± 199 mg/sesión con hemodiafiltración con membrana de helixona de 2,1 m2 (p = 0,057). En conclusión en nuestra experiencia, en la depuración de fósforo en un sesión de diálisis intervienen además del fósforo plasmático, la cantidad de sangre depurada que es en general superior cuando el acceso vascular es una FAVI. Otros factores como la duración de la sesión y la superficie del dializador eran muy homogéneos y no han podido por tanto mostrar diferencias. La ultrafiltración, el flujo del líquido de diálisis, la permeabiliad de la membrana o la técnica de hemodiafiltración on-line no la incrementa de forma significativa

Background: The sustained elevation of phosphorous among patients with endstage renal failure is associated with elevated mortality rates. Phosphate binding agents are usually necessary to control serum phosphate levels. Phosphate removal during dialysis is limited largely due to the intracellular location of most inorganic phosphorous. The membrane surface, the frequency and the duration of therapy have proved to be very important factors in the serum phosphate control. The aim of our work is to investigate the influence on phosphate removal of factors that normally participate in the haemodialysis session: Plasma phosphate level (Php), treatment duration, membrane surface, high or low-flux membranes, the vascular access, dialysate flux, the volume of blood passing through the dialyzer (L) in each dialysis session and the blood flow during the first hour of dialysis. On 16 patients, we also had the possibility of comparing phosphate removal with 1.8 m2 high-flux haemodialysis, 1.8 m2 on-line hemodiafiltration and the online technique with the new Helixone dialyzer Fresenius Fx100®. Methods: 108 haemodialysis patients, 62% men, 38% women aged 21-82 years (61 ± 14; mean ± sem), were selected for the study. Mean treatment time 4.14 ± 0.41 hours (range 3.5-5 hours).The vascular access was an arterio-venous fistula in eighty five (78%) and a double lumen tunnelled catheter 23 (22%). Patients were studied under their normal every day conditions. High-flux membrane was used by 31 (30%) patients and low-flux membrane by 77 (70%). Membrane surface was: 1.7 m2: 17 (16%); 1.8 m2: 77 (71%); 2,1 m2: 14 (13%). Dialysate flux was: 500 ml/min 55 patients; 700 ml/min 53 patients. In 16 out of 108 patients we had the possibility of using on-line hemodiafiltration with ultrapure bicarbonate-buffered dialysate. Phosphate mass removal (MPO4) was calculated using the formula: MPO4 = 0.1 t-17 + 50 Cds 60 + 11 Cb 60 (1), where t is treatment time in minutes, Cds 60 and Cb 60 are phosphate concentrations in dialysate and plasma measured at 60 min from the beginning of hemodialysis in mg/dl, and MPO4 is the estimated phosphate removed in mg/treatment Results: We found a good correlation between phosphate removal and serum phosphate levels (p = 0.01) , the volume of blood (L) that passed the dialyzer in each session (r = 0.01) and the AV fistula as vascular access (p = 0.05), but not with the membrane surface, KT/V, the dialysate flux, the ultra filtration or treatment duration. Phosphate removal was 640 ± 180 mg/session with low-flux membrane and 700 ± 170 mg/session with high-flux membrane (p = 0.280). The MPO4 was 720 ± 190 mg/treatment in patients with a AV fistula and 620 ± 180 in patients with a tunnelled catheter (p = 0.023). On-line technique did not increased the MPO4 (733 ± 280 mg, p = 0.383). The on-line technique with the new dialyzer (Fresenius Fx100), increased the phosphate removal to 759 ± 199 mg/session (p = 0.057)

In vivo endothelial cell infection by Anaplasma marginale.

Anaplasma marginale has recently been shown to infect endothelial cells in vitro, but it remains unknown as to whether endothelial infection also occurs in vivo. In this report, we demonstrate through dual fluorescence microscopy that A marginale, detected by the monoclonal antibody ANAF16C1, co-localizes with the endothelial cell marker, von Willebrand factor, in tissue sections from an experimentally inoculated calf. The results indicate that A marginale infection includes endothelial cells and has implications for both pathogenesis and immune mechanisms.

High throughput sequencing and comparative genomics of foot-and-mouth disease virus.

Despite a basic understanding of many aspects of FMD biology, much information regarding FMDV virulence, host range, and virus transmission remains poorly understood. Here we present how the use of high throughput sequencing for complete genome sequences of foot-and mouth disease virus (FMDV) led to a series of new insights into viral genome sequence conservation and variability, genetic diversity in nature and phylogenetic classification of isolates, including the first complete sequences of the South African Territories type 1 and 3 (SAT1 and SAT3) genomes. Comparative genomic analysis of full-length sequences of FMDV isolates did allow: (i) the identification of highly conserved regulatory or coding regions which are critical for aspects of virus biology as well as novel viral genomic motifs with likely biological relevance; (ii) characterization of the first complete sequences of the SAT1 and SAT3 genomes; (iii) identification of a novel SAT virus lineage genetically distinct from other SAT and Euro-Asiatic lineages; (iv) precise identification of strains circulating around the world for epidemiological and forensic attribution; (v) assessment of mutation and recombination processes as mechanisms equally involved in evolution; (vi) mutation rates, tolerance and constraints of genes and proteins during evolution of FMD viruses during in vivo replication and (vi) support for the hypothesis of a new evolutionary model.

[CA-P control in haemodialysis and K/DOQI guidelines]. / Control del metabolismo calcio-fósforo en hemodiálisis y su adecuación a las guías K/DOQI 2003.

BACKGROUND: The publication in 2003 of the K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease recommended targets levels for serum iPTH, Ca, P, and CaxP product. However, many patients do not achieved these target ranges. It is necessary to known the percentage of patients out of range in order to prevent the development of bone disease and to reduce mortality and morbidity. OBJECTIVES: To know the degree of control of Ca-P metabolism in haemodialysis patients in our haemodilalysis facilities and the achievement of target levels recommended by K/DOQI Guidelines. PATIENTS AND METHODS: We have retrospectively investigated in 190 prevalent haemodialysis patients (males 58.2%, ratio M/F 1.4, mean age 70 years, range 17-87 years, at least 3 months in haemodialysis) the serum levels of Ca, albumin-corrected serum Ca, P, CaxP product and iPTH in all analitycal determinations performed in 2004. In each patient we have obtained the average (and median) of these serum markers. Cut-off levels were carried out following the recommendations of the K/DOQI Guidelines. RESULTS: The average of serum Ca and albumin-corrected serum Ca is normal (means +/- SD = 8.9 +/- 0.6 mg/dL and 9.2 +/- 0.7 mg/dL, respectively); however, 53.7% has normal values, 9.1% hypocalcemia and 37.1% hypercalcemia. The average of serum P is also normal (mean +/- SD = 5.0 +/- 1.3 mg/dL); however, only 57.2% has normal values, and 11.7% has hypophosphoremia and the remaining 31, 1% hyperphosphoremia. The CaxP product is normal (mean +/- SD = 46.3 +/- 13.3 mg2/mL2), 4.9% with low values and 23.4% with high values. The median of serum iPTH is 253 pg/mL, but only 31.1% of them have normal values, 25.1% low range values and 43.7% has hyperparathyroidism; 9.3% with iPTH higher than 800 pg/mL. The percentage of patients with hyperphosphoremia is higher in the group with iPTH higher than 300 pg/mL (23.3% vs. 40%, chi2, p= 0.006). In patients with PTHi in normal range, 3.6% have low CaxP product and the remaining 17.8% high CaxP product. Overall, only 25% of patients falls within recommended ranges for all indicators of mineral metabolism and 17% has all serum markers outside these recommendations. CONCLUSIONS: The degree of control of mineral metabolism in haemodyalisis patients if clearly insufficient and a large percentage of them do not achieved the recommended serum targets recommended by K/DOQI Guidelines. This groups of patients are exposed to a increased risk for oseous and cardiovascular morbimortality. The analysis of adequacy must be performed with percentage of patients out of range in order to apply new therapeutical strategies.

Control del metabolismo calcio-fósforo en hemodiálisis y su adecuación a las guías K/DOQI 2003 / CA-P control in haemodialysis and k/doqi guidelines

Introducción: Desde la publicación de las Guías K/DOQI en 2003 sobre metabolismomineral en la enfermedad renal crónica se ha observado que algunospacientes no alcanzan en la práctica clínica un adecuado control y es necesarioconocer el porcentaje de ellos que están fuera de rango normal, para evitar complicacionesmetabólicas y cardiovasculares.Objetivos: Conocer el grado de control del metabolismo Ca-P en pacientes tratadoscon hemodiálisis en nuestra provincia, estudiando los valores de tendenciacentral y el porcentaje de casos que se encuentran dentro y fuera de rango.Pacientes y métodos: Estudio retrospectivo realizado en 190 pacientes (58,2%varones, V/H 1,4, mediana de edad 70 años, rango de edad 17-87 años) incluidosen hemodiálisis durante al menos 3 meses, durante todo el año 2004. Decada paciente se obtiene la media (y mediana) de los valores de Ca, Ca corregidocon albúmina, P, producto CaxP y PTHi. Los niveles de corte se establecensegún las recomendaciones de las Guías K/DOQI de 2003.Resultados: Las medias de Ca total y corregido con albúmina están en rangonormal (medias ± DE = 8,9 ± 0,6 mg/dL y 9,2 ± 0,7 mg/dL, respectivamente);no obstante el 53,7% de ellos tienen valores de normocalcemia, mientras que el9,1% tiene hipocalcemia y el 37,1% hipercalcemia. La media de P también seencuentra en rango normal (media ± DE = 5,0 ± 1,3 mg/dL); no obstante sóloel 57,1% de ellos tienen valores en rango normal, mientras que el 11,7% tienehipofosforemia y el 31,1% hiperfosforemia. El producto CaxP se encuentra enrango normal (media ± DE = 46,3 ± 13,3 mg2/mL2, pero un 4,9% tiene valoresdisminuidos y un 23,4% valores elevados. La mediana de PTHi es 253 pg/mL,pero sólo el 31,1% se encuentra en el rango normal mientras que el 25,1% tienevalores disminuidos y un 43,7% en rango de hiperparatiroidismo, entre ellos un9,3% con niveles por encima de 800 pg/mL. El porcentaje de casos con hiperfosforemiaes superior en el grupo de pacientes con niveles de PTHi superiores a300 pg/mL (23,3% vs 40%, chi2, p = 0,006). Entre los pacientes con valores dePTHi en rango normal, un 78,6% tienen un producto CaxP normal, un 3,6% disminuidoy el 17,8% restante elevado. Al analizar los resultados globales, sólo lacuarta parte de los pacientes presenta un perfil completo en rango normal y un17% tiene todos los parámetros fuera de rango. Conclusiones: El control del metabolismo Ca-P es insuficiente y muchos pacientesno se encuentran en los rangos recomendados por las Guías K/DOQI de2003, por lo que están expuestos un mayor riesgo de complicaciones óseas y cardiovasculares.El análisis de la adecuación de los parámetros del metabolismo Calcio-Fósforo debe realizarse mediante porcentajes para conocer el grupo de pacientesque requieren nuevas estrategias terapéuticas

Backgroung: The publication in 2003 of the K/DOQI Clinical Practice Guidelinesfor Bone Metabolism and Disease in Chronic Kidney Disease recommendedtargets levels for serum iPTH, Ca, P, and CaxP product. However, many patientsdo not achieved these target ranges. It is necessary to known the percentage ofpatients out of range in order to prevent the development of bone disease and toreduce mortality and morbidity.Objectives: To know the degree of control of Ca-P metabolism in haemodialysispatients in our haemodilalysis facilities and the achievement of target levels recommendedby K/DOQI Guidelines.Patients and methods: We have retrospectively investigated in 190 prevalenthaemodialysis patients (males 58,2%, ratio M/F 1,4, mean age 70 years, range 17-87 years, at least 3 months in haemodialysis) the serum levels of Ca, albumin-correctedserum Ca, P, CaxP product and iPTH in all analitycal determinations performedin 2004. In each patient we have obtained the average (and median) ofthese serum markers. Cut-off levels were carried out following the recommendationsof the K/DOQI Guidelines.Results: The average of serum Ca and albumin-corrected serum Ca is normal(means ± SD = 8,9 ± 0,6 mg/dL and 9,2 ± 0,7 mg/dL, respectively); however,53,7% has normal values, 9,1% hypocalcemia and 37,1% hypercalcemia. Theaverage of serum P is also normal (mean ± SD = 5,0 ± 1,3 mg/dL); however, only57,2% has normal values, and 11,7% has hypophosphoremia and the remaining31,1% hyperphosphoremia. The CaxP product is normal (mean ± SD = 46,3 ±13,3 mg2/mL2) , 4,9% with low values and 23,4% with high values. The medianof serum iPTH is 253 pg/mL, but only 31,1% of them have normal values, 25,1%low range values and 43,7% has hyperparathyroidism; 9,3% with iPTH higherthan 800 pg/mL. The percentage of patients with hyperphosphoremia is higher inthe group with iPTH higher than 300 pg/mL (23,3% vs 40%, chi2, p= 0,006). Inpatients with PTHi in normal range, 3,6% have low CaxP product and the remaining17,8% high CaxP product. Overall, only 25% of patients falls within recommendedranges for all indicators of mineral metabolism and 17% has all serummarkers outside these recommendations.Conclusions: The degree of control of mineral metabolism in haemodyalisis patientsif clearly insufficient and a large percentage of them do not achieved therecommended serum targets recommended by K/DOQI Guidelines. This groupsof patients are exposed to a increased risk for oseous and cardiovascular morbimortality.The analysis of adequacy must be performed with percentage of patientsout of range in order to apply new therapeutical strategies