Actualización de Clasificación y Tratamiento de la Hipertensión Pulmonar.

RESUMEN: La Hipertensión Pulmonar (HP) se define por un aumento en la presión arterial pulmonar media ≥ 25 mmHg en reposo calculada por el cateterismo cardiaco derecho, y la hipertensión arterial pulmonar (HAP) como un grupo de enfermedades crónicas que cursan con HP precapilar y unas resistencias pulmonares aumentadas, y que comparten mecanismos fisiopatológicos y síntomas similares. Existen diferentes alternativas terapéuticas para la HAP, aunque ninguna de ellas es curativa. Estas opciones terapéuticas engloban una serie de medidas generales y un tratamiento de soporte, al que se asocian diferentes fármacos específicos con diferentes dianas terapéuticas, bien sea en monoterapia o en combinación entre ellos en función de la clase funcional. Estos tratamientos específicos incluyen los análogos de la rostaglandinas, los antagonistas de los receptores de la endotelina, y los inhibidores de la osfodiesterasa 5. Todos ellos han demostrado mejoras en parámetros clínicos, hemodinámicos y tolerancia al ejercicio, entre otros.ABSTRACT: Pulmonary hypertension (PH) is defined as an increase in mean pulmonary arterial pressure ≥25 mmHg at rest as assessed by right heart catheterization. Pulmonary arterial hypertension (PAH) describes a group of PH patients characterized by the presence of pre-capillary PH with increased pulmonary resistance, and this disorders share similar symptoms and pathophysiologic mechanisms. There are different reatment options for PAH, although none is curative. These treatment options include general measures, supportive treatment, and specific drugs with different therapeutic targets. The specific treatments include prostacyclin analogues, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors. All of them have demonstrated improvements in clinical and hemodynamic parameters, exercise tolerance, and others

Increased numbers of circulating CD8 effector memory T cells before transplantation enhance the risk of acute rejection in lung transplant recipients.

The effector and regulatory T cell subpopulations involved in the development of acute rejection episodes in lung transplantation remain to be elucidated. Twenty-seven lung transplant candidates were prospectively monitored before transplantation and within the first year post-transplantation. Regulatory, Th17, memory and naïve T cells were measured in peripheral blood of lung transplant recipients by flow cytometry. No association of acute rejection with number of peripheral regulatory T cells and Th17 cells was found. However, effector memory subsets in acute rejection patients were increased during the first two months post-transplant. Interestingly, patients waiting for lung transplant with levels of CD8(+) effector memory T cells over 185 cells/mm(3) had a significant increased risk of rejection [OR: 5.62 (95% CI: 1.08-29.37), p=0.04]. In multivariate analysis adjusted for age and gender the odds ratio for rejection was: OR: 5.89 (95% CI: 1.08-32.24), p=0.04. These data suggest a correlation between acute rejection and effector memory T cells in lung transplant recipients. The measurement of peripheral blood CD8(+) effector memory T cells prior to lung transplant may define patients at high risk of acute lung rejection

IL-7 measurement in supernatant after 48hour-culture in Lung transplant recipients.

<p>Medians and interquartile ranges are depicted and Kruskall-Wallis test was used to compare medians.***p<0.001,** p<0.01, *p<0.05.</p

Density-plots of memory T cell subsets in lung transplant recipients.

<p>Representative density-plots of acute rejection-free lung transplant recipients (A) and suffering acute rejection episode (B) showing the different subpopulations of CD4⁺ and CD8⁺ T cells before transplantation. Four different subpopulations are depicted: naïve (CD62L+CD45RO-), TCM (CD62L+CD45RO+), TEM (CD62L-CD45RO+) and TEMRA (CD62L-CD45RO-).</p

Follow-up of the percentage of T cell subsets.

<p>Follow-up of the percentage of CD4+ subsets in lung transplant recipients within first year (A). The median of central memory (TCM) on black line and open squares, naïve on dotted line and open triangle, effector memory (TEM) on truncated line and open triangle and terminally differentiated effector memory (TEMRA) cells on thin dotted line and open diamond are depicted. Follow-up of the percentage of CD8+ subsets in lung transplant recipients within first year (B). The median of central memory (TCM) on black line and open squares, naïve on black line and open triangle, effector memory (TEM) on truncated line and open triangle and terminally differentiated effector memory (TEMRA) cells on thin dotted line and open diamond are depicted. Ranges are not depicted because of simplicity. Median percentage of T cell subset differences were tested by U-Mann Whitney test (* and §, p<0.05 and p<0.1 respectively).</p

Comparison of absolute numbers of effector memory (TEM) T cells in LTRs.

<p>The CD4⁺ (A) and CD8⁺ (B) TEM cells were measured in peripheral blood of rejection-free (Free) and lung transplant patients suffering an acute rejection episode (AR). Medians and interquartile ranges are depicted and compared using Mann-Whitney U test. The cut-off (C.O.) value of 185 CD8⁺ TEM cells/mm³ discriminate between Free and AR lung transplant recipients.</p

Percenteage of naïve and effector memory CD8+ T cells in lung transplant recipients.

<p>Comparison of the percentages of naïve (A) and effector memory (TEM) CD8+ T cells (B) between the groups of rejection-free (F, white box-plot) lung transplant recipients and with an episode of acute rejection (AR, grey box-plot) during several time points post-Tx: pre-Tx (basal), 1 week (wk), 2 weeks, and 1, 2, 3, 6, and 12 months (m) post-Tx. The medians and interquartile range are depicted and compared using Mann-Whitney U test.* p value <0.05. </p

Follow-up of regulatory T cells in lung transplant recipients (LTR).

<p>Absolute number of regulatory T cells (CD4⁺CD127^low/-Foxp3⁺CD27⁺) was measured before the transplant (Pre) and first, second week (wk), first, second, third, sixth, twelfth month (m) post-transplant in peripheral blood of lung transplant recipients (A), median and interquartile range are depicted. (Comparison of absolute number of Tregs in LTR (B)), the box plot shows the median and interquartile ranges of regulatory T (Treg) cells in peripheral blood of lung transplant recipients with acute rejection (AR) episode (grey boxes) and lung transplant recipients without rejection (F, white boxes). The whiskers show 5 and 95 percentile. Kruskall-Wallis and <i>U</i>-Mann-Whitney test were assessed to compare medians of Treg levels at different timepoints in AR and F groups, (*, p<0.05 and **, p<0.01).</p

DOCUGRAF. Laboratorio de documentación gráfica sobre el Patrimonio Arqueológico

Proyecto de innovación docente que pretende integrar la ciencia arqueológica y la investigación que se realiza en las universidades y otros centros científicos españoles a través de un proyecto de innovación y mejora de la calidad docente en el que se aúnan la experiencia investigadora del ámbito de la Arqueología, la Antropología, la Historia y las Humanidades con la experiencia tecnológica que poseen los distintos miembros participantes en el área de documentación de Patrimonio Arqueológico, en labores de docencia, de excavación arqueoantropológica y de apoyo a labores de documentación, estudio y restauración de diferentes elementos artefactuales arqueológicos, en distintos soportes físicos, así como de carácter arquitectónico-monumental