Loss of Direct Vascular Contact to Astrocytes in the Hippocampus as an Initial Event in Alzheimer's Disease. Evidence from Patients, In Vivo and In Vitro Experimental Models.

Alzheimer's disease (AD) is characterized by the accumulation of aggregated amyloid peptides in the brain parenchyma and within the walls of cerebral vessels. The hippocampus-a complex brain structure with a pivotal role in learning and memory-is implicated in this disease. However, there is limited data on vascular changes during AD pathological degeneration in this susceptible structure, which has distinctive vascular traits. Our aim was to evaluate vascular alterations in the hippocampus of AD patients and PDAPP-J20 mice-a model of AD-and to determine the impact of Aß40 and Aß42 on endothelial cell activation. We found a loss of physical astrocyte-endothelium interaction in the hippocampus of individuals with AD as compared to non-AD donors, along with reduced vascular density. Astrocyte-endothelial interactions and levels of the tight junction protein occludin were altered early in PDAPP-J20 mice, preceding any signs of morphological changes or disruption of the blood-brain barrier in these mice. At later stages, PDAPP-J20 mice exhibited decreased vascular density in the hippocampus and leakage of fluorescent tracers, indicating dysfunction of the vasculature and the BBB. In vitro studies showed that soluble Aß40 exposure in human brain microvascular endothelial cells (HBMEC) was sufficient to induce NFκB translocation to the nucleus, which may be linked with an observed reduction in occludin levels. The inhibition of the membrane receptor for advanced glycation end products (RAGE) prevented these changes in HBMEC. Additional results suggest that Aß42 indirectly affects the endothelium by inducing astrocytic factors. Furthermore, our results from human and mouse brain samples provide evidence for the crucial involvement of the hippocampal vasculature in Alzheimer's disease.

¿Han influido el algoritmo de prescripción de la Administración y las guías de manejo de la dislipemia de la ACC/AHA 2013 en el manejo de la dislipemia? Proyecto MEJORA-LO CV / Have the Government's prescription algorithm and the 2013 American College of Cardiology/American Heart Association guidelines for managing dyslipidaemia influenced the management of dyslipidaemia? The MEJORALO-CV Project

OBJETIVO: Conocer el manejo de la dislipemia en atención primaria tras la publicación de la Guía de la American College of Cardiology/American Heart Association (ACC/AHA) del año 2013 y el algoritmo de la Administración. MÉTODO: Estudio transversal descriptivo con encuesta a médicos de atención primaria de la Comunidad Valenciana entre enero y octubre de 2016. RESULTADOS: Participaron 199 facultativos con una media (desviación típica) de 48,9 (11) años de edad y 21,3 (11,1) años de experiencia. Las guías más seguidas eran las de la European Society of Cardiology (37,5%) y las de la Administración (23,4%). El 6,3% seguía la de la ACC/AHA 2013. El 88% establecía objetivos según colesterol LDL y riesgo cardiovascular. La elección del hipolipemiante estaba basada en su capacidad reductora de colesterol LDL (28,6%), algoritmo de la Administración (23,4%) y seguridad (20,4%). Estatinas, ezetimiba y fibratos eran los hipolipemiantes preferidos, y la combinación (51%) e incremento de dosis (35%) las estrategias en ausencia de control. Se determinaba perfil lipídico, transaminasas y creatincinasa cada 6 (59,5; 52,3 y 54,3%, respectivamente) o 12 meses (25,1; 29,2 y 30,3%, respectivamente). Un 41% era conocedor de la polémica con la Guía ACC/AHA 2013, y aunque un 60% reconocía su relevancia, solo un 21% modificó su quehacer diario por ella. CONCLUSIONES: El algoritmo de la Administración tuvo mayor impacto que la Guía ACC/AHA 2013 en atención primaria. Campos de mejora fueron el bajo uso de guías y tablas de riesgo validadas, y racionalización de la periodicidad de las analíticas

OBJECTIVE: To determine the management of dyslipidaemia in primary care after the publication of the American College of Cardiology/American Heart Association (ACC/AHA) 2013 guidelines and Valencian government's algorithm. METHOD: We conducted a cross-sectional descriptive study that employed a survey of primary care physicians of the Community of Valencia between January and October 2016. RESULTS: A total of 199 physicians (mean age, 48.9±11.0 years; experience, 21.3±11.1 years) participated in the survey. The most followed guidelines were those of the European Society of Cardiology (37.5% of respondents) and Valencian government (23.4% of respondents). Some 6.3% of the respondents followed the 2013 ACC/AHA guidelines, and 88.0% established objectives based on LDL cholesterol and cardiovascular risk. The choice of lipid-lowering drug was based on its LDL cholesterol lowering capacity (28.6% of respondents), on the Valencian government's algorithm (23.4%) and on the drug's safety (20.4%). Statins, ezetimibe and fibrates were the preferred hypolipemiant agents, and their combination (51% of respondents) and dosage increases (35%) were the strategies employed for poor control. Lipid profile and transaminase and creatine kinase levels were measured every 6 (59.5%, 52.3% and 54.3% of respondents, respectively) or 12 months (25.1%, 29.2% and 30.3%, respectively). Forty-one percent of the respondents were aware of the controversy surrounding the 2013 ACC/AHA guidelines. Although 60% of the respondents acknowledged its relevance, only 21% changed their daily practices accordingly. CONCLUSIONS: The Valencian government's algorithm had a greater impact than the 2013 ACC/AHA guidelines in primary care in Valencia. Areas for improvement included the low use of validated guidelines and risk tables and the streamlining of laboratory test periodicity

Have the Government's prescription algorithm and the 2013 American College of Cardiology/American Heart Association guidelines for managing dyslipidaemia influenced the management of dyslipidaemia? The MEJORALO-CV Project. / ¿Han influido el algoritmo de prescripción de la Administración y las guías de manejo de la dislipemia de la ACC/AHA 2013 en el manejo de la dislipemia? Proyecto MEJORA-LO CV.

OBJECTIVE: To determine the management of dyslipidaemia in primary care after the publication of the American College of Cardiology/American Heart Association (ACC/AHA) 2013 guidelines and Valencian government's algorithm. METHOD: We conducted a cross-sectional descriptive study that employed a survey of primary care physicians of the Community of Valencia between January and October 2016. RESULTS: A total of 199 physicians (mean age, 48.9±11.0 years; experience, 21.3±11.1 years) participated in the survey. The most followed guidelines were those of the European Society of Cardiology (37.5% of respondents) and Valencian government (23.4% of respondents). Some 6.3% of the respondents followed the 2013 ACC/AHA guidelines, and 88.0% established objectives based on LDL cholesterol and cardiovascular risk. The choice of lipid-lowering drug was based on its LDL cholesterol lowering capacity (28.6% of respondents), on the Valencian government's algorithm (23.4%) and on the drug's safety (20.4%). Statins, ezetimibe and fibrates were the preferred hypolipemiant agents, and their combination (51% of respondents) and dosage increases (35%) were the strategies employed for poor control. Lipid profile and transaminase and creatine kinase levels were measured every 6 (59.5%, 52.3% and 54.3% of respondents, respectively) or 12 months (25.1%, 29.2% and 30.3%, respectively). Forty-one percent of the respondents were aware of the controversy surrounding the 2013 ACC/AHA guidelines. Although 60% of the respondents acknowledged its relevance, only 21% changed their daily practices accordingly. CONCLUSIONS: The Valencian government's algorithm had a greater impact than the 2013 ACC/AHA guidelines in primary care in Valencia. Areas for improvement included the low use of validated guidelines and risk tables and the streamlining of laboratory test periodicity.

[Provision of continuous health care by a unit connected to primary care centres coordinated by specialist physicians]. / Aportación al continuo asistencial de una consulta de conexión con atención primaria coordinada con internistas.

OBJECTIVE: To evaluate the efficacy and efficiency of a system set up to overcome the current disparity between primary and specialist health care and with the capacity to detect patients with significant diseases. MATERIAL AND METHODS: To describe the activity of the Unit for Connection with Primary Care Centres (UCPCC) in the Alcoy Health Area (Alicante) during its first year. RESULTS: A total of 450 visits were made, with 6.5 (95% CI 5.7-7.3) first visits, and 3.9 (95% CI 3.1-4.8) successive ones per day. There were more than 50 reasons for consultation, and more than 60 final diagnoses (65.6% non-significant, 14% undefined and 12.4% significant). Digestive (31%) and functional (14.4%) diseases were the most frequently defined diagnoses, with neoplasic and autoimmune diseases among those defined as significant ones. The great majority (86.9%) of patients required 1-2 visits, with 40% diagnosed by just reviewing the hospital files. More than 20 different complementary examinations were performed, with 38.8%, 34.4%, 21.6%, and 5.2% of patients requiring 0, 1, 2, or ≥ 3, respectively. Patients with a significant pathology were diagnosed more quickly (12.4 ± 19.4 vs. 45.3 ± 52.8 days; P = .001), with less complementary examinations (0,5 ± 0,7 vs. 0,9 ± 0,9 per patient; P = .032. 58.6% vs. 39.6% patients without complementary examinations; P = .052), and were more frequently referred to specialised medicine (58.6% vs. 18.3%, P < .0001). CONCLUSIONS: The demonstrated differential management of patients with potentially significant pathology using existing resources, make the UCPCC with internists an efficient model for the connection between health care levels.

Aportación al continuo asistencial de una consulta de conexión con atención primaria coordinada con internistas / Provision of continuous health care by a unit connected to primary care centres coordinated by specialist physicians

Objetivo. Evaluar la eficacia y eficiencia de un sistema de conexión entre niveles asistenciales que supere la actual desconexión asegurando el acceso preferencial de pacientes con enfermedad significativa a atención especializada. Material y métodos. Descripción de la actividad de la Consulta de Conexión con Atención Primaria (CCAP) del Departamento de Salud de Alcoy (Alicante) en su primer año de funcionamiento. Resultados. Hubo 450 visitas con 6,5 (IC 95% 5,7-7,3) primeras visitas y 3,9 (IC 95% 3,1-4,8) sucesivas diarias. Fueron más de 50 los motivos de consulta, y más de 60 los diagnósticos finales, la mayoría no relevantes (65,6% definidos no significativos; 14% indefinidos). Globalmente los diagnósticos definidos predominantes fueron los digestivos (31%) y los funcionales (14,4%), y los definidos significativos las neoplasias y las enfermedades autoinmunes. Al 86,9% de los diagnósticos se llegó tras 1 o 2 visitas, y al 40% con la sola revisión de la historia clínica hospitalaria. Hubo 217 peticiones de más de 20 exploraciones complementarias distintas, con un 38,8; 34,4; 21,6; y 5,2% de pacientes que requirieron 0, 1, 2 y >= 3, mayoritariamente (21,6%) analíticas básicas. Los pacientes con diagnóstico significativo fueron diagnosticados más rápidamente (12,4 ± 19,4 vs. 45,3 ± 52,8 días; p = 0,001), con menos exploraciones complementarias (0,5 ± 0,7 vs. 0,9 ± 0,9 exploraciones complementarias por paciente; p = 0,032; 58,6 vs. 39,6% pacientes sin exploraciones complementarias; p = 0,052) y en mayor proporción derivados a especializada (58,6 vs. 18,3%, p < 0,0001). Conclusiones. El demostrado manejo diferencial del paciente con enfermedad potencialmente significativa aprovechando los recursos existentes hacen de la CCAP con internistas un modelo eficiente de conexión entre niveles (AU)

Objective: To evaluate the efficacy and efficiency of a system set up to overcome the current disparity between primary and specialist health care and with the capacity to detect patients with significant diseases. Material and methods: To describe the activity of the Unit for Connection with Primary Care Centres (UCPCC) in the Alcoy Health Area (Alicante) during its first year. Results: A total of 450 visits were made, with 6.5 (95% CI 5.7-7.3) first visits, and 3.9 (95% CI 3.1- 4.8) successive ones per day. There were more than 50 reasons for consultation, and more than 60 final diagnoses (65.6% non-significant, 14% undefined and 12.4% significant). Digestive (31%) and functional (14.4%) diseases were the most frequently defined diagnoses, with neoplasic and autoimmune diseases among those defined as significant ones. The great majority (86.9%) of patients required 1-2 visits, with 40% diagnosed by just reviewing the hospital files. More than 20 different complementary examinations were performed, with 38.8%, 34.4%, 21.6%, and 5.2% of patients requiring 0, 1, 2, or >=3, respectively. Patients with a significant pathology were diagnosed more quickly (12.4 ± 19.4 vs. 45.3 ± 52.8 days; P = .001), with less complementary examinations (0,5 ± 0,7 vs. 0,9 ± 0,9 per patient; P = .032. 58.6% vs. 39.6% patients without complementary examinations; P = .052), and were more frequently referred to specialised medicine (58.6% vs. 18.3%, P < .0001). Conclusions: The demonstrated differential management of patients with potentially significant pathology using existing resources, make the UCPCC with internists an efficient model for the connection between health care levels (AU)

Chronic inhibition of mammalian target of rapamycin by rapamycin modulates cognitive and non-cognitive components of behavior throughout lifespan in mice.

Aging is, by far, the greatest risk factor for most neurodegenerative diseases. In non-diseased conditions, normal aging can also be associated with declines in cognitive function that significantly affect quality of life in the elderly. It was recently shown that inhibition of Mammalian TOR (mTOR) activity in mice by chronic rapamycin treatment extends lifespan, possibly by delaying aging {Harrison, 2009 #4}{Miller, 2011 #168}. To explore the effect of chronic rapamycin treatment on normal brain aging we determined cognitive and non-cognitive components of behavior throughout lifespan in male and female C57BL/6 mice that were fed control- or rapamycin-supplemented chow. Our studies show that rapamycin enhances cognitive function in young adult mice and blocks age-associated cognitive decline in older animals. In addition, mice fed with rapamycin-supplemented chow showed decreased anxiety and depressive-like behavior at all ages tested. Levels of three major monoamines (norepinephrine, dopamine and 5-hydroxytryptamine) and their metabolites (3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindolacetic acid) were significantly augmented in midbrain of rapamycin-treated mice compared to controls. Our results suggest that chronic, partial inhibition of mTOR by oral rapamycin enhances learning and memory in young adults, maintains memory in old C57BL/6J mice, and has concomitant anxiolytic and antidepressant-like effects, possibly by stimulating major monoamine pathways in brain.

Synthesis of microporous eskolaite from Cr(VI) using activated carbon as a reductant and template.

A novel technique has been devised for the synthesis of microporous α-Cr(2)O(3) (eskolaite). The technique was based on the formation of amorphous-Cr(2)O(3) onto microporous activated carbon through adsorption-reduction of dichromate ions (Cr(2)O(7)(2-)) at the activated carbon/aqueous solution interface. Then, the Cr(2)O(3)-loaded carbon was thermally processed under oxidizing conditions to remove the carbon and recover the chromium oxide as α-Cr(2)O(3). Both the Cr(2)O(3)-loaded carbon and the synthetic product were characterized by XRD, SEM, surface area and pore volume measurements. The synthetic eskolaite assayed 97.3% Cr(2)O(3) and its specific surface area was 15.48 m(2)/g and pore size of 16.1 Å.

Utilidad del índice tobillo/brazo en un paciente aparentemente normotenso con lumbociatalgia crónica y disfunción eréctil / Utility of the ankle/brachial index (ABI) in apparently normotensive patient with chronic low back pain and erectile dysfunction

Los datos anamnésicos y exploratorios siguen siendo clave en el manejo del hipertenso. También, y en contra de la creciente parcelación del saber médico, es necesaria una visión global e integradora, lo que exige la búsqueda activa de la lesión del órgano diana. El índice tobillo/brazo (ITB) emerge como una herramienta sencilla que permite a través de la detección de estenosis arteriales proximales, corregir no solo limitaciones de la de ambulación sino de manifestaciones relacionadas y a menudo olvidadas como la disfunción eréctil o la HTA vasculorrenal. No olvidemos que el mejor marcador de riesgo son los valores adecuadamente obtenidos de presión arterial y su correcta interpretación y que conviene evitar errores tan comunes como la toma tensional única, el fenómeno del redondeo o el de alarma. Alrededor de la mitad de pacientes con ITB patológico, están asintomáticos o presentan claudicación atípica, por lo que se hace aconsejable la realización extensiva del ITB en la población de riesgo cardiovascular significativo, independientemente de la presencia de síntomas (AU)

Anamnesic and examination data are still the key for the management of the hypertensive subject. In addition, and against the growing division into parcels of medical knowledge ,it is necessary to have a global and integrating view. This requires the active search for the target organ injury. To do so, the ankle/brachial index (ABI) is a simple test which, simultaneously, makes it possible to detect reversible arterial lesions and therefore treat the symptoms by intermittent claudication or manifestations that are also related and often overlooked, such as erectile dysfunction or renovascular hypertension. We must not forget that the best marker of risk is the correct levels of BP and their correct interpretation and that such common errors as using a single measurement of blood pressure, and the phenomenon of rounding up or down or of alarm should be avoided. Approximately half of patients with pathological ABI are a symptomatic or have atypical claudication. Thus, it is recommendation to made extensive use of the ABI in the significant cardiovascular risk population independently of the presence of symptoms (AU)

Differential expression and redox proteomics analyses of an Alzheimer disease transgenic mouse model: effects of the amyloid-ß peptide of amyloid precursor protein.

Among the pathological factors known to be associated with Alzheimer disease (AD), oxidative stress induced by the amyloid-ß peptide (Aß) has been demonstrated to play a key role in human brain and animal models of AD. Recently, we reported elevated levels of oxidative damage in the brain of a transgenic (Tg) AD mouse model with Swedish and Indiana familial AD mutations in human amyloid precursor protein (APP) [PDAPP mice, line J20], as evidenced by increased levels of protein carbonyls, 3-nitrotyrosine, and protein-bound 4-hydroxy-2-nonenal. This oxidative damage was dependent on the methionine 35 residue within the Aß peptide. Further insight into the molecular pathways affected in this Tg model of AD may be gained with discovery-based proteomics studies; therefore, two-dimensional gel-based expression proteomics was performed to compare differences in brain protein levels of J20 Tg mice with non-transgenic (NTg) littermate controls. Based on our studies, we identified six proteins that had significantly increased levels in J20 Tg relative to NTg mice: calcineurin subunit B type 1, ρ GDP-dissociation inhibitor 1, T-complex protein 1 subunit α A, α-enolase, peptidyl-prolyl cis-trans isomerase (Pin-1), and ATP synthase subunit α mitochondrial. Several of these proteins have previously been implicated in in vitro and in vivo models and subjects with AD. Additionally, using redox proteomics analyses we identified two oxidatively-modified proteins: phosphatidylethanolamine-binding protein 1 and Pin-1 with decreased levels of protein 3-nitrotyrosine in J20 Tg mice relative to NTg. Western blotting and immunoprecipitation analyses were used to validate proteomics results. Overall, these studies provide information about changes in the brain proteome as a result of Aß deposition and clues with which to further direct studies on elucidating AD pathogenesis.

Abnormal neuronal networks and seizure susceptibility in mice overexpressing the APP intracellular domain.

Alterations in the processing of the amyloid precursor protein (APP) lead to familial Alzheimer's disease (AD). AD patients exhibit increased seizure susceptibility and alterations in their EEGs, which suggests that APP and its metabolites may modulate neuronal networks. Here we demonstrate that transgenic mice overexpressing APP intracellular domain (AICD) and its binding partner Fe65 exhibit abnormal spiking events and a susceptibility to induced seizures. These abnormalities are not observed in PDAPP(D664A) mice, which express high Aß levels but harbor a mutation in the APP intracellular domain. These data suggest that alterations in the levels of AICD contribute to network dysfunction in AD.

Netrin-1 interacts with amyloid precursor protein and regulates amyloid-beta production.

The beta-amyloid precursor protein (APP) is an orphan transmembrane receptor whose physiological role is largely unknown. APP is cleaved by proteases generating amyloid-beta (Abeta) peptide, the main component of the amyloid plaques that are associated with Alzheimer's disease. Here, we show that APP binds netrin-1, a multifunctional guidance and trophic factor. Netrin-1 binding modulates APP signaling triggering APP intracellular domain (AICD)-dependent gene transcription. Furthermore, netrin-1 binding suppresses Abeta peptide production in brain slices from Alzheimer model transgenic mice. In this mouse model, decreased netrin-1 expression is associated with increased Abeta concentration, thus supporting netrin-1 as a key regulator of Abeta production. Finally, we show that netrin-1 brain administration in Alzheimer model transgenic mice may be associated with an amelioration of the Alzheimer's phenotype.

Arteritis de Takayasu como causa de hipertensión secundaria / Takayasu’s arteritis as a cause of secondary hypertension

La baja prevalencia de hipertensión arterial secundaria(HTAS) en la población hipertensa general unido a susbajas tasas de reversibilidad y al ingente número de potencialesetiologías obliga a restringir su búsqueda a colectivosdeterminados y centrar esta búsqueda en lasformas más prevalentes y potencialmente corregibles.Las vasculitis son, dentro de las formas de HTAS, muypoco prevalentes. No obstante, su reversibilidad espotencialmente elevada cuando se detecta en fasestempranas; sin embargo, una vez en fase residual fibrótica,la lesión es irreversible. Presentamos un casode HTA debida a arteritis de Takayasu (AT), entidaden la que una de las formas principales de presentaciónes la HTA. El interés de su detección aún en fasefibrótica reside en que la población con esta arteritises joven (por definición, menor de 40 años) y con unriesgo cardiovascular incrementado derivado probablementede la disfunción endotelial asociada a lasvasculitis en general, así como a la rigidez arterial derivada.Se discute el diagnóstico diferencial de las aortitis,se incide en las formas más prevalentes en nuestromedio y se hace hincapié en el manejo terapéuticocomo pacientes de riesgo cardiovascular (RCV) incrementado.Siendo la AT una forma altamente infrecuentede HTAS, el que afecte a pacientes jóvenes yel que el diagnóstico de sospecha sea tan sencillo comola palpación de pulsos periféricos y el registro, almenos inicial, de los valores de PA en ambas extremidadessuperiores no hace sino recordarnos la importanciade seguir las guías terapéuticas a la hora deevaluar al paciente hipertenso general (AU)

The low prevalence of secondary hypertension (SH)in the overall hypertensive population, together withthe low rates of reversibility and the vast number ofpotential etiologies for this condition, makes it necessaryto limit the search to determinate groups and tofocus on the most prevalent and potentially correctabletypes. Although the vasculitides are not prevalent,they have potentially high reversibility when detectedin the early stages; however, lesions in the fibrotic residualstage are irreversible. We present a case of SHdue to Takayasu’s arteritis (TA), a disease in whichSH is one of the main presenting signs. It is importantto detect TA, even in the fibrotic stage, because TAaffects young people (by definition, under 40 years ofage) and involves increased cardiovascular risk, probablydue to the endothelial dysfunction that is associatedwith the vasculitides in general as well as to thearterial stiffness they cause. We discuss the differentialdiagnosis of aortitis and emphasize the most prevalenttypes in our environment and the therapeutic managementfor these patients with increased cardiovascularrisk. The fact that TA is a very rare type of SH thataffects young patients and that the diagnosis can besuspected simply palpating the peripheral pulses andrecording, at least at first, blood pressure in both arms,underlines the importance of following the recommendationsof the therapeutic guidelines when evaluatinggeneral hypertensive patients (AU)

Vómitos persistentes en mujer hipertensa / Persistent vomiting in a hypertensive woman

Numerosos documentos insisten en la necesidad deun control estricto de la presión arterial (PA). Contrasta la escasa información publicada al respecto de la reducción tensional estricta y sus potenciales consecuencias negativas. Presentamos una paciente con hipertensión arterial (HTA) crónica esencial en tratamiento farmacológico y dos ingresos hospitalarios por vómitos secundarios a hiponatremia (hNa+) por tiazidas. Discutimos las causas más comunes de hNa+ enel paciente hipertenso, igualmente con muy escasabibliografía. El caso expuesto ilustra varios errores comunes en la praxis clinica habitual: erróneo diagnóstico de HTA por incorrecta técnica de medida de laPA, inicio precoz de tratamiento farmacológico basadoúnicamente en valores de PA e inadecuado empleode la automedida domiciliaria de PA (AMPA). Todoello llevó a una iatrogenia y a la realización demaniobras invasivas en una paciente con una HTA debata blanca donde se echa de menos un abordaje menosfragmentario y más acorde con las guías terapéuticasen uso

Many documents stress the need for strict control ofblood pressure (BP) on the contrary to the scarce information published regarding strict tension reductionand its potential negative consequences.We present apatient suffering chronic essential AHT under drugtreatment and with two admissions to hospital dueto vomiting secondary to hyponatremia (hNa+) due tothiazides. We discuss the most common causes ofhNa+ in the hypertensive patient, this also being veryscarce in the literature. The case presented illustratesseveral common errors in the common clinical practice:erroneous diagnosis of AHT due to incorrect measurementtechnique of BP, early onset of drug treatmentonly based on BP values and inadequate use ofABPM. All of this led to an iatrogeny and conductionof invasive maneuvers in a female patient with whitecoat hypertension in whom a less fragmented approachand one more in agreement with the therapheuticguidelines in use should have been used

Enfermedad renal crónica, fórmulas de estimación de la función renal, hipertensión y envejecimiento. Réplica / Chronic kidney isease, formulae to estimate kidney function, hypertension and aging. Reply

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Estrategias para el despistaje de la HTA secundaria / Strategies for screening of secondary high blood pressure

La HTA secundaria (HTAs) es una entidad infrecuente en la población hipertensa general y, en contra de la idea generalizada, con tasas de reversibilidad bajas, lo que a menudo se relaciona con el diagnóstico y tratamiento tardío de la entidad etiológica. La potencial reversibilidad en estadios tempranos y la mayor morbimortalidad consecuencia de la elevación tensional mantenida justifican su despistaje, si bien el elevado coste económico derivado y el gran número de etiologías a considerar hacen que deba restringirse la búsqueda a pacientes con riesgo: HTA refractaria, HTA con importante daño orgánico, HTA iniciada en edades extremas de la vida o con empeoramiento de su control sin causa aparente. Es muy escasa la información contrastada que permita establecer algoritmos definitivos para el despistaje de la HTAs. Siempre deberá prevalecer el sentido común y la accesibilidad a las pruebas en el medio clínico concreto donde nos desenvolvamos. La búsqueda debe centrarse en las formas más prevalentes y con mayor potencial de reversibilidad: toma de sustancias presoras o que interaccionan con fármacos antihipertensivos, la enfermedad renal crónica, enfermedades endocrinológicas y síndrome de apnea obstructiva del sueño. Para la acotación de la búsqueda ayuda considerar el grupo de edad del paciente concreto y la búsqueda activa de rasgos clínicos y/o analíticos específicos. El adecuado despistaje de la HTAs en definitiva requiere de nuestra capacidad de visión global del proceso hipertensivo, así como de mucho sentido común en la elección de las exploraciones a realizar

Secondary high blood pressure (HB) is an uncommon entity in the general hypertensive population. On the contrary to the generalized idea, it has low reversibility rates, which is often related with the late diagnosis and treatment of the etiological entity. The reversibility potential in early stages and greater morbidity-mortality as a result of the maintained tensional elevation justify its screening. However, the elevated financial cost derived and large number of etiologies to be considered require restricting the search to patients at risk: refractory HBP, HBP with significant organic damage, HBP initiated in extreme ages of life or with worsening of its control without apparent cause. Contrasted information making it possible to establish definitive algorithms for screening of HBPs is very limited. Common sense and accessibility to the tests in the specific clinical setting where we work should always prevail. The search should be centered on more prevalent forms and with greater reversibility potential: using pressor substances or those that interact with antihypertensive drugs, chronic kidney disease, endocrinological diseases and COPDs. When limiting the search, it is helpful to consider the age group of the patient considered and the active search of specific clinical and/or analytic traits. Adequate screening of HBPs finally require us to have capacity to obtain a global view of the hypertensive condition and to use much common sense in the choice of the examinations to be made

Abeta induces cell death by direct interaction with its cognate extracellular domain on APP (APP 597-624).

Amyloid beta-peptide (Abeta) is postulated to play a central role in the pathogenesis of Alzheimer's disease. We recently proposed a pathway of Abeta-induced toxicity that is APP dependent and involves the facilitation of APP complex formation by Abeta. The APP-dependent component requires cleavage of APP at position 664 in the cytoplasmic domain, presumably by caspases or caspase-like proteases, with release of a potentially cytotoxic C31 peptide. In this study we show that Abeta interacted directly and specifically with membrane-bound APP to facilitate APP homo-oligomerization. Using chimeric APP molecules, this interaction was shown to take place between Abeta and its homologous sequence on APP. Consistent with this finding, we demonstrated that Abeta also facilitated the oligomerization of beta-secretase cleaved APP C-terminal fragment (C99). We found that the YENPTY domain in the APP cytoplasmic tail and contained within C31 is critical for this cell death pathway. Deletion or alanine- scanning mutagenesis through this domain significantly attenuated cell death apparently without affecting either APP dimerization or cleavage at position 664. This indicated that sequences within C31 are required after its release from APP. As the YENPTY domain has been shown to interact with a number of cytosolic adaptor molecules, it is possible that the interaction of APP, especially dimeric forms of APP, with these molecules contribute to cell death.