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Access to kidney transplantation for patients with high levels of antibodies against HLA is a major challenge. This issue makes it difficult to detect compatible donors for those patients in a certain geographical area. Consequently, hypersensitized patients remain on the waiting list for long periods and their quality of life deteriorates. Our purpose was to increase access to transplantation for highly sensitized patients by developing a national priority allocation system based on virtual crossmatch. Between June 15, 2015, and May 15, 2016, 675 patients on the kidney transplant waiting list with calculated panel-reactive antibodies ≥98% and undergoing dialysis for at least 12 months were included in the study; 86.1% of the patients had previously received at least one transplant. Solid-phase immunoassays were used to identify class I and II HLA antibodies in all patients. Participating hospitals assigned to the program one of the kidneys of every identified brain-dead real donor between 18 and 70 years old. Survival data were collected for the recipients transplanted between June 15, 2015, and December 31, 2015. In all, 475 (290 male and 185 female) brain-dead donors were assigned to the program. Virtual crossmatch was negative for 191 (41%) donors, 149 offers were accepted, and 102 (21.8%) kidneys were transplanted. At the end of the study, patient and graft survival were both 93.4%. The implementation of a national prioritization system based on virtual crossmatch increased access to transplantation for highly sensitized patients, with excellent results in terms of patient and graft survival.

The field work to assess the archaeological impact of the Gas pipeline in Galicia discovered a site with an interesting archaeological and environmental stratigraphy. Its base is dated lo preneolithic times and offers a small set of lithics related to that period. Then the location was used to establish a neolithic camp with complex firing structures. Once abandoned, the site was covered by a paleosoil that was cultivated in early·medieval times. The most complicated example of plough marks in Galician archeology was found here; they give us good information about agrarian technology. Archaeological interpretations were combined with pollen and soil analytics. The research strategy applied in this site allows us to define the landscape sequence for the period, showing not only the nature but also the land uses and patterns of change of this space. This paper is a good example of what could be called intensive micro-landscape archeology., En el marco de los trabajos de corrección del impacto arqueológico de la red del Gas en Galicia, se descubrió un yacimiento que ofreció una interesante estratigrafía arqueológica y ambiental. La base del mismo es de momentos preneolíticosy presenta industrias líticas. Sobre ese nivel aparece un yacimiento neolítico con interesantes estructuras de combustión. Una vez abandonado el yacimiento se generó sobre él un palesuelo que, en época medieval, fue cultivado con arado, apareciendo un interesante conjunto de huellas de arado que aportan información sobre la tecnología agraria de la época. El análisis arqueológico se combinó con análisis polínicos y edafológicos que, una vez integrados, permiten establecer la secuencia de la naturaleza, uso y cambio de esos paisajes a lo largo de casi ocho mil años. El trabajo es un buen ejemplo de un tipo de investigación de gran escala e hiperintensiva en arqueología del paisaje.

We have surveyed two areas with open air rock art in Monte Penide, finding in the process several artefact scatters near the petro glyphs of roughly the same age. Also, we have undertaken a soil analysis of a section already exposed in one of those places (Coto da Fenteira), looking for occurrences of enrichment in certain trace elements (Ti, Zr, Hg or Br) along the sequence. As a result of this studies in combination with 14C dating of charcoal and organic matter, we have been able to define two main erosive episodes, resulting from human activity: one in the first half of the third millennium BC and a second, less violent one, from the start of the second millennium BC. These episodes have to do mostly with the spread of a farming economy during the Chalcolithic and its consolidation along the Earlier Bronze Age, thus rejecting the notion of a socioeconomic crisis during the latter and showing, instead, a progressive interference with the environment by human groups up to the second Iron Age.Hemos prospectado dos áreas con manifestaciones de arte rupestre en Monte Penide, descubriendo en su cercanía concentraciones de material cerámico y lítico de cronología semejante. Uno de los lugares examinados (Coto da Fenteira) fue objeto de un análisis edafológico sobre un corte abierto por obras recientes. La combinación de estudios sobre elementos traza (Ti, Zr, Hg o Br) y de dataciones C-14 ha permitido definir un suelo policíclico que se extiende a lo largo del Holoceno y en el que se diferencian dos grandes episodios erosivos vinculados a la acción antrópica: uno a partir de la primera mitad del III milenio AC y otro menos violento desde inicios del II milenio, coincidentes grosso modo con la expansión del sistema agropastoril durante el Calcolítico y su continuación a lo largo del Bronce inicial/medio regional, desmintiendo así la noción de una crisis socioeconómica durante el segundo período y apoyando, en cambio, la hipótesis de una incidencia progresiva de los grupos humanos sobre el medio hasta bien entrada la Edad del Hierro.

En el Hospital Universitario de Canarias pusimos en marcha, en mayo de 2008, un protocolo de tratamiento de inducción para pacientes hipersensibilizados que reciben injerto renal de cadáver utilizando inmunoglobulinas intravenosas, plasmaféresis y rituximab más una inmunosupresión triple con prednisona, tacrolimus y micofenolato mofetil. Presentamos los resultados de 4 pacientes. Todos ellos presentaban una tasa de anticuerpos anti-HLA (PRA por CDC) superior al 75%, llevaban en lista de espera de 4 a 17 años, el tiempo de seguimiento posterior al trasplante fue de 10-14 meses y la supervivencia de paciente y del injerto en este período fue del 100%. Sólo un paciente sufrió un rechazo agudo mediado por anticuerpos y otro uno celular, en ambos casos reversibles con el tratamiento. En la evolución no se objetivó aparición de novo de anticuerpos donante-específicos. Todos los pacientes habían reducido significativamente el número de células CD19+ después de la infusión de rituximab. No se han detectado síntomas neurológicos indicativos de leucoencefalopatía multifocal progresiva ni infecciones virales graves después del trasplante y tampoco se han observado efectos secundarios inmediatos tras la administración de la medicación. En resumen, el tratamiento de inducción combinado con inmunoglobulinas, plasmaféresis y rituximab en pacientes hipersensibilizados permite la realización del trasplante renal procedente de donante cadáver con buenos resultados a corto y medio plazo y sin graves efectos secundarios. Queda por conocer si estos buenos resultados se mantendrán a más largo plazo.

En el Hospital Universitario de Canarias pusimos en marcha, en mayo de 2008, un protocolo de tratamiento de inducción para pacientes hipersensibilizados que reciben injerto renal de cadáver utilizando inmunoglobulinas intravenosas, plasmaféresis y rituximab más una inmunosupresión triple con prednisona, tacrolimus y micofenolato mofetil. Presentamos los resultados de 4 pacientes. Todos ellos presentaban una tasa de anticuerpos anti-HLA (PRA por CDC) superior al 75%, llevaban en lista de espera de 4 a 17 años, el tiempo de seguimiento posterior al trasplante fue de 10-14 meses y la supervivencia de paciente y del injerto en este período fue del 100%. Sólo un paciente sufrió un rechazo agudo mediado por anticuerpos y otro uno celular, en ambos casos reversibles con el tratamiento. En la evolución no se objetivó aparición de novo de anticuerpos donante-específicos. Todos los pacientes habían reducido significativamente el número de células CD19+ después de la infusión de rituximab. No se han detectado síntomas neurológicos indicativos de leucoencefalopatía multifocal progresiva ni infecciones virales graves después del trasplante y tampoco se han observado efectos secundarios inmediatos tras la administración de la medicación. En resumen, el tratamiento de inducción combinado con inmunoglobulinas, plasmaféresis y rituximab en pacientes hipersensibilizados permite la realización del trasplante renal procedente de donante cadáver con buenos resultados a corto y medio plazo y sin graves efectos secundarios. Queda por conocer si estos buenos resultados se mantendrán a más largo plazo. In our Universitary Hospital of Canarias we iniciated in May 2008 a induction therapy protocol for sensitized patients receiving cadaveric renal graft using intravenous immunoglobulins, plasmapheresis and rituximab plus immunosuppression with prednisone, tacrolimus and mycophenolate mofetil. We present the results of four patients. Everyone had anti-HLA antibodies rate (PRA by CDC) more than 75%, were on a waiting list during 4 to 17 years and follow-up time was 10-14 months after transplantation. Patient and graft survival in this period was 100%. Only one patient suffered a humoral acute rejection and another one cellular rejection, in both cases reversible with treatment. During the first year, no evidence of de novo donor-specific antibodies was detected. All patients had significantly reduced the CD19+ cells percentage after infusion of rituximab. Neurological symptoms suggestive of progressive multifocal leukoencephalopathy or serious viral infections after transplantation have not been observed. Additionally, no immediate side effects were observed after administration of medication. In summary, induction therapy by combining immunoglobulin, plasmapheresis and rituximab in hypersensitive patients allows the realization of deceased kidney transplantation with good results in the short and medium-term without serious side effects. It remains to know whether this success will continue in the long term.

In our Universitary Hospital of Canarias we iniciated in May 2008 a induction therapy protocol for sensitized patients receiving cadaveric renal graft using intravenous immunoglobulins, plasmapheresis and rituximab plus immunosuppression with prednisone, tacrolimus and mycophenolate mofetil. We present the results of four patients. Everyone had anti-HLA antibodies rate (PRA by CDC) more than 75%, were on a waiting list during 4 to 17 years and follow-up time was 10-14 months after transplantation. Patient and graft survival in this period was 100%. Only one patient suffered a humoral acute rejection and another one cellular rejection, in both cases reversible with treatment. During the first year, no evidence of de novo donor-specific antibodies was detected. All patients had significantly reduced the CD19+ cells percentage after infusion of rituximab. Neurological symptoms suggestive of progressive multifocal leukoencephalopathy or serious viral infections after transplantation have not been observed. Additionally, no immediate side effects were observed after administration of medication. In summary, induction therapy by combining immunoglobulin, plasmapheresis and rituximab in hypersensitive patients allows the realization of deceased kidney transplantation with good results in the short and medium-term without serious side effects. It remains to know whether this success will continue in the long term.

Se describe la experiencia pionera llevada a cabo entre 2008 y 2009 con el estudio Avall en 16 escuelas catalanas al objeto de analizar la efectividad de una intervención educativa en los hábitos alimentarios y la actividad física de los niños de primero de educación primaria. Se empleó la metodología IVAC (investigación, visión, acción y cambio), donde los escolares son los protagonistas al evaluar sus propios comportamientos e influir en las variables o indicadores determinantes de la obesidad.. Cataluña Consejería de Educación, Formación y Empleo. Servicio de Publicaciones y Estadística; Avda. de la Fama, 15 - 1ª Planta; 30006 Murcia; Tel. +34968279685; Fax +34968279835; mjesus.ruiz@carm.es ESP

Besides the role of histamine (HA) as a neurotransmitter, a new concept has emerged presenting HA as an immunomodulator. Several studies have demonstrated interactions among HA, interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF), suggesting a possible bidirectional communication among them. In this study we have investigated the effects of i.p. administrations of HA diphosphate (6 mumol/kg) and alpha-fluoromethylhistidine (FMH; 100 mg/kg) on TNF-alpha levels in the hippocampus, hypothalamus, and posterior hypothalamic region of the rat brain. The concentrations of TNF-alpha at 0 (Control, C) and 30 min after i.p. administration of HA were 0.26 +/- 0.02 pg/mg and 0.32 +/- 0.02 pg/mg in the hippocampus, 0.46 +/- 0.04 pg/mg and 0.09 +/- 0.006 pg/mg (p0.01) in the hypothalamus, and 0.47 +/- 0.05 pg/mg and 0.26 +/- 0.05 pg/mg in the posterior hypothalamic region. Three hours after FMH administration, an increase in the hippocampal levels of TNF-alpha was observed (0.43 +/- 0.04 pg/mg; p0.01), while in the hypothalamus (0.11 +/- 0.02 pg/mg; p0.01) and in the posterior hypothalamic region (0.21 +/- 0.04 pg/mg; p0.05) a decrease in TNF-alpha levels was detected. These results suggest that changes in the histaminergic system influence TNF-alpha production in the brain in an area-specific fashion.

The field work to assess the archaeological impact of the Gas pipeline in Galicia discovered a site with an interesting archaeological and environmental stratigraphy. Its base is dated lo preneolithic times and offers a small set of lithics related to that period. Then the location was used to establish a neolithic camp with complex firing structures. Once abandoned, the site was covered by a paleosoil that was cultivated in early·medieval times. The most complicated example of plough marks in Galician archeology was found here; they give us good information about agrarian technology. Archaeological interpretations were combined with pollen and soil analytics. The research strategy applied in this site allows us to define the landscape sequence for the period, showing not only the nature but also the land uses and patterns of change of this space. This paper is a good example of what could be called intensive micro-landscape archeology.En el marco de los trabajos de corrección del impacto arqueológico de la red del Gas en Galicia, se descubrió un yacimiento que ofreció una interesante estratigrafía arqueológica y ambiental. La base del mismo es de momentos preneolíticosy presenta industrias líticas. Sobre ese nivel aparece un yacimiento neolítico con interesantes estructuras de combustión. Una vez abandonado el yacimiento se generó sobre él un palesuelo que, en época medieval, fue cultivado con arado, apareciendo un interesante conjunto de huellas de arado que aportan información sobre la tecnología agraria de la época. El análisis arqueológico se combinó con análisis polínicos y edafológicos que, una vez integrados, permiten establecer la secuencia de la naturaleza, uso y cambio de esos paisajes a lo largo de casi ocho mil años. El trabajo es un buen ejemplo de un tipo de investigación de gran escala e hiperintensiva en arqueología del paisaje.

The cholinergic dysfunction present in Alzheimer's disease (AD) might be due to a specific vulnerability of cholinergic neurons linked to neurotrophic imbalance, neuroimmune impairment, and/or direct effects of beta-amyloid deposition and NFT formation in ACh neurons. The presence of abnormal epitopes exposed on neuronal membranes may contribute to the activation of resting microglia initiating a neuroimmune cascade leading to cell destruction. According to this hypothesis, a multifactorial treatment in AD should produce: 1) inhibition of beta-amyloid and NFT formation; 2) restoration of neuronal membrane integrity; and 3) control of neuroimmune auto-aggression. Since interleukin-1 (IL-1) is an APP gene promoter showing a progressive increase in body fluids in parallel with mental deterioration in AD patients, we have studied the effects of CDP-choline on cognition, several biological parameters, and IL-1 beta production in AD and multi-infarct dementia (MID) in order to elucidate whether this compound alone or in combination with other drugs is able to restore immune function and improve mental performance in senile dementia.

Unidad Didáctica correspondiente al Módulo 4 del Curso de Especialización en Gestión Arqueológica del Patrimonio Cultural, editado por de Laboratorio de Arqueoloxía e Formas Culturais, e impartido en el año 2001. El curso tiene 7 módulos de temática especializada que se encuentran íntegramente depositados en este repositorio., [ES] Este módulo presenta una propuesta teórico-metodológica concreta para interpretar y valorar el Patrimonio Arqueológico y Cultural basada en la Arqueología del Paisaje. El primer objetivo es presentar la forma de estudiar y reconstruir las diferentes dimensiones (ambientales, sociales, simbólicas y formales) de los paisajes arqueológicos y prehistóricos. En este sentido, se pretende mostrar de qué forma es posible desde la Arqueología del Paisaje comprender el contexto histórico del registro arqueológico, valorar la dimensión histórica de las entidades patrimoniales, y establecer la relación entre forma, función, uso y sentido de esas entidades. Como un beneficio u objetivo complementario de este módulo, se pretenden definir las tipologías formales fundamentales de cada uno de los principales periodos de la Prehistoria e Historia Antigua, tomando Galicia como ejemplo práctico y tratando no sólo la entidad o forma concreta, sino también su inclusión dentro de un territorio determinado. De este modo, al tiempo que se presenta la Arqueología del paisaje y se caracterizan los principales modelos de paisaje y periodos culturales de la Prehistoria, se muestra la potencialidad que para el estudio y gestión del Patrimonio ofrece una perspectiva basada en valorar las entidades arqueológicas desde el contexto espacial del que formaron parte., [EN] This module offers a specific theoretical and methodological proposal for interpreting and appraising Archaeological and Cultural Heritage, based on Landscape Archaeology. The main objective is to show how the different environmental, social, symbolic and formal aspects of archaeological and prehistoric landscapes are studied and reconstructed. The aim is to show how it is possible to use Landscape Archaeology to help understand the historical context of the archaeological record, evaluate the historical dimension of heritage elements, and establish the relationship between the form, function, use and meaning of these elements. As a complementary aspect to this module, the aim will be to define the basic formal typologies of each of the main periods from Prehistory and Ancient History, using Galicia as a practical example and not only dealing with the specific form or entity, but also its inclusion within a given territory. In this way, at the same time as presenting Landscape Archaeology and characterising the main landscape models and cultural periods from Prehistory, the module will show the potential that a perspective based on evaluating archaeological elements through the spatial context of which they form a part offers for the study and management of Heritage.

We have surveyed two areas with open air rock art in Monte Penide, finding in the process several artefact scatters near the petro glyphs of roughly the same age. Also, we have undertaken a soil analysis of a section already exposed in one of those places (Coto da Fenteira), looking for occurrences of enrichment in certain trace elements (Ti, Zr, Hg or Br) along the sequence. As a result of this studies in combination with 14C dating of charcoal and organic matter, we have been able to define two main erosive episodes, resulting from human activity: one in the first half of the third millennium BC and a second, less violent one, from the start of the second millennium BC. These episodes have to do mostly with the spread of a farming economy during the Chalcolithic and its consolidation along the Earlier Bronze Age, thus rejecting the notion of a socioeconomic crisis during the latter and showing, instead, a progressive interference with the environment by human groups up to the second Iron Age., Hemos prospectado dos áreas con manifestaciones de arte rupestre en Monte Penide, descubriendo en su cercanía concentraciones de material cerámico y lítico de cronología semejante. Uno de los lugares examinados (Coto da Fenteira) fue objeto de un análisis edafológico sobre un corte abierto por obras recientes. La combinación de estudios sobre elementos traza (Ti, Zr, Hg o Br) y de dataciones C-14 ha permitido definir un suelo policíclico que se extiende a lo largo del Holoceno y en el que se diferencian dos grandes episodios erosivos vinculados a la acción antrópica: uno a partir de la primera mitad del III milenio AC y otro menos violento desde inicios del II milenio, coincidentes grosso modo con la expansión del sistema agropastoril durante el Calcolítico y su continuación a lo largo del Bronce inicial/medio regional, desmintiendo así la noción de una crisis socioeconómica durante el segundo período y apoyando, en cambio, la hipótesis de una incidencia progresiva de los grupos humanos sobre el medio hasta bien entrada la Edad del Hierro.

Rats with neurotoxic lesions, induced by single or double bilateral injections of ibotenic acid into different parts of the nucleus basalis of Meynert (nbM), showed increased psychomotor activity (PMA) and impaired learning in a passive avoidance task. Behavioral deficits were similar in all the groups of lesioned animals, suggesting that the lesion site was not relevant for the ibotenic effects under testing procedures used here. In another experiment, nbM-lesioned rats received acute or daily (5 days) i.p. injections of vehicle or anapsos (100 mg/kg) from the 7th day after surgery. Data indicated that nbM lesions induced an increased production of interleukin-1 beta (IL-1 beta), motor hyperactivity and learning impairment, and that anapsos, a vegetal extract with immunomodulatory activity, reversed brain IL-1 beta overexpression and behavioral alterations in lesioned rats. These results confirm the involvement of IL-1 beta in neurodegeneration associated with cholinergic deficits and the potential utility of compounds with neuroimmunotrophic activity as a new therapeutic strategy in neurodegenerative disorders.

The enzyme Cu-Zn-SOD is a metalloenzyme that catalyzes the dismutation of the superoxide radical into hydrogen peroxide and molecular oxygen, being a defense system against free radical formation. Free radical reactions are implicated in a variety of physiological and pathological processes as aging, apoptosis and neurodegenerative diseases, and abnormalities associated with SOD have been recently documented in several neurodegenerative processes. In this study, we have evaluated the effect of anapsos on Cu-Zn-SOD activity in rats with injections of beta-amyloid protein or water bilaterally into the hippocampus. These injections caused severe cell depletion in the gyrus dentatus. Anapsos is a biological extract obtained from the fern Polypodium leucotomos with immunomodulatory and anti-neoplastic effects tested in animals and humans. Cu-Zn-SOD activity was measured in the hypothalamus, hippocampus, cerebral cortex, liver and spleen of rats treated i.p. with three doses of anapsos for 7 days (4, 20 and 100 mg/kg/day). Control animals were treated with saline solution under the same conditions. Anapsos significantly modified enzyme activity in all the areas tested. Lower doses of anapsos produced decreased SOD activity in the hypothalamus, hippocampus, liver and spleen, while in the cerebral cortex, a significant dose-dependent increase in SOD activity was observed. These results indicate that anapos was able to modify Cu-Zn-SOD activity in this animal model of neuronal degeneration, which may indicate the participation of anapsos in mechanisms of tissue repair after brain damage.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by an heterogeneous etiopathogenesis on a genetic basis. The most prominent neuropathological findings in AD are senile plaques, neurofibrillary tangles (NFT), amyloid deposition in neural tissues and vessels, synaptic loss and subsequent neuronal death (Cacabelos et al., 1993, 1995; Hardy and Allsop, 1991; Terry et al., 1991). However, other neurochemical mechanisms may also account for cell death and neurodegeneration in AD, including neuroimmune dysfunction, free radical formation, neurotransmitter deficits and alterations in brain calcium homeostasis (Cacabelos et al., 1994, 1995; Richardson, 1993). So, new approaches to AD treatment are oriented to search for agents acting on etiopathogenic events and pleiotropic compounds displaying multifactorial effects.

CDP-choline was given to patients with Alzheimer's disease (AD) at a daily dose of 1000 mg/day p.o. for one month. This compound slightly improved mental performance, tended to reduce theta activity in fronto-temporal regions, increasing alpha power in occipital areas, and enhanced cerebrovascular perfusion by increasing blood flow velocity and reducing pulsatility and resistance indexes. In addition, CDP-choline diminished histamine and interleukin-1 levels in blood and serum, respectively, and increased plasma TNF.

CDP-choline participates in brain phospholipid metabolism and acts as an endogenous intermediate in a biosynthetic pathway incorporating free choline into phosphatidylcholine and choline plasmalogens in several tissues, including the central nervous system (CNS). In patients with chronic cerebrovascular disorders, CDP-choline reduces the slow delta frequencies and increases alpha activity in spectral electroencephalogram analysis. We have studied the effect of CDP-choline (cytidine-S-diphosphate-choline; 1000 mg/day x 30 days, p.o.) on brain electrical activity mapping and mental performance in 19 Alzheimer's disease (AD) patients (10 males/9 females; age: 66.21 +/- 1.48 years; Mini-Mental State Examination (MMSE): 26.55 +/- 1.22, Spanish version max. score 35). EEG was registered from 19 electrodes placed according to the 10-20 system and digitalized online. Artefact-free 2-s periods were visually selected, submitted to a frequency analysis and averaged across periods. CDP-choline significantly decreased spectral amplitude in the theta band in F4, F8, and T4 electrodes, and did not modify relative power parameters in any of the frequency bands (delta, theta, alpha, beta) as compared to basal recordings. In patients with late-onset AD (LOAD; N = 6; age: 73.5 +/- 1.34 years; MMSE: 28.75 +/- 2.33), CDP-choline tended to increase relative alpha power in O1 and O2 electrodes. No changes were found in early-onset AD patients (EOAD; N = 13; age: 62.85 +/- 1.21 years; MMSE: 25.54 +/- 1.4). We detected a significant improvement in mental performance after 1 month of treatment with CDP-choline in patients with early-onset AD in whom brain electrical activity data correlated with cognitive parameters. It is likely that the bioelectrical changes induced by CDP-choline in AD are the result of its immunogenic and/or neurotrophic activity in the vicinity of the vascular microenvironment.

Histamine (HA) is a known neurotransmitter with a wide spectrum of biological actions at the central and peripheral levels. Recently, it has been found that HA is involved in the regulation of immune cell function, acting as an immunomodulator. A hyperactivation in the histaminergic system has been demonstrated in Alzheimer's disease (AD), including increased levels of HA in brain, serum, and cerebrospinal fluid of AD patients. In addition, changes in phospholipid metabolism and neuroimmune function have been reported in AD. CDP-choline (cytidine-5-diphosphate-choline) participates in the phospholipid metabolism pathway incorporating free choline into phosphatidyl-choline and choline plasmalogens in several tissues, including the central nervous system. In this study we have measured the concentration of HA in blood from patients with early-onset AD (EOAD) and late-onset AD (LOAD) under treatment with CDP-choline (1000 mg p.o. x30 days). HA was measured by high performance liquid chromatography (HPLC) with fluorometric detection. CDP-choline reduced the basal levels of blood HA in both EOAD and LOAD by 2-fold. The reduction in blood HA content was observed 2 h after CDP-choline administration and gradually progressed for 30 days of treatment. These results confirm the potential immunogenic effects of CDP-choline and also that an excess of HA might influence some etiopathogenic events in AD.

Changes in neuroimmune parameters and cytokine production have been reported in patients with Alzheimer's disease, including increased levels of interleukin-1 (IL-1) and histamine in brain tissue, cerebrospinal fluid and serum. Specific neuroimmune reactions may be responsible in part for astrogliosis and neuronal death in particular circumstances. Since IL-1 and tumor necrosis factor (TNF) tend to act synergistically in physiological conditions and in some pathological processes, we have studied the concentration of TNF-alpha in patients with Alzheimer's disease (AD) or multi-infarct dementia (MID) and in age-matched control subjects (CS) in order to evaluate possible changes in the levels of this cytokine with potential influence on the pathogenesis of AD. Serum TNF-alpha levels were significantly lower in AD (2.5 +/- 1.25 pg/ml, p0.01) and MID (1.64 +/- 1.17 pg/ml, p0.001) than in CS (10.66 +/- 8.92 pg/ml). A negative correlation between serum TNF-alpha levels and age in AD was found (r = -0.645, p0.01); however, no significant correlations were detected between serum TNF-alpha levels and mental performance, cerebrovascular risk, heart rate and blood pressure in either AD or MID. In conclusion, there is a marked reduction in the concentration of serum TNF-alpha in both AD and MID which seems to be poorly related to cognitive dysfunction and/or neurovascular damage, probably reflecting an endogenous immune dysregulation and/or an inhibitory reactive process in demented patients.

Recent data indicate that a neuroimmune reaction might be responsible in part for neuronal death and cognitive deterioration in senile dementia. The potential involvement of brain histamine (HA) and interleukin-1 (IL-1) in this process has been previously documented. We have studied the concentration of serum HA in patients with Alzheimer's disease (AD) or multi-infarct dementia (MID) and in age-matched control subjects. Serum HA levels were significantly higher in AD (10.935 +/- 5.692 nM) and MID (8.521 +/- 3.44 nM) than in controls (5.533 +/- 2.567 nM) and correlated with mental performance as evaluated with the Mini-Mental State Examination (MMSE) (r = +0.493, p0.009). No correlation was found with cardiovascular parameters, cerebrovascular risk factors or age. Hyperactivation of the histaminergic system in AD at central and peripheral levels might reflect a neuroimmune reaction to brain tissue damage, a neurotrophic response, and/or a reactive process to regulate the IL-1 induced amyloid precursor protein (APP) overproduction.