Socioeconomic, health-care access and clinical determinants of disease severity in Multiple Sclerosis in Chile.

BACKGROUND: MS severity may be affected by genetic, patient-related, disease-related and environmental factors. Socioeconomic status, including income and healthcare access, amongst others, may also have a role in affecting diagnostic delay or therapy prescription. In Chile, two main healthcare systems exist, public-healthcare and private-healthcare, nonetheless universal care laws (e.g., access to High Efficacy Therapy-HET), including both systems, have been recently enacted for people with MS. OBJECTIVE: To assess the role of Socioeconomic Conditions (SEC), clinical variables and public health policies on the impact of disease severity of MS patients in Chile. METHODS: Multicentric, observational, cross-sectional study including patients from two reference centres (1 national reference centre from the private-health system and 1 regional reference centre from the public-health system). SEC and clinical variables included healthcare insurance (private or public), subclassification of health insurance according to monthly income, sex, age at onset, diagnostic delay, disease duration, diagnosis before HET law (as a proxy of HET delay), and current HET treatment. Progression Index (PI), EDSS ≥6.0 and Progressive MS diagnosis were used as outcome measures. Multivariable binary logistic regression was performed. RESULTS: We included 604 patients (460 private-health, 144 public-health), 67% women, 100% white/mestizo, 88% RRMS, mean age 42±12 years, mean age at onset 32±11 years, mean disease duration 10±6 years, median diagnostic delay 0 (0-34) years, 86% currently receiving any DMT, 55% currently receiving HET, median EDSS at last visit of 2.0 (0-10), and median PI 0.17 (0-4.5). Lower monthly income was associated with higher EDSS and higher PI. In the multivariable analysis, public-healthcare (OR 10.2), being diagnosed before HET-law (OR 4.89), longer diagnostic delay (OR 1.26), and older age at onset (OR 1.05) were associated with a higher risk of PI>0.2, while current HET (OR 0.39) was a protective factor. Diagnosis before HET-law (OR 7.59), public-healthcare (OR 6.49), male sex (OR 2.56), longer disease duration (OR 1.2) and older age at onset (OR 1.1) were associated with a higher risk of Progressive MS. Public-healthcare (OR 5.54), longer disease duration (OR 1.14) and older age at onset (OR 1.08) were associated with a higher risk of EDSS ≥6.0 while current treatment with HET had a trend as being a protective factor (OR 0.44, p = 0.05). CONCLUSION: MS severity is impacted by non-modifiable factors such as sex and age at onset. Interventions focused on shortening diagnostic delay and encouraging early access to high-efficacy therapies, as well as initiatives that may reduce the disparities inherent to lower socioeconomic status, may improve outcomes in people with MS.

Disfunción inmunológica en enfermedad de Alzheimer; proinflamatoria en etapas iniciales y regulatoria, y exhausta en etapas avanzadas / Immune dysfunction in disease Alzheimer's; proinflammatory in stages initial and regulatory, and exhaustive in advanced stages

Alzheimer disease (AD) is the main cause of dementia worldwide and a source of important population morbidity and mortality. It is estimate that its prevalence will increase dramatically in the upcoming years. The classical clinical presentation of AD is an amnesic hippocampal syndrome, and Mild Cognitive impairment (MCI) is considered the initial stage between normal cognition and dementia. The most accepted pathogenesis establishes amyloid beta (Ab) deposition in brain parenchyma as the initial mechanism, followed by the intracellular accumulation of hyperphosphorylated tau finally leading to the loss of synapses and neurons. Recently, the study of AD pathogenesis is focusing on immune mechanisms as main actors of disease development. Microglia is the macrophagic resident cell in the central nervous system (CNS), and initiates the inflammatory response and Ab phagocytosis, interacting with other glia and recruiting diverse immune cells to the CNS. The role of the adaptive immune system, and, especially T lymphocytes' role, is still controversial. We hypothesize that the pathogenesis of AD is dynamic; with a preponderant proinflammatory activity initially, but later on, the persistent presence of Ab due to the lack of its proper elimination leads to a phenomena of lymphocyte dysfunction and immunological tolerance that have a deleterious role at advanced stages of the disease. (AU)

LGI1-antibody associated epilepsy successfully treated in the outpatient setting.

We report six patients with anti-LGI1 associated epilepsy. Two patients presented with new-onset generalized tonic-clonic seizures, four developed faciobrachial dystonic seizures and two piloerection. All patients had significant cognitive complaints at the time of diagnosis. All patients described seizure reduction during the first week of carbamazepine, and seizure freedom was obtained at a median of 13 days (range 7-22), sustained after the initiation of immunosuppression. Median time from symptom onset to carbamazepine initiation was 164 days (range 38-206 days). We discuss the particular seizure response to sodium channel blocking antiepileptic drugs, alone or associated with immunosuppression in this antibody mediated seizures.

Fístula aorto-duodenal primaria: caso clínico / Primary aorto-duodenal fistula: clinical case

Resumen Introducción Las fístulas aorto-entéricas (FAE) son una causa infrecuente de hemorragia digestiva. El pronóstico, generalmente ominoso, depende de una alta sospecha clínica y diagnóstico oportuno. Caso clínico Reportamos el caso de una mujer de 66 años intervenida por un aneurisma sacular aórtico abdominal (AAA) yuxtarrenal, con rotura contenida, fistulizado al duodeno. Presentó una hemorragia digestiva en el preoperatorio; sin embargo, el diagnóstico de la fístula se hizo en el intraoperatorio. La paciente fue sometida a reparación quirúrgica urgente con instalación de una prótesis aórtica bifemoral y resección duodenal. En el postoperatorio inmediato presentó una trombosis parcial de las ramas de la prótesis aórtica e isquemia de extremidades, siendo reintervenida exitosamente. Discusión La FAE es una causa potencialmente fatal de hemorragia digestiva. El diagnóstico continúa siendo un desafío debido a su presentación inespecífica y siempre debiese ser considerado frente a una hemorragia digestiva sin causa aparente. Existen varias opciones para el enfrentamiento quirúrgico que deben ser analizadas caso a caso, sin retrasar la reparación de la fístula. Es preferible la resección duodenal ante la simple duodenorrafia.

Introduction Aorto-enteric fistulae (AEF) are a rare cause of gastrointestinal bleeding. The prognosis tends to be ominous, depending greatly in a high level of clinical suspicion and prompt diagnosis. Clinical case We report a case of a 66-year-old female with a saccular juxta-renal abdominal aortic aneurysm (AAA), with a contained rupture. The patient was urgently submitted to surgical repair using an bifemoral aortic prosthesis. A duodenal partial resection was performed. During the immediate postoperative time she presented partial thrombosis of prosthesis and ischemia of lower extremities so she was reoperated successfully. Discussion AEF is a potentially fatal cause of gastrointestinal bleeding. Diagnosis is still troublesome due to its vague presentation and it should always be considered when facing gastrointestinal haemorrhage with no apparent cause. There are several surgical approaches that should be pondered case to case without delaying the repair of the defect.

Refractory epilepsy associated with anti-ribosomal P antibodies successfully treated with topiramate.

We report the case of a 25-year-old woman who developed temporal lobe epilepsy associated with systemic lupus erythematosus (SLE). Serum and cerebrospinal fluid samples showed high titers of anti-ribosomal P (anti-P) antibodies with negative anti-NMDAR antibodies. She was receiving prednisone and azathioprine, with normalization of SLE serum markers, but without changes in titers of anti-P antibodies. No seizure control was achieved using valproic acid, levetiracetam and lamotrigine. However, she had a selective response to topiramate, an AMPAR blocker, maintained during 6 years of follow-up. We discuss the pathophysiology of this autoimmune epilepsy associated with high titer anti-P antibodies.

[Thyroid effects of treatment with biotin]. / Efectos tiroideos del tratamiento con biotina.

TITLE: Efectos tiroideos del tratamiento con biotina.

Relationship between Social Cognition and traditional cognitive impairment in Progressive Multiple Sclerosis and possible implicated neuroanatomical regions.

BACKGROUND: Cognitive impairment is a relevant contributor of the medical and social burden in Progressive MS. Social Cognition, the neurocognitive processes underlying social interaction, has been explored mainly in European and North American cohorts, influencing social aspects of quality of life (QOL) of early MS patients and families. Few studies have studied Social Cognition in Progressive MS and the literature on its neuroanatomical bases or brain atrophy measurements is still scarce. OBJECTIVES: To explore the relationship between Social Cognition performance and its correlations with traditional cognitive domains, brain atrophy and QOL in primary and secondary Progressive MS patients. METHODS: Cross-sectional analysis including: mini-Social-Cognition-and-Emotional-Assessment (mini-SEA), neuropsychological battery, disability, depression, fatigue, QOL, and brain volume. RESULTS: Forty-three MS patients, 23 primary and 20 secondary Progressive, 65% women, mean age and disease duration of 57.2 and 15.7 years, respectively, with high levels of disability (median EDSS 6.0) and a widespread impairment in traditional domains (mostly episodic verbal/visual and working memories) were assessed. The Mini-SEA score was correlated with executive functions (cognitive shifts Rho:0.55; p = 0.001) analyzing the whole group, and with visual episodic memory (Rho:0.58, p = 0.009) in the primary Progressive MS group. Mini-SEA score was also correlated with total normalized grey matter volume (Rho:0.48; p = 0.004). Particularly, atrophy within bilateral cortical regions of orbitofrontal, insula and cerebellum, and right regions of fusiform gyrus and precuneus were significantly associated with higher Social Cognition impairment. In this cohort, QOL was not correlated with Social Cognition, but with EDSS, fatigue and depression. CONCLUSIONS: In Progressive MS, Social Cognition is directly correlated with traditional cognitive domains such as executive function and episodic memory. It is also associated with global grey matter atrophy and regional atrophy within associative visual and executive cortical areas, but no correlations with QOL were found in this cohort. These findings may contribute to the understanding of the pathological bases behind Social Cognition in Progressive MS.

[Neuromyelitis optica spectrum disorders: profile of a cohort according to the 2015 diagnostic criteria]. / Espectro de neuromielitis optica: descripcion de una cohorte segun los criterios diagnosticos de 2015.

INTRODUCTION: The new 2015 criteria for neuromyelitis optica spectrum disorders (NMOSD) have been recently incorporated in the study of different international cohorts. AIM: To describe clinical-radiological characteristics and prognostic factors in patients with NMOSD according to the 2015 criteria. PATIENTS AND METHODS: Retrospective analysis of 36 patients diagnosed with NMOSD according to serologic AQP4 status (positive, negative, unknown and negative + unknown). Clinical and radiological characteristics were compared and possible disability prognostic factors were evaluated. RESULTS: AQP4 were positive in 7 patients, negative in 12 and unknown in 17. Age of presentation was 36.6 ± 16 years, with higher female proportion (4:1). Mean disease duration was 7.4 ± 7.6 years. Most frequent presenting symptoms were acute myelitis (61%), optic neuritis (33%) and area postrema syndrome (11%). Most frequent MRI lesion was longitudinally extensive transverse myelitis (75%). All patients received acute treatment during attacks, and preventive treatment was used in 81% (azathioprine and rituximab mostly prescribed). Median EDSS was 2.0 at the end of follow-up. No differences were observed in any of the variables comparing serologic status. Age of first attack was prognostic, with direct correlation with EDSS. First attack in < 30 years was protective, meanwhile > 50 years old patients had increased risk of disability. CONCLUSIONS: The 2015 criteria allow the description and classification of NMOSD patients within different cohorts. Age of first attack seems to be a prognostic factor for developing disability.

TITLE: Espectro de neuromielitis optica: descripcion de una cohorte segun los criterios diagnosticos de 2015.Introduccion. Los nuevos criterios diagnosticos de 2015 del espectro de neuromielitis optica (NMO) estan comenzando a utilizarse en diferentes poblaciones en el mundo. Objetivo. Describir las caracteristicas clinicorradiologicas y pronosticas de pacientes diagnosticados de NMO con los criterios de 2015. Pacientes y metodos. Analizamos retrospectivamente 36 pacientes diagnosticados de NMO con los actuales criterios. Se generaron cuatro grupos segun la serologia de antiacuaporina 4 (positivos, negativos, desconocidos y negativos mas desconocidos agrupados). Se compararon sus caracteristicas clinicorradiologicas y se evaluaron posibles variables pronosticas de discapacidad. Resultados. Encontramos siete pacientes seropositivos, 12 negativos y 17 desconocidos. La edad de inicio fue de 36 ± 16 años, con mayor proporcion de mujeres (4 a 1). La duracion de la enfermedad fue de 7,4 ± 7,6 años. Los sintomas iniciales mas frecuentes fueron mielitis (61%), neuritis optica (33%) y sindrome del area postrema (11%). La lesion mas frecuente en la resonancia magnetica fue la mielitis longitudinalmente extensa (75%). Todos los pacientes recibieron tratamiento agudo, y el preventivo se utilizo en el 81%; la azatioprina y el rituximab fueron los que mas se usaron. La mediana de la Expanded Disability Status Scale (EDSS) fue de 2 al final del seguimiento. No hubo diferencias significativas en las variables clinicorradiologicas entre los distintos grupos de pacientes. La edad de inicio fue pronostica y presenta correlacion directa con la EDSS. El inicio antes de los 30 años fue protector y, despues de los 50 años, un factor de riesgo para mayor discapacidad. Conclusiones. Los actuales criterios permiten describir diferentes cohortes. La edad de inicio parece ser un factor pronostico para desarrollar discapacidad.

Aumento de detección de lesiones gástricas premalignas mediante protocolo Sydney en comparación con biopsias no protocolizadas / Increased detection of premalignant gastric lesions through Sydney protocol in comparison with non-protocolized gastric biopsies

Introduction: Gastric cancer (GC) is the leading cause of cancer mortality in Chile. The development ofgastric adenocarcinoma its preceded by a histopathologic cascade composed of gastric atrophy, intestinal metaplasia and gastric dysplasia. Sydney protocol has been proposed as the standard method for diagnosingthese conditions. The aim of this research study was to establish whether Sydney protocol increase thedetection of premalignant gastric lesions, as gastric atrophy and intestinal metaplasia, compared to non protocolizedendoscopies/biopsies. Methods: Upper gastroduodenal endoscopies (GDE) from Hospital Clí-nico Universidad Católica de Chile between April-May 2015 and April-May 2016 was analyzed. Patientswith histological study with 18 years-old or older were included. Patients with history of GC or malignantlesions at GDE where excluded. Detection of gastric atrophy, intestinal metaplasia and suggestive findingsof autoimmune gastritis where compared between Sydney protocol and non-protocolized endoscopies/biopsies...

Introducción: El cáncer gástrico (CG) es la principal causa de muertes por cáncer en Chile. El desarrollo del adenocarcinoma gástrico es precedido por una cascada histopatológica (gastritis; atrofia gástrica/AG; metaplasia intestinal/MI). Se ha propuesto la biopsia del cuerpo, ángulo y antro a través del protocolo de Sydney para la búsqueda de estas condiciones. Objetivo: Determinar la diferencia en la detección delesiones premalignas gástricas a través del protocolo de Sydney comparado con el estudio endoscópico habitual. Métodos: Se analizaron las endoscopias digestivas altas (EDA) realizadas en el Centro de Endoscopia Digestiva del Hospital Clínico de la Universidad Católica en los períodos entre abril y mayo del 2015 y 2016. Se incluyeron las EDA de pacientes mayores de 18 años con estudio histológico. Fueron excluidos los pacientes con antecedente personal de CG o lesiones de aspecto maligno macroscópicas. Se comparó la detección de AG, MI y gastritis autoinmune (GA) en el estudio histológico entre los pacientes con protocolo Sydney y el estudio endoscópico no protocolizado...

Increased levels of adenosine and ecto 5'-nucleotidase (CD73) activity precede renal alterations in experimental diabetic rats.

The pathogenesis of diabetic nephropathy (DN) has not been clearly established, making diagnosis and patient management difficult. Recent studies using experimental diabetic models have implicated adenosine signaling with renal cells dysfunction. Therefore, the study of the biochemical mechanisms that regulate extracellular adenosine availability during DN is of emerging interest. Using streptozotocin-induced diabetic rats we demonstrated that urinary levels of adenosine were early increased. Further analyses showed an increased expression of the ecto 5'-nucleotidase (CD73), which hydrolyzes AMP to adenosine, at the renal proximal tubules and a higher enzymatic activity in tubule extracts. These changes precede the signs of diabetic kidney injury recognized by significant proteinuria, morphological alterations and the presence of the renal fibrosis markers alpha smooth muscle actin and fibronectin, collagen deposits and thickening of the glomerular basement membrane. In the proximal tubule cell line HK2 we identified TGF-ß as a key modulator of CD73 activity. Importantly, the increased activity of CD73 could be screened in urinary sediments from diabetic rats. In conclusion, the increase of CD73 activity is a key component in the production of high levels of adenosine and emerges as a new tool for the early diagnosis of tubular injury in diabetic kidney disease.

Accuracy of ultrasound elastography in the diagnosis of thyroid cancer in a low-risk population.

OBJECTIVE: Stiffness has been associated to malignancy in prostate and breast, as well as thyroid. Ultrasound elastography objectively measures tissue elasticity, and previous studies have described it as a high sensitivity and specificity technique for the detection of malignant thyroid nodules in high-risk populations. The aim was to assess the accuracy of elastography in a population with low risk of malignancy. DESIGN AND PATIENTS: 128 consecutive patients with nodular goiter were recruited. Elastography and ultrasound-guided fine-needle aspiration were performed. When malignancy was suspected by citology, surgery was recommended. Thyroid nodules were classified by elastography according the criteria described by Ueno, and an alternative classification. Sensitivity, specificity, predictive values, and odds ratio were calculated. RESULTS: Most patients were female, aged 56.1 year, with single nodule (52.0%) or multinodular goiter (45.6%), and a few thyroiditis (2.4%). The majority of nodules were mostly elastic. Fine-needle aspiration found 86% of benign nodules, 9.3% of indeterminate, and 4.7% possibly malignant. After surgery, 3 malignant nodules were confirmed, all of them being papillary carcinomas. All the malignant nodules were mostly elastic, as well as 75% of indeterminate nodules. Low values of sensitivity and specificity were found for elastic nodules being benign and hard nodules malignant. CONCLUSION: In a low-risk population for thyroid cancer, elastography lacks accuracy for the diagnosis of malignant nodules.

[Musculoskeletal tissue banks in Mexico. Part I. Regulation and organization]. / Bancos de tejidos musculoesqueléticos en México. Parte I. Regulación y organización.

Although Tissue Banks and their activities are not new in Mexico, the specific regulations for the activities of tissue banks and musculoskeletal tissues considered as health supplies are still under development. This review paper intends to provide information on the national situation of musculoskeletal tissue banks, major aspects concerning their regulation and organization, and the recognition of the national instances pertaining to the Coordination for Organ and Tissue Donation for Transplant Purposes for the obtention of (musculoskeletal) tissues from deceased donors.

Hypoxia-reduced nitric oxide synthase activity is partially explained by higher arginase-2 activity and cellular redistribution in human umbilical vein endothelium.

Hypoxia relates with altered placental vasodilation, and in isolated endothelial cells, it reduces activity of the endothelial nitric oxide synthase (eNOS) and l-arginine transport. It has been reported that arginase-2 expression, an alternative pathway for l-arginine metabolism, is increased in adult endothelial cells exposed to hypoxia as well as in pre-eclamptic placentae. We studied in human umbilical vein endothelial cells (HUVEC) whether hypoxia-reduced NO synthesis results from increased arginase-mediated l-arginine metabolism and changes in subcellular localization of eNOS and arginase-2. In HUVEC exposed (24 h) to 5% (normoxia) or 2% (hypoxia) oxygen, l-arginine transport kinetics, arginase activity (urea assay), and NO synthase (NOS) activity (l-citrulline assay) were determined. Arginase-1, arginase-2 and eNOS expression were determined by RT-PCR and Western blot. Subcellular localization of arginase-2 and eNOS were studied using confocal microscopy and indirect immunofluorescence. Experiments were done in absence or presence of S-(2-boronoethyl)-l-cysteine-HCl (BEC, arginase inhibitor) or N(G)-nitro-l-arginine methyl ester (l-NAME). Hypoxia-induced reduction in eNOS activity was associated with a reduction in eNOS phosphorylation at Serine-1177 and increased phosphorylation at Threonine-495. This was paralleled with an induction in arginase-2 expression and activity, and decreased l-arginine transport. In hypoxia the arginase inhibition, restored NO synthesis and l-arginine transport, without changes in the eNOS post-translational modification status. Hypoxia increased arginase-2/eNOS colocalization, and eNOS redistribution to the cell periphery. Altogether these data reinforce the thought that eNOS cell location, post-translational modification and substrate availability are important mechanisms regulating eNOS activity. If these mechanisms occur in pregnancy diseases where feto-placental oxygen levels are reduced remains to be clarified.

FK506 confers chemosensitivity to anticancer drugs in glioblastoma multiforme cells by decreasing the expression of the multiple resistance-associated protein-1.

Glioblastoma multiforme (GBM) is the most aggressive of brain tumors and is extremely insensitive to anticancer drugs. Studies have attributed the ABC transporter Mrp1 (ABCC1, multiple-drug resistance protein 1) with conferring chemoresistance in this tumor by extrusion of a wide spectrum of anticancer drugs. Therefore it is crucial to search for and investigate inhibitors of Mrp1 activity in GBM cells, particularly those that could be safe as chemosensitizers to anticancer drugs in clinical studies. We find that in primary cultured or T98G GBM cells exposed to therapeutic plasma concentrations of FK506 (tacrolimus), the expression of Mrp1 was decreased in a dose-dependent manner. The activity of this transporter, measured by CFDA fluorescent substrate extrusion, decreased significantly in primary cultured GBM cells on exposure to FK506 at concentrations of 15 ng/ml. When GBM cells were exposed to anticancer drugs vincristine, etoposide or taxol, cell viability was not affected. However when the anticancer drugs were assayed in combination with FK506, cell viability was significantly decreased by as much as 50% in GBM primary culture. We conclude that FK506 could be a valuable tool for chemosensitization of GBM cells, offering a possible improvement to the current poor therapy available for high-grade human gliomas.

Strategic noise map of a major road carried out with two environmental prediction software packages.

The main objective of this study is to analyze the differences found in the results of noise mapping using two of the most popular software techniques for the prediction of environmental noise. The location selected to conduct the comparative study is an area encompassed by the ring road that surrounds the city of Pamplona and on a grid, with a total of 6 x 10(5) points, approximately. In fact, and as the Environmental Noise Directive points out, it is a major road designated by a Member State (Spain). Configuration of the calculation parameters (discretization of the sources, ground absorption, reflection order, etc.) was as equivalent as possible as far as programs allow. In spite of that, a great number of differences appear in the findings. Although in 95.5% of the points the difference in the noise level calculated from the two programs was less than 3 dB, this general statistic result concealed some great differences. These are due to the various algorithms that programs implement to evaluate noise levels. Most differences pertain to highly screened receivers or remote ones. In the former, the algorithm of visibility is the main cause of such differences. In the latter, differences are mainly brought about by a different implementation of the propagation under homogeneous and favorable atmospheric conditions from both software systems.

Adenosine mediates transforming growth factor-beta 1 release in kidney glomeruli of diabetic rats.

Up regulation of the transforming growth factor-beta 1 (TGF-beta1) axis has been recognized as a pathogenic event for progression of glomerulosclerosis in diabetic nephropathy. We demonstrate that glomeruli isolated from diabetic rats accumulate up to sixfold more extracellular adenosine than normal rats. Both decreased nucleoside uptake activity by the equilibrative nucleoside transporter 1 and increased AMP hydrolysis contribute to raise extracellular adenosine. Ex vivo assays indicate that activation of the low affinity adenosine A2B receptor subtype (A2BAR) mediates TGF-beta1 release from glomeruli of diabetic rats, a pathogenic event that could support progression of glomerulopathy when the bioavailability of adenosine is increased.

Reduction of beta-amyloid-induced neurotoxicity on hippocampal cell cultures by moderate acidosis is mediated by transforming growth factor beta.

Progression of Alzheimer's disease (AD) is associated with chronic inflammation and microvascular alterations, which can induce impairment of brain perfusion because of vascular pathology and local acidosis. Acidosis can promote amyloidogenesis, which could further contribute to neurodegenerative changes. Nevertheless, there is also evidence that acidosis has neuroprotective effects in hypoxia models. Here we studied the effect of moderate acidosis on beta-amyloid (Abeta)-mediated neurotoxicity. We evaluated morphological changes, cell death, nitrite production and reductive metabolism of hippocampal cultures from Sprague-Dawley rats exposed to Abeta under physiological (pH 7.4) or moderate acidosis (pH 7.15-7.05). In addition, because transforming growth factor beta (TGFbeta) 1 is neuroprotective and is induced by several pathophysiological conditions, we assessed its presence at the different pHs. The exposure of hippocampal cells to Abeta induced a conspicuous reduction of neurites' arborization, as well as increased neuronal death and nitric oxide production. However, Abeta neurotoxicity was significantly attenuated when hippocampal cultures were kept at pH 7.15-7.05, showing a 68% reduction on lactate dehydrogenase release compared with cultures exposed to Abeta at pH 7.4 (P<0.01). Similarly, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction increased 3.5-fold (P<0.05), and Abeta-induced nitrite production was reduced by 65% when exposed to moderate acidosis compared with basal pH media (P<0.05). At the same time, moderate acidosis decreased intracellular TGFbeta1 precursor (latency associated protein-TGFbeta1) and increased up to fourfold TGFbeta1 bioactivity, detecting a 43% increase in the active TGFbeta levels in cultures exposed to Abeta and moderate acidosis. Inhibition of TGFbeta signaling abolished the neuroprotective effect of moderate acidosis. Our results show that moderate acidosis protected hippocampal cells from Abeta-mediated neurotoxicity through the increased activation and signaling potentiation of TGFbeta.