Gonzalo Farías

University of Chile

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Ricardo B. Maccioni

University of Chile

Leonardo Guzmán‐Martínez

Autonomous University of San Luis Potosí

Carolina Delgado

Hospital Universitario Puerta del Mar

Andrea Slachevsky

University of Chile

Inelia Morales

University of Chile

Patricio Fuentes

Clínica Las Condes

Agustín Ibáñez

Adolfo Ibáñez University

Paul H. Délano

University of Chile

Mario A. Parra

University of Strathclyde

Carlos Guevara

Multimedia Nusantara University

Cooperative Institutions

University of Chile

Consejo Nacional de Investigaciones Científicas y Técnicas

University of California, San Francisco

Global Brain Health Institute

University of Buenos Aires

Universidade de São Paulo

Hospital Clínico de la Universidad de Chile

Trinity College Dublin

Pontificia Universidad Católica de Chile

Adolfo Ibáñez University

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Exploring Neuroprotection against Radiation-Induced Brain Injury: A Review of Key Compounds

NeuroSci (2024)

Lucas González-Johnson Ariel Fariña Gonzalo Farías Gustavo Zomosa Víctor Pinilla-González

Brain radiation is a crucial tool in neuro-oncology for enhancing local tumor control, but it can lead to mild-to-profound and progressive impairments in cognitive function. Radiation-induced brain injury is a significant adverse effect of radiotherapy for cranioencephalic tumors, primarily caused by indirect cellular damage through the formation of free radicals. This results in late neurotoxicity manifesting as cognitive impairment due to free radical production. The aim of this review is to highlight the role of different substances, such as drugs used in the clinical setting and antioxidants such as ascorbate, in reducing the neurotoxicity associated with radiation-induced brain injury. Currently, there is mainly preclinical and clinical evidence supporting the benefit of these interventions, representing a cost-effective and straightforward neuroprotective strategy.

Neurotoxicity

Brain damage

Adverse Outcome Pathway

10.3390/neurosci5040034

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Sex Differences in the Diagnosis Latency of Parkinson’s Disease in Latin America

Parkinsonism & Related Disorders (2025)

Janvi Ramchandra Miguel Inca‐Martinez Thiago Peixoto Leal Henry Mauricio Chaparro-Solano Amira Salim

10.1016/j.parkreldis.2025.107344

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Encephalitis Associated to Metabotropic Glutamate Receptor 5 (mGluR5) Antibodies in Cerebrospinal Fluid

Frontiers in Immunology (2018)

Carlos Guevara Gonzalo Farías Carlos Silva‐Rosas Pablo Cisternas Alarcón Gabriel Abudinén

A 68-years-old Hispanic man, complained of night sweats, low grade fewer, unexplained weight loss, and memory problems over 3 months. Abdominal tomography showed multiple intra-abdominal adenopathy and biopsy confirmed classic Hodgkin's lymphoma. He commenced treatment with chemotherapy. Three months later, he had acute onset of inattention, auditory hallucinations and alterations of anterograde memory. The patient developed psychomotor agitation, unresponsive to a combination of neuroleptics and benzodiazepines. Brain MRI showed a small established cerebellar infarction. Electroencephalogram was normal. Tests for toxic metabolic encephalopathy were negative. One oligoclonal IgG bands was found in the Cerebrospinal fluid (CSF), which was not observed in corresponding serum, but cell count and protein were normal. Extensive testing for infectious encephalitis was unremarkable. CSF testing for commercially available neural and non-neural autoantibodies was negative. The patient fulfilled the Gultekin diagnostic criteria for paraneoplastic limbic encephalitis and methylprednisolone IV 1g/d for 5 days was given. He recovered rapidly, with progressive improvement in memory and psychomotor agitation. After treatment commenced, results for antibodies to mGluR5 in CSF taken prior to treatment were returned as positive. mGluR5 is found on post-synaptic terminals of neurons and microglia and is expressed primarily in the hippocampus and amygdala. This case highlights the difficulties in diagnosing this type of encephalitis: the CSF did not show pleocytosis, the MRI showed only chronic change and the electroencephalogram was normal. The dramatic recovery after methylprednisolone help to better characterized the clinical spectrum of auto-immune encephalitis. Diagnosing anti mGlutR5 encephalitis may lead to potentially highly effective treatment option and may anticipate the diagnostic of a cancer. A high index of suspicion is needed to avoid missed diagnosis. In patients with unexplained encephalitis, testing for antibodies to mGluR5 in CSF and serum should be considered. When there is a reasonable index of suspicion of auto-immune encephalitis, treatment should not be delayed for the antibody results.

Limbic Encephalitis

Pleocytosis

Brain biopsy

Autoimmune encephalitis

10.3389/fimmu.2018.02568

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Tau Oligomers as Potential Targets for Alzheimer’s Diagnosis and Novel Drugs

Frontiers in Neurology (2013)

Leonardo Guzmán‐Martínez Gonzalo Farías Ricardo B. Maccioni

A cumulative number of approaches have been carried out to elucidate the pathogenesis of Alzheimer´s disease (AD). Tangle formation has been identified as a major event involved in the neurodegenerative process, due to the conversion of either soluble peptides or oligomers into insoluble filaments. Most of recent studies share in common the observation that formation of tau oligomers and the subsequent pathological filaments arrays is a critical step in AD etiopathogenesis. Oligomeric tau species appear to be neurotoxic for neuronal cells, and therefore appear as an appropriate target for the design of molecules that may control morphological and functional alterations leading to cognitive impairment. Thus, current therapeutic strategies are aimed at three major types of molecules: 1) Inhibitors of protein kinases and phosphatases that may control neuronal degeneration, 2) Methylene blue, and 3) Natural phytocomplexes and polyphenolics compounds able to either inhibit the formation of tau filaments or disaggregate them. Only a few polyphenolic molecules have emerged to prevent tau aggregation. Fulvic acid, a humic substance, has a potential activity to protect cognitive impairment. In fact, formation of paired helical filaments (PHFs) in vitro, is inhibited by fulvic acid affecting the length of fibrils and their morphology.

Tangle

Tau Pathology

Tau protein

10.3389/fneur.2013.00167

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Alzheimer’s Disease as a potential diabetes type III: Pilot Study of comorbidities related to AD

Alzheimer s & Dementia (2023)

Andrea Gerard Gonzalez Camila Calfío Ricardo B. Maccioni Gonzalo Farías Patricio Fuentes

Abstract Background Alzheimer’s disease (AD) is the most prevalent cause of dementia in the elderly population. It is a multifactorial disease in which metabolic dysregulation and glucose metabolism impairment plays a major role in the etiopathogenesis. In this research, we evaluate the comorbidities in a clinical trial for the novel biomarker Alz‐tau®, based on platelet tau, in cognitive healthy controls, mild‐cognitive impairment (MCI) and AD patients, in particular TII diabetes. Alterations in this biomarker appear to indicate high risk of developing AD, as demonstrated in previous clinical trials. Methods From a cohort of 111 subjects, neuropsychology tests were performed to assign the respective group (control, MCI or AD). In addition, a health questionnaire to evaluate comorbidities. For the Alz‐tau® biomarker, platelets were obtained from plasma by centrifugation, lysed to obtain platelet protein extracts (containing tau) and further processed for a western blot analysis. The immuno‐ detection was performed with our novel monoclonal antibody tau51, which detects two variants of tau protein: a high molecular weight variant (HMW) and a low molecular weight variant (LMW). The results obtained were subjected to a densitometric analysis with ImageJ and the algorithm HWM/LMW was obtained. Result From 111 patients, 17 presented diabetes type 2 as a comorbidity (15,3%). Out of them, 11 were cognitive healthy subjects (64.7%), 4 EA patients (23.5%) and 2 MCI (11.8%). Out of the control patients, 6 have the Alz‐tau® biomarker altered (54.5%), which was similar to what was observed in the EA patients (2 patients, 50%) and the MCI (1 patient, 50%). Of the 17 patients with diabetes, 53% presented an altered Alz‐tau® biomarker (cut‐off 1.2 algorithm), which is considered a risk factor for AD. It should be considered that the area under the curve (AUC) of this novel biomarker Alz‐tau® is 0.69, appropriate for a novel technique. Conclusion Here, we discovered that this early detection biomarker is correlated with the high‐risk factor of having AD in the future, since non‐symptomatic subjects exhibited an altered biomarker. Moreover, more than 50% of the TII diabetic positive cognitive healthy controls, exhibit an altered biomarker, sustaining our hypothesis of the correlation between glucose‐metabolism impairment, AD and oligomeric tau.

10.1002/alz.078278

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Can Nutraceuticals Prevent Alzheimer's Disease? Potential Therapeutic Role of a Formulation Containing Shilajit and Complex B Vitamins

Archives of Medical Research (2012)

Carlos Carrasco‐Gallardo Gonzalo Farías Patricio Fuentes Fernando Crespo Ricardo B. Maccioni

Nutraceutical

Expansive

10.1016/j.arcmed.2012.10.010

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Platelet Tau Pattern Correlates with Cognitive Status in Alzheimer's Disease

Journal of Alzheimer s Disease (2012)

Gonzalo Farías Patricio Pérez Andrea Slachevsky Ricardo B. Maccioni

Platelets are major reservoirs of circulating amyloid-β and amyloid-β protein precursor (AβPP) and have been postulated as a reliable source for biological markers of Alzheimer's disease (AD). We have recently demonstrated that tau is also present in

Tau protein

Negative correlation

Cognitive Decline

10.3233/jad-2012-120304

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Estrategias no farmacológicas en personas con Demencia Avanzada: reporte de un caso.

Revista chilena de neuro-psiquiatría (2021)

Fabrizio Acevedo Pérez Carolina Delgado Gonzalo Farías

En el curso de la demencia, la etapa avanzada se caracteriza por un deterioro cognitivo y fÃsico severo, definiÃ©ndola como una etapa que incluye profundos dÃ©ficits de memoria, habilidades verbales mÃnimas, incapacidad para deambular de forma independiente, incontinencia urinaria y fecal, y necesidad de asistencia para realizar cualquier actividad de la vida diaria bÃ¡sica. El presente reporte tiene por objeto comunicar un caso de una usuaria con 89 aÃ±os con demencia avanzada que acude a control neurolÃ³gico en compaÃ±Ãa de su familia, quienes solicitan informaciÃ³n de cÃ³mo mejorar la calidad de vida en esa etapa. Describimos una propuesta desde el enfoque de cuidados paliativos, especÃficamente la concepciÃ³n terapÃ©utica activa, como una guÃa que permita observar a la persona no sÃ³lo desde el buen morir, sino tambiÃ©n desde la incorporaciÃ³n de una actitud proactiva en funciÃ³n del bienestar. Este enfoque permite facilitar experiencias placenteras, definidas dentro del marco de intervenciones no farmacolÃ³gicas, las cuales han demostrado en la Ãºltima dÃ©cada importantes beneficios en personas con demencia avanzada, permitiendo individualizar las estrategias de intervenciÃ³n en esta etapa de la enfermedad.

Persona

10.4067/s0717-92272021000400368

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La asimetría de información bursátil: entorno chileno, spread intradiario y factores que le afectan.

DOAJ (DOAJ: Directory of Open Access Journals) (2015)

Ricardo Campos-Espinoza Gonzalo Farías Norman Díaz

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Determinación y análisis comparativo de gasto cardíaco en enfermos críticos mediante Doppler transesofágico y termodilución en bolos: Experiencia preliminar

Revista médica de Chile (2005)

Max Andresen Mauricio Henríquez Marcelo Mercado F Gonzalo Farías Carmen Castillo S

Comparison of cardiac output measurement in critical patients using transesophageal Doppler or thermodilution.A preliminary report Background: Cardiac output can be measured non invasively by transesophageal Doppler.This is an alternative to measure it by thermodilution with a catheter in the pulmonary artery.Aim: To compare both methods of cardiac output measurement.Material and methods: Simultaneous measurement of cardiac output by transesophageal Doppler and thermodilution with a catheter in the pulmonary artery in four male critical patients, aged 60±12 years, hospitalized in a University Hospital.The Bland and Altman method to compare the concordance between two measurements, was used.Results: Forty measurements were performed.The results of both methods had a correlation coefficient of 0.98.According to the Bland and Altman method, the difference between both methods was -0.5 L with a precision of 0.52 L/min (95% confidence interval -1.51 to 0.52 L/min).Considering that a change between two sequential measurements is considered significant when the difference is more than 15%, both measurements agreed in 83% of cases, that there was a change in cardiac output.Conclusions: Transesophageal Doppler is a promising non invasive technique to measure cardiac output in critical care patients.It becomes a valid alternative to the thermodilution technique.This preliminary experience must be confirmed in a larger series (Rev Méd Chile 2005; 133: 761-6).

Pulmonary artery catheter

Concordance correlation coefficient

Concordance

10.4067/s0034-98872005000700002

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