Cholesterol homeostasis: a key to prevent or slow down neurodegeneration

Neurodegeneration, a common feature for many brain disorders, has severe consequences on the mental and physical health of an individual. Typically human neurodegenerative diseases are devastating illnesses that predominantly affect elderly people, progress slowly, and lead to disability and premature death; however they may occur at all ages. Despite extensive research and investments, current therapeutic interventions against these disorders treat solely the symptoms. Therefore, since the underlying mechanisms of damage to neurons are similar, in spite of etiology and background heterogeneous, it will be of interest to identify possible trigger point of neurodegeneration enabling development of drugs and/or prevention strategies that target many disorders simultaneously. Among the factors that have been identified so far to cause neurodegeneration, failures in cholesterol homeostasis are indubitably the best investigated. The aim of this review is to critically discuss some of the main results reported in the recent years in this field mainly focusing on the mechanisms that, by recovering perturbations of cholesterol homeostasis in neuronal cells, may correct clinically relevant features occurring in different neurodegenerative disorders and, in this regard, also debate the current potential therapeutic interventions

Infusional ECarboF in patients with advanced breast cancer: A very active and well-tolerated out-patient regimen

We performed a trial using the combination of epirubicin 50 mg/m2/day 1, carboplatinum AUC 5/day 1 and continuous 5-fluorouracil (5-FU) 200 mg/m2/day (every 4 weeks for 6 months) to confirm the efficacy and low toxicity profile of this regimen in breast cancer. In 51 patients with metastatic (n = 33) or locally advanced (n=18) breast cancer the overall response rate was 86% (95% confidence interval (95% CI): 73%-94%): 94% in locally advanced and 81% metastatic disease. Grade 3-4 toxicity was low: 4% of patients presented with febrile neutropenia, 16% with severe palmar-plantar syndrome, 10% with Port-a-cath thrombosis. This study confirms the high efficacy of infusional 5-FU-based regimens and justifies further research into novel promising oral 5-FU derivative

The effects of β1-adrenergic blockade on cardiovascular oxygen flow in normoxic and hypoxic humans at exercise

At exercise steady state, the lower the arterial oxygen saturation (SaO2), the lower the O2 return (\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2}). A linear relationship between these variables was demonstrated. Our conjecture is that this relationship describes a condition of predominant sympathetic activation, from which it is hypothesized that selective β1-adrenergic blockade (BB) would reduce O2 delivery (\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}{\text{aO}}_{2} ) and \ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2} . To test this hypothesis, we studied the effects of BB on \ifmmode\expandafter\dot\else\expandafter\.\fi{Q}{\text{aO}}_{2} and \ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2} in exercising humans in normoxia and hypoxia. O2 consumption (\ifmmode\expandafter\dot\else\expandafter\.\fi{V}{\text{O}}_{2} ), cardiac output (\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}, CO_{2}\; \hbox{rebreathing}), heart rate, SaO2 and haemoglobin concentration were measured on six subjects (age 25.5±2.4years, mass 78.1±9.0kg) in normoxia and hypoxia (inspired O2 fraction of 0.11) at rest and steady-state exercises of 50, 100, and 150W without (C) and with BB with metoprolol. Arterial O2 concentration (CaO2), \ifmmode\expandafter\dot\else\expandafter\.\fi{Q}{\text{aO}}_{2}, and \ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2} were then computed. Heart rate, higher in hypoxia than in normoxia, decreased with BB. At each \ifmmode\expandafter\dot\else\expandafter\.\fi{V}{\text{O}}_{2} , \ifmmode\expandafter\dot\else\expandafter\.\fi{Q} was higher in hypoxia than in normoxia. With BB, it decreased during intense exercise in normoxia, at rest, and during light exercise in hypoxia. SaO2 and CaO2 were unaffected by BB. The \ifmmode\expandafter\dot\else\expandafter\.\fi{Q}{\text{aO}}_{2} changes under BB were parallel to those in \ifmmode\expandafter\dot\else\expandafter\.\fi{Q}. \ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2} was unaffected by exercise in normoxia. In hypoxia the slope of the relationship between \ifmmode\expandafter\dot\else\expandafter\.\fi{Q}{\text{aO}}_{2} and \ifmmode\expandafter\dot\else\expandafter\.\fi{V}{\text{O}}_{2} was lower than 1, indicating a reduction of \ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2} with increasing workload. \ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2} was a linear function of SaO2 both in C and in BB. The line for BB was flatter than and below that for C. The resting \ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2} in normoxia, lower than the corresponding exercise values, lied on the BB line. These results agree with the tested hypothesis. The two observed relationships between \ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2} and SaO2 apply to conditions of predominant sympathetic or vagal activation, respectively. Moving from one line to the other implies resetting of the cardiovascular regulatio

In spite of D’Annunzio: Recoding femininity in Trionfo della morte

Ad un’analisi critica, la figura di Ippolita Sanzio in Trionfo della morte sembra oscillare tra rappresentazioni ideali e spirituali. Mutuando da Adriana Cavarero la nozione di “furto concettuale”, è possibile rileggere il corpo erotico di Ippolita come sistema semiotico capace di sfuggire al fallocentrisimo del suo creatore. Così, malgrado sia frutto del pensiero maschile, Ippolita contribuisce alla rappresentazione della soggettività femminile che può essere interpretata fuori dai canoni tradizionali del sistema patriarcale. Infine, l’oscillazione di Ippolita minacia la nozione di opposizioni incontaminate su cui si fonda la struttura binaria occidentale.Article text in Englis

Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06)

In this trial, stopping bevacizumab after completion of induction chemotherapy was associated with a shorter time to progression, but no statistically significant difference in overall survival compared with the bevacizumab continuation strategy. Non-inferiority could not be demonstrated. Treatment costs are substantially higher for continuous bevacizumab treatmen

Una descripción de casos de colecistitis, en la provincia de Chiriquí, del 2021 al 2023.

Introduction: Inflammatory pathologies of the gallbladder are frequent cause of morbidity worldwide. Although there are different etiologies for acute and chronic conditions, the vast majority are associated with gallstones. Materials and methods: A search was carried out in our database of cases received and diagnosed from January 1st, 2021 to December 31st, 2023. Data was captured by diagnosis, year, gender, age, stone size and stone thickness. the gallbladder wall. Results: A total of 198 cases were found. By gender, 145 (73.23%) cases were found in women and 53 (26.77%) in men. The age stated in the histopathological study request was available in 155 cases, comprising patients between 18 and 90 years old, with an average age of 51 years. Of the 198 cases, 28 were diagnosed as acute cholecystitis and 170 as chronic. Conclusion: Almost three quarters of the cases (72.23%) correspond to women and that by age group, two peaks of the curve are observed, one from 30 to 39 years (14.48%) and another from 60 to 69 years (17.24% ). The same trend by age group can be found in acute, acalculous cholecystitis, but in terms of acute, calculous cholecystitis, the peaks are seen 10 years earlier, in the groups of 20 to 29 years and 50 to 59 years, respectively. In men, it is between 30 and 69 years old, which represents a cumulative percentage of 60.37%.Introducción: Las patoloías inamatorias de la vesícula biliar son causas frecuentes de morbilidad a nivel mundial. Aunque hay diferentes etiologías para cuadros agudos y crónicos, la inmensa mayoría están asociados a cálculos biliares. Materiales y métodos: Se realizó una búsqueda en nuestra base de datos de casos recibidos y diagnosticados del 1 de enero del 2021 al 31 de diciembre del 2023. Se captaron los datos por diagnóstico, año, género, edad, tamaño del cálculo y espesor de la pared vesicular. Resultados: Se encontrararon un total de 198 casos. Por género se encontraron 145 (73.23%) casos en mujeres y 53 (26.77%) en hombres. Se contó con edad reseñada en la solicitud de estudio histopatológico en 155 casos, que comprenden pacientes entre 18 y 90 años, con una edad promedio de 51 años. De los 198 casos, 28 fueron diagnosticados como colecistitis aguda y 170 como crónica. Conclusión: Casi tres cuartas partes de los casos (72.23%) corresponden a mujeres y que por grupo de edad se observan dos cimas a la curva, uno de 30 a 39 años (14.48%) y otro de 60 a 69 años (17.24%). La misma tendencia por grupo de edad se puede encontrar en las colecistitis aguda, acalculosas, pero en cuanto a colecistitis aguda, calculosas, las cimas se ven 10 años antes, en los grupos de 20 a 29 años y 50 a 59 años, respectivamente. En hombres, se encuentra entre los 30 a 69 años, lo que representa un porcentaje acumulado de 60.37%