Con el Fuser por los caminos de su ciencia

Se realizó un estudio histórico-lógico acerca de la labor del Che en la Medicina, con el objetivo de valorar sus proyecciones como profesional de la salud y lo que ha aportado a las nuevas generaciones de galenos. Se confirmó que su labor como médico es trascendente, sobre todo desde el punto de vista del aporte ético-moral a la medicina con la concepción del médico social, que estuvo reforzada con sus viajes por América y que contribuyeron a la consolidación del pensamiento médico social del Che, que vivió en carne propia las múltiples necesidades que presentaban los pobladores de la América toda. Se gradúa como médico el 11 de abril de 1953, en la Universidad de Buenos Aires y luego de su encuentro con Fidel en México y de involucrarse en la lucha revolucionaria de Cuba, tendría que definir entre médico y guerrillero

Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction

INTRODUCTION: The structural correspondence of neurodevelopmental impairments related to intrauterine growth restriction (IUGR) that persists later in life remains elusive. Moreover, early postnatal stimulation strategies have been proposed to mitigate these effects. Long-term brain connectivity abnormalities in an IUGR rabbit model and the effects of early postnatal environmental enrichment (EE) were explored. MATERIALS AND METHODS: IUGR was surgically induced in one horn, whereas the contralateral one produced the controls. Postnatally, a subgroup of IUGR animals was housed in an enriched environment. Functional assessment was performed at the neonatal and long-term periods. At the long-term period, structural brain connectivity was evaluated by means of diffusion-weighted brain magnetic resonance imaging and by histological assessment focused on the hippocampus. RESULTS: IUGR animals displayed poorer functional results and presented altered whole-brain networks and decreased median fractional anisotropy in the hippocampus. Reduced density of dendritic spines and perineuronal nets from hippocampal neurons were also observed. Of note, IUGR animals exposed to enriched environment presented an improvement in terms of both function and structure. CONCLUSIONS: IUGR is associated with altered brain connectivity at the global and cellular level. A strategy based on early EE has the potential to restore the neurodevelopmental consequences of IUGR

Anti-CXCR4 Antibody Combined With Activated and Expanded Natural Killer Cells for Sarcoma Immunotherapy

Sarcoma is one of the most severe forms of pediatric cancer and current therapies -chemotherapy and surgery- fail to eradicate the disease in half of patients. Preclinical studies combining new therapeutic approaches can be useful to design better therapies. On one hand, it is known that CXCR4 expression is implicated in rhabdomyosarcoma progression, so we analyzed relapses and chemotherapy-resistant rhabdomyosarcoma tumors from pediatric patients and found that they had particularly high levels of CXCR4 expression. Moreover, in assays in vitro, anti-CXCR4 blocking antibody (MDX1338) efficiently reduced migration and invasion of alveolar rhabdomyosarcoma RH30 cells. On the other hand, activated and expanded natural killer (NKAE) cell therapy showed high cytotoxicity against sarcoma cells in vitro and completely inhibited RH30 tumor implantation in vivo. Only the combination of MDX1338 and NKAE treatments completely suppressed metastasis in mice. In this study, we propose a novel therapeutic approach based on anti-CXCR4 blocking antibody in combination with NKAE cell therapy to prevent rhabdomyosarcoma tumor implantation and lung metastasis. These results provide the first evidence for the efficacy of this combined immunotherapy for preventing sarcoma disease dissemination.This work was supported in part by the National Health Service of Spain, Instituto de Salud Carlos III (ISCIII), FONDOS FEDER grant (FIS) PI15/00973; Asociacion Espanola Contra el Cancer to AP-M; CRIS Foundation to Beat Cancer grant to JV, LF, and AE; and Patients' Support Associations Fundacion Mari Paz Jimenez Casado and La Sonrisa de Alex to MV and the research project

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Acción farmacológica de extractos y principios activos del género Hemerocallis

El género Hemerocallis es originario de Asia donde las plantas de algunas de sus especies han sido utilizadas en la alimentación y en la medicina tradicional. Estudios recientes están revelando la gran variedad de acciones farmacológicas que poseen tanto sus extractos como los metabolitos aislados de sus flores, partes aéreas y sus raíces lo que justifica el creciente interés de la Industria Farmacéutica por las plantas de este género. Hemos querido poner en evidencia la importancia de este género como fuente de nuevos metabolitos secundarios y el interés potencial de los mismos para la elaboración o el diseño de medicamentos más eficaces para tratamiento de algunas de las enfermedades más preocupantes en nuestro siglo. Datos recientes han mostrado que algunos de los compuestos sintetizados por estas plantas como la rutina, la hesperidina o las kwanzoquinonas podrían ser los responsables de las actividades antidepresiva, antioxidante, hipoglucemiante, hipnótica, lipolítica, antitumoral y antiparasitaria y explicarían el porqué de uso desde hace milenios por la medicina china.Plants of the genus Hemerocallis are native to Asia where some species of this genus are been used in food and traditional medicine. Recent studies have reveal the wide variety of pharmacological properties associated with extracts and isolated metabolites obtained from the flowers, aerial parts and roots of these plants. This is one reason for the growth in the pharmaceutical industry's interest in Hemerocallis. We wanted to highlight the importance of this genus as a new source of secondary metabolites. Such molecules might have the potential to provide compounds that could lead to the development of new medicines to treat diseases for which a pressing need exists for more effective therapies. Recent data have show that some of the compounds synthesized by Hemerocallis plants such as rutin, hesperidin or kwanzoquinone provide a range of beneficial medicinal effects. For example, some of these molecules have antidepressant or, antioxidant or, anticancer or, antiparasitic properties. This might explain why plant extracts containing such compounds have been used for millennia Chinese medicine

Cell fusion enhances energy metabolism of mesenchymal tumor hybrid cells to sustain their proliferation and invasion

Abstract Background Cell-to-cell fusion is emerging as a key element of the metastatic process in various cancer types. We recently showed that hybrids made from the spontaneous merging of pre-malignant (IMR90 E6E7, i.e. E6E7) and malignant (IMR90 E6E7 RST, i.e. RST) mesenchymal cells recapitulate the main features of human undifferentiated pleomorphic sarcoma (UPS), with a highly rearranged genome and increased spreading capacities. To better characterize the intrinsic properties of these hybrids, we investigated here their metabolic energy profile compared to their parents. Results Our results unveiled that hybrids harbored a Warburg-like metabolism, like their RST counterparts. However, hybrids displayed a much greater metabolic activity, enhancing glycolysis to proliferate. Interestingly, modifying the metabolic environmental conditions through the use of 5-aminoimidazole-4-carbox-amide-1-β-D-ribofuranoside (AICAR), an activator of the 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK), specifically reduced the growth of hybrids, and also abrogated the invasive capacity of hybrids displaying enhanced glycolysis. Furthermore, AICAR efficiently blocked the tumoral features related to the aggressiveness of human UPS cell lines. Conclusion Altogether, our findings strongly suggest that hybrids rely on higher energy flux to proliferate and that a drug altering this metabolic equilibrium could impair their survival and be potentially considered as a novel therapeutic strategy

Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; The structural correspondence of neurodevelopmental impairments related to intrauterine growth restriction (IUGR) that persists later in life remains elusive. Moreover, early postnatal stimulation strategies have been proposed to mitigate these effects. Long-term brain connectivity abnormalities in an IUGR rabbit model and the effects of early postnatal environmental enrichment (EE) were explored. &lt;b&gt;&lt;i&gt;Materials and Methods:&lt;/i&gt;&lt;/b&gt; IUGR was surgically induced in one horn, whereas the contralateral one produced the controls. Postnatally, a subgroup of IUGR animals was housed in an enriched environment. Functional assessment was performed at the neonatal and long-term periods. At the long-term period, structural brain connectivity was evaluated by means of diffusion-weighted brain magnetic resonance imaging and by histological assessment focused on the hippocampus. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; IUGR animals displayed poorer functional results and presented altered whole-brain networks and decreased median fractional anisotropy in the hippocampus. Reduced density of dendritic spines and perineuronal nets from hippocampal neurons were also observed. Of note, IUGR animals exposed to enriched environment presented an improvement in terms of both function and structure. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; IUGR is associated with altered brain connectivity at the global and cellular level. A strategy based on early EE has the potential to restore the neurodevelopmental consequences of IUGR.</jats:p