Optimization of iron oxide nanoparticles for MRI-guided magnetic hyperthermia tumor therapy: reassessing the role of shape in their magnetocaloric effect.

Superparamagnetic iron oxide nanoparticles have hogged the limelight in different fields of nanotechnology. Surprisingly, notwithstanding the prominent role played as agents in magnetic hyperthermia treatments, the effects of nanoparticle size and shape on the magnetic hyperthermia performance have not been entirely elucidated yet. Here, spherical or cubical magnetic nanoparticles synthesized by a thermal decomposition method with the same magnetic and hyperthermia properties are evaluated. Interestingly, spherical nanoparticles displayed significantly higher magnetic relaxivity than cubic nanoparticles; however, comparable differences were not observed in specific absorption rate (SAR), pointing out the need for additional research to better understand the connection between these two parameters. Additionally, the as-synthetized spherical nanoparticles showed negligible cytotoxicity and, therefore, were tested in vivo in tumor-bearing mice. Following intratumoral administration of these spherical nanoparticles and a single exposure to alternating magnetic fields (AMF) closely mimicking clinical conditions, a significant delay in tumor growth was observed. Although further in vivo experiments are warranted to optimize the magnetic hyperthermia conditions, our findings support the great potential of these nanoparticles as magnetic hyperthermia mediators for tumor therapy.

Engineering of stealth (maghemite/PLGA)/chitosan (core/shell)/shell nanocomposites with potential applications for combined MRI and hyperthermia against cancer.

(Maghemite/poly(d,l-lactide-co-glycolide))/chitosan (core/shell)/shell nanoparticles have been prepared reproducibly by nanoprecipitation solvent evaporation plus coacervation (production performance ≈ 45%, average size ≈ 325 nm). Transmission electron microscopy, energy dispersive X-ray spectroscopy, electrophoretic determinations, and X-ray diffraction patterns demonstrated the satisfactory embedment of iron oxide nanocores within the solid polymer matrix and the formation of an external shell of chitosan in the nanostructure. The adequate magnetic responsiveness of the nanocomposites was characterized in vitro by hysteresis cycle determinations and by visualization of the nanosystem under the influence of a 0.4 T permanent magnet. Safety and biocompatibility of the (core/shell)/shell particles were based on in vitro haemocompatibility studies and cytotoxicity tests against HFF-1 human foreskin fibroblasts and on ex vivo toxicity assessments on tissue samples from Balb/c mice. Transversal relaxivities, determined in vitro at a low magnetic field of 1.44 T, demonstrated their capability as T2 contrast agents for magnetic resonance imaging, being comparable to that of some iron oxide-based contrast agents. Heating properties were evaluated in a high frequency alternating electromagnetic gradient: a constant maximum temperature of ≈46 °C was generated within ≈50 min, while antitumour hyperthermia tests on T-84 colonic adenocarcinoma cells proved the relevant decrease in cell viability (to ≈ 39%) when treated with the nanosystem under the influence of that electromagnetic field. Finally, in vivo magnetic resonance imaging studies and ex vivo histology determinations of iron deposits postulated the efficacy of chitosan to provide long-circulating capabilities to the nanocomposites, retarding nanoparticle recognition by the mononuclear phagocyte system. To our knowledge, this is the first study describing such a type of biocompatible and long-circulating nanoplatform with promising theranostic applications (biomedical imaging and hyperthermia) against cancer.

Fluoxetine oral treatment discloses 5-HT1D receptor as vagoinhibitor of the cardiac cholinergic neurotransmission in rat.

Although depression and cardiovascular diseases are related, the role of antidepressants such as fluoxetine (increasing serotonin levels) within cardiac regulation remains unclear. We aimed to determine whether fluoxetine modifies the pharmacological profile of serotonergic influence on vagal cardiac outflow. Rats were treated with fluoxetine (10 mg/kg per day; p.o.) for 14 days or equivalent volumes of drinking water (control group); then, they were pithed and prepared for vagal stimulation. Bradycardic responses were obtained by electrical stimulation of the vagal fibers (3, 6, and 9 Hz) or i.v. acetylcholine (ACh; 1, 5, and 10 µg/kg). The i.v. administration of 5-hydroxytryptamine (5-HT; 10 and 50 µg/kg) inhibited the vagally induced bradycardia. 5-CT (5-HT1/7 agonist) and L-694,247 (5-HT1D agonist) mimicked the serotonin inhibitory effect while α-methyl-5-HT (5-HT2 agonist) was devoid of any action. SB269970 (5-HT7 antagonist) did not abolish 5-CT inhibitory action on the electrically induced bradycardia. Pretreatment with LY310762 (5-HT1D antagonist) blocked the effects induced by L-694,247 and 5-CT. 5-HT and 5-CT failed to modify the bradycardia induced by exogenous ACh. Our outcomes suggest that fluoxetine treatment modifies 5-HT modulation on heart parasympathetic neurotransmission in rats, evoking inhibition of the bradycardia via prejunctional 5-HT1D in pithed rats.

Acompañar al paciente oncológico en la etapa final de la vida / Accompanying oncology patients during their end-of-life stage

OBJETIVO: analizar los cuidados enfermeros dirigidos al ámbito emocional de pacientes oncológicos en la fase final de su vida. MÉTODO: revisión narrativa mediante búsqueda bibliográfica en bases de datos de Ciencias de la Salud, buscadores, sitios web y publicaciones periódicas relacionadas con la temática. RESULTADOS: de los 64 artículos obtenidos se han seleccionado 35, destacando como aspectos relevantes en el cuidado emocional enfermero la comunicación, el acompañamiento, el counseling y el apoyo familiar. El profesional enfermero es la figura clave en el acompañamiento en la etapa final de la vida del paciente y sus familiares, quienes relacionan el abordaje emocional con una atención de calidad durante este proceso. Por ello, unos buenos cuidados emocionales llevados a cabo por la enfermera en este momento único y personal de sus vidas serán recordados para siempre por sus familiares. CONCLUSIONES: la existencia en la actualidad de diversos profesionales especialistas, el desconocimiento de su función exacta y el hecho de que estén presentes o no en un equipo asistencial, hace que en algunas ocasiones la función del profesional enfermero sea muy difícil de delimitar, aspecto sobre el cual se debería seguir investigando

OBJECTIVES: to learn about the role of the Nursing Professional during the paracentesis procedure, based on scientific evidence, with the aim of designing clinical guidelines, and improving the quality of patient care. METHOD: a narrative review, where a bibliographic search was conducted in the Medline, Cinahl, Cochrane Library and UpToDate databases, as well as in Clinical Guidelines Databases: Guidelines International Networks, Practice Guideline, National Guideline Clearinghouse, New Zealand Clinical Guidelines Group, Primary Care Clinical Practice Guidelines and Scottish Intercollegiate Guidelines Network. The Clinical Guidelines Databases from the Hospital General Universitario Gregorio Marañón in Madrid, the Complexo Hospitalario Universitario de Vigo and the International Ascites Club were also consulted. RESULTS AND CONCLUSIONS: fifteen articles were selected, and after the analysis of the findings obtained, three categories were established, describing the role played by nurses during paracentesis: the care provided by nurses before, during and after the procedure. Apart from each of the nursing interventions at each stage of said procedure, the presence of a nursing professional to assess the patient in a holistic way was considered very important. In the near future, clinical guidelines will be implemented, that will have been designed based on the results obtained, and all aspects considered for these guidelines will be reviewed at one year, as well as the scientific literature which may have been published, assessing those items to be improved. Among the limitations of this study, we must point out the low methodological quality of the articles selected, and the little bibliography available about this matter; therefore, it would be convenient to conduct studies under stricter methodological designs, with higher quality, in order to have a higher impact on clinical practice

Identification of polyphenols from antiviral Chamaecrista nictitans extract using high-resolution LC-ESI-MS/MS.

Chamaecrista nictitans (L) extract possesses antiviral properties; it acts against the herpes simplex virus, and this may be attributed to its constituent phenolics. Here, high-resolution LC-ESI-MS/MS is used to identify the phenolic components of the most potent fraction of the extract. The fraction is a complex mixture rich in oligomeric proanthocyanidins with a high content of monohydroxyphenol moieties ((epi)fisetinidol, (epi)afzelechin and (epi)guibourtinidol) and A-type linkages, uncommon in other proanthocyanidin-rich phenolic extracts, such as those from grape seeds or pine bark. As monohydroxyphenolic structures and A-type linkages have been related to antiviral effects, particularly through the inhibition of late transcription, we suggest that the fraction of C. nictitans extract exerts its action through a particularly effective combination of proanthocyanidins that include these two structural features.

Effect of pressurized hot water extraction on antioxidants from grape pomace before and after enological fermentation.

Grape pomace was extracted with pressurized hot water at laboratory scale before and after fermentation to explore the effects of fermentation and extraction temperature (50-200 °C) and time (5 and 30 min) on total extracted antioxidant levels and activity and to determine the content and recovery efficiency of main grape polyphenols, anthocyanins, and tannins. Fermented pomace yielded more total antioxidants (TAs), antioxidant activity, and tannins, than unfermented pomace but fewer anthocyanins. Elevating the extraction temperature increased TA extraction and antioxidant activity. Maximum anthocyanin extraction yields were achieved at 100 °C and at 150 °C for tannins and tannin-anthocyanin adducts. Using higher temperatures and longer extraction times resulted in a sharp decrease of polyphenol extraction yield. Relevant proanthocyanidin amounts were extracted only at 50 and 100 °C. Finally, TA recovery and activity were not directly related to the main polyphenol content when performing pressurized hot water grape pomace extraction.

Profile of urinary and fecal proanthocyanidin metabolites from common cinnamon (Cinnamomum zeylanicum L.) in rats.

Cinnamon (Cinnamomum zeylanicum L.) bark is widely used as a spice and in traditional medicine. Its oligomeric and polymeric proanthocyanidins are believed to be partly responsible for the beneficial properties of the plant. We describe here the metabolic fate of cinnamon proanthocyanidins in the urine and feces of rats fed a suspension of the whole bark. The metabolites include ten mono-, di-, and tri- conjugated (epi)catechin phase II metabolites and more than 20 small phenolic acids from intestinal microbial fermentation. Some of these are sulfated conjugates. Feces contain intact (epi)catechin and dimers. This suggests that free radical scavenging species are in contact with the intestinal walls for hours after ingestion of cinnamon. The phenolic metabolite profile of cinnamon bark in urine is consistent with a mixture of proanthocyanidins that are depolymerized into their constitutive (epi)catechin units as well as cleaved into smaller phenolic acids during their transit along the intestinal tract, with subsequent absorption and conjugation into bioavailable metabolites.

Punicalagin and catechins contain polyphenolic substructures that influence cell viability and can be monitored by radical chemosensors sensitive to electron transfer.

Plant polyphenols may be free radical scavengers or generators, depending on their nature and concentration. This dual effect, mediated by electron transfer reactions, may contribute to their influence on cell viability. This study used two stable radicals (tris(2,3,5,6-tetrachloro-4-nitrophenyl)methyl (TNPTM) and tris(2,4,6-trichloro-3,5-dinitrophenyl)methyl (HNTTM)) sensitive only to electron transfer reduction reactions to monitor the redox properties of polyphenols (punicalagin and catechins) that contain phenolic hydroxyls with different reducing capacities. The use of the two radicals reveals that punicalagin's substructures consisting of gallate esters linked together by carbon-carbon (C-C) bonds are more reactive than simple gallates and less reactive than the pyrogallol moiety of green tea catechins. The most reactive hydroxyls, detected by TNPTM, are present in the compounds that affect HT-29 cell viability the most. TNPTM reacts with C-C-linked gallates and pyrogallol and provides a convenient way to detect potentially beneficial polyphenols from natural sources.

Non-extractable proanthocyanidins from grapes are a source of bioavailable (epi)catechin and derived metabolites in rats.

The non-extractable fraction of many fruit and vegetables contains putatively bioactive polyphenolic compounds that, in most cases, have not been well characterised structurally. Non-extractable proanthocyanidins (NEPA) of a polymeric nature are part of the dietary fibre fraction of food. Using liquid chromatography coupled to a mass spectrometer equipped with an electrospray ionisation chamber and a triple quadrupole mass analyser for tandem analysis (HPLC-ESI-QqQ-MS/MS) techniques, we examine the phenolic metabolites present in urine and faeces from rats 24 h after ingestion of an NEPA-rich fraction. We show that NEPA are partially depolymerised during their transit along the intestinal tract, as evidenced by the presence of (epi)catechin (EC) monomers and dimers in faeces and phase II conjugates of EC in urine. Moreover, NEPA are further metabolised by the intestinal microbiota into smaller metabolites including phenolic acids that are present in urine as both free phenolics and conjugates with glucuronate or sulphate moieties. For the first time, we report evidence that NEPA behave in vivo as a source of phenolics that are released progressively and deliver phenolic species that come into contact with the intestinal walls and are bioavailable for at least 24 h after ingestion.

Mechanisms of relaxation induced by flavonoid ayanin in isolated aorta rings from Wistar rats

Introduction: This study shows the relaxant effect induced by ayanin in aorta rings from Wistar rats linked to nitric oxide/cyclic-GMP pathway. This flavonoid is the prevalent compound obtained from Croton schiedeanus Schlecht (Euphorbiaceae), specie used in Colombian folk medicine for the treatment of arterial hypertension. Objectives: To identify possible action mechanisms of vascular relaxation induced by ayanin (quercetin 3,4',7-trimethyl ether).Methodology: Isolated aorta rings from Wistar rats obtained at the Animal House of the University of Salamanca were contracted with KCl (80 mM) or phenylephrine (PE, 10-6 M) and exposed to ayanin (10-6-10-4 M). Then, the effect of ayanin was assessed in deendothelized rings contracted with PE and in intact rings contracted with PE previously incubated with: ODQ (10-6 M), L-NAME (10-4 M), L-NAME plus D- and L-arginine (10-4 M), indomethacin (5x10-6 M), dipyridamole (3x10-7 M), glibenclamide (10-6 M), propranolol (10-6 M), verapamil (10-7 M) or atropine (3x10-5 M). In addition, the relaxant effect of acetylcholine (Ach, 10-8-3x10-4 M), and sodium nitroprusside (SNP, 10-9-3x10-5 M) was assessed in the presence and absence of ayanin (10-6 M).Results: Ayanin induced a greater concentration-dependent relaxation in vessels contracted with phenylephrine (pEC50: 5.84±0.05), an effect significantly reduced by deendothelization and by both ODQ and L-NAME. L-arginine was able to reverse the effect of L-NAME. Indomethacin weakly inhibited ayanin response. Dipyridamole, glibenclamide, propranolol, verapamil, and atropine did not affect ayanin relaxation. Ayanin did not have any effect on the relaxation elicited by acetylcholine (ACh), while weakly decreasing the relaxation induced by sodium nitroprusside (SNP).Conclusion: Ayanin induces endothelium-dependent relaxation in the rat aorta mainly related to nitric oxide/cGMP pathway, according to the response observed in the presence of L-NAME, L-arginine and ODQ.

Introdución: Este estudio muestra el efecto vasodilatador inducido por ayanina en anillos de aorta de ratas Wistar vinculado con la vía óxido nítrico/GMP-cíclico. Este flavonoide es el compuesto mayoritario aislado de Croton schiedeanus Schlecht (Euphorbiaceae), especie utilizada en la medicina popular colombiana para el tratamiento de la hipertensión arterial. Objetivos: Identificar los posibles mecanismos vasodilatadores inducidos por la ayanina (quercetin 3,4',7-trimetileter). Metodología: Se adicionó ayanina (10-6 - 10-4 M) a anillos aislados de aorta procedentes de ratas Wistar contraídos con KCl (80 mM) o fenilefrina (10-6 M). Luego se evaluó el efecto de la ayanina en anillos sin endotelio contraídos con fenilefrina y en anillos íntegros, contraídos con fenilefrina, previamente incubados con: ODQ (10-6 M), L-NAME (10-4 M), L-NAME más L- o D-arginina (10-4 M), indometacina (5x10-6 M), dipiridamol (3x10-7 M), glibenclamida (10-6 M), propranolol (10-6 M), verapamilo (10-7 M) o atropina (3x10-5 M). Además se examinó la relajación inducida por acetilcolina (Ach, 10-8-3x10-4 M) y nitroprusiato de sodio (SNP, 10-9-3x10-5 M) en presencia y ausencia de ayanina (10-6 M). Resultados: La ayanina produjo una mayor relajación en los anillos contraídos con fenilefrina (pEC50: 5.84±0.05), efecto que se redujo en anillos sin endotelio o en anillos íntegros preincubados con ODQ y L-NAME. L-arginina fue capaz de revertir la respuesta inducida por L-NAME. La indometacina inhibió discretamente la relajación generada por la ayanina. El dipyridamol, la glibenclamida, el propranolol, el verapamilo y la atropina no modificaron el efecto de la ayanina. La ayanina no afectó la relajación inducida por la acetilcolina y débilmente disminuyó la inducida por el nitroprusiato de sodio...

Arbuscular mycorrhizal fungi increased growth, nutrient uptake and tolerance to salinity in olive trees under nursery conditions.

Inoculating olive plantlets with the arbuscular mycorrhizal fungi (AMF) Glomus mosseae, Glomus intraradices or Glomus claroideum increased plant growth and the ability to acquire nitrogen, phosphorus, and potassium from non-saline as well as saline media. AMF-colonized plants also increased in survival rate after transplant. Osmotic stress caused by NaCl supply reduced stem diameter, number of shoots, shoot length and nutrients in olive plants, but AMF colonization alleviated all of these negative effects on growth. G. mosseae was the most efficient fungus in reducing the detrimental effects of salinity; it increased shoot growth by 163% and root growth by 295% in the non-saline medium, and by 239% (shoot) and by 468% (root) under the saline conditions. AMF colonization enhanced salt tolerance in terms of olive growth and nutrient acquisition. Mycorrhizal olive plants showed the lowest biomass reduction under salinity (34%), while growth was reduced by 78% in control plants. This G. mosseae effect seems to be due to increased K acquisition; K content was enhanced under salt conditions by 6.4-fold with G. mosseae, 3.4-fold with G. intraradices, and 3.7-fold with G. claroideum. Potassium, as the most prominent inorganic solute, plays a key role in the osmoregulation processes and the highest salinity tolerance of G. mosseae-colonized olive trees was concomitant with an enhanced K concentration in olive plants.