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The improvement of biodegradable metals is currently an active and promising research area for their capabilities in implant manufacturing. However, controlling their degradation rate once their surface is in contact with the physiological media is a challenge. Surface treatments are in the way of addressing the improvement of this control. Zinc is a biocompatible metal present in the human body as well as a metal widely used in coatings to prevent corrosion, due to its well-known metal protective action. These two outstanding characteristics make zinc coating worthy of consideration to improve the degradation behaviour of implants. Electrodeposition is one of the most practical and common technologies to create protective zinc coatings on metals. This article aims to review the effect of the different parameters involved in the electrochemical process on the topography and corrosion characteristics of the zinc coating. However, certainly, it also provides an actual and comprehensive description of the state-of-the-art of the use of electrodeposited zinc for biomedical applications, focusing on their capacity to protect against bacterial colonization and to allow cell adhesion and proliferation. [ABSTRACT FROM AUTHOR]

Wind energy requires accurate forecasts for adequate integration into the electric grid system. In addition, global atmospheric models are not able to simulate local winds in complex terrain, where wind farms are sometimes placed. For this reason, the use of mesoscale models is vital for estimating wind speed at wind turbine hub height. In this regard, the Weather Research and Forecasting (WRF) Model allows a user to apply different initial and boundary conditions as well as physical parameterizations. In this research, a sensitivity analysis of several physical schemes and initial and boundary conditions was performed for the Alaiz mountain range in the northern Iberian Peninsula, where several wind farms are located. Model performance was evaluated under various atmospheric stabilities and wind speeds. For validation purposes, a mast with anemometers installed at 40, 78, 90, and 118 m above ground level was used. The results indicate that performance of the Global Forecast System analysis and European Centre for Medium-Range Weather Forecasts interim reanalysis (ERA-Interim) as initial and boundary conditions was similar, although each performed better under certain meteorological conditions. With regard to physical schemes, there is no single combination of parameterizations that performs best during all weather conditions. Nevertheless, some combinations have been identified as inefficient, and therefore their use is discouraged. As a result, the validation of an ensemble prediction system composed of the best 12 deterministic simulations shows the most accurate results, obtaining relative errors in wind speed forecasts that are <15%. [ABSTRACT FROM AUTHOR]

pH-responsive nanogels (NGs) were used to prepare high-efficiency magnetic resonance imaging dual T1/T2 contrast agents for pH imaging. The polymeric NG matrix acts as a strong polydentate ligand that chelates the Mn cations in its inner cavity generating a hybrid NG structure. The Mn chelate NG is sensitive to pH changes, such that protonation induces a change of the polymer hydration state and consequent swelling. The swollen nanogel allows water molecules to enter and interact with the Mn chelate, shortening the relaxation time (switch ON) and giving rise to positive or negative contrast on T1- or T2-weighted magnetic resonance images. [ABSTRACT FROM AUTHOR]

We analyzed the modulation of serotonin on the bradycardia induced in vivo by vagal electrical stimulation in alloxan-induced long-term diabetic rats. Bolus intravenous administration of serotonin had a dual effect on the bradycardia induced either by vagal stimulation or exogenous Ach, increasing it at low doses and decreasing it at high doses of 5-hydroxytryptamine (5-HT), effect reproduced by 5-carboxamidotryptamine maleate (5-CT), a 5-HT1/7 agonist. The enhancement of the bradycardia at low doses of 5-CT was reproduced by 5-HT1A agonist 8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) and abolished by WAY-100,635, 5-HT1A antagonist. Pretreatment with 5-HT1 antagonist methiothepin blocked the stimulatory and inhibitory effect of 5-CT, whereas pimozide, 5-HT7 antagonist, only abolished 5-CT inhibitory action. In conclusion, long-term diabetes elicits changes in the subtype of the 5-HT receptor involved in modulation of vagally induced bradycardia. Activation of the 5- HT1A receptors induces enhancement, whereas attenuation is due to 5-HT7 receptor activation. This 5-HT dual effect occurs at pre- and postjunctional levels. [ABSTRACT FROM AUTHOR]

Summary: 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. [Copyright &y& Elsevier]

The application of metal-based nanoparticles (mNPs) in cancer therapy and diagnostics (theranostics) has been a hot research topic since the early days of nanotechnology, becoming even more relevant in recent years. However, the clinical translation of this technology has been notably poor, with one of the main reasons being a lack of understanding of the disease and conceptual errors in the design of mNPs. Strikingly, throughout the reported studies to date on in vivo experiments, the concepts of "tumor targeting" and "tumor cell targeting" are often intertwined, particularly in the context of active targeting. These misconceptions may lead to design flaws, resulting in failed theranostic strategies. In the context of mNPs, tumor targeting can be described as the process by which mNPs reach the tumor mass (as a tissue), while tumor cell targeting refers to the specific interaction of mNPs with tumor cells once they have reached the tumor tissue. In this review, we conduct a critical analysis of key challenges that must be addressed for the successful targeting of either tumor tissue or cancer cells within the tumor tissue. Additionally, we explore essential features necessary for the smart design of theranostic mNPs, where 'smart design' refers to the process involving advanced consideration of the physicochemical features of the mNPs, targeting motifs, and physiological barriers that must be overcome for successful tumor targeting and/or tumor cell targeting. [ABSTRACT FROM AUTHOR]

Background Serum levels of soluble urokinase-type plasminogen activator receptor (suPAR) are high in some patients with idiopathic nephrotic syndrome (INS). Given that suPAR constitutes a predictor of vascular disease and has been associated with endothelial dysfunction, we hypothesized that suPAR levels are related to endothelial activation or dysfunction in INS patients. The aims of this study were to evaluate the relationship between serum concentrations of endothelial biomarkers and suPAR in patients with different histological patterns of INS and healthy controls, and to determine the demographic, clinical and biochemical characteristics of INS patients that influence suPAR serum levels. Methods This observational, cross-sectional study included patients with INS, diagnosed with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) or membranous nephropathy (MN) by renal biopsy. Patient demographic, clinical and biochemical characteristics were recorded and blood samples were obtained at the time of diagnosis. Measurements of suPAR and endothelial molecules via serum levels were performed using Enzyme-Linked ImmunoSorbent Assay kits. Results Patients with nephrotic syndrome (n  = 152) caused by FSGS, MCD or MN had increased circulating levels of endothelial markers. suPAR levels positively correlated with age and the serum levels of almost all endothelial markers. Generally, endothelial cell molecules positively correlated with each other. suPAR levels were not associated with the histopathological pattern of INS. Conclusions In patients with INS secondary to FSGS, MCD and NM, circulating levels of suPAR are independent of the primary renal disease, and significantly associated with age, glomerular filtration rate and the levels of various endothelial markers. [ABSTRACT FROM AUTHOR]

Mountain lee waves present significant hazards to aviation, often inducing turbulence and aircraft icing. The current study focuses on understanding the potential impact of global climate change on the precursor environments to mountain lee wave cloud episodes over central Iberia. We examine the suitability of several Global Climate Models (GCMs) from CMIP6 in predicting these environments using the ERA5 reanalysis as a benchmark for performance. The dataset is divided into two periods: historical data (2001–2014) and projections for the SSP5–8.5 future climate scenario (2015–2100). The variations and trends in precursor environments between historical data and future climate scenarios are exposed, with a particular focus on the expansion of the Azores High towards the Iberian Peninsula, resulting in increased zonal winds throughout the Iberian Peninsula in the future. However, the increase in zonal wind is insufficient to modify the wind pattern, so future mountain lee wave cloud events will not vary significantly. The relative humidity trends reveal no significant changes. Moreover, the risk of icing precursor environments connected with mountain lee wave clouds is expected to decrease in the future, due to rising temperatures. Our results highlight that the EC-EARTH3 GCM reveals the closest alignment with ERA5 data, and statistically significant differences between the historical and future climate scenario periods are presented, making EC-EARTH3 a robust candidate for conducting future studies on the precursor environments to mountain lee wave cloud events. [ABSTRACT FROM AUTHOR]

The dopaminergic system influences the heart rhythm by inhibiting the rat cardiac sympathetic and parasympathetic neurotransmissions through activation of D2-like receptors (encompassing the D2, D3, and D4 subtypes). Whereas D2 receptor subtype activation results in cardiac sympatho-inhibition, the dopamine receptor subtypes involved in rat cardiac vago-inhibition remain unknown. Hence, this study investigated the specific functional role of the D2-like receptor subtypes (D2, D3, and/or D4) inhibiting the rat heart cholinergic drive. For this purpose, male Wistar rats were pithed and prepared for cardiac vagal stimulation. Bradycardic responses were obtained by electrical stimulation of vagal fibres (3, 6, 9 Hz; n = 100) or i.v. acetylcholine (ACh; 1, 5, 10 μg/kg; n = 15). Expression of D2, D3, and D4 receptors was studied in left and right atrium samples by PCR (n = 4). Intravenous injections of quinpirole (D2-like agonist; 1–30 μg/kg), but not of SFK-38393 (D1-like agonist; 1–30 μg/kg), dose-dependently inhibited the vagally induced bradycardia. The vago-inhibition induced by quinpirole (which failed to affect the bradycardia to i.v. ACh) was unchanged after i.v. injections of the antagonists L-741,626 (D2; 100 μg/kg) or SB-277011-A (D3; 100 μg/kg), but it was abolished by L-745,870 (D4; 100 μg/kg). mRNA levels of D2, D3, and D4 receptor subtype were detected in the left and right rat atria. Our results suggest that the quinpirole-induced vagolytic effect involves prejunctional D4 receptor subtypes, located in the left and right atria. This provides new evidence on the relevance of D4 receptor modulating the heart parasympathetic control. [ABSTRACT FROM AUTHOR]

Materials used for the manufacture of implants may suffer alterations in their surface properties as a result of continuous contact with physiological fluids. Moreover, in biodegradable and bioabsorbable materials, such as polylactic acid (PLA), these changes may be more accentuated, and their biological response may be affected by the presence of proteins, enzymes or other compounds of an oxidizing character. This research proposes to study the degradation of PLA in a close-to-reality environment by supplementing the physiological buffer m- SBF with concentrations of glucose and ketone bodies of healthy individuals. To this end, parameters such as hydrophobicity, surface tension, topography and surface chemical composition of PLA films and PLA films doped with magnesium particles after degradation were evaluated to determine how these components influence these properties compared to degradation in standard buffer. The presence of glucose and/or ketone bodies in the degradation medium of PLA doped with magnesium particles altered the composition of the salt layers absorbed on the surface of the material due to the action of gluconate and/or hydroxybutyrate anions, which were able to coordinate with ions from the solution as well as Mg2+ cations from polymer degradation. The salt accumulation on polymeric films changes the surface mechanical response increasing the Young's modulus after degradation. • Composition of physiological medium affects the biodegradability of polylactic acid. • Glucose promotes CaP layer formation on Mg-containing polylactic acid films. • Ketone bodies increase hydrophilicity of Mg-containing polylactic acid films. • Both compounds have to be considered in in vitro degradation models of biomaterials. [ABSTRACT FROM AUTHOR]

Dimethyl fumarate is an ester from the Krebs cycle intermediate fumarate. This drug is approved and currently used for the treatment of psoriasis and multiple sclerosis, and its anti-angiogenic activity was reported some years ago. Due to the current clinical relevance of this compound and the recently manifested importance of endothelial cell metabolism on the angiogenic switch, we wanted to elucidate whether dimethyl fumarate has an effect on energetic metabolism of endothelial cells. Different experimental approximations were performed in endothelial cells, including proteomics, isotope tracing and metabolomics experimental approaches, in this work we studied the possible role of dimethyl fumarate in endothelial cell energetic metabolism. We demonstrate for the first time that dimethyl fumarate promotes glycolysis and diminishes cell respiration in endothelial cells, which could be a consequence of a down-regulation of serine and glycine synthesis through inhibition of PHGDH activity in these cells. Dimethyl fumarate alters the energetic metabolism of endothelial cells in vitro and in vivo through an unknown mechanism, which could be the cause or the consequence of its pharmacological activity. This new discovery on the targets of this compound could open a new field of study regarding the mechanism of action of dimethyl fumarate. The ester drug dimethyl fumarate promotes glycolysis and lowers cell respiration in endothelial cells, and overall alters the energetic metabolism of endothelial cells. [ABSTRACT FROM AUTHOR]

Four tropical transition (TT) events in the North Atlantic basin are simulated with the Weather Research and Forecasting (WRF) and the HARMONIE‐AROME (HAR) models to study the main features of the horizontal kinetic energy (HKE) spectra of these kinds of high‐energetic atmospheric system. Though most of the times similar results are obtained with both models, HAR shows a more intense filtering and numerical dissipation, whereas WRF tends to represent overenergized spectra in the synoptic scale and especially at smaller wavelengths. Predictability is dissimilar for the four TTs studied due to the different spectral curve slope obtained for each case, ranging from unlimited to very poor predictability at synoptic scale. Additionally, an increased HKE is presented in the middle–upper troposphere spectra. A deep analysis of the different terms involved in the equation of the spectral energy budget is presented through a detailed study of one of these TTs. The role of all of them is studied, connecting the energy spectra and the meteorological processes involved. The energy budget terms related to the nonlinear spectral transfer, the three‐dimensional divergence, and diabatic process tendencies are identified as the key ones, whereas the potential and kinetic conversion terms and the vertical flux HKE and pressure divergence terms play a secondary role on modulating the spectrum behaviour. The major energetic contributions are found at the synoptic scale, but results show that a two‐dimensional energy cascade does not fully capture the whole spectrum of a TT. The role of convection, latent heat release, and moist convection outbursts is sketched and a link within different vertical levels is found. Results show that a high‐energetic system, such as a TT, can effectively alter the atmospheric energy behaviour. [ABSTRACT FROM AUTHOR]

Renal vasculature, which is highly innervated by sympathetic fibers, contributes to cardiovascular homeostasis. This renal sympathetic outflow is inhibited by 5-HT in normoglycaemic rats. Considering that diabetes induces cardiovascular complications, we aimed to determine whether diabetic state modifies noradrenergic input at renal level and its serotonergic modulation in rats. Alloxan diabetic rats were anaesthetized (pentobarbital; 60 mg/kg i.p.) and prepared for in situ autoperfusion of the left kidney to continuously measure systemic blood pressure (SBP), heart rate (HR), and renal perfusion pressure (RPP). Electrical stimulation of renal sympathetic outflow induces frequency-dependent increases (Δ) in RPP (23.9 ± 2.1, 59.5 ± 1.9, and 80.5 ± 3.5 mm Hg at 2, 4, and 6 Hz, respectively), which were higher than in normoglycaemic rats, without modifying HR or SBP. Intraarterial bolus of 5-HT and 5-CT (5-HT1/5/7 agonist) reduced electrically induced ΔRPP. Only L-694,247 (5-HT1D agonist) reproduced 5-CT inhibition on sympathetic-induced vasoconstrictions, whereas it did not modify exogenous noradrenaline-induced ΔRPP. 5-CT inhibition was exclusively abolished by i.v. bolus of LY310762 (5-HT1D antagonist). An inhibitor of guanylyl cyclase, ODQ (i.v.), completely reversed the L-694,247 inhibitory effect. In conclusion, diabetes induces an enhancement in sympathetic-induced vasopressor responses at the renal level. Prejunctional 5-HT1D receptors, via the nitric oxide pathway, inhibit noradrenergic-induced vasoconstrictions in diabetic rats. [ABSTRACT FROM AUTHOR]

The use of active components in biomaterials improves the properties of existing ones and makes it possible to obtain new devices with antibacterial properties that prevent infections after implantation, thus guaranteeing the success of the implant. In this work, cetyltrimethylammonium bromide (CTAB) and magnesium particles were incorporated into polylactic acid (PLA) films to assess the extent to which progressive aging of the new surfaces resists bacterial colonization processes. For this purpose, the films' surface was characterized by contact angle measurements, ToF-SIMS and AFM, and adhesion, viability and biofilm growth of Staphylococcus epidermidis bacteria on these films were also evaluated. The results show that the inclusion of Mg and CTAB in PLA films changes their surface properties both before and after aging and also modifies bacterial adhesion on the polymer. Complete bactericidal activity is exhibited on non-degraded films and films with CTAB. This antibacterial behavior is maintained after degradation for three months in the case of films containing a higher amount of CTAB. [ABSTRACT FROM AUTHOR]

Although serotonin has been shown to inhibit peripheral sympathetic outflow, serotonin regulation on renal sympathetic outflow has not yet been elucidated. This study investigated which 5-HT receptor subtypes are involved. Wistar rats were anesthetized (sodium pentobarbital; 60 mg/kg, i.p.), and prepared for in situ autoperfused rat kidney, which allows continuous measurement of systemic blood pressure (SBP), heart rate (HR) and renal perfusion pressure (PP). Electrical stimulation of renal sympathetic nerves resulted in frequency-dependent increases in PP (18.3 ± 1.0, 43.7 ± 2.7 and 66.7 ± 4.0 for 2, 4 and 6 Hz, respectively), without altering SBP or HR. 5-HT, 5-carboxamidotryptamine (5-HT 1/7 agonist) (0.00000125–0.1 μg/kg each) or l -694,247 (5-HT 1D agonist; 0.0125 μg/kg) i.a. bolus inhibited vasopressor responses by renal nerve electrical stimulation, unlike i.a. bolus of agonists α-methyl-5-HT (5-HT 2 ), 1-PBG (5-HT 3 ), cisapride (5-HT 4 ), AS-19 (5-HT 7 ), CGS-12066B (5-HT 1B ) or 8-OH-DPAT (5-HT 1A ) (0.0125 μg/kg each). The effect of l -694,247 did not affect the exogenous norepinephrine-induced vasoconstrictions, whereas was abolished by antagonist LY310762 (5-HT 1D ; 1 mg/kg) or l -NAME (nitric oxide; 10 mg/kg), but not by indomethacin (COX 1/2 ; 2 mg/kg) or glibenclamide (ATP-dependent K + channel; 20 mg/kg). These results suggest that 5-HT mechanism-induced inhibition of rat vasopressor renal sympathetic outflow is mainly mediated by prejunctional 5-HT 1D receptors via nitric oxide release. [ABSTRACT FROM AUTHOR]

Diabetes and derived complications, especially diabetic nephropathy and neuropathy annually cause great morbimortality worldwide. 5-hydroxytryptamine (5-HT) acts as a modulator of renal sympathetic input and vascular tone. In this line, 5-HT 2 receptor blockade has been linked with reduced incidence and progression of diabetic microvascular alterations. In this work, we aimed to determine, in diabetic rats, whether 5-HT 2 blockade ameliorates renal function and to characterize the serotonergic modulatory action on renal sympathetic neurotransmission. Diabetes was induced in male Wistar rats by alloxan administration (150 mg/kg, s.c.), and sarpogrelate (30 mg/kg·day, p.o.; 5-HT 2 antagonist) was administered for 14 days (DM-S). Normoglycemic and diabetic (DM) animals were maintained as aged-matched controls. At 28th day, DM-S animals were anesthetized and prepared for the in situ autoperfusion of the kidney. Renal vasoconstrictor responses were induced electrically or by i.a. noradrenaline (NA) administration. The role of 5-HT and selective 5-HT agonist/antagonist were studied on these renal vasopressor responses. Sarpogrelate treatment decreased renal sympathetic-induced vasopressor responses, reduced renal hypertrophy and kidney damage markers increased in DM. Intraarterial 5-HT inhibited the sympathetic-induced renal vasoconstrictions, effect reproduced by 5-CT, AS-19, L-694,247 and LY 344864 (5-HT 1/5/7 , 5-HT 7 , 5-HT 1D and 5-HT 1F receptor agonists, respectively). Blocking 5-HT 1D/1F/7 receptors completely abolished the 5-CT sympatho-inhibition. NA vasoconstrictions were not altered by any of the 5-HT agonists tested. Thus, in experimental diabetes, chronic sarpogrelate treatment reduces renal damage markers, kidney hypertrophy and renal sympathetic hyperactivity and modifies serotonergic modulation of renal sympathetic neurotransmission, causing a sympatho-inhibition by prejunctional 5-HT 1D/1F and 5-HT 7 activation. [Display omitted] • Sarpogrelate decreased renal sympathetic hyperactivity in diabetes. • The 5-HT renal sympatho-inhibition is modified by sarpogrelate in diabetic rats. • Prejunctional 5-HT 1D/1F and 5-HT 7 are responsible of renal sympatho-inhibition. • Sarpogrelate reduces renal hypertrophy in type 1 diabetic rats. • Renal damage parameters are diminished in sarpogrelate-treated diabetic rats. [ABSTRACT FROM AUTHOR]

Comorbid diabetes and depression constitutes a major health problem, worsening associated cardiovascular diseases. Fluoxetine's (antidepressant) role on cardiac diabetic complications remains unknown. We determined whether fluoxetine modifies cardiac vagal input and its serotonergic modulation in male Wistar diabetic rats. Diabetes was induced by alloxan and maintained for 28 days. Fluoxetine was administered the last 14 days (10 mg/kg/day; p.o). Bradycardia was obtained by vagal stimulation (3, 6 and 9 Hz) or i.v. acetylcholine administrations (1, 5 and 10 μg/kg). Fluoxetine treatment diminished vagally-induced bradycardia. Administration of 5-HT originated a dual action on the bradycardia, augmenting it at low doses and diminishing it at high doses, reproduced by 5-CT (5-HT1/7 agonist). 5-CT did not alter the bradycardia induced by exogenous acetylcholine. Decrease of the vagally-induced bradycardia evoked by high doses of 5-HT and 5-CT was reproduced by L-694,247 (5-HT1D agonist) and blocked by prior administration of LY310762 (5-HT1D antagonist). Enhancement of the electrical-induced bradycardia by 5-CT (10 μg/kg) was abolished by pretreatment with SB269970 (5-HT7 receptor antagonist). Thus, oral fluoxetine treatment originates a decrease in cardiac cholinergic activity and changes 5-HT modulation of bradycardic responses in diabetes: prejunctional 5-HT7 receptors augment cholinergic-evoked bradycardic responses, whereas prejunctional 5-HT1D receptors inhibit vagally-induced bradycardia. [ABSTRACT FROM AUTHOR]

5-HT is a powerful vasoconstrictor substance in renal vasculature (mainly by 5-HT2 activation). Nevertheless, 5-HT is notable for its dual cardiovascular effects, producing both vasodilator and vasoconstrictor actions. This study aimed to investigate whether, behind the predominant serotonergic vasoconstrictor action, THE 5-HT system may exert renal vasodilator actions, and, if so, characterize the 5-HT receptors and possible indirect pathways. Renal perfusion pressure ( PP), systemic blood pressure ( SBP) and heart rate ( HR) measurement in in situ autoperfused rat kidney was determined in phenylephrine infused rats. Intra arterial (i.a.) bolus administration of 5-HT (0.00000125-0.1 μg/kg) decreased renal PP in the presence of a phenylephrine continuous infusion (phenylephrine-infusion group), without modifying SBP or HR. These vasodilator responses were potentiated by 5-HT2 antagonism (ritanserin, 1 mg/kg i.v.), whereas the responses were abolished by 5-HT1/7 antagonist (methiothepin, 100 μg/kg i.v.) or 5-HT1D antagonist (LY310762, 1 mg/kg i.v.). The i.a. administration (0.00000125 to 0.1 μg/kg) of 5-CT or L-694,247 (5-HT1D agonist) mimicked 5-HT vasodilator effect, while other agonists (1-PBG, α-methyl-5-HT, AS-19 (5-HT7), 8-OH-DPAT (5-HT1A) or CGS-12066B (5-HT1B)) did not alter baseline haemodynamic variables. L-694,247 vasodilation was abolished by i.v. bolus of antagonists LY310762 (5-HT1D, 1 mg/kg) or L-NAME (nitric oxide, 10 mg/kg), but not by i.v. bolus of indomethacin (cyclooxygenase, 2 mg/kg) or glibenclamide (ATP-dependent K+ channel, 20 mg/kg). These outcomes suggest that 5-HT1D activation produces a vasodilator effect in the in situ autoperfused kidney of phenylephrine-infusion rats mediated by the NO pathway. [ABSTRACT FROM AUTHOR]

We have demonstrated that the antagonism of 5-HT2 receptors produces an enhancement of serotonergic sympathoinhibitory effect by 5-HT1D and 5-HT7 activation. The aim of this work was to determine mechanisms involved in the 5-hydroxytriptaminergic inhibitory action on the pressor responses elicited by sympathostimulation in pithed rats treated with a 5-HT2 receptor blocker. The blockade of 5-HT2 receptors was induced by orally sarpogrelate treatment (30mg/kg/day). Two weeks later, animals were anaesthetized and pithed. A bolus injection of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10µg/kg), a guanylyl cyclase inhibitor, or indomethacin (2mg/kg), a non-selective COX inhibitor, prior to the infusion of (2S)(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino)tetralin, AS-19 (5µg/kg/min) were not able to abolish its inhibitory action. However, i.v. administration of glibenclamide (20mg/kg), a blocker of ATP-sensitive K+ channels, completely reversed AS-19 sympathoinhibitory action. The inhibitory effect of 2-[5-[3-(4-methylsulfonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indol-3-yl]ethanamine, L-694,247 (5µg/kg/min) was abolished by indomethacin, whereas pretreatment with ODQ had no effect. Nimesulide (3mg/kg), a COX-2 inhibitor, completely reversed the inhibitory action of L-694,247, whereas 1-[[4,5-bis (4-methoxyphenyl)-2-thiazolyl]carbonyl]-4-methylpiperazine hydrochloride (FR122047) (3mg/kg), a COX-1 inhibitor, partially blocked this action. The sympathoinhibition by 5-HT (20µg/kg/min) could not be elicited after i.v. treatment with indomethacin plus glibenclamide. In conclusion, these results suggest that in chronic sarpogrelate-treated rats, the inhibitory serotonergic effect of the pressor responses induced by electrical stimulation of the sympathetic outflow via 5-HT7 and 5-HT1D receptor activation is mediated by KATP channel-mediated smooth muscle hyperpolarization and the COX pathway, respectively. [ABSTRACT FROM AUTHOR]

The influence of surface topographyon bacterial adhesion has beeninvestigated using a range of spatially organized microtopographicsurface patterns generated on polydimethylsiloxane (PDMS) and threeunrelated bacterial strains. The results presented indicate that bacterialcells actively choose their position to settle, differentiating upperand lower areas in all the surface patterns evaluated. Such selectiveadhesion depends on the cells’ size and shape relative to thedimensions of the surface topographical features and surface hydrophobicity/hydrophilicity.Moreover, it was found that all the topographies investigated provokea significant reduction in bacterial adhesion (30–45%) relativeto the smooth control samples regardless of surface hydrophobicity/hydrophilicity.This remarkable finding constitutes a general phenomenon, occurringin both Gram-positive and Gram-negative cells with spherical or rodshape, dictated by only surface topography. Collectively, the resultspresented in this study demonstrate that spatially organized microtopographicsurface patterns represent a promising approach to controlling/inhibitingbacterial adhesion and biofilm formation. [ABSTRACT FROM AUTHOR]

Abstract: 5-HT2 receptor activation induces vasoconstriction, hypertension and platelet aggregation; therefore, its blocking may be useful in cardiovascular diseases, probably due to alterations in the modulation of serotonergic system. The aim of this study was to evaluate whether 5-HT2 receptor blockade changes serotonergic modulation of sympathetic neurotransmission in pithed rats. Serotonergic modulation of sympathetic neurotransmission was investigated in Wistar rats treated with sarpogrelate, a 5-HT2 receptor antagonist, during 14 days (30mg/kg/day). After central nervous system destruction, we conducted electrical stimulation throughout the spinal cord flow to study the 5-HT-related products action on adrenergic system. 5-Hydroxytryptamine exerted inhibition of sympathetic outflow in sarpogrelate-treated pithed rats. This effect was mimicked and enhanced by 5-CT (5-HT1/7 receptor agonist). L-694,247 and AS-19, 5-HT1D and 5-HT7 receptor agonists respectively, reproduced this action. Pretreatment with LY310762+SB258719 (5-HT1D and 5-HT7 receptor antagonists, respectively) completely abolished 5-CT inhibitory action. The nature of this action was prejunctional since these agonists did not modify the pressor responses induced by exogenous noradrenaline. Western Blot analysis confirmed a higher expression of 5-HT1D receptors in sarpogrelate-treated rats. Experimental 5-HT2 receptor blockade induces changes in the 5-HT receptors involved in the serotonergic inhibition of sympathetic-induced pressor responses. Prejunctional activation of 5-HT1D and 5-HT7 receptors induces a significantly higher serotonergic inhibition on adrenergic neurotransmission in sarpogrelate-treated pithed rats. The antagonism of 5-HT2 receptors produces an enhancement of serotonergic sympathoinhibitory effect, which may explain the beneficial effects of this blockade in cardiovascular disorders where 5-hydroxytryptamine plays a crucial role. [Copyright &y& Elsevier]

Solid wettability is especially important for biomaterials and implants in the context of microbial adhesion to their surfaces. This adhesion can be inhibited by changes in biomaterial surface roughness and/or its hydrophilic–hydrophobic balance. The surface hydrophilic–hydrophobic balance can be changed by the specifics of the surface treatment (proper conditions of surface preparation) or adsorption of different substances. From the practical point of view, in systems that include biomaterials and implants, the adsorption of compounds characterized by bacteriostatic or bactericidal properties is especially desirable. Substances that are able to change the surface properties of a given solid as a result of their adsorption and possess at least bacteriostatic properties include sucrose ester surfactants. Thus, in our studies the analysis of a specific surface treatment effect (proper passivation conditions) on a biomaterial alloy's (Ti6Al4V ELI, Grade 23) properties was performed based on measurements of the contact angles of water, formamide and diiodomethane. In addition, the changes in the studied solid surface's properties resulting from the sucrose monodecanoate (SMD) and sucrose monolaurate (SML) molecules' adsorption at the solid–water interface were also analyzed. For the analysis, the values of the contact angles of aqueous solutions of SMD and SML were measured at 293 K, and the surface tensions of the aqueous solutions of studied surfactants measured earlier were tested. From the above-mentioned tests, it was found that water environment significantly influences the components and parameters of Ti6Al4V ELI's surface tension. It also occurred that the addition of both SMD and SML to water (separately) caused a drop in the water contact angle on Ti6Al4V ELI's surface. However, the sucrose monolaurate surfactant is characterized by a slightly better tendency towards adsorption at the solid–water interface in the studied system compared to sucrose monodecanoate. Additionally, based on the components and parameters of Ti6Al4V ELI's surface tension calculated from the proper values of components and parameters of model liquids, it was possible to predict the wettability of Ti6Al4V ELI using the aqueous solutions of SMD and SML at various concentrations in the solution. [ABSTRACT FROM AUTHOR]

Adpsortion of protein layers on biomaterials plays an important role in the interactions between implants and the bio-environment. In this context, human serum albumin (HSA) layers have been deposited on modified Ti6Al4V surfaces at different ultraviolet (UV-C) irradiation times to observe possible changes in the adsorbed protein layer. Protein adsorption was done from solutions at concentraions lower than the serum protein concentration, to follow the surface modifications at the beginning of the albumin adhesion process. For this purpose, the surface of the protein-coated samples has been characterized by time of flight secondary ion mass spectrometry (ToF-SIMS), contact angle and zeta potential measurements. The results obtained show a reduction in the total surface tension and zeta potential of samples treated with UV-C light when coated with a protein layer. Furthermore, the UV-C light treatment applied to titanium alloy surfaces is able to modify the conformation, orientation and packing of the proteins arranged in the adsorbed layer. Low irradiation time generates an unstable surface with the lowest protein adsorption and the highest hydrophobic/hydrophilic protein ratio, indicating a possible denaturalization of the protein on these surfaces. However, surface changes are stabilized after 15 h or UV-C irradiation, favoring the protein adsorption through electrical interactions. [ABSTRACT FROM AUTHOR]

Abstract: We evaluated the renal vascular effects of serotonin in Nω-Nitro-l-arginine-hypertensive rats (L-NAME, 30mg/kg/day, administered over 21days in drinking water), a model of systemic hypertension with glomerular capillary hypertension and renal disease due to chronic blockade of endogenous synthesis of nitric oxide (NO) and compared with those obtained in normotensive rats. Using several agonists and antagonists of 5-hydroxytryptamine (5-HT), we characterized the receptor subtypes involved in the contractile response to 5-HT in the in-situ autoperfused rat kidney. An intra-arterial (i.a.) bolus injection of 5-HT (0.00000125–0.1µg/kg) increased renal perfusion pressure in a dose-dependent manner, but did not affect systemic blood pressure. The selective 5-HT2 receptor agonist α-methyl-5-hydroxytryptamine (α-methyl-5-HT) caused a local vasoconstrictor effect in the autoperfused rat kidney. The selective 5-HT2B receptor agonist BW723C86, the non-selective 5-HT2C receptor agonist (1-(3-chlorophenyl) piperazine), m-CPP, the 5-HT1 receptor agonist 5-carboxamidotryptamine (5-CT) and the selective 5-HT3 receptor agonist (1-(m-chlorophenyl)-biguanide), m-CPBG, did not modify renal perfusion pressure. The vasoconstrictor effect elicited by α-methyl-5-HT was significantly decreased by the 5-HT2 receptor antagonist ritanserin and the 5-HT2A receptor antagonist spiperone, but was not modified by pretreatment with the selective 5-HT2B/2C receptor antagonist (3,5-dihydro-5-methyl-N-3pyridinylbenzo[1,2.b:4,5-b′]dipyrrole(1H)-carboxamide hydrochloride), SB206553. The results of protein expression analyses allow us to postulate that the 5-HT2A receptor protein 5HT-SRC is expressed in renal tissue and differentially expressed in the renal artery of hypertensive (L-NAME) rats. Our data suggest that the serotonergic vasoconstrictor response induced in the in-situ autoperfused hypertensive rat kidney would be mediated by local activation of the 5-HT2A receptor. [Copyright &y& Elsevier]

Preeclampsia (PE) and fetal growth restriction (FGR) are both placenta-mediated disorders with unclear pathogenesis. Metabolomics of maternal and fetal pairs might help in understanding these disorders. We recruited prospectively pregnancies with normotensive FGR, PE without FGR, PE + FGR and uncomplicated pregnancies as controls. Nuclear magnetic resonance metabolomics were applied on plasma samples collected at delivery. Advanced lipoprotein, glycoprotein and choline profiling was performed using the Liposcale test. The software package Dolphin was used to quantify 24 low-molecular-weight metabolites. Statistical analysis comprised the comparison between each group of complicated pregnancies versus controls, considering 5% false discovery rate correction. Lipid profiles were altered in accordance with the clinical presentation of these disorders. Specifically, PE mothers and FGR fetuses (with or without FGR or PE, respectively) exhibited a pro-atherogenic and pro-inflammatory profile, with higher concentrations of triglycerides, remnant cholesterol (VLDL, IDL) and Glc/GalNAc-linked and lipid-associated glycoproteins compared to controls. Low-molecular-weight metabolites were extensively disturbed in preeclamptic mothers, with or without FGR. Growth restricted fetuses in the presence of PE showed changes in low-molecular-weight metabolites similar to their mothers (increased creatine and creatinine), while normotensive FGR fetuses presented scarce differences, consistent with undernutrition (lower isoleucine). Further research is warranted to clarify maternal and fetal adaptations to PE and FGR. [ABSTRACT FROM AUTHOR]

Turbulence and aircraft icing associated with mountain waves are weather phenomena potentially affecting aviation safety. In this paper, these weather phenomena are analysed in the vicinity of the Adolfo Suárez Madrid-Barajas Airport (Spain). Mountain waves are formed in this area due to the proximity of the Guadarrama mountain range. Twenty different weather research and forecasting (WRF) model configurations are evaluated in an initial analysis. This shows the incompetence of some experiments to capture the phenomenon. The two experiments showing the best results are used to simulate thirteen episodes with observed mountain waves. Simulated pseudosatellite images are validated using satellite observations, and an analysis is performed through several skill scores applied to brightness temperature. Few differences are found among the different skill scores. Nevertheless, the Thompson microphysics scheme combined with the Yonsei university PBL scheme shows the best results. The simulations produced by this scheme are used to evaluate the characteristic variables of the mountain wave episodes at windward and leeward and over the mountain. The results show that north-northwest wind directions, moderate wind velocities, and neutral or slightly stable conditions are the main features for the episodes evaluated. In addition, a case study is analysed to evidence the WRF ability to properly detect turbulence and icing associated with mountain waves, even when there is no visual evidence available. [ABSTRACT FROM AUTHOR]

Kidney transplant (KT) is the best technique for renal replacement treatment in terms of survival, costs, and quality of life. Several factors have been related to health-related quality of life (HRQOL) at different times after KT. The objectives of the study were to quantify the HRQOL in a prevalent cohort of KT patients and to describe the variables that influenced HRQOL. In this cross-sectional study of a cohort of 64 KT patients, we measured HRQOL using the 36-item Short Form Health Survey. Variables measured included the following: physical functioning, role physical (RP), bodily pain (BP), general perception of health, vitality, social functioning (SF), role emotional (RE), and mental health. Demographic and analytical variables were collected. We describe the variables that influenced HRQOL. A large dispersion was observed in the RP, BP, SF, and RE categories. There were no differences in values between men and women who underwent KT. Diabetes, previous dialysis, deceased donor, age, kidney function, anemia, and malnutrition were associated with worse scores. This study suggests that HRQOL in KT patients is very heterogeneous and highly polarized. The factors that influence HRQOL are multiple and need to be addressed globally. Further studies are needed to understand the factors that influence HRQOL in the long term. [ABSTRACT FROM AUTHOR]

• Animal toxicity tests are essential for nanomaterials designed for in vivo use. • Toxicity screening on zebrafish embryos avoids the overuse of rodents. • Cell culture toxicity assays showed low toxicity for both Fe and Mn-based NPs. • Zebrafish assays revealed that Fe-based, but not Mn, NPs are suitable for in vivo use. • Cubic (20 nm) iron oxide NPs showed the best characteristics as MRI contrast agents. Magnetic nanoparticles (MNPs) represent one of the greatest promises for the development of a new generation of diagnostic agents for magnetic resonance imaging, with improved specificity and safety. Indeed, during the last decade the number of studies published in this field has grown exponentially. However, the clinical translation achieved so far has been very limited. This situation is likely related to the fact that most studies are focused on the in vitro characterization of these new nanomaterials, and very few provide an exhaustive in vivo characterization, where key aspects, such as pharmacokinetics, bioavailability, and, most importantly, toxicity, are properly evaluated. In this work, we propose a protocol for the comprehensive assessment of the toxicity of MNPs, based on the use of zebrafish embryos as an intermediate screening step between cell culture assays and studies in rodents. MNPs with different cores, ferrite and manganese ferrite oxide, and sizes between 3 and 20 nm, were evaluated. Cell viability at a concentration of 50 μg/mL of PEGylated MNPs was above 90 % in all cases. However, the exposure of zebrafish embryos to manganese based MNPs at concentrations above 100 μg/mL showed a low survival rate (<50 %). In contrast, no mortality (survival rate ∼100 %) and normal hatching rate were obtained for the iron oxide MNPs. Based on these results, together with the physicochemical and magnetic properties (r 2 = 153.6 mM-1·s-1), the PEGylated 20 nm cubic shape iron oxide MNPs were selected and tested in mice, showing very good MRI contrast and, as expected, absence of toxicity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Deep convection is a threat to many human activities, with a great impact on aviation safety. On 7 July 2017, a widespread torrential precipitation event (associated with a cut-off low at mid-levels) was registered in the vicinity of Madrid, causing serious flight disruptions. During this type of episode, accurate short-term forecasts are key to minimizing risks to aviation. The aim of this research is to improve early warning systems by obtaining the best WRF model setup. In this paper, the aforementioned event was simulated. Various model configurations were produced using four different physics parameterizations, 3-km and 1-km domain resolutions, and 0.25° and 1° initial condition resolutions. Simulations were validated using data from 17 rain gauge stations. Two validation indices are proposed, accounting for the temporal behaviour of the model. Results show significant differences between microphysics parameterizations. Validation of domain resolution shows that improvement from 3 to 1 km is negligible. Interestingly, the 0.25° resolution for initial conditions produced poor results compared with 1°. This may be linked to a timing error, because precipitation was simulated further east than observed. The use of ensembles generated by combining different WRF model configurations produced reliable precipitation estimates. [ABSTRACT FROM AUTHOR]

In this study, the influence of nanometer scale roughness on bacterial adhesion and subsequent biofilm formation has been evaluated using spatially organized microtopographic surface patterns for four major opportunistic pathogens of the genus Staphylococcus ( S. epidermidis and S. aureus ) responsible for associated-biofilm infections on biomedical devices. The results presented demonstrated that regardless of the strain employed the initial adhesion events to these surfaces are directed by cell-surface contact points maximisation and thus, bacterial cells actively choose their position to settle based on that principle. Accordingly, bacterial cells were found to preferably adhere to the square corners and convex walls of recessed surface features rather than the flat or concave walls of equal protruding features. This finding reveals, for the first time, that the particular shape of the surfaces features employed potentially determined the initial location of the adhering cells on textured surfaces. It was further shown that all surfaces patterns investigated produce a significant reduction in bacterial adhesion (40–95%) and biofilm formation (22–58%). This important observation could not be related to physical constrains or increased solid surface hydrophobicity, as previously suggested by other authors using engineered topographies with microscale surface roughness. It is evident that other causes, such as nanoscale surface roughness-induced interaction energies, might be controlling the process of bacterial adhesion and biofilm formation on surfaces with well-defined nanoscale topography. [ABSTRACT FROM AUTHOR]

Resveratrol is a naturally occurring stilbene which has shown promising results as treatment for several neurodegenerative diseases. However, its application is limited due to its low efficacy and bioavailability. Here, we have designed and synthesized alkylated resveratrol prodrugs combining structural modification to improve antioxidant and anti-inflammatory properties and the preparation of prodrugs to extend drug bioavailability. For comparison we also studied resveratrol prodrugs and alkylated resveratrol derivatives. Methylated and butylated resveratrol derivatives showed the best in vitro neuroprotective and anti-inflammatory activity. The glucosyl- and glucosyl-acyl- prodrugs of these derivatives showed lower toxicity on zebra fish embryo. When neuroprotection was examined on pentylenetetrazole challenged zebra fish, they were capable of reverting neuronal damage but to a lower extent than resveratrol. Nevertheless, 3- O -(6′- O -octanoyl)-β- d -glucopyranoside resveratrol (compound 8 ) recovered AChE activity over 100% whereas resveratrol only up to 92%. In a 3-nitropropionic acid mice model of Huntington's disease, resveratrol derivative 8 delayed the onset and reduced the severity of HD-like symptoms, by improving locomotor activity and protecting against weight loss. Its effects involved an equal antioxidant but better anti-inflammatory profile than resveratrol as shown by SOD2 expression in brain tissue and circulating levels of IL-6 (11 vs 18 pg/mL), respectively. Finally, the octanoyl chain in compound 8 could be playing a role in inflammation and neuronal development indicating it could be acting as a double-drug, instead of as a prodrug. [ABSTRACT FROM AUTHOR]

5-hydroxytryptamine (5- HT) modulates noradrenergic activity in different cardiovascular territories, but its effect on the mesenteric vasopressor outflow has not yet been clarified. This study investigated the in vivo serotonergic influence, characterizing 5- HT receptors implicated, in sympathetic innervation of mesenteric vasculature. Wistar rats were anaesthetised and prepared for the in situ autoperfused rat mesentery, monitoring systemic blood pressure ( SBP), heart rate ( HR) and mesenteric perfusion pressure ( MPP). Electrical stimulation of mesenteric sympathetic nerves resulted in frequency-dependent increases in MPP (9 ± 1.6, 25.7 ± 3.9 and 60.2 ± 5 mmHg for 2, 4 and 8 Hz, respectively), without altering SBP or HR. 5- HT (1-25 μg/kg), 5-carboxamidotryptamine (5- HT1/7 agonist; 25 μg/kg) or L-694,247 (5-HT1D agonist; 1-25 μg/kg) i.a. bolus inhibited vasopressor responses by mesenteric nerves electrical stimulation, unlike i.a. bolus of agonists 8- OH- DPAT (5- HT1A), CGS-12066B (5- HT1B), BRL 54443 (5- HT1e/1F), α-methyl-5- HT (5- HT2), 1- PBG (5- HT3), cisapride (5- HT4) or AS-19 (5- HT7) (25 μg/kg each). Interestingly, i.a. L-694,247 (25 μg/kg) also reduced the exogenous norepinephrine-induced vasoconstrictions. Pretreatment with selective 5- HT1D receptor antagonist, LY310762 (1 mg/kg, i.v.), completely abolished L-694,247- and 5- HT-induced mesenteric sympathoinhibition. Furthermore, ELISA analysis confirmed 5- HT1D receptors expression in mesenteric artery. These findings suggest that serotonergic mechanisms-induced sympathoinhibition of mesenteric noradrenergic outflow is mediated by pre and/or postjunctional 5- HT1D receptors. [ABSTRACT FROM AUTHOR]

• Patients who live far from transplant centers incur displacement costs. • Joint follow-up between transplant centers and referral hospitals may be the most economical and ecological option for follow-up in kidney transplant recipients living far away and visiting their referral hospital. • Professionalism in both centers was rated positively. • This is the first Spanish study that quantifies personal cost after kidney transplant and evaluates the solution. The number of kidney transplant (KT) recipients has increased in recent years, saturating kidney transplant visits at transplant centers (TCs). Furthermore, some patients live far from TCs, which adds displacement costs to their expenses. To solve these problems, joint follow-up of KT recipients has been initiated at TCs and referral hospitals. We performed a cross-sectional study in a cohort of 64 KT recipients during joint follow-up in TCs and the Hospital Arnau de Villanova (HAV) using a survey that evaluated the displacement costs as well as the advantages and disadvantages of each. Distance (320 km [IQR, 300-340 km] vs 15 km [IQR, 4-60 km]; P <.001), time (240 minutes [IQR, 210-240 minutes] vs 40 minutes [IQR, 30-68 minutes]; P <.001), total economic cost per visit (€60 [IQR, €50-90] vs €10 [IQR, €2-15]; P <.001), and annual CO 2 emission (32.3 kg vs 1.4 kg; P <.05) were greater when patients traveled to TCs. Nephrologists at both TCs and HAV were rated positively by patients, while the displacement costs associated with travel to the TCs and the smaller size of the HAV were seen as negative aspects. Overall, 93.75% of the KT recipients preferred joint follow-up. This study suggests that joint follow-up between TCs and referral hospitals is an economic and ecological solution for follow-up in KT recipients living far away and visiting their referral hospital, which is the preferred choice for most patients. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether the 5-HT 2 receptor blockade alters the 5-HT effect on vascular sympathetic neurotransmission and platelet activation in type 1 diabetes. 28-day diabetes was obtained by alloxan (150 mg/kg; s.c.) in male Wistar rats, administering sarpogrelate (5-HT 2 blocker; 30 mg/kg/day; p.o.) for 14 days. Blood glucose and body weight were monitored for 28 days. After 4 weeks of diabetes induction, food and drink intake, urine, plasma-platelet 5-HT, and platelet activation were determined in normoglycemic, non-treated diabetic and sarpogrelate-treated diabetic rats. Another set of diabetic rats were pithed to run the vascular sympathetic stimulation or exogenous noradrenaline administration, examining the induced vasoconstrictor responses. Sarpogrelate treatment significantly reduced drink intake and urine, whereas BW gain, hyperglycemia, and food intake were not modified in diabetic rats. The platelet activation and plasma 5-HT concentration were decreased (increasing the stored 5-HT platelet) by 5-HT 2 blockade in diabetic animals. The sympathetic-induced vasoconstrictions were higher in non-treated than in sarpogrelate-treated diabetic rats. 5-HT inhibited these vasopressor responses, reproduced exclusively by the 5-HT 1/5/7 receptor agonist, 5-CT. The 5-CT-produced inhibition was partly reversed by 5-HT 1D or 5-HT 7 antagonists (LY310762 or SB-258719, respectively), and totally annulled by the mixture of LY310762+SB‐258719. Noradrenaline-caused vasoconstrictions were also decreased by 5-CT. In conclusion, our results reveal that 14-day sarpogrelate treatment improves polydipsia and polyuria, reduces platelet hyperactivation, plasma 5-HT and the vascular sympathetic tone, and changes 5-HT receptors inhibiting noradrenergic drive in diabetic rats: pre and/or postjunctional 5-HT 1D/7 are involved in the sympatho-inhibition. [Display omitted] • Sarpogrelate decreases polyuria and polydipsia in type 1 diabetic rats. • Platelet activation is reduced in sarpogrelate-treated diabetic rats. • Sarpogrelate diminishes vascular sympathetic neurotransmission in diabetes. • The 5-HT vascular sympatho-inhibition is modified by sarpogrelate in diabetic rats. • Pre and/or postjunctional 5-HT1D and 5-HT7 are responsible of sympatho-inhibition. [ABSTRACT FROM AUTHOR]

Aims Here, we tested the hypothesis that glial responses via the production of cytokines such as transforming growth factor-beta 1 ( TGFβ1) and tumour necrosis factor alpha ( TNFα), which play important roles in neurodegenerative diseases, are correlated with the severity of congenital hydrocephalus in the hyh mouse model. We also searched for evidence of this association in human cases of primary hydrocephalus. Methods Hyh mice, which exhibit either severe or compensated long-lasting forms of hydrocephalus, were examined and compared with wild-type mice. TGFβ1, TNFα and TNFα R1 mRNA levels were quantified using real-time PCR. TNFα and TNFα R1 were immunolocalized in the brain tissues of hyh mice and four hydrocephalic human foetuses relative to astroglial and microglial reactions. Results The TGFβ1 mRNA levels were not significantly different between hyh mice exhibiting severe or compensated hydrocephalus and normal mice. In contrast, severely hydrocephalic mice exhibited four- and two-fold increases in the mean levels of TNFα and TNFα R1, respectively, compared with normal mice. In the hyh mouse, TNFα and TNFα R1 immunoreactivity was preferentially detected in astrocytes that form a particular periventricular reaction characteristic of hydrocephalus. However, these proteins were rarely detected in microglia, which did not appear to be activated. TNFα immunoreactivity was also detected in the glial reaction in the small group of human foetuses exhibiting hydrocephalus that were examined. Conclusions In the hyh mouse model of congenital hydrocephalus, TNFα and TNFα R1 appear to be associated with the severity of the disease, probably mediating the astrocyte reaction, neurodegenerative processes and ischaemia. [ABSTRACT FROM AUTHOR]

This study investigated whether fluoxetine treatment changes the 5-HT regulation on vascular sympathetic neurotransmission in type 1 diabetes. Four-week diabetes was obtained by a single alloxan s.c. administration in male Wistar rats, administering fluoxetine for 14 days (10 mg/kg/day; p.o.). Systolic blood pressure, heart rate, glycaemia, body weight (BW) evolution, creatinine, and blood urea nitrogen (BUN) were monitored. Afterward, rats were pithed to perform the vascular sympathetic stimulation. 5-HT 1A/1D/2A receptors expression was analysed by Western blot in thoracic aorta. Both i.v. norepinephrine and the electrical stimulation of the spinal sympathetic drive evoked vasoconstrictor responses. Fluoxetine treatment significantly reduced the BW gain, hyperglycaemia, creatinine, and BUN in diabetic rats. The electrical-produced vasopressor responses were greater in untreated than in fluoxetine-treated diabetic rats. 5-HT decreased the sympathetic-produced vasopressor responses. While 5-CT, 8-OH-DPAT and L-694,247 (5-HT 1/7 , 5-HT 1A and 5-HT 1D agonists, respectively) reproduced 5-HT-evoked inhibition, the 5-HT 2 activation by α-methyl-5-HT augmented the vasoconstrictions. The 5-CT sympatho-inhibition was reversed by 5-HT 1A plus 5-HT 1D antagonists (WAY-100,635 and LY310762, respectively), whereas ritanserin (5-HT 2A antagonist) blocked the α-methyl-5-HT potentiating effect. Norepinephrine-generated vasoconstrictions were increased or diminished by α-methyl-5-HT or 5-CT, respectively. 5-HT 1A/1D/2A receptors were expressed at vascular level, being 5-HT 1A expression increased by fluoxetine in diabetic rats. Our findings suggest that fluoxetine improves metabolic and renal profiles, changes the vasopressor responses, and 5-HT receptors modulating sympathetic activity in diabetic rats: 5-HT 1A/1D are involved in the sympatho-inhibition, while 5-HT 2A is implicated in the sympatho-potentiation, being both effects pre and/or postjunctional in nature. [Display omitted] • Fluoxetine decreases vascular noradrenergic outflow in type 1 diabetic rats. • The 5-HT vascular sympatho-regulation is changed by fluoxetine in diabetic rats. • Pre and/or postjunctional 5-HT 1A and 5-HT 1D are responsible of sympatho-inhibition. • Pre and/or postjunctional 5-HT 2A are involved in sympatho-excitation. [ABSTRACT FROM AUTHOR]

The Ti6Al4V surface, commonly employed in biomedical prostheses, has been chemically functionalized by non-covalent binding to obtain improved antibacterial responses. The methodology combines the well-known antibacterial activity of silver(I) ions with those of other common antimicrobials such as carboxylic acids, trans-cinnamaldehyde, farnesol, and the broad-range antibiotic chloramphenicol. To this end, on previously aminosilanizated Ti6Al4V surfaces (Material A) were attached via saline bonds (involving both ionic and dipole interactions) acetic, propanoic, benzoic, and sorbic acids (Material B). Likewise silver(I) acetate undergoes non-covalent cross-linking with the aminosiloxane-coated surface (Material C) after incubation at 60°C for 48h, thus resulting in a density of ca. 4.11×10−8 molcm−2. The coordinating ability of Ag(I) ions enables further attachment of the above-mentioned carboxylic acids onto the surface (Material D) and other neutral antimicrobials (Material E). Surface characterization has been accomplished using infrared spectroscopy and X-ray photoelectron spectroscopy, which support non-covalent binding. In particular, the existence of ammonium and carboxylate groups together with other intact functional groups (carbonyl, hydroxyl and amino) reveals that aminosiloxane-coated surfaces adhere via both ionic and weak interactions. As a proof of concept, adhesion and viability tests of Staphylococcus aureus on the functionalized surfaces show the adequate performance of the coverage at short and medium contact times with the surrounding cells. [ABSTRACT FROM AUTHOR]

Exogenous neuroprotective protein neuroglobin (Ngb) cannot cross the blood–brain barrier. To overcome this difficulty, we synthesized hyaluronate nanoparticles (NPs), able to deliver Ngb into the brain in an animal model of stroke (MCAO). These NPs effectively reached neurons, and were microscopically identified after 24 h of reperfusion. Compared to MCAO non-treated animals, those treated with Ngb-NPs showed survival rates up to 50% higher, and better neurological scores. Tissue damage improved with the treatment, but no changes in the infarct volume or in the oxidative/nitrosative values were detected. A proteomics approach (p-value < 0.02; fold change = 0.05) in the infarcted areas showed a total of 219 proteins that significantly changed their expression after stroke and treatment with Ngb-NPs. Of special interest, are proteins such as FBXO7 and NTRK2, which were downexpressed in stroke, but overexpressed after treatment with Ngb-NPs; and ATX2L, which was overexpressed only under the effect of Ngb. Interestingly, the proteins affected by the treatment with Ngb were involved in mitochondrial function and cell death, endocytosis, protein metabolism, cytoskeletal remodeling, or synaptic function, and in regenerative processes, such as dendritogenesis, neuritogenesis, or sinaptogenesis. Consequently, our pharmaceutical preparation may open new therapeutic scopes for stroke and possibly for other neurodegenerative pathologies. [ABSTRACT FROM AUTHOR]

Natural phenolic compounds found in food have demonstrated interesting preventive and therapeutic effects on a large variety of pathologies. Indeed, some of them, such as resveratrol (RES), have been examined in clinical trials. Nevertheless, their success has been scarce mainly due to their low bioavailability. In this study, we found serendipitously that O -silyl RES derivatives exerted a better neuroprotective activity than resveratrol itself and decided to explore them as potential drugs for neurodegenerative and neurological diseases. We have also designed and prepared a series of O -silyl RES prodrugs to improve their bioavailability. We found that di-triethylsilyl and di-triisopropylsilyl RES derivatives were better in vitro neuroprotective and anti-inflammatory agents than RES. Among these derivatives and their corresponding acyl-, glycosyl- and carbamoyl-prodrugs, 3,5-triethylsilyl-4'-(6″-octanoylglucopyranosyl) resveratrol 26 showed the best profile on toxicity and neuroprotective activity in zebra fish embryo. Compound 26 was also capable of reducing the loss of motor coordination in a 3-nitropropionic acid mice model of Huntington's disease, in a similar way to RES. However, 26 diminished pro-inflammatory cytokine IL-6 to a higher extent than RES and improved the latency to fall in the rotarod test by 10% with respect to RES. Finally, we investigated 26 and RES as potential treatments on an experimental autoimmune encephalomyelitis (EAE) multiple sclerosis mice model. We observed that, in a therapeutic regimen, 26 significantly diminished the progression of EAE severity and reduced the percentage of animals with moderate to severe clinical score, whereas RES showed no improvement. [Display omitted] • A series of O -silyl resveratrol (RES) and several prodrugs has been synthesized • Cytotoxicity, neuroprotective and anti-inflammatory activity were measured • Di-triethylsilyl and di-triisopropylsilyl resveratrol derivatives were better neuroprotective agents than RES • Compound 26 reduced the severity in a Huntington's disease mice model • Compound 26 diminished the clinical score in an EAE mice model of multiple sclerosis [ABSTRACT FROM AUTHOR]

Abstract: Formation of thin films on titanium alloys incorporating bioactive small molecules or macromolecules is a route to improve their biocompatibility. Aminoalkylsilanes are commonly employed as interface reagents that combine good adhesion properties with an amino tail group susceptible of further functionalization. This article introduces a reproducible methodology to obtain a cross-linked polymer-type brush structure of covalently-bonded aminoalkylsiloxane chains on Ti6Al4V. The experimental protocol can be fine-tuned to provide a high density of surface-coated amino groups (threshold value: 2.1±0.1×10−8 molcm−2) as proven by chemical and spectrophotometric analyses. Using a model reaction involving the condensation of 3-aminopropyltrimethoxysilane (APTMS) on Ti6Al4V alloy, we herein show the effects of reaction temperature, reaction time and solvent humidity on the composition and structure of the film. The stability of the resulting coating under physiological-like conditions as well as the possibility of surface re-silanization has also been evaluated. To verify if detrimental effects on the biological performance of the Ti6Al4V alloy were induced by this coverage, human primary osteoblasts behavior, Staphylococci adhesion and biofilm formation have been tested and compared to the Ti6Al4V oxidized surface. Reaction with trans-cinnamaldehyde has used in order to determine useful amino groups at aminosilanized surface, XPS and UV analyses of imino derivatives generated reveal that almost a 50% of these groups are actually available at the siloxane chains. [Copyright &y& Elsevier]

Abstract: Chromosomal abnormalities are detected in 40–60% of patients with de novo myelodysplastic syndromes (MDS). This study used the FISH technique in 773 patients with de novo MDS without evidence of monosomy 7 (−7) or 7q deletion (7q−) by conventional G-banding cytogenetics (CC) to analyze their prognostic impact by FISH alone. FISH detected −7/7q− in 5.2% of patients. Presence of −7/7q− was associated with shorter overall survival than absence of such aberrations. Our results suggest that FISH 7q could be beneficial in patients with intermediate WHO morphologic risk stratification and no evidence of −7/7q− by CC. [Copyright &y& Elsevier]

Abstract: TiO2-coated biomaterials that have been excited with UV irradiation have demonstrated biocidal properties in environmental applications, including drinking water decontamination. However, this procedure has not been successfully applied towards the killing of pathogens on medical titanium-based implants, mainly because of practical concerns related to irradiating the inserted biomaterial in situ. Previous researchers assumed that the photocatalysis on the TiO2 surface during UV application causes the bactericidal effects. However, we show that a residual post-irradiation bactericidal effect exists on the surface of Ti6Al4V, not related with photocatalysis. Using a combination of staining, serial dilutions, and a biofilm assay, we show a significant and time-dependent loss in viability of different bacterial strains of Staphylococcus epidermidis and Staphylococcus aureus on the post-irradiated surface. Although the duration of this antimicrobial effect depends on the strains selected, our experiments suggest that the effect lasts at least 60min after surface irradiation. The origin of such phenomena is discussed in terms of the physical properties of the irradiated surfaces, which include the emission of energy and changes in surfaces charge occurring during electron-hole recombination processes. The method here proposed for the preparation of antimicrobial titanium surfaces could become especially useful in total implant surgery for which the antimicrobial challenge is mainly during or shortly after surgery. [Copyright &y& Elsevier]

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 (5×10-6 M), dipyridamole (3×10-7 M), glibenclamide (10-6 M), propranolol (10-6 M), verapamil (10-7 M) or atropine (3×10-5 M). In addition, the relaxant effect of acetylcholine (Ach, 10-8-3×10-4 M), and sodium nitroprusside (SNP, 10-9-3×10-5 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. [ABSTRACT FROM AUTHOR]