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Diabetic vasculopathy is a significant cause of morbidity and mortality in the diabetic population. Hyperglycemia, one of the central metabolic abnormalities in diabetes, has been associated with vascular dysfunction due to endothelial cell damage. However, studies also point toward vascular smooth muscle as a locus for hyperglycemia-induced vascular dysfunction. Emerging evidence implicates hyperglycemia-induced regulation of vascular L-type Ca2+ channels CaV1.2 as a potential mechanism for vascular dysfunction during diabetes. This chapter summarizes our current understanding of vascular CaV1.2 channels and their regulation during physiological and hyperglycemia/diabetes conditions. We will emphasize the role of CaV1.2 in vascular smooth muscle, the effects of elevated glucose on CaV1.2 function, and the mechanisms underlying its dysregulation in hyperglycemia and diabetes. We conclude by examining future directions and gaps in knowledge regarding CaV1.2 regulation in health and during diabetes.
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Diabetes Mellitus , Hiperglicemia , Humanos , Miócitos de Músculo Liso/metabolismo , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo L/farmacologia , Músculo Liso Vascular/fisiologia , Diabetes Mellitus/metabolismo , Hiperglicemia/metabolismoRESUMO
OBJECTIVES: Haemorrhage control is a critical component of preventing traumatic death. Other than the battlefield, haemostatic devices, such as tourniquets or bandages, may not be available, allowing for significant avoidable blood loss. We hypothesised that compression of vascular pressure points using a position adapted from the martial art of Brazilian Jiu-Jitsu could be adapted to decrease blood flow velocity in major extremity arteries. METHODS: Knee mount compression was applied to the shoulder, groin and abdomen of healthy adult volunteer research subjects from Seattle, Washington, USA, from March through May 2018. Mean arterial blood flow velocity (MAV) was measured using ultrasound in the brachial and femoral arteries before and after compression. A MAV decrease greater than 20% with compression was deemed clinically relevant. RESULTS: For 11 subjects, median (IQR) MAV combining all anatomical locations tested was 29.2 (34.1, 24.1) cm/s at baseline and decreased to 3.3 (0, 19.1) cm/s during compression (Wilcoxon p<0.001). MAV was significantly decreased during compression for each individual anatomical position tested (Wilcoxon p≤0.004). Per cent (95% CI) MAV reduction was significantly greater than 20% for shoulder compression at 97.5%(94% to 100%) and groin compression at 78%(56% to 100%), but was not statistically greater for abdominal compression at 35%(12% to 57%). Complete vessel occlusion was most common with compression at the shoulder (73%), followed by groin (55%) and abdomen (9%) (χ² LR, p=0.018). CONCLUSION: The Brazilian Jiu-Jitsu knee mount position can significantly decrease blood flow in major arteries of the extremities. This technique may be useful for bleeding control after injury.
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Hemorragia/terapia , Artes Marciais , Pressão , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Artéria Braquial/fisiologia , Feminino , Artéria Femoral/fisiologia , Humanos , Masculino , Estudos Prospectivos , Ultrassonografia/métodosRESUMO
Plaster of Paris [poP, CaSO4·(1)/(2) H2O] is the standard phantom material used for the calibration of in vivo X-ray fluorescence (IVXRF)-based systems of bone metal quantification (i.e bone strontium and lead). Calibration of IVXRF systems of bone metal quantification employs the use of a coherent normalization procedure which requires the application of a coherent correction factor (CCF) to the data, calculated as the ratio of the relativistic form factors of the phantom material and bone mineral. Various issues have been raised as to the suitability of poP for the calibration of IVXRF systems of bone metal quantification which include its chemical purity and its chemical difference from bone mineral (a calcium phosphate). This work describes the preparation of a chemically pure hydroxyapatite phantom material, of known composition and stoichiometry, proposed for the purpose of calibrating IVXRF systems of bone strontium and lead quantification as a replacement for poP. The issue with contamination by the analyte was resolved by preparing pure Ca(OH)2 by hydroxide precipitation, which was found to bring strontium and lead levels to <0.7 and <0.3 µg/g Ca, respectively. HAp phantoms were prepared from known quantities of chemically pure Ca(OH)2, CaHPO4·2H2O prepared from pure Ca(OH)2, the analyte, and a HPO4(2-) containing setting solution. The final crystal structure of the material was found to be similar to that of the bone mineral component of NIST SRM 1486 (bone meal), as determined by powder X-ray diffraction spectrometry.
Assuntos
Osso e Ossos/química , Durapatita/química , Chumbo/análise , Estrôncio/análise , Humanos , Difração de Pó , Espectrometria por Raios XRESUMO
Hydroxyapatite (HAp) phantoms have been proposed as an alternative to plaster of Paris (poP) phantoms for the calibration of x-ray fluorescence-based systems for thein vivoquantification of bone lead and strontium which employ a coherent normalization procedure. The chemical composition of the material becomes critical in the calculation, or omission, of the coherent correction factor (CCF) required in this normalization procedure. This study evaluated the long-term chemical stability of HAp phantoms. Phantoms were prepared and allowed to age for a two week period and over a seven year period in ambient conditions. The chemical composition of the phantoms was then assessed by powder x-ray diffraction. Two week old phantoms were found to be composed of HAp with only a small amount of contamination from CaHPO4·2H2O. Seven year old phantoms were found to have converted nearly completely to a carbonate-bearing apatite in the form of Ca10(PO4)6(CO3)0.75(OH)0.5indicating that the HAp phantom material likely reacts with carbon dioxide in air over time forming a carbonate-bearing apatite. The influence of this chemical conversion was assessed at the level of relevant cross-sections. Calibration under the assumption that the material is HAp when in fact it is a carbonate-bearing apatite would result in not more than a 0.2%-2% bias in the total mass attenuation coefficient within the photon energy range of 0-100 keV. Differential scattering cross-section for coherent scattering was found to differ between HAp and carbonate-bearing apatite by 0.9%-2% for both a 35.5 keV and 88.0 keVγ-ray. This variation in the differential scattering cross-section for coherent scattering may introduce a ca. 2% bias in the CCF used within the coherent normalization-based calibration procedure. Using HAp phantoms as calibrators thus requires acknowledgement of this conversion in chemical form and possible introduction of uncertainty into the calibration procedure.
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Durapatita , Estrôncio , Estrôncio/análise , Calibragem , Espectrometria de Fluorescência , Espectrometria por Raios X/métodos , CarbonatosRESUMO
In order to assess their vaccination policy, the public health authorities in Isère (France) conducted several surveys to determine the vaccination coverage rate among adults. In France, the current state of knowledge in this area is limited. Four separate surveys were conducted in 2002-2003: (1) a telephone survey of 976 adults, 18% of whom had vaccination certificates; (2) a survey of 44 general practitioners (805 patients); (3) a survey of occupational health centers (82 practitioners and 1,119 employees); and (4) a survey of 1,214 patients vaccinated at the international vaccination center in Grenoble (France). The same data were recorded in all four surveys (last vaccination date, either declared by the patient or proven by a vaccination certificate). Based on certified evidence, vaccination coverage for tetanus, diphtheria, and poliomyelitis ranged from 31.6% to 83.9%, from 24.1% to 44.0%, and from 25.9% to 71.9%, respectively. Compared to general practitioners, vaccination coverage was higher among staff working at the occupational health center and lower in the general population. The four surveys covered only part of the adult population and provided only an estimate of vaccination coverage. The study found that tetanus vaccination coverage was the highest, but was still below expected levels. For the other vaccines, vaccination coverage among adults appears to be inadequate. The findings suggest that all health professionals involved in adult vaccination (occupational health doctors, general practitioners, hospital doctors, etc.) should be invited to participate in working groups on vaccination.
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Vacinação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Feminino , França , Clínicos Gerais/estatística & dados numéricos , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Serviços de Saúde do Trabalhador , Adulto JovemRESUMO
Ion channels that influence membrane potential and intracellular calcium concentration control vascular smooth muscle excitability. Voltage-gated calcium channels (VGCC), transient receptor potential (TRP) channels, voltage (KV), and Ca2+-activated K+ (BK) channels are key regulators of vascular smooth muscle excitability and contractility. These channels are regulated by various signaling cues, including protein kinases and phosphatases. The effects of these ubiquitous signaling molecules often depend on the formation of macromolecular complexes that provide a platform for targeting and compartmentalizing signaling events to specific substrates. This manuscript summarizes our current understanding of specific molecular complexes involving VGCC, TRP, and KV and BK channels and their contribution to regulating vascular physiology.
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Two chiral synthetic ß-dipeptides have been constructed, one with two trans-cyclobutane residues and the other with one trans and one cis fragment, 1 and 2, respectively, and investigated to get insight into the non-covalent interactions responsible for their self-assembly to form ordered aggregates, as well into parameters such as their morphology and size. Experimental evidence of the formation of these assemblies was provided by spectroscopy, microscopy and X-ray diffraction experiments that suggest the formation of nanoscale helical aggregates. This process involves a conformational change in the molecules of each dipeptide with respect to the preferred conformation of the isolated molecules in solution. A high-resolution NMR spectroscopy study allowed the determination of the dynamics of the gelation process in [D(8)]toluene and the sol-gel transition temperature, which was around 270 K in this solvent at a concentration of 15 mM. NMR spectroscopy experiments also provided some information about conformational changes involved in the sol-gel transition and also suggested a different gel packing for each dipeptide. These observations have been nicely explained by computational studies. The self-assembly of the molecules has been modelled and suggested a head-to-head molecular arrangement for 1 and a head-to-tail arrangement for 2 to give helical structures corresponding to hydrogen-bonded single chains. These chains interact with one another in an antiparallel way to afford bundles, the significant geometry parameters of which fit well to the main peaks observed in wide-angle X-ray diffraction spectra of the aggregates in the solid state.
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Ciclobutanos/química , Dipeptídeos/química , Modelos Moleculares , Géis , Ligação de Hidrogênio , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Conformação Proteica , Estrutura Secundária de Proteína , EstereoisomerismoRESUMO
ABSTRACT: Sepsis is an amplified systemic immune-inflammatory response produced by a microorganism, which involves activation of inflammatory cytokine signaling pathways and oxidative stress. A variety of studies have shown that hydralazine (HDZ) has potent antioxidant and anti-inflammatory proprieties. Therefore, we hypothesize that HDZ can improve the clinical outcome of sepsis. Thus, this work aimed to evaluate therapeutic value of HDZ in reducing inflammatory response, oxidative stress, and mortality in animal sepsis, and to investigate its possible mechanism of action. Sepsis was induced by the cecal ligation and puncture (CLP) method in Wistar rats. After surgery, the animals were randomly divided into three groups: sham, sepsis, and sepsis + HDZ (1âmg/kg,âs.c.). All groups were monitored for 48âh to assess survival rate, and clinical, hemodynamic, biochemical, and cellular parameters. After euthanasia, blood, spleen, liver, and kidneys were collected for analysis. Blood serum cytokines, tissue myeloperoxidase (MPO) activity, and oxidative stress parameters were assessed. Involvement of the PI3K/Akt pathway was also investigated. Sepsis was successfully induced by the CLP technique. HDZ treatment increased the survival rate (from 50% to 90%), improved glycemia control, reduced the clinical severity sepsis and mean arterial pressure; and prevented increased MPO activity, TNF-α, IL-1ß, IL-10 levels, and oxidative damage markers. Additionally, HDZ significantly prevented the increase of Akt activation in the liver and kidney. HDZ largely mitigated the effects of sepsis by suppressing inflammatory and antioxidant responses via the PI3K/Akt pathway. These findings provide evidence that HDZ can be a new therapeutic alternative for treating sepsis.
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Hidralazina/farmacologia , Hidralazina/uso terapêutico , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Sepse/tratamento farmacológico , Sepse/mortalidade , Animais , Ratos , Ratos Wistar , Transdução de SinaisRESUMO
Improved methodologies are provided to synthesize (1R,2S)-2-aminocyclobutane-1-carboxylic acid derivatives and their incorporation into beta-peptides of 2-8 residues bearing different N-protecting groups. The conformational analysis of these oligomers has been carried out by using experimental techniques along with theoretical calculations. This study shows that these oligomers adopt preferentially a strand-type conformation in solution induced by the formation of intra-residue six-membered hydrogen-bonded rings, affording cis-fused [4.2.0]octane structural units that confer high rigidity on these beta-peptides. Moreover, all of them are prone to self-assemble producing nano-sized fibres, as evidenced by TEM, AFM and SPFM, and, in some instances, they also form gels. These techniques and molecular modelling allowed us to suggest an aggregation model for the assembly structures in which a parallel molecular-arrangement is preferred and the conformation is similar to that observed in solution. According to this model, both hydrogen-bonding and hydrophobic interactions would account for formation of the assemblies.
Assuntos
Aminoácidos Cíclicos/química , Oligopeptídeos/química , Dobramento de Proteína , Dicroísmo Circular , Hidrólise , Espectroscopia de Ressonância Magnética , Microscopia , Simulação de Dinâmica Molecular , Oligopeptídeos/síntese química , Conformação Proteica , Soluções , EstereoisomerismoRESUMO
PURPOSE: Dual-energy X-ray absorptiometry (DXA) is the gold standard technique to measure areal bone mineral density (aBMD) for the diagnosis of osteoporosis. Because DXA relies on the attenuation of photon to estimate aBMD, deposition of bone-seeking metallic elements such as strontium, lead, and aluminum that differ in atomic numbers from calcium can cause inaccurate estimation of aBMD. Quantitative ultrasound (QUS) is another technique available to assess bone health by measuring broadband ultrasound attenuation (BUA), speed of sound (SOS), and an empirically derived quantity called stiffness index (SI). Because the acoustic properties are not prone to significant change due to changes in microscopic atomic composition of bone, it is hypothesized that QUS is unaffected by the presence of bone-seeking elements in the bone. The objective of this study was to investigate the effect of strontium, lead, and aluminum on DXA-derived aBMD and QUS parameters using bone-mimicking phantoms compatible with both techniques. METHODS: Bone-mimicking phantoms were produced by homogeneously mixing finely powdered hydroxyapatite compounds that contain varying concentrations of strontium, lead, or aluminum with porcine gelatin solution. Seven strontium-substituted phantoms were produced with varying molar ratio of Sr/(Sr + Ca) ranging from 0% to 2%. Four lead-doped phantoms and four aluminum-doped phantoms were constructed with the respective analyte concentrations ranging from 50 to 200 ppm. An additional 0 ppm phantom was produced to be used as a baseline for the lead and aluminum phantom measurements. All phantoms had uniform volumetric bone mineral density (vBMD) of 200 mg/cm3 , and were assessed using a Hologic Horizon® DXA device and a Hologic Sahara® QUS device. Furthermore, theoretical aBMD bias for mol/mol% substitution of calcium with the three bone-seeking elements was calculated. RESULTS: Strong positive linear relationship was found between aBMD measured by DXA and strontium concentration (P < 0.001, r = 0.995). From the measurement of lead and aluminum phantoms using DXA, no statistically significant relationship was observed between aBMD and the analyte concentrations. For the QUS system, with an exception of BUA and lead concentration that exhibited statistically significant relationship (P < 0.038, r = 0.899), no statistically significant change was observed in all QUS parameters with respect to the clinically relevant concentration of all three elements. The calculated theoretical aBMD bias induced by 1 mol/mol% substitution of calcium with strontium, lead, and aluminum were 10.8%, 4.6%, and -0.7%, respectively. CONCLUSION: aBMD measured by DXA was prone to overestimation in the presence of strontium, but acoustic parameters measured by QUS are independent of strontium concentration. The deviation in aBMD induced by the clinically relevant concentrations of lead and aluminum under 200 ppm could not be detected using the Hologic Horizon® DXA device. Furthermore, the SI measured by the QUS system was not affected by lead or aluminum concentrations used in this study.
Assuntos
Absorciometria de Fóton/instrumentação , Alumínio , Osso e Ossos/diagnóstico por imagem , Chumbo , Imagens de Fantasmas , Estrôncio , Ultrassonografia/instrumentação , Densidade Óssea , Osso e Ossos/fisiologiaRESUMO
OBJECTIVE: The calibration of in vivo x-ray fluorescence systems of bone strontium quantification, based on 125I excitation, is dependent on a coherent normalization procedure. Application of this procedure with the use of plaster of Paris (poP) as a phantom material requires the application of a coherent conversion factor (CCF) to make the calibration functions transferable between the phantom material and human bone. In this work we evaluate, with the use of Monte Carlo simulation, the potential benefit of employing a newly developed hydroxyapatite phantom material into the calibration protocol. APPROACH: Simulations being performed on bare bone phantoms, as the emission spectrum in this case is equivalent to an emission spectrum of an adequately corrected measurement for soft tissue attenuation of emitted strontium signal. We report that the application of hydroxyapatite phantoms does in fact remove the need for a coherent correction factor (CCF). MAIN RESULTS: The newly developed phantoms can thus be used for the calibration of in vivo bone strontium systems removing one step of the calibration protocol. Calibration is, however, limited to cases in which the concentration is relative to the amount of calcium in the specimen, which is, the most useful quantity in a clinical sense. Determining concentrations on a per-mass-of-material basis, that is, a concentration not normalized to the calcium content of the phantom/bone, results in large biases in estimated bone strontium content. SIGNIFICANCE: The use of an HAp phantom material was found to remove the need for a CCF. It was also found that in the case of an incomplete conversion ratio when preparing the phantom material that there would be little effect on the differential coherent cross-section and thereby the coherent normalization-based calibration protocol.
Assuntos
Osso Cortical/metabolismo , Durapatita/metabolismo , Radioisótopos do Iodo/química , Método de Monte Carlo , Imagens de Fantasmas , Espectrometria por Raios X/instrumentação , Estrôncio/metabolismo , Calibragem , HumanosRESUMO
OBJECTIVE: Lanthanum (La) is commonly used in phosphate binders in the form of lanthanum carbonate in patients with end-stage kidney disease undergoing hemodialysis treatments. With this administration, there is the potential for La storage in the body with bone being the main site of concern. However, the long-term effects of residual La in the body on bone health are not yet known. In this work, we investigate the feasibility of using a K x-ray fluorescence (K-XRF) spectroscopy system to measure bone La in vivo. APPROACH: A series of hydroxyapatite (HAp) bone mineral phantoms were created to represent human bone. A 1.09 GBq 241Am source was used to excite the HAp phantoms doped with various known concentrations of La placed in a 90° geometry relative to the photon source and high-purity germanium (HPGe) detector. MAIN RESULTS: For a detector live time of 2000 s, the minimum detection limit was calculated to be 1.7 µg La g-1 Ca or 0.7 µg La g-1 HAp and is comparable to previously reported in vivo bone La concentrations. SIGNIFICANCE: The technique developed in this study shows promising results and provides an alternative method to invasive biopsy sampling techniques to monitor the accumulation of bone La. To the best of our knowledge, this is the first reported work that seeks to non-invasively measure bone La via in vivo XRF.
Assuntos
Amerício , Lantânio/análise , Espectrometria por Raios X , Osso e Ossos/química , Estudos de Viabilidade , Humanos , Lantânio/química , Imagens de FantasmasRESUMO
PURPOSE: Bone quantity, as determined by the current gold standard, dual energy X-ray absorptiometry (DXA), through measured areal bone mineral density (aBMD), is subject to positive biases if bone strontium levels are high. This is of particular concern for populations administered strontium-based compounds for the treatment of osteoporosis. This study investigated the dependence of bone mineral density (BMD) determinations, and associated ultrasound-determined indices, obtained by quantitative ultrasound (QUS), on bone strontium content using a new generation of trabecular bone-mimicking phantoms. METHODS: A new generation of bone-mimicking phantoms, consisting of hydroxyapatite (HA) and gelatin, was developed. Castor oil layers were included in these phantoms to create a multilayer bone-mimicking phantom. These phantoms were prepared using a bone mineral fraction consisting of varying strontium concentrations in the range of 0-2.5% mol/mol as strontium-substituted HA. The effect of varying bone strontium content on determined quality indices was evaluated based on determined speed of sound (SOS), broadband ultrasound attenuation (BUA) and determined quantitative ultrasound index (QUI) for phantoms with varying BMD values and varying strontium concentration using two QUS systems: a clinical Sahara® system and an in-house research system with two identical transducers with center frequency of 1 MHz. The two QUS systems were also compared through a Bland-Altman analysis. RESULTS: Both the clinical system and the research QUS systems showed a strong dependency between BMD and BUA, indicating a potential for QUS to be used as a means of estimating BMD (p = 0.001). SOS was found to have no correlation to BMD (p = 0.546). There was no correlation observed between BUA and increasing bone strontium concentrations for the research (p = 0.749) and clinical (p = 0.609) QUS systems. Similarly, no dependency was observed between the SOS and bone strontium levels up to 2.5 mol/mol [Sr/(Sr+Ca)]% for the research (p = 0.862) and clinical (p = 0.481) QUS systems. No effect on the QUI values was observed with changing strontium levels with either research (p = 0.939) or clinical QUS systems (p = 0.931). A Bland-Altman analysis showed that there was a clear offset in determined QUI values for both systems but they are in agreement with one another. CONCLUSIONS: Bone quality can be assessed through the use of QUS while increasing bone strontium concentration was found to have no effect on QUS-determined quality indices. This study concludes that QUS can potentially be used for the determination of bone quality without introducing biases due to bone strontium levels as is known to be the case with DXA determined aBMD.
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Densidade Óssea , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/fisiologia , Imagens de Fantasmas , Estrôncio , Ultrassonografia/instrumentação , HumanosRESUMO
The crystal structure of the complex 12.calix-[4]-arene dihydroxyphosphonic acid, 12.propane diammonium, 12.ethanol and 40.water molecules is based on dimeric units of the calix, assembled via trigonal units into a hexameric tube of 15 A radius and 16 A depth, further assemby via spanning propane diammonium cations and ethanol molecules forms a channel (40 A), selectively containing all the water molecules.
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The solid-state structure of the complex of para-sulfonatocalix[4]arene with d-arginine, contains a water channel diagonal to a zigzag bilayer of the host, within the bilayer six crystallographically independent molecules of arginine are present, four being included in the calix cavities.
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Three tests of increasing complexity were used to assess the antioxidant activity of five synthetic gallic esters of sucrose bearing 3, 6, 7, or 8 galloyl units. In addition, two of these compounds had 1 or 2 hydrocarbon (C10-C12) acyl chains. Reaction with the DPPH radical led to the evaluation of the number of radicals trapped per galloyl unit n (3-4), as well as the apparent second-order rate constant for H atom donation k (1200-1500/M/s). These results indicated similar contribution and reactivity of all the galloyl units. Inhibition of the AAPH-initiated peroxidation of linoleic acid in a micellar medium confirmed the additive contribution of the galloyl units, whereas the presence of the hydrocarbon acyl chains had no influence. These results suggest an inhibition of initiation at high antioxidant levels and an underlying prooxidant effect of the galloyl radicals at low concentrations. Finally, LDL peroxidation was inhibited in proportion to the number of galloyl units, in agreement with the preceding tests.
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Ésteres/química , Sequestradores de Radicais Livres , Ácido Gálico/análogos & derivados , Taninos Hidrolisáveis , Peroxidação de Lipídeos , Sacarose/análogos & derivados , Sacarose/química , Amidinas/farmacologia , Compostos de Bifenilo , Radicais Livres/química , Ácido Gálico/química , Ácido Gálico/farmacologia , Ácido Linoleico/química , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoproteínas LDL/química , Oxidantes/farmacologia , Picratos/química , Sacarose/farmacologia , TaninosRESUMO
In this paper, we describe the haemolytic effect of parent para-sulphonato-calix-[n]-arenes and their derivatives bearing one pendant group at the lower rim of calix-arene towards human erythrocytes. A maximum of 30% of haemolysis has been observed for para-sulphonato-calix-[8]-arene for a concentration of 200 mM representing 300 g of calix-arene per liter of human blood, para-sulphonato-calix-[4]-arene and para-sulphonato-calix-[6]-arene show much lower haemolytic effects, 0.5 and 8%, respectively at 200 mM concentration. Coupling of a methoxy-carboxylate function at the phenolic group reduces haemolytic effects in all cases. The presence of an ethoxy-amine function increases the haemolytic behaviour for the calix-[4]-arene and calix-[6]-arene systems, but reduces the effect for the calix-[8]-arene derivatives.
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Sulfonatos de Arila/toxicidade , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Compostos Policíclicos/toxicidade , Sulfonatos de Arila/química , Calixarenos , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Portadores de Fármacos/toxicidade , Humanos , Técnicas In Vitro , Substâncias Macromoleculares , Compostos Policíclicos/química , Solubilidade , Relação Estrutura-AtividadeRESUMO
The preparation and stability parameters of para-acyl-calix[4]arene based solid lipid nanoparticles (SLNs) have been investigated. Atomic force microscopy (AFM) and photon correlation spectroscopy (PCS) show a mean particle size of 130 nm. In terms of preparation parameters, using the solvent displacement method, the nature and the volume of the organic solvent, the concentration of the amphiphile and the presence of a co-surfactant in the organic phase have been shown to affect significantly the size of the produced SLNs. In contrast, the stirring speed, the viscosity and the acidity of the aqueous phase and the amphiphile hydrophobic chain length have been shown to have no effect. In terms of stability parameters, the ionic strength has been shown to affect the short-time SLN stability depending on both the anion and the cation studied, with sodium sulphate causing precipitation. Ultrasonic, ultraviolet or microwave treatments of the SLN suspensions have no effect on the size of the SLNs. The study of the effects of short time thermal treatment revealed that the SLNs are not affected by one freezing-defreezing cycle and are stable at 100 degrees C in suspension. It is difficult to reconstitute the SLN suspensions after freeze-drying. Finally, the temporal stability of these suspensions in water has been shown to be superior to 1 year. The long-term temporal stability of suspensions stored in saline solution has been investigated. It has been demonstrated that the most destabilising effects arise from the presence in the storage suspension of sulphate ions.1H NMR, X-ray powder diffraction (XPD) and AFM have also been carried out on the calix-arene based SLNs and demonstrate the presence of a semi-organised matrix structure for the SLNs.
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Calixarenos , Portadores de Fármacos/química , Ácidos Graxos/química , Fenóis/química , Cristalização , Portadores de Fármacos/efeitos da radiação , Estabilidade de Medicamentos , Ácidos Graxos/efeitos da radiação , Liofilização , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Ressonância Magnética , Microscopia de Força Atômica , Microesferas , Micro-Ondas , Nanotecnologia , Concentração Osmolar , Tamanho da Partícula , Fenóis/efeitos da radiação , Solventes , Tensoativos , Temperatura , Ultrassom , Raios Ultravioleta , Viscosidade , Difração de Raios XAssuntos
Calixarenos/química , Éteres Cíclicos/química , Imidazóis/química , Compostos Organometálicos/síntese química , Fenantrolinas/química , Fenóis/química , Resorcinóis/química , Rênio/química , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/química , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , EstereoisomerismoRESUMO
Extrapolation chambers are instruments designed to measure doses of low-energy radiations, mainly beta radiation. In this work, a commercial extrapolation chamber and a homemade extrapolation chamber were applied in measurements using standard radiotherapy X-ray beams. Saturation curves and polarity effect as well as short- and medium-term stabilities were obtained, and these results are within the recommendations of the International Electrotechnical Commission (IEC). The response linearity and the extrapolation curves were also obtained, and they presented good behavior. The results show the usefulness of these extrapolation chambers in low-energy X-ray beams.