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1.
Hepatology ; 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38447019

RESUMEN

BACKGROUND AND AIMS: The landscape in primary biliary cholangitis (PBC) has changed with the advent of second-line treatments. However, the use of obeticholic acid (OCA) and fibrates in PBC-related cirrhosis is challenging. We assessed the impact of receiving a second-line therapy as a risk factor for decompensated cirrhosis in a real-world population with cirrhosis and PBC, and identify the predictive factors for decompensated cirrhosis in these patients. APPROACH AND RESULTS: Multicenter study enrolling 388 patients with PBC-cirrhosis from the Spanish ColHai registry. Biopsy (20%), ultrasound (59%), or transient elastography (21%) defined cirrhosis, and the presence of varices and splenomegaly defined clinically significant portal hypertension (CSPH). Paris-II and PBC OCA international study of efficacy criteria determined the response to ursodeoxycholic acid (UDCA), fibrates (n=93), and OCA (n=104). The incidence of decompensated cirrhosis decreased for UDCA versus OCA or fibrates in the real-world population, but they were similar considering the propensity score-matched cohort (UDCA 3.77 vs. second-line therapy 4.5 100 persons-year, respectively), as patients on second-line therapy exhibited advanced liver disease. Consequently, GGT, albumin, platelets, clinically significant portal hypertension, and UDCA response were associated with a decompensating event. OCA response (achieved in 52% of patients) was associated with bilirubin (OR 0.21 [95% CI: 0.06-0.73]) and AST (OR 0.97 [95% CI: 0.95-0.99]), while fibrate response (achieved in 55% of patients) with AST [OR 0.96 (95% CI: 0.95-0.98]). In patients treated with OCA, drug response (sHR 0.23 [95% CI: 0.08-0.64]), diabetes (sHR 5.62 [95% CI: 2.02-15.68]), albumin (sHR 0.34 [95% CI: 0.13-0.89]), and platelets (sHR 0.99 [95% CI: 0.98-1.00]) were related to decompensation. In patients treated with fibrate, drug response (sHR 0.36 (95% CI: 0.14-0.95]), albumin (sHR 0.36 (95% CI: 0.16-0.81]), and clinically significant portal hypertension (sHR 3.70 (95% CI: 1.17-11.70]) were associated with decompensated cirrhosis. CONCLUSIONS: Advanced PBC, rather than OCA and fibrates, was found to be associated with decompensating events. Therefore, biochemical and clinical variables should be considered when making decisions about the management of these drugs. Moreover, a positive response to OCA and fibrates reduced the risk of decompensation.

2.
Inorg Chem ; 62(28): 11016-11027, 2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37390399

RESUMEN

Understanding the fundamental chemistry of soft N,S-donor ligands with actinides across the series is critical for separation science toward sustainable nuclear energy. This task is particularly challenging when the ligands are redox active. We herein report a series of actinyl complexes with a N,S-donor redox-active ligand that stabilizes different oxidation states across the actinide series. These complexes are isolated and characterized in the gas phase, along with high-level electronic structure studies. The redox-active N,S-donor ligand in the products, C5H4NS, acts as a monoanion in [UVIO2(C5H4NS-)]+ but as a neutral radical with unpaired electrons localized on the sulfur atom in [NpVO2(C5H4NS•)]+ and [PuVO2(C5H4NS•)]+, resulting in different oxidation states for uranium and transuranic elements. This is rationalized by considering the relative energy levels of actinyl(VI) 5f orbitals and S 3p lone pair orbitals of the C5H4NS- ligand and the cooperativity between An-N and An-S bonds that provides additional stability for the transuranic elements.

3.
J Hepatol ; 76(5): 1013-1020, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35063601

RESUMEN

BACKGROUND & AIMS: Previous studies on the prognostic significance of non-invasive liver fibrosis tests in non-alcoholic fatty liver disease (NAFLD) lack direct comparison to liver biopsy. We aimed to evaluate the prognostic accuracy of fibrosis-4 (FIB4) and vibration-controlled transient elastography (VCTE), compared to liver biopsy, for the prediction of liver-related events (LREs) in NAFLD. METHODS: A total of 1,057 patients with NAFLD and baseline FIB4 and VCTE were included in a multicenter cohort. Of these patients, 594 also had a baseline liver biopsy. The main study outcome during follow-up was occurrence of LREs, a composite endpoint combining cirrhosis complications and/or hepatocellular carcinoma. Discriminative ability was evaluated using Harrell's C-index. RESULTS: FIB4 and VCTE showed good accuracy for the prediction of LREs, with Harrell's C-indexes >0.80 (0.817 [0.768-0.866] vs. 0.878 [0.835-0.921], respectively, p = 0.059). In the biopsy subgroup, Harrell's C-indexes of histological fibrosis staging and VCTE were not significantly different (0.932 [0.910-0.955] vs. 0.881 [0.832-0.931], respectively, p = 0.164), while both significantly outperformed FIB4 for the prediction of LREs. FIB4 and VCTE were independent predictors of LREs in the whole study cohort. The stepwise FIB4-VCTE algorithm accurately stratified the risk of LREs: compared to patients with "FIB4 <1.30", those with "FIB4 ≥1.30 then VCTE <8.0 kPa" had similar risk of LREs (adjusted hazard ratio [aHR] 1.3; 95% CI 0.3-6.8), whereas the risk of LREs significantly increased in patients with "FIB4 ≥1.30 then VCTE 8.0-12.0 kPa" (aHR 3.8; 95% CI 1.3-10.9), and even more for those with "FIB4 ≥1.30 then VCTE >12.0 kPa" (aHR 12.4; 95% CI 5.1-30.2). CONCLUSION: VCTE and FIB4 accurately stratify patients with NAFLD based on their risk of LREs. These non-invasive tests are alternatives to liver biopsy for the identification of patients in need of specialized management. LAY SUMMARY: The amount of fibrosis in the liver is closely associated with the risk of liver-related complications in non-alcoholic fatty liver disease (NAFLD). Liver biopsy currently remains the reference standard for the evaluation of fibrosis, but its application is limited by its invasiveness. Therefore, we evaluated the ability of non-invasive liver fibrosis tests to predict liver-related complications in NAFLD. Our results show that the blood test FIB4 and transient elastography stratify the risk of liver-related complications in NAFLD, and that transient elastography has similar prognostic accuracy as liver biopsy. These results support the use of non-invasive liver fibrosis tests instead of liver biopsy for the management of patients with NAFLD.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Enfermedad del Hígado Graso no Alcohólico , Biopsia , Diagnóstico por Imagen de Elasticidad/métodos , Fibrosis , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico
4.
Liver Int ; 42(8): 1783-1792, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35643936

RESUMEN

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem, but the prevalence of fibrosis associated with non-alcoholic steatohepatitis (NASH) is largely unknown in the general population. This study aimed to provide an updated estimation of the prevalence of NASH fibrosis in Spain. METHODS: This was an observational, retrospective, cross-sectional, population-based study with merged data from two Spanish datasets: a large (N = 12 246) population-based cohort (ETHON), including transient elastography (TE) data, and a contemporary multi-centric biopsy-proven NASH cohort with paired TE data from tertiary centres (N = 501). Prevalence for each NASH fibrosis stage was estimated by crossing TE data from ETHON dataset with histology data from the biopsy-proven cohort. RESULTS: From the patients with valid TE in ETHON dataset (N = 11 440), 5.61% (95% confidence interval [95% CI]: 2.53-11.97) had a liver stiffness measurement (LSM) ≥ 8 kPa. The proportion attributable to NAFLD (using clinical variables and Controlled Attenuation Parameter) was 57.3% and thus, the estimated prevalence of population with LSM ≥ 8 kPa because of NAFLD was 3.21% (95% CI 1.13-8.75). In the biopsy-proven NASH cohort, 389 patients had LSM ≥ 8 kPa. Among these, 37% did not have significant fibrosis (F2-4). The estimated prevalence of NASH F2-3 and cirrhosis in Spain's adult population were 1.33% (95% CI 0.29-5.98) and 0.70% (95% CI 0.10-4.95) respectively. CONCLUSIONS: These estimations provide an accurate picture of the current prevalence of NASH-related fibrosis in Spain and can serve as reference point for dimensioning the therapeutic efforts that will be required as NASH therapies become available.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Enfermedad del Hígado Graso no Alcohólico , Adulto , Estudios Transversales , Fibrosis , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/epidemiología , Cirrosis Hepática/etiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Prevalencia , Estudios Prospectivos , Estudios Retrospectivos , España/epidemiología
5.
Phys Chem Chem Phys ; 19(16): 10685-10694, 2017 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-28398437

RESUMEN

Actinide disulphide dications, AnS22+, were produced in the gas phase for An = Th and Np by reaction of An2+ cations with the sulfur-atom donor COS, in a sequential abstraction process of two sulfur atoms, as examined by FTICR mass spectrometry. For An = Pu and Am, An2+ ions were unreactive with COS and did not yield any sulphide species. High level multiconfigurational (CASPT2) calculations were performed to assess the structures and bonding of the new AnS22+ species obtained for An = Th, Np, as well as for An = Pu to examine trends along the An series, and for An = U to compare with a previous experimental study and DFT computational scrutiny of US22+. The CASPT2 results showed that, like in the case of uranium, the new AnS22+ ions have ground states with triangular geometries, corresponding to the presence of a persulphide in the case of thorium that formally leads to a stable ThIVS22+ species, while a supersulphide appears to be present in the case of U, Np and Pu, formally leading to a AnIIIS22+ species. The computations also revealed that linear thioactinyl structures are higher in energy, with a difference that increases fourfold upon moving from U to Pu, apparently indicating that it will be even more pronounced for Am.

7.
Phys Chem Chem Phys ; 17(15): 9942-50, 2015 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-25783464

RESUMEN

Several lanthanide and actinide tetranitrate ions, M(III)(NO3)4(-), were produced by electrospray ionization and subjected to collision induced dissociation in quadrupole ion trap mass spectrometers. The nature of the MO(NO3)3(-) products that result from NO2 elimination was evaluated by measuring the relative hydrolysis rates under thermalized conditions. Based on the experimental results it is inferred that the hydrolysis rates relate to the intrinsic stability of the M(IV) oxidation states, which correlate with both the solution IV/III reduction potentials and the fourth ionization energies. Density functional theory computations of the energetics of hydrolysis and atoms-in-molecules bonding analysis of representative oxide and hydroxide nitrates substantiate the interpretations. The results allow differentiation between those MO(NO3)3(-) that comprise an O(2-) ligand with oxidation to M(IV) and those that comprise a radical O(-) ligand with retention of the M(III) oxidation state. In the particular cases of MO(NO3)3(-) for M = Pr, Nd and Tb it is proposed that the oxidation states are intermediate between M(III) and M(IV).

8.
J Phys Chem A ; 119(15): 3628-35, 2015 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-25807358

RESUMEN

Gas-phase complexes of uranyl(V) ligated to anions X(-) (X = F, Cl, Br, I, OH, NO3, ClO4, HCO2, CH3CO2, CF3CO2, CH3COS, NCS, N3), [UO2X2](-), were produced by electrospray ionization and reacted with O2 in a quadrupole ion trap mass spectrometer to form uranyl(VI) anionic complexes, [UO2X2(O2)](-), comprising a superoxo ligand. The comparative rates for the oxidation reactions were measured, ranging from relatively fast [UO2(OH)2](-) to slow [UO2I2](-). The reaction rates of [UO2X2](-) ions containing polyatomic ligands were significantly faster than those containing the monatomic halogens, which can be attributed to the greater number of vibrational degrees of freedom in the polyatomic ligands to dissipate the energy of the initial O2-association complexes. The effect of the basicity of the X(-) ligands was also apparent in the relative rates for O2 addition, with a general correlation between increasing ligand basicity and O2-addition efficiency for polyatomic ligands. Collision-induced dissociation of the superoxo complexes showed in all cases loss of O2 to form the [UO2X2](-) anions, indicating weaker binding of the O2(-) ligand compared to the X(-) ligands. Density functional theory computations of the structures and energetics of selected species are in accord with the experimental observations.


Asunto(s)
Oxígeno/química , Superóxidos/química , Compuestos de Uranio/química , Aniones/química , Gases/química , Teoría Cuántica , Compuestos de Uranio/síntesis química
9.
Inorg Chem ; 53(4): 2163-70, 2014 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-24484174

RESUMEN

A challenge in actinide chemistry is activation of the strong bonds in the actinyl ions, AnO2(+) and AnO2(2+), where An = U, Np, or Pu. Actinyl activation in oxo-exchange with water in solution is well established, but the exchange mechanisms are unknown. Gas-phase actinyl oxo-exchange is a means to probe these processes in detail for simple systems, which are amenable to computational modeling. Gas-phase exchange reactions of UO2(+), NpO2(+), PuO2(+), and UO2(2+) with water and methanol were studied by experiment and density functional theory (DFT); reported for the first time are experimental results for UO2(2+) and for methanol exchange, as well as exchange rate constants. Key findings are faster exchange of UO2(2+) versus UO2(+) and faster exchange with methanol versus water; faster exchange of UO2(+) versus PuO2(+) was quantified. Computed potential energy profiles (PEPs) are in accord with the observed kinetics, validating the utility of DFT to model these exchange processes. The seemingly enigmatic result of faster exchange for uranyl, which has the strongest oxo-bonds, may reflect reduced covalency in uranyl as compared with plutonyl.

10.
J Phys Chem A ; 118(11): 2159-66, 2014 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-24571380

RESUMEN

Complementary experimental and computational methods for evaluating relative charge densities of metal cations in gas-phase clusters are presented. Collision-induced dissociation (CID) and/or density functional theory computations were performed on anion clusters of composition MM'A(m+n+1)(-), where the two metal ions have formal charge states M(m+) and M'(n+) and A is an anion, NO3(-), Cl(-), or F(-) in this work. Results for alkaline earth and lanthanide metal ions reveal that cluster CID generally preferentially produces MA(m+1)(-) and neutral M'An if the surface charge density of M is greater than that of M': the metal ion with the higher charge density takes the extra anion. Computed dissociation energies corroborate that dissociation occurs via the lowest energy process. CID of clusters in which one of the two metal ions is uranyl, UO2(2+), shows that the effective charge density of U in uranyl is greater than that of alkaline earths and comparable to that of the late trivalent lanthanides; this is in accord with previous solution results for uranyl, from which an effective charge of 3.2+ was derived.

11.
Inorg Chem ; 52(19): 10968-75, 2013 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-24047411

RESUMEN

Laser ionization of AnC4 alloys (An = Th, U) yielded gas-phase molecular thorium and uranium carbide cluster cations of composition An(m)C(n)(+), with m = 1, n = 2-14, and m = 2, n = 3-18, as detected by Fourier transform ion-cyclotron-resonance mass spectrometry. In the case of thorium, Th(m)C(n)(+) cluster ions with m = 3-13 and n = 5-30 were also produced, with an intriguing high intensity of Th13C(n)(+) cations. The AnC13(+) ions also exhibited an unexpectedly high abundance, in contrast to the gradual decrease in the intensity of other AnC(n)(+) ions with increasing values of n. High abundances of AnC2(+) and AnC4(+) ions are consistent with enhanced stability due to strong metal-C2 bonds. Among the most abundant bimetallic ions was Th2C3(+) for thorium; in contrast, U2C4(+) was the most intense bimetallic for uranium, with essentially no U2C3(+) appearing. Density functional theory computations were performed to illuminate this distinction between thorium and uranium. The computational results revealed structural and energetic disparities for the An2C3(+) and An2C4(+) cluster ions, which elucidate the observed differing abundances of the bimetallic carbide ions. Particularly noteworthy is that the Th atoms are essentially equivalent in Th2C3(+), whereas there is a large asymmetry between the U atoms in U2C3(+).

12.
Indian J Ophthalmol ; 71(2): 663-666, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36727384

RESUMEN

We describe a 68-year-old female patient with unilateral central retinal artery occlusion (CRAO) with cilioretinal artery sparing post-coronavirus disease 2019 (COVID-19) infection. The patient presented with acute vision loss in the left eye 11 days after discharge from a severe COVID-19 infection, with altered D-dimer, C-reactive protein, and fibrinogen levels. The best-corrected visual acuity (BCVA) in the left eye was 20/400; fundoscopic examination revealed diffuse pallor retina with a patent arterial branch from the optic disk to the fovea, confirmed by fluorescein angiography. CRAO with a cilioretinal artery sparing post-COVID-19 may be considered an additional ocular manifestation of the post-acute COVID-19 syndrome spectrum.


Asunto(s)
COVID-19 , Conjuntivitis , Oclusión de la Arteria Retiniana , Arteria Retiniana , Anciano , Femenino , Humanos , COVID-19/complicaciones , Angiografía con Fluoresceína , Retina , Oclusión de la Arteria Retiniana/etiología , Vasos Retinianos
13.
J Am Chem Soc ; 134(37): 15488-96, 2012 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-22963223

RESUMEN

Activation of uranyl(V) oxo bonds in the gas phase is demonstrated by reaction of U(16)O(2)(+) with H(2)(18)O to produce U(16)O(18)O(+) and U(18)O(2)(+). In contrast, neptunyl(V) and plutonyl(V) are comparatively inert toward exchange. Computed potential energy profiles (PEPs) reveal a lower yl oxo exchange transition state for uranyl(V)/water as compared with neptunyl(V)/water and plutonyl(V)/water. A correspondence between oxo exchange rates in gas phase and acid solutions is apparent; the contrasting oxo exchange rates of UO(2)(+) and PuO(2)(+) are considered in the context of covalent bonding in actinyls. Hydroxo exchange of U(16)O(2)((16)OH)(+) with H(2)(18)O to give U(16)O(2)((18)OH)(+) proceeded much faster than oxo exchange, in accord with a lower computed transition state for OH exchange. The PEP for the addition of H(2)O to UO(2)(+) suggests that both UO(2)(+)·(H(2)O) and UO(OH)(2)(+) should be considered as potential products.


Asunto(s)
Oxígeno/química , Plutonio/química , Uranio/química
14.
Inorg Chem ; 51(12): 6603-14, 2012 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-22656318

RESUMEN

The following monopositive actinyl ions were produced by electrospray ionization of aqueous solutions of An(VI)O(2)(ClO(4))(2) (An = U, Np, Pu): U(V)O(2)(+), Np(V)O(2)(+), Pu(V)O(2)(+), U(VI)O(2)(OH)(+), and Pu(VI)O(2)(OH)(+); abundances of the actinyl ions reflect the relative stabilities of the An(VI) and An(V) oxidation states. Gas-phase reactions with water in an ion trap revealed that water addition terminates at AnO(2)(+)·(H(2)O)(4) (An = U, Np, Pu) and AnO(2)(OH)(+)·(H(2)O)(3) (An = U, Pu), each with four equatorial ligands. These terminal hydrates evidently correspond to the maximum inner-sphere water coordination in the gas phase, as substantiated by density functional theory (DFT) computations of the hydrate structures and energetics. Measured hydration rates for the AnO(2)(OH)(+) were substantially faster than for the AnO(2)(+), reflecting additional vibrational degrees of freedom in the hydroxide ions for stabilization of hot adducts. Dioxygen addition resulted in UO(2)(+)(O(2))(H(2)O)(n) (n = 2, 3), whereas O(2) addition was not observed for NpO(2)(+) or PuO(2)(+) hydrates. DFT suggests that two-electron three-centered bonds form between UO(2)(+) and O(2), but not between NpO(2)(+) and O(2). As formation of the UO(2)(+)-O(2) bonds formally corresponds to the oxidation of U(V) to U(VI), the absence of this bonding with NpO(2)(+) can be considered a manifestation of the lower relative stability of Np(VI).


Asunto(s)
Neptunio/química , Plutonio/química , Teoría Cuántica , Uranio/química , Gases/química , Oxidación-Reducción , Agua/química
15.
Front Immunol ; 12: 667354, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34899679

RESUMEN

Metabolic associated fatty liver disease (MAFLD) is the most prevalent form of liver disease worldwide, accounting for a high liver-related mortality and morbidity with extensive multi-organ involvement. This entity has displaced viral hepatitis as the main cause of severe forms of hepatic diseases, although the onset and transition of MAFLD stages still remains unclear. Nevertheless, innate and adaptive immune responses seem to play an essential role in the establishment and further progression of this disease. The immune system is responsible of safeguard and preserves organs and systems function, and might be altered under different stimuli. Thus, the liver suffers from metabolic and immune changes leading to different injuries and loss of function. It has been stablished that cell-cell crosstalk is a key process in the hepatic homeostasis maintenance. There is mounting evidence suggesting that MAFLD pathogenesis is determined by a complex interaction of environmental, genetic and host factors that leads to a full plethora of outcomes. Therefore, herein we will revisit and discuss the interplay between immune mechanisms and MAFLD, highlighting the potential role of immunological markers in an attempt to clarify its relationship.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico/inmunología , Animales , Humanos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología
16.
J AAPOS ; 25(3): 169-170, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33689910

RESUMEN

We report the case of a 2-year-old girl with acute-onset divergent strabismus and ptosis in the right eye. She had an exotropia of 45Δ for near, eyelid ptosis affecting the visual axis, adduction, limitations of up- and downgaze, and a discrete mydriasis in the right eye. Neurological conditions were ruled out. Serology was positive for SARS-CoV-2 antibodies. The patient was managed conservatively with ocular physiotherapy and close visual acuity monitoring. On follow-up examination at 1 month, there was marked improvement of the exotropia (25Δ for near), adduction, ptosis, and mydriasis.


Asunto(s)
Blefaroptosis , COVID-19 , Exotropía , Enfermedades del Nervio Oculomotor , Blefaroptosis/diagnóstico , Preescolar , Exotropía/diagnóstico , Femenino , Humanos , Músculos Oculomotores , Enfermedades del Nervio Oculomotor/diagnóstico , SARS-CoV-2
17.
Chem Commun (Camb) ; 55(94): 14139-14142, 2019 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-31697296

RESUMEN

The diverse reactivity of [LnO2(NO3)2]- complexes with water in the gas phase, for Ln = Ce, Pr and Nd, examined in a quadrupole ion trap and complemented by ab initio computations, illuminates the chemical stability of Pr in the unusual +5 oxidation state.

18.
Neurosci Lett ; 434(1): 66-70, 2008 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-18281154

RESUMEN

The ketogenic diet (KD) is a high fat and low carbohydrate and protein diet. It is used in the clinical treatment of epilepsy, in order to decrease cerebral excitability. KD is usually composed by long-chain triglycerides (LCT) while medium-chain triglycerides (MCT) diet is beginning to be used in some clinical treatment of disorders of pyruvate carboxylase enzyme and long-chain fatty acid oxidation. Our study aimed to analyze the effects of medium- and long-chain KD on cerebral electrical activity, analyzing the propagation of the phenomenon of cortical spreading depression (CSD). Three groups of weaned rats (21 days old) received, for 7 weeks, either a control (AIN-93G diet), or a MCT-KD (rich in triheptanoin oil), or a LCT-KD (rich in soybean oil). They were compared to another three groups (21 days old) receiving the same diets for just 10 days. CSD propagation was evaluated just after ending the dietary treatments. Results showed that short-term KD treatment resulted in a significant reduction of the CSD velocity of propagation (control group: 4.02+/-1.04mm/min; MCT-KD: 0.81+/-1.46mm/min and LCT-KD: 2.26+/-0.41mm/min) compared to the control group. However, long-term treatment with both KDs had no effect on the CSD velocity (control group: 3.10+/-0.41mm/min, MCT-KD: 2.91+/-1.62mm/min, LCT-KD: 3.02+/-2.26mm/min) suggesting that both short-term KDs have a positive effect in decreasing brain cerebral excitability in young animals. These data show for the first time that triheptanoin has an effect on central nervous system.


Asunto(s)
Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Depresión de Propagación Cortical/efectos de los fármacos , Grasas de la Dieta/farmacología , Triglicéridos/metabolismo , Triglicéridos/farmacología , Animales , Corteza Cerebral/fisiopatología , Depresión de Propagación Cortical/fisiología , Grasas de la Dieta/uso terapéutico , Suplementos Dietéticos/normas , Modelos Animales de Enfermedad , Esquema de Medicación , Potenciales Evocados/efectos de los fármacos , Potenciales Evocados/fisiología , Ácidos Grasos/metabolismo , Alimentos Formulados/normas , Ácidos Heptanoicos/metabolismo , Ácidos Heptanoicos/farmacología , Ácidos Heptanoicos/uso terapéutico , Cetonas/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/fisiología , Masculino , Ratas , Ratas Wistar , Aceite de Soja/metabolismo , Aceite de Soja/farmacología , Aceite de Soja/uso terapéutico , Resultado del Tratamiento , Triglicéridos/uso terapéutico
19.
J Chromatogr A ; 1566: 13-22, 2018 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-29945788

RESUMEN

Polycyclic Aromatic Hydrocarbons (PAHs) have been detected in rubber and plastic components of a number of consumer products such as toys, tools for domestic use, sports equipment, and footwear, with carbon black and extender oils having been identified as principal sources. In response to these findings, the European Union Regulation (EU) No. 1272/2013 was adopted in December 2013, amending entry 50 in Annex XVII to the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH) directive establishing a restriction on the content of eight individual carcinogenic PAHs in plastic and rubber parts of products supplied to the public. This work proposes a simple, relatively fast, and cost effective method for determining the concentrations of each of these eight carcinogenic PAHs for compliance testing. Existing methodologies were taken as a starting point, improving in particular the extraction and the clean-up procedures. Randall hot extraction and ultrasonic extraction were compared with regard to their extraction efficiency. Randall hot extraction proved to be more efficient (10-40%, depending on PAH). Sample extract clean-up performance was qualitatively assessed for silica-packed columns and molecularly imprinted polymers (MIPs) solid phase extraction (SPE) cartridges. The use of highly selective MIP-SPE cartridges removed most of the undesired contaminants, highlighting their superiority with regard to traditional, silica-based purification methodologies. The introduction of Randall-hot extraction for sample extraction and MIP-based solid phase extraction cartridges for selective clean-up represents a novel advance compared with previously reported methods in this field. In combination with gas chromatography-mass spectrometry (GC-MS) analyses in selected ion mode, the method was found to be excellent in terms of extraction efficiency, extract purity, and speed.


Asunto(s)
Técnicas de Química Analítica/métodos , Plásticos/química , Hidrocarburos Policíclicos Aromáticos/análisis , Goma/química , Cromatografía de Gases y Espectrometría de Masas , Reproducibilidad de los Resultados , Extracción en Fase Sólida
20.
Rev. bras. oftalmol ; 78(6): 389-393, nov.-dez. 2019. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1057911

RESUMEN

Abstract Purpose: To evaluate visual outcomes of levodopa treatment associated with full occlusion of the dominant eye in patients with refractory amblyopia. Methods: A prospective study of 19 attended patients who were subject to treatment with Levodopa and Carbidopa on doses of 0.7mg/kg/day, a ratio of 4:1 divided into three daily doses for 5 weeks, combined with full occlusion (24 hours/day) of the dominant eye. The ophthalmologic exam from previous consultations up to treatment and after 8 weeks of therapy were collected from medical record data. Patients who had completed treatment for more than 12 months were included for complete eye examination. Results: The mean age before treatment with levodopa was 11.0 ± 4.2 years old (varying from 7 to 23 years). The best-corrected visual acuity (Snellen chart) of the amblyopic eye before treatment was 0.24 (0.6 in logMAR) ± 0.16, after 8 weeks of treatment it was 0.47(0.3 in logMAR) ± 0.33, while during the final evaluation it was 0.46 (0.3 in logMAR) ± 0.34. There was a statistically significant improvement in vision after 8 weeks of therapy which was maintained until the final evaluation (p = 0.007). Conclusion: Levodopa/Carbidopa therapyat doses of 0.7 mg/kg/day at a ratio of 4:1 divided in three daily doses, associated with full occlusion of the dominant eye during 5 weeks had a significant improvement on the visual acuity of the amblyopic eye, and persisted up to 1 year after the treatment.


Resumo Objetivo: Avaliar os resultados visuais do tratamento com levodopa associada à oclusão total do olho dominante em pacientes amblíopes. Métodos: Estudo prospectivo de 19 pacientes atendidos e submetidos ao tratamento com levodopa e carbidopa na dose de 0,7 mg/kg/dia e proporção de 4:1, divididos em três doses diárias, durante cinco semanas, combinada a oclusão total (24 horas/dia) do olho dominante. Foram coletados dados do prontuário referentes ao exame oftalmológico da consulta anterior ao tratamento e após 8 semanas de terapia. Os pacientes com término do tratamento com mais de 12 meses foram reconvocados para exame oftalmológico completo. Resultados: A média de idade dos pacientes previamente ao tratamento com levodopa foi de 11,0 ± 4,2 anos (variando de 7 a 23 anos). A acuidade visual melhor corrigida (Snellen) do olho amblíope antes do tratamento foi de 0,24 (0,6 em logMAR) ± 0,16, após 8 semanas de tratamento foi de 0,47 (0,3 em logMAR) ± 0,33 e na avaliação final foi de 0,46 (0,3 em logMAR) ± 0,34. Houve melhora estatisticamente significante da visão após 8 semanas de tratamento que se manteve até a avaliação final (p = 0,007) Conclusão: A terapia com levodopa/carbidopa em doses de 0,7mg/kg/dia na proporção de 4:1 dividida em três doses diárias, associada à oclusão total do olho dominante durante 5 semanas, apresentou uma melhora significativa na acuidade visual do olho ambliópico e persistiu até 1 ano após o tratamento.


Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Privación Sensorial , Carbidopa/uso terapéutico , Levodopa/uso terapéutico , Ambliopía/terapia , Terapia Combinada , Carbidopa/administración & dosificación , Levodopa/administración & dosificación , Agudeza Visual , Administración Oral , Estudios Prospectivos , Predominio Ocular , Combinación de Medicamentos
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