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1.
BMC Med Res Methodol ; 22(1): 155, 2022 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-35637426

RESUMEN

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Clorhidrato de Fingolimod/uso terapéutico , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/uso terapéutico , Resultado del Tratamiento
2.
J Acoust Soc Am ; 149(5): 2943, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34241124

RESUMEN

A baseline-free defect localization method in thin plates is proposed and tested. In this proof-of-concept work, a steel ball pressed against an aluminum plate is used to mimic a surface contact defect. The technique takes benefit of a repetitive nonlinear pump-probe interaction with a backpropagation imaging algorithm. High-frequency probe waves are periodically emitted by a piezoelectric patch transducer glued to the plate. Propagated flexural waves are recorded using a distributed array of transducers. At the same time, a continuous low-frequency pump vibration provided by a shaker fixed to the plate modulates the contact state. By combining multiple probe signals, the contact can be successfully localized. Contrast of the localization images is finally improved by a factor of 3 to 5 by implementing a modified version based on synchronous detection of the imaging algorithm.

3.
Soft Matter ; 15(44): 9085-9092, 2019 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-31657434

RESUMEN

We investigate the Poisson ratio ν of fluid lipid bilayers, i.e., the question how area strains compare to the changes in membrane thickness (or, equivalently, volume) that accompany them. We first examine existing experimental results on the area- and volume compressibility of lipid membranes. Analyzing them within the framework of linear elasticity theory for homogeneous thin fluid sheets leads us to conclude that lipid membrane deformations are to a very good approximation volume-preserving, with a Poisson ratio that is likely about 3% smaller than the common soft matter limit . These results are fully consistent with atomistic simulations of a DOPC membrane at varying amount of applied lateral stress, for which we instead deduce ν by directly comparing area- and volume strains. To assess the problematic assumption of transverse homogeneity, we also define a depth-resolved Poisson ratio ν(z) and determine it through a refined analysis of the same set of simulations. We find that throughout the membrane's thickness, ν(z) is close to the value derived assuming homogeneity, with only minor variations of borderline statistical significance.


Asunto(s)
Membrana Dobles de Lípidos/química , Modelos Químicos , Fosfatidilcolinas/química , Simulación por Computador , Elasticidad , Distribución de Poisson , Tensión Superficial , Termodinámica
4.
J Chem Phys ; 151(16): 164108, 2019 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-31675861

RESUMEN

The tilt of a lipid molecule describes the deviation of its orientation away from the local normal of its embedding membrane. Tilt is the subleading degree of freedom after a membrane's geometry, and it becomes relevant at scales comparable to lipid bilayer thickness. Building on earlier work by Hamm and Kozlov [Eur. Phys. J. E 3, 323 (2000)], who envisioned lipid membranes as thin prestressed fluid elastic films, and Terzi and Deserno [J. Chem. Phys. 147, 084702 (2017)], who discovered a new coupling term between splay and tilt divergence, we construct a theory of membrane elasticity that is quadratic in geometry and tilt and complete at order 1/length2. We show that a general and consistent treatment of both lateral and transverse depth-dependent shear stresses creates several contributions to the elastic energy density, of which only a subset had previously been identified. Apart from the well-known penalty of lipid twist (the curl of tilt), these terms generate no qualitatively new phenomenology, but they quantitatively revise the connections between the moduli of a tilt-curvature theory and its underlying microscopic foundation. In particular, we argue that the monolayer Gaussian curvature modulus κ¯m, widely believed to be equal to the second moment of the transmonolayer stress profile, acquires a second contribution from lipid twist, which is always negative. This could resolve the long-standing conundrum that many measured values of κ¯m appeared to have a sign that violates basic stability considerations. We also show that the previously discovered novel coupling between splay and tilt divergence is not simply proportional to κ¯m but acquires its own splay-tilt coupling modulus, κst,m. We explore the predictions of our theory for various elastic moduli and their mutual interrelations and use an extensive set of existing atomistic molecular dynamics simulations for 12 different lipid types to collectively reason about such predictions. We find that bending rigidities are captured fairly well by existing theories, while reliable predictions for local moduli, especially the splay-tilt coupling modulus, remain challenging.

5.
J Chem Phys ; 147(8): 084702, 2017 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-28863515

RESUMEN

On mesoscopic scales, lipid membranes are well described by continuum theories whose main ingredients are the curvature of a membrane's reference surface and the tilt of its lipid constituents. In particular, Hamm and Kozlov [Eur. Phys. J. E 3, 323 (2000)] have shown how to systematically derive such a tilt-curvature Hamiltonian based on the elementary assumption of a thin fluid elastic sheet experiencing internal lateral pre-stress. Performing a dimensional reduction, they not only derive the basic form of the effective surface Hamiltonian but also express its emergent elastic couplings as trans-membrane moments of lower-level material parameters. In the present paper, we argue, though, that their derivation unfortunately missed a coupling term between curvature and tilt. This term arises because, as one moves along the membrane, the curvature-induced change of transverse distances contributes to the area strain-an effect that was believed to be small but nevertheless ends up contributing at the same (quadratic) order as all other terms in their Hamiltonian. We illustrate the consequences of this amendment by deriving the monolayer and bilayer Euler-Lagrange equations for the tilt, as well as the power spectra of shape, tilt, and director fluctuations. A particularly curious aspect of our new term is that its associated coupling constant is the second moment of the lipid monolayer's lateral stress profile-which within this framework is equal to the monolayer Gaussian curvature modulus, κ¯m. On the one hand, this implies that many theoretical predictions now contain a parameter that is poorly known (because the Gauss-Bonnet theorem limits access to the integrated Gaussian curvature); on the other hand, the appearance of κ¯m outside of its Gaussian curvature provenance opens opportunities for measuring it by more conventional means, for instance by monitoring a membrane's undulation spectrum at short scales.


Asunto(s)
Membrana Dobles de Lípidos/química , Lípidos de la Membrana/química , Algoritmos , Membrana Celular/química , Elasticidad , Fluidez de la Membrana , Modelos Moleculares , Distribución Normal
6.
Eur Rev Med Pharmacol Sci ; 27(16): 7728-7737, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37667951

RESUMEN

OBJECTIVE: The impact of COVID-19 vaccination on parental and childhood stress levels has not been thoroughly investigated. Our aim was to explore the above relationship and identify factors that may influence the dissemination of stress within the family during the pandemic. SUBJECTS AND METHODS: A cross-sectional e-survey was conducted among a nationwide sample of parents in May 2021 in Greece. Parental stress was assessed using the Perceived Stress Scale (PSS) and the Revised Impact of Event Scale (IES-R) tools. Childhood mental well-being was evaluated with the Children's Revised Impact of Event 13 (CRIES 13) scale. RESULTS: 1,703 unique questionnaires were analyzed; 19.5% of responders were completely vaccinated, 23.7% were partially vaccinated, 38.3% were awaiting vaccination, and 18.5% were classified as vaccine-hesitant (15.2% would delay, and 3.3% refused the vaccination). Stress levels were significantly lower in completely or partially vaccinated parents than in vaccine-hesitant ones (p<0.001 for PSS/IES-R). Vaccination status emerged as a strong and independent predictor of PSS and IES-R. A significant decrease in PSS and IES-R scores was observed in 991 participants between March 2020 and May 2021 (p<0.001 for PSS/IES-R). Vaccine uptake was associated with lower PSS and IES-R scores, irrespective of the phase of the pandemic or other sociodemographic factors. The CRIES 13 score of the participant's children (n=2,969) was 19.4 ±14.9 and positively correlated with the PSS and IES-R scores. Children whose parents were vaccinated had lower stress levels than those of vaccine-hesitant parents (p<0.001). CONCLUSIONS: Parental vaccination against COVID-19 is a significant stress and anxiety predictor for both parents and their offspring. Parental and childhood stress levels were correlated, while the effect of vaccination was independent of the pandemic phase. The campaigns to promote vaccine uptake against COVID-19 should also highlight its potential benefit on the psychological well-being of the family.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Niño , Humanos , Grecia/epidemiología , Estudios Transversales , COVID-19/epidemiología , COVID-19/prevención & control , Vacunación , Padres
7.
Mult Scler ; 18(10): 1448-53, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22419670

RESUMEN

BACKGROUND: Demyelinating lesions over 20 mm in size, referred to as tumefactive demyelinating lesions, can be misdiagnosed as being either a tumor or an abscess. Although some radiological characteristics can help make a differential diagnosis easier, a cerebral biopsy may still be necessary. OBJECTIVE: Our objective was to assess the clinical characteristics of tumefactive lesions, with or without a diagnosis of multiple sclerosis (MS), and present follow-up data for 54 patients with tumefactive lesions. METHODS: Demographic, clinical, radiological and laboratory data were gathered and treatment responses were evaluated in a total of 54 patients from five medical centers. RESULT: Twenty-nine patients were diagnosed with tumefactive lesions at the onset, whereas 25 patients were diagnosed with tumefactive lesions after a diagnosis of MS. Median follow-up was 38.12 months. At final examination, 19 of the patients with a tumefactive lesion diagnosis at the onset eventually developed relapsing-remitting MS, while 10 remained with the condition as a clinically isolated syndrome. The tumefactive lesions studied were mostly focal, with closed-ring enhancement. We found that oligoclonal band positivity was less frequent in the patients with tumefactive onset. CONCLUSION: Although our demographic data were similar to formerly collected Turkish MS data, we found that the distribution of the patients' clinical course differed if there was an absence of primary progressive MS and that there was a lower frequency of secondary progressive MS cases in our group of patients. We believe that less frequent oligoclonal band positivity and the difference we witnessed in the clinical course of disease in our study groups suggest that there is a need for further studies to compare all the biological and immunological differences between MS and tumefactive lesion cases, in order to reveal whether there are different pathogenetic mechanisms involved.


Asunto(s)
Enfermedades Desmielinizantes/diagnóstico , Esclerosis Múltiple/diagnóstico , Adolescente , Adulto , Encéfalo/patología , Absceso Encefálico/diagnóstico , Neoplasias Encefálicas/diagnóstico , Enfermedades Desmielinizantes/inmunología , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/inmunología , Bandas Oligoclonales , Estudios Retrospectivos , Adulto Joven
8.
Mult Scler Relat Disord ; 52: 102968, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33940495

RESUMEN

BACKGROUND: The pandemic of the new type of corona virus infection 2019 [Covid-19] also affect people with Multiple Sclerosis (pwMS). Currently, the accumulating information on the effects of the infection regarding the demographic and clinical characteristics of the disease, as well as outcomes within different DMTs¸ enable us to have better practices on the management of the Covid-19 infection in pwMS. OBJECTIVE: To investigate the incidence of coronavirus disease 2019 (Covid-19) and to reveal the relationship between the demographic-clinical and therapeutic features and the outcome of Covid-19 infection in a multi-center national cohort of pwMS. METHODS: The Turkish Neurological Society-MS Study Group in association with the Italian MuSC-19 Study Group initiated this study. A web-based electronic Case Report Form (eCRF) of Study-MuSC-19 were used to collect the data. The demographic data and MS histories of the patients were obtained from the file tracking forms of the relevant clinics. RESULTS: 309 MS patients with confirmed Covid-19 infection were included in this study. Two hundred nineteen (219) were females (70.9%). The mean age was 36.9, ranging from 18 to 66, 194 of them (62.8%) were under 40. The clinical phenotype was relapsing-remitting in 277 (89.6%) and progressive in 32 (10.4%). Disease duration ranged from 0.2 years to 31.4 years. The median EDSS was 1.5, ranging from 0 to 8.5. The EDSS score was<= 1 in 134 (43%) of the patients. 91.6% of the patients were on a DMT, Fingolimod was the most frequently used drug (22.0%), followed by Interferon (20.1%). The comorbidity rate is 11.7%. We were not able to detect any significant association of DMTs with Covid-19 severity. CONCLUSION: The Turkish MS-Covid-19 cohort had confirmed that pwMS are not at risk of having a more severe COVID-19 outcome irrespective of the DMT that they are treated. In addition, due to being a younger population with less comorbidities most had a mild disease further highlight that the only associated risk factors for having a moderate to severe COVID-19 course are similar with the general population such as having comorbid conditions and being older.


Asunto(s)
COVID-19 , Esclerosis Múltiple , Adulto , Estudios de Cohortes , Femenino , Clorhidrato de Fingolimod , Humanos , SARS-CoV-2
9.
Phys Rev E ; 102(1-1): 012122, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32795063

RESUMEN

The Preisach model has been useful as a null model for understanding memory formation in periodically driven disordered systems. In amorphous solids, for example, the athermal response to shear is due to localized plastic events (soft spots). As shown recently by Mungan et al. [Phys. Rev. Lett. 123, 178002 (2019)PRLTAO0031-900710.1103/PhysRevLett.123.178002], the plastic response to applied shear can be rigorously described in terms of a directed network whose transitions correspond to one or more soft spots changing states. The topology of this graph depends on the interactions between soft spots and when such interactions are negligible, the resulting description becomes that of the Preisach model. A first step in linking transition graph topology with the underlying soft-spot interactions is therefore to determine the structure of such graphs in the absence of interactions. Here we perform a detailed analysis of the transition graph of the Preisach model. We highlight the important role played by return-point memory in organizing the graph into a hierarchy of loops and subloops. Our analysis reveals that the topology of a large portion of this graph is actually not governed by the values of the switching fields that describe the hysteretic behavior of the individual elements but by a coarser parameter, a permutation ρ which prescribes the sequence in which the individual hysteretic elements change their states as the main hysteresis loop is traversed. This in turn allows us to derive combinatorial properties, such as the number of major loops in the transition graph as well as the number of states |R| constituting the main hysteresis loop and its nested subloops. We find that |R| is equal to the number of increasing subsequences contained in the permutation ρ.

10.
Mult Scler Relat Disord ; 33: 94-99, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31176296

RESUMEN

Susac's Syndrome (SS), which was first described in 1979, is a rare and presumably autoimmune disorder characterized by encephalopathy, hearing loss, and visual disturbance resulting from branch retinal artery occlusion (BRAO). This study reports 19 SS patients' clinical characteristics, MRI features, CSF analysis, treatment strategies and outcomes. At initial presentation, only three of 19 patients demonstrated the complete clinical triad. Clinic presentation varied from isolated hemiparesis to the full triad (encephalopathy, hearing loss and visual disturbances). Corpus callosum (CC) involvement was noted in the MRI of 18 patients (97%) and BRAO was detected in 17 (95%) patients. All patients were treated with intravenous methylprednisolone after the initial assessment. This case series is presented to emphasize the differences in clinical presentation of SS and the importance of MRI and FFA in diagnosis.


Asunto(s)
Síndrome de Susac/diagnóstico , Síndrome de Susac/tratamiento farmacológico , Síndrome de Susac/patología , Adulto , Anciano , Antiinflamatorios/uso terapéutico , Femenino , Angiografía con Fluoresceína/métodos , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
11.
Plant Cell ; 5(6): 615-620, 1993 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12271077

RESUMEN

At a nonpermissive temperature, somatic embryos of the temperature-sensitive (ts) carrot cell mutant ts11 only proceed beyond the globular embryo stage in the presence of medium conditioned by wild-type embryos. The causative component in the conditioned medium has previously been identified as a 32-kD acidic endochitinase. In search of a function for this enzyme in plant embryogenesis, several compounds that contain oligomers of N-acetylglucosamine were tested for their ability to promote ts11 embryo formation. Of these compounds, only the Rhizobium lipooligosaccharides or nodulation (Nod) factors were found to be effective in rescuing the formation of ts11 embryos. These results suggest that N-acetylglucosamine-containing lipooligosaccharides from bacterial origin can mimic the effect of the carrot endochitinase. This endochitinase may therefore be involved in the generation of plant analogs of the Rhizobium Nod factors.

12.
G Ital Med Lav Ergon ; 27(4): 427-30, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16512340

RESUMEN

The study regards workers employed in manual metal are welding of stainless steel (MMA/SS). For two weeks they collected their urine during the work shift and the 16 hours following in order to evaluate the kinetics of nickel. Using one-compartment mathematical modelling we calculated the values of the toxicant's urinary half life during the two phases of exposure and postexposure and also during non working weekends. The aim of the study was to find correlations between inhaled doses and excreted quantities and to acquire practical data for use in biological monitoring. In the welders the mean urinary half life in the exposure period was 59.5 hours, in the post exposure it was 95.6 hours, while in weekend it was 95.5 hours. The study showed that exposure to fumes containing nickel could determine the accumulation of the metal in slow elimination speed compartment. As a consequence of the accumulation of nickel in compartments with different elimination speeds, the collection of single urinary portions in biological monitoring seems to give little information about the actual exposure. In our opinion this indicates collecting urine samples throughout the entire work shift and the 16 hours following exposure.


Asunto(s)
Contaminantes Ocupacionales del Aire/efectos adversos , Monitoreo del Ambiente/métodos , Níquel/orina , Exposición Profesional/efectos adversos , Acero Inoxidable , Soldadura , Humanos , Cinética , Masculino , Modelos Teóricos , Factores de Tiempo
13.
Eur J Cell Biol ; 79(4): 294-8, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10826497

RESUMEN

Programmed cell death (apoptosis) in plants - and plant cells in culture - has received much less attention than its animal counterpart. In the present work, using agents producing biotic or abiotic stress on cultivated cells from carrot - and, in a few experiments, Arabidopsis -, we show that DNA fragmentation, random or oligonucleosomal, can be induced by different treatments. Moreover, we demonstrate that the same cultures may or may not respond to the inducing signal according to their physiological state. In particular, stationary cells are more responsive to the inducing signal than actively proliferating ones, and cells growing in an unorganized way are more responsive than cells carrying out the embryogenic programme. Senescent cells in culture also appear to die by apoptosis, but healthy cells can also be induced to die apoptotically if exposed to the medium conditioned by senescent cells of the same or different species.


Asunto(s)
Apoptosis , Daucus carota/metabolismo , Arabidopsis/metabolismo , Células Cultivadas , Senescencia Celular , Medios de Cultivo , ADN/metabolismo , Fragmentación del ADN , Protoplastos/metabolismo , Factores de Tiempo
14.
FEBS Lett ; 447(2-3): 191-4, 1999 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-10214943

RESUMEN

Protein tyrosine phosphorylation plays a central role in a variety of signal transduction pathways regulating animal cell growth and differentiation, but its relevance and role in plants are controversial and still largely unknown. We report here that a large number of proteins from all plant subcellular fractions are recognized by recombinant, highly specific, anti-phosphotyrosine antibodies. Protein tyrosine phosphorylation patterns vary among different adult plant tissues or somatic embryo stages and somatic embryogenesis is blocked in vivo by a cell-permeable tyrosyl-phosphorylation inhibitor, demonstrating the involvement of protein tyrosine phosphorylation in control of specific steps in plant development.


Asunto(s)
Proteínas de Plantas/metabolismo , Plantas/metabolismo , Tirosina/metabolismo , Animales , Anticuerpos , Fosforilación , Desarrollo de la Planta , Proteínas de Plantas/química , Proteínas de Plantas/inmunología , Plantas/embriología , Transducción de Señal , Fracciones Subcelulares/metabolismo
15.
Am J Clin Nutr ; 60(4): 510-7, 1994 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8092085

RESUMEN

To investigate the relationships between aging and selenium status, vitamins A and E, and plasma and erythrocyte fatty acids, we studied 105 healthy subjects (53 women, 52 men) living in Nove, a village near Vicenza (Veneto Region, northern Italy). The subjects were distributed equally for age and sex into four groups: group 1, 20-39 y; group 2, 40-59 y; group 3, 60-75 y; and group 4, > 75 y. A careful selection of subjects to exclude those with chronic or acute diseases was obtained with the collaboration of the three general practitioners operating in Nove. Aging was associated with a progressive decrease in selenium status and in the ratio of plasma and erythrocyte polyunsaturated to saturated fatty acids (P:S). Stepwise multiple linear analysis revealed age, vitamin A, and n-6 polyunsaturated fatty acids (PUFAs) as useful predictors of a substantial proportion of the selenium variability (R = 0.618, R2 = 0.382; P < 0.001) and age and erythrocyte oleic acid as predictors of erythrocyte glutathione peroxidase variability (R = 0.413, R2 = 0.17; P < 0.001).


Asunto(s)
Envejecimiento/sangre , Ácidos Grasos/sangre , Estado Nutricional , Selenio/sangre , Vitamina A/sangre , Vitamina E/sangre , Adulto , Anciano , Anciano de 80 o más Años , Eritrocitos/metabolismo , Ácidos Grasos Insaturados , Femenino , Glutatión Peroxidasa/sangre , Humanos , Italia , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Análisis de Regresión , Superóxido Dismutasa/sangre
16.
J Pharm Sci ; 84(1): 93-5, 1995 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7714752

RESUMEN

An accurate and sensitive HPLC method has been developed for the determination of nitrofenac, a new, original diclofenac derivate showing a good tolerability and a wide anti-inflammatory profile, diclofenac, and its metabolites in plasma. This method has been applied to evaluate the pharmacokinetic parameters of the drugs, using a noncompartmental model, after the oral administration of 5 mg/kg nitrofenac to rats. Nitrofenac and the internal standard flufenamic acid were dissolved in acetonitrile, and diclofenac was dissolved in methanol. The drugs were eluted from a 5 microns LC-8 column with a mobile phase consisting of acetonitrile/water (50/50 v/v) adjusted to pH 3.3 with glacial acetic acid, at a flow rate of 2 mL/min with UV detection at 280 nm for diclofenac and 275 nm for nitrofenac. The detection limit for the drugs in plasma was 25 ng/mL. The peak concentration of nitrofenac was reached 7 h after drug administration, while with diclofenac we observed three peaks at 2, 5, and 10 h; the mean residence time and the elimination rate constant for nitrofenac were 6.18 +/- 0.09 h and 0.37 +/- 0.03 h-1 respectively, while those for diclofenac were 12.24 +/- 0.11 h and 0.11 +/- 0.04 h-1. Under our conditions, the metabolism of nitrofenac produced 23% diclofenac and other metabolites: the plasma concentrations and kinetic characteristics of diclofenac are enough to induce an anti-inflammatory activity, while the clinical importance of the other metabolites remains to be elucidated.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacocinética , Diclofenaco/análogos & derivados , Animales , Antiinflamatorios no Esteroideos/sangre , Cromatografía Líquida de Alta Presión , Diclofenaco/sangre , Diclofenaco/farmacocinética , Concentración de Iones de Hidrógeno , Indicadores y Reactivos , Masculino , Ratas , Ratas Sprague-Dawley , Espectrofotometría Ultravioleta
17.
J Pharm Pharmacol ; 48(5): 468-73, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8799869

RESUMEN

A biocompatible and biodegradable polyphosphazene bearing phenylalanine ethyl ester, imidazole and chlorine (10.7:1:2.5 molar ratio) as substituents of the phosphorus atoms of the polymer backbone was studied for the preparation of polymeric naproxen slow-release systems. Discs 2.5 cm in diameter and 0.5 mm (thin) or 0.65 mm (thick), loaded, respectively, with 20 and 13.5% naproxen, showed different drug release kinetics, the thin matrices releasing naproxen at a faster rate and for a shorter time. In-vivo studies in rats demonstrated the pharmacological efficacy of these two different delivery systems in the inhibition of acute or chronic inflammatory diseases. Subcutaneous implantation of the thin matrices in rats was found to reduce carrageenan oedema induced both 1 h and 7 days after implantation. Rats implanted with thick matrices showed a reduction in chronic inflammation caused by adjuvant arthritis. Approximately 78% inhibition of arthritic oedema was found 28 days after subcutaneous administration of the matrices whereas 28.7% inhibition was found after daily oral administration of naproxen. Blood levels of naproxen in arthritic rats after matrix implantation showed the presence of drug up to day 28. These positive results have encouraged us to study a controlled-release system suitable for use in man.


Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Naproxeno/administración & dosificación , Compuestos Organofosforados , Polímeros , Administración Oral , Animales , Antiinflamatorios no Esteroideos/sangre , Antiinflamatorios no Esteroideos/farmacocinética , Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Carragenina , Cromatografía Líquida de Alta Presión , Preparaciones de Acción Retardada , Implantes de Medicamentos , Edema/inducido químicamente , Edema/tratamiento farmacológico , Adyuvante de Freund , Masculino , Naproxeno/sangre , Naproxeno/farmacocinética , Naproxeno/uso terapéutico , Ratas , Ratas Endogámicas Lew , Ratas Sprague-Dawley
18.
Surg Laparosc Endosc Percutan Tech ; 12(5): 342-6, 2002 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12409701

RESUMEN

Intraabdominal adhesions represent a significant problem because of the morbidity associated with adhesive disease, including small bowel obstruction, difficulties in reoperative surgery, and possibly chronic pain. Coating solution of sodium hyaluronate (Sepracoat; Genzyme Production-Surgical Products, Cambridge, MA) was studied in New Zealand white rabbits to determine its potential role for prevention of postoperative adhesions following laparoscopic intraabdominal mesh insertion. A 2-cm polypropylene mesh was inserted laparoscopically to the left iliac fossa and fixed to anterior abdominal wall using a single prolen suture. Group 1 (n = 10) acted as the control group. Mesh was coated using 4% sodium hyaluronate in phosphate buffered saline (Sepracoat) in Group 2 (n = 10). Fourteen days later, all animals underwent diagnostic laparoscopy, and findings were recorded. All animals then were killed, the abdominal cavities were inspected, and adhesions were graded from 0 to 4. All meshes were removed and sent for histologic examination. The degrees of inflammation, fibrosis, and congestion were scored. No adhesions were seen on trocar sites on both groups. Eight of 10 animals in the control group and 5 of 10 animals in the study group had intraabdominal adhesions. The scoring of adhesions revealed that study group had only one (10%) significant adhesion, whereas the control group had eight (80%; < 0.001). Our study suggests that the Sepracoat reduces the incidence and severity of abdominal adhesions following laparoscopic mesh insertion and should be considered as a prophylactic agent, especially in those undergoing laparoscopic transabdominal mesh repair for hernia.


Asunto(s)
Materiales Biocompatibles/efectos adversos , Materiales Biocompatibles/uso terapéutico , Hernia Ventral/cirugía , Laparoscopía/efectos adversos , Complicaciones Posoperatorias , Mallas Quirúrgicas/efectos adversos , Adherencias Tisulares/etiología , Adherencias Tisulares/prevención & control , Abdomen/patología , Abdomen/cirugía , Animales , Modelos Animales de Enfermedad , Hernia Ventral/patología , Ácido Hialurónico , Conejos , Índice de Severidad de la Enfermedad , Adherencias Tisulares/patología
19.
Minerva Med ; 94(4 Suppl 1): 27-38, 2003 Aug.
Artículo en Italiano | MEDLINE | ID: mdl-15108609

RESUMEN

Migraine is a typical "women's disease": the fluctuations of sex hormones, in particular estrogens, during woman's reproductive life show a direct and major influence on migraine course. Even if during pregnancy a high percentage of migraineurs report an improvement of symptomatology, it is still controversial how to manage migraine crises occurring during pregnancy, considering that almost all drugs are partially or totally contraindicated during gestation. The most important drugs employed in acute attack management (triptans, non steroidal anti-inflammatory drugs, analgesics, antiemetics, ergot derivatives and combination products) are reviewed and the indications and contraindications of their use during the 3 trimesters of pregnancy and during lactation, taking into consideration the indications of the Food and Drug Administration and of the American Academy of Pediatrics, are analysed. Furthermore, the therapeutic effects of the 2 most important non pharmacological therapies used for migraine prophylaxis, biofeedback and acupuncture, are discussed. For this latter therapy, the personal preliminary positive experience using a predetermined formula of acupoints for the combined treatment of migraine and hyperemesis gravidarum is reported.


Asunto(s)
Terapia por Acupuntura , Biorretroalimentación Psicológica , Lactancia , Trastornos Migrañosos/terapia , Complicaciones del Embarazo/terapia , Terapia por Relajación , Anomalías Inducidas por Medicamentos/etiología , Acetaminofén/efectos adversos , Acetaminofén/uso terapéutico , Puntos de Acupuntura , Adulto , Analgésicos/efectos adversos , Analgésicos/uso terapéutico , Analgésicos no Narcóticos/efectos adversos , Analgésicos no Narcóticos/uso terapéutico , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Antieméticos/efectos adversos , Antieméticos/uso terapéutico , Aspirina/efectos adversos , Aspirina/uso terapéutico , Ensayos Clínicos Controlados como Asunto , Domperidona/efectos adversos , Domperidona/uso terapéutico , Ergotamina/efectos adversos , Ergotamina/uso terapéutico , Femenino , Feto/efectos de los fármacos , Humanos , Hiperemesis Gravídica/terapia , Recién Nacido , Trastornos Migrañosos/diagnóstico , Trastornos Migrañosos/tratamiento farmacológico , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Tercer Trimestre del Embarazo , Pronóstico , Factores de Riesgo , Estados Unidos , United States Food and Drug Administration , Vasoconstrictores/efectos adversos , Vasoconstrictores/uso terapéutico
20.
G Ital Med Lav Ergon ; 23(1): 18-20, 2001.
Artículo en Italiano | MEDLINE | ID: mdl-11386181

RESUMEN

We report the case of a 73-year-old worker who died of pleural mesothelioma, after being employed for 35 years in a wool textile plant of Biella (Italy). Close investigations revealed that he provided for the maintenance of materials and machines. In particular, he used to replace asbestos parts such as rings, joints and insulations of pipelines (dyeing unit), as well as brake linings of warping, looming and combing machines. Beside confirming the importance of an accurate occupational anamnesis to recognize work-induced cancers, the case draws the attention on the risk of mesothelioma in the wool industry, an occupational setting that is not usually considered as a potential source of exposure to asbestos fibres. Such pollution might explain the increased mortality due to pleural mesothelioma in the Biella area (characterized by a prosperous textile industry), reported in previous epidemiological studies.


Asunto(s)
Asbestosis/etiología , Mesotelioma/etiología , Exposición Profesional , Neoplasias Pleurales/etiología , Lana , Anciano , Animales , Humanos , Masculino
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