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1.
Am J Infect Control ; 52(4): 400-409, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37422066

ABSTRACT

BACKGROUND: To analyze whether the application of topical formulas as cosmetics or sunscreens could affect the skin thermographic readings in terms of infection control in pandemic situations. METHODS: The temperature of the skin of the dorsal region of the back and the face of 20 volunteers was followed after the application of 6 different types of gels, sunscreens, and make-up under controlled temperature and humidity conditions. High-resolution thermographic images were analyzed to calculate the temperature of treated skin compared to skin free of topical products. RESULTS: The application of hydroalcoholic gel resulted in a mean drop of more than 2°C just after 1 minute followed by organic sunscreens until 1.7°C. Recovery was observed progressively until minute 9. Color make-up type formulas, rich in iron oxide as well as sunscreens with mineral filters had little or no effect on the skin thermal response. CONCLUSIONS: It is possible to alter the skin temperature almost immediately by using hydroalcoholic gels and sunscreen cosmetics. So, it is possible to produce false negative data in the readings of patients screened thermically.


Subject(s)
Cosmetics , Sunscreening Agents , Humans , Skin , Gels , Ultraviolet Rays
2.
Front Med (Lausanne) ; 10: 1260514, 2023.
Article in English | MEDLINE | ID: mdl-37928475

ABSTRACT

Background: Summer and spring eruptions on the elbows are a variant of polymorphous light eruption described on clinical and histopathological grounds; however, to our knowledge, they have not been confirmed by photobiological studies. Objective: Based on photobiological studies, this study aimed to demonstrate the involvement of ultraviolet-A (UVA) radiation in this variant of polymorphous light eruption occurring exclusively on the elbows. Methods: A series of five patients with polymorphous light eruption lesions on the elbows were included in our study. All patients underwent phototesting and photoprovocation of the skin lesions after exposure to a UVA light source [Philips UVA HPA lamp (400 W)]. All patients underwent punch biopsy and histopathological and immunohistochemical studies with anti-CD123. Results: In all the cases, UVA irradiation caused the appearance of skin lesions on the elbows with characteristic polymorphous light eruption. Histological data showed edema in the superficial dermis and a perivascular lymphocytic infiltrate compatible with polymorphous light eruption. Immunohistochemical staining for CD1-23 showed negative results. Conclusions: For the first time, photobiological photoprovocation studies demonstrated that repeated exposure to UVA radiation leads to the generation of skin lesions on the elbows, which are clinically and histologically consistent with summer and spring eruptions, confirming that elbow rash is a variant of polymorphous light eruption.

4.
Photochem Photobiol ; 99(1): 184-192, 2023 01.
Article in English | MEDLINE | ID: mdl-35877464

ABSTRACT

The use of technical sportswear is now widespread, but the degree of protection these fabrics offer against UV radiation is not known. We have analyzed the capacity of different types of technical sportswear fabrics to protect against different UV biological effects. A sample of 34 100% polyester t-shirts from different manufactures was classified by color, fabric structure, cover factor, and due to different tonalities, dark, and clear color. Ultraviolet protection factor was calculated according to UNE-EN13758. The protection factor for other biological effects as pre-vitamin D3 production, non-melanoma skin cancer, photoimmunosuppression, and photoaging was analyzed. The effects of moisture and sweat in protection were also evaluated. From the analyzed sample garments, more than 75% achieved an excellent protection value (protection factor 40-50+). Higher values were found in double-layer type (P < 0.05). Cover factor was the main determinant of biological protection factors with correlation coefficients of 0.81 for UPF (erythema), 0.77 for NMSC, and 0.63 for photoimmunosuppression. Water or sweat humidity saturation increased biological protection factors over a 20% (P < 0.05). The 83% of the fabrics analyzed showed less than 5% of transmittance with labeling as UVA protective elements. No effect of fabric color was found related to biological protection factors. The 100% polyester sports T-shirts of the analyzed sample offer general protection against UV for different biological effects that can be increased by humidity but no affected by fabric color.


Subject(s)
Sweat , Ultraviolet Rays , Humans , Polyesters , Textiles , Erythema
5.
J Photochem Photobiol B ; 228: 112405, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35189578

ABSTRACT

Our exposure to blue light from artificial sources such as indoor lights (mainly light-emitting diodes [LEDs]) and electronic devices (e.g., smartphones, computer monitors, and television screens), has increased in recent years, particularly during the recent coronavirus disease 2019 lockdown. This radiation has been associated to skin damage across its potential in generating reactive oxygen species in both the epidermis and the dermis, skin water imbalances and of potential activating melanin production. These circumstances make it important to determine whether current blue light exposure levels under artificial illumination and electronic devices exposure can cause the previously indicated disorders as compared to solar UV and visible radiation in a typical summer day. Blue light accounted for 25% of the sun's rays, approximately 30% of radiation emitted by electronic devices, and approximately from 6% to 40% of that emitted by indoor lights. The reference equations showed that the sun was the main source of effective irradiance for immediate and persistent pigmentation as well as for potential oxidative stress in our skin. Effective blue light exposure to artificial devices is significantly lower than the solar contribution. However, its contribution must be considered as accumulative dose effect, and especially in people with hypersensitivity promoting skin hyperpigmentation.


Subject(s)
Light , Melanins/metabolism , Oxidative Stress/radiation effects , Ultraviolet Rays , Electronics , Humans , Skin Pigmentation/radiation effects
6.
Photodiagnosis Photodyn Ther ; 37: 102719, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35021108

ABSTRACT

One of the key aspects of photodynamic therapy is the light source that is used to irradiate the lesion to be treated. The devices used must ensure that their emission spectrum matches the absorption spectrum of the photosensitizer, so that treatment radiation is delivered only on the target area, without irradiating healthy tissue at superficial or deep levels. Irradiance values must be adequate in order to avoid thermal damage, exceed the oxygen replenishment rate and avoid long treatment times. Furthermore, the device should be user-friendly, inexpensive, and able to be adapted to different photosensitizers. We have developed an easy-to-use and highly customizable device based on LED technology. Its innovative geometric design allows radiation to be delivered to a small treatment surface, since the LEDs are arranged in three arms, the configuration of which directs their radiation on the treatment point. Different high-power color LEDs are disposed on the arms, and can be independently selected based on the most effective wavelengths for exciting the different photodynamic therapy photosensitizers. We have tested the prototype in 5 different patients (1 actinic keratose, 1 actinic cheilitis, 1 superficial basal cell carcinoma and 2 Bowen's disease) and after 1-2 sessions of total cumulative dose of 25-50 J / cm2, 100% clearance of lesions were obtained. Our device can be used by any professional in the field, whether for medical or research purposes. It facilitates the development of treatment protocols and trials with different photosensitizers.


Subject(s)
Bowen's Disease , Carcinoma, Basal Cell , Photochemotherapy , Skin Neoplasms , Bowen's Disease/drug therapy , Carcinoma, Basal Cell/drug therapy , Humans , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Skin Neoplasms/drug therapy
7.
Photochem Photobiol ; 96(6): 1267-1272, 2020 11.
Article in English | MEDLINE | ID: mdl-32533856

ABSTRACT

Photodynamic therapy is taking importance as a nonintrusive treatment for nail onychomycosis. Knowledge of true transmittance values across nails could lead to qualitative and quantitative improvements in light-based treatments. We have characterized the spectral transmittance of healthy and fungally infected human fingernails and toenails according to nail thickness, and we propose a surface transmittance model for the small-scale optimization of light-based treatments. Transmittance of fingernails and toenails was analyzed by means of spectroradiometric measurements under solar-simulated visible light radiation (400 nm to 750 nm). The nail thickness was measured by means of microscope measurement. Transmittance was highest at longer wavelengths and decreased gradually as the wavelengths became shorter but with a significant nail transmittance of around 20% in the blue region of the spectrum. In the case of nails affected by onychomycosis, transmittance fell to under 10% because of the thickness of the nails, with no changes in spectral characteristics of transmitted light. Nail thickness is the main variable controlling exponentially light transmission in the visible spectrum and not only red radiation is effective for nail onychomycosis PDT. Blue light, the spectral band more effective for PPIX absorption is also effectively transmitted.


Subject(s)
Nails/drug effects , Onychomycosis/drug therapy , Photochemotherapy , Humans
8.
Rev. nefrol. diál. traspl ; 38(4): 273-279, dic. 2018. tab
Article in Spanish | LILACS | ID: biblio-1006999

ABSTRACT

Los reportes de pacientes gestantes con enfermedad renal crónica en hemodiálisis (ERCHD) con partos exitosos son cada vez más frecuentes. En el Ministerio de Salud no hay registros oficiales publicados de pacientes en diálisis y, por lo tanto, se desconocen datos de gestantes en diálisis. Se realizó un estudio retrospectivo y multicéntrico de los casos de pacientes con ERCHD que tuvieron partos éxitos en los Hospitales Públicos de Lima. Se encontraron solo 4 con datos suficientes para el reporte. Las pacientes tuvieron una edad promedio de 29 años (DE: 4,8), con un tiempo de gestación promedio al finalizar la gestación de 30,5 semanas (DE: 3,69). La preeclampsia fue la complicación más frecuente en 2 de 4 pacientes y todas las pacientes tuvieron menos de 20 hs. semanales de tratamiento. El Ministerio de Salud debe planear medidas de contingencia para el manejo de estas pacientes que serán cada vez más frecuentes


Reports of pregnant patients with chronic kidney disease on hemodialysis (CKDHD) with successful births are becoming more frequent. In the Ministry of Health there are no publications of official records of patients on dialysis and, therefore, data about pregnant women on dialysis are unknown. A retrospective and multicenter study was conducted on patients with CKDHD who had successful births in the public hospitals of Lima. Only 4 were found to have enough data for the report. The patients had an average age of 29 years (SD: 4.8), with an average gestation time at the end of pregnancy of 30.5 weeks (SD: 3.69). Preeclampsia was the most common complication in 2 out of 4 patients and all patients had less than 20 hours of treatment per week. The Ministry of Health should propose contingency measures for the management of these cases, which will be more and more frequent


Subject(s)
Humans , Female , Pregnancy , Renal Dialysis , Delivery, Obstetric , Kidney Failure, Chronic
9.
J Biophotonics ; 11(10): e201800026, 2018 10.
Article in English | MEDLINE | ID: mdl-29575820

ABSTRACT

Nacre is a complex biomaterial made of aragonite-tablet bricks and organic mortar that is considerably resilient against breakage. Nacre has been studied with a wide range of laboratory techniques, leading to understanding key fundamentals and informing the creation of bio-inspired materials. In this article, we present an optical polarimetric technique to investigate nacre, taking advantage of the translucence and birefringence of its microcomponents. We focus our study on 3 classes of mollusks that have nacreous shells: bivalve (Pinctada fucata), gastropod (Haliotis asinina and Haliotis rufescens) and cephalopod (Nautilus pompilius). We sent polarized light from a laser through thin samples of nacre and did imaging polarimetry of the transmitted light. We observed clear distinctions between the structures of bivalve and gastropod, due to the spatial variation of their birefringence. The patterns for cephalopod were more similar to bivalve than gastropod. Bleaching of the samples disrupted the transmitted light. Subsequent refilling of the bivalve and gastropod nacre samples with oil produced optical patterns similar to those of unbleached samples. In cephalopod samples, we found that bleaching produced irreversible changes in the optical pattern.


Subject(s)
Nacre/metabolism , Scanning Laser Polarimetry , Animals , Cephalopoda/metabolism , Gastropoda/metabolism , Pinctada/metabolism
10.
Sci Rep ; 7(1): 13653, 2017 10 20.
Article in English | MEDLINE | ID: mdl-29057888

ABSTRACT

The polarization of light can exhibit unusual features when singular optical beams are involved. In 3-dimensional polarized random media the polarization orientation around singularities describe 1/2 or 3/2 Möbius strips. It has been predicted that if singular beams intersect non-collinearly in free space, the polarization ellipse rotates forming many-turn Möbius strips or twisted ribbons along closed loops around a central singularity. These polarization features are important because polarization is an aspect of light that mediate strong interactions with matter, with potential for new applications. We examined the non-collinear superposition of two unfocused paraxial light beams when one of them carried an optical vortex and the other one a uniform phase front, both in orthogonal states of circular polarization. It is known that these superpositions in 2-dimensions produce space-variant patterns of polarization. Relying on the symmetry of the problem, we extracted the 3-dimensional patterns from projective measurements, and confirmed the formation of many-turn Möbius strips or twisted ribbons when the topological charge of one of the component beams was odd or even, respectively. The measurements agree well with the modelings and confirmed that these types of patterns occur at macroscopic length scales and in ordinary superposition situations.

11.
Opt Express ; 25(13): 14935-14943, 2017 Jun 26.
Article in English | MEDLINE | ID: mdl-28788929

ABSTRACT

Space-variant polarization patterns present in the transverse mode of optical beams highlight disclination patterns of polarization about a singularity, often a C-point. These patterns are important for understanding rotational dislocations and for characterizing complex polarization patterns. Liquid-crystal devices known as q-plates have been used to produce two of the three types of disclination patterns in optical beams: lemons and stars. Here we report the production of the third type of disclination, which is asymmetric, known as the monstar. We do so with elliptically-symmetric q-plates. We present theory and measurements, and find excellent agreement between the two.

12.
R Soc Open Sci ; 4(2): 160893, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28386442

ABSTRACT

The inner layer of many bivalve and gastropod molluscs consists of iridescent nacre, a material that is structured like a brick wall with bricks consisting of crystalline aragonite and mortar of organic molecules. Myostracal layers formed during shell growth at the point of muscle attachment to the shell can be found interspersed within the nacre structure. Little has been done to examine the effect the myostracal layer has on subsequent nacre structure. Here we present data on the structure of the myostracal and nacre layers from a bivalve mollusc, Pinctada fucata. Scanning electron microscope imaging shows the myostracal layer consists of regular crystalline blocks. The nacre before the layer consists of tablets approximately 400 nm thick, while after the myostracal layer the tablets are approximately 500 nm thick. A new technique, imaging polarimetry, indicates that the aragonite crystals within the nacre following the myostracal layer have greater orientation uniformity than before the myostracal layer. The results presented here suggest a possible interaction between the myostracal layer and subsequent shell growth.

13.
J Opt Soc Am A Opt Image Sci Vis ; 34(4): 568-575, 2017 Apr 01.
Article in English | MEDLINE | ID: mdl-28375326

ABSTRACT

The control of spatial and polarization modes of optical beams enables the production of topological singularities encoded on the polarization of the light. This allows the study of topological disclinations not easily found in the natural setting. In this article we report on the observation of new features in disclinations realized with singular optical beams. They were prepared using three spatial modes bearing optical vortices in non-separable superpositions with circular polarization states. The disclinations involve asymmetric rotational dislocations, whose optical counterparts in the optical far field are known as C-points, and which are classified as monstars. They have been known to have a singularity index that can be positive, or negative as reported by us recently. Here we report on monstars with an index of zero. Monstars are characterized by having sectors bound by radial lines that involve curved lines radiating from the singularity. We found that kinks in otherwise smooth line patterns of asymmetric disclinations are scars of a separate but related pattern of line-slope discontinuities, carried optically by C-lines in the far field. These scars are indicative of the underlying structure or symmetry of the pattern. We present a general formalism to understand and generate monstars, along with measurements: the experimental results are in excellent agreement with theoretical modelings.

14.
Opt Lett ; 42(8): 1516-1519, 2017 Apr 15.
Article in English | MEDLINE | ID: mdl-28409786

ABSTRACT

The topological charge of a beam carrying an optical vortex is an important parameter that specifies the amount of orbital angular momentum carried by the beam and the azimuthal order of the beam mode. We present an experimental method to determine the sign and magnitude of the topological charge using a wedged optical flat as a lateral shearing interferometer. When the curvature of the wavefront is adjusted to be planar, the fringe pattern generated by the shearing interferometer consists of two conjoined forks that unambiguously identify the topological charge of the beam. We also investigated the changes in the pattern when the wedged flat is rotated.

15.
Sci Rep ; 6: 37714, 2016 12 20.
Article in English | MEDLINE | ID: mdl-27995952

ABSTRACT

Photon entanglement, the cornerstone of quantum correlations, provides a level of coherence that is not present in classical correlations. Harnessing it by study of its passage through organic matter may offer new possibilities for medical diagnosis technique. In this work, we study the preservation of photon entanglement in polarization, created by spontaneous parametric down-conversion, after one entangled photon propagates through multiphoton-scattering brain tissue slices with different thickness. The Tangle-Entropy (TS) plots show the strong preservation of entanglement of photons propagating in brain tissue. By spatially filtering the ballistic scattering of an entangled photon, we find that its polarization entanglement is preserved and non-locally correlated with its twin in the TS plots. The degree of entanglement correlates better with structure and water content than with sample thickness.


Subject(s)
Brain/metabolism , Photons , Animals , Kidney/metabolism , Rats , Tomography
16.
Biochem Pharmacol ; 86(2): 267-78, 2013 Jul 15.
Article in English | MEDLINE | ID: mdl-23648307

ABSTRACT

Human cardiac inward rectifier current (IK1) is generated by Kir2.x channels. Inhibition of IK1 could offer a useful antiarrhythmic strategy against fibrillatory arrhythmias. Therefore, elucidation of Kir2.x channels pharmacology, which still remains elusive, is mandatory. We characterized the electrophysiological and molecular basis of the inhibition produced by the antiarrhythmic propafenone of the current generated by Kir2.x channels (IKir2.x) and the IK1 recorded in human atrial myocytes. Wild type and mutated human Kir2.x channels were transiently transfected in CHO and HEK-293 cells. Macroscopic and single-channel currents were recorded using the patch-clamp technique. At concentrations >1µM propafenone inhibited IKir2.x the order of potency being Kir2.3∼IK1>Kir2.2>Kir2.1 channels. Blockade was irrespective of the extracellular K(+) concentration whereas markedly increased when the intracellular K(+) concentration was decreased. Propafenone decreased inward rectification since at potentials positive to the K(+) equilibrium potential propafenone-induced block decreased in a voltage-dependent manner. Importantly, propafenone favored the occurrence of subconductance levels in Kir2.x channels and decreased phosphatidylinositol 4,5-bisphosphate (PIP2)-channel affinity. Blind docking and site-directed mutagenesis experiments demonstrated that propafenone bound Kir2.x channels at the cytoplasmic domain, close to, but not in the pore itself, the binding site involving two conserved Arg residues (residues 228 and 260 in Kir2.1). Our results suggested that propafenone incorporated into the cytoplasmic domain of the channel in such a way that it decreased the net negative charge sensed by K(+) ions and polyamines which, in turn, promotes the appearance of subconductance levels and the decrease of PIP2 affinity of the channels.


Subject(s)
Cytoplasm/drug effects , Potassium Channels, Inwardly Rectifying/antagonists & inhibitors , Propafenone/pharmacology , Static Electricity , Aged , Animals , CHO Cells , Cricetinae , Cricetulus , Cytoplasm/metabolism , Female , HEK293 Cells , Humans , Male , Middle Aged , Patch-Clamp Techniques
17.
Appl Opt ; 51(15): 2925-34, 2012 May 20.
Article in English | MEDLINE | ID: mdl-22614595

ABSTRACT

We present a study of Poincaré-beam polarization patterns produced by collinear superposition of two Laguerre-Gauss spatial modes in orthogonal polarization eigenstates (circular or linear). We explore theoretically and experimentally the combinations that are possible. We find that the resulting patterns can be explained in terms of mappings of points on the Poincaré sphere onto points in the transverse plane of the beam mode. The modes that we produced yielded many types of polarization singularities.

18.
Eur J Med Chem ; 52: 251-62, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22503231

ABSTRACT

The synthesis, pharmacological evaluation and molecular modeling of heterocyclic substituted alkyl and cycloalkyl propargyl amines 1-7 of type I, and 9-12 of type II, designed as multipotent inhibitors able to simultaneously inhibit monoamine oxidases (MAO-A/B) as well as cholinesterase (AChE/BuChE) enzymes, as potential drugs for the treatment of Alzheimer's disease, are described. Indole derivatives 1-7 of type I are well known MAO inhibitors whose capacity to inhibit AChE and BuChE was here investigated for the first time. As a result, compound 7 was identified as a MAO-B inhibitor (IC(50) = 31 ± 2 nM) and a moderately selective eqBuChE inhibitor (IC(50) = 4.7 ± 0.2 µM). Conversely, the new and readily available 5-amino-7-(prop-2-yn-1-yl)-6,7,8,9-tetrahydropyrido[2,3-b][1,6]naphthyridine derivatives 9-13 of type II are poor MAO inhibitors, but showed AChE selective inhibition, compound 12 being the most attractive as it acts as a non-competitive inhibitor on EeAChE (IC(50) = 25 ± 3 nM, K(i) = 65 nM). The ability of this compound to interact with the AChE peripheral binding site was confirmed by kinetic studies and by molecular modeling investigation. Studies on human ChEs confirmed that 12 is a selective AChE inhibitor with inhibitory potency in the submicromolar range. Moreover, in agreement with its mode of action, 12 was shown to be able to inhibit Aß aggregation induced by hAChE by 30.6%.


Subject(s)
Alzheimer Disease/drug therapy , Cholinesterases/metabolism , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/pharmacology , Models, Molecular , Monoamine Oxidase/metabolism , Pargyline/analogs & derivatives , Propylamines/chemistry , Acetylcholinesterase/metabolism , Amyloid beta-Peptides/chemistry , Animals , Butyrylcholinesterase/metabolism , Chemistry Techniques, Synthetic , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/therapeutic use , Cholinesterases/chemistry , Electrophorus , Heterocyclic Compounds/chemistry , Heterocyclic Compounds/therapeutic use , Humans , Kinetics , Monoamine Oxidase/chemistry , Monoamine Oxidase Inhibitors/chemical synthesis , Monoamine Oxidase Inhibitors/chemistry , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase Inhibitors/therapeutic use , Pargyline/chemistry , Peptide Fragments/chemistry , Protein Multimerization/drug effects , Protein Structure, Secondary , Rats
20.
Eur J Med Chem ; 46(12): 6119-30, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22000936

ABSTRACT

The synthesis and pharmacological analyses of a number of furo[2,3-b]quinolin-4-amine, and pyrrolo[2,3-b]quinolin-4-amine derivatives are reported. Thus, we synthesized diversely substituted tacrine analogues 1-11 and 12-16 by Friedländer-type reaction of readily available o-amino(furano/pyrrolo)nitriles with suitable and selected cycloalkanones. The biological evaluation of furanotacrines1-11 and pyrrolotacrine13 showed that these are good, in the micromolar range, and highly selective inhibitors of BuChE. In the furanotacrine group, the most interesting inhibitor was 2-(p-tolyl)-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-amine (3) [IC(50) (eqBuChE)=2.9 ± 0.4 µM; IC(50) (hBuChE)=119 ± 15 µM]. Conversely, pyrrolotacrines 12 and 14 proved moderately equipotent for both cholinesterases, being 1,2-diphenyl-5,6,7,8-tetrahydro-1H-pyrrolo[2,3-b]quinolin-4-amine (12) the most potent for the inhibition of both enzymes [IC(50) (EeAChE)=0.61 ± 0.04 µM; IC(50) (eqBuChE)=0.074 ± 0.009 µM]. Moreover, pyrrolotacrine 12, at concentrations as low as 300 nM can afford significant neuroprotective effects against Aß-induced toxicity. Docking studies show that compounds 3 and 12 bind in the middle of the AChE active site gorge, but are buried deeper inside BuChE active site gorge, as a consequence of larger BuChE gorge void. All these data suggest that these new tacrine analogues could be used for the potential treatment of Alzheimer's disease.


Subject(s)
Aminoquinolines/chemistry , Aminoquinolines/pharmacology , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Tacrine/analogs & derivatives , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/enzymology , Aminoquinolines/chemical synthesis , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/chemical synthesis , Humans , Models, Molecular
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