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1.
Obes Surg ; 33(2): 635-664, 2023 02.
Article in English | MEDLINE | ID: mdl-36571582

ABSTRACT

BACKGROUND: Persons submitted to bariatric metabolic surgery present micronutrient deficiency before and after surgery, due to the lack of proper supplementation. The aim of this study is to establish the prevalence of micronutrient deficiency in people before and after bariatric metabolic surgery in Latin America. METHODS: This review was conducted in accordance with the 2020 PRISMA Guidelines. RESULTS: Twenty-seven studies and 2135 participants were included. The highest prevalence of deficiency before surgery was reported for vitamin D (74%), zinc (71%), and hemoglobin (62%); after surgery, they were vitamin A (90.6%), vitamin D (90%), and zinc (68%). CONCLUSIONS: There is a high prevalence of micronutrient deficiency before and after bariatric metabolic surgery from Latin American persons; the micronutrients with the highest deficiency prevalence were vitamin D before and vitamin A after bariatric metabolic surgery.


Subject(s)
Bariatric Surgery , Obesity, Morbid , Humans , Latin America/epidemiology , Obesity, Morbid/surgery , Vitamin A , Micronutrients , Vitamins , Vitamin D , Zinc
2.
Materials (Basel) ; 14(5)2021 Feb 25.
Article in English | MEDLINE | ID: mdl-33668741

ABSTRACT

New medical devices with anti-inflammatory properties are critical to prevent inflammatory processes and infections in medical/surgical procedures. In this work, we present a novel functionalization of silicone for medical use with a polymeric prodrug and a thermosensitive polymer, by graft polymerization (gamma rays), for the localized release of salicylic acid, an analgesic, and anti-inflammatory drug. Silicone rubber (SR) films were functionalized in two stages using graft polymerization from ionizing radiation (60Co). The first stage was grafting poly(N-vinylcaprolactam) (PNVCL), a thermo-sensitive polymer, onto SR to obtain SR-g-PNVCL. In the second stage, poly(2-methacryloyloxy-benzoic acid) (P2MBA), a polymeric prodrug, was grafted to obtain (SR-g-PNVCL)-g-P2MBA. The degree of functionalization depended on the concentrations of monomers and the irradiation dose. The films were characterized by attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy/energy-dispersive X-ray spectrometry (SEM-EDX), thermogravimetric analysis (TGA), and contact angle. An upper critical solution temperature (UCST) of the films was demonstrated by the swelling degree as a temperature function. (SR-g-PNVCL)-g-P2MBA films demonstrated hydrolysis-mediated drug release from the polymeric prodrug, pH, and temperature sensitivity. GC-MS confirmed the presence of the drug (salicylic acid), after polymer hydrolysis. The concentration of the drug in the release media was quantified by HPLC. Cytocompatibility and thermo-/pH sensitivity of functionalized medical silicone were demonstrated in cancer and non-cancer cells.

3.
Polymers (Basel) ; 12(6)2020 Jun 05.
Article in English | MEDLINE | ID: mdl-32517004

ABSTRACT

Silicone rubber (SR) is a material used for medical procedures, with a common example of its application being in implants for cosmetic or plastic surgeries. It is also an essential component for the development of medical devices. SR was functionalized with the polymeric prodrug of poly(2-methacryloyloxy-benzoic acid) (poly(2MBA)) to render the analgesic anti-inflammatory drug salicylic acid by hydrolysis. The system was designed by functionalizing SR films (0.5 cm × 1 cm) with a direct grafting method, using gamma irradiation (60Co source) to induce the polymerization process. The absorbed dose (from 20 to 100 kGy) and the monomer concentration (between 0.4 and 1.5 M) were critical in controlling the surface and the bulk modifications of SR. Grafting poly(2MBA) onto SR (SR-g-2MBA) were characterized by attenuated total reflectance Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy/energy-dispersive X-ray spectrometry, fluorescence microscopy, the contact angle, and the swelling. SR-g-2MBA demonstrated the drug's sustained and pH-dependent release in simulated physiological mediums (pH = 5.5 and 7.4). The drug's release was quantified by high-performance liquid chromatography and confirmed by gas chromatography-mass spectrometry. Finally, cytocompatibility was demonstrated in murine fibroblast and human cervical cancer cell lines. The developed systems provide new polymeric drug release systems for medical silicone applications.

4.
Sensors (Basel) ; 19(22)2019 Nov 08.
Article in English | MEDLINE | ID: mdl-31717425

ABSTRACT

In this work, we present an integrated photogrammetric-acoustic technique that, together with the construction of a scaled wind tunnel, allows us to experimentally analyze the permeability behavior of a new type of acoustic screen based on a material called sonic crystal. Acoustic screens are devices used to reduce noise, mostly due to communication infrastructures, in its transmission phase from the source to the receiver. The main constructive difference between these new screens and the classic ones is that the first ones are formed by arrays of acoustic scatterers while the second ones are formed by continuous walls. This implies that, due to their geometry, screens based on sonic crystals are permeable to wind and water, unlike the classic ones. This fact may allow the use of these new screens in sandy soils, where sand would pass through the screen, avoiding the formation of sand dunes that are formed in classic screens and drastically reducing their acoustic performance. In this work, the movement of the sand and the resulting acoustic attenuation in these new screens are analyzed qualitatively, comparing the results with those obtained with the classic ones, and obtaining interesting results from the acoustic point of view.

5.
Sensors (Basel) ; 19(22)2019 Nov 14.
Article in English | MEDLINE | ID: mdl-31739529

ABSTRACT

The conservation and authentication of pictorial artworks is considered an important part of the preservation of cultural heritage. The use of non-destructive testing allows the obtention of accurate information about the state of pictorial artworks without direct contact between the equipment used and the sample. In particular, the use of this kind of technology is recommended in obtaining three-dimensional surface digital models, as it provides high-resolution information that constitutes a kind of fingerprint of the samples. In the case of pictorial artworks with some kind of surface relief, one of the most useful technologies is structured light (SL). In this paper, the minimum difference in height that can be distinguished with this technology was estimated, establishing experimentally both the error committed in the measurement process and the precision in the use of this technology. This study focused on the case of oil paintings on canvas and developed a low-cost system to ensure its wide use.

6.
Ultrasound Med Biol ; 45(3): 867-884, 2019 03.
Article in English | MEDLINE | ID: mdl-30600128

ABSTRACT

The correction of transcranial focused ultrasound aberrations is a relevant issue for enhancing various non-invasive medical treatments. The emission through multi-element phased arrays has been the most widely accepted method to improve focusing in recent years; however, the number and size of transducers represent a bottleneck that limits the focusing accuracy of the technique. To overcome this limitation, a new disruptive technology, based on 3-D-printed acoustic lenses, has recently been proposed. As the submillimeter precision of the latest generation of 3-D printers has been proven to overcome the spatial limitations of phased arrays, a new challenge is to improve the accuracy of the numerical simulations required to design this type of ultrasound lens. In the study described here, we evaluated two improvements in the numerical model applied in previous works for the design of 3-D-printed lenses: (i) allowing the propagation of shear waves in the skull by means of its simulation as an isotropic solid and (ii) introduction of absorption into the set of equations that describes the dynamics of the wave in both fluid and solid media. The results obtained in the numerical simulations are evidence that the inclusion of both s-waves and absorption significantly improves focusing.


Subject(s)
High-Intensity Focused Ultrasound Ablation/instrumentation , Lenses , Printing, Three-Dimensional , Acoustics , Computer Simulation , Humans , Skull/diagnostic imaging
7.
Rev Chilena Infectol ; 35(4): 377-385, 2018 Aug.
Article in Spanish | MEDLINE | ID: mdl-30534924

ABSTRACT

BACKGROUND: Factors associated with candidiasis and colonization in HIV-positive children and adolescents in developing countries are not well understood. AIM: To identify the factors associated with oral Candida colonization and candidiasis in institutionalized HIV-positive children and adolescents in Tijuana, México, as well as the response of the isolates to antifungals. MATERIALS AND METHODS: Sample of the oral mucosa of 30 HIV positive children and adolescents were obtained to isolate and identify Candida species by culture and metabolic profile. Antifungal drugs susceptibility was determined according to CLSI. Indicators of immunological and virologic failure were classified in accordance to WHO criteria. RESULTS: Six Candida species were identified from oral mucosa, 53% colonizers and 47% in candidiasis. Factors associated with candidiasis and oral colonization were viral load (p = 0,001), CD4+ counts (p = 0,002) and HAART regimen (p ≤ 0,014). The most prevalent species was C. glabrata (33%), but C. albicans (27%) was more resistant to fluconazole (p = 0,001). Itraconazol resistant species were identified in regimens that include an NNRTI (p = 0,041). CONCLUSION: HIV-positive children and adolescents living in an orphanage showed high prevalence of colonizing Candida spp. and resistance to antifungals, related to NNRTI.


Subject(s)
AIDS-Related Opportunistic Infections/microbiology , Candida albicans/isolation & purification , Candidiasis, Oral/microbiology , HIV Infections/complications , Mouth Mucosa/microbiology , AIDS-Related Opportunistic Infections/drug therapy , Adolescent , Adult , Antifungal Agents/therapeutic use , Candida albicans/classification , Candidiasis, Oral/classification , Candidiasis, Oral/drug therapy , Child , Child, Preschool , Cross-Sectional Studies , Drug Resistance, Fungal , Female , Fluconazole/therapeutic use , HIV Infections/drug therapy , Humans , Infant , Itraconazole/therapeutic use , Male , Mexico , Prospective Studies , Risk Factors , Viral Load , Young Adult
8.
Rev. chil. infectol ; 35(4): 377-385, ago. 2018. tab
Article in Spanish | LILACS | ID: biblio-978048

ABSTRACT

Resumen Introducción: Se desconocen los factores asociados a la candidiasis oral en población pediátrica con infección por VIH de los países en desarrollo. Objetivo: Identificar los factores asociados a la colonización por Candida, candidiasis oral y la susceptibilidad in vitro a antifúngicos, en niños y adolescentes con infección por VIH institucionalizados en la ciudad de Tijuana, México. Materiales y Métodos: Se examinó la cavidad oral de 30 niños y adolescentes con infección por VIH, se obtuvo una muestra de la mucosa oral para identificar las especies de Candida mediante cultivo y auxonograma. La susceptibilidad a los antifúngicos se determinó de acuerdo al CLSI. Los indicadores del estado inmunológico y falla virológica se clasificaron conforme a la OMS. Resultados: Se identificaron seis especies de Candida, 53% colonizantes y 47% causantes de candidiasis. Los factores asociados a candidiasis fueron alta carga viral (p = 0,001), menor recuento de LTCD4+ (p = 0,002) y esquema TARAA (p ≤ 0,014). La especie prevalente fue C. glabrata (33%); sin embargo, C. albicans (27%) fue más resistente a fluconazol (p = 0,001). Las especies resistentes a itraconazol se identificaron en esquemas que incluyen un INNTR (p = 0,041). Conclusiones: Los niños y adolescentes con infección por VIH institucionalizados mostraron una prevalencia elevada de Candida spp. colonizante y resistencia a los antifúngicos relacionada con los INNTR .


Background: Factors associated with candidiasis and colonization in HIV-positive children and adolescents in developing countries are not well understood. Aim: To identify the factors associated with oral Candida colonization and candidiasis in institutionalized HIV-positive children and adolescents in Tijuana, México, as well as the response of the isolates to antifungals. Materials and Methods: Sample of the oral mucosa of 30 HIV positive children and adolescents were obtained to isolate and identify Candida species by culture and metabolic profile. Antifungal drugs susceptibility was determined according to CLSI. Indicators of immunological and virologic failure were classified in accordance to WHO criteria. Results: Six Candida species were identified from oral mucosa, 53% colonizers and 47% in candidiasis. Factors associated with candidiasis and oral colonization were viral load (p = 0,001), CD4+ counts (p = 0,002) and HAART regimen (p ≤ 0,014). The most prevalent species was C. glabrata (33%), but C. albicans (27%) was more resistant to fluconazole (p = 0,001). Itraconazol resistant species were identified in regimens that include an NNRTI (p = 0,041). Conclusion: HIV-positive children and adolescents living in an orphanage showed high prevalence of colonizing Candida spp. and resistance to antifungals, related to NNRTI.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Young Adult , Candida albicans/isolation & purification , Candidiasis, Oral/microbiology , HIV Infections/complications , AIDS-Related Opportunistic Infections/microbiology , Mouth Mucosa/microbiology , Candida albicans/classification , Candidiasis, Oral/classification , Candidiasis, Oral/drug therapy , Fluconazole/therapeutic use , HIV Infections/drug therapy , Cross-Sectional Studies , Prospective Studies , Risk Factors , AIDS-Related Opportunistic Infections/drug therapy , Itraconazole/therapeutic use , Viral Load , Drug Resistance, Fungal , Mexico , Antifungal Agents/therapeutic use
9.
Comput Intell Neurosci ; 2018: 1983897, 2018.
Article in English | MEDLINE | ID: mdl-30728832

ABSTRACT

Population pharmacokinetic (PopPK) models allow researchers to predict and analyze drug behavior in a population of individuals and to quantify the different sources of variability among these individuals. In the development of PopPK models, the most frequently used method is the nonlinear mixed effect model (NLME). However, once the PopPK model has been developed, it is necessary to determine if the selected model is the best one of the developed models during the population pharmacokinetic study, and this sometimes becomes a multiple criteria decision making (MCDM) problem, and frequently, researchers use statistical evaluation criteria to choose the final PopPK model. The used evaluation criteria mentioned above entail big problems since the selection of the best model becomes susceptible to the human error mainly by misinterpretation of the results. To solve the previous problems, we introduce the development of a software robot that can automate the task of selecting the best PopPK model considering the knowledge of human expertise. The software robot is a fuzzy expert system that provides a method to systematically perform evaluations on a set of candidate PopPK models of commonly used statistical criteria. The presented results strengthen our hypothesis that the software robot can be successfully used to evaluate PopPK models ensuring the selection of the best PopPK model.


Subject(s)
Models, Biological , Nonlinear Dynamics , Pharmacokinetics , Software , Algorithms , Data Analysis , Humans
10.
Comput Biol Med ; 88: 100-109, 2017 09 01.
Article in English | MEDLINE | ID: mdl-28711766

ABSTRACT

AIM: This paper presents a methodology and first results of an automatic detection system of first signs of Diabetic Retinopathy (DR) in fundus images, developed for the Health Ministry of the Andalusian Regional Government (Spain). MATERIAL AND METHODS: The system detects the presence of microaneurysms and haemorrhages in retinography by means of techniques of digital image processing and supervised classification. Evaluation was conducted on 1058 images of 529 diabetic patients at risk of presenting evidence of DR (an image of each eye is provided). To this end, a ground-truth diagnosis was created based on gradations performed by 3 independent ophthalmology specialists. RESULTS: The comparison between the diagnosis provided by the system and the reference clinical diagnosis shows that the system can work at a level of sensitivity that is similar to that achieved by experts (0.9380 sensitivity per patient against 0.9416 sensitivity of several specialists). False negatives have proven to be mild cases. Moreover, while the specificity of the system is significantly lower than that of human graders (0.5098), it is high enough to screen more than half of the patients unaffected by the disease. CONCLUSION: Results are promising in integrating this system in DR screening programmes. At an early stage, the system could act as a pre-screening system, by screening healthy patients (with no obvious signs of DR) and identifying only those presenting signs of the disease.


Subject(s)
Diabetic Retinopathy/diagnostic imaging , Diagnostic Techniques, Ophthalmological , Image Interpretation, Computer-Assisted/methods , Retina/diagnostic imaging , Algorithms , Early Diagnosis , Fundus Oculi , Humans , Retinal Vessels/diagnostic imaging
11.
Int J Pharm ; 511(1): 579-585, 2016 Sep 10.
Article in English | MEDLINE | ID: mdl-27452418

ABSTRACT

Medical devices decorated with salicylic acid-based polymer chains (polymeric prodrug) that slowly release this anti-inflammatory and anti-biofilm drug at the implantation site were designed. A "grafting from" method was implemented to directly grow chains of a polymerizable derivative of salicylic acid (2-methacryloyloxy-benzoic acid, 2MBA) onto polypropylene (PP). PP was modified both at bulk and on the surface with poly(2MBA) by means of an oxidative pre-irradiation method ((60)Co source), in order to obtain a grafted polymer in which salicylic acid units were linked by means of labile ester bonds. The grafting percent depended on absorbed dose, reaction time, temperature and monomer concentration. The functionalized films were analyzed regarding structure (FTIR-ATR, SEM-EDX, fluorescence microscopy), temperature stability (TGA), interaction with aqueous medium (water contact angle and swelling), pH-responsive release and cytocompatibility (fibroblasts). In the obtained poly(2MBA)-grafted biomaterial, poly(2MBA) behaved as a polymeric prodrug that regulates salicylic acid release once in contact with aqueous medium, showing pH-dependent release rate.


Subject(s)
Polymers/chemistry , Polypropylenes/chemistry , Prodrugs/chemistry , Salicylic Acid/chemistry , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Drug Liberation , Polymers/administration & dosage , Polymers/pharmacokinetics , Polypropylenes/pharmacokinetics , Prodrugs/administration & dosage , Prodrugs/pharmacokinetics , Salicylic Acid/pharmacokinetics
12.
Comput Methods Programs Biomed ; 118(2): 173-85, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25433912

ABSTRACT

Development of automatic retinal disease diagnosis systems based on retinal image computer analysis can provide remarkably quicker screening programs for early detection. Such systems are mainly focused on the detection of the earliest ophthalmic signs of illness and require previous identification of fundal landmark features such as optic disc (OD), fovea or blood vessels. A methodology for accurate center-position location and OD retinal region segmentation on digital fundus images is presented in this paper. The methodology performs a set of iterative opening-closing morphological operations on the original retinography intensity channel to produce a bright region-enhanced image. Taking blood vessel confluence at the OD into account, a 2-step automatic thresholding procedure is then applied to obtain a reduced region of interest, where the center and the OD pixel region are finally obtained by performing the circular Hough transform on a set of OD boundary candidates generated through the application of the Prewitt edge detector. The methodology was evaluated on 1200 and 1748 fundus images from the publicly available MESSIDOR and MESSIDOR-2 databases, acquired from diabetic patients and thus being clinical cases of interest within the framework of automated diagnosis of retinal diseases associated to diabetes mellitus. This methodology proved highly accurate in OD-center location: average Euclidean distance between the methodology-provided and actual OD-center position was 6.08, 9.22 and 9.72 pixels for retinas of 910, 1380 and 1455 pixels in size, respectively. On the other hand, OD segmentation evaluation was performed in terms of Jaccard and Dice coefficients, as well as the mean average distance between estimated and actual OD boundaries. Comparison with the results reported by other reviewed OD segmentation methodologies shows our proposal renders better overall performance. Its effectiveness and robustness make this proposed automated OD location and segmentation method a suitable tool to be integrated into a complete prescreening system for early diagnosis of retinal diseases.


Subject(s)
Fundus Oculi , Optic Disk/pathology , Automation , Humans , Retinal Vessels/pathology
13.
Sensors (Basel) ; 14(5): 7992-8002, 2014 May 05.
Article in English | MEDLINE | ID: mdl-24803191

ABSTRACT

Artworks are a valuable part of the World's cultural and historical heritage. Conservation and authentication of authorship are important aspects to consider in the protection of cultural patrimony. In this paper we present a novel application of a well-known method based on the phase-shift analysis of an ultrasonic signal, providing an integrated encoding system that enables authentication of the authorship of wooden panel paintings. The method has been evaluated in comparison with optical analysis and shows promising results. The proposed method provides an integrated fingerprint of the artwork, and could be used to enrich the cataloging and protection of artworks. Other advantages that make particularly attractive the proposed technique are its robustness and the use of low-cost sensors.


Subject(s)
Image Interpretation, Computer-Assisted/methods , Materials Testing/instrumentation , Paint/analysis , Paintings/classification , Robotics/instrumentation , Ultrasonography/instrumentation , Wood/analysis , Algorithms , Equipment Design , Equipment Failure Analysis , Image Interpretation, Computer-Assisted/instrumentation , Materials Testing/methods , Robotics/methods , Transducers , Ultrasonography/methods
14.
Comput Med Imaging Graph ; 37(5-6): 386-93, 2013.
Article in English | MEDLINE | ID: mdl-23838458

ABSTRACT

A new methodology for detecting the fovea center position in digital retinal images is presented in this paper. A pixel is firstly searched for within the foveal region according to its known anatomical position relative to the optic disc and vascular tree. Then, this pixel is used to extract a fovea-containing subimage on which thresholding and feature extraction techniques are applied so as to find fovea center. The methodology was evaluated on 1200 fundus images from the publicly available MESSIDOR database, 660 of which present signs of diabetic retinopathy. In 93.92% of these images, the distance between the methodology-provided and actual fovea center position remained below 1/4 of one standard optic disc radius (i.e., 17, 26, and 27 pixels for MESSIDOR retinas of 910, 1380 and 1455 pixels in size, respectively). These results outperform all the reviewed methodologies available in literature. Its effectiveness and robustness with different illness conditions makes this proposal suitable for retinal image computer analyses such as automated screening for early diabetic retinopathy detection.


Subject(s)
Algorithms , Fovea Centralis/anatomy & histology , Image Interpretation, Computer-Assisted/methods , Pattern Recognition, Automated/methods , Databases, Factual , Diabetic Retinopathy/diagnosis , Fundus Oculi , Humans , Optic Disk/anatomy & histology , Pattern Recognition, Automated/statistics & numerical data , Retinal Vessels/anatomy & histology
15.
Pharm Dev Technol ; 17(2): 170-6, 2012.
Article in English | MEDLINE | ID: mdl-21047274

ABSTRACT

Poly(carboxyalkyl methacrylates) were studied as a cationic-drug delivery system, at pH 6.8 and 8.0. Different polymer/drug complexes were used to prepare compressed tablets. By kinetics experiments, we have found that drug release is dependent on both the hydrophobicity of the whole complex and the pH of the environment. Furthermore, a mechanism of dissociation/erosion clearly describes the drug release from a complex formed by a polymer soluble at target pH; otherwise, a mechanism of dissolution/diffusion is depicted. Additionally, we have observed that hydrophilic fillers increase the drug release rate. Since our results using different polymer/drug complexes exhibit pH-sensitive drug release, we propose that the poly(carboxyalkyl methacrylates) have potential as a colon-specific drug-delivery system.


Subject(s)
Delayed-Action Preparations/chemistry , Pharmaceutical Preparations/administration & dosage , Polymethacrylic Acids/chemistry , Cations/chemistry , Electrolytes/chemistry , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Kinetics , Solubility
16.
J Asthma ; 47(8): 835-40, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20874438

ABSTRACT

BACKGROUND: It is unclear whether premenstrual asthma is associated with premenstrual syndrome. The objective of this study is to compare premenstrual symptoms among asthmatic women according to whether they have premenstrual asthma or not. METHODS: A questionnaire on respiratory symptoms during a single menstrual cycle was developed for asthmatics of fertile age, together with another on symptoms related to premenstrual syndrome. These included dysphoric-psychiatric symptoms (anxiety, depression, fatigue, irritability, and mood swings), edematous symptoms (abdominal and mammary tension, swelling, acne, and migraine), and other symptoms (leg pains, nausea, sweating, vomiting, and tiredness). Morning and evening peak flow scores were collected to evaluate lung function. Premenstrual asthma was determined to be a ≥ 20% objective exacerbation in the premenstrual phase over the preovulatory phase in terms of both respiratory symptoms and/or peak flow. The intensity of the change in symptoms was evaluated according to the effect size. RESULTS: The study examined 103 patients of fertile age, 46 of whom (44.7%) presented with premenstrual asthma. Practically all of the monitored symptoms increased in the premenstrual phase with respect to the preovulatory phase. This increase was greater in women with premenstrual asthma, especially for abdominal tension (effect size .88 against .33; p = .009) and mammary tension (.95 against .49; p = .018). CONCLUSIONS: A clear link was found between premenstrual asthma and the premenstrual exacerbation of dysphoric symptoms, and certain edematous symptoms such as abdominal and mammary tension as well as a swelling sensation.


Subject(s)
Asthma/physiopathology , Menstrual Cycle/physiology , Premenstrual Syndrome/physiopathology , Adolescent , Adult , Asthma/psychology , Female , Humans , Menstrual Cycle/psychology , Middle Aged , Premenstrual Syndrome/psychology , Young Adult
17.
J Med Chem ; 52(12): 3735-41, 2009 Jun 25.
Article in English | MEDLINE | ID: mdl-19459645

ABSTRACT

Agonists activating nicotinic acetylcholine receptors (nAChR) include potential therapeutic agents and also toxicants such as epibatidine and neonicotinoid insecticides with a chloropyridinyl substituent. Nicotinic agonist interactions with mollusk (Aplysia californica) acetylcholine binding protein, a soluble surrogate of the nAChR extracellular domain, are precisely defined by scanning with 17 methionine and tyrosine mutants within the binding site by photoaffinity labeling with 5-azido-6-chloropyridin-3-yl probes that have similar affinities to their nonazido counterparts. Methionine and tyrosine are the only residues found derivatized, and their reactivity exquisitely depends on the direction of the azido moiety and its apposition to the reactive amino acid side chains.


Subject(s)
Azides/analysis , Methionine/chemistry , Methionine/metabolism , Photoaffinity Labels/analysis , Pyridines/analysis , Receptors, Nicotinic/chemistry , Receptors, Nicotinic/metabolism , Tyrosine/chemistry , Animals , Aplysia/chemistry , Azides/chemistry , Binding Sites , Computer Simulation , Mass Spectrometry , Models, Chemical , Molecular Structure , Photoaffinity Labels/chemistry , Pyridines/chemistry , Tyrosine/metabolism
18.
Parasitol Int ; 58(3): 311-3, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19361571

ABSTRACT

PDI enzymes are oxidoreductases that catalyze oxidation, reduction and isomerization of disulfide bonds in polypeptide substrates. We have previously identified an E. histolytica PDI enzyme (EhPDI) that exhibits oxidase activity in vivo. However, little is known about the specific role of its redox-related structural features on the enzymatic activity. Here, we have studied the in vivo oxidative folding of EhPDI by mutagenic analysis and functional complementation assays as well as the in vitro oxidative folding and reductive activities by comparative kinetics using functional homologues in standard assays. We have found that the active-site cysteine residues of the functional domains (Trx-domains) are essential for catalysis of disulfide bond formation in polypeptides and proteins, such as the bacterial alkaline phosphatase. Furthermore, we have shown that the recombinant EhPDI enzyme has some typical properties of PDI enzymes: oxidase and reductase activities. These activities were comparable to those observed for other functional equivalents, such as bovine PDI or bacterial thioredoxin, under the same experimental conditions. These findings will be helpful for further studies intended to understand the physiological role of EhPDI.


Subject(s)
Entamoeba histolytica/enzymology , Protein Disulfide-Isomerases/chemistry , Protein Disulfide-Isomerases/metabolism , Protein Folding , Animals , Catalytic Domain , Entamoeba histolytica/genetics , Genetic Complementation Test , Mutation , Oxidation-Reduction , Protein Disulfide-Isomerases/genetics , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Structure-Activity Relationship
19.
Mol Med Rep ; 1(6): 875-9, 2008.
Article in English | MEDLINE | ID: mdl-21479500

ABSTRACT

Isoniazid (INH) is a drug extensively used as a prophylactic and therapeutic agent for human tuberculosis (TB). INH is metabolized by the enzymatic activity of N-acetyltransferase 2 (NAT2). Human NAT2, encoded by a highly polymorphic gene, is involved in the biotransformation of xenobiotics, including drugs and certain chemical carcinogens. Numerous studies have established the correlation between the acetylator phenotype and the NAT2 genotype in several populations; however, little is known regarding Latin-American populations and the pharmacogenetics of NAT2. Here, we report the molecular genotyping of the NAT2 gene, the acetylator phenotype, and the incidence of INH-related adverse reactions in a group of 25 Mexican individuals enrolled in a prophylactic protocol for TB. Using both the NAT2 genotyping and acetylation phenotyping approach, we found a ratio of 69.2 and 30.8% of slow and fast acetylators, respectively. Concordance of the NAT2 genotype and phenotype classification was 88% in the bimodal model. Regarding INH-related adverse reactions, only 2 individuals (8%) exhibited declared gastric intolerance. In our study group, we found an association between the NAT2 genotype and acetylator phenotype (OR=7.78, 95% CI, 0.87-87.98, Fisher's exact test, p<0.05), but did not find any genotype or phenotype association with the incidence of INH-related adverse reactions (Fisher's exact test, p>0.05).

20.
Comput Biol Chem ; 32(1): 66-70, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17981509

ABSTRACT

Protein disulfide isomerase (PDI) enzymes are eukaryotic oxidoreductases that catalyze the correct formation of disulfide bonds during protein folding. Structurally they are characterized by the presence of functional thioredoxin-like (Trx) domains. For the protozoan parasite causative of the human amebiasis (Entamoeba histolytica), the correct formation of disulfide bonds is important for an accurate folding of its proteins, including some virulence factors. However, little is known about the enzymes involved in this mechanism. We undertook a post-genomic approach to identify the PDI family of this parasite. The genome database survey revealed a set of 11 PDI-encoding sequences with predictable protein thiol/disulfide oxidoreductase activities.


Subject(s)
Entamoeba histolytica/enzymology , Protein Disulfide-Isomerases/metabolism , Protozoan Proteins/metabolism , Amino Acid Sequence , Animals , Molecular Sequence Data , Structure-Activity Relationship
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