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1.
J Endocrinol Invest ; 44(12): 2819-2830, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33991317

RESUMEN

BACKGROUND: Obesity promotes cellular immunometabolism changes that trigger the activation of macrophages and lymphocytes, leading to systemic inflammation. Activated leukocytes undergo metabolic reprogramming, increasing glycolytic activity. OBJECTIVE: To examine whether the reduction in the inflammatory state associated with bariatric surgery is associated with decreased glycolytic activity in leukocytes. Setting Single-center, prospective observational study. METHODS: This study involved 18 patients with obesity undergoing bariatric surgery. All measurements were performed preoperatively and six months postoperatively. Peripheral blood mononuclear cells and plasma were obtained to determine the glycolytic rate and mitochondrial membrane potential as surrogates of the metabolic switching and high-sensitivity C-reactive protein, adipokines, and CD69 expression as inflammatory and activation markers. RESULTS: Glycolytic activity engaged by CD3/CD28 activation was reduced six months after bariatric surgery, associated with decreased levels of T helper (Th) 1 and Th17 signature cytokines. An overall reduction in inflammatory markers was observed, which correlated with a higher adiponectin/leptin ratio. CONCLUSIONS: Metabolic and bariatric surgery-induced weight loss leads to reprogramming in T cells' metabolic machinery, resulting in reduced stimulation of glycolysis after activation, which may explain the decrease in systemic inflammation mediated by cytokines such as interferon-γ and interleukin-17A.


Asunto(s)
Activación Metabólica/inmunología , Cirugía Bariátrica/métodos , Glucólisis/inmunología , Leucocitos Mononucleares , Obesidad Mórbida , Células TH1 , Células Th17 , Adulto , Recuento de Células/métodos , Reprogramación Celular , Metabolismo Energético/inmunología , Femenino , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Masculino , Obesidad Mórbida/metabolismo , Obesidad Mórbida/cirugía , Periodo Posoperatorio , Células TH1/metabolismo , Células TH1/patología , Células Th17/metabolismo , Células Th17/patología
2.
Anim Genet ; 48(3): 353-357, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28094447

RESUMEN

Local chicken populations are a major source of food in the rural areas of South America. However, very little is known about their genetic composition and diversity. Here, we analyzed five populations from South America to investigate their maternal genetic origin and diversity, hoping to mitigate the lack of information on local chicken populations from this region. We also included three populations of chicken from the Iberian Peninsula and one from Easter Island, which are potential sources of the first chickens introduced in South America. The obtained sequencing data from South American chickens indicate the presence of four haplogroups (A, B, E and D) that can be further subdivided into nine sub-haplogroups. Of these, four (B1, D1a, E1a(b), E1b) were absent from local Iberian Peninsula chickens and one (D1a) was present only on Easter Island. The presence of the sub-haplogroups A1a(b) and E1a(b) in South America, previously only observed in Eastern Asia, and the significant population differentiation between Iberian Peninsula and South American populations, suggest a second maternal source of the extant genetic pool in South American chickens.


Asunto(s)
Pollos/genética , Variación Genética , Genética de Población , Animales , ADN Mitocondrial/genética , Pool de Genes , Haplotipos , Filogenia , Análisis de Secuencia de ADN/veterinaria , América del Sur
3.
Reprod Domest Anim ; 49(4): e40-e43, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24975137

RESUMEN

The aim of this research was to evaluate the effectiveness of three pFSH doses (80 mg; 145 mg and 215 mg) on ovarian response and on quantity and quality of transferable embryos of goats during the breeding and the non-breeding seasons. Ovary structures were exposed (laparatomy under general anaesthesia) and numbers of follicles and corpora lutea were registered. Surgical embryo flushing was conducted to count and classify embryos. There were more follicles (3.4 ± 1.1) in does administered 80 mg of pFSH (p < 0.05) than in goats administered 145 mg of pFSH (2.2 ± 1.1) and 215 mg of pFSH (0.9 ± 0.6). Numbers of corpora lutea, blastocysts, and recovered and transferable embryos of goats administered 145 mg pFSH (13.4 ± 3.7, 2.42 ± 1.0, 3.4 ± 1.2 and 3.2 ± 1.1, respectively) and those of goats administered 215 mg pFSH (11.6 ± 2.6, 3.2 ± 0.9, 5.7 ± 1.5, and 5.6 ± 1.5) were greater (p < 0.05) than values obtained from goats administered 80 mg pFSH (4.0 ± 1.5, 0.5 ± 0.3, 1.0 ± 0.5, and 0.8 ± 0.5). Numbers of morula of does administered 80 and 145 mg pFSH (0.4 ± 0.4 and 0.8 ± 0.3) were lower (p < 0.05) than those obtained from animals treated with 215 mg pFSH (2.4 ± 0.9). There was no effect of season upon the analyzed variables. In conclusion, under the prevalent conditions in north-eastern Mexico, administration of 145 or 215 mg pFSH in a decreasing dose schedule over 3.5 days to bred goats provided a satisfactory superovulatory result.


Asunto(s)
Cruzamiento/métodos , Embrión de Mamíferos/fisiología , Hormona Folículo Estimulante/administración & dosificación , Cabras/fisiología , Superovulación/efectos de los fármacos , Administración Intravaginal , Animales , Blastocisto , Cuerpo Lúteo/anatomía & histología , Relación Dosis-Respuesta a Droga , Transferencia de Embrión/veterinaria , Femenino , Cabras/embriología , Acetato de Medroxiprogesterona/administración & dosificación , México , Folículo Ovárico/anatomía & histología , Estaciones del Año , Recolección de Tejidos y Órganos/veterinaria
5.
Sci Rep ; 13(1): 1591, 2023 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-36709214

RESUMEN

Traditionally, smear microscopy has been used to estimate bacillary burden in order to assess infectiousness in tuberculosis (TB) patients. Since Xpert MTB assays might replace smear microscopy as the first-line diagnostic test for pulmonary tuberculosis, an alternative measure of bacillary load that correlates with smear positivity is needed. This study assessed the correlation between CT (with and without normalization), smear status, culture time-to-positivity (TTP), and clinical factors in patients with Xpert ultra positive sputum during a four-year period. A cut-off CT value for smear positivity was also estimated. 204 samples were included. Strong correlation between both Xpert Ultra CT values (raw and normalized) and smear status was obtained (r = 0.78 and - 0.79, respectively). The association between Raw-CT and TTP was weaker than normalized-CT (N-CT) and TTP (r = 0.50 and r = - 0.70, respectively). A Raw-CT cut-off value of 21.4 was identified with 85.7% (95% CI 65.4-95) sensitivity and 92.9% (95% CI 84.3-96.9) specificity. A N-CT cut-off value of 5.2 yielded a sensitivity of 94.3% (95% CI 86.2-97.8) and specificity of 85.7% (95% CI 65.4-95). Our study demonstrates that Xpert Ultra CT value correlates well with other measures of bacillary load such as smear status or TTP. The correlation with TTP is stronger when the CT value is normalized using the internal control. The proposed N-CT cut-off value of 5.2 shows a better sensitivity than the Raw-CT when predicting smear positive status.


Asunto(s)
Bacillus , Lacticaseibacillus casei , Mycobacterium tuberculosis , Tuberculosis Pulmonar , Humanos , Mycobacterium tuberculosis/genética , Esputo , Sensibilidad y Especificidad , Tuberculosis Pulmonar/diagnóstico por imagen , Firmicutes , Tomografía Computarizada por Rayos X
6.
Rev Gastroenterol Mex (Engl Ed) ; 87(2): 170-175, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34794922

RESUMEN

INTRODUCTION AND AIMS: Percutaneous liver biopsy with histopathologic analysis is a valuable tool for the diagnosis, prognosis, and treatment evaluation of liver diseases. Its ultrasound-guided performance is useful, making the procedure safer and reducing the risk for complications and hospital stay. Our aim was to describe the indications, histopathologic study, and complications associated with the performance of ultrasound-guided percutaneous liver biopsy in pediatric patients. MATERIAL AND METHODS: The study included 102 ultrasound-guided percutaneous liver biopsies performed on patients <16 years of age, within the time frame of January 2014 and December 2019. The information was obtained from electronic files and histopathologic studies and the data were analyzed through descriptive statistics. RESULTS: A total of 102 procedures were carried out on 99 patients. Mean patient age was 72 months and 58.8% of the patients were female. Over 65% of the indications for liver biopsy included autoimmune hepatitis (23.5%), elevated liver enzymes (21.5%), and chronic liver disease (20.5%). Four patients presented with immediate complications (3.9%), three of which were major (2.9%), concurring with that reported in the international literature. CONCLUSIONS: Our study corroborates the importance of ultrasound-guided liver biopsy in the diagnosis and follow-up of pediatric patients. The procedure also had a low complication rate of only 3.9%.


Asunto(s)
Hepatopatías , Ultrasonografía Intervencional , Niño , Femenino , Humanos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Hepatopatías/diagnóstico por imagen , Masculino , Estudios Retrospectivos , Centros de Atención Terciaria , Ultrasonografía Intervencional/métodos
7.
Phys Rev E ; 103(1-1): 012706, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33601506

RESUMEN

Electrorheological response of a nematic liquid crystal confined in the region between two coaxial and rotating circular cylinders is studied theoretically. Utilizing weak anchoring conditions, the physical properties of 4-n-pentyl-4-cyanobiphenyl (5CB), nonslip boundary conditions, and contrasting surface anchoring energies, we numerically obtain the equilibrium configurations for the nematic director under the influence of an external low-frequency radial electric field and the corresponding (angular) velocity profiles. The Fréedericksz transition is parametrized by the cylinders' radii ratio for different values of the surface energies. The averaged apparent viscosity of the nematic is calculated also.

8.
Biochim Biophys Acta Mol Basis Dis ; 1867(1): 165992, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33091565

RESUMEN

The mitochondrial permeability transition pore (mPTP) opening is involved in the pathophysiology of multiple cardiac diseases, such as ischemia/reperfusion injury and heart failure. A growing number of evidence provided by proteomic screening techniques has demonstrated the role of post-translational modifications (PTMs) in several key components of the pore in response to changes in the extra/intracellular environment and bioenergetic demand. This could lead to a fine, complex regulatory mechanism that, under pathological conditions, can shift the state of mitochondrial functions and, thus, the cell's fate. Understanding the complex relationship between these PTMs is still under investigation and can provide new, promising therapeutic targets and treatment approaches. This review, using a systematic review of the literature, presents the current knowledge on PTMs of the mPTP and their role in health and cardiac disease.


Asunto(s)
Insuficiencia Cardíaca/metabolismo , Mitocondrias Cardíacas/metabolismo , Poro de Transición de la Permeabilidad Mitocondrial/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Procesamiento Proteico-Postraduccional , Insuficiencia Cardíaca/patología , Humanos , Mitocondrias Cardíacas/patología , Daño por Reperfusión Miocárdica/patología , Proteómica
9.
Artículo en Inglés, Español | MEDLINE | ID: mdl-33810931

RESUMEN

INTRODUCTION AND AIMS: Percutaneous liver biopsy with histopathologic analysis is a valuable tool for the diagnosis, prognosis, and treatment evaluation of liver diseases. Its ultrasound-guided performance is useful, making the procedure safer and reducing the risk for complications and hospital stay. Our aim was to describe the indications, histopathologic study, and complications associated with the performance of ultrasound-guided percutaneous liver biopsy in pediatric patients. MATERIAL AND METHODS: The study included 102 ultrasound-guided percutaneous liver biopsies performed on patients <16 years of age, within the time frame of January 2014 and December 2019. The information was obtained from electronic files and histopathologic studies and the data were analyzed through descriptive statistics. RESULTS: A total of 102 procedures were carried out on 99 patients. Mean patient age was 72 months and 58.8% of the patients were female. Over 65% of the indications for liver biopsy included autoimmune hepatitis (23.5%), elevated liver enzymes (21.5%), and chronic liver disease (20.5%). Four patients presented with immediate complications (3.9%), three of which were major (2.9%), concurring with that reported in the international literature. CONCLUSIONS: Our study corroborates the importance of ultrasound-guided liver biopsy in the diagnosis and follow-up of pediatric patients. The procedure also had a low complication rate of only 3.9%.

10.
J Parasitol ; 106(5): 689-698, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-33113554

RESUMEN

Information regarding trichodinid ectoparasites on marine fishes of North America is relatively scarce. In this study, 5 ciliate species from the family Trichodinidae were found associated with 8 fish hosts from the rocky intertidal zone of the western coast of the Baja California Peninsula (BCP), Mexico. All of the host-parasite relationships recorded here are new. Furthermore, 3 of the trichodinid species found are recorded for the first time for Mexico. Trichodinids taxa do not show a noticeable distributional gradient along the BCP, which suggests a wide-continuous distribution of the species throughout the study area.


Asunto(s)
Infecciones por Cilióforos/veterinaria , Cilióforos/clasificación , Enfermedades de los Peces/parasitología , Animales , Cilióforos/ultraestructura , Infecciones por Cilióforos/parasitología , Peces , Branquias/parasitología , Interacciones Huésped-Parásitos , México , Océano Pacífico
11.
Oxid Med Cell Longev ; 2020: 4587024, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33194003

RESUMEN

A large number of cannabinoids have been discovered that could play a role in mitigating cardiac affections. However, none of them has been as widely studied as cannabidiol (CBD), most likely because, individually, the others offer only partial effects or can activate potential harmful pathways. In this regard, CBD has proven to be of great value as a cardioprotective agent since it is a potent antioxidant and anti-inflammatory molecule. Thus, we conducted a review to condensate the currently available knowledge on CBD as a therapy for different experimental models of cardiomyopathies and heart failure to detect the molecular pathways involved in cardiac protection. CBD therapy can greatly limit the production of oxygen/nitrogen reactive species, thereby limiting cellular damage, protecting mitochondria, avoiding caspase activation, and regulating ionic homeostasis. Hence, it can affect myocardial contraction by restricting the activation of inflammatory pathways and cytokine secretion, lowering tissular infiltration by immune cells, and reducing the area of infarct and fibrosis formation. These effects are mediated by the activation or inhibition of different receptors and target molecules of the endocannabinoid system. In the final part of this review, we explore the current state of CBD in clinical trials as a treatment for cardiovascular diseases and provide evidence of its potential benefits in humans.


Asunto(s)
Antiinflamatorios/uso terapéutico , Cannabidiol/uso terapéutico , Cardiomiopatías , Cardiotónicos/uso terapéutico , Insuficiencia Cardíaca , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/metabolismo , Cardiomiopatías/fisiopatología , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Humanos , Contracción Miocárdica/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
12.
Trends Biochem Sci ; 18(8): 284-7, 1993 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-8236439

RESUMEN

The measurement and analysis of sedimentation equilibrium provide one of the most powerful techniques for quantitative characterization of reversible and irreversible macromolecular associations in solution. The use of this technique by nonspecialists has been greatly helped in recent years by the development of new instrumentation, new types of experiments and new PC-based software for computer-aided analysis of experimental results.


Asunto(s)
Soluciones/química , Ultracentrifugación , Fenómenos Químicos , Química Física , Sustancias Macromoleculares , Proteínas/química
13.
Anal Chim Acta ; 1065: 12-20, 2019 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-31005144

RESUMEN

We are reporting an innovative building-block for the development of biosensors based on the non-covalent functionalization of multi-walled carbon nanotubes (MWCNTs) with avidin (MWCNTs-avidin). In this work, at variance with previous reports, avidin has the double role of simultaneously being the exfoliating agent of MWCNTs and the platform for anchoring different biotinylated biomolecules. The optimum dispersion was obtained by sonicating for 5.0 min 0.50 mgmL-1 MWCNTs with 1.00 mgmL-1 avidin solution prepared in 50:50 v/v ethanol/water. As proof-of-concept, we immobilized biotinylated horseradish peroxidase (b-HRP) at glassy carbon electrodes (GCE) modified with MWCNTs-avidin to develop a hydrogen peroxide biosensor using hydroquinone as redox mediator. Surface plasmon resonance, electrochemical impedance spectroscopy, cyclic voltammetry and amperometry demonstrated that, even after the partial denaturation of avidin due to the drastic conditions used to functionalize the MWCNTs, it preserves the biorecognition properties and efficiently interacts with biotinylated horseradish peroxidase (b-HRP). The analytical characteristics of the resulting hydrogen peroxide biosensor are the following: linear range between 1.0 × 10-6 M and 1.4 × 10-5 M, sensitivity of (1.37 ±â€¯0.04) x 105 µAM-1, detection limit of 24 nM and reproducibility of 2.9%. The sensor was challenged with different samples, a mouthwash solution, human blood serum and milk, with very good performance.


Asunto(s)
Avidina/química , Técnicas Biosensibles , Técnicas Electroquímicas , Peroxidasa de Rábano Silvestre/metabolismo , Peróxido de Hidrógeno/análisis , Nanotubos de Carbono/química , Animales , Espectroscopía Dieléctrica , Electrodos , Peroxidasa de Rábano Silvestre/química , Humanos , Leche/química , Resonancia por Plasmón de Superficie
14.
Sci Total Environ ; 648: 601-608, 2019 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-30121537

RESUMEN

This paper represents a first approach in the study of photoreactor selection to treat industrial wastewater using solar photo-Fenton. In this context, simulated textile industry effluent containing a mixture of four dyes at different initial dissolved organic carbon (DOC) concentrations (45, 90, 180 and 270 mg/L) was treated by using three different solar reactor geometries: (i) tubular (5 cm diameter) provided with compound parabolic collector (ii) tubular (5 cm diameter) provided with flat collector and (iii) open channels forming raceway ponds with two liquid depths (5 and 15 cm). For comparison purposes, mineralisation percentages over 75% and chronic toxicity reduction were set as treatment goals. Regardless of the initial DOC concentration, negligible differences in terms of treatment time and hydrogen peroxide consumptions were found between the flat collector and compound parabolic collector photoreactors. Conversely, the treatment in the raceway pond reactors always resulted in higher values. In spite of this, when the photoreactors were compared in terms of treatment capacity (mg of DOC removed/m2 min) the raceway pond reactor at 15 cm of liquid depth presented the best results, with values as much as two or three times higher than those of the tubular reactors, except for the wastewater with 270 mg of DOC/L for which the raceway pond reactor at 5 cm liquid depth became the best option. When the treatment capacity is modified to include the photoreactor investment (mg of DOC removed/€ m2) the differences between the raceway pond reactor at both liquid depths and the photoreactors with solar collectors increased by as much as two orders of magnitude, which demonstrates the potential application of the former for the treatment of industrial wastewater by solar photo-Fenton.

15.
Med Vet Entomol ; 22(3): 288-90, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18816278

RESUMEN

Lutzomyia longipalpis s.l. (Lutz & Neiva) (Diptera: Psychodidae) is the main vector of visceral leishmaniasis in Latin America. Differences in copulation songs, pheromones and molecular markers show that L. longipalpis is a species complex in Brazil. The patterns of activity of insect vectors are important in disease transmission. In addition, differences in activity rhythms have a potential role as a temporal reproductive isolation mechanism in closely related species. We compared the activity patterns of males and females of two sympatric species of the Longipalpis complex from Sobral (Ceará State, Brazil) in controlled laboratory conditions. We observed small but significant differences between the two species in the activity phase in both males and females.


Asunto(s)
Psychodidae/clasificación , Psychodidae/fisiología , Animales , Conducta Animal , Brasil , Ritmo Circadiano/fisiología , Femenino , Masculino , Actividad Motora/fisiología
16.
Phys Rev E Stat Nonlin Soft Matter Phys ; 77(1 Pt 1): 011902, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18351871

RESUMEN

FtsZ is a bacterial protein that forms filaments that play an essential role in midcell constriction during the process of cell division. The shape of individual filaments of different lengths imaged with atomic force microscopy was modeled considering the protein monomers as beads in a chain and a few parameters to represent their effective interactions. The flexural rigidity and persistence length of the filaments were estimated. This latter value was comparable to the filament length, implying that these biological polymers are halfway between the perfectly stiff linear aggregate whose shapes are fully controlled by the angle between the monomers and highly flexible polymers whose shapes follow a random walk model. The lateral interactions between adjacent filaments, also estimated in the modeling, were found to play an essential role in determining the final shape and kinetics of the coiled structures found in longer polymers. The estimated parameters were used to model the behavior of the polymers also on a cylindrical surface. This analysis points to the formation of helical structures that suggest a mechanism for force generation and amplification through the development of FtsZ spirals at the midcell division point.


Asunto(s)
Bacterias/citología , Fenómenos Fisiológicos Bacterianos , Proteínas Bacterianas/química , Proteínas Bacterianas/fisiología , División Celular/fisiología , Proteínas del Citoesqueleto/química , Proteínas del Citoesqueleto/fisiología , Mecanotransducción Celular/fisiología , Modelos Biológicos , Bacterias/química , Proteínas de Filamentos Intermediarios/química , Proteínas de Filamentos Intermediarios/fisiología , Modelos Químicos , Proteínas Motoras Moleculares/química , Proteínas Motoras Moleculares/fisiología , Estrés Mecánico
18.
Environ Sci Pollut Res Int ; 24(2): 1093-1104, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27335017

RESUMEN

Some pollutants can be resistant to wastewater treatment, hence becoming a risk to aquatic and terrestrial biota even at the very low concentrations (ng L-1-µg L-1) they are commonly found at. Tertiary treatments are used for micropollutant removal but little is known about the ecotoxicity of the treated effluent. In this study, a municipal secondary effluent was treated by a solar photo-Fenton reactor at initial neutral pH in a raceway pond reactor, and ecotoxicity was evaluated before and after micropollutant removal. Thirty-nine micropollutants were identified in the secondary effluent, mainly pharmaceuticals, with a total concentration of ≈80 µg L-1. After treatment, 99 % microcontaminant degradation was reached. As for ecotoxicity reduction, the assayed organisms showed the following sensitivity levels: Tetrahymena thermophila > Daphnia magna > Lactuca sativa > Spirodela polyrhiza ≈ Vibrio fischeri. The initial effluent showed an inhibitory effect of 40 % for T. thermophila and 20 % for D. magna. After 20 min of photo-Fenton treatment, no toxic effect was observed for T. thermophila and toxicity dropped to 5 % for D. magna. Graphical abstract Ecotoxicity removal by solar photo-Fenton at neutral pH. ᅟ.


Asunto(s)
Estanques , Luz Solar , Aguas Residuales/química , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodos , Aliivibrio fischeri/efectos de los fármacos , Animales , Daphnia/efectos de los fármacos , Peróxido de Hidrógeno/química , Concentración de Iones de Hidrógeno , Hierro/química
19.
Br J Pharmacol ; 149(7): 829-37, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17031386

RESUMEN

BACKGROUND AND PURPOSE: The mitochondrial permeability transition pore (mPTP), an energy-dissipating channel activated by calcium, contributes to reperfusion damage by depolarizing the mitochondrial inner membrane potential. As mitochondrial Ca(2+) overload is a main inductor of mPTP opening, we examined the effect of Ru(360), a selective inhibitor of the mitochondrial calcium uptake system against myocardial damage induced by reperfusion in a rat model. EXPERIMENTAL APPROACH: Myocardial reperfusion injury was induced by a 5-min occlusion of the left anterior descending coronary artery, followed by a 5-min reperfusion in anaesthetized open-chest rats. We measured reperfusion-induced arrhythmias and functions indicative of unimpaired mitochondrial integrity to evaluate the effect of Ru(360) treatment. KEY RESULTS: Reperfusion elicited a high incidence of arrhythmias, haemodynamic dysfunction and loss of mitochondrial integrity. A bolus intravenous injection of Ru(360) (15-50 nmol kg(-1)), given 30-min before ischaemia, significantly improved the above mentioned variables in the ischaemic/reperfused myocardium. Calcium uptake in isolated mitochondria from Ru(360)-treated ventricles was partially diminished, suggesting an interaction of this compound with the calcium uniporter. CONCLUSIONS AND IMPLICATIONS: We showed that Ru(360) treatment abolishes the incidence of arrhythmias and haemodynamic dysfunction elicited by reperfusion in a whole rat model. Ru(360) administration partially inhibits calcium uptake, preventing mitochondria from depolarization by the opening of the mPTP. We conclude that myocardial damage could be a consequence of failure of the mitochondrial network to maintain the membrane potential at reperfusion. Hence, it is plausible that Ru(360) could be used in reperfusion therapy to prevent the occurrence of arrhythmia.


Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio/efectos de los fármacos , Calcio/metabolismo , Mitocondrias Cardíacas/efectos de los fármacos , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Reperfusión Miocárdica/efectos adversos , Compuestos de Rutenio/farmacología , Aconitato Hidratasa/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/metabolismo , Bloqueadores de los Canales de Calcio/uso terapéutico , Canales de Calcio/metabolismo , Respiración de la Célula/efectos de los fármacos , Circulación Coronaria/efectos de los fármacos , Ciclosporina/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Electrocardiografía , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Mitocondrias Cardíacas/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/efectos de los fármacos , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Poro de Transición de la Permeabilidad Mitocondrial , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/fisiopatología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Ratas , Ratas Wistar , Compuestos de Rutenio/metabolismo , Compuestos de Rutenio/uso terapéutico , Rojo de Rutenio/farmacología , Factores de Tiempo , Fibrilación Ventricular/metabolismo , Fibrilación Ventricular/prevención & control
20.
Biochim Biophys Acta ; 1252(1): 95-102, 1995 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-7548171

RESUMEN

The 205-316 C-terminal fragment of thermolysin has been studied by differential scanning calorimetry at pH values 2.5, 3.0, 3.5, 4.0 and 5.0 and at a constant ionic strength of 130 mM. The thermal unfolding of the fragment occurs at thermodynamic equilibrium under our experimental conditions. The effect of sample concentration at the different pH values on the calorimetric traces is consistent with a monomer-dimer equilibrium of the folded fragment, which undergoes thermal unfolding into individual fragments. Equilibrium sedimentation experiments at 10 degrees C and different pH values confirm the presence of the association equilibrium and provide the value of the dimerization constants. The global analysis of the calorimetric, heat capacity curves has been carried out by a multidimensional fitting to the model N2<-->2N<-->2U. The analysis leads to a complete thermodynamic characterization of both the association and unfolding processes of the fragment. The resulting thermodynamic functions suggest a partially unfolded structure for both the monomeric and dimeric fragment, as well as a conformational change linked to the association process. Our results are discussed in terms of the structural information currently available and compared with the energetics of unfolding of the shorter 255-316 dimeric C-terminal fragment of thermolysin (Conejero-Lara, F., De Filippis, V., Fontana, A. and Mateo, P.L. (1994) FEBS Lett. 344, 154-156). The presence of the additional 50 residues increases the relative population of the 205-316 monomeric fragment versus that of the 255-316 fragment.


Asunto(s)
Termolisina/química , Rastreo Diferencial de Calorimetría , Concentración de Iones de Hidrógeno , Pliegue de Proteína , Termodinámica
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