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1.
Health Educ Res ; 39(1): 68-83, 2024 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-38183268

RESUMEN

Mothers of children with chronic conditions or disabilities have benefited from mindfulness programs, yet culturally relevant mindfulness programs for Spanish-speaking mothers are lacking. We aimed to explore how this population experienced a peer-led mindfulness program to inform adaptations. Sixteen mothers attended a 6-week program and completed semi-structured interviews. Using a realist evaluation framework, we explored relationships between participants' context, the program's mechanisms and outcomes. Our thematic analysis found that four contextual factors-faith, self-concept as a woman and mother, trauma, and level of social support-influenced how participants experienced the mechanisms. Mechanisms included having positive experiences when trying practices, engaging in self-reflection, and sharing life experiences and learning in community. The mechanisms led to four outcomes: emotion regulation, savoring daily life experiences, empowerment to practice self-care and common humanity. Faith was an important enabling factor because participants had positive experiences when integrating their faith with program content. Future research should examine adaptations that invite participants to explore this synergy. Self-reflection should also be emphasized because it increased motivation to use practices and helped address barriers to engagement. Because the four contextual factors apply to many Spanish-speaking immigrants, these adaptations could enhance mindfulness programs for this population more broadly.


Asunto(s)
Atención Plena , Madres , Femenino , Niño , Humanos , Madres/psicología , Grupo Paritario , Apoyo Social , Enfermedad Crónica
2.
Extremophiles ; 27(3): 31, 2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37848738

RESUMEN

There are few biophysical studies or structural characterizations of the type IV pilin system of extremophile bacteria, such as the acidophilic Acidithiobacillus thiooxidans. We set out to analyze their pili-comprising proteins, pilins, because these extracellular proteins are in constant interaction with protons of the acidic medium in which At. thiooxidans grows. We used the web server Operon Mapper to analyze and identify the cluster codified by the minor pilin of At. thiooxidans. In addition, we carried an in-silico characterization of such pilins using the VL-XT algorithm of PONDR® server. Our results showed that structural disorder prevails more in pilins of At. thiooxidans than in non-acidophilic bacteria. Further computational characterization showed that the pilins of At. thiooxidans are significantly enriched in hydroxy (serine and threonine) and amide (glutamine and asparagine) residues, and significantly reduced in charged residues (aspartic acid, glutamic acid, arginine and lysine). Similar results were obtained when comparing pilins from other Acidithiobacillus and other acidophilic bacteria from another genus versus neutrophilic bacteria, suggesting that these properties are intrinsic to pilins from acidic environments, most likely by maintaining solubility and stability in harsh conditions. These results give guidelines for the application of extracellular proteins of acidophiles in protein engineering.


Asunto(s)
Acidithiobacillus , Proteínas Fimbrias , Proteínas Fimbrias/genética , Proteínas Fimbrias/química , Proteínas Fimbrias/metabolismo , Acidithiobacillus thiooxidans/genética , Acidithiobacillus thiooxidans/metabolismo , Aminoácidos/metabolismo , Acidithiobacillus/genética , Acidithiobacillus/metabolismo , Ácidos
3.
Rev Esp Enferm Dig ; 112(7): 520-524, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31617364

RESUMEN

OBJECTIVE AND METHODS: an observational, longitudinal, prospective study was performed to assess changes in perceived quality of life in asymptomatic patients with hepatitis C under treatment with direct-acting antivirals. Questionnaires SF-36 and EQ-5D-5L were administered to 86 treated patients and 12 controls. RESULTS: there were improvements in several parameters such as physical functioning, bodily pain, general health, vitality and social functioning, particularly when the perceptions were compared before treatment and after treatment completion and following recovery. CONCLUSION: these data support the hypothesis that the hepatitis C virus may worsen quality of life in asymptomatic patients.


Asunto(s)
Hepatitis C Crónica , Calidad de Vida , Antivirales/uso terapéutico , Hepacivirus , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Estudios Prospectivos , Encuestas y Cuestionarios
4.
Rev Esp Enferm Dig ; 112(7): 532-537, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32579001

RESUMEN

INTRODUCTION: data on the prevalence and characteristics of hepatitis C patients lost to follow-up are lacking. In addition, the identification of this population clashes with data protection regulations. METHODS: the identification and contact protocol was submitted to the Health Care Ethics Committee. The protocol was based on anti-HCV serology test results for 2010-2018, which were obtained from the Microbiology Department. In addition, the situation of the patients in the hospital and regional database was analyzed, based on the following classification: a) chronic hepatitis C, if the last HCV RNA determination was positive; b) cured hepatitis C, if the last HCV RNA determination was negative after 12 weeks of treatment; and c) possible hepatitis C, if anti-HCV antibodies were positive with no result for HCV RNA. Lost patients were defined as those with chronic or possible hepatitis C and no follow-up in the Digestive Diseases or Internal Medicine Departments. The patients were contacted by postal mail and then by telephone, so that they could be offered treatment. RESULTS: the Ethics Committee considered that the protocol fulfilled the bioethical principles of autonomy, beneficence, non-maleficence and justice and that contact was ethically desirable. From 4,816 positive anti-HCV serology results, 677 patients were identified who were lost to follow-up (14.06 %; 95 % CI, 13.2-15.2). The mean age was 54 years, 61 % were male, 12 % were foreign born and 95 % were mono-infected. The study of each serology result took 1.3 minutes. One-quarter (25 %) of the losses corresponded to the Digestive Diseases and Internal Medicine Departments. Of the 677 losses, serology testing had only been ordered for 449 patients (66.3 %) and the remaining 228 (33.7 %) also had a positive HCV RNA result. CONCLUSION: a large number of patients with hepatitis C are lost to follow-up. Searching for and contacting these patients is legally and ethically viable.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Hepacivirus/genética , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Anticuerpos contra la Hepatitis C , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia
5.
Bioessays ; 39(6)2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28370099

RESUMEN

Kv10.1 is a voltage-gated potassium channel relevant for tumor biology, but the underlying mechanism is still unclear. We propose that Kv10.1 plays a role coordinating primary cilium disassembly with cell cycle progression through localized changes of membrane potential at the ciliary base. Most non-dividing cells display a primary cilium, an antenna-like structure important for cell physiology. The cilium is disassembled when the cell divides, which requires an increase of Ca2+ concentration and a redistribution of phospholipids in its basal region, both of which would be facilitated by local hyperpolarization. Cells lacking Kv10.1 show impaired ciliary disassembly and delayed entrance into mitosis. Kv10.1 is predominantly expressed during G2/M, a critical period for ciliary resorption, and localizes to the ciliary base and vesicles associated with the centrosome. This could explain the influence of Kv10.1 in cell proliferation, as well as phenotypic features of patients carrying gain of function mutations in the gene.


Asunto(s)
Puntos de Control del Ciclo Celular/fisiología , Cilios/metabolismo , Mitosis , Canales de Potasio con Entrada de Voltaje/metabolismo , Animales , Proteínas de Ciclo Celular , Humanos , Potenciales de la Membrana , Canales de Potasio con Entrada de Voltaje/fisiología
6.
EMBO Rep ; 17(5): 708-23, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-27113750

RESUMEN

The primary cilium, critical for morphogenic and growth factor signaling, is assembled upon cell cycle exit, but the links between ciliogenesis and cell cycle progression are unclear. KV10.1 is a voltage-gated potassium channel frequently overexpressed in tumors. We have previously reported that expression of KV10.1 is temporally restricted to a time period immediately prior to mitosis in healthy cells. Here, we provide microscopical and biochemical evidence that KV10.1 localizes to the centrosome and the primary cilium and promotes ciliary disassembly. Interference with KV10.1 ciliary localization abolishes not only the effects on ciliary disassembly, but also KV10.1-induced tumor progression in vivo Conversely, upon knockdown of KV10.1, ciliary disassembly is impaired, proliferation is delayed, and proliferating cells show prominent primary cilia. Thus, modulation of ciliogenesis by KV10.1 can explain the influence of KV10.1 expression on the proliferation of normal cells and is likely to be a major mechanism underlying its tumorigenic effects.


Asunto(s)
Cilios/metabolismo , Canales de Potasio Éter-A-Go-Go/genética , Regulación de la Expresión Génica , Animales , Línea Celular , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Centrosoma , Cortactina/metabolismo , Canales de Potasio Éter-A-Go-Go/metabolismo , Fibroblastos , Técnicas de Silenciamiento del Gen , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Potenciales de la Membrana , Ratones , Ratones Noqueados , Transporte de Proteínas , ARN Interferente Pequeño/genética , Transducción de Señal
7.
J Biol Chem ; 290(51): 30351-65, 2015 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-26518875

RESUMEN

KV10.1 is a voltage-gated potassium channel expressed selectively in the mammalian brain but also aberrantly in cancer cells. In this study we identified short splice variants of KV10.1 resulting from exon-skipping events (E65 and E70) in human brain and cancer cell lines. The presence of the variants was confirmed by Northern blot and RNase protection assays. Both variants completely lacked the transmembrane domains of the channel and produced cytoplasmic proteins without channel function. In a reconstituted system, both variants co-precipitated with the full-length channel and induced a robust down-regulation of KV10.1 current when co-expressed with the full-length form, but their effect was mechanistically different. E65 required a tetramerization domain and induced a reduction in the overall expression of full-length KV10.1, whereas E70 mainly affected its glycosylation pattern. E65 triggered the activation of cyclin-dependent kinases in Xenopus laevis oocytes, suggesting a role in cell cycle control. Our observations highlight the relevance of noncanonical functions for the oncogenicity of KV10.1, which need to be considered when ion channels are targeted for cancer therapy.


Asunto(s)
Empalme Alternativo/fisiología , Ciclo Celular/fisiología , Quinasas Ciclina-Dependientes/metabolismo , Canales de Potasio Éter-A-Go-Go/metabolismo , Animales , Secuencia de Bases , Quinasas Ciclina-Dependientes/genética , Activación Enzimática , Canales de Potasio Éter-A-Go-Go/genética , Células HEK293 , Células HeLa , Humanos , Datos de Secuencia Molecular , Oocitos/citología , Oocitos/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Xenopus laevis
8.
Biochim Biophys Acta ; 1838(3): 921-31, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24269539

RESUMEN

KV10.1 potassium channels are implicated in a variety of cellular processes including cell proliferation and tumour progression. Their expression in over 70% of human tumours makes them an attractive diagnostic and therapeutic target. Although their physiological role in the central nervous system is not yet fully understood, advances in their precise cell localization will contribute to the understanding of their interactions and function. We have determined the plasma membrane (PM) distribution of the KV10.1 protein in an enriched mouse brain PM fraction and its association with cholesterol- and sphingolipid-rich domains. We show that the KV10.1 channel has two different populations in a 3:2 ratio, one associated to and another excluded from Detergent Resistant Membranes (DRMs). This distribution of KV10.1 in isolated PM is cholesterol- and cytoskeleton-dependent since alteration of those factors changes the relationship to 1:4. In transfected HEK-293 cells with a mutant unable to bind Ca(2+)/CaM to KV10.1 protein, Kv10.1 distribution in DRM/non-DRM is 1:4. Mean current density was doubled in the cholesterol-depleted cells, without any noticeable effects on other parameters. These results demonstrate that recruitment of the KV10.1 channel to the DRM fractions involves its functional regulation.


Asunto(s)
Membrana Celular/metabolismo , Canales de Potasio Éter-A-Go-Go/metabolismo , Microdominios de Membrana/metabolismo , Neuronas/metabolismo , Canales de Potasio con Entrada de Voltaje/metabolismo , Animales , Western Blotting , Membrana Celular/química , Colesterol/metabolismo , Citoesqueleto/metabolismo , Detergentes/metabolismo , Electrofisiología , Canales de Potasio Éter-A-Go-Go/química , Canales de Potasio Éter-A-Go-Go/genética , Femenino , Células HEK293 , Humanos , Microdominios de Membrana/química , Ratones , Ratones Endogámicos C57BL , Neuronas/citología , Canales de Potasio con Entrada de Voltaje/química , Canales de Potasio con Entrada de Voltaje/genética , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
9.
Bioorg Med Chem ; 23(24): 7535-42, 2015 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-26631442

RESUMEN

Testosterone (T) plays a crucial role in prostate growth. In androgen-dependent tissues T is reduced to dihydrotestosterone (DHT) because of the presence of the 5α-reductase enzyme. This androgen is more active than T, since it has a higher affinity for the androgen receptor (AR). When this mechanism is altered, androgen-dependent diseases, including prostate cancer, could result. The aim of this study was to synthesize several 16-dehydropregnenolone acetate derivatives containing a triazole ring at C-21 and a linear or alicyclic ester moiety at C-3 of the steroidal skeleton. These steroids were designed as potential inhibitors of the activity of both types (1 and 2) of 5α-reductase. The cytotoxic activity of these compounds was also evaluated on a panel of PC-3, MCF7, and SK-LU-1 human cancer cell lines. The results from this study showed that with the exception of steroids 20-oxo-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-3ß-yl-propionate and 20-oxo-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-3ß-yl-pentanoate, the compounds exhibit a lower inhibitory activity for both isoenzymes of 5α-reductase than finasteride. Furthermore the 3ß-hydroxy-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-20-one and 20-oxo-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-3ß-yl-acetate derivatives display 80% cytotoxic activity on the SK-LU-1 cell line. These results also indicated that the triazole derivatives, which have a hydroxyl or acetoxy group at C-3, could have an anticancer effect, whereas the derivatives with a alicyclic ester group at C-3 do not show biological activity.


Asunto(s)
Inhibidores de 5-alfa-Reductasa/química , Inhibidores de 5-alfa-Reductasa/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Pregnenolona/análogos & derivados , Inhibidores de 5-alfa-Reductasa/síntesis química , Animales , Antineoplásicos/síntesis química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colestenona 5 alfa-Reductasa/metabolismo , Humanos , Masculino , Mesocricetus , Neoplasias/tratamiento farmacológico , Neoplasias/enzimología , Pregnenolona/síntesis química , Pregnenolona/química , Pregnenolona/farmacología , Ratas
10.
J Enzyme Inhib Med Chem ; 30(1): 152-9, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24666307

RESUMEN

The role of progesterone in women's cancers as well as the knowledge of the progesterone receptor (PR) structure has prompted the design of different therapies. The aim of this review is to describe the basic structure of PR agonists and antagonists as well as the recent treatments for illness associated with the progesterone receptor. The rational design for potent and effective drugs for the treatment of female cancer must consider the structural changes of the androgen and progestogen skeleton which are an indicator of their activity as progestins or antiprogestins. The presence of a hydroxyl group at C-17 in the progesterone skeleton brings about a loss of progestational activity whereas acetylation induces a progestational effect. The incorporation of an ethynyl functional group to the testosterone framework results in a loss of androgenic activity with a concomitant enhancement of the progestational effect. On the other hand, an ester function at C-3 of dehydroepiandrosterone skeleton induces partial antagonism to the PR.


Asunto(s)
Antineoplásicos Hormonales/química , Neoplasias de la Mama/tratamiento farmacológico , Progestinas/química , Receptores de Progesterona/agonistas , Receptores de Progesterona/antagonistas & inhibidores , Acetilación , Antineoplásicos Hormonales/síntesis química , Antineoplásicos Hormonales/farmacología , Sitios de Unión , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Deshidroepiandrosterona/química , Diseño de Fármacos , Femenino , Humanos , Hidroxilación , Progesterona/química , Progestinas/síntesis química , Progestinas/farmacología , Unión Proteica , Receptores de Progesterona/metabolismo , Relación Estructura-Actividad , Testosterona/química
11.
Bioorg Med Chem ; 22(21): 6233-41, 2014 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-25261928

RESUMEN

It is well known that testosterone (T) under the influence of 5α-reductase enzyme is converted to dihydrotestosterone (DHT), which causes androgen-dependent diseases. The aim of this study was to synthesize new dehydroepiandrosterone derivatives (3a-e, 4a-i, 6 and 7) having potential inhibitory activity against the 5α-reductase enzyme. This paper also reports the in vivo pharmacological effect of these steroidal molecules. The results from this study showed that all compounds exhibited low inhibitory activity for 5α-reductase type 1 and 2 enzymes and they failed to bind to the androgen receptor. Furthermore, in the in vivo experiment, steroids 3b, 4f, and 4 g showed comparable antiandrogenic activity to that of finasteride; only derivatives 4d and 7 produced a considerable decrease in the weight of the prostate gland of gonadectomized hamsters treated with (T). On the other hand, compounds 4a, f and h showed 100% inhibition of the growth of prostate cancer cell line PC-3, with compound 4 g having a 98.2% antiproliferative effect at 50 µM. The overall data indicated that these steroidal molecules, having an aromatic ester moiety at C-3 (4f-h), could have anticancer properties.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Colestenona 5 alfa-Reductasa/antagonistas & inhibidores , Deshidroepiandrosterona/análogos & derivados , Deshidroepiandrosterona/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Animales , Línea Celular Tumoral , Células Cultivadas , Colestenona 5 alfa-Reductasa/metabolismo , Cricetinae , Femenino , Humanos , Isoenzimas/antagonistas & inhibidores , Isoenzimas/metabolismo , Masculino , Ratones , Persona de Mediana Edad , Próstata/efectos de los fármacos , Próstata/metabolismo , Neoplasias de la Próstata/metabolismo , Ratas
12.
Biochem Biophys Rep ; 39: 101797, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39161578

RESUMEN

Thirty years since the first report on the PilY1 protein in bacteria, only the C-terminal domain has been crystallized; there is no study in which the N-terminal domain, let alone the complete protein, has been crystallized. In our laboratory, we are interested in characterizing the Type IV Pili (T4P) of Acidithiobacillus thiooxidans. We performed an in silico characterization of PilY1 and other pilins of the T4P of this acidophilic bacterium. In silico characterization is crucial for understanding how proteins adapt and function under extreme conditions. By analyzing the primary and secondary structures of proteins through computational methods, researchers can gain valuable insights into protein stability, key structural features, and unique amino acid compositions that contribute to resilience in harsh environments. Here, it is presented a description of the particularities of At. thiooxidans PilY1 through predictor software and homology data. Our results suggest that PilY1 from At. thiooxidans may have the same role as has been described for other PilY1 associated with T4P in neutrophilic bacteria; also, its C-terminal interacts (interface interaction) with the minor pilins PilX, PilW and PilV. The N-terminal region comprises domains such as the vWA and the MIDAS, involved in signaling, ligand-binding, and protein-protein interaction. In fact, the vWA domain has intrinsically disordered regions that enable it to maintain its structure over a wide pH range, not only at extreme acidity to which At. thiooxidans is adapted. The results obtained helped us design the correct methodology for its heterologous expression. This allowed us partially experimentally characterize it by obtaining the N-terminal domain recombinantly and evaluating its acid stability through fluorescence spectroscopy. The data suggest that it remains stable across pH changes. This work thus provides guidance for the characterization of extracellular proteins from extremophilic organisms.

13.
J Microbiol Biotechnol ; 34(3): 527-537, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38346803

RESUMEN

Pilins are protein subunits of pili. The pilins of type IV pili (T4P) in pathogenic bacteria are well characterized, but anything is known about the T4P proteins in acidophilic chemolithoautotrophic microorganisms such as the genus Acidithiobacillus. The interest in T4P of A. thiooxidans is because of their possible role in cell recruitment and bacterial aggregation on the surface of minerals during biooxidation of sulfide minerals. In this study we present a successful ad hoc methodology for the heterologous expression and purification of extracellular proteins such as the minor pilin PilV of the T4P of A. thiooxidans, a pilin exposed to extreme conditions of acidity and high oxidation-reduction potentials, and that interact with metal sulfides in an environment rich in dissolved minerals. Once obtained, the model structure of A. thiooxidans PilV revealed the core basic architecture of T4P pilins. Because of the acidophilic condition, we carried out in silico characterization of the protonation status of acidic and basic residues of PilV in order to calculate the ionization state at specific pH values and evaluated their pH stability. Further biophysical characterization was done using UV-visible and fluorescence spectroscopy and the results showed that PilV remains soluble and stable even after exposure to significant changes of pH. PilV has a unique amino acid composition that exhibits acid stability, with significant biotechnology implications such as biooxidation of sulfide minerals. The biophysics profiles of PilV open new paradigms about resilient proteins and stimulate the study of other pilins from extremophiles.


Asunto(s)
Acidithiobacillus thiooxidans , Proteínas Fimbrias , Proteínas Fimbrias/genética , Acidithiobacillus thiooxidans/metabolismo , Fimbrias Bacterianas , Sulfuros/metabolismo , Minerales/metabolismo
14.
Front Immunol ; 15: 1310472, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38576621

RESUMEN

We analyzed 136 children with tuberculosis disease or infection and a positive QuantiFERON-TB (QFT) assay, followed-up for a median of 21 months (0.4-11years). QFT reversed in 16.9% of cases, with significant decreases in TB1 (-1.72 vs. -0.03 IU/ml, p=0.001) and TB2 (-1.65 vs. -0.43 IU/ml, p=0.005) levels compared to non-reverters. We found a higher QFT reversion rate among children under 5 years (25.0% vs 11.9%, p=0.042), and those with TST induration <15mm (29% vs 13.3%, p=0.055). Our data reveal that, although QFT test remained positive in the majority of children, reversion occurred in 16% of cases in a progressive and stable pattern. Younger age and reduced TST induration were associated with QFT reversion.


Asunto(s)
Prueba de Tuberculina , Tuberculosis , Niño , Humanos , Adolescente , Preescolar , Tuberculosis/diagnóstico
15.
J Enzyme Inhib Med Chem ; 28(6): 1247-54, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23051174

RESUMEN

The aim of these studies was to synthesize twelve ester derivatives of dehydroepiandrosterone with therapeutic potential. The effect of 1-12 was demonstrated in the flank organs of gonadectomized hamsters treated with testosterone and the synthesized steroids. In vitro studies were carried out determining the IC50 values for the inhibition of the activity of 5α-reductase type 1 and 2, which are present in rat liver and human prostate respectively. The binding of 1-12 to the androgen receptors (AR) was determined using rat's prostate cytosol. Steroids 1-12 containing different substituents in the phenyl group of the ester moiety in C-3 reduced the flank organs and inhibited the activity of 5α-R type 1; however only steroids 1 and 2 inhibited 5α-R type 2. 1-12 did not bind to the AR. The modification of one atom of the substituents in the phenyl group of the ester moiety in C-3 changed their biological potency (IC50).


Asunto(s)
Inhibidores de 5-alfa-Reductasa/farmacología , Androstenos/farmacología , Colestenona 5 alfa-Reductasa/antagonistas & inhibidores , Inhibidores de 5-alfa-Reductasa/síntesis química , Inhibidores de 5-alfa-Reductasa/química , Androstenos/síntesis química , Androstenos/química , Animales , Colestenona 5 alfa-Reductasa/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Concentración de Iones de Hidrógeno , Hígado/enzimología , Masculino , Mesocricetus , Persona de Mediana Edad , Estructura Molecular , Próstata/enzimología , Ratas , Relación Estructura-Actividad
16.
Mol Biol Rep ; 39(3): 2187-94, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21643953

RESUMEN

Transfection has become an everyday technique widely used for functional studies in living cells. The choice of the particular transfection method is usually determined by its efficiency and toxicity, and possible functional consequences specific to the method used are normally overlooked. We describe here that nucleofection, a method increasingly used because of its convenience and high efficiency, increases the metabolic rate of some cancer cells, which can be misleading when used as a measure of proliferation. Moreover, nucleofection can alter the subcellular expression pattern of the transfected protein. These undesired effects are independent of the transfected nucleic acid, but depend on the particular cell line used. Therefore, the interpretation of functional data using this technology requires further controls and caution.


Asunto(s)
Núcleo Celular/metabolismo , Electroporación/métodos , Metabolismo Energético/fisiología , Transfección/métodos , Análisis de Varianza , Animales , Línea Celular , Proliferación Celular , Citometría de Flujo , Humanos , Ratones , Microscopía Fluorescente , Oxazinas/metabolismo , Oxidación-Reducción , Reacción en Cadena en Tiempo Real de la Polimerasa , Sales de Tetrazolio/metabolismo , Tiazoles/metabolismo , Xantenos/metabolismo
17.
Farm Hosp ; 45(3): 126-134, 2021 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-33941056

RESUMEN

OBJECTIVE: To review the available literature on the administration of oral antineoplastic drugs in patients with swallowing disorders and  ystematize the information obtained. METHOD: Between September 2019 and April 2020, two hospital  harmacists drew up a list of the oral antineoplastic drugs available in  Spain, which was then distributed to three hospital pharmacists, each of  whom carried out a literature search and a review. An analysis was made  of the prescribing information and searches were performed in Pubmed, Micromedex, Uptodate, the Cancer Care Ontario website,  different pharmaceutical bulletins, feeding tube administration guidelines,  and tertiary information sources. Lastly, the pharmaceutical industry was  contacted. The group systematized the information obtained, after which a fourth hospital pharmacist and an independent physician reviewed the  work carried out. RESULTS: A total of 64 oral antineoplastic drugs were reviewed. Relevant information was obtained for 48 drugs, of which 44 were  amenable to administration to these patients (69% of the investigated  drugs). A systematization of the information found was carried out. Conclusions: Despite having found different methods for preparing and administering most of the oral antineoplastic drugs reviewed, the  information compiled was rather scarce and with a low level of evidence.  Further studies, based on pharmacokinetic and stability studies, are  necessary in this field as there is a sore need for oral liquid pharmaceutical forms or extemporaneous preparations allowing administration of oral  antineoplastic drugs to these patients.


Objetivo: Revisar la literatura disponible sobre la administración de  antineoplásicos orales en pacientes con trastornos de la deglución y  realizar una síntesis de la información hallada.Método: En el periodo septiembre 2019-junio 2020, tres farmacéuticos hospitalarios elaboraron una lista con los antineoplásicos  orales disponibles en España, la cual fue repartida, y cada cual llevó a  cabo la búsqueda y revisión bibliográfica de los medicamentos asignados.  Se revisaron las fichas técnicas y así como Pubmed, Micromedex,  Uptodate, la página web del Cancer Care Ontario, diferentes boletines  farmacéuticos, guías de administración por sonda y otras fuentes terciarias de información. En último lugar, se contactó con la industria farmacéutica. Posteriormente cada uno sintetizó la información que había  hallado y para concluir, un médico y un cuarto farmacéutico hospitalario  revisaron todo el trabajo llevado a cabo.Resultados: Se revisaron un total de 64 fármacos antineoplásicos orales. Se obtuvo información pertinente en el caso de 48, de los cuales 44  presentaban posibilidad de administración en estos pacientes (un 69% de  los fármacos investigados). Se realizó una síntesis de la información  hallada.Conclusiones: Pese a haber encontrado posibles métodos de preparación y administración para la mayoría de los antineoplásicos orales  revisados, se constata que la información es más bien escasa y con bajo  nivel  de evidencia. Es necesario seguir investigando en este campo, ya  que se precisan formas farmacéuticas líquidas, o preparaciones  extemporáneas, que en base a estudios farmacocinéticos y de estabilidad  permitan la administración de antineoplásicos orales en este grupo de  pacientes.


Asunto(s)
Antineoplásicos , Trastornos de Deglución , Preparaciones Farmacéuticas , Administración Oral , Antineoplásicos/efectos adversos , Trastornos de Deglución/tratamiento farmacológico , Humanos , Farmacéuticos
18.
Cancers (Basel) ; 12(4)2020 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-32283712

RESUMEN

Reprogramming of energy metabolism constitutes one of the hallmarks of cancer and is, therefore, an emerging therapeutic target. We describe here that the potassium channel Kv10.1, which is frequently overexpressed in primary and metastatic cancer, and has been proposed a therapeutic target, participates in metabolic adaptation of cancer cells through regulation of mitochondrial dynamics. We used biochemical and cell biological techniques, live cell imaging and high-resolution microscopy, among other approaches, to study the impact of Kv10.1 on the regulation of mitochondrial stability. Inhibition of Kv10.1 expression or function led to mitochondrial fragmentation, increase in reactive oxygen species and increased autophagy. Cells with endogenous overexpression of Kv10.1 were also more sensitive to mitochondrial metabolism inhibitors than cells with low expression, indicating that they are more dependent on mitochondrial function. Consistently, a combined therapy using functional monoclonal antibodies for Kv10.1 and mitochondrial metabolism inhibitors resulted in enhanced efficacy of the inhibitors. Our data reveal a new mechanism regulated by Kv10.1 in cancer and a novel strategy to overcome drug resistance in cancers with a high expression of Kv10.1.

19.
Int J Biol Macromol ; 164: 1600-1607, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-32768477

RESUMEN

The acyl-CoA dehydrogenase (FadE) and (R)-specific enoyl-CoA hydratase (PhaJ) are functionally related to the degradation of fatty acids and the synthesis of polyhydroxyalkanoates (PHAs). To verify this, a recombinant Cupriavidus necator H16 harboring the plasmid -pMPJAS03- with fadE from Escherichia coli strain K12 and phaJ1 from Pseudomonas putida strain KT2440 under the arabinose promoter (araC-PBAD) was constructed. The impact of co-expressing fadE and phaJ genes on C. necator H16/pMPJAS03 maintaining the wild-type synthase on short-chain-length/medium-chain-length PHA formation from canola or avocado oil at different arabinose concentrations was investigated. The functional activity of fadEE.c led to obtaining higher biomass and PHA concentrations compared to the cultures without expressing the gene. While high transcriptional levels of phaJ1P.p, at 0.1% of arabinose, aid the wild-type synthase to polymerize larger-side chain monomers, such as 3-Hydroxyoctanoate (3HO) and 3-Hydroxydecanoate (3HD). The presence of even small amounts of 3HO and 3HD in the co-polymers significantly depresses the melting temperature of the polymers, compared to those composed of pure 3-hydroxybutyrate (3HB). Our data presents supporting evidence that the synthesis of larger-side chain monomers by the recombinant strain relies not only upon the affinity of the wild-type synthase but also on the functionality of the intermediate supplying enzymes.


Asunto(s)
Acil-CoA Deshidrogenasa/genética , Cupriavidus necator/genética , Enoil-CoA Hidratasa/genética , Aceites de Plantas/metabolismo , Polihidroxialcanoatos/biosíntesis , Polihidroxialcanoatos/genética , Acil-CoA Deshidrogenasa/metabolismo , Arabinosa/genética , Arabinosa/metabolismo , Caprilatos/metabolismo , Cupriavidus necator/metabolismo , Ácidos Decanoicos/metabolismo , Enoil-CoA Hidratasa/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Ácidos Grasos/genética , Ácidos Grasos/metabolismo , Hidroxibutiratos/metabolismo , Plásmidos/genética , Polihidroxialcanoatos/metabolismo , Regiones Promotoras Genéticas/genética , Pseudomonas putida/genética , Pseudomonas putida/metabolismo , Transcripción Genética/genética
20.
Rev Esp Salud Publica ; 942020 07 06.
Artículo en Español | MEDLINE | ID: mdl-32627766

RESUMEN

The objective of this study was to describe the measures introduced at the Hospital Germans Trias i Pujol, Barcelona, aimed at achieving a smoke-free environment, and encouraging research, training, and clinical approaches with respect to smoking. The experience gained as a center attached to the Catalan Network of Smokeless Hospitals since 2002 shows that preventing and controlling smoking requires a specific agenda developed by a competent committee comprising workers from all hospital areas. Likewise, coordination with other centers in the network is essential as it permits the sharing of experiences. The involvement of hospital management is critical for the effective introduction of health protection and promotion strategies, both in workers and in users. The raising of awareness and the ongoing training of all health workers and coordination with other health care providers in the Health network are the main aspects that require strengthening in the future.


El objetivo de este trabajo fue describir las medidas llevadas a cabo en el Hospital Germans Trias i Pujol de Barcelona, destinadas a conseguir un entorno libre de humo, así como al desarrollo de actividades de investigación, formación y abordaje clínico en relación al tabaquismo. La experiencia como centro adherido a la Red Catalana de Hospitales Sin Humo desde 2002 nos revela que para la prevención y control del tabaquismo es necesaria una agenda específica desarrollada por un Comité competente, compuesto por trabajadores de diferentes estamentos y servicios del centro. Del mismo modo, consideramos fundamental la coordinación con otros centros de la Red que permita compartir experiencias, así como la implicación de la Dirección del Centro para la implementación efectiva de las estrategias de promoción y protección de la salud, tanto en los trabajadores como en los usuarios. La sensibilización y formación continuada de todo el personal sanitario y la coordinación con otros servicios proveedores de salud de la red sanitaria se perfilan como los principales puntos a reforzar en el futuro.


Asunto(s)
Hospitales , Cese del Hábito de Fumar/métodos , Prevención del Hábito de Fumar/métodos , Promoción de la Salud/métodos , Humanos , España/epidemiología , Nicotiana
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