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1.
Acta Paediatr ; 113(3): 517-522, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38014571

RESUMEN

AIM: This study addresses the scarcity of longitudinal research on the influence of screen media on children. It aims to explore the longitudinal relationship between children's vocabulary development and their exposure to screen media. METHODS: The study, initiated in 2017, included 72 children (37 boys) in Östergötland, Sweden, at three key developmental stages: preverbal (9.7 months), early verbal (25.5 months) and preliterate (5.4 years). Parents completed online surveys at each time point, reporting their child's screen time. At 10 months and 2 years, age-appropriate vocabulary assessments were conducted online. At age 5, children's vocabulary was laboratory assessed. RESULTS: Correlational analysis revealed a negative relationship between language scores and screen media use across all time points. Furthermore, a cross-lagged panel model demonstrated that screen media use showed significant continuity over time, with screen use at age 2 predicting language development at ages 2 and 5. CONCLUSION: This longitudinal study, spanned from 9 months to 5 years of age, established a predictive negative association between children's exposure to screen media and their vocabulary development. These findings underscore the need to consider the impact of screen media on early childhood development and may inform guidelines for screen media use in young children.


Asunto(s)
Desarrollo Infantil , Vocabulario , Masculino , Niño , Humanos , Preescolar , Estudios Longitudinales , Desarrollo del Lenguaje , Lenguaje
2.
Infancy ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39024123

RESUMEN

Memory develops across the course of the first years of life and is influenced by daily experiences, such as exposure to media like books and television. Memory as tapped by Deferred imitation (DI) requires that toddlers form a representation of the target actions that they can later use to reproduce the actions and in addition to measuring memory for real live events, it can also be used to measure memory for events viewed through media. Toddlers are frequently exposed to multiple forms of digital media in addition to more traditional forms of picture book reading. In a within-subjects design, memory was assessed with a DI task in 2-year-olds (n = 89) using the Frankfurt Imitation Test. Deferred imitation was assessed after live and video demonstrations. Parents completed a survey about children's media use. Picture book reading for less than 30 min a day predicted lower memory scores for actions demonstrated live. Watching video content for more than 1 h a day predicted lower memory scores for actions demonstrated on video. Results are interpreted in terms of individual differences in experiences of traditional and digital media and the development of symbolic understanding.

3.
Transfusion ; 63(8): 1546-1553, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37422880

RESUMEN

BACKGROUND: Extracorporeal photopheresis (ECP) treatment, mostly based on apheresis technology, is used for immunomodulation in various diseases such as cutaneous T-cell lymphoma, graft versus host disease and other (auto)immune disorders. The aim of this study was to collect high cell counts and purity in shorter procedure times using an ECP off-line system with an increased collection flow rate of 2 mL/min to a target volume of 200 mL buffy coat. STUDY DESIGN AND METHODS: In this prospective study, data of routinely performed off-line photopheresis treatments were collected and analyzed at the Central Institute for Blood Transfusion & Department of Immunology (ZIB) of the Tirol Kliniken, to assess absolute cell counts and procedure times and to calculate collection efficiencies (CE2). RESULTS: A total of 22 patients participated in this study. The processed blood volume was 4312 mL, the collection time 120 min, overall procedure time 157 min and the absolute cell counts of treated white blood cells (WBC) and mononuclear cells (MNC) were 5.0 and 4.3 × 109 respectively (median values). The calculated CE2 for WBC and MNC was 21.1% and 58.5%, the proportion of treated MNCs of the total number of MNCs present was 55.0%. CONCLUSION: The data presented in this study show high therapeutically effective cell counts collected with a high MNC purity within a shorter overall collection/procedure time due to an increased collection flow rate.


Asunto(s)
Eliminación de Componentes Sanguíneos , Enfermedad Injerto contra Huésped , Fotoféresis , Neoplasias Cutáneas , Humanos , Fotoféresis/métodos , Estudios Prospectivos , Leucocitos , Enfermedad Injerto contra Huésped/terapia
4.
Infancy ; 27(4): 682-699, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35526265

RESUMEN

Although prior research has independently linked vocabulary development with toddlers' media usage, parental mental state talk (MST), and parent-child conversational turn-taking (CTT), these variables have not been investigated within the same study. In this study, we focus on associations between these variables and 2-year-old's (N = 87) vocabulary. Child vocabulary and digital media use were measured through online questionnaires. We took a multimethod approach to measure parents' child-directed talk. First, we used a home sound environment recording (Language ENvironment Analysis technology) to estimate parents' talk (CTT). Second, parents narrated a picture book, the Frog story, to assess the parent's MST. There was a negative association between how much children watched video content and their vocabulary. However, parents reported that they frequently co-viewed and engaged with the child and media. The negative association first displayed between the amount of video content viewed and the child's developing vocabulary was fully mediated by the parents' qualitative and quantitative talk as measured by MST and CCT, respectively. We propose that the parent relative level of MST and CTT also occurs when parents engage with the child during media use.


Asunto(s)
Relaciones Padres-Hijo , Vocabulario , Humanos , Internet , Desarrollo del Lenguaje , Padres
5.
J Exp Child Psychol ; 191: 104733, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31805463

RESUMEN

Procedural memory underpins the learning of skills and habits. It is often tested in children and adults with sequence learning on the serial reaction time (SRT) task, which involves manual motor control. However, due to infants' slowly developing control of motor actions, most procedures that require motor control cannot be examined in infancy. Here, we investigated procedural memory using an SRT task adapted for infants. During the task, images appeared at one of three locations on a screen, with the location order following a five-item recurring sequence. Three blocks of recurring sequences were followed by a random-order fourth block and finally another block of recurring sequences. Eye movement data were collected for infants (n = 35) and adults (n = 31). Reaction time was indexed by calculating the saccade latencies for orienting to each image as it appeared. The entire protocol took less than 3 min. Sequence learning in the SRT task can be operationalized as an increase in latencies in the random block as compared with the preceding and following sequence blocks. This pattern was observed in both the infants and adults. This study is the first to report learning in an SRT task in infants as young as 9  months. This SRT protocol is a promising procedure for measuring procedural memory in infants.


Asunto(s)
Desarrollo Infantil/fisiología , Memoria/fisiología , Aprendizaje Seriado/fisiología , Percepción Visual/fisiología , Adulto , Tecnología de Seguimiento Ocular , Femenino , Humanos , Lactante , Masculino , Adulto Joven
6.
Chemistry ; 23(65): 16681-16690, 2017 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-28976037

RESUMEN

Sulfur-bridged binuclear structures [2M-2S] play a pivotal role in a variety of chemical processes such as bond breaking and formation and electron transfer. In general, structural persistence is deemed essential to the respective function but owing to the lack of a suitable molecular model system, the current understanding of the factors that control the thermodynamic and kinetic stability of [2M-2S] cores clearly is limited. This work reports a series of binuclear complexes of nickel derived from a 1,4-terphenyldithiophenol ligand platform that is ideally suited for mechanistic work to overcome this limitation. Redox-induced assembly and disassembly of S-bridged [2M-2S] fragments have been investigated at the molecular level. As part of an extended square scheme, metastable binuclear structures that are significant mechanistically have been identified, characterized, and their reactivity studied quantitatively. Electronic properties that are inherent to [2M-2S] structures and determine thermodynamic and kinetic stability are differentiated from steric effects imposed by co-ligands.

7.
Chemistry ; 22(41): 14640-7, 2016 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-27554625

RESUMEN

This work reports on the redox and acid-base properties of binuclear complexes of nickel from 1,4-terphenyldithiophenol ligands. The results provide insight into the cooperative electronic interaction between a dinickel core and its ligand. Donor/acceptor contributions flexibly adjust to stabilize different redox states at the metals, which is relevant for redox reactions like proton reduction. Proton transfer to the [S2 Ni2 ] core and Ni-H bond formation are kinetically favored over the thermodynamically favored yet unproductive proton transfer to ligand.

8.
J Exp Child Psychol ; 151: 109-19, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-26925719

RESUMEN

Deferred imitation (DI) may be regarded as an early declarative-like memory ability shaping the infant's ability to learn about novelties and regularities of the surrounding world. In the current longitudinal study, infants were assessed at 9 and 16months. DI was assessed using five novel objects. Each infant's communicative development was measured by parental questionnaires. The results indicate stability in DI performance and early communicative development between 9 and 16months. The early achievers at 9months were still advanced at 16months. Results also identified a predictive relationship between the infant's gestural development at 9months and the infant's productive and receptive language at 16months. Moreover, the results show that declarative memory, measured with DI, and gestural communication at 9months independently predict productive language at 16months. These findings suggest a connection between the ability to form non-linguistic and linguistic mental representations. These results indicate that the child's DI ability when predominantly preverbal might be regarded as an early domain-general declarative memory ability underlying early productive language development.


Asunto(s)
Gestos , Conducta Imitativa , Desarrollo del Lenguaje , Lenguaje , Memoria , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Padres , Encuestas y Cuestionarios
9.
Diabetologia ; 58(6): 1188-97, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25870022

RESUMEN

AIMS/HYPOTHESIS: The aim of this study was to prospectively investigate whether psychological stress during childhood may be a risk factor for manifest type 1 diabetes. METHODS: The All Babies In Southeast Sweden (ABIS) study invited all families with babies born between 1 October 1997 and 30 September 1999 in southeast Sweden to participate. Our study subsample includes 10,495 participants in at least one of the data collections at 2-3, 5-6, 8 and 10-13 years of age not yet diagnosed with type 1 diabetes at inclusion; 58 children were subsequently diagnosed. Age at diagnosis was obtained from the national register SweDiabKids in 2012. Family psychological stress was measured via questionnaires given to the parents assessing serious life events, parenting stress, parental worries and the parent's social support. RESULTS: Childhood experience of a serious life event was associated with a higher risk of future diagnosis of type 1 diabetes (HR 3.0 [95% CI 1.6, 5.6], p = 0.001) after adjusting for heredity of type 1 diabetes and age at entry into the study. The result was still valid when controlling for heredity of type 2 diabetes, size for gestational age, the parents' education level and whether the mother worked at least 50% of full time before the child's birth (HR 2.8 [95% CI 1.5, 5.4], p = 0.002), and also when childhood BMI was added to the model (HR 5.0 [95% CI 2.3, 10.7], p < 0.001). CONCLUSIONS/INTERPRETATION: This first prospective study concluded that experience of a serious life event in childhood may be a risk factor for manifest type 1 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 1/etiología , Diabetes Mellitus Tipo 1/psicología , Acontecimientos que Cambian la Vida , Estrés Psicológico , Adolescente , Niño , Preescolar , Muerte , Diabetes Mellitus Tipo 2/genética , Familia , Femenino , Humanos , Masculino , Padres , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Apoyo Social , Encuestas y Cuestionarios , Suecia
10.
Clin Oral Investig ; 19(8): 1791-7, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25595865

RESUMEN

OBJECTIVES: Since development of oral squamous cell cancer (OSCC) is triggered by various noxa, different variants of the antioxidant glutathione S-transferases (GSTs) can counteract toxic compounds (e.g., tobacco smoke). Because different polymorphisms of GST are known to have an increased sensitivity to carcinogenic agents, the aim of this study was to analyze whether GSTM1 or GSTT1 polymorphisms increase the risk for the development of OSCC. MATERIALS AND METHODS: GSTM1 and GSTT1 polymorphism was examined in healthy volunteers (n = 93) and in patients with OSCC (n = 100) by PCR after brush biopsy of oral mucosa. Odds ratio (OR) was calculated to evaluate the risk of oral cancer development. RESULTS: GSTM1 and GSTT1 deletion was found in 57% (53/93) and 18% (17/93), respectively, in healthy patients, while the OSCC group showed 57% (57/100) for GSTM1 deletion and 22% (22/100) with a deletion of GSTT1. Odds ratio for GSTM1 polymorphism was 1.00 and for GSTT1 1.26. Comparing smokers and nonsmokers with GSTM1 deletion polymorphism, OR was 4.35, while smokers without GSTM1 deletion showed an OR of 1.45. Adapting these data to the smoking habits of the general population in Germany, the OR was 9.25 for smokers with a GSTM1 deletion and OR 6.68 for smokers without a GSTM1 deletion. In smokers with GSTT1 deletion polymorphism, OR was 1.6 (adapted to the smoking habits of the general population: OR 6.16) and 3.16 (OR 8.56) in smokers without deletion in GSTT1 gene. CONCLUSIONS: Analysis of GST-M1 polymorphism in smokers could help to identify patients with a higher risk for the development of oral cancer. CLINICAL RELEVANCE: Early detection of OSCC due to a close meshed monitoring program for patients with GST-M1 polymorphism could help to improve the patient outcome. For polymorphism investigations, the oral brush biopsy is a sufficient method to gain DNA material.


Asunto(s)
Glutatión Transferasa/genética , Neoplasias de la Boca/genética , Proteínas de Neoplasias/genética , Neoplasias de Células Escamosas/genética , Polimorfismo Genético , Femenino , Humanos , Masculino , Neoplasias de la Boca/enzimología , Neoplasias de Células Escamosas/enzimología , Factores de Riesgo , Fumar/efectos adversos , Fumar/genética
11.
Nat Mater ; 12(11): 1038-44, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23913173

RESUMEN

Conjugated polymer chains have many degrees of conformational freedom and interact weakly with each other, resulting in complex microstructures in the solid state. Understanding charge transport in such systems, which have amorphous and ordered phases exhibiting varying degrees of order, has proved difficult owing to the contribution of electronic processes at various length scales. The growing technological appeal of these semiconductors makes such fundamental knowledge extremely important for materials and process design. We propose a unified model of how charge carriers travel in conjugated polymer films. We show that in high-molecular-weight semiconducting polymers the limiting charge transport step is trapping caused by lattice disorder, and that short-range intermolecular aggregation is sufficient for efficient long-range charge transport. This generalization explains the seemingly contradicting high performance of recently reported, poorly ordered polymers and suggests molecular design strategies to further improve the performance of future generations of organic electronic materials.

12.
J Craniofac Surg ; 25(3): 766-71, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24820707

RESUMEN

Transport distraction osteogenesis (DO) can be used to autologously reconstitute calvarial defects. The purpose of this study is to histomorphologically interrogate osteogenic formation during cranial transport distraction using a novel device. We also evaluate the effect of fat grafting on the regenerate and soft-tissue stability during distraction. This study was approved by Yale IACUC. Ten male New Zealand white rabbits (3 mo; 3.5 kg) were used (8 treatment, 2 control). A 16 × 16 mm defect was created abutted by a 10 × 16 mm transport disc. The device was fixated anterioposteriorly. Four animals were fat-grafted using 2 mL of subdermal intrascapular fat deposited along the distraction site. Latency (1 d), active distraction (12-14 d) (1.5 mm/d), and consolidation (4 wk) followed. Calcein and xylene orange fluorochromes were injected subcutaneously during and post-distraction to mark sites of bone formation. Following sacrifice, osteogenesis was assessed using microCT, histology, and fluorescence. Treatment animals demonstrated regenerate bone between distracted segments on microCT. MicroCT analysis of non-fat-grafted and fat-grafted animals revealed a mean density of 2271.95 mgHA/ccm and 2254.27 mgHA/ccm (P = 0.967), respectively, and defect bone versus total volume (BV/TV) of 0.0999 and 0.0766 (P = 0.5979), respectively. Controls had minimal reossification. Histologically, mean densities measured 43.63% and 8.19%, respectively. Fluorescence revealed ossification from the callus as well as from dura and periosteum in the cranial defect. Transport distraction is effective to reconstruct critically sized rabbit calvarial defects. Regenerate bone arises predominantly from the callus with contribution from surrounding dura and periosteum. Adipose grafting is well tolerated but does not enhance osseous regeneration.


Asunto(s)
Tejido Adiposo/trasplante , Osteogénesis por Distracción/métodos , Procedimientos de Cirugía Plástica/métodos , Cráneo/cirugía , Animales , Densidad Ósea/fisiología , Enfermedades Óseas/cirugía , Regeneración Ósea/fisiología , Callo Óseo/patología , Duramadre/patología , Fluoresceínas , Colorantes Fluorescentes , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Osteogénesis/fisiología , Osteogénesis por Distracción/instrumentación , Periostio/patología , Conejos , Distribución Aleatoria , Procedimientos de Cirugía Plástica/instrumentación , Microtomografía por Rayos X/métodos
13.
Jurisprudence ; 15(1): 35-47, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38654813

RESUMEN

What exactly do we need to do in order to make a promise, or to exercise some other normative power? On a view relied on by many philosophers writing on promising, consent, and related phenomena, the answer is that we must communicate a suitable kind of intention. On this view, power-conferring principles assert that specific normative consequences, determined in part by the content of the communicated intention, attach to such communicative acts, and these principles need not be socially practised or accepted to be true. The paper offers a defense of this convention-independent view against the forceful challenge developed by Jed Lewinsohn in 'The "Natural Unintelligibility" of Normative Powers'. Lewinsohn appeals to action-theoretic considerations to show that the relevant type of communicative act could not be performed under conditions of rationality and full information, and that therefore promissory power and other normative powers require the existence of social rules conferring such powers. The defense of the view targeted by Lewinsohn turns partly on the exact content of plausible constraints on the intelligibility of actions done with a particular aim, and partly on the question just how the social acceptance of power-conferring rules should be thought to matter.

14.
J Am Chem Soc ; 135(37): 13695-8, 2013 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-23947437

RESUMEN

We describe a new synthetic approach to regioregular monodisperse oligo(3-alkylthiophene)s allowing for simple separation of regioregular material in gram quantities. The number of repeat units follows the Fibonacci numbers up to a length of 21. In a small adaption of this approach, introduction of a protecting group was used to synthesize an oligo(3-hexylthiophene) with 36 repeating units, the longest regioregular 3-hexylthiophene oligomer synthesized to date.

15.
J Am Chem Soc ; 135(37): 13699-709, 2013 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-23957887

RESUMEN

This study is concerned with the thermal and structural characteristics of a series of precisely defined, monodisperse, regioregular oligo(3-hexylthiophene)s (3HT)n of n = 4-36. We find that these model compounds can feature two distinctly different solid-state structures, i.e., the more classical polymorph Form I in which the hexyl side-chains are not interdigitated and Form II in which they are. The thermodynamic equilibrium melting temperatures of these phases differ as much as ~180 °C, with 116 °C for Form II and 298 °C for Form I. Furthermore, polymorph II featured an enthalpy of melting of ~3 times that of Form I and a rate of crystallization that is ~1 order of magnitude lower than that of Form I. A crossover of the thermodynamically preferred Form II into the kinetically favored Form I is observed at a number of repeat units of 12. In the regime 10 ≤ n ≤ 21 the oligo(3-hexylthiophene)s could readily be reversibly converted from one polymorph to another by appropriate processing treatments. The relevance of these findings for the polymeric form (P3HT) is discussed.

16.
Clin Oral Investig ; 16(1): 87-93, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21225298

RESUMEN

Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is one of the most often seen side effects in patients treated with bisphosphonates, presenting clinically as a non-healing wound. One theory of BP-ONJ etiology describes a negative effect on soft tissues, especially on keratinocytes, which play an important role in oral wound healing and oral soft tissue regeneration. A high cell viability of keratinocytes, which can migrate to the affected location, is essential for wound healing. The aim of this in vitro study was to investigate the effect of differently potent bisphosphonates on human oral keratinocytes (HOK).Three nitrogen-containing bisphosphonates (ibandronate, pamidronate, and zoledronate) and one non-nitrogen-containing bisphosphonate (clodronate) were compared concerning their potency on cell viability (calcein assay and MTT assay), migration ability (Boyden chamber migration assay and scratch wound proliferation assay), and apoptosis (TUNEL assay) of HOK.The nitrogen-containing bisphosphonates, particularly highly potent pamidronate and zoledronate preparations, had a strong negative influence on cell viability, migration ability, and apoptosis of HOK. The non-nitrogen-containing clodronate even increased cell viability in higher concentrations.This study demonstrates that bisphosphonates have a strong influence on HOK on different cellular levels like cell viability, migration ability, and apoptosis rate. The results support the theory that BP-ONJ is a multifactorially caused disease.Furthermore, this in vitro study confirms the theory that perioperative interruption of bisphosphonate application during dental surgical procedures might be feasible to promote better tissue regeneration and wound healing.


Asunto(s)
Apoptosis/efectos de los fármacos , Conservadores de la Densidad Ósea/farmacología , Difosfonatos/farmacología , Queratinocitos/efectos de los fármacos , Mucosa Bucal/efectos de los fármacos , Conservadores de la Densidad Ósea/administración & dosificación , Técnicas de Cultivo de Célula , Línea Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ácido Clodrónico/administración & dosificación , Ácido Clodrónico/farmacología , Colorantes , Difosfonatos/administración & dosificación , Fluoresceínas , Colorantes Fluorescentes , Humanos , Ácido Ibandrónico , Imidazoles/administración & dosificación , Imidazoles/farmacología , Etiquetado Corte-Fin in Situ , Mucosa Bucal/citología , Pamidronato , Sales de Tetrazolio , Tiazoles , Ácido Zoledrónico
17.
Clin Oral Investig ; 16(1): 79-86, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20938793

RESUMEN

Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are widely known to be associated with osteonecrosis of the jaw (BONJ). The objective of this study was to evaluate the effect of bisphosphonates on the gene expression of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) in vitro. Nitrogen-containing and non-nitrogen containing bisphosphonates have been compared. Human osteoblasts were stimulated with zoledronate and ibandronate at concentrations of 5 × 10(-5) M, 5 × 10(-6) M, and 5 × 10(-7) M over the experimental period of 14 days. Furthermore, the hOB cell lines were stimulated by clodronate at concentrations of 5 × 10(-3) M, 5 × 10(-5) M, and 5 × 10(-6) M. At each point in time, the gene expression levels of RANKL and OPG were quantified by real-time RT-PCR. The results showed a moderate enhancement of OPG gene expression whereas RANKL gene expression was strongly increased by nitrogen-containing bisphosphonates reaching a maximum after 14 days at high concentrations of 5 × 10(-5) M. Lower concentrations did not enhance the RANKL and OPG expression considerably. The non-nitrogen-containing bisphosphonate clodronate, however, effected OPG and RANKL gene expression much less, even at higher concentrations of 5 × 10(-3) M. The above-mentioned data suggest an enhanced RANKL/OPG gene expression after stimulation by bisphosphonates. Interestingly, clodronate might have little influence on osteoblast/osteoclast interaction with respect to OPG and RANKL gene expression.


Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Difosfonatos/farmacología , Osteoblastos/efectos de los fármacos , Osteoprotegerina/efectos de los fármacos , Ligando RANK/efectos de los fármacos , Conservadores de la Densidad Ósea/administración & dosificación , Técnicas de Cultivo de Célula , Línea Celular , Ácido Clodrónico/administración & dosificación , Ácido Clodrónico/farmacología , Difosfonatos/administración & dosificación , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Ácido Ibandrónico , Imidazoles/administración & dosificación , Imidazoles/farmacología , Osteoprotegerina/genética , Ligando RANK/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Ácido Zoledrónico
18.
Angew Chem Int Ed Engl ; 51(44): 11131-5, 2012 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-23023651

RESUMEN

Sowing the seeds: A simple strategy based on self-seeding allows large single crystals of long regioregular poly(3-hexylthiophene) chains to be grown from solution. When appropriately crystallized, materials differing in their degrees of regioregularity and molecular weights formed monoclinic form II crystals with interdigitated hexyl side groups (see picture).


Asunto(s)
Tiofenos/síntesis química , Cristalización , Modelos Moleculares , Tiofenos/química
20.
J Gene Med ; 13(2): 123-33, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21308899

RESUMEN

BACKGROUND: Poly(ethylene imine) (PEI) is a widely used transfection reagent for mammalian cells, but in vivo application of PEI 25 kDa is restricted by its toxicity. Low molecular weight (LMW) PEI is less toxic, but also less efficient than its high molecular weight equivalent, and prone to aggregation. METHOD: A set of polymers was synthesized by coupling poly(ethylene glycol) (PEG) that contained either C(16/18) -chains (Cx-EO) or butyl-poly(propylene oxide)-co-poly(ethylene glycol) (ButPP). Critical micelle concentration (CMC) was determined for copolymers. Polyplexes were characterized by DNA binding ability, polyplex size and aggregation, hemolysis, and cytotoxicity. Transfection efficiency was tested in vitro and in vivo in mouse lungs. RESULTS: Copolymers formed stable complexes with DNA, and showed enhanced complex stability in isotonic solution for at least 1 h. CMC was determined for Cx-EO-PEI 4.7 and 8.3 at 0.0019 and 0.0037 mM, respectively; membrane activity in a haemolysis assay was demonstrated for ButPP-PEI: both factors possibly enhance endosomal escape effect after PEGylation. IC(50) values of all synthesized polymers were in the range 6-33 ng/ml. Transfection efficiency of unmodified LMW-PEIs was equivalent or better than that of PEI 25 as a result of aggregation in vitro. Cells treated with polyplexes of amphiphilic polymers showed reduced transfection compared to PEI 25. After instillation in mouse lungs, highest transfection efficiency was demonstrated with Cx-EO copolymer of lowest molecular weight PEI. CONCLUSIONS: A new set of polymers with low toxicity and high stability was synthesized, which contains promising candidates for pulmonary gene transfer, as documented by in vivo experiments in mice.


Asunto(s)
Técnicas de Transferencia de Gen , Iminas , Pulmón/metabolismo , Polietilenos , Tensoactivos , Animales , Línea Celular , Membrana Celular/efectos de los fármacos , ADN/genética , Eritrocitos/efectos de los fármacos , Vectores Genéticos/genética , Vectores Genéticos/metabolismo , Humanos , Iminas/síntesis química , Iminas/química , Iminas/farmacología , Iminas/toxicidad , Ratones , Ratones Endogámicos C57BL , Micelas , Plásmidos/genética , Plásmidos/metabolismo , Polietilenos/síntesis química , Polietilenos/química , Polietilenos/farmacología , Polietilenos/toxicidad , Tensoactivos/síntesis química , Tensoactivos/química , Tensoactivos/farmacología , Tensoactivos/toxicidad , Transfección/métodos
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