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There is increasing interest in understanding the tissue biology of human amniotic membrane (hAM) given its applications in medicine. One cellular component is mesenchymal cells, which can be extracted, cultured and differentiated "in vitro" into various cell types. These studies show that there is heterogeneity among mesenchymal cells. The aim of this work is to study the membrane "in situ" to determine whether this cellular heterogeneity exists. The hAMs were obtained from caesarean deliveries at term and analyzed by histological techniques. Types I-III mesenchymal cells and Hofbauer were distinguished by light microscopy. Histochemically, mesenchymal cell types showed successively increasing positivity to: PAS, vimentin, fibronectin, and Concanavalin-A; VGEF, TGF-ß2, PDGF-C, FGF-2. By the semiquantitative point of view, the percentage of Type II cells was 60%, significantly higher than the other types. With transmission electron microscopy, an intermediate cell type between II-III was observed. Strong vesiculation of the rough endoplasmic reticulum (RER) with exocytosis was observed. In addition, an accumulation of a similar material to the extracellular matrix in the RER caused its dilation especially in type III cells. Some of this material acquired a globular structure. These structures were also found free in the extracellular matrix. In conclusion, the mesenchymal cells of the fibroblastic layer of the hAMs studied are heterogeneous, with some undifferentiated and others with a probably senescent fibroblastic phenotype with accumulation in their RER of fibronectin. These results may be of interest to extract mesenchymal cells from hAMs for use in regenerative medicine and to better understand the mechanisms of fetal membrane rupture.
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OBJECTIVE: Establish reference ranges for the Elecsys® soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) immunoassay ratio in twin pregnancies. METHODS: Data analyzed were from 3 prospective studies: Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia (PE) (PROGNOSIS), Study of Early-onset PE in Spain (STEPS), and a multicenter case-control study. Median, 5th, and 95th percentiles for sFlt-1, PlGF, and the sFlt-1/PlGF ratios were determined for normal twin pregnancies for 7 gestational windows and compared with the previous data for singleton pregnancies. RESULTS: The reference range analysis included 269 women with normal twin pregnancies. Before 29 weeks' gestation, median, 5th, and 95th percentiles for sFlt-1/PlGF ratios did not differ between twin and singleton pregnancies. From 29 weeks' gestation to delivery, median, 5th, and 95th percentiles for sFlt-1/PlGF ratios were substantially higher in twin versus singleton pregnancies. sFlt-1 values were higher in women with twin pregnancies across all gestational windows. PlGF values were similar or higher in twin versus singleton pregnancies; PlGF concentrations increased from 10 weeks + 0 days to 28 weeks + 6 days' gestation. CONCLUSIONS: Reference ranges for the sFlt-1/PlGF ratio are similar in women with twin and singleton pregnancies until 29 weeks' gestation but appear higher in twin pregnancies thereafter.
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Preeclampsia , Embarazo Gemelar , Biomarcadores , Estudios de Casos y Controles , Femenino , Edad Gestacional , Humanos , Inmunoensayo , Factor de Crecimiento Placentario , Preeclampsia/diagnóstico , Embarazo , Estudios Prospectivos , Valores de Referencia , Receptor 1 de Factores de Crecimiento Endotelial VascularRESUMEN
OBJECTIVE: To determine the contribution of short femur diaphysis length (FDL) at 19-22 weeks of gestation in the prediction of adverse pregnancy outcomes. METHODS: The study included singleton pregnant women who underwent a routine anomaly scan at 19-22 weeks of gestation at the Virgen de la Arrixaca University Clinical Hospital (Murcia, Spain) between August 2011 and August 2012. Fetal biometry and Doppler ultrasound of uterine arteries were assessed as part of the anomaly scan, and the mean pulsatility index of both uterine arteries was recorded. Maternal obstetric characteristics, such as ethnicity, age, weight, parity, cigarette smoking, and medical history including hypertension and diabetes mellitus were collected from our database system. RESULTS: A total of 6,366 women were included in the study after excluding cases with abnormal karyotype, major fetal abnormalities, or termination of pregnancy. There were 88 cases of preeclampsia (PE) (1.4%). Logistic regression was performed including maternal and fetal characteristics. Short FDL at 19-22 weeks was significantly associated with subsequent development of PE (OR = 0.89, 95% CI: 0.80-0.99, p = 0.025). The best model to predict PE from our sample included gestational age at scan, parity, maternal weight, chronic hypertension, mean pulsatility index in the uterine arteries, and FDL (AUC = 0.78, 95% CI: 0.71-0.84). Regarding small for gestational age (SGA) neonates, there were also significant differences in FDL and FDL <5th centile between the control group and SGA newborns below the 3rd, 5th, and 10th centile. In the groups of preterm births (delivery before 32, 34, and 37 weeks), there were no differences in FDL compared with the control group (term births). DISCUSSION: Our results suggest that FDL at 19-22 weeks of gestation is an independent predictor of PE and SGA newborns.
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Fémur/diagnóstico por imagen , Preeclampsia/diagnóstico por imagen , Segundo Trimestre del Embarazo , Adulto , Biometría/métodos , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Embarazo , Resultado del Embarazo , Ultrasonografía Prenatal , Adulto JovenRESUMEN
OBJECTIVE: Symptoms of genitourinary syndrome of menopause (GSM) are bothersome to middle-aged and older women, and affect their quality of life (QoL), sexuality, and daily activities. The objective of the study was to evaluate the impact of vaginal symptoms and GSM on the well-being, functioning, and QoL of postmenopausal women from Spain. METHODS: This study involved 423 postmenopausal women participating in the GENISSE study (a multicenter, cross-sectional, descriptive, observational study) who presented at least 1 vaginal symptom. All women completed the "day-to-day impact of vaginal aging" (DIVA) questionnaire. Analysis of total scores and subdomains of the questionnaire were performed in women diagnosed with GSM and those without the condition. RESULTS: In these women, the highest mean scores on the DIVA questionnaire were found in the sexual functioning domain long version (mean 1.8; SD 1.0), followed by the sexual functioning domain short version (mean 1.7; SD 1.1), self-perception and body image (mean 1.4; SD 1.1), activities of daily living (mean 0.7; SD 0.8), and emotional well-being (mean 0.7; SD 0.8) scales. A total of 299 women (70.7%) had vaginal symptoms with a diagnosis of GSM, whereas 124 (29.3%) had no GSM diagnosis. Scores on the DIVA questionnaire were significantly higher in women with a diagnosis of GSM than in those without this condition. CONCLUSIONS: Vaginal symptoms impact the well-being, functioning, and QoL of postmenopausal women, especially sexual function, self-perception, and body image. This impact is significantly higher in women with GSM. Identifying and treating patients affected by vaginal symptoms and GSM may be beneficial for improving their QoL.
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Enfermedades Urogenitales Femeninas/fisiopatología , Enfermedades Urogenitales Femeninas/psicología , Posmenopausia/fisiología , Posmenopausia/psicología , Calidad de Vida , Actividades Cotidianas , Adulto , Anciano , Imagen Corporal , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Autoimagen , Conducta Sexual , Disfunciones Sexuales Fisiológicas , Disfunciones Sexuales Psicológicas , España , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Vagina/fisiopatologíaRESUMEN
Neonatal platelets are hypo-reactive to the tyrosine kinase-linked receptor agonist collagen. Here, we have investigated whether the hypo-responsiveness is related to altered levels of glycoprotein VI (GPVI) and integrin α2ß1, or to defects in downstream signalling events by comparison to platelet activation by C-type lectin-like receptor 2 (CLEC-2). GPVI and CLEC-2 activate a Src- and Syk-dependent signalling pathway upstream of phospholipase C (PLC) γ2. Phosphorylation of a conserved YxxL sequence known as a (hemi) immunotyrosine-based-activation-motif (ITAM) in both receptors is critical for Syk activation. Platelets from human pre-term and full-term neonates display mildly reduced expression of GPVI and CLEC-2, as well as integrin αIIbß3, accounted for at the transcriptional level. They are also hypo-responsive to the two ITAM receptors, as shown by measurement of integrin αIIbß3 activation, P-selectin expression and Syk and PLCγ2 phosphorylation. Mouse platelets are also hypo-responsive to GPVI and CLEC-2 from late gestation to 2 weeks of age, as determined by measurement of integrin αIIbß3 activation. In contrast, the response to G protein-coupled receptor agonists was only mildly reduced and in some cases not altered in neonatal platelets of both species. A reduction in response to GPVI and CLEC-2, but not protease-activated receptor 4 (PAR-4) peptide, was also observed in adult mouse platelets following immune thrombocytopenia, whereas receptor expression was not impaired. Our results demonstrate developmental differences in platelet responsiveness to GPVI and CLEC-2, and also following immune platelet depletion leading to reduced Syk activation. The rapid generation of platelets during development or following platelet depletion is achieved at the expense of signalling by ITAM-coupled receptors.
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Plaquetas/fisiología , Lectinas Tipo C/metabolismo , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana Plaquetaria/metabolismo , Nacimiento Prematuro/metabolismo , Púrpura Trombocitopénica Idiopática/metabolismo , Quinasa Syk/metabolismo , Animales , Células Cultivadas , Femenino , Humanos , Recién Nacido , Integrina alfa2beta1/metabolismo , Ratones , Selectina-P/metabolismo , Fosfolipasa C gamma/metabolismo , Activación Plaquetaria , Embarazo , Nacimiento Prematuro/patología , Púrpura Trombocitopénica Idiopática/patología , Receptores de Trombina/metabolismo , Transducción de SeñalRESUMEN
A series of [60]fullerenes covalently functionalized with the polymer poly(ethylene glycol) is presented. These new [60]fullerene-based materials have been incorporated as additives in CH3 NH3 PbI3 (MAPbI3 ), the most common organic-inorganic perovskite used in perovskite solar cells. The extensive photovoltaic study performed by using these materials shows several beneficial effects on the performance of these cells, including a reduction in hysteresis and an increased stability against moisture, whereby the solar cells retain up to 97 % of their initial power conversion efficiency in an ambient atmosphere.
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Neonatal platelets are hyporeactive and show impaired agonist-induced secretion despite no obvious abnormalities in their granules. Here, we examined, for the first time, the ultrastructure of neonatal and adult platelets following agonist activation. Under resting conditions, neonatal and adult platelets appeared ultrastructurally identical. Following agonist stimulation, however, noticeable degranulation occurred in adult platelets, while granules in neonatal platelets remained clearly visible and apparently unable to centralize or fuse. To investigate the underlying mechanisms, we first examined the expression levels of the main SNARE proteins, which mediate the membrane fusion events required for exocytosis. Neonatal platelets showed significantly reduced levels of syntaxin-11 and its regulator, Munc18b. Since granule centralization depends on contraction of the microtubule ring, we also examined the expression of its main component, ß1-tubulin. Noteworthy, we found decreased TUBB1 mRNA and protein levels in neonatal platelets, while TUBB2A and TUBB isoforms were overexpressed, partially compensating for that deficiency. Finally, supporting the functional consequences of defective exocytosis, adhesion kinetic assays, performed in plasma-free medium, demonstrated delayed adhesion and spreading of neonatal platelets. This is the first report showing marked reductions of syntaxin-11-Munc18b complex and ß1-tubulin in neonatal platelets, indicating that these proteins, required for platelet degranulation, are developmentally regulated.
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Plaquetas/metabolismo , Degranulación de la Célula , Forma de la Célula , Exocitosis , Proteínas Munc18/metabolismo , Proteínas Qa-SNARE/metabolismo , Tubulina (Proteína)/metabolismo , Adulto , Factores de Edad , Plaquetas/efectos de los fármacos , Plaquetas/ultraestructura , Degranulación de la Célula/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Exocitosis/efectos de los fármacos , Sangre Fetal/citología , Humanos , Recién Nacido , Cinética , Complejos Multiproteicos , Proteínas Munc18/genética , Fragmentos de Péptidos/farmacología , Adhesividad Plaquetaria , Proteínas Qa-SNARE/genética , Transducción de Señal , Tubulina (Proteína)/genéticaRESUMEN
OBJECTIVE: To evaluate the association between fetal and maternal catechol-O-methyltransferase (COMT) Val158Met and methyl tetrahydrofolate reductase (MTHFR) C677T functional polymorphisms and preeclampsia, examining its influence on placental COMT and in maternal 2-methoxyestradiol (2-ME) plasma levels. DESIGN: Prospective case-control study. SETTING: University hospital. PATIENT(S): A total of 53 preeclamptic and 72 normal pregnant women. INTERVENTION(S): Maternal and cord blood samples and placental tissue samples were obtained. MAIN OUTCOME MEASURE(S): Maternal and fetal COMT and MTHFR polymorphisms were genotyped. Maternal plasma 2-ME and homocysteine levels, and expression and activity of placental COMT were measured. RESULT(S): The odds ratio for the risk of preeclampsia for fetal COMT Met/Met was 3.22, and it increased to 8.65 when associated with fetal MTHFR TT. Placental COMT activity and expression were influenced by genotype, but COMT activity in preeclamptic placentas did not differ from control pregnancies. There was no association between any genotypes and maternal 2-ME. Homocysteine levels were higher in women with preeclampsia than in normal pregnancies, and were inversely correlated with 2-ME plasma levels, indicating that its altered metabolism may lower COMT activity in vivo. CONCLUSION(S): Fetal Met-Met COMT genotype reduces COMT placental expression and activity in vitro and increases preeclampsia, risk but it does not explain the difference in maternal 2-ME levels between preeclamptic and normal pregnancies. However, the preeclamptic patients had elevated homocysteine levels that correlated inversely with 2-ME, indicating that an altered methionine-homocysteine metabolism may contribute to reduce COMT activity in vivo and explain the decreased levels of 2-ME in preeclamptic women.
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Presión Sanguínea/genética , Catecol O-Metiltransferasa/genética , Polimorfismo de Nucleótido Simple , Preeclampsia/genética , 2-Metoxiestradiol , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Catecol O-Metiltransferasa/sangre , Distribución de Chi-Cuadrado , Estradiol/análogos & derivados , Estradiol/sangre , Femenino , Sangre Fetal/enzimología , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Homocisteína/sangre , Hospitales Universitarios , Humanos , Modelos Logísticos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Análisis Multivariante , Oportunidad Relativa , Fenotipo , Placenta/enzimología , Preeclampsia/sangre , Preeclampsia/diagnóstico , Preeclampsia/enzimología , Preeclampsia/fisiopatología , Embarazo , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , EspañaRESUMEN
We investigated whether clinical severity indices and biomarkers for preeclampsia (PE) are associated with low plasmatic 2-methoxyestradiol (2ME) in the third trimester of gestation. Blood was collected from 53 women with PE and 73 control pregnant women before parturition. The concentration of 2ME was significantly higher in controls than in patients with PE (2906.43 ± 200.69 pg/mL vs 1818.41 ± 189.25 pg/mL). The risk of PE decreased as 2ME levels increased. The 2ME values were negatively correlated with systolic peak arterial pressure and proteinuria in PE. Additionally, those women with PE with lower 2ME had a more serious clinical situation and needed a more aggressive therapy. Finally, 2ME levels (in patients with PE and total population) were significantly correlated with concentrations of soluble fms-like tyrosine kinase 1 and placental growth factor . Summarizing, patients with PE had lower 2ME levels that were correlated with different clinical indices and biomarkers of severity, indicating that 2ME could be taken into account for the clinical management of this syndrome.
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Estradiol/análogos & derivados , Preeclampsia/sangre , 2-Metoxiestradiol , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Regulación hacia Abajo , Estradiol/sangre , Femenino , Humanos , Factor de Crecimiento Placentario , Preeclampsia/diagnóstico , Preeclampsia/terapia , Valor Predictivo de las Pruebas , Embarazo , Proteínas Gestacionales/sangre , Tercer Trimestre del Embarazo/sangre , Pronóstico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangreRESUMEN
OBJECTIVE: The objective of this study was to determine the contribution of uterine (UtA) and umbilical arteries (UA) Doppler examination at 28 weeks to predict adverse pregnancy outcomes in women who had increased resistance in UtA in the early second trimester. METHODS: Women with UtA mean pulsatility index (PI) above the 95th centile at 19-22 weeks of gestation were offered a growth scan including Doppler examination of UtA and UA at 28 weeks. Adverse pregnancy outcomes included small for gestational age (SGA), defined as birth weight below the tenth centile, preeclampsia (PE) and early-onset PE (PE before 34 weeks). RESULTS: We studied 266 pregnant women with elevated PI in the UtAs in the second trimester and ultrasound reassessment at 28 weeks. UtA PI >95th centile at 28 weeks was associated with subsequent PE [odds ratio (OR): 10.0, 95% CI: 2.3-43.5], early-onset PE (OR: 57.7, 95% CI: 3.8-87.6) and SGA less than the tenth centile (OR: 5.5, 2.2-13.9). UA PI >95th centile at 28 weeks was not significantly associated with any adverse outcome. CONCLUSIONS: In women with abnormal UtA Doppler in the early second trimester scan, persistence of elevated UtA PI, but not abnormal UA PI, is associated with adverse pregnancy outcomes including PE, early-onset PE and SGA. © 2014 John Wiley & Sons, Ltd.
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Preeclampsia/epidemiología , Resultado del Embarazo/epidemiología , Arterias Umbilicales/diagnóstico por imagen , Arteria Uterina/diagnóstico por imagen , Resistencia Vascular , Adulto , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Oportunidad Relativa , Embarazo , Segundo Trimestre del Embarazo , Flujo Pulsátil , Estudios Retrospectivos , Ultrasonografía Doppler , Ultrasonografía Prenatal , Arteria Uterina/fisiopatologíaRESUMEN
OBJECTIVE: The aim of this study was to determine the clinical utility of Doppler assessment of the umbilical artery in the second trimester scan for predicting adverse pregnancy outcomes. METHODS: Singleton pregnancies that had undergone routine anomaly scan at 19 to 22 weeks of gestation with umbilical and uterine artery Doppler measurements. Receiver operating characteristic curves were constructed to evaluate the ability of umbilical artery pulsatility index (PI) to predict small for gestational age and preeclampsia. RESULTS: The final study population comprised 4565 singleton pregnancies. Multiple regression analysis showed significant independent contribution of umbilical artery PI in predicting SGA <10th and SGA <5th centiles (adjusted odds ratios of 2.51 and 3.51, respectively). By using a cutoff of umbilical artery PI >90th centile, the likelihood ratio of SGA <5th centile is 2.3 (95% CI: 1.7-3.0). CONCLUSIONS: Umbilical artery PI at 19 to 22 weeks of gestation is significantly associated with SGA below the tenth and fifth centiles. A multivariate model combining umbilical and uterine artery Doppler measurements with additional maternal and sonographic characteristics may help predict small for gestational age, particularly those below the fifth centile.
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Complicaciones del Embarazo/diagnóstico por imagen , Segundo Trimestre del Embarazo , Ultrasonografía Doppler , Ultrasonografía Prenatal/métodos , Arterias Umbilicales/diagnóstico por imagen , Adulto , Femenino , Edad Gestacional , Humanos , Recién Nacido , Preeclampsia/diagnóstico por imagen , Embarazo , Resultado del Embarazo , Pronóstico , Arteria Uterina/diagnóstico por imagenRESUMEN
Buckyballs represent a new and fascinating molecular allotropic form of carbon that has received a lot of attention by the chemical community during the last two decades. The unabating interest on this singular family of highly strained carbon spheres has allowed the establishing of the fundamental chemical reactivity of these carbon cages and, therefore, a huge variety of fullerene derivatives involving [60] and [70]fullerenes, higher fullerenes, and endohedral fullerenes have been prepared. Much less is known, however, of the chemistry of the uncommon non-IPR fullerenes which currently represent a scientific curiosity and which could pave the way to a range of new fullerenes. In this review on buckyballs we have mainly focused on the most recent and novel covalent chemistry of fullerenes involving metal catalysis and asymmetric synthesis, as well as on some of the most significant advances in supramolecular chemistry, namely H-bonded fullerene assemblies and the search for efficient concave receptors for the convex surface of fullerenes. Furthermore, we have also described the recent advances in the macromolecular chemistry of fullerenes, that is, those polymer molecules endowed with fullerenes which have been classified according to their chemical structures. This review is completed with the study of endohedral fullerenes, a new family of fullerenes in which the carbon cage of the fullerene contains a metal, molecule, or metal complex in the inner cavity. The presence of these species affords new fullerenes with completely different properties and chemical reactivity, thus opening a new avenue in which a more precise control of the photophysical and redox properties of fullerenes is possible. The use of fullerenes for organic electronics, namely in photovoltaic applications and molecular wires, complements the study and highlights the interest in these carbon allotropes for realistic practical applications. We have pointed out the so-called non-IPR fullerenes - those that do not follow the isolated pentagon rule - as the most intriguing class of fullerenes which, up to now, have only shown the tip of the huge iceberg behind the examples reported in the literature. The number of possible non-IPR carbon cages is almost infinite and the near future will show us whether they will become a reality.
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OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of a new low-concentration estriol formulation (0.005% estriol vaginal gel), providing an ultra low dose of estriol per application (50 µg), for the local treatment of postmenopausal vaginal atrophy. METHODS: Postmenopausal women with symptoms and signs of vaginal atrophy were enrolled in a prospective, double-blind, placebo-controlled study. Women received either 1 g of vaginal gel containing 50 µg of estriol or placebo gel, daily for 3 weeks and then twice weekly up to 12 weeks. A cytological vaginal study, evaluation of vaginal pH, and assessment of symptoms and signs of vaginal atrophy were performed, and changes between baseline and weeks 3 and 12 were assessed. Adverse events were recorded. RESULTS: A total of 167 women were included (114 received estriol and 53 received placebo). After 12 weeks of therapy, a superiority of estriol compared with placebo gel was shown in the change in maturation value and vaginal pH (P < 0.001 and P < 0.001, respectively). The superiority of estriol was well demonstrated in improvement of vaginal dryness (P = 0.001) and the Global Symptom Score (P = 0.018). Estriol gel proved also superior in the improvement of several of the most outstanding vaginal signs of vaginal atrophy evaluated. After 3 weeks, estriol gel also showed a superiority over the placebo gel in most symptoms and signs evaluated. Treatment-related adverse events were similar among groups. CONCLUSIONS: 0.005% Estriol vaginal gel, a new formulation providing an ultra low dose of estriol per application, was shown to be safe and effective in the treatment of postmenopausal vaginal atrophy.
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Estriol/administración & dosificación , Estrógenos/administración & dosificación , Posmenopausia , Vagina/patología , Enfermedades Vaginales/tratamiento farmacológico , Atrofia/tratamiento farmacológico , Método Doble Ciego , Estriol/efectos adversos , Estrógenos/efectos adversos , Femenino , Humanos , Concentración de Iones de Hidrógeno/efectos de los fármacos , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , España , Resultado del Tratamiento , Cremas, Espumas y Geles Vaginales/administración & dosificación , Cremas, Espumas y Geles Vaginales/efectos adversosRESUMEN
OBJECTIVE: Topical estrogen therapy is recommended for the treatment of vaginal atrophy. This study was designed to compare the uterotrophic effects of a new estrogen vaginal formulation (0.005% estriol vaginal gel) and other existing topical treatments (Ovestinon(®) and Colpotrofin(®)). METHODS: Each one of the studied formulations was administered intravaginally to groups of ovariectomized rats with cytologically confirmed vaginal atrophy. The doses were adjusted by animal weight according to human dosage. After daily treatment for 14days, the animals were sacrificed and their vaginas and uteri removed. All uteri were weighted. Uteri and vaginas were fixed for histological evaluation. RESULTS: All three active formulations proved to be very effective in the cytological reversal of vaginal atrophy. However, they differ in their effects in the uteri. Ovestinon(®) and Colpotrofin(®) produced a significant increase in uterine weight, myometrial and endometrial thickness as well as histological modifications in the endometrium suggestive of estrogenic activity. Conversely, animals treated with 0.005% estriol vaginal gel, did not show significant weight increase or any other macroscopical or microcospical modifications of the uteri, an effect comparable to placebo. CONCLUSIONS: There are significant differences in the uterotrophic effect of three different topical estrogen formulations as tested in a rat model of vaginal postmenopausal atrophy. While the three formulations were equally effective in reversing vaginal atrophy, only the newly developed ultra-low dose 0.005% estriol vaginal gel has proved to lack any significant estrogenic effect on the uterus.
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Estradiol/análogos & derivados , Estriol , Estrógenos , Enfermedades Uterinas/inducido químicamente , Útero/efectos de los fármacos , Vagina/efectos de los fármacos , Enfermedades Vaginales/tratamiento farmacológico , Administración Intravaginal , Animales , Atrofia/tratamiento farmacológico , Atrofia/etiología , Endometrio/efectos de los fármacos , Endometrio/patología , Estradiol/efectos adversos , Estradiol/uso terapéutico , Estriol/efectos adversos , Estriol/uso terapéutico , Estrógenos/efectos adversos , Estrógenos/uso terapéutico , Femenino , Miometrio/efectos de los fármacos , Miometrio/patología , Tamaño de los Órganos/efectos de los fármacos , Ovariectomía , Ratas , Ratas Wistar , Enfermedades Uterinas/patología , Útero/patología , Vagina/patología , Enfermedades Vaginales/etiología , Enfermedades Vaginales/patologíaRESUMEN
A new family of fullerene-based compounds, namely, soluble [60]- and [70]fullerene homodimers and the [60]/[70]heterodimer linked through 2-pyrazolino-pyrrolidino bridges, has been synthesised by simple procedures and in high yield. Electrochemical studies confirm their suitability to act as electron acceptors in combination with poly(3-hexylthiophene-2,5-diyl) (P3HT). Their optical properties in solution and in the solid state were studied. A significantly stronger absorption in [70]fullerene-containing dimers relative to [60]homodimer in solution in the visible range was observed. Furthermore, in all donor-acceptor blends studied an efficient charge transfer was observed by means of photoluminescence (PL), photoinduced absorption and light-induced electron spin resonance spectroscopy. The [70]homodimer was found to be a distinctive species, being the strongest PL quencher and most efficient acceptor with the longest lifetime of the charge-separated (polaron) states. As a consequence, bulk-heterojunction solar cells based on this novel [70]homodimer blended with P3HT demonstrated the highest quantum and power conversion efficiencies of 37 and 1 %, respectively, compared to those of [60]fullerene dimers.
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Pyrazolino[60]fullerene covalently-linked to ferrocene and N,N-dimethylaniline groups has been prepared and studied using time-resolved spectroscopic methods. The fluorescence quenching of the C(60) moiety indicates that charge-separation takes place via the singlet excited state of the C(60) moiety in both polar and non-polar solvents. The charge-separated state, in which an electron is localized on the C(60) sphere and a hole is located on the whole donor moieties of ferrocene, pyrazole, and N,N-dimethylaniline groups, has been confirmed by nanosecond transient spectra in the visible and near-IR spectral region. The lifetimes of the radical ion-pairs are as long as 30 - 50 ns in both polar and non-polar solvents.
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A soluble, functionalized Py-SWNT has been synthesized and characterized by solution (1)H and (13)C NMR, FT-Raman, and electron microscopy. Experimental data indicate that Py-SWNT has short tubes with pentyl esters at the tips and pyridyl isoxazolino units along the walls. The synthesis of Py-SWNT is based on a 1,3-dipolar cycloaddition of a nitrile oxide on the SWNT walls, similar to 1,3-dipolar cycloadditions that are common for fullerene functionalization. The resulting Py-SWNT forms a complex with a zinc porphyrin (ZnPor) in a way similar to that reported for pyridyl-functionalized [60]-fullerenes. Formation of this metal-ligand complex was firmly established by a detailed electrochemical study. However, in contrast to the behavior observed for the ZnPor/Py-C(60) complex, photochemical excitation of the complex between ZnPor/Py-SWNT does not lead to electron transfer with the generation of charge-separated states. Fluorescence and laser flash studies indicate that the main process is energy transfer from the singlet ZnPor excited state to the Py-SWNT with observation of emission from Py-SWNT. Triplet ZnPor excited-state quenching by Py-SWNT is only observed in polar solvents such as DMF, but not in benzonitrile.
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The first Diels-Alder cycloaddition of o-quinodimethane to SWNT has been performed under microwave irradiation.
RESUMEN
A series of isoindazole-C(60) dyads 4a-c based on pyrazolino[60]fullerene have been prepared by 1,3-dipolar cycloadditions of the nitrile imines, generated in situ from hydrazones 3a-c, to C(60). Molecular orbital calculations for 4b revealed that the electron distribution of the HOMO is located on the isoindazole moiety, while the electron distribution of the LUMO is located on the C(60) moiety. Electrochemical properties of the new dyads 4a-c show a similar electron affinity with respect to C(60). Charge-transfer interactions in the ground state between the isoindazole ring and the fullerene cage are predicted by the molecular orbital calculations and confirmed by electrochemical studies in 4a,b. Steady-state fluorescence emission spectra of dyads 4a-c show that fluorescence intensities in polar benzonitrile solvent decrease with increasing electron-donating ability of the substituent attached on the isoindazole group. This was confirmed by the shortening of fluorescence lifetimes, from which intramolecular charge-separation rates and efficiencies via the excited singlet states of the fullerene moiety were evaluated. The yields of the triplet states in polar solvent decrease with the electron-donating ability, supporting the competitive formation of the charge-separated state with the intersystem crossing from the excited states. Thus, isoindazole[60]fullerene 4b can be considered a molecular switch with an AND logic gate.