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1.
Phys Rev Lett ; 129(17): 175901, 2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-36332258

RESUMEN

We study the temperature-dependent diffusion of many types of metal and semimetal ions in soda-lime glass using thermal relaxation ion spectroscopy, a technique that provides an electrical readout of thermally activated diffusion of charge carriers driven by built-in concentration gradients and electric fields. We measure the temperature of the onset of the motion, relevant to the long term storage of radioactive elements. We demonstrate the unique behavior of silver in soda-lime glass, enabling a thermal battery with rapid discharge of stored energy above a threshold temperature. We show that the Meyer-Neldel rule applies when comparisons of temperature-dependent diffusion rates are made between related measurements on one sample or between the same measurements on related samples. The results support a thermodynamic interpretation of the Meyer-Neldel rule as an enthalpy-entropy correlation where the Meyer-Neldel temperature (T_{MN}) is the temperature that enables liquidlike, barrier-free motion of the ions, with an upper limit set by the melting point of the host medium. This interpretation explains the observed reduction in T_{MN} by built-in electric fields in depletion layers and why the upper limit for T_{MN} for all ions is set by the glass transition temperature.

2.
J Am Chem Soc ; 142(1): 502-511, 2020 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-31814397

RESUMEN

Substituted triphenylamine (TPA) radical cations show great potential as oxidants and as spin-containing units in polymer magnets. Their properties can be further tuned by supramolecular assembly. Here, we examine how the properties of photogenerated radical cations, intrinsic to TPA macrocycles, are altered upon their self-assembly into one-dimensional columns. These macrocycles consist of two TPAs and two methylene ureas, which drive the assembly into porous organic materials. Advantageously, upon activation the crystals can undergo guest exchange in a single-crystal-to-single-crystal transformation generating a series of isoskeletal host-guest complexes whose properties can be directly compared. Photoinduced electron transfer, initiated using 365 nm light-emitting diodes, affords radicals at room temperature as observed by electron paramagnetic resonance (EPR) spectroscopy. The line shape of the EPR spectra and the quantity of radicals can be modulated by both polarity and heavy atom inclusion of the encapsulated guest. These photogenerated radicals are persistent, with half-lives between 1 and 7 d and display no degradation upon radical decay. Re-irradiation of the samples can restore the radical concentration back to a similar maximum concentration, a feature that is reproducible over several cycles. EPR simulations of a representative spectrum indicate two species, one containing two N hyperfine interactions and an additional broad signal with no resolvable hyperfine interaction. Intriguingly, TPA analogues without bromine substitution also exhibit similar quantities of photogenerated radicals, suggesting that supramolecular strategies can enable more flexibility in stable TPA radical structures. These studies will help guide the development of new photoactive materials.

3.
J Am Chem Soc ; 140(40): 13064-13070, 2018 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-30212205

RESUMEN

Supramolecular assembly of urea-tethered benzophenone molecules results in the formation of remarkably persistent triplet radical pairs upon UV irradiation at room temperature, whereas no radicals were observed in solution. The factors that lead to emergent organic radicals are correlated with the microenvironment around the benzophenone carbonyl, types of proximal hydrogens, and the rigid supramolecular network. The absorption spectra of the linear analogues were rationalized using time-dependent density functional theory calculations on the crystal structure and in dimethyl sulfoxide, employing an implicit solvation model to describe structural and electronic solvent effects. Inspection of the natural transition orbitals for the more important excitation bands of the absorption spectra indicates that crystallization of the benzophenone-containing molecules should present a stark contrast in photophysical properties versus that in solution, which was indeed reflected by their quantum efficiencies upon solid-state assembly. Persistent organic radicals have prospective applications ranging from organic light-emitting diode technology to NMR polarizing agents.

4.
Chemistry ; 23(34): 8315-8319, 2017 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-28423212

RESUMEN

UV-irradiation of a self-assembled benzophenone bis-urea macrocycle generates µm amounts of radicals that persist for weeks under ambient conditions. High-field EPR and variable-temperature X-band EPR studies suggest a resonance stabilized radical pair through H-abstraction. These endogenous radicals were applied as a polarizing agent for magic angle spinning (MAS) dynamic nuclear polarization (DNP) NMR enhancement. The field-stepped DNP enhancement profile exhibits a sharp peak with a maximum enhancement of ϵon/off =4 superimposed on a nearly constant DNP enhancement of ϵon/off =2 over a broad field range. This maximum coincides with the high field EPR absorption spectrum, consistent with an Overhauser effect mechanism. DNP enhancement was observed for both the host and guests, suggesting that even low levels of endogenous radicals can facilitate the study of host-guest relationships in the solid-state.

5.
Alcohol Alcohol ; 51(4): 402-9, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26672793

RESUMEN

AIM: To assess the effectiveness of a 12 week specialized, integrated intervention for alcohol dependence with comorbid anxiety and/or mood disorder using a randomized design in an outpatient hospital setting. METHODS: Out of 86 patients meeting the inclusion criteria for alcohol dependence with suspicion of comorbid anxiety and/or depressive disorder, 57 completed a 3-week stabilization period (abstinence or significantly reduced consumption). Of these patients, 37 (65%) met a formal diagnostic assessment of an anxiety and/or depressive disorder and were randomized to either (a) integrated intervention (cognitive behavioural therapy) for alcohol, anxiety and/or depression, or (b) usual counselling care for alcohol problems. RESULTS: Intention-to-treat analyses revealed a beneficial treatment effect of integrated treatment relative to usual counselling care for the number of days to relapse (χ(2) = 6.42, P < 0.05) and lapse (χ(2) = 10.73, P < 0.01). In addition, there was a significant interaction effect of treatment and time for percentage days of abstinence (P < 0.05). For heavy drinking days, the treatment effect was mediated by changes in DASS anxiety (P < 0.05). There were no significant treatment interaction effects for DASS depression or anxiety symptoms. CONCLUSIONS: These results provide support for integrated care in improving drinking outcomes for patients with alcohol dependence and comorbid depression/anxiety disorder. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01941693.


Asunto(s)
Alcoholismo/terapia , Ansiedad/terapia , Depresión/terapia , Adulto , Alcoholismo/complicaciones , Alcoholismo/psicología , Ansiedad/complicaciones , Terapia Cognitivo-Conductual , Consejo , Depresión/complicaciones , Femenino , Hospitales Públicos , Humanos , Masculino , Resultado del Tratamiento
6.
Alcohol Alcohol ; 49(6): 654-60, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25246489

RESUMEN

AIM: To conduct a double-blind, placebo-controlled randomized clinical trial of baclofen in the treatment of alcohol dependence. METHODS: Out of 69 participants consecutively screened, 42 alcohol-dependent patients were randomized to receive placebo, baclofen 30 mg/day or baclofen 60 mg/day for 12 weeks. All subjects were offered BRENDA, a structured psychosocial therapy for alcohol dependence that seeks to improve motivation for change, enhance strategies to prevent relapse and encourage compliance with treatment. RESULTS: Intention-to-treat analyses revealed that alcohol consumption (heavy drinking days, drinks per drinking day) significantly reduced across all three groups during the treatment period. There were no statistically significant advantages to treatment on time to first heavy drinking day (relapse) (P = 0.08), nor time to first drink (lapse) (P = 0.18). A post hoc analysis stratifying according to whether there had been a comorbid anxiety disorder, revealed a beneficial effect of baclofen 30 mg/day versus placebo on time to lapse and relapse (P < 0.05). There was also a beneficial effect for baclofen 60 mg/day relative to placebo on time to relapse in this comorbid group (P < 0.05). Both doses of baclofen were well tolerated. There were no serious adverse events. CONCLUSIONS: In spite of the small sample for a 3-arm clinical trial, this study suggests a specific role of baclofen in alcohol-dependent individuals with comorbid anxiety. Replication in larger, fully-powered studies is required.


Asunto(s)
Alcoholismo/tratamiento farmacológico , Ansiedad/complicaciones , Baclofeno/uso terapéutico , Agonistas de Receptores GABA-B/uso terapéutico , Adulto , Abstinencia de Alcohol/estadística & datos numéricos , Alcoholismo/complicaciones , Alcoholismo/psicología , Ansiedad/psicología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Resultado del Tratamiento
7.
Case Rep Womens Health ; 42: e00605, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38681744

RESUMEN

Massive perivillous fibrin deposition (MPVFD) is a potentially devastating complication of pregnancy that occurs in 0.03-0.5% of deliveries and is associated with severe fetal growth restriction, stillbirth, and neurologic injury due to uteroplacental insufficiency. The management of patients with recurrent pregnancy loss secondary to MPVFD has not been widely studied. We describe the case of a healthy 19-year-old with a history of two prior intrauterine fetal demises at 35w6d and 36w6d secondary to MPVFD of the placenta who subsequently delivered a healthy infant at 33w6d after she had been treated in the prenatal period with aspirin and prophylactic enoxaparin. Antenatal treatment with daily aspirin and prophylactic enoxaparin as well as close antenatal follow-up may be an option for patients with recurrent pregnancy loss due to MPVFD.

8.
Am J Obstet Gynecol MFM ; 5(7): 100956, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37023986

RESUMEN

BACKGROUND: Preeclampsia is an obstetrical disorder, which complicates 3% to 6% of pregnancies and contributes to 21.6% of readmissions in the postpartum period. The optimal strategy for inpatient monitoring of blood pressures to minimize readmissions for postpartum patients with hypertensive disorders is not known. We hypothesized that extended monitoring of postpartum patients with hypertensive disorders of pregnancy for at least 36 hours after the last blood pressure that was ≥150/100 mm Hg would result in decreased readmission rates for preeclampsia with severe features compared with those who were not observed by these blood pressure goals. OBJECTIVE: This study aimed to evaluate whether extended inpatient monitoring of postpartum patients with hypertensive disorders of pregnancy for at least 36 hours after their last blood pressure that was ≥150/100 mm Hg would improve readmission rates for preeclampsia with severe features within 6 weeks of delivery. STUDY DESIGN: This was a retrospective cohort study in patients with a singleton pregnancy and a diagnosis of a hypertensive disorder of pregnancy at their delivery admission or at any point during pregnancy who delivered 1 year before and 1 year after the implementation of extended inpatient monitoring of postpartum hypertension. The primary outcome was readmission for preeclampsia with severe features within 6 weeks of delivery. The secondary outcomes were length of stay during first admission, number of readmissions for any indication, intensive care unit admission, postpartum day at readmission, median systolic blood pressure in the 24-hour period before discharge, median diastolic blood pressure in the 24-hour period before discharge, intravenous antihypertensive medication required during first admission, and intravenous antihypertensive medication required during second admission. Univariable analysis was performed for the association between baseline maternal characteristics and the primary outcome. Multivariable analysis was performed, adjusting for baseline maternal characteristic differences between exposure groups. RESULTS: A total of 567 patients met the inclusion criteria of which 248 patients delivered before and 319 delivered after the implementation of extended monitoring. For baseline characteristics, the extended monitoring group had a significantly higher proportion of patients who were non-Hispanic Black and Hispanic, more diagnoses of hypertensive disorders and/or diabetes mellitus at the time of admission for delivery, a difference in the distribution of hypertensive diagnoses at the time of discharge from the first admission, and fewer discharged patients from their first admission on labetalol than the preintervention group. In a univariable analysis of the primary outcome, there was a significantly increased risk of readmission for preeclampsia with severe features in the extended monitoring group (62.5% vs 96.2% of total readmissions; P=.004). In multivariable analysis, patients in the extended monitoring group were more likely to be readmitted for preeclampsia with severe features than patients in the preintervention group (adjusted odds ratio, 3.45; 95% confidence interval, 1.03-11.5; P=.044). CONCLUSION: Extended monitoring with a strict blood pressure goal of <150/<100 mm Hg did not decrease readmissions for preeclampsia with severe features in patients with a previous diagnosis of a hypertensive disorder of pregnancy.


Asunto(s)
Hipertensión Inducida en el Embarazo , Preeclampsia , Embarazo , Femenino , Humanos , Preeclampsia/diagnóstico , Preeclampsia/epidemiología , Preeclampsia/prevención & control , Hipertensión Inducida en el Embarazo/diagnóstico , Hipertensión Inducida en el Embarazo/epidemiología , Hipertensión Inducida en el Embarazo/prevención & control , Readmisión del Paciente , Antihipertensivos/uso terapéutico , Estudios Retrospectivos , Pacientes Internos , Periodo Posparto
9.
J Surg Educ ; 78(4): 1103-1110, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33199253

RESUMEN

OBJECTIVE: The purpose of this study was to examine stakeholder perspectives on recommended standards for the obstetrics and gynecology (OBGYN) residency application and interview processes proposed for the 2019 to 2020 application cycle. The authors aimed to assess the acceptance and perception of key stakeholders on the feasibility of implementing the standards as well as the effect of these changes on applicant anxiety. DESIGN AND SETTING: The authors electronically distributed an anonymous survey in February 2020 to OBGYN residency applicants, clerkship directors, student affairs deans, program directors, and program managers. Participants received a 15-item survey, with questions assessing the importance and adoption of the guidelines, as well as their effect on perceived applicants' anxiety. Responses were measured on a 5-item Likert scale. Multiple regression analysis was used to explore which residency factors were associated with compliance with the standards. IRB exemption was granted by the University of Michigan. PARTICIPANTS: A total of 1358 participants completed the survey for an overall response rate of 39.26%. Response rates were 36.04% for applicants (904/2508), 46.67% for CDs (105/225), 34.84% for members of GSAs (34/155), 59.43% for program directors (167/281), and 51.03% for program managers (148/290). RESULTS: The overall response rate was 39.26% (1358/3459) with 36.04% of applicants (904/2508), 46.67% of clerkship directors (105/225), 34.84% of student affairs deans (34/155), 59.43% of program directors (167/281), and 51.03% of program managers (148/290). The recommendations were perceived as important by all stakeholders. More than 90% of program directors reported compliance with some or all of the recommendations and more than 90% of all applicants, clerkship directors and student affairs deans reported that the standards reduced applicant anxiety. All stakeholders rated each guideline to be important to extremely important. CONCLUSIONS: This study demonstrates the feasibility and acceptance of universal standards for the residency application process in the field of OBGYN. The vast majority of stakeholders surveyed supported the initiative and participated in the guidelines. Applicant respondents perceived the guidelines to be important and to decrease anxiety surrounding the application and interview timelines. These findings are important for other specialties when considering similar interventions.


Asunto(s)
Ginecología , Internado y Residencia , Obstetricia , Ginecología/educación , Humanos , Obstetricia/educación , Selección de Personal , Encuestas y Cuestionarios
10.
Psychol Med ; 40(7): 1113-23, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19891809

RESUMEN

BACKGROUND: Large community-based epidemiological surveys have consistently identified high co-morbidity between major depressive episode (MDE) and generalized anxiety disorder (GAD). Some have suggested that this co-morbidity may be artificial and the product of the current diagnostic system. Because of the added direct and indirect costs associated with co-morbidity, it is important to investigate whether methods of diagnostic classification are artificially increasing the level of observed co-morbidity. METHOD: The item response theory (IRT) log-likelihood ratio procedure was used to test for differential item functioning (DIF) of MDE symptoms between respondents with and without a diagnosis of GAD in the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC). RESULTS: The presence of GAD significantly increased the chances of reporting any symptom of MDE, with odds ratios ranging from 2.54 to 5.36. However, there was no indication of significant DIF of MDE symptoms in respondents with and without GAD. CONCLUSIONS: The lack of any significant DIF indicates that cases with GAD do not present with a distinct MDE symptom profile, one that is consistent with the endorsement of symptoms that are conceptually similar in nature between the two disorders, compared to cases without GAD. This does not support the hypothesis that co-morbidity between MDE and GAD is artificially inflated because of the similar symptom criteria required by the current diagnostic system. Instead, MDE and GAD may be thought of as two distinct diagnostic entities that frequently co-occur because of a shared underlying trait.


Asunto(s)
Trastornos de Ansiedad/epidemiología , Trastorno Depresivo Mayor/epidemiología , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/psicología , Comorbilidad , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Teoría Psicológica , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factores de Tiempo , Adulto Joven
11.
ACS Omega ; 4(5): 8290-8298, 2019 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-31459915

RESUMEN

Herein, we examine the photochemical formation of reactive oxygen species (ROS) by a porous benzophenone-containing bis-urea host (1) to investigate the mechanism of photooxidations that occur within the confines of its nanochannels. UV irradiation of the self-assembled host in the presence of molecular oxygen generates both singlet oxygen and superoxide when suspended in solution. The efficiency of ROS generation by the host is lower than that of benzophenone (BP), which could be beneficial for reactions carried out catalytically, as ROS species react quickly and often unselectively. Superoxide formation was detected through reaction with 5,5-dimethyl-1-pyrroline N-oxide in the presence of methanol. However, it is not detected in CHCl3, as it reacts rapidly with the solvent to generate methaneperoxy and chloride anions, similar to BP. The lifetime of airborne singlet oxygen (τΔairborne) was examined at the air-solid outer surface of the host and host·quencher complexes and suggests that quenching is a surface phenomenon. The efficiency of the host and BP as catalysts was compared for the photooxidation of 1-methyl-1-cyclohexene in solution. Both the host and BP mediate the photooxidation in CHCl3, benzene, and benzene-d 6, producing primarily epoxide-derived products with low selectivity likely by both type I and type II photooxidation processes. Interestingly, in CHCl3, two chlorohydrins were also formed, reflecting the formation of chloride in this solvent. In contrast, UV irradiation of the host·guest crystals in an oxygen atmosphere produced no epoxide and appeared to favor mainly the type II processes. Photolysis afforded high conversion to only three products: an enone, a tertiary allylic alcohol, and a diol, which demonstrates the accessibility of the encapsulated reactants to oxygen and the influence of confinement on the reaction pathway.

12.
Chem Sci ; 10(9): 2670-2677, 2019 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-30996983

RESUMEN

UV-irradiation of assembled urea-tethered triphenylamine dimers results in the formation of persistent radicals, whereas radicals generated in solution are reactive and quickly degrade. In the solid-state, high quantities of radicals (approximately 1 in 150 molecules) are formed with a half-life of one week with no significant change in the single crystal X-ray diffraction. Remarkably, after decay, re-irradiation of the solid sample regenerates the radicals to their original concentration. The photophysics upon radical generation are also altered. Both the absorption and emission are significantly quenched without external oxidation likely due to the delocalization of the radicals within the crystals. The factors that influence radical stability and generation are correlated to the rigid supramolecular framework formed by the urea tether of the triphenylamine dimer. Electrochemical evidence demonstrates that these compounds can be oxidized in solution at 1.0 V vs. SCE to generate radical cations, whose EPR spectra were compared with spectra of the solid-state photogenerated radicals. Additionally, these compounds display changes in emission due to solvent effects from fluorescence to phosphorescence. Understanding how solid-state assembly alters the photophysical properties of triphenylamines could lead to further applications of these compounds for magnetic and conductive materials.

13.
Nanoscale ; 8(4): 1926-31, 2016 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-26753563

RESUMEN

After unprecedented development of organic-inorganic lead halide perovskite solar cells over the past few years, one of the biggest barriers towards their commercialization is the stability of the perovskite material. It is thus important to understand the interaction between the perovskite material and oxygen and/or humidity and the associated degradation process in order to improve device and encapsulation design for better durability. Here we characterize the dynamic aging process in vapour-assisted deposited (VASP) CH3NH3PbBr3 perovskite thin films using advanced optical techniques, such as time-resolved photoluminescence and fluorescence lifetime imaging microscopy (FLIM). Our investigation reveals that the perovskite grains grow spontaneously and the larger grains are formed at room temperature in the presence of moisture and oxygen. This crystallization process leads to a higher density of defects and a shorter carrier lifetime, specifically in the larger grains. Excitation-intensity-dependent steady-state photoluminescence shows both N2 stored and aged perovskite exhibit a super-linear increase of photoluminescence intensity with increasing excitation intensity; and the larger slope in aged sample suggests a larger density of defects is generated, consistent with time-resolved PL measurements.

14.
Mol Cell Endocrinol ; 149(1-2): 153-61, 1999 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-10375027

RESUMEN

We tested the hypothesis that ERalpha and ERbeta mRNAs in the rat ovary are regulated during the post-natal period and in immature rats in response to estrogen treatment. Total ovarian ERbeta mRNA was more abundant than ERalpha mRNA and expression of ERbeta increased between post-natal days 4 and 12, coinciding with advancing folliculogenesis and an increase in granulosa cell numbers. In contrast, ERalpha mRNA levels remained relatively constant during this period. In situ hybridisation studies localised both ERalpha and ERbeta to granulosa cells of growing follicles, in 25 day old ovaries, although not all granulosa cells in a follicle or all follicles expressed the ERs. Diethylstilboestrol (DES) administered in vivo to 21 day old rats, for up to 4 days, did not significantly alter the expression of either ER as determined by RT-PCR, despite a 5.5-fold increase in granulosa cell number in these ovaries. In situ hybridisation studies established that DES-treatment down-regulated granulosa cell ER mRNAs. RT-PCR analyses on isolated granulosa cells confirmed that ERalpha was significantly down-regulated by DES. The predominance of ERbeta over ERalpha in the ovary and the regulation of ERbeta mRNA expression during ovarian development, is consistent with an important biological role for ERbeta in granulosa cell proliferation and differentiation.


Asunto(s)
Ovario/crecimiento & desarrollo , Ovario/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Estrógenos/genética , Animales , Secuencia de Bases , Diferenciación Celular , División Celular , Cartilla de ADN/genética , Dietilestilbestrol/farmacología , Regulación hacia Abajo/efectos de los fármacos , Receptor alfa de Estrógeno , Receptor beta de Estrógeno , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Células de la Granulosa/citología , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Hibridación in Situ , Modelos Biológicos , Ovario/efectos de los fármacos , Ratas , Ratas Sprague-Dawley
15.
Mol Cell Endocrinol ; 180(1-2): 139-44, 2001 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-11451583

RESUMEN

Evidence to enhance the premise that inhibin and activin are local regulators of ovarian folliculogenesis is presented in this review. Granulosa cells (GC) have been identified as the source of inhibin/activin in the ovary on the basis of mRNA and protein localisation and the measurement of the inhibin forms in GC conditioned media. Expression of the subunit mRNAs changed with follicular development, being maximal in the ovaries of 8-day-old rats, where secondary follicles predominate. The expression of beta subunit mRNAs by GC isolated from diethylstilboestrol (DES)-treated immature rats, was reduced in the absence of any change in alpha subunit mRNA expression. Dimeric inhibin-A, -B and free alpha subunit were produced by ovarian cell cultures prepared from 4- to 12-day-old rats. Inhibin-A production by these cultures was responsive to FSH and TGF-beta, with preantral follicles of day 8 ovaries exerting effects so profound that the inhibin A/alpha subunit ratio increased, most likely due to a stimulation of beta(A) subunit production. In contrast, inhibin-B was not stimulated by TGF-beta until day 8 and FSH until day 12. Fractionation of GC conditioned media revealed a prominence of free alpha subunit and inhibin-A, but little inhibin-B, suggesting that inhibin-B production declines with follicular development. Activin receptor types I and II, Smads 1-8 and betaglycan (beta-glycan) mRNAs were present in the rat ovary and showed distinct patterns of expression between postnatal days 4 and 12. Oocytes and GC localised activin receptor, Smad and beta-glycan proteins, with beta-glycan also present in theca cells (TC). These data indicate that activin/TGF-beta signalling machinery and factors which influence these pathways, are present in the postnatal rat ovary. Our hypothesis that inhibin and activin play important and changing autocrine/paracrine roles in the growth and differentiation of follicles, including the oocyte, has been supported by these studies.


Asunto(s)
Activinas/farmacología , Inhibinas/farmacología , Folículo Ovárico/fisiología , Ratas/fisiología , Activinas/biosíntesis , Activinas/genética , Animales , Dimerización , Femenino , Células de la Granulosa/efectos de los fármacos , Inhibinas/biosíntesis , Inhibinas/genética , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/crecimiento & desarrollo , Subunidades de Proteína , ARN Mensajero/biosíntesis , Transducción de Señal
16.
Mol Cell Endocrinol ; 191(1): 35-43, 2002 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-12044917

RESUMEN

Peripheral endocrine hormones and local paracrine and autocrine factors contribute, in a coordinated fashion, to the processes of recruitment, development or atresia, selection and ovulation of follicles. Among the local ovarian factors, there is growing evidence from genetic and experimental data that many members of the transforming growth factor (TGFbeta) superfamily have a biological role to play in folliculogenesis. These members include activin, inhibin, TGFbeta, BMP, GDF9 and perhaps MIS. In this review, we discuss the potential roles of the TGFbeta superfamily members, in particular activin, during folliculogenesis. Since the actions of these factors are determined by ligand availability, receptor expression and modulation of their signal transduction pathways, we also collate information on the expression of their signalling components in the follicle. We conclude that the TGFbeta superfamily signalling pathways, in particular activin's pathway, reside in the ovary. Furthermore, follistatin and beta-glycan-components of the accessory binding protein system that modifies activin action-are also present in follicles. In the post-natal rat ovary, the changes in receptor/Smad expression coincide with granulosa cell proliferation and antrum formation. We hypothesise that these pathway components are expressed in a temporal and cell-specific manner to meet the changing demands of cells during follicular development. The analysis of the components of the signal transduction pathways of the TGFbeta family members in populations of defined follicles and the identification of activated pathways in individually stimulated follicles should help clarify the roles of the TGFbeta members in folliculogenesis.


Asunto(s)
Folículo Ovárico/crecimiento & desarrollo , Transducción de Señal/fisiología , Factor de Crecimiento Transformador beta/metabolismo , Receptores de Activinas/genética , Receptores de Activinas/metabolismo , Activinas/metabolismo , Animales , Comunicación Autocrina/fisiología , Proteínas Morfogenéticas Óseas/metabolismo , Femenino , Humanos , Ligandos , Familia de Multigenes , Folículo Ovárico/citología , Folículo Ovárico/metabolismo , Comunicación Paracrina/fisiología
17.
J Reprod Immunol ; 39(1-2): 77-87, 1998 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9786454

RESUMEN

Previous observations from our laboratory have demonstrated that the levels of immunoreactive inhibin (ir-inh) are elevated in almost all patients with granulosa cell tumours and in the majority of postmenopausal women with mucinous ovarian cancers. The present manuscript confirms these findings in a larger group of postmenopausal women. Immunohistochemistry for the inhibin alpha, betaA and betaB subunits shows predominantly epithelial staining in granulosa cell tumours and in the majority of mucinous cancers. Serous cystadenocarcinomas also frequently show positive staining. Studies seeking to identify G alpha(i-2) or FSH receptor mutations have provided negative results in contrast to other reports. Further studies of the roles of the inhibin-related family of peptides in ovarian cancer diagnosis and monitoring are clearly indicated.


Asunto(s)
Inhibinas/sangre , Neoplasias Ováricas/sangre , Anciano , Anciano de 80 o más Años , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/genética , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Receptores de HFE/análisis
18.
J Appl Physiol (1985) ; 71(3): 1020-4, 1991 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-1721901

RESUMEN

Muscle growth was established in specific muscles in the hindlimb of adult female rats by tenotomy of the gastrocnemius muscle. Seven days after surgery there was an increase in the wet weight of the soleus (Sol) and plantaris (P) muscles and a decrease in that of the gastrocnemius (G) muscle from the tenotomized limb compared with the respective control muscles from the contralateral limb from the same animal. In all three muscles there was a significant increase in the fractional rate of protein synthesis (ks) in the muscles from the tenotomized limb above the rate of the respective control muscles. In contrast, the extensor digitorum longus (EDL) muscle showed no change in wet weight or ks 7 days after tenotomy of G. Fasting for 12 or 36 h had no significant effect on ks in G, P, or Sol muscles from either the control or tenotomized limbs. In EDL from the control limb, both fasting periods resulted in a significant decrease in ks, although this effect was not seen in the EDL from the tenotomized limbs of the same animals. A subsequent 30-min insulin infusion was similarly ineffectual in G, P, and Sol, with its only effect evident in the EDL from the control limb, where it was sufficient to reverse the decreased ks resulting from the fasting, even though after 36 h fasting the reversal was only partial.


Asunto(s)
Ayuno/fisiología , Insulina/farmacología , Proteínas Musculares/biosíntesis , Músculos/metabolismo , Tendones/fisiología , Envejecimiento/fisiología , Animales , Glucemia/metabolismo , Femenino , Miembro Posterior/fisiología , Músculos/efectos de los fármacos , Fenilalanina/metabolismo , ARN/metabolismo , Ratas , Ribosomas/metabolismo
19.
Phys Med Biol ; 45(11): 3367-72, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11098910

RESUMEN

A modified sector-integration method is presented that can predict the output factors of irregular shaped electron fields even in the case of extended source to surface distance (SSD). The model takes as input measured output factors for circular inserts of various radii. These circular fields were measured at SSDs of 100, 105 and 110 cm to determine the effective source distance as a function of radius (ESD(r)). For an arbitrary electron field at any SSD, the shape is divided into small sectors, and the contribution calculated from the radius and ESD(r). The calculated output factors were verified by direct measurements of various types of electron fields mainly based on clinical use. The energies modelled were 8, 10 and 12 MeV for applicator sizes of 10 cm x 10 cm and 14 cm x 14 cm (defined at 95 cm). The calculated values agreed with the measured data within 1% for the various rectangular cutouts including extended source to surface distance. We retrospectively modelled 97 patient inserts of irregular shape, and found agreement within 2% of measured values.


Asunto(s)
Electrones , Radioterapia Conformacional/instrumentación , Radioterapia Conformacional/métodos , Algoritmos , Modelos Estadísticos
20.
J Drug Target ; 3(1): 1-7, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-7655816

RESUMEN

Five non-ionic surfactants (Surfactants V-IX) were screened for their ability to produce vesicles for the delivery of sodium stibogluconate. Mean vesicle diameter and antimony content were determined prior to in vivo assessment of antiparasitic activity in a mouse model of acute visceral leishmaniasis. V/D suspensions (i.e. stibogluconate loaded vesicles kept in the hydrating drug solution) were more effective against spleen, liver and bone marrow parasites than drug loaded vesicle suspensions that had unentrapped drug removed. A Surfactant IX V/D suspension was the most active antileishmanial preparation causing 74 +/- 10%, 99 +/- 1% and 38 +/- 8% suppression of liver, spleen and bone marrow parasite burdens respectively. Contrary to previous findings, a reduction in splenic and bone marrow parasite burdens was achieved using large vesicles (mean diameter > 800nm). The significance of these results is discussed.


Asunto(s)
Gluconato de Sodio Antimonio/uso terapéutico , Leishmaniasis Visceral/tratamiento farmacológico , Animales , Antimonio/análisis , Gluconato de Sodio Antimonio/administración & dosificación , Gluconato de Sodio Antimonio/análisis , Médula Ósea/parasitología , Portadores de Fármacos , Femenino , Leishmaniasis Visceral/parasitología , Hígado/parasitología , Masculino , Ratones , Ratones Endogámicos BALB C , Microesferas , Tamaño de la Partícula , Bazo/parasitología , Tensoactivos
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