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1.
Diabet Med ; : e15379, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38881382

RESUMEN

BACKGROUND AND AIMS: Gastrointestinal (GI) symptoms, common in type 2 diabetes (T2D), are typically bothersome, socially embarrassing, and impact negatively on quality of life. They may also contribute to diabetes distress (DD), but this has never been formally evaluated. We aimed to investigate the relationships between GI symptoms, DD and depressive symptoms in a large cohort of individuals with T2D in Bangladesh. MATERIALS AND METHODS: 1406 unselected T2D individuals (female 58.8%; mean age 51.0 ± 12.5 years) from four diabetes clinics in Bangladesh completed validated questionnaires evaluating GI symptoms (PAGI-SYM), DD (DDS-17) and depressive symptoms (PHQ-9). RESULTS: 31.1% of participants reported GI symptoms (36.2% females, 23.7% males), while 51.1% had elevated DD and 37.8% depressive symptoms. GI symptoms exhibited independent relationships with both DD and depressive symptoms, and their likelihood was higher among those with DD (OR: 3.6 [2.2-5.6] and with depressive symptoms (OR: 5.9 [3.5-9.9]). CONCLUSIONS: GI symptoms are independently associated with both DD and depressive symptoms in people with T2D in Bangladesh.

2.
Phys Rev Lett ; 130(21): 212701, 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37295108

RESUMEN

The rate of the final step in the astrophysical αp process, the ^{34}Ar(α,p)^{37}K reaction, suffers from large uncertainties due to a lack of experimental data, despite having a considerable impact on the observable light curves of x-ray bursts and the composition of the ashes of hydrogen and helium burning on accreting neutron stars. We present the first direct measurement constraining the ^{34}Ar(α,p)^{37}K reaction cross section, using the Jet Experiments in Nuclear Structure and Astrophysics gas jet target. The combined cross section for the ^{34}Ar,Cl(α,p)^{37}K,Ar reaction is found to agree well with Hauser-Feshbach predictions. The ^{34}Ar(α,2p)^{36}Ar cross section, which can be exclusively attributed to the ^{34}Ar beam component, also agrees to within the typical uncertainties quoted for statistical models. This indicates the applicability of the statistical model for predicting astrophysical (α,p) reaction rates in this part of the αp process, in contrast to earlier findings from indirect reaction studies indicating orders-of-magnitude discrepancies. This removes a significant uncertainty in models of hydrogen and helium burning on accreting neutron stars.


Asunto(s)
Helio , Hidrógeno , Modelos Estadísticos , Neutrones
3.
Alcohol ; 99: 49-58, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34942330

RESUMEN

The potential of micronutrients to ameliorate the impact of prenatal alcohol exposure (PAE) on attentional regulation skills was explored in a randomized clinical trial conducted in Ukraine. Women who differed in prenatal alcohol use were recruited during pregnancy and assigned to one of three groups [No study-provided supplements, Multivitamin/Mineral Supplement (MVM), or MVM plus Choline]. Their offspring were seen in the preschool period and a reaction time task was administered. Participants were asked to press a response button as quickly as possible as 30 stimuli from the same category (animals) were presented consecutively and then followed by six stimuli from a novel category (vehicles). Number correct, mean latency of the response over trials, and variability in the latency were analyzed separately by sex. During the initial animal trials, boys whose mothers received MVM during pregnancy had more correct responses and reduced response latency compared to boys whose mothers had no MVM treatment. During vehicle trials, maternal choline supplementation was associated with increased response speed in males without a PAE history. Females receiving supplements did not show the same benefits from micronutrient supplementation and were more adversely impacted by prenatal alcohol exposure. Relationships between maternal levels of choline, betaine, and dimethylglycine (DMG) and task performance were also assessed. Although no effects were found for choline after adjusting for multiple comparisons, lower baseline DMG level was associated with greater accuracy and shorter latency of responses in the initial animal trials and shorter latency in the vehicle trials in female preschoolers. Level of betaine in Trimester 3 was associated with reduced variability in the latency of male responses during the animal trials. Maternal micronutrient supplementation in pregnancy appears to improve preschool reaction time performance, but the effects varied as a function of sex and PAE exposure status.


Asunto(s)
Efectos Tardíos de la Exposición Prenatal , Preescolar , Suplementos Dietéticos , Femenino , Humanos , Masculino , Micronutrientes , Embarazo , Tiempo de Reacción , Ucrania
5.
Phys Rev Lett ; 125(6): 062501, 2020 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-32845657

RESUMEN

Precise antineutrino measurements are very sensitive to proper background characterization. We present an improved measurement of the ^{13}C(α,n)^{16}O reaction cross section which constitutes significant background for large ν[over ¯] detectors. We greatly improve the precision and accuracy by utilizing a setup that is sensitive to the neutron energies while making measurements of the excited state transitions via secondary γ-ray detection. Our results shows a 54% reduction in the background contributions from the ^{16}O(3^{-},6.13 MeV) state used in the KamLAND analysis.

6.
Phys Rev Lett ; 122(5): 052701, 2019 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-30822026

RESUMEN

Detection of nuclear-decay γ rays provides a sensitive thermometer of nova nucleosynthesis. The most intense γ-ray flux is thought to be annihilation radiation from the ß^{+} decay of ^{18}F, which is destroyed prior to decay by the ^{18}F(p,α)^{15}O reaction. Estimates of ^{18}F production had been uncertain, however, because key near-threshold levels in the compound nucleus, ^{19}Ne, had yet to be identified. We report the first measurement of the ^{19}F(^{3}He,tγ)^{19}Ne reaction, in which the placement of two long-sought 3/2^{+} levels is suggested via triton-γ-γ coincidences. The precise determination of their resonance energies reduces the upper limit of the rate by a factor of 1.5-17 at nova temperatures and reduces the average uncertainty on the nova detection probability by a factor of 2.1.

7.
Genome Announc ; 5(45)2017 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-29122874

RESUMEN

Here, we report the draft genome sequences of three laboratory variants of Bacillus anthracis Sterne and their double (Δlef Δcya) and triple (Δpag Δlef Δcya) toxin gene deletion derivatives.

8.
Mol Psychiatry ; 22(2): 273-279, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27217154

RESUMEN

Immune abnormalities have been described in some individuals with autism spectrum disorders (ASDs) as well as their family members. However, few studies have directly investigated the role of prenatal cytokine and chemokine profiles on neurodevelopmental outcomes in humans. In the current study, we characterized mid-gestational serum profiles of 22 cytokines and chemokines in mothers of children with ASD (N=415), developmental delay (DD) without ASD (N=188), and general population (GP) controls (N=428) using a bead-based multiplex technology. The ASD group was further divided into those with intellectual disabilities (developmental/cognitive and adaptive composite score<70) (ASD+ID, N=184) and those without (composite score⩾70) (ASD-noID, N=201). Levels of cytokines and chemokines were compared between groups using multivariate logistic regression analyses, adjusting for maternal age, ethnicity, birth country and weight, as well as infant gender, birth year and birth month. Mothers of children with ASD+ID had significantly elevated mid-gestational levels of numerous cytokines and chemokines, such as granulocyte macrophage colony-stimulating factor, interferon-γ, interleukin-1α (IL-1α) and IL-6, compared with mothers of children with either ASD-noID, those with DD, or GP controls. Conversely, mothers of children with either ASD-noID or with DD had significantly lower levels of the chemokines IL-8 and monocyte chemotactic protein-1 compared with mothers of GP controls. This observed immunologic distinction between mothers of children with ASD+ID from mothers of children with ASD-noID or DD suggests that the intellectual disability associated with ASD might be etiologically distinct from DD without ASD. These findings contribute to the ongoing efforts toward identification of early biological markers specific to subphenotypes of ASD.


Asunto(s)
Trastorno Autístico/etiología , Quimiocinas/efectos adversos , Citocinas/efectos adversos , Adulto , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/etiología , Trastorno Autístico/complicaciones , Estudios de Casos y Controles , Quimiocinas/sangre , Niño , Desarrollo Infantil , Trastornos Generalizados del Desarrollo Infantil/epidemiología , Trastornos Generalizados del Desarrollo Infantil/etiología , Preescolar , Citocinas/sangre , Discapacidades del Desarrollo/complicaciones , Femenino , Humanos , Lactante , Discapacidad Intelectual/etiología , Masculino , Madres , Embarazo , Efectos Tardíos de la Exposición Prenatal/patología
9.
Int J Obes (Lond) ; 41(2): 225-232, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27840416

RESUMEN

BACKGROUND/OBJECTIVES: Studies concerning the glycaemic response to oral glucose, or meals in obesity have usually failed to account for gastric emptying. It has been suggested that the incretin effect may be diminished in obesity as a result of a reduction in glucagon-like peptide-1 (GLP-1) secretion. We sought to determine the effect of two different rates of intraduodenal glucose infusions on glycaemic, insulinaemic and incretin hormone responses in lean and obese subjects and compare the effects of oral and intraduodenal glucose in obese subjects. SUBJECTS/METHODS: Eleven obese subjects (age 37.5±4.1 years, body mass index (BMI) 35.7±1.4 kg m-2) and 12 controls (age 34.7±4.0 years, BMI 23.9±0.7 kg m-2) received intraduodenal infusions of glucose at 1 or 3 kcal min-1, or saline for 60 min (t=0-60 min), followed by intraduodenal saline (t=60-120 min). In obese subjects, an oral glucose tolerance test was performed. Blood glucose, serum insulin, plasma total GLP-1 and total gastric inhibitory polypeptide (GIP) were measured. RESULTS: In both the groups (P<0.001), the incremental areas under the curve (iAUC)0-60 min for glucose was greater with the 3 kcal min-1 than the 1 kcal min-1 infusion; the iAUC0-120 min for glucose during 3 kcal min-1 was greater (P<0.05), in the obese. Insulin responses to 1 kcal min-1 and, particularly, 3 kcal min-1 were greater (P<0.001) in the obese. Stimulation of GLP-1 and GIP were greater (P<0.001) in response to 3 kcal min-1, compared with 1 kcal min-1 and saline, without any difference between the groups. In the obese, glycaemic, insulinaemic and GIP, but not GLP-1, responses to oral and intraduodenal glucose were related (P<0.05). CONCLUSIONS: The rate of duodenal glucose delivery is a major determinant of glycaemia, insulinaemia and incretin hormone release in obese subjects. Obesity is not apparently associated with impaired GLP-1 secretion.


Asunto(s)
Regulación del Apetito/fisiología , Duodeno/metabolismo , Nutrición Enteral , Vaciamiento Gástrico/fisiología , Glucosa/administración & dosificación , Incretinas/metabolismo , Obesidad/fisiopatología , Adulto , Glucemia/metabolismo , Índice de Masa Corporal , Duodeno/fisiopatología , Femenino , Polipéptido Inhibidor Gástrico/metabolismo , Motilidad Gastrointestinal , Péptido 1 Similar al Glucagón/metabolismo , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Obesidad/metabolismo , Periodo Posprandial
10.
Alcohol ; 49(7): 647-56, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26493109

RESUMEN

The potential of micronutrients to ameliorate the impact of prenatal alcohol exposure (PAE) was explored in a clinical trial conducted in Ukraine. Cardiac orienting responses (ORs) during a habituation/dishabituation learning paradigm were obtained from 6 to 12 month-olds to assess neurophysiological encoding and memory. Women who differed in prenatal alcohol use were recruited during pregnancy and assigned to a group (No study-provided supplements, multivitamin/mineral supplement, or multivitamin/mineral supplement plus choline supplement). Heart rate was collected for 30 s prior to stimulus onset and 12 s post-stimulus onset. Difference values (∆HR) for the first 3 trials of each condition were aggregated for analysis. Gestational blood samples were collected to assess maternal nutritional status and changes as a function of the intervention. Choline supplementation resulted in a greater ∆HR on the visual habituation trials for all infants and for the infants with no PAE on the dishabituation trials. The latency of the response was reduced in both conditions for all infants whose mothers received choline supplementation. Change in gestational choline level was positively related to ∆HR during habituation trials and levels of one choline metabolite, dimethylglycine (DMG), predicted ∆HR during habituation trials and latency of responses. A trend was found between DMG and ∆HR on the dishabituation trials and latency of the response. Supplementation did not affect ORs to auditory stimuli. Choline supplementation when administered together with routinely recommended multivitamin/mineral prenatal supplements during pregnancy may provide a beneficial impact to basic learning mechanisms involved in encoding and memory of environmental events in alcohol-exposed pregnancies as well as non- or low alcohol-exposed pregnancies. Changes in maternal nutrient status suggested that one mechanism by which choline supplementation may positively impact brain development is through prevention of fetal alcohol-related depletion of DMG, a metabolic nutrient that can protect against overproduction of glycine, during critical periods of neurogenesis.


Asunto(s)
Depresores del Sistema Nervioso Central/efectos adversos , Suplementos Dietéticos , Etanol/efectos adversos , Trastornos del Espectro Alcohólico Fetal/prevención & control , Procesos Mentales/efectos de los fármacos , Micronutrientes , Efectos Tardíos de la Exposición Prenatal/prevención & control , Efectos Tardíos de la Exposición Prenatal/psicología , Adulto , Colina/administración & dosificación , Colina/uso terapéutico , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Lactante , Recién Nacido , Aprendizaje/efectos de los fármacos , Pruebas Neuropsicológicas , Embarazo , Sarcosina/análogos & derivados , Sarcosina/metabolismo , Factores Socioeconómicos , Ucrania
11.
Phys Rev Lett ; 114(21): 212501, 2015 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-26066430

RESUMEN

The Galactic 1.809-MeV γ-ray signature from the ß decay of ^{26g}Al is a dominant target of γ-ray astronomy, of which a significant component is understood to originate from massive stars. The ^{26g}Al(p,γ)^{27}Si reaction is a major destruction pathway for ^{26g}Al at stellar temperatures, but the reaction rate is poorly constrained due to uncertainties in the strengths of low-lying resonances in ^{27}Si. The ^{26g}Al(d,p)^{27}Al reaction has been employed in inverse kinematics to determine the spectroscopic factors, and hence resonance strengths, of proton resonances in ^{27}Si via mirror symmetry. The strength of the 127-keV resonance is found to be a factor of 4 higher than the previously adopted upper limit, and the upper limit for the 68-keV resonance has been reduced by an order of magnitude, considerably constraining the ^{26g}Al destruction rate at stellar temperatures.

12.
Nutr Diabetes ; 5: e156, 2015 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-25985092

RESUMEN

The region of enteral nutrient exposure may be an important determinant of postprandial incretin hormone secretion and blood glucose homoeostasis. We compared responses of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon, and blood glucose to a standardised glucose infusion into the proximal jejunum and duodenum in healthy humans. Ten healthy males were evaluated during a standardised glucose infusion (2 kcal min(-1) over 120 min) into the proximal jejunum (50 cm post pylorus) and were compared with another 10 healthy males matched for ethnicity, age and body mass index who received an identical glucose infusion into the duodenum (12 cm post pylorus). Blood was sampled frequently for measurements of blood glucose and plasma hormones. Plasma GLP-1, GIP and insulin responses, as well as the insulin:glucose ratio and the insulinogenic index 1 (IGI1) were greater (P<0.05 for each) after intrajejunal (i.j.) than intraduodenal glucose infusion, without a significant difference in blood glucose or plasma glucagon. Pooled analyses revealed direct relationships between IGI1 and the responses of GLP-1 and GIP (r=0.48 and 0.56, respectively, P<0.05 each), and between glucagon and GLP-1 (r=0.70, P<0.001). In conclusion, i.j. glucose elicits greater incretin hormone and insulin secretion than intraduodenal glucose in healthy humans, suggesting regional specificity of the gut-incretin axis.

13.
Heredity (Edinb) ; 115(5): 452-9, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26014526

RESUMEN

Sex chromosomes contribute disproportionately to species boundaries as they diverge faster than autosomes and often have reduced diversity. Their hemizygous nature contributes to faster divergence and reduced diversity, as do some types of selection. In birds, other factors (mating system and bottlenecks) can further decrease the effective population size of Z-linked loci and accelerate divergence (Fast-Z). We assessed Z-linked divergence and effective population sizes for two polygynous sage-grouse species and compared them to estimates from birds with various mating systems. We found lower diversity and higher FST for Z-linked loci than for autosomes, as expected. The π(Z)/π(A) ratio was 0.38 in Centrocercus minimus, 0.48 in Centrocercus urophasianus and 0.59 in a diverged, parapatric population of C. urophasianus, a broad range given the mating system among these groups is presumably equivalent. The full data set had unequal males and females across groups, so we compared an equally balanced reduced set of C. minimus and individuals pooled from both C. urophasianus subgroups recovering similar estimates: 0.54 for C. urophasianus and 0.38 for C. minimus. We provide further evidence that N(eZ)/N(eA) in birds is often lower than expected under random mating or monogamy. The lower ratio in C. minimus could be a consequence of stronger selection or drift acting on Z loci during speciation, as this species differs strongly from C. urophasianus in sexually selected characters with minimal mitochondrial divergence. As C. minimus also exhibited lower genomic diversity, it is possible that a more severe demographic history may contribute to its lower ratio.


Asunto(s)
Galliformes/genética , Genética de Población , Cromosomas Sexuales/genética , Animales , Femenino , Galliformes/clasificación , Frecuencia de los Genes , Masculino , América del Norte , Polimorfismo de Nucleótido Simple , Densidad de Población , Análisis de Secuencia de ADN , Conducta Sexual Animal
14.
Diabet Med ; 32(11): 1500-3, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25981372

RESUMEN

AIM: In healthy subjects, the oral disposition index (ratio of insulin response to insulin sensitivity) is predictive of the development of Type 2 diabetes. Gastric emptying, which exhibits a substantial interindividual variation, is a major determinant of postprandial glycaemia in health and diabetes. We sought to determine whether the rate of intraduodenal glucose delivery affects the disposition index in people without diabetes. METHODS: Nineteen Caucasian males received glucose infusions via an intraduodenal catheter at either 2 kcal/min (ID2) or 4 kcal/min (ID4) for 120 min, on two separate days with measurements of blood glucose (G) and plasma insulin (I) at frequent intervals. The insulin response was estimated by the ratio of the change in insulin to that of change in glucose at 30 min (∆I(0-30)/∆G(0-30)) and 60 min (∆I(0-60)/∆G(0-60)). Insulin sensitivity was estimated as 1/fasting insulin. The oral disposition index (DI) was calculated as ∆I(0-30)/∆G(0-30) × 1/fasting insulin and ∆I(0-60)/∆G(0-60) × 1/fasting insulin. RESULTS: The overall glycaemic response was comparable on both days, but the insulin response was much greater at ID4 when calculated at either 30 or 60 min (P < 0.05). DI was also greater (P < 0.05) in response to ID4 than ID2. CONCLUSIONS: The rate of duodenal glucose delivery has a major impact on insulin release and, thereby, DI. This suggests that the rate of gastric emptying, which determines duodenal glucose delivery, is a determinant of DI.


Asunto(s)
Carbohidratos de la Dieta/metabolismo , Duodeno/metabolismo , Vaciamiento Gástrico , Glucosa/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Mucosa Intestinal/metabolismo , Adulto , Algoritmos , Glucemia/análisis , Carbohidratos de la Dieta/administración & dosificación , Glucosa/administración & dosificación , Carga Glucémica , Humanos , Insulina/sangre , Resistencia a la Insulina , Secreción de Insulina , Absorción Intestinal , Intubación Gastrointestinal , Cinética , Masculino
15.
Cereb Cortex ; 25(12): 4761-71, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25092900

RESUMEN

Functional magnetic resonance imaging (fMRI) reveals brain activation abnormalities during visuo-spatial attention and working memory among those with fetal alcohol spectrum disorders (FASD) in cross-sectional reports, but little is known about how activation changes over time during development within FASD or typically developing children. We studied 30 controls and 31 individuals with FASD over 2 years (7-14 years at first participation) with a total of 122 scans, as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders. Despite comparable performance, there were significant group differences in visuo-spatial activation over time bilaterally in frontal, parietal, and temporal regions. Controls showed an increase in signal intensity in these multiple regions whereas FASD participants showed a decrease in brain activation. Effects were also found in 2 small independent samples from the USA, corroborating the findings from the larger group. Results suggest that the long-lasting effect of prenatal alcohol may impact the maturation of visuo-spatial attention and differentiate those with FASD from controls. Based on this first longitudinal fMRI study in FASD children, our novel findings suggest a possible neural mechanism for attention deficits common among individuals with FASD.


Asunto(s)
Atención/fisiología , Encéfalo/crecimiento & desarrollo , Encéfalo/fisiopatología , Etanol/efectos adversos , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Percepción Espacial/fisiología , Percepción Visual/fisiología , Adolescente , Atención/efectos de los fármacos , Encéfalo/efectos de los fármacos , Mapeo Encefálico , Niño , Desarrollo Infantil , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Lóbulo Parietal/efectos de los fármacos , Lóbulo Parietal/crecimiento & desarrollo , Lóbulo Parietal/fisiopatología , Embarazo , Percepción Espacial/efectos de los fármacos , Percepción Visual/efectos de los fármacos
16.
Diabet Med ; 32(5): 595-600, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25388434

RESUMEN

AIMS: To evaluate the effects of the dipeptidyl peptidase-4 inhibitor sitagliptin on blood pressure and heart rate, measured during a previously reported study, in which the effects of sitagliptin during intraduodenal glucose infusion at the rate of 2 kcal/min on glucose homeostasis were examined in patients with Type 2 diabetes. METHODS: A total of 10 people with Type 2 diabetes were studied on two different days, 30 min after oral ingestion of sitagliptin (100 mg) or placebo. Intraduodenal glucose was infused at 2 kcal/min (60 g over 120 min), and blood pressure, heart rate, plasma glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (total and intact), glucose, insulin and glucagon responses were evaluated. RESULTS: In response to intraduodenal glucose infusion, heart rate (treatment effect: P = 0.001) and serum insulin concentration (treatment × time interaction: P = 0.041) were higher after sitagliptin treatment than placebo, without a significant difference in blood pressure, plasma glucagon or glucose. During intraduodenal glucose infusion, there was a substantial increase in plasma total glucose-dependent insulinotropic polypeptide on both days (time effect: P < 0.001), but not in total glucagon-like peptide-1. After sitagliptin, plasma intact glucagon-like peptide-1 concentration increased slightly (treatment × time interaction: P = 0.044) and glucose-dependent insulinotropic polypeptide concentration increased substantially (treatment × time interaction: P = 0.003).The heart rate response to intraduodenal glucose was related directly to plasma intact glucose-dependent insulinotropic polypeptide concentrations (r = 0.75, P = 0.008). CONCLUSIONS: Sitagliptin increased the heart rate response to intraduodenal glucose infusion at 2 kcal/min in people with Type 2 diabetes, which was associated with augmentation of plasma intact glucose-dependent insulinotropic polypeptide concentrations. These observations warrant further clarification of a potential role for glucose-dependent insulinotropic polypeptide in the control of the 'gut-heart' axis.


Asunto(s)
Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 2/fisiopatología , Polipéptido Inhibidor Gástrico/fisiología , Glucosa/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Fosfato de Sitagliptina/farmacología , Administración Oral , Anciano , Presión Sanguínea/fisiología , Diabetes Mellitus Tipo 2/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Método Doble Ciego , Duodeno/efectos de los fármacos , Duodeno/metabolismo , Glucosa/administración & dosificación , Glucosa/metabolismo , Frecuencia Cardíaca/fisiología , Homeostasis/efectos de los fármacos , Homeostasis/fisiología , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Masculino , Estudios Retrospectivos , Fosfato de Sitagliptina/administración & dosificación , Factores de Tiempo
17.
Pediatr Blood Cancer ; 62(4): 598-602, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25546733

RESUMEN

BACKGROUND: Topotecan has been variably incorporated in the treatment of patients with relapsed Wilms tumour (WT) who failed initial treatment with three or more effective drugs. Our objective was to describe outcome and to retrospectively investigate the potential role of topotecan in relapsed WT patients. METHODS: Children who were treated with topotecan as part of their chemotherapeutic regimens for relapsed WT were identified and included in our retrospective study. Patient charts were reviewed for general patient characteristics, histology and stage at initial diagnosis, number and type of relapse, salvage treatment schedules, toxicity, response to treatment and outcome. RESULTS: From 2000 to 2012, 30 children (median age at relapse 5.5 years, range 1.6-14.5 years) were identified to have received topotecan as part of their salvage regimens (primary progressive disease n = 3, first, second and third relapse n = 13, 9 and 2 respectively, partial response n = 3). Topotecan was administered as a single agent (12 patients) or in combination with other drugs (18 patients). Sixteen patients had high-risk histology according to the SIOP classification, 15 died within 12 months because of progressive disease. Fourteen patients had SIOP intermediate-risk histology of which four patients displayed objective responses to topotecan. Overall, 6 out of 14 intermediate-risk patients survived (median follow up of 6 years), however, three of whom (stage V) had bilateral nephrectomy after topotecan treatment. CONCLUSIONS: Topotecan does not seem to show effectiveness in the treatment of relapsed WT patients with initial high-risk histology. In patients with intermediate-risk histology, the role of topotecan might deserve further attention, to prove its efficacy.


Asunto(s)
Neoplasias Renales , Recurrencia Local de Neoplasia , Topotecan/administración & dosificación , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Inhibidores de Topoisomerasa I , Tumor de Wilms/tratamiento farmacológico , Tumor de Wilms/mortalidad , Tumor de Wilms/patología
18.
Phys Rev Lett ; 112(17): 172701, 2014 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-24836240

RESUMEN

Single-neutron states in (133)Sn and (209)Pb, which are analogous to single-electron states outside of closed atomic shells in alkali metals, were populated by the ((9)Be, (8)Be) one-neutron transfer reaction in inverse kinematics using particle-γ coincidence spectroscopy. In addition, the s(1/2) single-neutron hole-state candidate in (131)Sn was populated by ((9)Be, (10)Be). Doubly closed-shell (132)Sn (radioactive) and (208)Pb (stable) beams were used at sub-Coulomb barrier energies of 3 MeV per nucleon. Level energies, γ-ray transitions, absolute cross sections, spectroscopic factors, asymptotic normalization coefficients, and excited-state lifetimes are reported and compared with shell-model expectations. The results include a new transition and precise level energy for the 3p(1/2) candidate in (133)Sn, new absolute cross sections for the 1h(9/2) candidate in (133)Sn and 3s(1/2) candidate in (131)Sn, and new lifetimes for excited states in (133)Sn and (209)Pb. This is the first report on excited-state lifetimes of (133)Sn, which allow for a unique test of the nuclear shell model and (132)Sn double-shell closure.

19.
Diabetologia ; 56(6): 1236-42, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23471488

RESUMEN

AIMS/HYPOTHESES: Glucagon-like peptide-1 (GLP-1), an important mediator of postprandial glycaemia, could potentially be stimulated by delivering small quantities of nutrient to a long length of distal gut. We aimed to determine whether enteric-coated pellets, releasing small amounts of lauric acid throughout the ileum and colon, could reduce glycaemic responses to meals in type 2 diabetes, associated with stimulation of GLP-1. METHODS: Eligible patients, who had type 2 diabetes controlled by diet or metformin, were each studied on two occasions in a hospital setting. After an overnight fast, patients consumed 5 g active pellets (47% lauric acid by weight) or placebo with breakfast (T = 0 min) and lunch (T = 240 min), in a crossover design with order randomised by the hospital pharmacy and allocation concealed by numbered containers. Patients and investigators making measurements were blinded to the intervention. Blood was sampled frequently for blood glucose (the primary outcome) and hormone assays. RESULTS: Eight patients were randomised (four to receive either intervention first), and all completed the study without adverse effects. Blood glucose was lower after breakfast (T = 0-240 min, area under the curve (AUC) 2,075 ± 368 vs 2,216 ± 163 mmol/l × min) and lunch (T = 240-480 min, AUC 1,916 ± 115 vs 2,088 ± 151 mmol/l × min) (p = 0.02 for each) after active pellets than after placebo. Plasma GLP-1 concentrations were higher after breakfast (p = 0.08) and lunch (p = 0.04) for active pellets. While there were no differences in insulin or glucose-dependent insulinotropic polypeptide concentrations, glucagon concentrations were higher after breakfast and lunch (p = 0.002 for each) for active pellets. CONCLUSIONS/INTERPRETATION: Delivering small amounts of nutrient to the ileum and colon can stimulate substantial endogenous GLP-1 release and attenuate postprandial glycaemia. This novel approach has therapeutic potential in type 2 diabetes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000600842. FUNDING: The study was funded by Meyer Nutriceuticals.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/metabolismo , Hiperglucemia/complicaciones , Comprimidos Recubiertos/uso terapéutico , Área Bajo la Curva , Glucemia/metabolismo , Colon/metabolismo , Estudios Cruzados , Femenino , Glucagón/metabolismo , Humanos , Íleon/metabolismo , Insulina/metabolismo , Ácidos Láuricos/uso terapéutico , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Factores de Tiempo
20.
Theriogenology ; 79(6): 911-7, 2013 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-23434205

RESUMEN

The objective was to conduct a preliminary evaluation of the efficacy of two media for in vitro culture of equine preantral follicles. Ovarian cortical strips were obtained from mares (N = 10) via the Biopsy Pick-Up method during the breeding season. Ovarian tissue was immediately submitted to histological analysis (noncultured control; D0) or cultured in situ for 1 day (D1) or 7 days (D7) in either α-MEM or TCM-199 and submitted to histological analysis, generating five treatment groups: noncultured control, α-MEM:D1, TCM-199:D1, α-MEM:D7, and TCM-199:D7. Preantral follicles were evaluated for follicle class (primordial, transitional, primary, and secondary) and morphology (normal vs. abnormal). A total of 142 preantral follicles were analyzed in five replicates. No follicles were observed in the TCM-199:D7 treatment group. The proportion of primordial follicles was higher (P < 0.03) in the control compared to the α-MEM:D7 treatment group. The proportion of primary follicles was higher (P < 0.04) in the α-MEM:D7 treatment group compared to the control. The proportion of developing follicles (transitional, primary, and secondary) was higher (P < 0.03) in the α-MEM:D7 treatment group compared to the control group. There was a greater (P < 0.004) percentage of morphologically normal developing follicles in the α-MEM:D1 treatment group compared to the TCM-199:D1 treatment group. Overall, the percentage of morphologically normal follicles was higher in the control group (72%; P < 0.02) and α-MEM:D1 group (84%; P < 0.0001) compared to the α-MEM:D7 (27%) treatment group. Mean follicle diameter was greater (P < 0.04) in the α-MEM:D7 treatment group (40.6 ± 1.1 µm) compared to the control group (37.3 ± 0.7 µm). Mean oocyte diameter was greater in the α-MEM:D1 (31.0 ± 0.7 µm; P < 0.006), TCM-199:D1 (30.7 ± 1.8 µm; P < 0.006), and α-MEM:D7 (33.2 ± 1.8 µm; P < 0.006) treatment groups compared to the control group (27.4 ± 0.9 µm). In conclusion, based on these preliminary data, in vitro culture of equine ovarian fragments obtained in vivo via the Biopsy Pick-Up method promoted preantral follicle development and follicle and oocyte growth in α-MEM for 7 days, with some follicles remaining morphologically normal throughout the culture period.


Asunto(s)
Técnicas de Cultivo de Célula/veterinaria , Caballos/fisiología , Folículo Ovárico/citología , Animales , Biopsia/métodos , Biopsia/veterinaria , Medios de Cultivo , Femenino , Folículo Ovárico/crecimiento & desarrollo
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