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1.
Phys Rev Lett ; 130(21): 212701, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37295108

RESUMO

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.


Assuntos
Hélio , Hidrogênio , Modelos Estatísticos , Nêutrons
2.
Alcohol ; 99: 49-58, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34942330

RESUMO

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.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Pré-Escolar , Suplementos Nutricionais , Feminino , Humanos , Masculino , Micronutrientes , Gravidez , Tempo de Reação , Ucrânia
4.
Phys Rev Lett ; 125(6): 062501, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32845657

RESUMO

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.

5.
Phys Rev Lett ; 122(5): 052701, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30822026

RESUMO

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.

6.
Genome Announc ; 5(45)2017 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-29122874

RESUMO

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.

7.
Mol Psychiatry ; 22(2): 273-279, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27217154

RESUMO

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.


Assuntos
Transtorno Autístico/etiologia , Quimiocinas/efeitos adversos , Citocinas/efeitos adversos , Adulto , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/etiologia , Transtorno Autístico/complicações , Estudos de Casos e Controles , Quimiocinas/sangue , Criança , Desenvolvimento Infantil , Transtornos Globais do Desenvolvimento Infantil/epidemiologia , Transtornos Globais do Desenvolvimento Infantil/etiologia , Pré-Escolar , Citocinas/sangue , Deficiências do Desenvolvimento/complicações , Feminino , Humanos , Lactente , Deficiência Intelectual/etiologia , Masculino , Mães , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia
8.
Int J Obes (Lond) ; 41(2): 225-232, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27840416

RESUMO

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.


Assuntos
Regulação do Apetite/fisiologia , Duodeno/metabolismo , Nutrição Enteral , Esvaziamento Gástrico/fisiologia , Glucose/administração & dosagem , Incretinas/metabolismo , Obesidade/fisiopatologia , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Duodeno/fisiopatologia , Feminino , Polipeptídeo Inibidor Gástrico/metabolismo , Motilidade Gastrointestinal , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Teste de Tolerância a Glucose , Humanos , Masculino , Obesidade/metabolismo , Período Pós-Prandial
9.
Alcohol ; 49(7): 647-56, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26493109

RESUMO

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.


Assuntos
Depressores do Sistema Nervoso Central/efeitos adversos , Suplementos Nutricionais , Etanol/efeitos adversos , Transtornos do Espectro Alcoólico Fetal/prevenção & controle , Processos Mentais/efeitos dos fármacos , Micronutrientes , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal/psicologia , Adulto , Colina/administração & dosagem , Colina/uso terapêutico , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Aprendizagem/efeitos dos fármacos , Testes Neuropsicológicos , Gravidez , Sarcosina/análogos & derivados , Sarcosina/metabolismo , Fatores Socioeconômicos , Ucrânia
10.
Phys Rev Lett ; 114(21): 212501, 2015 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-26066430

RESUMO

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.

11.
Heredity (Edinb) ; 115(5): 452-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26014526

RESUMO

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.


Assuntos
Galliformes/genética , Genética Populacional , Cromossomos Sexuais/genética , Animais , Feminino , Galliformes/classificação , Frequência do Gene , Masculino , América do Norte , Polimorfismo de Nucleotídeo Único , Densidade Demográfica , Análise de Sequência de DNA , Comportamento Sexual Animal
12.
Diabet Med ; 32(11): 1500-3, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25981372

RESUMO

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.


Assuntos
Carboidratos da Dieta/metabolismo , Duodeno/metabolismo , Esvaziamento Gástrico , Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Mucosa Intestinal/metabolismo , Adulto , Algoritmos , Glicemia/análise , Carboidratos da Dieta/administração & dosagem , Glucose/administração & dosagem , Carga Glicêmica , Humanos , Insulina/sangue , Resistência à Insulina , Secreção de Insulina , Absorção Intestinal , Intubação Gastrointestinal , Cinética , Masculino
13.
Nutr Diabetes ; 5: e156, 2015 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-25985092

RESUMO

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.

14.
Cereb Cortex ; 25(12): 4761-71, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25092900

RESUMO

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.


Assuntos
Atenção/fisiologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiopatologia , Etanol/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Percepção Espacial/fisiologia , Percepção Visual/fisiologia , Adolescente , Atenção/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Mapeamento Encefálico , Criança , Desenvolvimento Infantil , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Lobo Parietal/efeitos dos fármacos , Lobo Parietal/crescimento & desenvolvimento , Lobo Parietal/fisiopatologia , Gravidez , Percepção Espacial/efeitos dos fármacos , Percepção Visual/efeitos dos fármacos
15.
Diabet Med ; 32(5): 595-600, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25388434

RESUMO

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.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/fisiopatologia , Polipeptídeo Inibidor Gástrico/fisiologia , Glucose/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Fosfato de Sitagliptina/farmacologia , Administração Oral , Idoso , Pressão Sanguínea/fisiologia , Diabetes Mellitus Tipo 2/metabolismo , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Inibidores da Dipeptidil Peptidase IV/farmacologia , Método Duplo-Cego , Duodeno/efeitos dos fármacos , Duodeno/metabolismo , Glucose/administração & dosagem , Glucose/metabolismo , Frequência Cardíaca/fisiologia , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Masculino , Estudos Retrospectivos , Fosfato de Sitagliptina/administração & dosagem , Fatores de Tempo
16.
Pediatr Blood Cancer ; 62(4): 598-602, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25546733

RESUMO

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.


Assuntos
Neoplasias Renais , Recidiva Local de Neoplasia , Topotecan/administração & dosagem , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Inibidores da Topoisomerase I , Tumor de Wilms/tratamento farmacológico , Tumor de Wilms/mortalidade , Tumor de Wilms/patologia
17.
Phys Rev Lett ; 112(17): 172701, 2014 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-24836240

RESUMO

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.

18.
Diabetologia ; 56(6): 1236-42, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23471488

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hiperglicemia/complicações , Comprimidos com Revestimento Entérico/uso terapêutico , Área Sob a Curva , Glicemia/metabolismo , Colo/metabolismo , Estudos Cross-Over , Feminino , Glucagon/metabolismo , Humanos , Íleo/metabolismo , Insulina/metabolismo , Ácidos Láuricos/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Fatores de Tempo
19.
Theriogenology ; 79(6): 911-7, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23434205

RESUMO

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.


Assuntos
Técnicas de Cultura de Células/veterinária , Cavalos/fisiologia , Folículo Ovariano/citologia , Animais , Biópsia/métodos , Biópsia/veterinária , Meios de Cultura , Feminino , Folículo Ovariano/crescimento & desenvolvimento
20.
Diabet Med ; 30(5): e185-8, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23350946

RESUMO

AIM: To evaluate the prognosis of diabetic gastroparesis. METHODS: Eighty-six patients with diabetes had measurements of gastric emptying of a mixed meal using a dual isotope test of solid and liquid meal components, mean blood glucose levels, HbA1c , upper gastrointestinal symptoms and autonomic nerve function performed in 1984-1989. These patients were followed up in 2011, after a mean period of ~25 years. RESULTS: Of the 86 patients, gastric emptying of solid (the percentage remaining in the stomach at 100 min) was delayed in 35 (41%), and of liquid (the time taken for 50% of the liquid to empty) was delayed in 38 (44%). In 2011, 53 patients were known to be alive, 29 had died and four were lost to follow-up. In those who had died, both age at baseline (P < 0.001) and the score for autonomic nerve dysfunction (P < 0.001) were greater than those who were alive, while there was no difference in emptying of either the solid or liquid between the two groups. When patients with delayed gastric emptying were divided according to the median value ('delayed' and 'markedly delayed'), mortality tended to be greater in the 'markedly delayed' group for both solids (P = 0.12) and liquids (P = 0.09). Of the 82 patients who could be followed up, 23 of the 35 (66%) with delayed gastric emptying of solid and 25 of 38 (66%) with delayed gastric emptying of liquid were alive. After adjustment for age and autonomic dysfunction, there was no association between gastric emptying of either solid or liquid and death. CONCLUSIONS: Over a period of ~25 years, diabetic gastroparesis is apparently not usually associated with a poor prognosis, or increased mortality. ABBREVIATIONS: T100 min, the percentage remaining in the stomach at 100 mins; T50%, the time taken for 50% of the liquid to empty.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/etiologia , Gastroparesia/etiologia , Adolescente , Adulto , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/fisiopatologia , Feminino , Seguimentos , Esvaziamento Gástrico , Gastroparesia/sangue , Gastroparesia/fisiopatologia , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Tempo
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