Correlations among antiangiogenic factors and trace elements in hypertensive disorders of pregnancy

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Dendrimer nanocarriers for transport modulation across models of the pulmonary epithelium

The purpose of this study was to determine the effect of PEGylation on the interaction of poly(amidoamine) (PAMAM) dendrimer nanocarriers (DNCs) with in vitro and in vivo models of the pulmonary epithelium. Generation-3 PAMAM dendrimers with varying surface densities of PEG 1000 Da were synthesized and characterized. The results revealed that the apical to basolateral transport of DNCs across polarized Calu-3 monolayers increases with an increase in PEG surface density. DNC having the greatest number of PEG groups (n = 25) on their surface traversed at a rate 10-fold greater than its non-PEGylated counterpart, in spite of their larger size. This behavior was attributed to a significant reduction in charge density upon PEGylation. We also observed that PEGylation can be used to modulate cellular internalization. The total uptake of PEG-free DNC into polarized Calu-3 monolayers was 12% (w/w) vs 2% (w/w) for that with 25 PEGs. Polarization is also shown to be of great relevance in studying this in vitro model of the lung epithelium. The rate of absorption of DNCs administered to mice lungs increased dramatically when conjugated with 25 PEG groups, thus supporting the in vitro results. The exposure obtained for the DNC with 25PEG was determined to be very high, with peak plasma concentrations reaching 5 mu gmL(-1) within 3 h. The combined in vitro and in vivo results shown here demonstrate that PEGylation can be potentially used to modulate the internalization and transport of DNCs across the pulmonary epithelium. Modified dendrimers thereby may serve as a valuable platform that can be tailored to target the lung tissue for treating local diseases, or the circulation, using the lung as pathway to the bloodstream, for systemic delivery.

Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats

Exenatide extended-release (ER) is a microencapsulated formulation of the glucagon-like peptide 1-receptor agonist exenatide: It has a protracted pharmacokinetic profile that allows a once-weekly injection with comparable efficacy to insulin with an improved safety profile in type II diabetic people. Here, we studied the pharmacology of exenatide ER in 6 healthy cats. A single subcutaneous injection of exenatide ER (0.13 mg/kg) was administered on day 0. Exenatide concentrations were measured for 12 wk. A hyperglycemic clamp (target = 225 mg/dL) was performed on days 7 (clamp I) and 21 (clamp II) with measurements of insulin and glucagon concentrations. Glucose tolerance was defined as the amount of glucose required to maintain hyperglycemia during the clamp. Continuous glucose monitoring was performed on weeks 0, 2, and 6 after injection. Plasma concentrations of exenatide peaked at 1 h and 4 wk after injection. Comparing clamp I with clamp II, fasting blood glucose decreased (mean standard deviation = 11 8 mg/dL, P = 0.02), glucose tolerance improved (median [range] +33% 14%-138%], P = 0.04), insulin concentrations increased (+36.5% [-9.9% to 274.1%], P = 0.02), and glucagon concentrations decreased (-4.7% [0%-12.1%], P = 0.005). Compared with preinjection values on continuous glucose monitoring, glucose concentrations decreased and the frequency of readings <50 mg/dL increased at 2 and 6 wk after injection of exenatide ER. This did not correspond to clinical hypoglycemia. No other side effects were observed throughout the study. Exenatide ER was safe and effective in improving glucose tolerance 3 wk after a single injection. Further evaluation is needed to determine its safety, efficacy, and duration of action in diabetic cats. (C) 2015 Elsevier Inc. All rights reserved.

Effect of vitamin D supplementation alone on muscle function in postmenopausal women: a randomized, double-blind, placebo-controlled clinical trial

The present study investigates the effects of vitamin D on muscle function in postmenopausal women. It has been shown that vitamin D supplementation in postmenopausal women with hypovitaminosis D provides significant protective factor against sarcopenia, with significant increases in muscle strength and control of progressive loss of lean mass. We aimed to evaluate the effect of supplementation of vitamin D (VITD) alone on muscle function in younger postmenopausal women. In this double-blind, placebo-controlled clinical trial, 160 Brazilian postmenopausal women were randomized into two groups: VITD group consisting of patients receiving vitamin D3 1000 IU/day orally (n = 80) or placebo group (n = 80). Women with amenorrhea for more than 12 months and age 50-65 years, with a history of falls (previous 12 months), were included. The intervention time was 9 months, with assessments at two points, start and end. Lean mass was estimated by total-body dual-energy X-ray absorptiometry (DXA) and muscle strength by handgrip strength and chair rising test. The plasma concentrations of 25-hydroxyvitamin D [25(OH)D] were measured by high-performance liquid chromatography (HPLC). Statistical analysis was by intention to treat (ITT), using ANOVA, Student's t test, and Tukey's test. After 9 months, average values of 25(OH)D increased from 15.0 ± 7.5 to 27.5 ± 10.4 ng/ml (+45.4 %) in the VITD group and decreased from 16.9 ± 6.7 to 13.8 ± 6.0 ng/ml (-18.5 %) in the placebo group (p < 0.001). In the VITD group, there was significant increase in muscle strength (+25.3 %) of the lower limbs by chair rising test (p = 0.036). In women in the placebo group, there was considerable loss (-6.8 %) in the lean mass (p = 0.030). The supplementation of vitamin D alone in postmenopausal women provided significant protective factor against the occurrence of sarcopenia, with significant increases in muscle strength and control of progressive loss of lean mass.

Positive correlations between circulating adiponectin and MMP2 in preeclampsia pregnant

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)

Activity of neurons in the preoptic area and their participation in reproductive senescence: preliminary findings

Alterations in the hypothalamic-pituitary-gonadal axis in females determine the transition from regular to irregular reproductive cycles, with loss of fertility. Stimulation of noradrenergic neurons of the anteroventral periventricular neurons (AVPV) is essential for regular reproductive cycles. Therefore, we examined the activity of neurons of the AVPV and measure the noradrenaline (NE) of acyclic rats, in constant estrus, and compared it with that of cyclic rats in estrus. Female cyclic (4-5months) and acyclic (17-18months) rats were euthanized at 10, 14, and 18h in estrus. Brains were processed for immunoreactivity to antigens related to Fos (FRA) in AVPV, and the NE was determined by HPLC-ED. Plasma concentrations of LH, FSH, E2 and P4 were determined. In the acyclic animals, plasma LH was higher but the FSH was lower. There was decreasing P4 at different times, while the E2 was constant and lower in acyclic rats. FRA-ir expression in AVPV neurons of acyclic rats as well as turnover of NE was higher when compared with cyclic group. The preliminary findings showed increased activity in AVPV neurons in aging contribute to changes in the temporal pattern of neuroendocrine signaling, compromising the accuracy of inhibitory and stimulatory effects, causing irregularity in the estrous cycle and determining reproductive senescence.

Adrenomedullin induces pulmonary vasodilation but does not attenuate pulmonary hypertension in a sheep model of acute pulmonary embolism

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos da adrenomodulina no tratamento da hipertensão pulmonar induzida por microesferas em ovinos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estresse calórico sobre a luteólise de vacas holandesas não lactantes

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Farmacocinética do Benznidazol administrado em coelhos na forma de comprimidos de liberação imediata e comprimidos de liberação prolongada

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos do treinamento aeróbio no fator de crescimento endotelial vascular (VEGF), funções cognitivas e funcionalidade motora na Doença de Alzheimer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos da suplementação com semente de girassol em fêmeas bovinas na produção de oócitos e embriões in vitro

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeitos do desuso e da deficiência de estrógeno sobre a microarquitetura óssea e suas propriedades biomecânicas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeitos da administração de eritropoietina na dislipidemia e na hipertrofia ventricular esquerda de camundongos hiperlipidêmicos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito da progesterona na expressão do RNAm do receptor de LH e enzimas esteroidogênicas reguladoras do desenvolvimento folicular em células da granulosa de novilhas nelore

Pós-graduação em Zootecnia - FMVZ