The anti-epileptic drug Valproic Acid (VPA) inhibits steroidogenesis in bovine theca and granulosa cells in vitro

Valproic acid (VPA) is used widely to treat epilepsy and bipolar disorder. Women undergoing VPA treatment reportedly have an increased incidence of polycystic ovarian syndrome (PCOS)-like symptoms including hyperandrogenism and oligo- or amenorrhoea. To investigate potential direct effects of VPA on ovarian steroidogenesis we used primary bovine theca (TC) and granulosa (GC) cells maintained under conditions that preserve their 'follicular' phenotype. Effects of VPA (7.8-500 µg/ml) on TC were tested with/without LH. Effects of VPA on GC were tested with/without FSH or IGF analogue. VPA reduced (P<0.0001) both basal (70% suppression; IC(50) 67±10 µg/ml) and LH-induced (93% suppression; IC(50) 58±10 µg/ml) androstenedione secretion by TC. VPA reduced CYP17A1 mRNA abundance (>99% decrease; P<0.0001) with lesser effects on LHR, STAR, CYP11A1 and HSD3B1 mRNA (<90% decrease; P<0.05). VPA only reduced TC progesterone secretion induced by the highest (luteinizing) LH dose tested; TC number was unaffected by VPA. At higher concentrations (125-500 µg/ml) VPA inhibited basal, FSH- and IGF-stimulated estradiol secretion (P<0.0001) by GC without affecting progesterone secretion or cell number. VPA reversed FSH-induced upregulation of CYP19A1 and HSD17B1 mRNA abundance (P<0.001). The potent histone deacetylase (HDAC) inhibitors trichostatin A and scriptaid also suppressed TC androstenedione secretion and granulosal cell oestrogen secretion suggesting that the action of VPA reflects its HDAC inhibitory properties. In conclusion, these findings refute the hypothesis that VPA has a direct stimulatory action on TC androgen output. On the contrary, VPA inhibits both LH-dependent androgen production and FSH/IGF-dependent estradiol production in this in vitro bovine model, likely by inhibition of HDAC.

Inverse modeling of the 14C bomb pulse in stalagmites to constrain the dynamics of soil carbon cycling at selected European cave sites

The decomposition of soil organic matter (SOM) is temperature dependent, but its response to a future warmer climate remains equivocal. Enhanced rates of decomposition of SOM under increased global temperatures might cause higher CO2 emissions to the atmosphere, and could therefore constitute a strong positive feedback. The magnitude of this feedback however remains poorly understood, primarily because of the difficulty in quantifying the temperature sensitivity of stored, recalcitrant carbon that comprises the bulk (>90%) of SOM in most soils. In this study we investigated the effects of climatic conditions on soil carbon dynamics using the attenuation of the 14C ‘bomb’ pulse as recorded in selected modern European speleothems. These new data were combined with published results to further examine soil carbon dynamics, and to explore the sensitivity of labile and recalcitrant organic matter decomposition to different climatic conditions. Temporal changes in 14C activity inferred from each speleothem was modelled using a three pool soil carbon inverse model (applying a Monte Carlo method) to constrain soil carbon turnover rates at each site. Speleothems from sites that are characterised by semi-arid conditions, sparse vegetation, thin soil cover and high mean annual air temperatures (MAATs), exhibit weak attenuation of atmospheric 14C ‘bomb’ peak (a low damping effect, D in the range: 55–77%) and low modelled mean respired carbon ages (MRCA), indicating that decomposition is dominated by young, recently fixed soil carbon. By contrast, humid and high MAAT sites that are characterised by a thick soil cover and dense, well developed vegetation, display the highest damping effect (D = c. 90%), and the highest MRCA values (in the range from 350 ± 126 years to 571 ± 128 years). This suggests that carbon incorporated into these stalagmites originates predominantly from decomposition of old, recalcitrant organic matter. SOM turnover rates cannot be ascribed to a single climate variable, e.g. (MAAT) but instead reflect a complex interplay of climate (e.g. MAAT and moisture budget) and vegetation development.

Respostas hematológicas em tuvira após anestesia com diferentes concentrações de óleo de cravo

The hematological responses in tuvira (Gymnotus aff. inaequilabiatus) after clove oil anesthesia at different concentrations were evaluated in this study. Fish (n = 25) with average length of 26.8 +/- 2.4 cm and weighing 94.4 +/- 23.6 g were separated in five groups composed with five animals each and submitted individually to respective concentrations of clove oil: 40, 80, 120, 160 and 200 mg L-1. After anesthetic recuperation, the blood samples collection were performed, as well as complete hemogram. The results were submitted to analysis of variance, Tukey test (P<0.05) and Sperman's correlation analysis. There was an increase (P<0.05) on hematocrit, red blood cells count, thrombocytes count and in the values of neutrophils with increasing of clove oil concentrations. In addition, positive correlation (P<0.05) were observed on total leukocytes, as well as negative linear correlation (P<0.05) for mean corpuscular hemoglobin concentration (MCHC). The clove oil anesthesia on tuvira cause hematological changes with an effect dose-dependent. These changes should be considered mainly in future studies designed to establish the reference values of hematologic variables for this specie.

Efeito da deriva de Glyphosate sobre algumas características fisiológicas em plantas de eucalipto

This work aims to evaluate the effects of a simulated drift of glyphosate at different doses on some physiological characteristics of Eucalyptus grandis. A completely randomized design with five replications was used, where each pot contained an eucalyptus plant and was considered as one repetition. The plants received doses of glyphosate corresponding to 0, 30, 60, 90 and 120g.ha(-1), in the Scout (R) commercial formulation: The application was performed in three forms: leaves, stem and whole plant (leaf + stem). For foliar application, the stem was covered with plastic tape to avoid being hit by the solution, and leaves with a plastic bag when the stem was spayed. The application was performed by means of a steady spray gun equipped with four XR 11002 tips, with a pressure of 200Kpa and a volume of 2001 ha(-1). Stomatal conductance, transpiration and leaf temperature were measured at 7 days after application (DAA). The eucalypt plants receiving applications in leaves and whole plant showed, at the highest glyphosate dosis (120g.ha(-1)), a transpiration reduced by 22% and an 18% increase of stomatal resistance at 7 DAA. The lowest dose (30g-ha(-1)) applied to the whole plant caused a transpiration stimulation of 18%, and a leaf to air difference in temperature of -1.66 degrees C, while the difference between the highest and lowest dose used was 3.5 degrees C.

In vitro cytotoxicity and in vivo-biocompatibility of contemporary resin-modified glass-ionomer cements

Objectives. To evaluate the effects of current resin-modified glass-ionomer cements (RMGICs) applied on culture of cells or implanted into subcutaneous tissue of rats.Methods. Experiment 1 - Thirty round-shaped samples of every RMGICs: Rely X Luting Cement (RL), Vitremer (VM), and Vitrebond (VB) were placed into wells with 1.1 mL of culture medium (DMEM), and incubated for 24,48 or 72 h. The extracts from every sample were applied on the MDPC-23 cells. Fresh DMEM was used as control group. The MTT assay was carried out for mitochondrial respiration. Experiment 2 - Fifty-four polyethylene tubes filled with the experimental materials were implanted into the dorsal subcutaneous tissue of rats. At 7, 30, and 90 days the animals were killed and the biopsies were processed for histological evaluation.Results. Experiment 1 - Both time of elution and material significantly influenced cell respiratory activity. in general, the extracts obtained at 24 h were less cytotoxic than 48 and 72 h incubation. The cytotoxic effect of VM and RL were not statistically different (P < 0.05) for the 24-hour period. VB showed the highest cytotoxic effect. Experiment 2 - All RMGICs elicited at 7 days a moderate to intense inflammatory reaction which decreased over time. However, connective healing occurred for most of samples at 90-day evaluation.Significance. Glass-ionomer cements may cause noticeable inflammatory response when in direct contact to connective tissue. The toxic effects of this kind of soluble material depend on the amount of components released in the aqueous environment. (C) 2005 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Nutrição e produtividade da nogueira-macadâmia em função de doses de nitrogênio

The objective of this work was to evaluate the influence of nitrogen doses on mineral nutrition and yield of macadamia nut (Macadamia integrifolia). The experiment was carried out during three agricultural years, in Jaboticabal, SP, Brazil. The experimental design was a complete block with four replicates. Five doses of N (0, 50, 100, 150, and 200 kg ha-1 per year), applied as urea, were evaluated. The increase in N doses increased the nutrient concentration in the leaves and the yield of nuts and almonds. Ca, Mg, and S contents decreased and the ones of Fe and Mg increased linearly with N fertilization. Nut and almond yields were positively correlated with leaf N concentration, and the range from 14 to 18 g kg-1 allowed the highest yields. The dose of 150 kg ha-1 of N per year provides higher nut yields, without reducing the recovery rate of almonds.

Caracterização agronômica e morfológica de populações de milho

Pós-graduação em Agronomia (Genética e Melhoramento de Plantas) - FCAV

Chemical reduction of carboxyl groups in heparin abolishes its vasodilatory activity

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

Ação de enxaguatórios clareadores e sua associação ao clareamento caseiro com peróxido de carbamida

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Inhibition of nuclear factor-kappa B by dehydroxymethylepoxyquinomicin induces schedule-dependent chemosensitivity to anticancer drugs and enhances chemoinduced apoptosis in osteosarcoma cells

Osteosarcoma (OS) is the most common primary malignant bone tumor, usually developing in children and adolescents, and is highly invasive and metastatic, potentially developing chemoresistance. Thus, novel effective treatment regimens are urgently needed. This study was the first to investigate the anticancer effects of dehydroxymethylepoxyquinomicin (DHMEQ), a highly specific nuclear factor-kappa B (NF-kappa B) inhibitor, on the OS cell lines HOS and MG-63. We demonstrate that NF-kappa B blockade by DHMEQ inhibits proliferation, decreases the mitotic index, and triggers apoptosis of OS cells. We examined the effects of combination treatment with DHMEQ and cisplatin, doxorubicin, or methotrexate, drugs commonly used in OS treatment. Using the median effect method of Chou and Talalay, we evaluated the combination indices for simultaneous and sequential treatment schedules. In all cases, combination with a chemotherapeutic drug produced a synergistic effect, even at low single-agent cytotoxic levels. When cells were treated with DHMEQ and cisplatin, a more synergistic effect was obtained using simultaneous treatment. For the doxorubicin and methotrexate combination, a more synergistic effect was achieved with sequential treatment using DHMEQ before chemotherapy. These synergistic effects were accompanied by enhancement of chemoinduced apoptosis. Interestingly, the highest apoptotic effect was reached with sequential exposure in both cell lines, independent of the chemotherapeutic agent used. Likewise, DHMEQ decreased cell invasion and migration, crucial steps for tumor progression. Our data suggest that combining DHMEQ with chemotherapeutic drugs might be useful for planning new therapeutic strategies for OS treatment, mainly in resistant and metastatic cases. Anti-Cancer Drugs 23:638-650 (C) 2012 Wolters Kluwer Health broken vertical bar Lippincott Williams & Wilkins.

Chemical reduction of carboxyl groups in heparin abolishes its vasodilatory activity

Previous studies have shown that heparin induces vascular relaxation via integrin-dependent nitric oxide (NO)-mediated activation of the muscarinic receptor. The aim of this study was to identify the structural features of heparin that are necessary for the induction of vasodilatation. To address this issue, we tested heparin from various sources for their vasodilatation activities in the rat aorta ring. Structural and chemical characteristics of heparin, such as its molecular weight and substitution pattern, did not show a direct correlation with the vasodilation activity. Principal component analysis (PCA) of circular dichroism (CD), 1H-nuclear magnetic resonance (NMR) and vasodilation activity measurements confirmed that there is no direct relationship between the physico-chemical nature and vasodilation activity of the tested heparin samples. To further understand these observations, unfractionated heparin (UFH) from bovine intestinal mucosa, which showed the highest relaxation effect, was chemically modified. Interestingly, non-specific O- and N-desulfation of heparin reduced its anticoagulant, antithrombotic, and antihemostatic activities, but had no effect on its ability to induce vasodilation. On the other hand, chemical reduction of the carboxyl groups abolished heparin-induced vasodilation and reduced the affinity of heparin toward the extracellular matrix (ECM). In addition, dextran and dextran sulfate (linear non-sulfated and highly sulfated polysaccharides, respectively) did not induce significant relaxation, showing that the vasodilation activity of polysaccharides is neither charge-dependent nor backbone unspecific. Our results suggest that desulfated heparin molecules may be used as vasoactive agents due to their low side effects. J. Cell. Biochem. 113: 13591367, 2012. (c) 2011 Wiley Periodicals, Inc.

In vitro cytotoxicity of white MTA, MTA Fillapex® and Portland cement on human periodontal ligament fibroblasts

The aim of this study was to compare the in vitro cytotoxicity of white mineral trioxide aggregate (MTA), MTA Fillapex® and Portland cement (PC) on human cultured periodontal ligament fibroblasts. Periodontal ligament fibroblast culture was established and the cells were used for cytotoxic tests after the fourth passage. Cell density was set at 1.25 X10 4 cells/well in 96-well plates. Endodontic material extracts were prepared by placing sealer/cement specimens (5X3mm) in 1mL of culture medium for 72 h. The extracts were then serially two-fold diluted and inserted into the cell-seeded wells for 24, 48 and 72 h. MTT assay was employed for analysis of cell viability. Cell supernatants were tested for nitric oxide using the Griess reagent system. MTA presented cytotoxic effect in undiluted extracts at 24 and 72 h. MTA Fillapex® presented the highest cytotoxic levels with important cell viability reduction for pure extracts and at ½ and ¼ dilutions. In this study, PC did not induce alterations in fibroblast viability. Nitric oxide was detected in extract-treated cell supernatants and also in the extracts only, suggesting presence of nitrite in the soluble content of the tested materials. In the present study, MTA Fillapex displayed the highest cytotoxic effect on periodontal ligament fibroblasts followed by white MTA and PC.

Use of ampicillin-sulbactam for treatment of experimental meningitis caused by a beta-lactamase-producing strain of Escherichia coli K-1

We evaluated the pharmacokinetics and therapeutic efficacy of ampicillin combined with sulbactam in a rabbit model of meningitis due to a beta-lactamase-producing strain of Escherichia coli K-1. Ceftriaxone was used as a comparison drug. The MIC and MBC were 32 and greater than 64 micrograms/ml (ampicillin), greater than 256 and greater than 256 micrograms/ml (sulbactam), 2.0 and 4.0 micrograms/ml (ampicillin-sulbactam [2:1 ratio, ampicillin concentration]) and 0.125 and 0.25 micrograms/ml (ceftriaxone). All antibiotics were given by intravenous bolus injection in a number of dosing regimens. Ampicillin and sulbactam achieved high concentrations in cerebrospinal fluid (CSF) with higher dose regimens, but only moderate bactericidal activity compared with that of ceftriaxone was obtained. CSF bacterial titers were reduced by 0.6 +/- 0.3 log10 CFU/ml/h with the highest ampicillin-sulbactam dose used (500 and 500 mg/kg of body weight, two doses). This was similar to the bactericidal activity achieved by low-dose ceftriaxone (10 mg/kg), while a higher ceftriaxone dose (100 mg/kg) produced a significant increase in bactericidal activity (1.1 +/- 0.4 log10 CFU/ml/h). It appears that ampicillin-sulbactam, despite favorable CSF pharmacokinetics in animals with meningitis, may be of limited value in the treatment of difficult-to-treat beta-lactamase-producing bacteria, against which the combination shows only moderate in vitro activity.

Inverse modelling of the 14C bomb pulse in stalagmites to constrain the dynamics of soil carbon cycling at selected European cave sites

The decomposition of soil organic matter (SOM) is temperature dependent, but its response to a future warmer climate remains equivocal. Enhanced rates of decomposition of SOM under increased global temperatures might cause higher CO2 emissions to the atmosphere, and could therefore constitute a strong positive feedback. The magnitude of this feedback however remains poorly understood, primarily because of the difficulty in quantifying the temperature sensitivity of stored, recalcitrant carbon that comprises the bulk (>90%) of SOM in most soils. In this study we investigated the effects of climatic conditions on soil carbon dynamics using the attenuation of the 14C ‘bomb’ pulse as recorded in selected modern European speleothems. These new data were combined with published results to further examine soil carbon dynamics, and to explore the sensitivity of labile and recalcitrant organic matter decomposition to different climatic conditions. Temporal changes in 14C activity inferred from each speleothem was modelled using a three pool soil carbon inverse model (applying a Monte Carlo method) to constrain soil carbon turnover rates at each site. Speleothems from sites that are characterised by semi-arid conditions, sparse vegetation, thin soil cover and high mean annual air temperatures (MAATs), exhibit weak attenuation of atmospheric 14C ‘bomb’ peak (a low damping effect, D in the range: 55–77%) and low modelled mean respired carbon ages (MRCA), indicating that decomposition is dominated by young, recently fixed soil carbon. By contrast, humid and high MAAT sites that are characterised by a thick soil cover and dense, well developed vegetation, display the highest damping effect (D = c. 90%), and the highest MRCA values (in the range from 350 ± 126 years to 571 ± 128 years). This suggests that carbon incorporated into these stalagmites originates predominantly from decomposition of old, recalcitrant organic matter. SOM turnover rates cannot be ascribed to a single climate variable, e.g. (MAAT) but instead reflect a complex interplay of climate (e.g. MAAT and moisture budget) and vegetation development.

Impact of anti-inflammatory treatment on the onset of uveitis in juvenile idiopathic arthritis: Longitudinal analysis from a nation-wide paediatric rheumatological database

PURPOSE Based on a nation-wide database, this study analysed the influence of methotrexate (MTX), TNF inhibitors and a combination of the two on uveitis occurrence in JIA patients. METHODS Data from the National Paediatric Rheumatological Database in Germany were used in this study. Between 2002 and 2013, data from JIA patients were annually documented at the participating paediatric rheumatological sites. Patients with JIA disease duration of less than 12 months at initial documentation and ≥2 years of follow-up were included in this study. The impact of anti-inflammatory treatment on the occurrence of uveitis was evaluated by discrete-time survival analysis. RESULTS A total of 3,512 JIA patients (mean age 8.3±4.8 years, female 65.7%, ANA-positive 53.2%, mean age at arthritis onset 7.8±4.8 years) fulfilled the inclusion criteria. Mean total follow-up time was 3.6±2.4 years. Uveitis developed in a total of 180 patients (5.1%) within one year after arthritis onset. Uveitis onset after the first year was observed in another 251 patients (7.1%). DMARD treatment in the year before uveitis onset significantly reduced the risk for uveitis: MTX (HR 0.63, p=0.022), TNF inhibitors (HR 0.56, p<0.001) and a combination of the two (HR 0.10, p<0.001). Patients treated with MTX within the first year of JIA had an even a lower uveitis risk (HR 0.29, p<0.001). CONCLUSION The use of DMARDs in JIA patients significantly reduced the risk for uveitis onset. Early MTX use within the first year of disease and the combination of MTX with a TNF inhibitor had the highest protective effect. This article is protected by copyright. All rights reserved.