Silver(I) 1,10-Phenanthroline Complexes Are Active against Fonsecaea Pedrosoi Viability and Negatively Modulate Its Potential Virulence Attributes

The genus Fonsecaea is one of the etiological agents of chromoblastomycosis (CBM), a chronic subcutaneous disease that is difficult to treat. This work aimed to evaluate the effects of copper(II), manganese(II) and silver(I) complexes coordinated with 1,10-phenanthroline (phen)/1,10- phenanthroline-5,6-dione (phendione) on Fonsecaea spp. Our results revealed that most of these complexes were able to inhibit F. pedrosoi, F. monophora and F. nubica conidial viability with minimum inhibitory concentration (MIC) values ranging from 0.6 to 100 M. The most effective complexes against F. pedrosoi planktonic conidial cells, the main etiologic agent of CBM, were [Ag(phen)2]ClO4 and [Ag2(3,6,9-tdda)(phen)4].EtOH, (tdda: 3,6,9-trioxaundecanedioate), displaying MIC values equal to 1.2 and 0.6 M, respectively. These complexes were effective in reducing the viability of F. pedrosoi biofilm formation and maturation. Silver(I) tdda-phen, combined with itraconazole, reduced the viability and extracellular matrix during F. pedrosoi biofilm development. Moreover, both silver(I) complexes inhibited either metallo- or aspartic-type peptidase activities of F. pedrosoi as well as its conidia into mycelia transformation and melanin production. In addition, the complexes induced the production of intracellular reactive oxygen species in F. pedrosoi. Taken together, our data corroborate the antifungal action of metal-phen complexes, showing they represent a therapeutic option for fungal infections, including CBM

Prevalence and Severity of Asthma, Rhinitis, and Atopic Eczema in 13- to 14-Year-Old Schoolchildren from Southern Brazil

The objective of this study was to investigate the prevalence and severity of asthma, rhinitis, and atopic eczema in schoolchildren from southern Brazil. A cross-sectional study was carried out with the International Study of Asthma and Allergies in Childhood phase III written questionnaire. The questionnaire was self-applied by 2,948 randomly selected schoolchildren aged 13 to 14 years. The lifetime prevalence rates of symptoms were as follows: wheezing, 40.8%; rhinitis, 40.7%; eczema, 13.6%; self-reported asthma, 14.6%; rhinitis, 31.4%; eczema, 13.4%. Rhinitis was reported by 55% of adolescents with current asthma (60% females vs 46.9% males). Girls 13 to 14 years of age had higher prevalence rates of asthma, rhinitis, and eczema than boys had. Atopic eczema was reported by 42.7% of girls and 31.4% of boys with asthma. The prevalence rates were statistically significant for symptoms of asthma, rhinitis, and atopic eczema in females. However, there were no statistically significant differences between the sexes in regard to reported asthma and bronchospasm induced by exercise

Impact of dense-water flow over a sloping bottom on open-sea circulation: Laboratory experiments and an Ionian Sea (Mediterranean) example

The North Ionian Gyre (NIG) displays prominent inversions on decadal scales. We investigate the role of internal forcing induced by changes in the horizontal pressure gradient due to the varying density of Adriatic Deep Water (AdDW), which spreads into the deep layers of the northern Ionian Sea. In turn, the AdDW density fluctuates according to the circulation of the NIG through a feedback mechanism known as the bimodal oscillating system. We set up laboratory experiments with a two-layer ambient fluid in a circular rotating tank, where densities of 1000 and 1015ĝ€¯kgĝ€¯m-3 characterize the upper and lower layers, respectively. From the potential vorticity evolution during the dense-water outflow from a marginal sea, we analyze the response of the open-sea circulation to the along-slope dense-water flow. In addition, we show some features of the cyclonic and anticyclonic eddies that form in the upper layer over the slope area. We illustrate the outcome of the experiments of varying density and varying discharge rates associated with dense-water injection. When the density is high (1020ĝ€¯kgĝ€¯m-3) and the discharge is large, the kinetic energy of the mean flow is stronger than the eddy kinetic energy. Conversely, when the density is lower (1010ĝ€¯kgĝ€¯m-3) and the discharge is reduced, vortices are more energetic than the mean flow - that is, the eddy kinetic energy is larger than the kinetic energy of the mean flow. In general, over the slope, following the onset of dense-water injection, the cyclonic vorticity associated with current shear develops in the upper layer. The vorticity behaves in a two-layer fashion, thereby becoming anticyclonic in the lower layer of the slope area. Concurrently, over the deep flat-bottom portion of the basin, a large-scale anticyclonic gyre forms in the upper layer extending partly toward a sloping rim. The density record shows the rise of the pycnocline due to the dense-water sinking toward the flat-bottom portion of the tank. We show that the rate of increase in the anticyclonic potential vorticity is proportional to the rate of the rise of the interface, namely to the rate of decrease in the upper-layer thickness (i.e., the upper-layer squeezing). The comparison of laboratory experiments with the Ionian Sea is made for a situation when the sudden switch from cyclonic to anticyclonic basin-wide circulation took place following extremely dense Adriatic water overflow after the harsh winter in 2012. We show how similar the temporal evolution and the vertical structure are in both laboratory and oceanic conditions. The demonstrated similarity further supports the assertion that the wind-stress curl over the Ionian Sea is not of paramount importance in generating basin-wide circulation inversions compared with the internal forcing

Continuous positive airway pressure and body position alter lung clearance of the radiopharmaceutical 99mtechnetium-diethylenetriaminepentaacetic acid (99mTc-DTPA)

The purpose of this investigation was to evaluate the pulmonary clearance rate of 99mtechnetium-diethylenetriaminepentaacetic acid (99mTc-DTPA) through the use of continuous positive airway pressure (CPAP) in different postures. It was a quasi-experimental study involving 36 healthy individuals with normal spirometry. 99mTc-DTPA, as aerosol, was nebulized for 3 min with the individual in a sitting position. The pulmonary clearance rate was assessed through pulmonary scintigraphy under spontaneous breathing and under 20 and 10 cmH2O CPAP in the sitting and supine positions. The clearance rate was expressed as the half-time (T1/2), that is, the time for the activity to decrease to 50% of the peak value. 20 cmH2O CPAP produced significant reduction of the T1/2 of 99mTc-DTPA in the supine position (P = 0.009) and in the sitting position (P = 0.005). However, 10 cmH2O CPAP did not alter the T1/2 of DTPA in both positions. The postural variation from supine to the sitting position with 10 cmH2O CPAP (P = 0.01) and 20 cmH2O (P = 0.02) also reduced the T1/2 of 99mTc-DTPA. High levels of positive pressure in normal lungs resulted in faster 99mTc-DTPA clearance. Moreover, the sitting position further increased the clearance rate of the 99mTc radioaerosol imaging in the two pressure levels studied.Key words: Continuous positive airway pressure, 99mTc-DTPA, scintigraphy, posture

Experimental Chemotherapy for Chagas Disease: A Morphological, Biochemical, and Proteomic Overview of Potential Trypanosoma cruzi Targets of Amidines Derivatives and Naphthoquinones

Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately eight million individuals in Latin America and is emerging in nonendemic areas due to the globalisation of immigration and nonvectorial transmission routes. Although CD represents an important public health problem, resulting in high morbidity and considerable mortality rates, few investments have been allocated towards developing novel anti-T. cruzi agents. The available therapy for CD is based on two nitro derivatives (benznidazole (Bz) and nifurtimox (Nf)) developed more than four decades ago. Both are far from ideal due to substantial secondary side effects, limited efficacy against different parasite isolates, long-term therapy, and their well-known poor activity in the late chronic phase. These drawbacks justify the urgent need to identify better drugs to treat chagasic patients. Although several classes of natural and synthetic compounds have been reported to act in vitro and in vivo on T. cruzi, since the introduction of Bz and Nf, only a few drugs, such as allopurinol and a few sterol inhibitors, have moved to clinical trials. This reflects, at least in part, the absence of well-established universal protocols to screen and compare drug activity. In addition, a large number of in vitro studies have been conducted using only epimastigotes and trypomastigotes instead of evaluating compounds' activities against intracellular amastigotes, which are the reproductive forms in the vertebrate host and are thus an important determinant in the selection and identification of effective compounds for further in vivo analysis. In addition, due to pharmacokinetics and absorption, distribution, metabolism, and excretion characteristics, several compounds that were promising in vitro have not been as effective as Nf or Bz in animal models of T. cruzi infection. In the last two decades, our team has collaborated with different medicinal chemistry groups to develop preclinical studies for CD and investigate the in vitro and in vivo efficacy, toxicity, selectivity, and parasite targets of different classes of natural and synthetic compounds. Some of these results will be briefly presented, focusing primarily on diamidines and related compounds and naphthoquinone derivatives that showed the most promising efficacy against T. cruzi

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Impact of protozoan cell death on parasite-host interactions and pathogenesis

PCD in protozoan parasites has emerged as a fascinating field of parasite biology. This not only relates to the underlying mechanisms and their evolutionary implications but also to the impact on the parasite-host interactions within mammalian hosts and arthropod vectors. During recent years, common functions of apoptosis and autophagy in protozoa and during parasitic infections have emerged. Here, we review how distinct cell death pathways in Trypanosoma, Leishmania, Plasmodium or Toxoplasma may contribute to regulation of parasite cell densities in vectors and mammalian hosts, to differentiation of parasites, to stress responses, and to modulation of the host immunity. The examples provided indicate crucial roles of PCD in parasite biology. The existence of PCD pathways in these organisms and the identification as being critical for parasite biology and parasite-host interactions could serve as a basis for developing new anti-parasitic drugs that take advantage of these pathways