Expression Profile and Distribution of Efhc1 Gene Transcript During Rodent Brain Development

One of the putative causative genes for juvenile myoclonic epilepsy (JME) is EFHC1. We report here the expression profile and distribution of Efhc1 messenger RNA (mRNA) during mouse and rat brain development. Real-time polymerase chain reaction revealed that there is no difference in the expression of Efhc1 mRNA between right and left hemispheres in both species. In addition, the highest levels of Efhc1 mRNA were found at intra-uterine stages in mouse and in adulthood in rat. In common, there was a progressive decrease in Efhc1 expression from 1-day-old neonates to 14-day-old animals in both species. In situ hybridization studies showed that rat and mouse Efhc1 mRNAs are expressed in ependymal cells of ventricle walls. Our findings suggest that Efhc1 expression is more important during initial phases of brain development and that at this stage it could be involved in key developmental mechanisms underlying JME.

Transdural motor cortex stimulation reverses neuropathic pain in rats: A profile of neuronal activation

Motor cortex stimulation (MCS) has been used to treat patients with neuropathic pain resistant to other therapeutic approaches; however, the mechanisms of pain control by MCS are still not clearly understood. We have demonstrated that MCS increases the nociceptive threshold of naive conscious rats, with opioid participation. In the present study, the effect of transdural MCS on neuropathic pain in rats subjected to chronic constriction injury of the sciatic nerve was investigated. In addition, the pattern of neuronal activation, evaluated by Fos and Zif268 immunolabel, was performed in the spinal cord and brain sites associated with the modulation of persistent pain. MCS reversed the mechanical hyperalgesia and allodynia induced by peripheral neuropathy. After stimulation, Fos immunoreactivity (Fos-IR) decreased in the dorsal horn of the spinal cord and in the ventral posterior lateral and medial nuclei of the thalamus, when compared to animals with neuropathic pain. Furthermore, the MCS increased the Fos-IR in the periaqueductal gray, the anterior cingulate cortex and the central and basolateral amygdaloid nuclei. Zif268 results were similar to those obtained for Fos, although no changes were observed for Zif268 in the anterior cingulate cortex and the central amygdaloid nucleus after MCS. The present findings suggest that MCS reverts neuropathic pain phenomena in rats, mimicking the effect observed in humans, through activation of the limbic and descending pain inhibitory systems. Further investigation of the mechanisms involved in this effect may contribute to the improvement of the clinical treatment of persistent pain. (c) 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Lack of effects of isoflavones on the lipid profile of Brazilian postmenopausal women

Objective: To evaluate the effects of soy isoflavone supplementation on profile lipid and endogenous hormone levels. Methods: In this double-blind, placebo-controlled Study, 47 post menopausal women 47-66 v of age received 40 mg of isoflavone (n = 25) or 40 mg of casein placebo (11 = 22). Cardiovascular risk factors were assessed by evaluating lipid profile at baseline and after 6 mo of treatment. To examine the effects of this regime on endogenous hormone levels, follicle-stimulating hormone and beta-estradiol were measured. Urinary isoflavone concentrations (genistein and daidzein) were measured as markers of both compliance and absorption using high performance liquid chromatography. Baseline characteristics were compared by the unpaired Student`s t-test. Within-group changes were determined by paired Student`s t-test and comparison between the isoflavone and casein placebo groups were determined by analysis of variance. Results: Lipid levels (low-density lipoprotein and total cholesterol) similarly decreased in both,groups. High-density lipoprotein increased significantly in both groups and cannot thus be attributable to treatment: the reason for Such variation is unknown and can be attributed to chance or to bias (even that of a real placebo effect in both groups or perhaps in spontaneous changes in exercise and dietary habits of patients after their inclusion). Furthermore, in both groups very low-density lipoprotein and triacylglycerol levels increased in a non-significant manner. Conclusion: The results of the present Study do not support any biologically significant estrogenic effects of isoflavone on the parameters assessed. Further research will he necessary to definitively assess the safety and efficacy of isoflavone. (C) 2008 Elsevier Inc. All rights reserved.

Microbiological profile of untreated subjects with localized aggressive periodontitis

Aim The microbial profile of localized aggressive periodontitis (LAgP) has not yet been determined. Therefore, the aim of this study was to evaluate the subgingival microbial composition of LAgP. Material and Methods One hundred and twenty subjects with LAgP (n=15), generalized aggressive periodontitis (GAgP, n=25), chronic periodontitis (ChP, n=30) or periodontal health (PH, n=50) underwent clinical and microbiological assessment. Nine subgingival plaque samples were collected from each subject and analysed for their content of 38 bacterial species using checkerboard DNA-DNA hybridization. Results Red complex and some orange complex species are the most numerous and prevalent periodontal pathogens in LAgP. The proportions of Aggregatibacter actinomycetemcomitans were elevated in shallow and intermediate pockets of LAgP subjects in comparison with those with GAgP or ChP, but not in deep sites. This species also showed a negative correlation with age and with the proportions of red complex pathogens. The host-compatible Actinomyces species were reduced in LAgP. Conclusion A. actinomycetemcomitans seems to be associated with the onset of LAgP, and Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Campylobacter gracilis, Eubacterium nodatum and Prevotella intermedia play an important role in disease progression. Successful treatment of LAgP would involve a reduction in these pathogens and an increase in the Actinomyces species.

Transcriptome and gene expression profile of ovarian follicle tissue of the triatomine bug Rhodnius prolixus

Insect oocytes grow in close association with the ovarian follicular epithelium (OFE), which escorts the oocyte during oogenesis and is responsible for synthesis and secretion of the eggshell. We describe a transcriptome of OFE of the triatomine bug Rhodnius prolixus, a vector of Chagas disease, to increase our knowledge of the role of FE in egg development. Random clones were sequenced from a cDNA library of different stages of follicle development. The transcriptome showed high commitment to transcription, protein synthesis, and secretion. The most abundant cDNA was a secreted (S) small, proline-rich protein with maximal expression in the vitellogenic follicle, suggesting a role in oocyte maturation. We also found Rp45, a chorion protein already described, and a putative chitin-associated cuticle protein that was an eggshell component candidate. Six transcripts coding for proteins related to the unfolded-protein response (UPR) by were chosen and their expression analyzed. Surprisingly, transcripts related to UPR showed higher expression during early stages of development and downregulation during late stages, when transcripts coding for S proteins participating in chorion formation were highly expressed. Several transcripts with potential roles in oogenesis and embryo development are also discussed. We propose that intense protein synthesis at the FE results in reticulum stress (RS) and that lowering expression of a set of genes related to cell survival should lead to degeneration of follicular cells at oocyte maturation. This paradoxical suppression of UPR suggests that ovarian follicles may represent an interesting model for studying control of RS and cell survival in professional S cell types. (C) 2011 Elsevier Ltd. All rights reserved.

Ethanol consumption and pineal melatonin daily profile in rats

It is well known that melatonin participates in the regulation of many important physiological functions such as sleep-wakefulness cycle, motor coordination and neural plasticity, and cognition. However, as there are contradictory results regarding the melatonin production diurnal profile under alcohol consumption, the aim of this paper was to study the phenomenology and mechanisms of the putative modifications on the daily profile of melatonin production in rats submitted to chronic alcohol intake. The present results show that rats receiving 10% ethanol in drinking water for 35 days display an altered daily profile of melatonin production, with a phase delay and a reduction in the nocturnal peak. This can be partially explained by a loss of the daily rhythm and the 25% reduction in tryptophan hydroxylase activity and, mainly, by a phase delay in arylalkylamine N-acetyltransferase gene expression and a 70% reduction in its peak activity. Upstream in the melatonin synthesis pathway, the results showed that noradrenergic signaling is impaired as well, with a decrease in beta 1 and alpha 1 adrenergic receptors` mRNA contents and in vitro sustained loss of noradrenergic-stimulated melatonin production by glands from alcohol-treated rats. Together, these results confirm the alterations in the daily melatonin profile of alcoholic rats and suggest the possible mechanisms for the observed melatonin synthesis modification.

Study of Blood Porphyrin Spectral Profile for Diagnosis of Chronic Renal Failure

The progression to end-stage renal failure is independent of the initial pathogenic mechanism. Metabolic acidosis is a common consequence of chronic renal failure that results from inadequate ammonium excretion and decreased tubular bicarbonate reabsorption. Protoporphyrin IX (PpIX) is the immediate metabolic precursor of the heme molecule. The purpose of this study was to evaluate the levels of erythrocytes protoporphyrin IX at an animal model during progressive renal disease. A total of 36 eight-week-old male Wistar rats were divided into six groups: Normal, 4 and 8 weeks after 5/6 nephrectomy (NX). Renal function was evaluated by creatinine clearance and plasma creatinine levels. The autofluorescence of erythrocytes porphyrin of healthy and NX rats was analyzed using fluorescence spectroscopy. Emission spectra were obtained by exciting the samples at 405 nm. Significant differences between normal and NX rats autofluorescence shape occurred in the 600-700 nm spectral region. A correlation was observed between emission band intensity at 635 nm and progression of renal disease.

Femtosecond laser ablation on dental hard tissues-Analysis of ablated profile near an interface using local effective intensity

This study evaluated the process of ablation produced by a Ti:Sapphire femtosecond laser under different average powers taking place at the enamel/dentin interface. Based on the geometry of ablated microcavities the effective intensity for ablation was obtained. This study shows the validity for the local effective intensity analysis and allows a quantification of the variation in the ablation geometry taking place at the interface of two naturally different materials. It shows that the variation of the diameter of the ablated region as a function of the cavity depth comes essentially from a mechanism of effective intensity attenuation, as a result of a series of complex effects. Additionally, our data are sufficient to predict that a discontinuity on the ablation profile will occur on the interface between two biological media: enamel-dentin, showing a suddenly jump on the ablated cavity dimensions.

Influence of fixed electric charges on potential profile across the squid axon membrane

The potential profile for a model of squid axon membrane has been determined for two physiological states: resting and action states. The non-linear Poisson-Boltzmann equation has been solved by considering the volumetric charge densities due to charges dissolved in an electrolytic solution and fixed on both glycocalyx and cytoplasmatic proteins. Results showing the features of the potential profile along the outer electrolytic region are similar for both resting and action states. However, the potential fall along glycocalyx at action state is lower than at resting. A small variation in the Na+ concentration drastically affects the surface membrane potentials and vice versa. We conclude that effects on the potential profile due to surface lipidic bilayer charge and contiguous electric double layers are more relevant than those provoked by fixed charges distributed along the cell cytoplasm. (c) 2007 Elsevier B.V. All rights reserved.

Synthesis and analgesic profile of conformationally constrained N-acylhydrazone analogues: Discovery of novel N-arylideneamino quinazolin-4(3H)-one compounds derived from natural safrole

In this work we reported the synthesis and evaluation of the analgesic, anti-inflammatory, and platelet anti-aggregating properties of new 3-(arylideneamino)-2-methyl-6,7-methylenedioxy-quinazolin-4 (3H)-one derivatives (3a-j), designed as conformationally constrained analogues of analgesic 1,3- benzodioxolyl-N- acylhydrazones (1) previously developed at LASSBio. Target compounds were synthesized in very good yields exploiting abundant Brazilian natural product safrole (2) as starting material. The pharmacological assays lead us to identify compounds LASSBio-1240 (3b) and LASSBio-1272 (3d) as new analgesic prototypes, presenting an antinociceptive pro. le more potent and effective than dipyrone and indomethacin used, respectively, as standards in AcOH-induced abdominal constrictions assay and in the formalin test. These results confirmed the success in the exploitation of conformation restriction strategy for identification of novel cyclic N-acylhydrazone analogues with optimized analgesic profile (C) 2009 Elsevier Ltd. All rights reserved.

Morphology and composition of gold in a lateritic profile, Fazenda Pison ""Garimpo"", Amazon, Brazil

This study describes the morphological evolution of gold grains in a lateritic weathering profile in an equatorial rainforest climate. Primary sources of gold are quartz veins associated with shallow granophyric intrusion. Gold grains were found in fresh ore, saprolite, transition zones, ferruginous duricrust, red latosol, and yellow latosol. Irregularly shaped grains predominate, with smaller proportions of dendritic and prismatic forms. Gold grains are weathered in the uppermost 10 m of the regolith. Mean gold grain size is maximum in the duricrust (> 125 mu m) and decreases progressively upward into the yellow latosol (<90 mu m). Voids and corrosion pits appear on grain surfaces, and progressive rounding is observed from the bottom of the profile to the top. Gold grains can be classified as either homogeneous or zoned with respect to their chemical composition. Homogeneous grains contain 2-15% Ag (mean 8.3%). Zoned grains have more variable Ag contents; grain cores have means of approximately 10% or 23% Ag, with Ag-poor zones of approximately 3.7% Ag along internal discontinuities and/or outer rims. Formation of Ag-poor rims is due to preferential depletion of silver. Processes responsible for duricrust formation may preserve some grains as large aggregates, but subsequent transformation into latosol further modifies them. (c) 2007 Elsevier Ltd. All rights reserved.

Columnar joints in the Patino Formation sandstones, Eastern Paraguay: a dynamic interaction between dyke intrusion, quartz dissolution and cooling-induced fractures

The Patino Formation sandstones, which crop out in Aregua neighborhood in Eastern Paraguay and show columnar joints near the contact zone with a nephelinite dyke, have as their main characteristics the high proportion of syntaxial quartz overgrowth and a porosity originated from different processes, initially by dissolution and later by partial filling and fracturing. Features like the presence of floating grains in the syntaxial cement, the transitional interpenetrative contact between the silica-rich cement and grains as well as the intense fracture porosity are strong indications that the cement has been formed by dissolution and reprecipitation of quartz from the framework under the effect of thermal expansion followed by rapid contraction. The increase of the silica-rich cement towards the dyke in association with the orthogonal disposition of the columns relative to dyke walls are indicative that the igneous body may represent the main heat source for the interstitial aqueous solutions previously existing in the sediments. At macroscopic scale, the increasing of internal tensions in the sandstones is responsible for the nucleation of polygons, leading to the individualization of prisms, which are interconnected by a system of joints, formed firstly on isotherm surfaces of low temperature and later on successive adjacent planes towards the dyke heat source.

Density-Profile Processes Describing Biological Signaling Networks: Almost Sure Convergence to Deterministic Trajectories

We introduce jump processes in R(k), called density-profile processes, to model biological signaling networks. Our modeling setup describes the macroscopic evolution of a finite-size spin-flip model with k types of spins with arbitrary number of internal states interacting through a non-reversible stochastic dynamics. We are mostly interested on the multi-dimensional empirical-magnetization vector in the thermodynamic limit, and prove that, within arbitrary finite time-intervals, its path converges almost surely to a deterministic trajectory determined by a first-order (non-linear) differential equation with explicit bounds on the distance between the stochastic and deterministic trajectories. As parameters of the spin-flip dynamics change, the associated dynamical system may go through bifurcations, associated to phase transitions in the statistical mechanical setting. We present a simple example of spin-flip stochastic model, associated to a synthetic biology model known as repressilator, which leads to a dynamical system with Hopf and pitchfork bifurcations. Depending on the parameter values, the magnetization random path can either converge to a unique stable fixed point, converge to one of a pair of stable fixed points, or asymptotically evolve close to a deterministic orbit in Rk. We also discuss a simple signaling pathway related to cancer research, called p53 module.

Effects of the antimicrobial peptide gomesin on the global gene expression profile, virulence and biofilm formation of Xylella fastidiosa

In the xylem vessels of susceptible hosts, such as citrus trees, Xylella fastidiosa forms biofilm-like colonies that can block water transport, which appears to correlate to disease symptoms. Besides aiding host colonization, bacterial biofilms play an important role in resistance against antimicrobial agents, for instance antimicrobial peptides (AMPs). Here, we show that gomesin, a potent AMP from a tarantula spider, modulates X. fastidiosa gene expression profile upon 60 min of treatment with a sublethal concentration. DNA microarray hybridizations revealed that among the upregulated coding sequences, some are related to biofilm production. In addition, we show that the biofilm formed by gomesin-treated bacteria is thicker than that formed by nontreated cells or cells exposed to streptomycin. We have also observed that the treatment of X. fastidiosa with a sublethal concentration of gomesin before inoculation in tobacco plants correlates with a reduction in foliar symptoms, an effect possibly due to the trapping of bacterial cells to fewer xylem vessels, given the enhancement in biofilm production. These results warrant further investigation of how X. fastidiosa would respond to the AMPs produced by citrus endophytes and by the insect vector, leading to a better understanding of the mechanism of action of these molecules on bacterial virulence.

Thermoanalytical Characterization and Dissolution Profiles Studies of Metronidazole Tablets

In the present study dissolution tests and thermoanalytical (TA) techniques were applied to metronidazole tablets from five laboratories (R, G, SA, SB, SC) available on the Brazilian market. The TA profiles indicated that in some formulations interactions between components led to eutectic products with lower melting points than metronidazole. The formulations SB and SC showed dissolution profiles that did not agree with published standards, confirming the TA results. All dissolution data were mathematically compared with kinetic models of release, demonstrating the main release mechanism was first order in all the tablets. The formulations were statistically compared by ANOVA and post-hoc tests (Tukey and Newman-Keuls), reveling significant differences in dissolution efficiency (DE).