The effect of spider toxin PhTx3-4, ω-conotoxins MVIIA and MVIIC on glutamate uptake and on capsaicin-induced glutamate release and [Ca2+]i in spinal cord synaptosomes.

In spinal cord synaptosomes, the spider toxin PhTx3-4 inhibited capsaicin-stimulated release of glutamate in both calcium-dependent and -independent manners. In contrast, the conus toxins, ω-conotoxin MVIIA and xconotoxin MVIIC, only inhibited calcium-dependent glutamate release. PhTx3-4, but not ω-conotoxin MVIIA or xconotoxin MVIIC, is able to inhibit the uptake of glutamate by synaptosomes, and this inhibition in turn leads to a decrease in the Ca(2+)-independent release of glutamate.

Differential effects of p,p'-DDE on testis and liver mitochondria: implications for reproductive toxicology.

The release of environmental contaminants can contribute to impaired male fertility. The bioenergetics of isolated liver mitochondria have been used as a toxicological indicator, an inexpensive first line model to screen possible effects of several substances. Here we report the effects of 2,2-bis(4-chlorophenyl)-1,1-dichloro-ethylene (DDE) on the bioenergetical parameters of testicular mitochondria.

Developmental biology of the Brazilian 'Armed' spider Phoneutria nigriventer (Keyserling, 1891): microanatomical and molecular analysis of the embryonic stages.

Phoneutria (Ctenidae) is among the most dangerous venomous spiders in Brazil. Its venom is composed of a mixture of pharmacologically active components, some of which have been quite extensively studied due to their potentiality as models for new pharmaceutical drugs. Nevertheless, literature data on the venom-producing glands are very limited.

Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging.

Aim: To evaluate near-infrared (NIR) autofluorescence (AF) in patients with geographic atrophy (GA) secondary to age-related macular degeneration and to investigate the origin of the signal by in vivo and histological analysis in rats and in a human donor eye.

Methods: Confocal scanning laser ophthalmoscopy in vivo imaging, including blue (excitation: 488 nm, emission 500-700 nm) and NIR (excitation: 790 nm, emission >810 nm) AF was performed in 21 eyes of 18 GA patients. Pigmented and albino rats underwent with the same device both in vivo and post-mortem imaging.

Calibration sets and the accuracy of vibrational scaling factors: a case study with the X3LYP hybrid functional.

A linear least-squares methodology was used to determine the vibrational scaling factors for the X3LYP density functional. Uncertainties for these scaling factors were calculated according to the method devised by Irikura et al. [J.

Pattern of fluoride-containing dentifrice use and associated factors in preschool children from Ijuí, South Brazil.

Purpose: The aim of the present study was to evaluate the pattern of fluoride-containing dentifrice use and associated factors in Brazilian preschoolers.

Materials And Methods: A structured questionnaire was answered by parents of 432 children, who were aged 2 to 6 years, from 12 public preschools in Ijuí, South Brazil. Primary outcomes were age of starting fluoride-containing dentifrice use and amount of dentifrice applied to the toothbrush.

On the stability of metal-aminoacid complexes in water based on water-ligand exchange reactions and electronic properties: detailed study on iron-glycine hexacoordinated complexes.

Thermodynamic stability of metal-aminoacid complexes in water is discussed in terms of the Gibbs free energy of water-ligand exchange processes, and the electronic stabilizing factors thoroughly investigated by means of 1-electron and 2-electron density properties. Hexacoordinated complexes formed between iron cations and glycine molecules acting as monodentate or bidentate ligands have been chosen as targets for the current study. Results agree with experimental findings, and complexes formed with bidentate ligands are found to be more stable than those formed with monodentate ones.

Neuroprotection in glaucoma - Is there a future role?

In glaucoma, the major cause of global irreversible blindness, there is an urgent need for treatment modalities that directly target the RGCs. The discovery of an alternative therapeutic approach, independent of IOP reduction, is highly sought after, due to the indirect nature and limited effectiveness of IOP lowering therapy in preventing RGC loss. Several mechanisms have been implicated in initiating the apoptotic cascade in glaucomatous retinopathy and numerous drugs have been shown to be neuroprotective in animal models of glaucoma.

Nitric oxide-induced vasorelaxation in response to PnTx2-6 toxin from Phoneutria nigriventer spider in rat cavernosal tissue.

Introduction: Priapism is one of several symptoms observed in accidental bites by the spider Phoneutria nigriventer. The venom of this spider is comprised of many toxins, and the majority has been shown to affect excitable ion channels, mainly sodium (Na(+) ) channels. It has been demonstrated that PnTx2-6, a peptide extracted from the venom of P.

Tracking longitudinal retinal changes in experimental ocular hypertension using the cSLO and spectral domain-OCT.

Purpose: Involvement of the outer retina is controversial in glaucoma. The aim of this study was to test, first, whether the outer retina is affected in experimental ocular hypertension (OHT) and, second, whether whole retinal thickness can be used as a surrogate marker of glaucomatous change.

Methods: OHT was surgically induced in 20 Dark Agouti rats.

Host-mineral trioxide aggregate inflammatory molecular signaling and biomineralization ability.

Introduction: The biological processes underlying the ability of mineral trioxide aggregate (MTA) to promote hard-tissue deposition and wound healing remain unclear. To further study these processes, specific signaling molecules related to the inflammatory response and the biomineralization process were analyzed to assess host-MTA interactions in vivo.

Methods: For cytokine level quantification and immunohistochemical analysis, human dentin tubes were filled with ProRoot MTA (Dentsply, Tulsa Dental, OK) or kept empty and were implanted in subcutaneous tissues in the backs of mice.

Co-Occurrence of ADHD and high IQ: a case series empirical study.

Objective: The validity of a diagnosis of ADHD in children with a high intelligence quotient (IQ) remains controversial. Using a multidisciplinary approach, rigorous diagnostic criteria, and worldwide-validated psychometric instruments, we identified a group of children attending public schools in southern Brazil for co-occurrence of high IQ and ADHD.

Method: Students attending public schools, in the first to fifth grades, were referred to our Research Center for behavioral and/or learning difficulties.

Population genomic analysis of Tunisian Medicago truncatula reveals candidates for local adaptation.

Genome-wide association studies rely upon segregating natural genetic variation, particularly the patterns of polymorphism and correlation between adjacent markers. To facilitate association studies in the model legume Medicago truncatula, we present a genome-scale polymorphism scan using existing Affymetrix microarrays. We develop and validate a method that uses a simple information-criteria algorithm to call polymorphism from microarray data without reliance on a reference genotype.

Quantitative structure-activity relationship modelling of the carcinogenic risk of nitroso compounds using regression analysis and the TOPS-MODE approach.

Worldwide, legislative and governmental efforts are focusing on establishing simple screening tools for identifying those chemicals most likely to cause adverse effects without experimentally testing all chemicals of regulatory concern. This is because even the most basic biological testing of compounds of concern, apart from requiring a huge number of test animals, would be neither resource nor time effective. Thus, alternative approaches such as the one proposed here, quantitative structure-activity relationship (QSAR) modelling, are increasingly being used for identifying the potential health hazards and subsequent regulation of new industrial chemicals.

Patient-based dengue virus surveillance in Aedes aegypti from Recife, Brazil.

Background & Objectives: Dengue is currently one of the most important arthropod-borne diseases and may be caused by four different dengue virus serotypes (DENV-1 to DENV-4), transmitted mainly by Aedes aegypti (Diptera: Culicidae) mosquitoes. With the lack of a dengue vaccine, vector control strategies constitute a crucial mode to prevent or reduce disease transmission. In this context, DENV detection in natural Ae.

[Thyroid adenolipoma].

Thyroid adenolipomas or thyrolipomas are rare benign neoplasms composed of mature adipose tissue and glandular elements. The most common clinical manifestation is a slowly enlarging neck mass. If thyroid fine-needle aspiration biopsy discloses a mixed population of adipocytes and follicular cells, the possibility of an adenolipoma should be considered in the differential diagnosis.

Long-term follow-up of breast capsule contracture rates in cosmetic and reconstructive cases.

Background: Silicone gel breast implants are associated with long-term adverse events, including capsular contracture, with reported incidence rates as high as 50 percent. However, it is not clear how long the follow-up period should be and whether there is any association with estrogen or menopausal status. In addition, the placement of Baker grade II subjects in the majority of reports has been in data sets of controls instead of capsular contracture.

Changes in NMDA receptor contribution to synaptic transmission in the brain in a rat model of glaucoma.

In the age-related, blinding disease glaucoma, retinal ganglion cells (RGCs) degenerate, possibly affecting glutamatergic retinofugal transmission to the brain. The superior colliculus (SC) is a major central target of retinofugal axons in the rodent, a much used disease model. We investigated the contribution of NMDA-type glutamate receptors to retinocollicular transmission in a rat glaucoma model, using a SC brain slice preparation to determine the sensitivity of synaptic responses to the NMDAR antagonist D-AP5.

Manganese in children with attention-deficit/hyperactivity disorder: relationship with methylphenidate exposure.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder that affects children worldwide. The etiology of ADHD is complex and not fully understood. Earlier studies associated elevated levels of manganese (Mn) with learning problems, attention deficits, and ADHD.

Multidimensional drug design: simultaneous analysis of binding and relative efficacy profiles of N(6)-substituted-4'-thioadenosines A3 adenosine receptor agonists.

Desirability theory (DT) is a well-known multi-criteria decision-making approach. In this work, DT is employed as a prediction model (PM) interpretation tool to extract useful information on the desired trade-offs between binding and relative efficacy of N(6)-substituted-4'-thioadenosines A3 adenosine receptor (A3AR) agonists. At the same time, it was shown the usefulness of a parallel but independent approach providing a feedback on the reliability of the combination of properties predicted as a unique desirability value.

Quantification, morphology and ultrastructure of preantral follicles of buffalo (Bubalus bubalis) foetuses.

The objective of this study was to determine the number, morphology and ultrastructure of preantral ovarian follicles of buffalo (Bubalus bubalis) foetuses at different ages. Quantification revealed number of primordial, primary and secondary follicles of 48,857 ± 17,506, 26,000 ± 20,452, 18,428 ± 10,875 and 18,375 ± 19,690, 225 ± 349, 326 ± 288 at 12-34 cm and 35-60 cm crown rump length (CRL), respectively. Follicular diameter values were 28.

Prioritizing Hits with Appropriate Trade-Offs Between HIV-1 Reverse Transcriptase Inhibitory Efficacy and MT4 Blood Cells Toxicity Through Desirability-Based Multiobjective Optimization and Ranking.

Nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) constitute a promising therapeutic option for AIDS. However, the emergence of virus-NNRTIs resistance was found to be a major problem in the field. Toward that goal, a "knock-out" strategy stands out between the several options to circumvent the problem.

Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: in vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissive cells.

Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAIV) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies.

Design, Synthesis, and Evaluation of Antineoplastic Activity of Novel Carbocyclic Nucleosides.

Cancer is the leading cause of death among men and women under age 85. Every year, millions of individuals are diagnosed with cancer. But finding new drugs is a complex, expensive, and very time-consuming task.

Alzheimer's disease and retinal neurodegeneration.

Alzheimer's disease (AD) is the major cause of dementia in the world. Although the entorhinal cortex and hippocampal complex are best known as the sites of early pathology in AD, increasing evidence shows that the eye, particularly the retina, is also affected. The AD-related changes in the retina are associated with degeneration and loss of neurons, reduction of the retinal nerve fibres, increase in optic disc cupping, retinal vascular tortusity and thinning, and visual functional impairment.