Prodrugs for the treatment of neglected diseases

Recently, World Health Organization ( WHO) and Medicins San Frontieres (MSF) proposed a classification of diseases as global, neglected and extremely neglected. Global diseases, such as cancer, cardiovascular and mental (CNS) diseases represent the targets of the majority of the R&D efforts of pharmaceutical companies. Neglected diseases affect millions of people in the world yet existing drug therapy is limited and often inappropriate. Furthermore, extremely neglected diseases affect people living under miserable conditions who barely have access to the bare necessities for survival. Most of these diseases are excluded from the goals of the R&D programs in the pharmaceutical industry and therefore fall outside the pharmaceutical market. About 14 million people, mainly in developing countries, die each year from infectious diseases. From 1975 to 1999, 1393 new drugs were approved yet only 1% were for the treatment of neglected diseases [ 3]. These numbers have not changed until now, so in those countries there is an urgent need for the design and synthesis of new drugs and in this area the prodrug approach is a very interesting field. It provides, among other effects, activity improvements and toxicity decreases for current and new drugs, improving market availability. It is worth noting that it is essential in drug design to save time and money, and prodrug approaches can be considered of high interest in this respect. The present review covers 20 years of research on the design of prodrugs for the treatment of neglected and extremely neglected diseases such as Chagas' disease ( American trypanosomiasis), sleeping sickness ( African trypanosomiasis), malaria, sickle cell disease, tuberculosis, leishmaniasis and schistosomiasis.

Antioxidant Activity and Total Phenols from the Methanolic Extract of Miconia albicans (Sw.) Triana Leaves

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

Minimum size for the occurrence of vortex matter in a square mesoscopic superconductor

The study of superconducting samples in mesoscopic scale presented a remarkable improvement during the last years. Certainly, such interest is based on the fact that when the size of the samples is close to the order of the temperature dependent coherence length xi(T), and/or the size of the penetration depth lambda(T), there are some significant modifications on the physical properties of the superconducting state. This contribution tests the square cross-section size limit for the occurrence (or not) of vortices in mesoscopic samples of area L-2, where L varies discretely from 1 xi(0) to 8 xi(0).The time dependent Ginzburg-Landau (TDGL) equations approach is used upon taking the order parameter and the local magnetic field invariant along the z-direction. The vortex configurations at the equilibrium can be obtained from the TDGL equations for superconductivity as the system relaxes to the stationary state.The obtained results show that the limit of vortex penetration is for the square sample of size 3 xi(0) x 3 xi(0) in which only a single vortex are allowed into the sample. For smaller specimens, no vortex can be formed and the field entrance into the sample is continuous and the total flux penetration occurs at higher values of H/H-c2(0), where H-c2(T) is the upper critical field. Otherwise, for larger samples different vortices patterns can be observed depending on the sample size. (c) 2007 Elsevier B.V. All rights reserved.

Prevalence and Correlates of Cognitive Impairment among the Elderly in a General Hospital

Aims: To estimate the prevalence and correlates of cognitive impairment (CI) among the elderly in a general hospital. Methods: A cross-sectional study, including 200 Brazilian inpatients aged 60 years or over, using the Mini Mental State Examination to evaluate CI (dependent variable), and the Geriatric Depression Scale and the Katz and Lawton Index to evaluate basic (BADL) and instrumental activities of daily living (IADL). Results: 56% were women, 29% were dependent for BADL and 77.5% for IADL. The prevalence of CI was 29% and, in the logistic regression, it remained associated with higher age (1 74 years old), number of previous hospitalizations (1 3) and dependency for BADL (being dependent raised the odds of being cognitively impaired). Conclusions: It is essential to train the hospital staff to properly assist these patients, and to orient and support their caregivers. Copyright (C) 2009 S. Karger AG, Basel

Prevalence of anti-Toxoplasma gondii antibodies in dairy cattle, dogs, and humans from the Jauru micro-region, Mato Grosso state, Brazil

In order to determine the prevalence of anti-Toxoplasma gondii antibodies, 2000 serum samples from female dairy cattle belonging to 50 farms in the southwest of Mato Grosso state were analyzed by the indirect fluorescent antibody test (IFAT >= 64). Serum samples from 61 dogs (IFAT >= 40) and 116 humans (IFAT = 40), all from the same farm, were also tested. Among these samples, 1420 (71.0%) cattle, 54 (88.5%) dogs, and 113 (97.4%) humans were seropositive for the infection. No significant differences (P >= 0.05) were observed for risk factors associated with the occurrence of toxoplasmosis in humans due to contaminated sources such as fresh milk, cheese/sausage, and contact with felines or other animals. The presence of felines can indicate the likelihood of a contaminated environment, posing a risk to the human population and other animals. The work presented herein is the first report to evaluate the seroprevalence of T gondii in bovines from the Southwest region of the Mato Grosso state, Brazil. (C) 2009 Elsevier B.V. All rights reserved.

Effect of Artificial Aging on the Roughness and Microhardness of Sealed Composites

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

Enamel microabrasion followed by dental bleaching for patients after orthodontic treatment - Case reports

This article reports clinical procedures used to remove residual bonded resin and enamel stains following bracket debonding at the conclusion of orthodontic treatment. A water-cooled fine-tapered diamond bur was used for resin removal, followed by enamel surface finishing using a commercially available microabrasion paste. It was noted that residual tooth coloration remained yellowish because of enamel translucency; the yellow dentin shade showed through. Additional tooth shade lightening was achieved using carbamide peroxide dental bleaching solution in custom-formed trays. This report describes a safe and effective technique that optimizes tooth appearance at the conclusion of orthodontic therapy. Mechanical resin removal, enamel microabrasion, and tooth bleaching are employed.

The influence of time interval between bleaching and enamel bonding

Objectives: the purpose of this study was to investigate the penetration of a conventional adhesive material into enamel bleached with 16% carbamide peroxide and 38% hydrogen peroxide using optical light microscopy.Methods: Extracted human teeth were randomly divided into eight experimental groups with six specimens each, according to the bleaching material and time interval after bleaching and before the bonding procedure. Groups were designated as follows: control group, restorations in unbleached teeth; restorations performed immediately after bleaching; restorations performed 7 days after bleaching; restorations performed 14 days after bleaching; and restorations performed 30 days after bleaching. The length of resin tags was measured with an Axiophot photomicroscope at 400x magnification for the calculation of the proportion of tags of study groups compared to the respective control groups. Analysis of variance was applied for comparison between groups; data were transformed into arcsine (p < 0.05).Results: the specimens of experimental groups, in which restorations were performed 7, 14, and 30 days after bleaching, showed better penetration of adhesive material into enamel than specimens restored immediately after bleaching. There was no statistically significant difference between the bleaching materials employed or in the interaction between bleaching agent and time interval.Conclusions: This suggests that a time interval of at least 7 days should be allowed between enamel bleaching and placement of adhesive bonding agents for accomplishment of composite resin restorations.

Effect of Different Light-Curing Modes on Degree of Conversion, Staining Susceptibility and Stain's Retention Using Different Beverages in a Nanofilled Composite Resin

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Direct Esthetic Restorations Based on Translucency and Opacity of Composite Resins

Light dynamics is a relevant phenomenon with respect to esthetic restorations, as incorrect analysis of the optical behavior of natural dentition may lead to potential clinical failures. The nature of incident light plays a major role in determining the amount of light transmission or reflection, and how an object is perceived depends on the nature of the light source. Natural teeth demonstrate translucency, opalescence, and fluorescence, all of which must be replicated by restorative materials in order to achieve clinical success. Translucency is the intermediary between complete opacity and complete transparency, making its analysis highly subjective. In nature, the translucency of dental enamel varies from tooth to tooth, and from individual to individual. Therefore, four important factors must be considered when appraising translucency. Presence or absence of color, thickness of the enamel, degree of translucency, and surface texture are essential components when determining translucency. State-of-the-art resin composites provide varying shades and opacities that deliver a more faithful reproduction of the chromaticity and translucency/opacity of enamel and dentin. This enables the attainment of individualized and customized composite restorations. The objective of this article is to provide a review of the phenomena of translucency and opacity in the natural dentition and composite resins, under the scope of optics, and to describe how to implement these concepts in the clinical setting.CLINICAL SIGNIFICANCEChoosing composite resins, based on optical properties alone, in order to mimic the properties of natural tooth structures, does not necessarily provide a satisfactory esthetic outcome. In many instances, failure ensues from incorrect analysis of the optical behaviors of the natural dentition as well as the improper use of restorative materials. Therefore, it is necessary to implement a technique that enables a restorative material to be utilized to its full potential to correctly replicate the natural teeth.(J Esthet Restor Dent 23:73-88, 2011).

The Antigerminative Activity of Twenty-Seven Monoterpenes

Monoterpenes, the main constituents of essential oils, are known for their many biological activities. The present work studied the potential biological activity of twenty-seven monoterpenes, including monoterpene hydrocarbons and oxygenated ones, against seed germination and subsequent primary radicle growth of Raphanus sativus L. (radish) and Lepidium sativum L. (garden cress), under laboratory conditions. The compounds, belonging to different chemical classes, showed different potency in affecting both parameters evaluated. The assayed compounds demonstrated a good inhibitory activity in a dose-dependent way. In general, radish seed is more sensitive than garden cress and its germination appeares more inhibited by alcohols; at the highest concentration tested, the more active substances were geraniol, borneol, (+/-)-beta-citronellol and alpha-terpineol. Geraniol and carvone inhibited, in a significant way, the germination of garden cress, at the highest concentration tested. Radicle elongation of two test species was inhibited mainly by alcohols and ketones. Carvone inhibited the radicle elongation of both seeds, at almost all concentrations assayed, while 1,8-cineole inhibited their radicle elongation at the lowest concentrations (10(-5) M, 10(-6) M).

Phytotoxic Activities of Mediterranean Essential Oils

Twelve essential oils from Mediterranean aromatic plants were tested for their phytotoxic activity, at different doses, against the germination and the initial radicle growth of seeds of Raphanus sativus, Lactuca sativa and Lepidium sativum. The essential oils were obtained from Hyssopus officinalis, Lavandula angustifolia, Majorana hortensis, Melissa officinalis, Ocimum basilicum, Origanum vulgare, Salvia officinalis and Thymus vulgaris (Lamiaceae), Verbena officinalis (Verbenaceae), Pimpinella anisum, Foeniculum vulgare and Carum carvi (Apiaceae). The germination and radicle growth of tested seeds were affected in different ways by the oils. Thyme, balm, vervain and caraway essential oils were more active against both germination and radicle elongation.

Embryo transfer in Bos indicus cattle

In the present short review superovulation treatments commonly used for Bos taurus and/or Bos indicus will be addressed with emphasis in recent superstimulation protocols associated with pharmacological manipulation of the follicular dynamics to improve donor management and potentially embryo yield. Results obtained after superovulation treatments in which the time of LH surge is selectively delayed as an attempt to improve embryo yield are presented and discussed. (C) 2001 by Elsevier B.V.

The evolution of jumping performance in anurans: morphological correlates and ecological implications

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

Mechanisms of the Gastric Antiulcerogenic Activity of Anacardium humile St. Hil on Ethanol-Induced Acute Gastric Mucosal Injury in Rats

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