Enriched Flavonoid Fraction from <Emphasis Type="Italic">Cecropia pachystachya</Emphasis> Trécul Leaves Exerts Antidepressant-like Behavior and Protects Brain Against Oxidative Stress in Rats Subjected to Chronic Mild Stress

The purpose of this study was to assess the effect of an enriched C-glycosyl flavonoids fraction (EFF-Cp) from Cecropia Pachystachya leaves on behavior, mitochondrial chain function, and oxidative balance in the brain of rats subjected to chronic mild stress. Male Wistar rats were divided into experimental groups (saline/no stress, saline/stress, EFF-Cp/no stress, and EFF-Cp/stress). ECM groups were submitted to stress for 40 days. On the 35th ECM day, EFF-Cp (50 mg/kg) or saline was administrated and the treatments lasted until the 42nd day. On the 41st and 42nd days, the animals were submitted to the splash test and the forced swim test. After these behavioral tests, the enzymatic activity of mitochondrial chain complexes and oxidative stress were analyzed. EFF-Cp reversed the depressive-like behavior induced by ECM. It also reversed the increase in thiobarbituric acid reactive species, myeloperoxidase activity, and nitrite/nitrate concentrations in some brain regions. The reduced activities of the antioxidants superoxide dismutase and catalase in some brain regions were also reversed by EFF-Cp. The most pronounced effect of EFF-Cp on mitochondrial complexes was an increase in complex IV activity in all studied regions. Thus, it is can be concluded that EFF-Cp exerts an antidepressant-like effect and that oxidative balance may be an important physiological process underlying these effects.     

Psoralen analogues: synthesis, inhibitory activity of growth of human tumor cell lines and computational studies

Eight psoralens have been evaluated for their ability to inhibit the in vitro growth of three human tumor cell lines representing different tumor types, MCF-7 (breast cancer), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer). The synthesis of four new psoralens (benzofurocoumarins) is presented as well as the results of the ab initio calculations to find the parameters that relate the structure with the antitumor activity. This work provides supplementary information that could allow the development of new psoralen analogues with this type of biological activity.     

Synthesis,biological evaluation,and molecular modeling of nitrile-containing compounds: Exploring multiple activities as anti-Alzheimer agents

Based on the monoamine oxidase (MAO) inhibition properties of aminoheterocycles with a carbonitrile group we have carried out a systematic exploration to discover new classes of carbonitriles endowed with dual MAO and AChE inhibitory activities, and Aβ anti-aggregating properties. Eighty-three nitrile-containing compounds, 13 of which are new, were synthesized and evaluated. in vitro screening revealed that 31 , a new compound, presented the best lead for trifunctional inhibition against MAO A (0.34 μM), MAO B (0.26 μM), and AChE (52 μM), while 32 exhibited a lead for selective MAO A (0.12 μM) inhibition coupled to AChE (48 μM) inhibition. Computational analysis revealed that the malononitrile group can find an advantageous position with the aromatic cleft and FAD of MAO A or MAO B. However, the total binding energy can be handicapped by an internal penalty caused by twisting of the ligand molecule and subsequent disruption of the conjugation ( 32 in MAO B compared to the conjugated 31 ). Conjugation is also important for AChE as well as the hydrophilic character of malononitrile that allows this group to be in close contact with the aqueous environment as seen for 83 . Although the effect of 31 and 32 against Aβ_1–42, was very weak, the effect of 63 and 65 , and of the new compound 75 , indicated that these compounds were able to disaggregate Aβ_1–42 fibrils. The most effective was 63 , a (phenylhydrazinylidene)propanedinitrile derivative that also inhibited MAO A (1.65 μM), making it a potential lead for Alzheimer's disease application.     

Synthesis of novel benzofurocoumarin analogues and their anti-proliferative effect on human cancer cell lines

The synthesis of five new tetracyclic benzofurocoumarin (benzopsoralen) analogues is described. Their inhibitory effects on the growth of three human tumor cell lines (MDA MB 231 (breast adenocarcinoma), HeLa (cervix adenocarcinoma) and TCC-SUP (bladder transitional cell carcinoma) were evaluated, and discussed in terms of structure-activity relationship.     

Sorbitol-modified hyaluronic acid reduces oxidative stress,apoptosis and mediators of inflammation and catabolism in human osteoarthritic chondrocytes

Objective and design

Our study was designed to elucidate the precise molecular mechanisms by which sorbitol-modified hyaluronic acid (HA/sorbitol) exerts beneficial effects in osteoarthritis (OA).

Methods

Human OA chondrocytes were treated with increasing doses of HA/sorbitol ± anti-CD44 antibody or with sorbitol alone and thereafter with or without interleukin-1beta (IL-1β) or hydrogen peroxide (H₂O₂). Signal transduction pathways and parameters related to oxidative stress, apoptosis, inflammation, and catabolism were investigated.

Results

HA/sorbitol prevented IL-1β-induced oxidative stress, as measured by reactive oxygen species, p47-NADPH oxidase phosphorylation, 4-hydroxynonenal (HNE) production and HNE-metabolizing glutathione-S-transferase A4-4 expression. Moreover, HA/sorbitol stifled IL-1β-induced metalloproteinase-13, nitric oxide (NO) and prostaglandin E2 release as well as inducible NO synthase expression. Study of the apoptosis process revealed that this gel significantly attenuated cell death, caspase-3 activation and DNA fragmentation elicited by exposure to a cytotoxic H₂O₂ dose. Examination of signaling pathway components disclosed that HA/sorbitol prevented IL-1β-induced p38 mitogen-activated protein kinase and nuclear factor-kappa B activation, but not that of extracellular signal-regulated kinases 1 and 2. Interestingly, the antioxidant as well as the anti-inflammatory and anti-catabolic effects of HA/sorbitol were attributed to sorbitol and HA, respectively.

Conclusions

Altogether, our findings support a beneficial effect of HA/sorbitol in OA through the restoration of redox status and reduction of apoptosis, inflammation and catabolism involved in cartilage damage.     

Population dynamics and the profile of mortality in the municipality of Montes Claros, Minas Gerais State, Brazil

This study is an ecological study of time trend. The objective of this study is to assess the population dynamics as the 1980 Census, 1991 and 2000, and the profile of mortality in the period between 1996 and 2005, in Montes Claros, Minas Gerais State. We used the information systems database of Datasus and IBGE. The main results indicate that the elderly group increased from 4.1% in 1980, 5.0% in 1991 to 6.6% in 2000. On the proportional mortality by cause, diseases of the circulatory system were the first cause of death, and 23.05% in 1996 and 28.26% in 2005, followed by cancer 14.13% in 1996 and 15.69% in 2005, external causes of morbidity and mortality 11.87% in 1996 and 12.74% in 2005 and infectious and parasitic diseases 8.42% in 1996 and 5.43% in 2005. The profile of mortality followed the population dynamics of the city observed a reduction of infectious diseases and an increase in chronic diseases, consistent with the process of population aging.     

Clinical management of childhood apraxia of speech: A survey of speech-language pathologists in Australia and New Zealand

Abstract

Purpose: A number of studies have been published that have investigated the practices of speech-language pathologists in relation to speech sound disorder intervention; however, specific research about the treatment of childhood apraxia of speech is not available. This study aimed to describe the treatment approaches being used by speech-language pathologists, explore their perspectives of evidence-based practice and identify perceived barriers to implementing empirical research recommendations.

Method: An online survey was distributed to speech-language pathologists in Australia and New Zealand. In total, 109 valid surveys were completed by participants who answered a series of multiple choice, yes/no, short answer and Likert-scaled questions.

Result: Speech-language pathologists demonstrated a strong preference for eclectic interventions to treat childhood apraxia of speech. When asked to identify the primary treatment approach they used (whether as a stand-alone; or as the primary approach within an eclectic intervention), the most frequently used intervention was the Nuffield Dyspraxia Programme. Many speech-language pathologists reported valuing empirical research evidence, despite identifying a range of barriers that impact their ability to implement evidence-based practice in childhood apraxia of speech treatment.

Conclusion: Although many speech-language pathologists use the Nuffield Dyspraxia Programme as their primary intervention, most clinicians use it as part of an eclectic/hybrid intervention. The effectiveness of eclectic interventions for childhood apraxia of speech has not been empirically evaluated.