Synthesis and biological assessment of diversely substituted furo[2,3-b]quinolin-4-amine and pyrrolo[2,3-b]quinolin-4-amine derivatives, as novel tacrine analogues

The synthesis and pharmacological analyses of a number of furo[2,3-b]quinolin-4-amine, and pyrrolo[2,3-b]quinolin-4-amine derivatives are reported. Thus, we synthesized diversely substituted tacrine analogues 1–11 and 12–16 by Friedländer-type reaction of readily available o-amino(furano/pyrrolo)nitriles with suitable and selected cycloalkanones. The biological evaluation of furanotacrines1–11 and pyrrolotacrine13 showed that these are good, in the micromolar range, and highly selective inhibitors of BuChE. In the furanotacrine group, the most interesting inhibitor was 2-(p-tolyl)-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-amine (3) [IC₅₀ (eqBuChE) = 2.9 ± 0.4 μM; IC₅₀ (hBuChE) = 119 ± 15 μM]. Conversely, pyrrolotacrines12 and 14 proved moderately equipotent for both cholinesterases, being 1,2-diphenyl-5,6,7,8-tetrahydro-1H-pyrrolo[2,3-b]quinolin-4-amine (12) the most potent for the inhibition of both enzymes [IC₅₀ (EeAChE) = 0.61 ± 0.04 μM; IC₅₀ (eqBuChE) = 0.074 ± 0.009 μM]. Moreover, pyrrolotacrine 12, at concentrations as low as 300 nM can afford significant neuroprotective effects against Aβ-induced toxicity. Docking studies show that compounds 3 and 12 bind in the middle of the AChE active site gorge, but are buried deeper inside BuChE active site gorge, as a consequence of larger BuChE gorge void. All these data suggest that these new tacrine analogues could be used for the potential treatment of Alzheimer’s disease.     

Synthesis and evaluation of quinonoid compounds against tumor cell lines

Thirty two compounds were synthesized in moderate to high yields and showed activity against cancer cells HL-60 (leukemia), MDA-MB435 (melanoma), HCT-8 (colon) and SF295 (central nervous system), with IC₅₀ below 2 μM for some compounds. The β-lapachone-based 1,2,3-triazoles showed the best cytoxicity profile and emerge as promising anticancer prototypes. Insights about the reactive oxygen species (ROS) mechanism of anticancer action for some compounds were obtained by addition of 1-bromoheptane that deplete reduced glutathione (GSH) content and by using N-acetylcysteine that protects cells against apoptotic cellular death, as well by analysis of thiobarbituric acid reactive substances (TBARS) formation, and oxidative DNA damage after treatment detected by the comet assay with the bacterial enzymes formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (ENDOIII).     

Bolsa Família Program and child nutritional status: strategic challenges

The main nutritional deficiencies during childhood, namely anemia and malnutrition, are predominantly related to socio-economic factors. Thus, as the Bolsa Família Program (BFP) is the main policy to combat poverty, it is expected that it will have an impact on child nutrition. The aim was to analyze the differences in the nutritional situation of children registered with the BFP of a municipality located in Zona da Mata of Minas Gerais state. 446 children aged between 6 and 84 months were evaluated, of which 262 were non-beneficiaries and 184 were beneficiaries. Nutritional evaluation included analysis of weight and height parameters through weight/age, weight/height, height/age and Body Mass Index/age indexes and hemoglobin levels, using the Hemocue. The prevalence of anemia, short stature and obesity were 22.6, 6.3 and 5.2%, respectively, and there were no statistical differences between beneficiaries and non-beneficiaries. The beneficiary group initially had worse socio-economic conditions, but with the BFP it managed to financially match the non-beneficiary group. It is possible that the similarity between the two groups, also in the nutritional status, can be attributed to the program benefits, due to the financial funding as well as to the nutritional monitoring required as a condition of the program.     

Social and biological determinants of iron deficiency anemia

This cross-sectional study aimed to identify the social and biological determinants of anemia in children enrolled in the Brazilian Income Transfer Program (PBF). The study evaluated 446 children (69.1% of the total enrolled) ranging from 6 to 84 months of age, of whom 262 were receiving the income transfer (60.2% of the beneficiaries) and 184 were not (87.6% of the non-beneficiaries). Testing for anemia was performed with the Hemocue portable hemoglobinometer, and the cutoff points were set at 11.0 and 11.5 g/dL, according to age bracket. The data were analyzed using Poisson hierarchical regression with robust variance for multivariate analysis. There was no difference in the anemia prevalence rates between the beneficiary and non-beneficiary groups. Risk factors for anemia were low paternal schooling, cesarean birth, consumption of untreated water, stunting, and age less than 24 months. Prevalence of anemia in the group of non-beneficiary children under two years of age was significantly higher than in the beneficiary group in the same age bracket, suggesting the importance of the PBF income transfer for preventing anemia in children.     

Prenatal care and management of hypertension in pregnant women in the public healthcare system in Rio de Janeiro, Brazil

The aim of this study was to assess the adequacy of prenatal care for pregnant women with hypertension as compared to those at low risk. Adequate management of hypertension and associated factors were also investigated. A cross-sectional study was conducted with 1,947 women, 187 of whom with hypertension, in public prenatal care units in Rio de Janeiro, Brazil, in 2007-2008. Demographic and socioeconomic data, obstetric history, and information on adequacy of prenatal care were collected using interviews and prenatal care cards. Adequacy of management of hypertension was evaluated according to performance of health professionals and health services and women's individual characteristics. Chi-square and multivariate logistic regression were used to compare groups and identify factors associated with management of hypertension. Adequacy of prenatal care was 79% and did not differ between groups. Only 27% of pregnant women with hypertension received appropriate management, with poor professional performance. Hypertensive pregnant women with better prenatal care were those with previous neonatal deaths and/or stillbirths and those with 35 years of age and older. Despite adequate use of prenatal care, management of hypertension in pregnant women was inadequate.     

Nutritional status and associated factors among the elderly in Viçosa, Minas Gerais State, Brazil

This cross-sectional study in 2009 focused on the prevalence of underweight and overweight and associated factors in a sample of 621 elderly individuals in Vi?osa, Minas Gerais State, Brazil. Data were obtained through home interviews on nutritional status and socio-demographic and health conditions. Of the total sample, 53.3% were females. Median BMI was 26.40 kg/m2 (range = 15.20-46.82) and was lower for men than for women. Prevalence of overweight was high (45%; 95%CI: 40%-49%), decreased with age, was positively associated with female gender and history of arthritis/arthrosis, and was negatively associated with age 80 years or older and smoking. Prevalence of underweight was high in men (18.2%), increased with age, and was positively associated with worse self-rated health. The findings highlight the importance of health strategies that favor lifestyle changes and healthy eating habits.     

Scientific journalism and epidemiological risk

The importance of the communications media in the construction of symbols has been widely acknowledged. Many of the articles on health published in the daily newspapers mention medical studies, sourced from scientific publications focusing on new risks. The disclosure of risk studies in the mass media is also a topic for editorials and articles in scientific journals, focusing the problem of distortions and the appearance of contradictory news items. The purpose of this paper is to explore the meaning and content of disclosing scientific risk studies in large-circulation daily newspapers, analyzing news items published in Brazil and the scientific publications used as their sources during 2000. The "risk" is presented in the scientific research projects as a "black box" in the meaning of Latour, with the news items downplaying scientific disputes and underscoring associations between behavioral habits and the occurrence of diseases, emphasizing individual aspects of the epidemiological approach, to the detriment of the group.     

Governance and regulation in health: challenges for health management in Greater Metropolitan São Paulo, Brazil

This paper discusses the relationship between the public and private sectors in the Unified National Health System (SUS), based on research whose objective was to identify governance strategies and mechanisms for public/private relations in the health sector, considering the search for equity in Greater Metropolitan Sao Paulo, Brazil. Governance was used as an analytical category, with health system regulation as the issue. Municipal and State health secretaries, members of health councils, and SUS staff were interviewed, and the empirical material was classified as: (a) regulatory mechanisms and instruments; (b) power loci; and (c) actors' positions concerning the SUS and its relationship to the private sector. Mechanisms and instruments have been created and used in the municipalities for regulation of their own services. Regulatory measures for the complementary and supplementary healthcare sector are practically nonexistent. There are numerous institutional power loci, seen more as places for submitting demands than as forums for negotiation. Despite some progress, governance appears to be more of a formal issue. Discussion is needed on the relationship between the public and private sectors and its regulation by municipalities in order to improve the health system.     

Nantenine blocks muscle contraction and Ca2+ transient induced by noradrenaline and K+ in rat vas deferens

The effect of nantenine, an aporphine alkaloid isolated from Ocotea macrophylla H.B.K., was studied on contractions and Ca(2+) translocation induced by noradrenaline, Ca(2+), or K(+) in the isolated rat vas deferens from reserpinized animals. Concentration-response curves of calcium chloride (CaCl(2)) were performed in the vas deferens, in a Ca(2+)-free nutrient solution, using potassium chloride (KCl, 80 mM) as a depolarizing agent. In these conditions, nantenine (2.35 x 10(-4) and 4.7 x 10(-4) M) significantly reduced the maximum contractions (E(max)) of Ca(2+) (IC(50)=2.6 x 10(-4) M) and noradrenaline (IC(50)=2.9 x 10(-4) M). The contractile responses were totally recovered after the withdrawal of nantenine. In addition, experiments performed to measure simultaneously the contraction and the increase of intracellular Ca(2+) induced by noradrenaline (10(-5) M) or KCl (80 mM) showed that nantenine (2.35 x 10(-4) and 4.7 x 10(-4) M) significantly decreased both effects. The results suggest that a reversible block of Ca(2+) entry could be involved on the non-competitive-like antagonism of nantenine in rat vas deferens.