Atherosclerosis,Oxidation and Endometriosis

Endometriosis affects younger women of childbearing age. Atherosclerosis is considered as a disease of the old and increases with the ageing process. Both diseases are characterized by the increased presence of activated macrophages and associated increases in growth promoting activity and the production of inflammatory cytokines. In this review, we propose that oxidative stress and the presence of forms of oxidized low-density lipoprotein (LDL) might contribute to both Atherosclerosis and Endometriosis.     

Selective Autophagy: Talking with the UPS

Far from now are the days when investigators raced to identify the proteolytic system responsible for the degradation of their favorite protein. Nowadays, it is well accepted that a given protein can be degraded by different systems depending on factors such as cell type, cellular conditions, or functionality of each proteolytic pathway. The realization of this sharing of substrates among pathways has also helped to unveil deeper levels of communication among the different proteolytic systems. Thus, cells often respond to blockage of one degradative mechanism by upregulating any of the other available pathways. In addition, effectors and regulators of one proteolytic system can be degraded by a different proteolytic pathway that exerts, in this way, a regulatory function. In this mini review, we describe the different levels of cross-talk among autophagic pathways and the ubiquitin/proteasome system. We also provide examples of how this proteolytic communication is used for compensatory purposes in different pathological conditions and discuss the possible therapeutic potential of targeting the modulators of the cross-talk among proteolytic pathways.     

Turbellarian assemblages in freshwater lagoons in southern Brazil

Turbellarians, which typically feed on bacteria, algae, rotifers, oligochaetes, dipteran larvae, microcrustaceans, and other organisms, are abundant in diverse types of wetlands. Despite their importance, abundance, and species richness in freshwater environments, turbellarians are seldom considered in studies on biodiversity. We analyzed the structure of turbellarian communities in shore areas of three categories of permanent wetlands classified according to their perimeter as small, intermediate, and large during an annual cycle. In total, 1847 turbellarians were collected representing 42 species and 15 genera, from the orders Catenulida, Macrostomida, Lecithoepitheliata, Rhabdocoela, and Tricladida. Sixteen species were common to the three categories of wetlands, whereas nineteen species were unique to a particular category. Species composition varied among wetlands of different sizes; small, intermediate, and large wetlands had different dominant species. We found seasonal differences in community composition over the year, but no significant differences in mean values of observed species richness among wetlands with different sizes and among seasonal samples. The estimated species richness was, however, higher in the small wetlands, followed by the large and intermediate wetlands. In the summer, abundance was significantly lower in the small water bodies than in the intermediate and large bodies of water. Our results reinforce the need for conservation of wetlands of different sizes.     

Isolated respiring heart mitochondria release reactive oxygen species in states 4 and 3

Isolated mitochondria respiring on physiological substrates, both in state 4 and 3, are reported to be or not to be a source of reactive oxygen species (ROS). The cause of these discrepancies has been investigated. As protein concentration was raised in in vitro assays at 37°C, the rate of H₂O₂ release by rat heart mitochondria supplemented with pyruvate/malate or with succinate (plus rotenone) was shown to increase (0.03–0.15?mg?protein/ml), to decrease (0.2–0.5?mg?protein/ml) and to be negligible (over 0.5?mg?protein/ml). The inhibition of mitochondrial respiration (with rotenone or antimycin A) or the increase in the oxygen concentration dissolved in the assay medium allowed an enhancement of ROS production rate throughout the studied range of protein concentrations. In mitochondria respiring in state 3 on pyruvate/malate or on succinate (plus rotenone), ROS release vanished for protein concentrations over 0.5 or 0.2?mg/ml, respectively. However, ROS production rates measured with low protein concentrations (below 0.1?mg/ml) or in oxygen-enriched media were similar or even slightly higher in the active respiratory state 3 than in the resting state 4 for both substrates. Consequently, these findings indicate that isolated mitochondria, respiring in vitro under conditions of forward electron transport, release ROS with Complex I- and II-linked substrates in the resting condition (state 4) and when energy demand is maximal (state 3), provided that there is sufficient oxygen dissolved in the medium.     

Characterization of Indoor Environmental Quality in Primary Schools in Maia: A Portuguese Case Study

Scientific evidence associates indoor environment pollutants with respiratory effects (asthma and allergies), and children constitute one of most sensitive groups. Indoor air quality (IAQ) in schools may indeed be a significant health factor for children, with effects on school attendance and performance. Our aim was to characterize IAQ of classrooms in Maia County (north of Portugal) for which there was no information available. The study was conducted in 21 of the 40 primary schools, selected by stratified random sampling. Depending on the dimension, one or two classrooms were tested at each school. Walkthrough surveys of school grounds, buildings, and individual classrooms were done. Continuous measurements were taken of temperature, relative humidity, airborne respirable particles, total volatile organic compounds, and carbon dioxide, whereas bioaerosols were counted on Plate Count Agar during regular school activities. The indoor arithmetic mean for PM₁₀, CO₂, TCOV, and bioaerosol concentrations were 0.14 mg/m³, 999 ppm, 0.41 mg/m³, and 4140 UCF/m³, respectively. The values of PM₁₀ and CO₂ were close to their acceptable maximum values, but bioaerosols were much higher. This study supports previous studies conducted in school environments and emphasizes the need for proactive indoor air quality audits in school buildings.     

Review ArticleNaphthalene Combretastatin Analogues: Synthesis,Cytotoxicity and Antitubulin Activity

Synthesis and evaluation of new combretastatin analogues with varied modifications on the bridge and the aromatic rings, have shown that the 2-naphthyl moiety is a good surrogate for the 3-hydroxy-4-methoxyphenyl (B-ring) of combretastatin A-4. Other bicyclic systems, such as 6(7)-quinolyl and 5-indolyl, can replace the B-ring, but they produce less potent analogues in the cytotoxicity and tubulin polymerization inhibition assays. Other modifications are detrimentral for the potency of the studied analogues. The 2-naphthyl combretastatin 53 and the related 6-quinolyl combretastatin 106 analogues are the most potent among the derivatives of this type, whereas 92 and 95 are the most potent among the naphthalene derivatives with a heterocycle in the bridge. Previous and new results in this family of combretastatin analogues are discussed.     

Design,synthesis and cholinesterase inhibitory properties of new oxazole benzylamine derivatives

Abstract

The enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are primary targets in attenuating the symptoms of neurodegenerative diseases. Their inhibition results in elevated concentrations of the neurotransmitter acetylcholine which supports communication among nerve cells. It was previously shown for trans-4/5-arylethenyloxazole compounds to have moderate AChE and BChE inhibitory properties. A preliminary docking study showed that elongating oxazole molecules and adding a new NH group could make them more prone to bind to the active site of both enzymes. Therefore, new trans-amino-4-/5-arylethenyl-oxazoles were designed and synthesised by the Buchwald-Hartwig amination of a previously synthesised trans-chloro-arylethenyloxazole derivative. Additionally, naphthoxazole benzylamine photoproducts were obtained by efficient photochemical electrocyclization reaction. Novel compounds were tested as inhibitors of both AChE and BChE. All of the compounds exhibited binding preference for BChE over AChE, especially for trans-amino-4-/5-arylethenyl-oxazole derivatives which inhibited BChE potently (IC₅₀ in µM range) and AChE poorly (IC₅₀?100?µM). Therefore, due to the selectivity of all of the tested compounds for binding to BChE, these compounds could be applied for further development of cholinesterase selective inhibitors.

• HIGHLIGHTS

• Series of oxazole benzylamines were designed and synthesised

• The tested compounds showed binding selectivity for BChE

• Naphthoxazoles were more potent AChE inhibitors

     

Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Introduction

Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.

Methods

Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO₂, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise).

Results

The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO₂ (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.

Conclusion

A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.

Trial registration

NCT01515163.