Selective activity against Mycobacterium tuberculosis of new quinoxaline 1,4-di-N-oxides

New series of 3-phenylquinoxaline 1,4-di-N-oxide with selective activity against Mycobacterium tuberculosis have been prepared and evaluated. Thirty-four of the seventy tested compounds showed an MIC value less than 0.2 μg/mL, a value on the order of the MIC of rifampicin. Furthermore, 45% of the evaluated derivatives showed a good in vitro activity/toxicity ratio. The most active and selective compounds carry a fluorine atom in the quinoxaline 7-position or in the phenyl substituent para-position. In conclusion, the potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for synthesizing new analogues, particularly compound 7-methyl-3-(4’-fluoro)phenylquinoxaline-2-carbonitrile 1,4-di-N-oxide (MIC <0.2 μg/mL and SI >500).     

Synthesis and anti-inflammatory/antioxidant activities of some new ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives and of their 4,5-dihydro-(1H)-pyrazole analogues

We report the synthesis, anti-inflammatory and antioxidant activities of novel ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives and of their 4,5-dihydro-(1H)-pyrazole analogues. The tested compounds inhibit the carrageenin-induced rat paw edema (4.5-56.1%) and present important scavenging activities. Compound 2a is the most potent (56.1%) in the in vivo experiment and exhibits promising in vitro inhibition of soybean lipoxygenase (IC(50)<1microM).     

Environmental assessment of the Atlantic mackerel (<Emphasis Type="Italic">Scomber scombrus</Emphasis>) season in the Basque Country. Increasing the timeline delimitation in fishery LCA studies

Purpose  

The purpose of this study was to evaluate the environmental impacts linked to fish extraction on a temporal basis, in order to analyze the effect that stock abundance variations may have on reporting environmental burdens. Inventory data for the North-East Atlantic Mackerel (NEAM) fishing season were collected over an 8-year period and used to carry out a life cycle assessment (LCA). The selected fishery corresponds to the Basque coastal purse seining fleet.     

The physiological implications of urease inhibitors on N metabolism during germination of Pisum sativum and Spinacea oleracea seeds

The development of new nitrogen fertilizers is necessary to optimize crop production whilst improving the environmental aspects arising from the use of nitrogenous fertilization as a cultural practice. The use of urease inhibitors aims to improve the efficiency of urea as a nitrogen fertilizer by preventing its loss from the soil as ammonia. However, although the action of urease inhibitors is aimed at the urease activity in soil, their availability for the plant may affect its urease activity. The aim of this work was therefore to evaluate the effect of two urease inhibitors, namely acetohydroxamic acid (AHA) and N-(n-butyl) thiophosphoric triamide (NBPT), on the germination of pea and spinach seeds. The results obtained show that urease inhibitors do not affect the germination process to any significant degree, with the only process affected being imbibition in spinach, thus also suggesting different urease activities for both plants. Our findings therefore suggest an activity other than the previously reported urolytic activity for urease in spinach. Furthermore, of the two inhibitors tested, NBPT was found to be the most effective at inhibiting urease activity, especially in pea seedlings.     

Características y manejo del cáncer de mama primario en pacientes octogenarias: estudio retrospectivo

Background

The number of elderly patients with breast cancer is increasing, and a large proportion of these older patients do not receive conventional treatment. Clinical and biological characteristics of tumours at this age and survival according to local or systemic therapy were analysed.

Material and method

A total of 96 consecutive early breast cancer patients over 80 years of age diagnosed in our Unit between January 2002 and September 2008 were retrospectively investigated. Of them, 54 underwent surgery with or without adjuvant hormonal treatment, and 42 received primary hormonal therapy.

Results

Tumours of patients 80 years old or older had more favourable biological characteristics, including expression of steroid receptors, and absence of c-erb B2 expression. Overall survival was 50 months for the group subjected to surgery, and 44 months for the group who did not undergo surgery. The survival free of local recurrence in the surgery group was 44 months, whereas it was 18 months in the non-surgery group.

Conclusion

In a cohort of patients aged 80 years and older, survival was similar in those who received hormonal or surgical therapy, although the former had a shorter period of progression-free survival or local recurrence.     

Short term physiological implications of NBPT application on the N metabolism of Pisum sativum and Spinacea oleracea

The application of urease inhibitors in conjunction with urea fertilizers as a means of reducing N loss due to ammonia volatilization requires an in-depth study of the physiological effects of these inhibitors on plants. The aim of this study was to determine how the urease inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) affects N metabolism in pea and spinach. Plants were cultivated in pure hydroponic culture with urea as the sole N source. After 2 weeks of growth for pea, and 3 weeks for spinach, half of the plants received NBPT in their nutrient solution. Urease activity, urea and ammonium content, free amino acid composition and soluble protein were determined in leaves and roots at days 0, 1, 2, 4, 7 and 9, and the NBPT content in these tissues was determined 48 h after inhibitor application. The results suggest that the effects of NBPT on spinach and pea urease activity differ, with pea being most affected by this treatment, and that the NBPT absorbed by the plant caused a clear inhibition of the urease activity in pea leaf and roots. The high urea concentration observed in leaves was associated with the development of necrotic leaf margins, and was further evidence of NBPT inhibition in these plants. A decrease in the ammonium content in roots, where N assimilation mainly takes place, was also observed. Consequently, total amino acid contents were drastically reduced upon NBPT treatment, indicating a strong alteration of the N metabolism. Furthermore, the amino acid profile showed that amidic amino acids were major components of the reduced pool of amino acids. In contrast, NBPT was absorbed to a much lesser degree by spinach plants than pea plants (35% less) and did not produce a clear inhibition of urease activity in this species.     

Short Term Minimum Water Temperatures Determine Levels of Infection by the Amphibian Chytrid Fungus in Alytes obstetricans Tadpoles

Amphibians are one of the groups of wildlife most seriously threatened by emerging infectious disease. In particular, chytridiomycosis, caused by the aquatic fungus Batrachochytrium dendrobatidis, is responsible for amphibian species declines on a worldwide scale. Population-level outcomes following the introduction of the pathogen are context dependent and mediated by a large suite of abiotic and biotic variables. In particular, studies have shown that temperature has a key role in determining infection dynamics owing to the ectothermic nature of the amphibian host and temperature-dependency of pathogen growth rates. To assess the temperature-dependent seasonality of infectious burdens in a susceptible host species, we monitored lowland populations of larval midwife toads, Alytes obstetricians, in Central Spain throughout the year. We found that infections were highly seasonal, and inversely correlated against water temperature, with the highest burdens of infection seen during the colder months. Short-term impacts of water-temperature were found, with the minimum temperatures occurring before sampling being more highly predictive of infectious burdens than were longer-term spans of temperature. Our results will be useful for selecting the optimal time for disease surveys and, more broadly, for determining the key periods to undertake disease mitigation.     

Temporal Effects of a Begomovirus Infection and Host Plant Resistance on the Preference and Development of an Insect Vector,Bemisia tabaci,and Implications for Epidemics

Persistent plant viruses, by altering phenotypic and physiological traits of their hosts, could modulate the host preference and fitness of hemipteran vectors. A majority of such modulations increase vector preference for virus-infected plants and improve vector fitness, ultimately favouring virus spread. Nevertheless, it remains unclear how these virus-induced modulations on vectors vary temporally, and whether host resistance to the pathogen influences such effects. This study addressed the two questions using a Begomovirus-whitefly-tomato model pathosystem. Tomato yellow leaf curl virus (TYLCV) -susceptible and TYLCV-resistant tomato genotypes were evaluated by whitefly-mediated transmission assays. Quantitative PCR revealed that virus accumulation decreased after an initial spike in all genotypes. TYLCV accumulation was less in resistant than in susceptible genotypes at 3, 6, and 12 weeks post inoculation (WPI). TYLCV acquisition by whiteflies over time from resistant and susceptible genotypes was also consistent with virus accumulation in the host plant. Furthermore, preference assays indicated that non-viruliferous whiteflies preferred virus-infected plants, whereas viruliferous whiteflies preferred non-infected plants. However, this effect was prominent only with the susceptible genotype at 6 WPI. The development of whiteflies on non-infected susceptible and resistant genotypes was not significantly different. However, developmental time was reduced when a susceptible genotype was infected with TYLCV. Together, these results suggest that vector preference and development could be affected by the timing of infection and by host resistance. These effects could play a crucial role in TYLCV epidemics.     

Resveratrol directly affects in vitro lipolysis and glucose transport in human fat cells

Resveratrol is a naturally occurring polyphenol found in many dietary sources and red wine. Recognized as a cancer chemoprevention agent, an anti-inflammatory factor and an antioxidant molecule, resveratrol has been proposed as a potential anti-obesity compound and to be beneficial in diabetes. Most of the studies demonstrating the anti-adipogenic action of resveratrol were performed as long-term treatments on cultured preadipocytes. The aim of this study was to analyse the acute effects of resveratrol on glucose uptake and lipolysis in human mature adipocytes. Samples of subcutaneous abdominal adipose tissue were obtained from overweight humans and immediately digested by liberase. Fat cells were incubated (from 45 min to 4 h) with resveratrol 1 μM–1 mM. Then, glycerol release or hexose uptake was determined. Regarding lipolysis, the significant effects of resveratrol were found at 100 μM, consisting in a facilitation of isoprenaline stimulation and an impairment of insulin antilipolytic action. At 1 and 10 μM, resveratrol only tended to limit glucose uptake. Resveratrol 100 μM did not change basal glucose uptake but impaired its activation by insulin or by benzylamine. This inhibition was not found with other antioxidants. Such impairment of glucose uptake activation in fat cells may led to a reduced availability of glycerol phosphate and then to a decreased triacylglycerol assembly. Therefore, resveratrol increased triacylglycerol breakdown triggered by β-adrenergic activation and impaired lipogenesis. Consequently, our data indicate that resveratrol can be considered as limiting fat accumulation in human fat cells and further support its use for the mitigation of obesity.