Drug concentration response relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist.

The aim of this study was to investigate the relationships between plasma concentrations of losartan, an orally active angiotensin II inhibitor, its active metabolite EXP3174, and angiotensin II blockade. Six healthy subjects received single oral doses of 40, 80, or 120 mg losartan and placebo at 1-week intervals in a crossover study. Angiotensin II blockade was assessed by the blood pressure response to exogenous angiotensin II before and after losartan administration. EXP3174 reached higher plasma concentrations and was eliminated more slowly than its parent compound; its levels paralleled the profile of angiotensin II blockade closer than losartan. Inhibition of the pressure response was dose dependent. The Hill-shaped relationship between response and EXP3174 concentration (or time-integrated variables) approached a plateau with 80 mg. The dose-dependent increase in plasma renin and angiotensin II exhibited a considerable individual scatter. We conclude that losartan produces a dose-dependent, effective angiotensin II blockade that is largely determined by the active metabolite EXP3174.

Dinâmica do pH da água das chuvas em Passo Fundo, RS

O objetivo deste trabalho foi avaliar a dinâmica do pH da água das chuvas em Passo Fundo, RS, de 1992 a 2007. A água foi coletada em recipiente de PVC (diâmetro de 10 cm) acoplado a um pluviômetro, e as amostras foram armazenadas em congelador para posterior determinação do pH. A dinâmica do pH da água foi avaliada por meio das médias mensais e anuais do pH, da probabilidade empírica da distribuição dos valores anuais de pH por estação do ano e da frequência relativa acumulada do pH. A água das chuvas incidentes na região de Passo Fundo apresentou pH acima de 5,6, que é o limite para que a chuva seja considerada ácida. A análise do período de 16 anos indicou tendência de redução do pH da água das chuvas em 0,023 ao ano. Nesse período, a redução foi de 6,1 para 5,8. As chuvas foram ligeiramente mais ácidas no verão e na primavera do que no outono e no inverno. Em geral, as chuvas incidentes na região não apresentaram riscos imediatos de acidificação ambiental.

Impaired chemical coupling of cerebral blood flow is compatible with intact neurological outcome in neonates with perinatal risk factors.

Early detection of pathophysiological factors associated with permanent brain damage is a major issue in neonatal medicine. The aim of our study was to evaluate the significance of the CO2 reactivity of cerebral blood flow (CBF) in neonates with perinatal risk factors. Fourteen ventilated neonates with perinatal risk factors (pathological cardiotocogramm, low cord pH, postpartal encephalopathy) were enrolled into this prospective study. The study was performed 18-123 h after birth. CBF was measured using the noninvasive intravenous 133Xe method. Two measurements were taken with a minimal PaCO2-difference of 5 mm Hg. From the two CBF values the CO2 reactivity was calculated. Outcome was evaluated 1 year after birth. The CBF values at a lower PaCO2 ranged from 6.6 to 115. 2 ml/100 g brain issue/min (median = 18.2) and at a higher PaCO2 level from 7.1 to 125.7 ml/100 g brain tissue/min (median = 18.75). The calculated CO2 reactivity ranged from -9.6 to 6.6% (median 1.1%) change in CBF/mm Hg change in PaCO2. CO2 reactivity correlated with lowest pH (r2 = 0.35, p = 0.02). Two infants died, one of neonatal sepsis, the other of heart failure. Neurological outcome at the age of 1 year was normal in 11 patients, 1 had severe cerebral palsy. From the 12 surviving patients the patient with severe neurological deficit showed the highest CBF values (125.7 ml/100 g/min). Impaired chemical coupling of cerebral blood flow is compatible with intact neurological outcome in neonates with perinatal risk factors. CO2 reactivity in these newborns correlates with the lowest pH and may reflect the severity of perinatal asphyxia.

Eficácia e pH de caldas de glifosato após a adição de fertilizantes nitrogenados e utilização de pulverizador pressurizado por CO2

Este trabalho foi desenvolvido com o objetivo de avaliar a eficácia e o pH de caldas de glifosato após a adição de fertilizantes nitrogenados e utilização de pulverizador pressurizado por CO2. Em campo, foram aplicadas duas doses de glifosato (360 e 720 g ha-1), isoladas ou combinadas a duas concentrações de ureia (2,5 e 5,0 g L-1) ou sulfato de amônio (7,5 e 15,0 g L-1). Em laboratório, mensurou-se o pH de caldas de glifosato após o uso de diferentes concentrações do produto e dos fertilizantes nitrogenados e após a utilização do pulverizador pressurizado por CO2. Em todas as avaliações do experimento em campo, a menor dose de glifosato teve maior eficácia biológica após a adição de sulfato de amônio (15 g L-1) à calda. A ureia (5 g L-1) proporcionou efeitos benéficos somente na avaliação aos 28 dias após a aplicação. Em laboratório, o aumento da concentração de glifosato promoveu gradativa acidificação da calda de pulverização, com estabilização do pH da solução em 4,5. O sulfato de amônio causou pequena acidificação da calda herbicida, enquanto a ureia não alterou o pH. O uso do pulverizador pressurizado por CO2 pouco alterou o pH da calda de glifosato. A maior eficácia do glifosato após a adição de fertilizantes nitrogenados à calda está pouco relacionada com alterações no pH da solução.

Aspergillus protein degradation pathways with different secreted protease sets at neutral and acidic pH.

Aspergillus fumigatus grows well at neutral and acidic pH in a medium containing protein as the sole nitrogen source by secreting two different sets of proteases. Neutral pH favors the secretion of neutral and alkaline endoproteases, leucine aminopeptidases (Laps) which are nonspecific monoaminopeptidases, and an X-prolyl dipeptidase (DppIV). Acidic pH environment promotes the secretion of an aspartic endoprotease of pepsin family (Pep1) and tripeptidyl-peptidases of the sedolisin family (SedB and SedD). A novel prolyl peptidase, AfuS28, was found to be secreted in both alkaline and acidic conditions. In previous studies, Laps were shown to degrade peptides from their N-terminus until an X-Pro sequence acts as a stop signal. X-Pro sequences can be then removed by DppIV, which allows Laps access to the following residues. We have shown that at acidic pH Seds degrade large peptides from their N-terminus into tripeptides until Pro in P1 or P'1 position acts as a stop for these exopeptidases. However, X-X-Pro and X-X-X-Pro sequences can be removed by AfuS28 thus allowing Seds further sequential proteolysis. In conclusion, both alkaline and acidic sets of proteases contain exoprotease activity capable of cleaving after proline residues that cannot be removed during sequential digestion by nonspecific exopeptidases.

Carbohydrate and nitrogen stores in Festuca paniculata under mowing explain dominance in subalpine grasslands

Cessation of traditional management threatens semi-natural grassland diversity through the colonisation or increase of competitive species adapted to nutrient-poor conditions. Regular mowing is one practice that controls their abundance. This study evaluated the ecophysiological mechanisms limiting short- and long-term recovery after mowing for Festuca paniculata, a competitive grass that takes over subalpine grasslands in the Alps following cessation of mowing. We quantified temporal variations in carbon (C) and nitrogen (N) content, starch, fructan and total soluble sugars in leaves, stem bases and roots of F. paniculata during one growth cycle in mown and unmown fields and related them to the dynamics of soil mineral N concentration and soil moisture. Short-term results suggest that the regrowth of F. paniculata following mowing might be N-limited, first because of N dilution by C increments in the plant tissue, and second, due to low soil mineral N and soil moisture at this time of year. However, despite short-term effects of mowing on plant growth, C and N content and concentration at the beginning of the following growing season were not affected. Nevertheless, total biomass accumulation at peak standing biomass was largely reduced compared to unmown fields. Moreover, lower C storage capacity at the end of the growing season impacted C allocation to vegetative reproduction during winter, thereby dramatically limiting the horizontal growth of F. paniculata tussocks in the long term. We conclude that mowing reduces the growth of F. paniculata tussocks through both C and N limitation. Such results will help understanding how plant responses to defoliation regulate competitive interactions within plant communities.

A decrease of plasma macrophage migration inhibitory factor concentration is associated with lower numbers of circulating lymphocytes in experimental Plasmodium falciparum malaria.

Macrophage migration inhibitory factor (MIF) has recently been implicated in the pathogenesis of malarial anaemia. However, field studies have reported contradictory results on circulating MIF concentrations in patients with clinically overt Plasmodium falciparum malaria. We determined plasma MIF levels over time in 10 healthy volunteers during experimental P. falciparum infection. Under fully controlled conditions, MIF levels decreased significantly during early blood-stage infection and reached a nadir at day 8 post-infection. A decrease in the number of circulating lymphocytes, which are an important source of MIF production, paralleled the decrease in MIF levels. Monocyte/macrophage counts remained unchanged. At MIF nadir, the anti-inflammatory cytokine interleukin (IL)-10, which is an inhibitor of T-cell MIF production, was detectable in only 2 of 10 volunteers. Plasma concentrations of the pro-inflammatory cytokines IL-8 and IL-1beta were only marginally elevated. We conclude that circulating MIF levels decrease early in blood-stage malaria as a result of the decline in circulating lymphocytes.

Simbiose de bactérias fixadoras de nitrogênio com feijoeiro-comum em diferentes valores de pH

O objetivo deste trabalho foi avaliar o efeito do pH do meio de cultivo na eficiência simbiótica de estirpes de Rhizobium, em solo com e sem calagem. Foram realizados experimentos em casa de vegetação, com e sem calagem, e no campo, apenas com calagem. O delineamento experimental utilizado foi de blocos ao acaso com quatro repetições, e os tratamentos foram cinco estirpes de Rhizobium (UFLA 02-100, UFLA 02-68, UFLA 04-195, UFLA 04-202 e CIAT 899), cultivadas em meio de cultura 79 com diferentes valores de pH (5,0, 6,0 e 6,9), e testemunhas sem inoculação, com ou sem nitrogênio mineral. Foram avaliados número e massa de matéria seca de nódulos, massa de matéria seca da parte aérea, eficiência relativa, teor e acúmulo de nitrogênio na parte aérea e nos grãos, número de vagens por planta, número de grãos por vagem e rendimento e massa de 100 grãos. O valor de pH ideal para o meio de cultivo variou com as estirpes e com a variável analisada. Os tratamentos que receberam calagem foram superiores aos demais. No campo, independentemente do pH do inoculante, as populações nativas do solo e as estirpes introduzidas promoveram rendimento de grãos semelhante ao da testemunha com 70 kg ha-1 de N e ao da estirpe referência CIAT 899.

IL-10 controls cystatin C synthesis and blood concentration in response to inflammation through regulation of IFN regulatory factor 8 expression.

Cystatin C (CstC) is a cysteine protease inhibitor of major clinical importance. Low concentration of serum CstC is linked to atherosclerosis. CstC can prevent formation of amyloid β associated with Alzheimer's disease and can itself form toxic aggregates. CstC regulates NO secretion by macrophages and is a TGF-β antagonist. Finally, the serum concentration of CstC is an indicator of kidney function. Yet, little is known about the regulation of CstC expression in vivo. In this study, we demonstrate that the transcription factor IFN regulatory factor 8 (IRF-8) is critical for CstC expression in primary dendritic cells. Only those cells with IRF-8 bound to the CstC gene promoter expressed high levels of the inhibitor. Secretion of IL-10 in response to inflammatory stimuli downregulated IRF-8 expression and consequently CstC synthesis in vivo. Furthermore, the serum concentration of CstC decreased in an IL-10-dependent manner in mice treated with the TLR9 agonist CpG. CstC synthesis is therefore more tightly regulated than hitherto recognized. The mechanisms involved in this regulation might be targeted to alter CstC production, with potential therapeutic value. Our results also indicate that caution should be exerted when using the concentration of serum CstC as an indicator of kidney function in conditions in which inflammation may alter CstC production.

Spittlebug impacts on sugarcane quality and ethanol production

The objective of this work was to evaluate the impacts of spittlebug (Mahanarva fimbriolata) attack on sugarcane quality and ethanol production. Technological and microbiological parameters of juice and fermentation process were evaluated in ten fermentation cycles and two harvest seasons. Treatments consisted of different spittlebug stalk damage levels: control, with 100% of apparently healthy stalks; medium, with 15% of damaged or dry stalks (DDS); high, with 30% of DDS; and very high, with 60% of DDS. Spittlebug attack caused significant losses in cane quality, reducing total soluble solids, sucrose content, total reducing sugars, and pH, and increasing total phenolic compounds, and total and volatile juice acidity. The fermentation process was also significantly affected, resulting in lower ethanol content in wine. There was an increase in acetaldehyde concentration in the distillate. The spittlebug attack caused negative impacts on sugarcane quality and fermentation process, and these impacts are stronger in late season harvests.

Cambios de color y pH causados por el PVAc en bienes culturales

Este artículo presenta los primeros resultados del estudio "Identificación de patologías causadas por el PVAc en bienes culturales" que se está realizando en la Sección de Conservación-Restauración de la Facultad de Bellas Artes, Universidad de Barcelona. El trabajo se basa en el estudio de obras originales que fueron tratadas con PVAc en los años 70-80 y pretende identificar los problemas que genera el PVAc en materiales de archivo, arqueológicos, pintura sobre tela, sobre madera y pintura mural. Tras el análisis de las obras originales, se han preparado muestras probeta que reproducen sus características, así como de adhesivos de PVAc comerciales y de uso específico en restauración. Éstas han sido analizadas antes y después de someterlas a dos fases consecutivas de envejecimiento acelerado. También se han analizado obras originales con PVAc aplicado hace aproximadamente 30 años. El artículo presenta los resultados de las mediciones de color y pH en las muestras probeta antes y después de la primera fase de envejecimiento acelerado y, también, en las muestras envejecidas de forma natural durante 10 años.

A study of the effects of PVAC on works of art on paper and wood: pH and colour change

This paper presents the preliminary findings of pH and colour measurements carried out on artworks on paperand on wood that had been treated with a poly(vinyl acetate) (PVAC) based adhesive in the 1980s. In both cases, areas treated with PVAC proved to be less acidic than untreated areas. Contrary to expectations, the conservation treatments have not, as yet, increased acidity levels in the objects under study. Colour measurements of the works on paper showed that those that had been backed with a cotton fabric using a mixture of methylcellulose and PVAC were less yellow than those from the same print run that had not been backed. This finding suggests that the backing somehow prevented the natural degradation of the support. In view of these preliminary results, further research is clearly needed. This study forms part of a broader ongoing project to assess the role of PVAC in the conservation of a range of cultural assets.

Cambios de color y pH causados por el PVAc en bienes culturales

Este artículo presenta los primeros resultados del estudio "Identificación de patologías causadas por el PVAc en bienes culturales" que se está realizando en la Sección de Conservación-Restauración de la Facultad de Bellas Artes, Universidad de Barcelona. El trabajo se basa en el estudio de obras originales que fueron tratadas con PVAc en los años 70-80 y pretende identificar los problemas que genera el PVAc en materiales de archivo, arqueológicos, pintura sobre tela, sobre madera y pintura mural. Tras el análisis de las obras originales, se han preparado muestras probeta que reproducen sus características, así como de adhesivos de PVAc comerciales y de uso específico en restauración. Éstas han sido analizadas antes y después de someterlas a dos fases consecutivas de envejecimiento acelerado. También se han analizado obras originales con PVAc aplicado hace aproximadamente 30 años. El artículo presenta los resultados de las mediciones de color y pH en las muestras probeta antes y después de la primera fase de envejecimiento acelerado y, también, en las muestras envejecidas de forma natural durante 10 años.