Chiral pharmacokinetics of rac-flurbiprofen and pharmacodynamics of anabolic bone response in the normal rat

The route of administration of the NSAID, flurbiprofen (sq vs. po) resulted in positive and negative results respectively with regard to enhanced cancellous and cortical bone accumulation in the immature rat. This pharmacokinetic study was an effort to understand the pharmacodynamic difference between the two routes of administration observed when the same dose range of drug, given as single daily doses, had been employed in both studies. Conventional chiral pharmacokinetics were evaluated in young rats. A significant difference was observed in the T_max of the active (S)-enantiomer by both administration routes (sq 4 h and po 1 h). The bioavailability, as evaluated by AUCs favored the sq route as expected. The plasma concentrations over 18 h, at steady state, for one po dose group (0.5 mg/kg/day) fell well within the therapeutic window described by the 0.1 and 0.5 mg/kg sq doses which had demonstrated anabolic bone activity. Oral dosing had exhibited no significant bone activity. We conclude that the pharmacodynamic difference between routes of administration cannot be simply explained on a pahrmacokinetic basis. Consequently, experiments detailing the pharmacodynamics and pharmacokinetics of single and multiple dose administration of aryl-propionic acids in normal and osteopenic states need further pharmacologic study. © 1994 Wiley-Liss, Inc.     

细胞电穿孔动态过程的荧光测量

利用改进后的Ｔｈ／ＤＰＡ荧光方法及探针ＥＢ对人血影及大鼠骨髓细胞电穿孔的动态过程及其与电脉冲参数的关系进行了系统的研究．测量结果表明,在临界点以上电场作用下,血影电穿孔在电击后０．２—０．３ｓ时达最大,在约０．８ｓ时愈合;而大鼠骨髓细胞电穿孔在电击后０．４—０．９ｓ达到最大,３－５ｓ左右愈合;电穿孔大小及扩大、愈合速率与电脉冲参数有关。１０－４０ｍｍｏｌ／Ｌ乙醇和５－２０ｍｍｏｌ／Ｌ成二醛抑制血影对Ｔｂ３＋离子的电通透,相同浓度的成二醛作用强于乙醇。这些结果将为电穿孔技术的合理应用提供参考。     

Nitrogen losses in puddled soils as affected by timing of water deficit and nitrogen fertilization

Erratic rainfall in rainfed lowlands and inadequate water supply in irrigated lowlands can results in alternate soil drying and flooding during a rice (Oryza sativa L.) cropping period. Effects of alternate soil drying and flooding on N loss by nitrification-denitrification have been inconsistent in previous field research. To determine the effects of water deficit and urea timing on soil NO₃ and NH₄, floodwater NO₃, and N loss from added ¹⁵N-labeled urea, a field experiment was conducted for 2 yr on an Andaqueptic Haplaquoll in the Philippines. Water regimes were continuously flooded, not irrigated from 15 to 35 d after transplanting (DT), or not irrigated from 41 to 63 DT. The nitrogen treatments in factorial combination with water regimes were no applied N and 80 kg urea-N ha^–1, either applied half basally and half at 37 DT or half at 11 DT and half at 65 DT. Water deficit at 15 to 35 DT and 41 to 63 DT, compared with continuous soil flooding, significantly reduced extractable NH₄ in the top 30-cm soil layer and resulted in significant but small (<1.0 kg N ha^–1) soil NO₃ accumulations. Soil NO₃, which accumulated during the water deficit, rapidly disappeared after reflooding. Water deficit at 15 to 35 DT, unlike that at 41 to 63 DT, increased the gaseous loss of added urea N as determined from unrecovered ¹⁵N in ¹⁵N balances. The results indicate that application of urea to young rice in saturated or flooded soil results in large, rapid losses of N (mean = 35% of applied N), presumably by NH₃ volatilization. Subsequent soil drying and flooding during the vegetative growth phase can result in additional N loss (mean = 14% of applied N), presumably by nitrification-denitrification. This additional N loss due to soil drying and flooding decreases with increasing crop age, apparently because of increased competition by rice with soil microorganisms for NH₄ and NO₃.     

Field investigations of ammonia exchange between barley plants and the atmosphere. I. Concentration profiles and flux densities of ammonia

The exchange of ammonia between the atmosphere and the canopy of spring barley crops growing at three levels of nitrogen application (medium N, high N and excessive N) was studied over two consecutive growing seasons by use of micrometeorological techniques. In most cases, ammonia was emitted from the canopy to the atmosphere. The emission started around 2 weeks before anthesis, and peaked about or shortly after anthesis. The volatilization of ammonia only took place in the daytime. During the night-time, atmospheric ammonia was frequently aborbed by the canopy. Occasionally, plants in the medium and high N treatments also absorbed ammonia from the atmosphere during the daytime. Daytime absorption of ammonia never occurred in the excessive N canopy. The loss of ammonia from the canopy amounted in both years to 0.5–1.5 kg NH₃-N ha^?1 and increased with the N status of the canopy. In agreement with the small losses of ammonia, the content of ¹⁵N-labelled nitrogen in the plants did not decline during the grain-filling period. The experimental years were characterized by very favourable conditions for grain dry matter formation, and for re-utilization of nitrogen mobilized from leaves and stems. Consequently, a very high part of the nitrogen in the mature plants was located in grain dry matter (80–84% in 1989; 74–80% in 1990). The efficient re-utilization of nitrogen may have reduced the volatilization of ammonia.     

Insulin-like growth factor I enhances the formation of type I collagen in hydrocortisone-treated human osteoblasts

We have studied the effect of insulin-like growth factor I (IGF-I) on the formation of osteocalcin and type I collagen in isolated human osteoblasts. IGF-I at and above 0.1 nM stimulated the formation of type I collagen as measured by the type I procollagen carboxyterminal peptide (PICP), in human osteoblasts, incubated for 72 hrs in serumfree conditions. The secretion of osteocalcin was not affected by IGF-I while 1,25(OH)₂ vitamin D₃ significantly enhanced the formation of osteocalcin. When human osteoblast-like cells were incubated with hydrocortisone (1 M), a significant decrease in the release of both PICP and osteocalcin was seen. Addition of IGF-I to human osteoblasts also treated with hydrocortisone normalized the PICP-formation but did not affect the suppressed osteocalcin-formation. These data indicate that IGF-I reverses selective effects of hydrocortisone on bone.     

渍水对冬小麦生长的危害及其生理效应

小麦受渍后叶片的光合和蒸腾速率迅速下降,而后则显微弱的回升趋势。渍害不仅削弱小麦光合产物的积累,并且改变光合产物在地上部分和根系中的分配比例;植株根／冠比下降,而黄叶的发展与根／冠比的变化呈显著负相关;渍害改变小麦的发育进程,尤其是后期渍害明显促使小麦早衰。认为清水使叶片光合速率降低、光合有效面积损失和衰老加速,从而危害小麦的生长。     

Stimulatory effect of β-alanyl-L-histidinato zinc on cell proliferation is dependent on protein synthesis in osteoblastic MC3T3-E1 cells

The effect of -alanyl-L-histidinato zinc (AHZ) on bone metabolism was investigated in osteoblastic MC3T3-El cells. Cells were cultured for 3 days at 37°C in a CO₂ incubator in plastic dishes containing -modified minimum essential medium supplemented with 10% fetal bovine serum. After the cultures, the medium was exchanged for that containing 0.1% bovine serum albumin plus various concentrations of AHZ or other reagents, and the cells were cultured further for appropriate periods of time. The presence of AHZ (10^–7–10^–5M) stimulated the proliferation of cells. AHZ (10^–6 and 10^–5M) increased deoxyribonucleic acid (DNA) content in the cells with 48hr-culture. This increase was completely blocked by the presence of cycloheximide (10^–6M) or hydroxyurea (10^–3M). Also, the presence of cycloheximide (10^–6M) completely inhibited the AHZ (10^–5M)-induced increase in the proliferation of cells. Meanwhile, parathyroid hormone (10^–7M), estrogen (10^–9M) and insulin (10^–M) significantly increased cellular DNA content. However, these hormonal effects clearly lowered in comparison with that of AHZ (10^–5M). Dibutyryl cyclic AMP (10^–4M) and zinc sulfate (10^–5M) did not cause a significant increase in cellular DNA content. The present results support the view that AHZ has a direct specific proliferative effect on osteoblastic cellsin vitro and that this effect is dependent on protein synthesis.     

The influence of ethnic differences upon human responses due to thermal environment

1. 1. The influence of ethnic differences is discussed with reference to the following issues.

2. 2. It has been found that total numbers of active sweat glands increase in tropical populations compared with people from northern latitudes.

3. 3. It has also been observed that the active sweat glands of Eskimos are fewer than those of Caucasians.

4. 4. The rate of the evaporated sweat loss was calculated by measuring body weight loss and it was found that the evaporated sweat loss of Caucasians is larger than that of Japanese in the same climate.

5. 5. Meteorological factors might have been responsible for the smaller loss in Japanese compared with that of Japanese-Americans.

6. 6. Under the same experimental conditions, it was observed that there were little or no differences between the Caucasians and Negros.

Pan-Arctic soil moisture control on tundra carbon sequestration and plant productivity

Long-term atmospheric CO₂ concentration records have suggested a reduction in the positive effect of warming on high-latitude carbon uptake since the 1990s. A variety of mechanisms have been proposed to explain the reduced net carbon sink of northern ecosystems with increased air temperature, including water stress on vegetation and increased respiration over recent decades. However, the lack of consistent long-term carbon flux and in situ soil moisture data has severely limited our ability to identify the mechanisms responsible for the recent reduced carbon sink strength. In this study, we used a record of nearly 100 site-years of eddy covariance data from 11 continuous permafrost tundra sites distributed across the circumpolar Arctic to test the temperature (expressed as growing degree days, GDD) responses of gross primary production (GPP), net ecosystem exchange (NEE), and ecosystem respiration (ER) at different periods of the summer (early, peak, and late summer) including dominant tundra vegetation classes (graminoids and mosses, and shrubs). We further tested GPP, NEE, and ER relationships with soil moisture and vapor pressure deficit to identify potential moisture limitations on plant productivity and net carbon exchange. Our results show a decrease in GPP with rising GDD during the peak summer (July) for both vegetation classes, and a significant relationship between the peak summer GPP and soil moisture after statistically controlling for GDD in a partial correlation analysis. These results suggest that tundra ecosystems might not benefit from increased temperature as much as suggested by several terrestrial biosphere models, if decreased soil moisture limits the peak summer plant productivity, reducing the ability of these ecosystems to sequester carbon during the summer.     

The ecosystem wilting point defines drought response and recovery of a Quercus-Carya forest

Soil and atmospheric droughts increasingly threaten plant survival and productivity around the world. Yet, conceptual gaps constrain our ability to predict ecosystem-scale drought impacts under climate change. Here, we introduce the ecosystem wilting point (Ψ_EWP), a property that integrates the drought response of an ecosystem's plant community across the soil–plant–atmosphere continuum. Specifically, Ψ_EWP defines a threshold below which the capacity of the root system to extract soil water and the ability of the leaves to maintain stomatal function are strongly diminished. We combined ecosystem flux and leaf water potential measurements to derive the Ψ_EWP of a Quercus-Carya forest from an “ecosystem pressure–volume (PV) curve,” which is analogous to the tissue-level technique. When community predawn leaf water potential (Ψ_pd) was above Ψ_EWP (=−2.0 MPa), the forest was highly responsive to environmental dynamics. When Ψ_pd fell below Ψ_EWP, the forest became insensitive to environmental variation and was a net source of carbon dioxide for nearly 2 months. Thus, Ψ_EWP is a threshold defining marked shifts in ecosystem functional state. Though there was rainfall-induced recovery of ecosystem gas exchange following soaking rains, a legacy of structural and physiological damage inhibited canopy photosynthetic capacity. Although over 16 growing seasons, only 10% of Ψ_pd observations fell below Ψ_EWP, the forest is commonly only 2–4 weeks of intense drought away from reaching Ψ_EWP, and thus highly reliant on frequent rainfall to replenish the soil water supply. We propose, based on a bottom-up analysis of root density profiles and soil moisture characteristic curves, that soil water acquisition capacity is the major determinant of Ψ_EWP, and species in an ecosystem require compatible leaf-level traits such as turgor loss point so that leaf wilting is coordinated with the inability to extract further water from the soil.