Kinetics of propranolol uptake in muscle, skin, and fat of the isolated perfused rat hindlimb

The tissue distribution kinetics of a highly bound solute, propranolol, was investigated in a heterogeneous organ, the isolated perfused limb, using the impulse-response technique and destructive sampling. The propranolol concentration in muscle, skin, and fat as well as in outflow perfusate was measured up to 30 min after injection. The resulting data were analysed assuming (1) vascular, muscle, skin and fat compartments as well mixed (compartmental model) and (2) using a distributed-in-space model which accounts for the noninstantaneous intravascular mixing and tissue distribution processes but consists only of a vascular and extravascular phase (two-phase model). The compartmental model adequately described propranolol concentration-time data in the three tissue compartments and the outflow concentration-time curve (except of the early mixing phase). In contrast, the two-phase model better described the outflow concentration-time curve but is limited in accounting only for the distribution kinetics in the dominant tissue, the muscle. The two-phase model well described the time course of propranolol concentration in muscle tissue, with parameter estimates similar to those obtained with the compartmental model. The results suggest, first that the uptake kinetics of propranolol into skin and fat cannot be analysed on the basis of outflow data alone and, second that the assumption of well-mixed compartments is a valid approximation from a practical point of view las, e.g., in physiological based pharmacokinetic modelling). The steady-state distribution volumes of skin and fat were only 16 and 4%, respectively, of that of muscle tissue (16.7 ml), with higher partition coefficient in fat (6.36) than in skin (2.64) and muscle (2.79. (C) 2000 Elsevier Science B.V. All rights reserved.

Nitrogen dynamics and the physiological basis of stay-green in sorghum

Sorghum [Sorghum bicolor (L,) Moench] hybrids containing the stay-green trait retain more photosynthetically active leaves under drought than do hybrids that do not contain this trait. Since the Longevity and photosynthetic capacity of a leaf are related to its N status, it is important to clarify the role of N in extending leaf greenness in stay-green hybrids. Field studies were conducted in northeastern Australia to examine the effect of three water regimes and nine hybrids on N uptake and partitioning among organs. Nine hybrids varying in the B35 and KS19 sources of stay-green were grown under a fully irrigated control, post-flowering water deficit, and terminal water deficit. For hybrids grown under terminal water deficit, stay-green was viewed as a consequence of the balance between N demand by the grain and N supply during gain filling. On the demand side, grain numbers were 16% higher in the four stay-green than in the five senescent hybrids. On the supply side, age-related senescence provided an average of 34 and 42 kg N ha(-1) for stay-green and senescent hybrids, respectively. In addition, N uptake during grain filling averaged 116 and 82 kg ha(-1) in stay-green and senescent hybrids. Matching the N supply from these two sources with grain N demand found that the shortfall in N supply for grain filling in the stay-green and senescent hybrids averaged 32 and 41 kg N ha(-1) resulting in more accelerated leaf senescence in the senescent hybrids. Genotypic differences in delayed onset and reduced rate of leaf senescence were explained by differences in specific leaf nitrogen and N uptake during grain filling. Leaf nitrogen concentration at anthesis was correlated with onset (r = 0.751**, n = 27) and rate (r = -0.783**, n = 27) of leaf senescence ender terminal water deficit.

A twin study of psychometric intelligence and efficiency of information processing

Intelligence (IQ) can be seen as the efficiency of mental processes or cognition, as can basic information processing (IP) tasks like those used in our ongoing Memory, Attention and Problem Solving (MAPS) study. Measures of IQ and IP are correlated and both have a genetic component, so we are studying how the genetic variance in IQ is related to the genetic variance in IP. We measured intelligence with five subscales of the Multidimensional Aptitude Battery (MAB). The IP tasks included four variants of choice reaction time (CRT) and a visual inspection time (IT). The influence of genetic factors on the variances in each of the IQ, IP, and IT tasks was investigated in 250 identical and nonidentical twin pairs aged 16 years. For a subset of 50 pairs we have test–retest data that allow us to estimate the stability of the measures. MX was used for a multivariate genetic analysis that addresses whether the variance in IQ and IP measures is possibly mediated by common genetic factors. Analyses that show the modeled genetic and environmental influences on these measures of cognitive efficiency will be presented and their relevance to ideas on intelligence will be discussed.

Experimental methods for studying drug uptake in the head and brain

A number of techniques have been developed to study the disposition of drugs in the head and, in particular, the role of the blood-brain barrier (BBB) in drug uptake. The techniques can be divided into three groups: in-vitro, in-vivo and in-situ. The most suitable method depends on the purpose(s) and requirements of the particular study being conducted. In-vitro techniques involve the isolation of cerebral endothelial cells so that direct investigations of these cells can be carried out. The most recent preparations are able to maintain structural and functional characteristics of the BBB by simultaneously culturing endothelial cells with astrocytic cells,The main advantages of the in-vitro methods are the elimination of anaesthetics and surgery. In-vivo methods consist of a diverse range of techniques and include the traditional Brain Uptake Index and indicator diffusion methods, as well as microdialysis and positron emission tomography. In-vivo methods maintain the cells and vasculature of an organ in their normal physiological states and anatomical position within the animal. However, the shortcomings include renal acid hepatic elimination of solutes as well as the inability to control blood flow. In-situ techniques, including the perfused head, are more technically demanding. However, these models have the ability to vary the composition and flow rate of the artificial perfusate. This review is intended as a guide for selecting the most appropriate method for studying drug uptake in the brain.

Heterogeneity in inoculum potential and effectiveness of arbuscular mycorrhizal fungi

Arbuscular mycorrhizae are symbiotic associations among glomalean fungi and plant roots that often lead to enhanced water and nutrient uptake and plant growth. We describe experiments to test whether inoculum potential of arbuscular mycorrhizal (AM) fungal communities varies spatially within a broadleaf temperate forest, and also whether there is variability in the effectiveness of AM fungal communities in enhancing seedling growth. Inoculum potential of arbuscular mycorrhizal fungi in a temperate broad-leaved forest did not vary significantly among sites. Inoculum potential, measured as the extent to which the roots of red maple seedlings that had been germinated on sterile sand and then transplanted into the forest, were colonized by AM fungi, was similar in floodplain and higher elevation sites. It was as similar under ectomycorrhizal oaks as it was under red maples and other AM tree species. It was also similar among sites with deciduous understory shrubs with arbuscular mycorrhizae (spicebush, Lindera benzoin) and those with evergreen vegetation with ericoid mycorrhizae (mountain laurel, Kalmia latifolia). Where spicebush was the dominant understory shrub, inoculum potential was greater under gaps in the canopy than within the understory. Survivorship of transplanted red maple seedlings varied significantly over sites but was not strongly correlated with measures of inoculum potential. In a greenhouse growth experiment, arbuscular mycorrhizal fungal communities obtained from tree roots from the forest had different effects on plant growth. Seedlings inoculated with roots of red maple had twice the leaf area after 10 wk of growth compared to the AM community obtained from roots of southern red oaks. Thus, although there appears to be little heterogeneity in inoculum potential in the forest, there are differences in the effectiveness of different inocula. These effects have the potential to affect tree species diversity in forests by modifying patterns of seedling recruitment.

A coiled-coil region of an insect immune suppressor protein is involved in binding and uptake by hemocytes

Polydnaviruses are associated with certain parasitoid wasps and are introduced into the body cavity of the host caterpillar during oviposition. Some of the viral genes are expressed in host tissues and corresponding proteins are secreted into the hemocoel causing suppression of the host immune system. The Cotesia rubecula polydnavirus gene product, CrV1, effectively inactivates hemocytes by mediating cytoskeleton break-down. A precondition for the CrV1 function is the incorporation of the extracellular protein by hemocytes. Here, we show that a coiled-coil domain containing a putative leucine zipper is required for CrV1 function, since removal of this domain abolishes binding and uptake of the CrV1 protein by hemocytes. (C) 2002 Elsevier Science Ltd. All rights reserved.

Simultaneous X-ray imaging of plant root growth and water uptake in thin-slab systems

Direct and simultaneous observation of root growth and plant water uptake is difficult because soils are opaque. X-ray imaging techniques such as projection radiography or Computer Tomography (CT) offer a partial alternative to such limitations. Nevertheless, there is a trade-off between resolution, large field-of-view and 3-dimensionality: With the current state of the technology, it is possible to have any two. In this study, we used X-ray transmission through thin-slab systems to monitor transient saturation fields that develop around roots as plants grow. Although restricted to 2-dimensions, this approach offers a large field-of-view together with high spatial and dynamic resolutions. To illustrate the potential of this technology, we grew peas in 1 cm thick containers filled with soil and imaged them at regular intervals. The dynamics of both the root growth and the water content field that developed around the roots could be conveniently monitored. Compared to other techniques such as X-ray CT, our system is relatively inexpensive and easy to implement. It can potentially be applied to study many agronomic problems, such as issues related to the impact of soil constraints (physical, chemical or biological) on root development.

A comparison of the performance and biological efficiency of new knapsack sprayers and a controlled droplet application (CDA) sprayer for the control of the diamondback moth, Plutella xylostella L. (Lepidoptera : Plutellidae)

Field trials and laboratory bioassays were undertaken to compare the performance and efficacy (mortality of diamondback moth larvae) of insecticides applied to cabbages with three high volume hydraulic knapsack sprayers (NS-16, PB-20 and Selecta 12V) and a controlled droplet application (CDA) sprayer. In field experiments, the high volume knapsack sprayers (application rate 500-600 L ha(-1)) provided better spray coverage on the upper and lower surfaces of inner leaves, the upper surfaces of middle and outer leaves, and greater biological efficacy than the CDA sprayer (application rate 20similar to40 L ha(-1)). The PB-20 provided better spray coverage on the upper surface of middle leaves and both surfaces of outer leaves when compared with the Selecta 12V. However, its biological efficacy in the field was not significantly different from that of the other high volume sprayers. Increasing the application rate from 20 to 40 L ha(-1) for the CDA sprayer significantly increased droplet density but had no impact on test insect mortality. Laboratory evaluations of biological efficacy yielded higher estimates than field evaluations and there was no significant difference between the performance of the PB-20 and the CDA sprayer. Significant positive relationships were detected between insect mortality and droplet density deposited for both the PB-20 and the CDA sprayers.

Production efficiency and financing of public health: an analysis of small municipalities in the state of Sao Paulo - Brazil

This paper measured the variations in performance of small municipalities in the State of Sao Paulo, Brazil, regarding the technical efficiency in the use of public funds in public primary health care actions concerning the funding profile, in a scenario of fiscal federalism. Technical efficiency is one of the parameters of evaluation of public sector performance and was measured by means of Data Envelopment Analysis (DEA). The correlation analysis of DEA score was used to verify possible associations between technical efficiency and the funding profile of expenses with health care. The results showed that 6.41% of the municipalities were considered efficient. They also showed that the level of municipality dependence to inter-governmental general purpose grants and the national health funding specific purpose grants have negative correlation with efficiency scores.

Neighborhood and Efficiency in Manufacturing in Brazilian Regions: A Spatial Markov Chain Analysis

This paper analyzes the geography of regional competitiveness in manufacturing in Brazil. The authors estimate stochastic frontiers to calculate regional efficiency of representative firms in 137 regions in the period 2000-2006, in four sectors defined by technological intensity. The efficiency results are analyzed using Markov Spatial Transition Matrices to provide insights into the transition of regions between efficiency levels, considering their local spatial context. The results indicate that geography plays an important role in manufacturing competitiveness. In particular, regions with more competitive neighbors are more likely to improve their relative efficiency (pull effect) over time, and regions with less competitive neighbors are more likely to lose relative efficiency (drag effect). The authors find that the pull effect is stronger than the drag effect.

Evaluating the efficiency of fractional integration parameter estimators

This article deals with the efficiency of fractional integration parameter estimators. This study was based on Monte Carlo experiments involving simulated stochastic processes with integration orders in the range]-1,1[. The evaluated estimation methods were classified into two groups: heuristics and semiparametric/maximum likelihood (ML). The study revealed that the comparative efficiency of the estimators, measured by the lesser mean squared error, depends on the stationary/non-stationary and persistency/anti-persistency conditions of the series. The ML estimator was shown to be superior for stationary persistent processes; the wavelet spectrum-based estimators were better for non-stationary mean reversible and invertible anti-persistent processes; the weighted periodogram-based estimator was shown to be superior for non-invertible anti-persistent processes.

Application of Ti/RuO(2)-Ta(2)O(5) electrodes in the electrooxidation of ethanol and derivants: Reactivity versus electrocatalytic efficiency

The influence of the preparation method on the performance of RuO(2)-Ta(2)O(5) electrodes was evaluated toward the ethanol oxidation reaction (EOR). Freshly prepared RuO(2)-Ta(2)O(5) thin films containing between 30 and 80 at.% Ru were prepared by two different methods: the modified Pechini-Adams method (DPP) and standard thermal decomposition (STD). Electrochemical investigation of the electrode containing RuO(2)-Ta(2)O(5) thin films was conducted as a function of electrode composition in a 0.5-mol dm(-3) H(2)SO(4) solution, in the presence and absence of ethanol and its derivants (acetaldehyde and acetic acid). At a low ethanol concentration (5 mmol dm(-3)), ethanol oxidation leads to high yields of acetic acid and CO(2). On the other hand, an increase in ethanol concentration (15-1000 mmol dm(-3)) favors acetaldehyde formation, so acetic acid and CO(2) production is hindered, in this case. Electrodes prepared by DPP provide higher current efficiency than STD electrodes for all the investigated ethanol concentrations. This may be explained by the increase in electrode area obtained with the DPP preparation method compared with STD. (c) 2008 Elsevier Ltd. All rights reserved.

Determination of fluoxetine and norfluoxetine enantiomers in human plasma by polypyrrole-coated capillary in-tube solid-phase microextraction coupled with liquid chromatography-fluorescence detection

A sensitive, selective, and reproducible in-tube polypyrrole-coated capillary (PPY) solid-phase microextraction and liquid chromatographic method for fluoxetine and norfluoxetine enantiomers analysis in plasma samples has been developed, validated, and further applied to the analysis of plasma samples from elderly patients undergoing therapy with antidepressants. Important factors in the optimization of in-tube SPME efficiency are discussed, including the sample draw/eject volume, draw/eject cycle number, draw/eject flow-rate, sample pH, and influence of plasma proteins. Separation of the analytes was achieved with a Chiralcel OD-R column and a mobile phase consisting of potassium hexafluorophosphate 7.5 mM and sodium phosphate 0.25 M solution, pH 3.0, and acetonitrile (75:25, v/v) in the isocratic mode, at a flow rate of 1.0 mL/min. Detection was carried out by fluorescence absorbance at Ex/Em 230/290 nm. The multifunctional porous surface structure of the PPY-coated film provided high precision and accuracy for enantiomers. Compared with other commercial capillaries, PPY-coated capillary showed better extraction efficiency for all the analytes. The quantification limits of the proposed method were 10 ng/mL for R- and S-fluoxetine, and 15 ng/mL for R- and S-norfluoxetine, with a coefficient of variation lower than 13%. The response of the method for enantiomers is linear over a dynamic range, from the limit of quantification to 700ng/mL, with correlation coefficients higher than 0.9940. The in-tube SPME/LC method can therefore be successfully used to analyze plasma samples from ageing patients undergoing therapy with fluoxetine. (C) 2009 Elsevier B.V. All rights reserved.

Structural and Biochemical Correlates of Na(+), K(+)-ATPase Driven Ion Uptake Across the Posterior Gill Epithelium of the True Freshwater Crab, Dilocarcinus pagei (Brachyura, Trichodactylidae)

To better comprehend the structural and biochemical underpinnings of ion uptake across the gills of true freshwater crabs, we performed an ultrastructural, ultracytochemical and morphometric investigation, and kinetically characterized the Na(+), K(+)-ATPase, in posterior gill lamellae of Dilocarcinus pagei. Ultrastructurally, the lamellar epithelia are markedly asymmetrical: the thick, mushroom-shaped, proximal ionocytes contain elongate mitochondria (41% cell volume) associated with numerous (approximate to 14 mu m(2) membrane per mu m(3) cytoplasm), deep invaginations that house the Na(+), K(+)-ATPase, revealed ultracytochemically. Their apical surface is amplified (7.5 mu m(2) mu m(-2)) by stubby evaginations whose bases adjoin mitochondria below the subcuticular space. The apical membrane of the thin, distal ionocytes shows few evaginations (1.6 mu m(2) mu m(-2)), each surrounding a mitochondrion, abundant in the cytoplasm below the subcuticular space; basolateral invaginations and mitochondria are few. Fine basal cytoplasmic bridges project across the hemolymph space, penetrating into the thick ionocytes, suggesting ion movement between the epithelia. Microsomal Na(+), K(+)-ATPase specific activity resembles marine crabs but is approximate to 5-fold less than in species from fluctuating salinities, and freshwater shrimps, suggesting ion loss compensation by strategies other than Na(+) uptake. Enzyme apparent K(+) affinity attains 14-fold that of marine crabs, emphasizing the relevance of elevated K(+) affinity to the conquest of fresh water. Western blotting and biphasic ouabain inhibition disclose two alpha-subunit isoforms comprising distinct functional isoenzymes. While enzyme activity is not synergistically stimulated by NH(4)(+) and K(+), each increases affinity for the other, possibly assuring appropriate intracellular K(+) concentrations. These findings reveal specific structural and biochemical adaptations that may have allowed the establishment of the Brachyura in fresh water. J. Exp. Zool. 313A:508-523, 2010. (C) 2010 Wiley-Liss, Inc.