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Occurrence, absorption and metabolism of short chain fatty acids in the digestive tract of mammals.

Short chain fatty acids (SCFA) also named volatile fatty acids, mainly acetate, propionate and butyrate, are the major end-products of the microbial digestion of carbohydrates in the alimentary canal. The highest concentrations are observed in the forestomach of the ruminants and in the large intestine (caecum and colon) of all the mammals. Butyrate and caproate released by action of gastric lipase on bovine milk triacylglycerols ingested by preruminants or infants are of nutritional importance too. Both squamous stratified mucosa of rumen and columnar simple epithelium of intestine absorb readily SCFA. The mechanisms of SCFA absorption are incompletely known. Passive diffusion of the unionized form across the cell membrane is currently admitted. In the lumen, the necessary protonation of SCFA anions could come first from the hydration of CO2. The ubiquitous cell membrane process of Na+-H+ exchange can also supply luminal protons. Evidence for an acid microclimate (pH = 5.8-6.8) suitable for SCFA-protonation on the surface of the intestinal lining has been provided recently. This microclimate would be generated by an epithelial secretion of H+ ions and would be protected by the mucus coating from the variable pH of luminal contents. Part of the absorbed SCFA does not reach plasma because it is metabolized in the gastrointestinal wall. Acetate incorporation in mucosal higher lipids is well-known. However, the preponderant metabolic pathway for all the SCFA is catabolism to CO2 except in the rumen wall where about 80% of butyrate is converted to ketone bodies which afterwards flow into bloodstream. Thus, SCFA are an important energy source for the gut mucosa itself.

Animals↗

From critical levels to critical loads for ozone: a discussion of a new experimental and modelling approach for establishing flux-response relationships for agricultural crops and native plant species.

Present critical levels for ozone (O3) for protecting vegetation against adverse effects are based on exposure-response relationships mainly derived from open-top chamber experiments and are expressed as an Accumulated exposure Over a Threshold of 40 ppb (AOT40). In that context with a revision of the UN (United Nations)-ECE (Economic Commission for Europe) Gothenburg protocol, AOT40 values should be replaced by flux-oriented quantities, i.e. in the end by critical loads. At present, the database for the derivation of critical loads for O3 is extremely inadequate. Furthermore, the currently available flux-response relationships are also derived from open-top chamber experiments. The use of a relationship for spring wheat in a risk assessment for an agricultural site in Hesse, Germany, demonstrates in principle, the applicability of the critical load concept for O3. Comparisons of diurnal variation of stomatal uptake and AOT40 showed that a major part of toxicologically effective stomatal uptake occurred before noon whereas the AOT40 values were dominated by the O3 concentrations during afternoon. In other words, the AOT40 exposure index do not adequately address the O3 burden during hours when plants are sensitive to O3 uptake. However, due to the differences in radiation, air temperature and humidity between the chamber and the ambient microclimates, a derivation of flux-response relationships from chamber experiments is likely to be questionable, especially for species rich ecosystems: Here, without any changes in the pollution climate, significant modifications of species composition as well as an earlier beginning of the growing season has been previously observed. To overcome the problems associated with chamber-derived flux-response relationships, a new experimental and modelling concept, was developed. The approach, briefly described in this paper, combines methods in air pollution toxicology and micrometeorology. As an analogy to the free-air fumigation concept, O3 is released into the air by an injection system above the plant canopy. The assessment of dispersion and surface deposition of O3 released is based on Lagrangian trajectory modelling. Depending on wind direction and velocity, atmospheric stratification and surface roughness, without any disturbance of the microclimate and micrometeorology, several sub-areas can be identified around the source position with differing deposition rates above the ambient level. Taking into account the actual O3 background deposition, deposition rates and vegetation responses observed in these sub-areas can easily be used to derive flux-effect relationships under ambient conditions and more realistic limiting values to protect our environment.

Air Pollutants↗

Environmental control of stomatal conductance in forest trees of the Great Smoky Mountains National Park.

To determine if stomatal conductance (g(s)) of forest trees could be predicted from measures of leaf microclimate, diurnal variability in in situ g(s) was measured in black cherry (Prunus serotina), red maple (Acer rubrum), and northern red oak (Quercus rubra). Relative to overstory trees, understory saplings exhibited little diurnal variability in g(s) and ozone uptake. Depending on species and site, up to 30% of diurnal and seasonal variation in g(s )of overstory trees was explained by photosynthetically active radiation and vapor pressure deficit. Daily maximum g(s) was significantly related to soil moisture in overstory northern red oak and black cherry (R(2) ranged from 33 to 65%). Although g(s) was not fully predicted using instantaneous measures of leaf microclimate, ozone uptake of large forest trees was reduced by low soil moisture.

Journal Article↗

Stimulation of three distinct guanylate cyclases induces mucosal surface alkalinisation in rat small intestine in vitro.

The absorptive surface of the small intestine is isolated from bulk pH changes in the luminal contents by a zone of maintained low pH, the acid microclimate. The present study set out to compare the effects of stimulation of each of the three guanylate cyclases (GCs) expressed in the intestinal mucosa on the pH microclimate of rat jejunum in vitro. The tissue was exposed to specific ligands for each of the GCs and mucosal surface pH determinations were made by a miniaturised glass pH electrode. The ligands used were E. coli STa enterotoxin, atrial natriuretic peptide (ANP) and nitric oxide (NO, via the donor sodium nitroprusside (SNP)). Challenge from all three agonists resulted in significant alkalinisation of the jejunal mucosa. The actions of SNP were blocked by the soluble GC inhibitor, methylene blue (MB) whereas those of STa were unaffected by MB. The data are consistent with previous observations that cGMP-induced inhibition of brush border Na+/H+ exchange results in elevation of mucosal surface pH. We conclude that all three of the identified GC pathways in the intestinal mucosa are capable of contributing to the control of mucosal acidification in the upper small intestine.

Alkalies↗

Thermal biology of the fossorial rodent Ctenomys fulvus from the Atacama desert, northern Chile.

The Andean tuco-tuco, Ctenomys fulvus (Rodentia: Ctenomyidae) inhabits one of the most arid regions of the world, the Salar de Atacama, Northeast of Antofagasta, Chile (23 degrees 17'06"S, 68 degrees 05'43"W; 2.240 m.a.s.l). We found that a stable microclimate in burrows, a low evaporative water loss (EWL), and a diet of roots (59% water content) are the main factors that permit the survival of this fossorial species in harsh desert conditions. Large circadian variation in T(a) was observed above ground. Daily DeltaT(a) (T(a) max - T(a) min) = 37.9+/-0.2 degrees C in summer and in winter. In contrast, circadian variation of T(a) inside the burrows was only 5.8+/-0.5 degrees C in the same seasons. Relative humidity (RH) was 1.9-3.1% during the day, increasing to maximum values of 27% at night and early morning. Inside the burrows RH was higher and quite stable, ranging between 53.1 and 65%, independent of the time of day and season. EWL, measured between 10 and 25 degrees C, was low (1.26 mg/g h), and a moderate increase of 13-20% was observed at higher temperatures. The low EWL may prevent dehydration. However, because of the low heat loss capability, animals became hyperthermic (0.8-1.6 degrees C) in dry air at T(a)=30-35 degrees C. As T(a) during afternoon normally exceeded 35 degrees C, the microclimate of burrows provided the only way to avoid the lethal effects of hyperthermia.

Journal Article↗

Acylation of peptides by lactic acid solutions.

To simplify the search for effective mechanisms to suppress peptide acylation inside drug delivery devices made of poly(D,L-lactic acid) (PLA) and poly(lactic-co-glycolic acid), we were looking for a suitable model system that would allow screening of strategies for peptide stabilization. With their low pH and the presence of lactic acid oligomers, diluted lactic acid solutions promised to be a suitable test system that mimics the microclimate in degrading PLA devices. We created solutions of 1-50% (w/w) lactic acid by dilution of concentrated lactic acid. Using high performance liquid chromatography (HPLC) and high performance liquid chromatography coupled with mass spectrometry (HPLC-MS) analysis, oligomer hydrolysis was monitored during the equilibration process of the diluted solutions. Their final oligomer content was determined by titration and by calculations based on HPLC data. HPLC-MS analysis of human atrial natriuretic peptide (ANP) stability in different lactic acid solutions at 37 degrees C for 4 weeks demonstrated that ANP underwent acylation even in diluted solutions containing only 0.05% (w/w) lactic acid oligomers. Purity analysis of lactic acid solutions allowed us to compare the conditions in the solution test-system to the microclimate that prevails inside degrading PLA microspheres.

Acylation↗

A method for determining the heat transfer and water vapour permeability of patient support systems.

The formation of pressure ulcers can be exacerbated by a breakdown in the integrity of the patient's skin caused by poor maintenance of the skin microclimate. Patient support systems (PSSs-specialised beds, mattresses, chairs, cushions and pads) play an important role in the dissipation of heat and moisture away from the skin/support interface which is necessary in order to maintain the physiological skin microclimate. This paper reports a laboratory method and theory for the simultaneous measurement of the heat and water vapour dissipating properties of PSSs. The results demonstrate that the method is extremely selective, exhibiting very significant differences between the PSSs tested. It also shows that assessing PSS covers independently does not necessarily indicate the overall performance of the complete PSS.

Air↗

Using experimental manipulation to assess the roles of leaf litter in the functioning of forest ecosystems.

The widespread use of forest litter as animal bedding in central Europe for many centuries gave rise to the first litter manipulation studies, and their results demonstrated that litter and its decomposition are a vital part of ecosystem function. Litter plays two major roles in forest ecosystems: firstly, litterfall is an inherent part of nutrient and carbon cycling, and secondly, litter forms a protective layer on the soil surface that also regulates microclimatic conditions. By reviewing 152 years of litter manipulation experiments, I show that the effects of manipulating litter stem from changes in one, or both, of these two functions, and interactions between the variables influenced by the accumulation of litter can result in feedback mechanisms that may intensify treatment effects or mask responses, making the interpretation of results difficult.Long-term litter removal increased soil bulk density, overland flow, erosion, and temperature fluctuations and upset the soil water balance, causing lower soil water content during dry periods. Soil pH increased or decreased in response to manipulation treatments depending on forest type and initial soil pH, but it is unclear why there was no uniform response. Long-term litter harvesting severely depleted the forests of nutrients. Decreases in the concentrations of available P, Ca, Mg, and K in the soil occurred after only three to five years. The decline in soil N occurred over longer periods of time, and the relative loss was greater in soils with high initial nitrogen concentration. Tree growth declined with long-term litter removal, probably due to lower nutrient availability. Litter manipulation also added or removed large amounts of carbon thereby affecting microbial communities and altering soil respiration rates. Litter manipulation experiments have shown that litter cover acts as a physical barrier to the shoot emergence of small-seeded species; further, the microclimate maintained by the litter layer may be favourable to herbivores and pathogens and is important in determining later seedling survival and performance. Litter manipulation altered the competitive outcomes between tree seedlings and forbs, thereby influencing species composition and diversity; changes in the species composition of understorey vegetation following treatments occurred fairly rapidly. By decreasing substrate availability and altering the microclimate, litter removal changed fungal species composition and diversity and led to a decline in populations of soil fauna. However, litter addition did not provoke a corresponding increase in the abundance or diversity of fungi or soil fauna.Large-scale long-term studies are still needed in order to investigate the interactions between the many variables affected by litter, especially in tropical and boreal forests, which have received little attention. Litter manipulation treatments present an opportunity to assess the effects of increasing primary production in forest ecosystems; specific research aims include assessing the effects of changes in litter inputs on the carbon and nutrient cycles, decomposition processes, and the turnover of organic matter.

Biomass↗

Stabilization of vinca alkaloids encapsulated in poly(lactide-co-glycolide) microspheres.

PURPOSE: The purpose of this study was to stabilize the vinca alkaloids, vincristine sulfate (VCR) and vinblastine sulfate (VBL), in poly(lactide-co-glycolide) (PLGA) microspheres and to release the drugs in a sustained manner for more than a month. METHODS: An oil-in-oil emulsion-solvent extraction method was used to encapsulate VCR and VBL in PLGA50/50 microspheres. Stability and release kinetics of the drugs during the incubation at 37 degrees C in PBS/Tween 80 were assessed by HPLC. Degradation products were identified with HPLC-MS. RESULTS: VCR and VBL were encapsulated in PLGA microspheres unchanged. During the microsphere incubation, however, VCR degraded inside the particles with a t1/2 approximately 7.5 days. The degradation product was identified by LC-MS as the deformyl derivative, commonly formed at acidic pH. VBL, which differs only by a stable methyl group in place of the N-formyl group in VCR, was completely stable in the PLGA microclimate. The neutralization of acidic PLGA microclimate by addition of 3-10% Mg(OH)2 completely inhibited deformylation of VCR during release. but introduced a new degradation product formed under the more alkaline conditions used during the preparation. The substitution of Mg(OH)2 with a weaker base, ZnCO3, inhibited the formation of both degradation products resulting in VCR stabilization of >92% for 4 weeks. The optimal formulations of VCR (containing ZnCO3) and VBL (no additives) slowly and continuously released stable drugs for over a month. CONCLUSIONS: VCR and VBL were successfully stabilized and released in a sustained manner from PLGA microspheres. Co-encapsulation of ZnCO3 stabilizes VCR against acid-catalyzed degradation during release from the polymer and minimizes VCR decomposition during encapsulation.

Drug Carriers↗

Stabilization of proteins encapsulated in injectable poly (lactide- co-glycolide)

Controlled release from biodegradable polymers is a novel approach to replace daily painful injections of protein drugs. A major obstacle to development of these polymers is the need to retain the structure and biological activity of encapsulated proteins during months of incubation under physiological conditions. We encapsulated bovine serum albumin (BSA) in injectable poly(DL-lactide- co-glycolide) (PLGA) 50/50 cylindrical implants and determined the mechanism of BSA instability. Simulations of the polymer microclimate revealed that moisture and acidic pH (<3) triggered unfolding of encapsulated BSA, resulting in peptide bond hydrolysis and noncovalent aggregation. To neutralize the acids liberated by the biodegradable lactic/glycolic acid-based polyester, we coincorporated into the polymer an antacid, Mg(OH)2, which increased microclimate pH and prevented BSA structural losses and aggregation for over one month. We successfully applied this stabilization approach in both cylinder- and microsphere-injectable configurations and for delivery of angiogenic basic fibroblast growth factor and bone-regenerating bone morphogenetic protein-2.

3T3 Cells↗

Aggregation and habitat use by Lucilia blowflies (Diptera: Calliphoridae) in pasture.

The spatial distribution of blowflies of the genus Lucilia within fields in south west England was examined in 1999 and 2000. Blowflies are economically important agents of sheep myiasis in the UK and understanding local aggregation is an essential step in the development of appropriate sampling and fly control regimes. Fifty, 20 x 20 cm, non-odour-baited, sticky traps were used to catch flies, at randomized, 10 x 10 m grid co-ordinates in fields of permanent pasture. Clear aggregations were evident in all Lucilia distributions. All values of the sigma2:mean ratio were greater than 1. The catches were shown to be highly aggregated using Morisita's index of aggregation. Generalized linear modelling of binary presence/absence catch data was used to relate aggregation to microclimate and habitat. Deletion testing was used to identify significant terms in the models. In general, Lucilia blowflies were predominantly caught around the edges, in warmer and more humid areas of the field. The relationship between microhabitat and the distribution of Lucilia collected in 1999 was used as predictive model to explain the catches made in two fields in 2000. This gave a highly significant fit in one field (P = 0.001) and a relationship which approached significance in the second (P = 0.08). However, these regressions suggest that the relationships between abundance and microhabitat are complex and that 'hot spots' of blowfly catches were not necessarily found in the most extreme microclimate conditions. Nevertheless, microhabitat features do give a relatively good guide to presence or absence of Lucilia in the trap catches, thereby providing important information about the most appropriate location of traps to maximize and standardize sampling and control regimes.

Animals↗

Effects of an electric blanket on sleep stages and body temperature in young men.

The aim of this study was to investigate any effects of electric blanket on sleep stages and body temperature. Nine male subjects slept under two conditions: using the electric blanket (HB); and not using the electric blanket (C). The ambient condition was controlled at 3 degrees C relative humidity 50-80%. Electroencephalography, electrooculography (EOG) and electromyography, rectal temperature, skin temperature and microclimate temperature and humidity were recorded continuously through the night. Body weight was measured before and after sleep. The amount of stage 1 and number of stage 1 and rapid eye movement sleep decreased in HB compared to C. No significant difference was observed in other sleep stages. Rectal temperature was higher in HB compared to C. The thigh, leg and foot skin temperature was higher in HB than C. The microclimate temperature of the foot area was higher in HB compared to C. No significant difference was observed in whole body sweat loss between the conditions. These results suggest that use of an electric blanket under low ambient temperature may decrease cold stress to support sleep stability and thermoregulation during sleep.

Adult↗

Variability in thermal response of primed and non-primed seeds of squirreltail [Elymus elymoides (Raf.) Swezey and Elymus multisetus (J. G. Smith) M. E. Jones].

Bottlebrush squirreltail [Elymus elymoides (Raf.) Swezey = Sitanion hystrix (Nutt.) J. G. Smith] and big squirrel-tail [Elymus multisetus (J. G. Smith) M. E. Jones = Sitanion jubatum (J. G. Smith)] have a broad geographical distribution and have been identified as high priority species for restoration of degraded rangelands in the western United States. These rangelands exhibit high annual and seasonal variability in seedbed microclimate. The objective of this study was to examine variability in thermal response of both primed and non-primed seeds of these species in the context of field-variable temperature regimes. Seed priming treatments were selected to optimize germination rate in a low-temperature test environment. Primed and non-primed seeds were evaluated for laboratory germination response under 12 constant temperature treatments between 3 and 36 degrees C. Thermal time and base temperature were estimated by regression analysis of germination rate as a function of temperature in the sub-optimal temperature range. The thermal germination model and 6 years of field temperature data were used to simulate the potential germination response under different field planting scenarios. Seed priming reduced the total germination percentage of some seedlots, especially at higher germination temperatures. Seed priming increased the germination rate (reduced the number of days to 50 % germination) by 3.8-8.4 d at 6 degrees C with a mean germination advancement of 6.9 +/- 0.6 d. Maximum germination advancement in the model simulations was 5-10 d for planting dates between I March and 15 May. Model simulations can be used to expand germination analysis beyond simple treatment comparisons, to include a probabilistic description of potential germination response under historical or potential future conditions of seedbed microclimate.

Germination↗

Integrated analysis of tropical trees growth: a multivariate approach.

BACKGROUND AND AIMS: One of the problems analysing cause-effect relationships of growth and environmental factors is that a single factor could be correlated with other ones directly influencing growth. One attempt to understand tropical trees' growth cause-effect relationships is integrating research about anatomical, physiological and environmental factors that influence growth in order to develop mathematical models. The relevance is to understand the nature of the process of growth and to model this as a function of the environment. METHODS: The relationships of Aphananthe monoica, Pleuranthodendron lindenii and Psychotria costivenia radial growth and phenology with environmental factors (local climate, vertical strata microclimate and physical and chemical soil variables) were evaluated from April 2000 to September 2001. The association among these groups of variables was determined by generalized canonical correlation analysis (GCCA), which considers the probable associations of three or more data groups and the selection of the most important variables for each data group. KEY RESULTS: The GCCA allowed determination of a general model of relationships among tree phenology and radial growth with climate, microclimate and soil factors. A strong influence of climate in phenology and radial growth existed. Leaf initiation and cambial activity periods were associated with maximum temperature and day length, and vascular tissue differentiation with soil moisture and rainfall. The analyses of individual species detected different relationships for the three species. CONCLUSIONS: The analyses of the individual species suggest that each one takes advantage in a different way of the environment in which they are growing, allowing them to coexist.

Climate↗

Effect of metabolizable sugars on the mucosal surface pH of rat intestine.

In a layer juxtaposed to the mucosal surface of distal duodenum and of jejunum, and designated as "acid microclimate," the proton concentration is significantly higher than in the bulk phase of the intestinal lumen. The aim of the present study was to quantify the effect of different sugars on the mucosal surface pH value when these substrates were either added to the in vitro preparation of rat distal duodenal and mid-jejunal segments or administered by intragastric intubation and by i.v. infusion. All pH measurements were carried out in vitro by surface microelectrodes in oxygenated phosphate buffer. Glucose, fructose, mannose, galactose and 3-O-methylglucose were applied in vitro, glucose, maltose, fructose, galactose, 3-O-methylglucose and whey protein for the intragastric intubation and glucose, fructose and galactose for the intravenous infusion. Only substrates that could be metabolized in the intestinal epithelia were able to depress surface pH to a considerable extent. Substrate concentration at which half-maximum decrease of surface pH was obtained (K delta pH) was calculated to be 4.5 mM for glucose, 14.5 mM for fructose and 34.5 mM for mannose. The study was the first to demonstrate that metabolizable sugars are not only able to lower surface pH of intestinal epithelia when they are added in vitro but that they are also effective after intragastric intubation or i.v. infusion. It is plausible that generation of the protons, which are secreted into the acid microclimate zone, is closely related to the intracellular metabolization of glucose. The existence of a high proton concentration on the immediate mucosal surface could be of considerable significance for the absorption of weak electrolytes, a group to which different nutrients belong.

3-O-Methylglucose↗

Midday stomatal closure in Norway spruce--reactions in the upper and lower crown.

We used local microclimatic conditions and twig sap flow rates to interpret midday stomatal closure in the canopies of two 250-year-old Norway spruce (Picea abies (L.) Karst.) trees at a subalpine site in the Swiss Alps (1,650 m a.s.l.). Both trees showed midday stomatal closure on most clear summer days, despite the permanently wet soil. We used a modified Penman-Monteith formula to simulate potential transpiration of single twigs (ET(T)) based on high-resolution temporal and spatial microclimate data obtained both inside and outside the crowns. Comparison of calculated ET(T) values and measured twig sap flow rates enabled us to pinpoint the occurrence of midday stomatal closure and the microclimatic conditions present at that time. We found that vapor pressure deficit (and for upper-crown twigs, ET(T)) largely explained the timing of initial midday stomatal closure but gave no explanation for the different patterns of stomatal behavior after initial closure in upper- and lower-crown twigs. After the initial stomatal closure, upper-crown twigs maintained high transpiration rates by continuously regulating stomatal aperture, whereas stomatal aperture decreased rapidly in lower-crown twigs and did not increase later in the day. Midday stomatal closure in lower-crown twigs occurred on average 1 h later than in upper-crown twigs. However, the microclimate at the time of initial stomatal closure was similar at both crown locations except that lower-crown twigs received significantly less solar radiation than upper-crown twigs both at the time of initial stomatal closure and afterwards. High rates of sap flow in twigs did not always lead to stomatal closure and therefore could not explain the phenomenon. We conclude that stomatal conductance can be modeled accurately only when both local microclimatic conditions and tree water status are known. Further, we hypothesize that both the quantity and quality of light play an important role in the reopening of closed stomata during the day.

Biomass↗

New insights into butterfly-environment relationships using partitioning methods.

Variation partitioning and hierarchical partitioning are novel statistical approaches that provide deeper understanding of the importance of different explanatory variables for biodiversity patterns than traditional regression methods. Using these methods, the variation in occupancy and abundance of the clouded apollo butterfly (Parnassius mnemosyne L.) was decomposed into independent and joint effects of larval and adult food resources, microclimate and habitat quantity. The independent effect of habitat quantity variables (habitat area and connectivity) captured the largest fraction of the variation in the clouded apollo patterns, but habitat connectivity had a major contribution only for occupancy data. The independent effects of resources and microclimate were higher on butterfly abundance than on occupancy. However, a considerable amount of variation in the butterfly patterns was accounted for by the joint effects of predictors and may thus be causally related to two or all three groups of variables. Abundance of the butterfly in the surroundings of the focal grid cell had a significant effect in all analyses, independently of the effects of other predictors. Our results encourage wider applications of partitioning methods in biodiversity studies.

Animals↗

The effect of E. coli STa enterotoxin on the absorption of weakly dissociable drugs from rat proximal jejunum in vivo.

1. The effect of E. coli heat stable (STa) enterotoxin on the absorption of radio-labelled weak electrolytes and their appearance in peripheral blood was assessed in vivo by use of an intestinal recirculation procedure. 2. STa reduced the luminal disappearance (P less than 0.02) and peripheral blood appearance (P less than 0.02) of label from salicylic acid as well as the luminal disappearance (P less than 0.02) of diphenylhydantoin. 3. In contrast, STa increased the appearance in peripheral blood and disappearance from the lumen of label from morphine (P less than 0.05), amphetamine (P less than 0.01) and lignocaine (P less than 0.01). 4. Increased weak base (lignocaine) absorption can also be achieved by a combination of forskolin and theophylline which resembles STa in its ability to neutralise the usually acid surface pH of the proximal jejunum. 5. Increased weak base absorption and hindered weak acid absorption occurs despite a uniform reduction in net fluid absorption after STs exposure, making it unlikely that variations in fluid absorption account for the variations in drug absorption. 6. The ability of STa to elevate the mucosal surface pH (or acid microclimate) to neutral values, thereby altering the proportion of uncharged weak-electrolyte, may explain its different effects on weak acids and bases: neutralisation of the acid microclimate would increase the amount of undissociate weak base available for uptake.

Amphetamine↗