Pathogenesis and pharmacology of diarrhea

The etiological factors involved in diarrhea are multiple. Also the mechanisms and mediators involved are multiple: intracellular mediators (Ca, cAMP, cGMP, calmodulin, phospholipids), extracellular mediators (hormones, neurotransmitters, prostaglandins, enterotoxins...), intramural blood flow and oxygen, intestinal motility (local- and peristaltic motility). Till now, antidiarrheals are not so versatile that they provide a solution to all types of diarrhea. The mechanisms of action of fluid replacement therapy, loperamide, alpha 2 agonist and some nonsteroidal anti-inflammatory substances are reviewed.     

Alleviation of excessive gas accumulation in the ruminant stomach by ritanserin

The relationships between forestomach motility and eructation rate were studied in sheep and cattle. Three ewes and 2 heifers were implanted with strain gauges on the reticulo-rumen and fitted with a cannula in the dorsal sac of the rumen. Studies were performed in sheep after induction of hypocalcemia by Na2EDTA infusion and cattle were studied after ruminal distension. Experiments were performed by measuring the rate and volume of eructated ruminal gases, using a technique by which the trachea is transected. The frequency of reticulo-ruminal contractions decreased 40% within 30 minutes of Na2EDTA infusion to the sheep. The volume of eructated gas (for 30-minute periods) decreased from 10.7 L to 5.5 L at the end of the 60-minute infusion period. Pretreatment with ritanserin (0.1 mg/kg, subcutaneously) not only prevented bloating during the ruminal stasis induced by hypocalcemia, but also significantly increased the eructated volume of gas. In cattle, ritanserin given at the same dose level (0.1 mg/kg, subcutaneously) significantly increased the volume of eructated gas after ruminal distension. This study supports the hypothesis that the caudal esophageal sphincter has a role in the rate of ruminal gas eructation and indicates that its relaxation may be due to a 5-hydroxytryptamine antagonist.     

Enhanced sorption and fixation of radiocaesium in soils amended with K-bentonites, submitted to wetting–drying cycles

The use of bentonites as soil amendment has met with little success in reducing plant uptake of radiocaesium. However, bentonites exchanged with K⁺ have pronounced Cs⁺ binding capacity when subjected to wetting–drying cycles. Fifty‐four different bentonites were collected and characterized for cation exchange capacity and chemical composition. The radiocaesium interception potential (RIP) increased up to 160‐fold (mean 25) when the bentonites were converted to the K‐form and subjected to wetting–drying cycles. This increase in radiocaesium sorption was ascribed to a collapse of the clay sheets into an illite‐like structure, and was most pronounced in bentonites with a high layer charge. The RIP values of K‐bentonites subjected to 25 wetting–drying cycles ranged from 0.22 to 44.3 mol kg^?1. The RIP yields, i.e. the RIP in soil–bentonite mixtures expressed per unit bentonite added, were even higher and ranged up to 99 mol kg^?1. This upper limit is about 10‐fold higher than the RIP value of illite (～ 10 mol kg^?1), the principal ¹³⁷Cs sorbent in soils of temperate climates. Wetting–drying also promoted fixation of radiocaesium in soils amended with K‐bentonites. About 30% of added ¹³⁷Cs could be desorbed with 1 m ammonium acetate (NH₄Ac) from an unamended soil after 25 wetting–drying cycles, while only between 8 and 21% of ¹³⁷Cs could be desorbed from a soil amended with bentonite and a K‐salt. These findings support the proposition that addition of K‐bentonite may be effective in reducing availability of ¹³⁷Cs in soils.     

Mobility of Cd and Zn in polluted and unpolluted Spodosols

Leaching of Cd and Zn in polluted acid, well‐drained soils is a critical pathway for groundwater pollution. Models predicting future groundwater contamination with these metals have rarely been validated at the field scale. Spodosol profiles (pH 3.2–4.5) were sampled in an unpolluted (reference) field and in a field contaminated with Cd and Zn through atmospheric deposition near a zinc smelter. Average metal concentrations in the upper horizons were 0.2 mg Cd kg^?1 and 9 mg Zn kg^?1 in the unpolluted field, and 0.8 mg Cd kg^?1 and 71 mg Zn kg^?1 in the contaminated field. Isotopic dilution was used to measure the labile concentration of Cd and Zn, and the metal transport was modelled using measured sorption parameters that describe the distribution between the labile metal pool (instead of the total metal pool) and the solution phase obtained by centrifugation. Solutions were also collected by wick samplers in two polluted and one unpolluted profile at a depth of 70 cm. Concentrations in these solutions were in the order of 15 µg Cd litre^?1 and 0.8 mg Zn litre^?1 for the polluted profiles, and 1 µg Cd litre^?1 and 0.04 mg Zn litre^?1 for the unpolluted profile. The concentrations in these solutions agreed well with those in soil solutions obtained by centrifugation, which supported the use of the local equilibrium assumption (LEA). Present‐day Cd profiles in the polluted field were calculated with the LEA, based on the emission history of the nearby smelter and taking spatial variability into account. Observed and predicted depth profiles agreed reasonably well, but total Cd concentrations in the topsoil were generally underestimated by the model. This may be attributed to the presence of non‐labile Cd in the atmospheric deposition, which was not accounted for in the retrospective modelling. The large concentrations of non‐labile Zn in the topsoil of the polluted field were also indicative that metals in the atmospheric deposition were (partly) in a sparingly soluble form, and that release of these non‐labile metals is a slow process. The presence of non‐labile metals should be taken into account when evaluating metal mobility or predicting their transport.     

R 8110, a new short-acting hypnotic in dogs

The clinical, respiratory and cardiovascular effects of intravenous injections of R 8110, a fluor analogue of etomidate, were studied in unpremedicated dogs. Clinical observations were carried out after intravenous injections of 3 and 4 mg kg-1 of R 8110. Cardiovascular studies were conducted after an intravenous injection of 3 mg kg-1. The drug proved to be a safe and reliable agent for induction and produced a short-lasting hypnosis and some analgesia. Both induction and recovery were smooth and rapid. Heart rate and systolic and diastolic blood pressure decreased significantly (P less than or equal to 0.05) 10 minutes after injection; the influence on arterial blood parameters was minimal.     

Modelling the effects of ageing on Cd,Zn, Ni and Cu solubility in soils using an assemblage model

Ageing reactions can reduce trace metal solubility and can explain natural attenuation of contaminated soils. We modelled ageing reactions in soil with an assemblage model that considers slow reactions in Fe‐oxyhydroxides and reversible sorption on organic matter and clay minerals. Metal adsorption kinetics on Fe‐oxyhydroxides was obtained from data with synthetic oxyhydroxides. Metal solubility and isotopic exchangeability data were obtained from 28 soils amended with Ni, Zn, Cu and Cd metal salts and monitored for 850 days. The assemblage model was constructed in WHAM 6.0 and used soil properties and dissolved organic matter as input data. The model was first validated to predict dissolved metal concentrations, based on the concentration of isotopic exchangeable metals. The model overestimated metal solubility without parameter adjustment by mean factors of 4–7, and successful fits were obtained by increasing the specific surface area of Fe‐oxyhydroxides from measured values of synthetic systems to a value of 600 m² g^?1 recommended by other authors. The effect of ageing on the isotopic exchangeable metal fraction was subsequently modelled starting from the predicted fraction of metals present on Fe‐oxyhydroxides immediately after soil spiking. The observed isotopic exchangeable metal fractions of Ni, Zn and Cd agreed reasonably well with predicted values. The model predicts that ageing reactions are more pronounced at higher pH because metal sorption is increasingly directed to oxyhydroxide surfaces with increasing soil pH. Modelling fixation of Cu requires more information on fixation of that metal in organic matter.     

New insights on 3-mercaptohexanol (3MH) biogenesis in Sauvignon Blanc wines: Cys-3MH and (E)-hexen-2-al are not the major precursors

The molar conversion yield of Cys-3MH into 3MH, during alcoholic fermentation, was traced using a deuterated isotope of the precursor added to different Sauvignon Blanc musts. This yield is close to that found in synthetic media supplemented with synthetic Cys-3MH, that is, below 1%. Yet, this represents only 3-7% of the total 3MH production in wine. This clearly shows that Cys-3MH is a precursor of 3MH, but not the main one in the different musts tested. The contribution of ( E)-hex-2-enal, which has been suggested as another potential precursor of 3MH, was discarded as well, as shown using also a deuterated analogue. The third suggested precursor of 3MH is a glutathionyl-3MH (G-3MH), which upon proteolytic degradation could release Cys-3MH. The knockout of the OPT1 gene, which encodes the major glutathione transporter, reduces 3MH accumulation by a 2-fold factor in grape must as compared to the wild type strain. Consequently, it is deduced that major 3MH precursor(s) are transported into yeast via Opt1p, which is in favor of G-3MH being a 3MH precursor. This work opens the search for the major natural precursor(s) of 3MH in Sauvignon Blanc must.     

Mobilization of Zn upon waterlogging riparian Spodosols is related to reductive dissolution of Fe minerals

Contaminated riparian soils can release metals to surface water. Periodic waterlogging affects metal mobility but the processes and soil factors governing net trends are not well understood. Experiments were combined with geochemical modelling to identify processes explaining the dynamics of zinc (Zn) in contaminated soils following waterlogging. Samples were collected from 12 Spodosols near streams in a metal‐contaminated area and four similar but uncontaminated soils were sampled in a reference area. Air‐dried samples were submerged and incubated under N₂. The soil redox potential decreased from 470 mV initially to approximately 30 mV over 2 months. The pore‐water Zn concentrations surprisingly increased over the same period by, on average, a factor of 18 (range 0.6–80; immobilization in one soil only) despite an increase in pH of 1.8 units, on average. Dissolved organic matter (DOM) in the soil solution increased during waterlogging but the observed increase in Zn solubility could not be explained by increased complexation with DOM, because the estimated Zn²⁺ activity also increased by a factor of 18 on average (range 0.2–82). Speciation modelling suggests that Zn mobilization during waterlogging results from Fe²⁺ displacing sorbed Zn²⁺ from particulate organic matter and from dissolution of Zn‐bearing Fe/Mn oxyhydroxides. This hypothesis is supported by the significant positive correlation (r = 0.87, n = 13) between the factor change in pore‐water Zn concentration and the ratio of dithionite‐extractable Fe to organic carbon content. These results show that Fe dynamics are important for predicting the fate of trace metals in anoxic soils.     

Amino acid catalysis of 2-alkylfuran formation from lipid oxidation-derived α,β-unsaturated aldehydes

The formation of 2-alkylfurans from the corresponding lipid-derived α,β-unsaturated aldehydes under dry-roasting conditions was investigated in detail. The addition of an amino acid to an α,β-unsaturated aldehyde drastically increased 2-alkylfuran formation. Peptides and proteins as well were able to catalyze 2-alkylfuran formation from the corresponding α,β-unsaturated aldehydes. Further investigation of 2-alkylfuran formation showed the need of oxidizing conditions and the involvement of radicals in the reaction. This way, the formation of 2-methylfuran from 2-pentenal, 2-ethylfuran from 2-hexenal, 2-propylfuran from 2-heptenal, 2-butylfuran from 2-octenal, 2-pentylfuran from 2-nonenal, and 2-hexylfuran from 2-decenal was shown. The impact of amino acids on 2-alkylfuran formation from lipid-derived α,β-unsaturated aldehydes represents an interesting example of the complex role of amino acids in the multitude of chemical reactions occurring during thermal processing of lipid-rich foods.     

Mechanistic insights into furan formation in Maillard model systems

Furan has recently received considerable attention as a possibly carcinogenic compound occurring in thermally processed foods. Although several food constituents have been identified as furan precursors, multiple formation pathways remain unclear. Therefore, the mechanisms of furan formation in Maillard model systems were studied by means of the carbon module labeling (CAMOLA) technique. Under both roasting and pressure-cooking conditions, furan was formed from glucose via the intact skeleton, and its formation pathways from glucose alone were not amino acid-dependent. However, some amino acids, especially alanine and serine, did influence the furan production by providing an additional formation pathway. Furthermore, most amino acids enhanced the furan production from glucose. Roasting conditions produced 25-100 times higher amounts of furan as compared to pressure-cooking conditions. Surprisingly, in the alanine/glucose model systems, the relative importance of furan production from glucose alone and from the combination of a glucose-derived and an alanine-derived fragment changed completely over a limited time course of 60 min.