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Assessment and management of chemotherapy-induced mucositis in children.

Oral mucositis is one of the most common side effects of cancer treatment. The oral mucosa is comprised of membranes of a high mitotic index with rapid epithelial turnover and maturation rates. This causes the mucosa to be vulnerable to the adverse effects of chemotherapy. Chemotherapy alters the integrity of the mucosa, the microbial flora which normally inhabit the oral cavity, salivary quantity and composition, as well as the epithelial maturation. As a result, the child receiving chemotherapy may experience significant pain, dysphagia, alteration in nutritional status, and risk of infection. Severe mucositis can also delay therapy that may compromise the child's treatment and chance for cure. Not all chemotherapy-induced mucositis can be prevented. However, with proper management, the severity and duration of oral complications can be minimized.

Antineoplastic Agents↗

Dynamics of large ciliate protozoa in the rumen of cattle fed on diets of freshly cut grass.

1. The dynamics of large ciliate (holotrich) protozoa (Isotricha and Dasytricha spp.) in the rumen of cattle given cut, fresh ryegrass (Lolium multiflorium Lam) were studied by means of a single intrarumen injection of 14C-labelled protozoa prepared in vitro by adding [Me14C]choline to rumen fluid containing protozoa and incubating at 39 degrees for 2 h. 2. An indication of the lysis rate of protozoa in the rumen was obtained from the radioactivity apparently lost through the methane pool. 3. The turnover time of the holotrich protozoa indicates that these protozoa were extensively retained in the rumen and that only a small proportion of those produced in the rumen flowed out in the digesta. This was supported by the estimation of the rate of lysis which was approximately 85% of the turnover rate in the rumen. 4. The apparent production rate of the larger protozoa indicates that they contribute only about 9% of the predicted net microbial protein synthesis in the rumen.

Animals↗

Control of ribonucleic acid synthesis in eukaryotes. 3. The effect of cycloheximide and edeine on rna synthesis in yeast.

The addition of cycloheximide to a thermosensitive conditional yeast mutant (ts-187) before and after transfer to the nonpermissive temperature (36 degrees C) for initiation of protein synthesis produces the uncoupling of the RNA and protein synthetic machineries. Since the drug can produce this relaxation in the presence and absence of protein synthesis, it is concluded that the coupling of protein and RNA synthesis, which a temperature shift produces, is not exclusively related to the inhibition of protein synthesis. Support for this assumption has been obtained using the parental (A364A) strain. Transferring this strain to 36 degrees C produces inhibition of RNA synthesis in the presence of stimulation of protein synthesis. Furthermore, cycloheximide and edeine prevent this inhibtion of RNA synthesis that temperature shift produces. It is, therefore, postulated that this inhibition of RNA synthesis results from the synthesis or activation of a factor(s) elicited by the increase in temperature whose function is to repress the transcriptional apparatus. Cycloheximide or edeine can prevent the function of this repressor-like factor by binding to the factor or by preventing its synthesis. The fact that inhibition of protein synthesis either by cycloheximide action or temperature shift in ts-187 produces inhibition of RNA synthesis in isolated nuclei indicates that, in addition to the aforementioned repressor, other factor(s) having a promoter function may exist. Since a slight inhibition of protein synthesis produces nuclear template restrictions, it is postulated that the promoter-like factor(s) is a polypeptide different from the RNA polymerase and, at least in yeast, has a high turnover.

Amanitins↗

Myeloperoxidase-mediated inhibition of microbial respiration: damage to Escherichia coli ubiquinol oxidase.

A microbicidal system, mediated by neutrophil myeloperoxidase, inhibits succinate-dependent respiration in Escherichia coli at rates that correlate with loss of microbial viability. Succinate dehydrogenase, the initial enzyme of the succinate oxidase respiratory pathway, catalyzes the reduction of ubiquinone to ubiquinol, which is reoxidized by terminal oxidase complexes. The steady-state ratio of ubiquinol to total quinone (ubiquinol + ubiquinone) reflects the balance between dehydrogenase-dependent ubiquinone reduction and terminal oxidase-dependent ubiquinol oxidation. Myeloperoxidase had no effect on total quinone content of E. coli but altered the steady-state ratio of ubiquinol to total quinone. The ratio doubled for organisms incubated with the myeloperoxidase system for 10 min, suggesting decreased ubiquinol oxidase activity, which was confirmed by observation of a 50% decrease in oxidation of the ubiquinol analogue 2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinol. Despite inhibition of ubiquinol oxidase, overall succinate oxidase activity remained unchanged, suggesting that succinate dehydrogenase activity was preserved and that the dehydrogenase was rate limiting. Microbial viability was unaffected by early changes in ubiquinol oxidase activity. Longer (60 min) exposure of E. coli to the myeloperoxidase system resulted in only modest further inhibition of the ubiquinol oxidase, but the ubiquinol to total quinone ratio fell to 0%, reflecting complete loss of succinate dehydrogenase activity. Succinate oxidase activity was abolished, and there was extensive loss of microbial viability. Early myeloperoxidase-mediated injury to ubiquinol oxidase appeared to be compensated for by higher steady-state levels of ubiquinol which sustained electron turnover by mass effect. Later myeloperoxidase-mediated injuries eliminated succinate-dependent ubiquinone reduction, through inhibition of succinate dehydrogenase, with loss of succinate oxidase activity, effects which were associated with, although not clearly causal for, microbicidal activity.

Animals↗

Labile substrates quality as the main driving force of microbial mineralization activity in a poplar plantation soil under elevated CO2 and nitrogen fertilization.

Soil carbon (C) long term storage is influenced by the balance among ecosystem net primary productivity (NPP), the rate of delivery of new organic matter to soil pools and the decomposition of soil organic matter (SOM). The increase of NPP under elevated CO(2) can result in a greater production and higher turnover of fine roots or root exudation and, in turn, in an increase of labile C belowground. The aim of this work was to detect if changes in labile C substrates influenced the organic C storage in soils, verifying (i) whether treatments with elevated CO(2) and N fertilization induced changes in the amount and quality of labile C pools and in microbial C immobilization and (ii) whether these changes provoked modifications in the microbial C mineralization activity, and therefore changes in soil C losses. The effect of elevated CO(2) was a significant increase in both seasons (June and October 2004), of all labile C fractions: microbial biomass C (MBC), K(2)SO(4) extractable C (ExC), and water soluble C (WSC). The C/N ratio of the microbial biomass and of the K(2)SO(4) extractable SOM presented a seasonal fluctuation showing higher values in June, whereas the elevated CO(2) increased significantly the C/N ratio of these fractions independent of the season and the N addition, indicating a lower quality of labile SOM. Microbial respiration was more than doubled in October compared to June, confirming that changes in substrate quality and nutrient availability, occurring in the plantation at the beginning and at the end of the vegetative period, influenced the microbial activity in the bulk soil. Furthermore, the microbial respiration response to N fertilization was dependent on the season, with an opposite effect between June and October. The kinetic parameters calculated according to the first-order equation C(m)=C(0)(1-e(-kt)) were unaffected by elevated CO(2) treatment, except C(0)k and MR(basal), that showed a significant reduction, ascribable to (i) a lower quality of labile pools, and (ii) a more efficient microbial biomass in the use of available substrates. The C surplus found in elevated CO(2) soils was indeed immobilized and used for microbial growth, thus excluding a priming effect mechanism of elevated CO(2) on SOM decomposition.

Carbon↗

Acute copper and cupric ion toxicity in an estuarine microbial community.

Copper was acutely toxic to the estuarine microbial community of Middle Marshes, N.C. Under ambient water quality conditions, 10 mug of added total copper [Cu(II)] liter reduced the CFU bacterial abundance by up to 60% and inhibited the amino acid turnover rate (AATR) by as much as 30%. Copper toxicity, however, was a quantitative function of free cupric ion (Cu) activity that was not directly related to Cu(II) or ligand-bound copper. By using a nitrilotriacetic acid-cupric ion buffer to control pCu (-log Cu activity), it was found that an in situ pCu of 10.1 was bactericidal, reducing the CFU by 60%, but inhibited the AATR by only about 10%. A bacterial bioassay that was used to estimate the pCu in Cu(II)-treated Middle Marshes samples indicated that less than 0.5% of added Cu(II) was in the free cupric ion form. CFU was a more sensitive indicator of low-level copper stress than was AATR. When tested at different times, native microbial community responses to acute cupric ion stress were quantitatively quite similar even when there were large differences in bacterial abundances and in situ metabolic rates. Variations were observed in response to Cu(II) treatments at different times, but these were likely due to differences in water quality, which would quantitatively influence the distribution of copper complexes that were present. Asymptotic response curves suggest that some degree of copper resistance exists in this community. At a pCu of 8, more than 2 orders of magnitude above the minimum inhibitory level, the CFU was still 5 to 10% and the AATR was about 3% of the control values.

Journal Article↗

Microbial biomass and utilization of dissolved organic matter in the okefenokee swamp ecosystem.

The Okefenokee Swamp exhibited levels of microbial biomass and aerobic glucose uptake comparable to those of other organically rich, detritus-based aquatic ecosystems. In contrast to other peat-accumulating systems, this acidic (pH 3.7), low-nutrient environment does not show diminished water column or surface sediment microbial biomass or heterotrophic activity. The total particular ATP varied between 0.03 and 6.6 mug liter (mean, 1.6 mug liter) in water and between 1 and 28 mug g (dry weight) (mean, 10.0 mug g [dry weight] in sediments. The turnover times for dissolved d-glucose were 1.26 to 701.25 h (mean, 110.25 h) in aerobic waters and 2.4 to 72 min (mean, 10.2 min) in aerobic surface sediments. Water column bacterial secondary production, measured as the incorporation of [H]thymidine into cold-trichloroacetic acid-insoluble material, ranged from 0.06 to 1.67 nmol liter day (mean, 0.45 nmol liter day). The kinetics of d-glucose uptake by water column microflora are multiphasic and suggest the presence of a diverse microbial population capable of using labile substrates at nanomolar concentrations and at substantial rates. The presence of a large and active aerobic microbial community in the Okefenokee Swamp is indicative of an important role for microbes in swamp geochemistry and strongly suggests the existence of a detritus-based food web.

Journal Article↗

Stability of the Listeria monocytogenes ActA protein in mammalian cells is regulated by the N-end rule pathway.

Upon infection of mammalian cells, Listeria monocytogenes lyses the phagosome and enters the cytosol, where it secretes proteins necessary for its intracellular growth cycle. Consequently, bacterial proteins exposed to the cytosol are potential targets for degradation by host cytosolic proteases. One pathway for degradation of host cytosolic proteins, the N-end rule pathway, involves recognition of the N-terminal amino acid and is mediated by the proteasome. However, very few natural N-end rule substrates have been identified. We have examined the L. monocytogenes ActA protein as a potential target for this pathway. ActA is an essential determinant of L. monocytogenes pathogenesis that is required to induce actin-based motility and cell-to-cell spread. We show that the half-life of a secreted form of ActA can be altered in the mammalian cytosol by changing the N-terminal amino acid. Moreover, the introduction of a destabilizing N-terminus into the functional, surface-bound form of ActA results in a small-plaque phenotype in L2 cells, which is partially reversible by an inhibitor of the proteasome. These results indicate that the L. monocytogenes ActA protein is a natural N-end rule substrate, and that optimal function of ActA in mediating cell-to-cell spread is dependent upon its intracellular turnover rate.

Animals↗

[Total number and biomass of microorganisms in the depths of the Black Sea].

The total number and biomass of microorganisms, as well as the ratio between their main morphological forms, were determined by capillary microscopy in 22 water samples taken at various depths from the surface to 1500 m in the eastern part of the Black Sea. The total number of microorganisms was several times higher at depths over 150 m in the hydrogen sulfide zone than in the oxygen zone (0--150 m), whereas the biomass was greater by an order of magnitude. The number of microorganisms varied within a range of 1.4--12.4X10(3) cells/ml in the oxygen zone and 3.8--34.9X10(3) cells/ml in the hydrogen sulfide zone, whereas the biomass was 0.9--6.9 mg/m3 and 10.8--55.6 mg/m3, respectively. The bulk of the microbial biomass in the hydrogen sulfide zone was constituted by peculiar filamentous forms described for the first time by Lebedeva (1953, 1963) and, apparently, participating in sulfur turnover.

Bacteria↗

A novel method for the measurement of dissolved adenosine and guanosine triphosphate in aquatic habitats: applications to marine microbial ecology.

A novel method for the measurement of dissolved adenosine-5'-triphosphate and guanosine-5'-triphosphate (D-ATP and D-GTP, respectively) in marine and freshwater habitats was developed and applied to samples collected from the oligotrophic North Pacific Ocean. Both D-ATP and D-GTP are co-precipitated by authigenically formed Mg(OH)(2) and can be concentrated by factors greater than 200-fold, for subsequent measurement by the firefly luciferin-luciferase bioluminescence reaction. The detection limit for this method was 2-3 pmol ml(-1) of concentrated sample (equivalent to an in situ concentration of 10 pM) with a 5% precision at concentrations of 10 pmol ml(-1) or above.A significant positive correlation (P<0.001) was observed between particulate ATP (P-ATP) and D-ATP in water samples collected from Station ALOHA (22.75 degrees N, 158 degrees W; depth profiles 0-1000 m). The highest concentrations of dissolved nucleotides were found in the euphotic zone (0-175 m) below which the concentrations were low and relatively invariant. The dissolved nucleotide pools generally exceeded their corresponding particulate pools.Using radioisotopic tracer techniques and the new concentration method, turnover times for both particulate and dissolved nucleotides can be determined. The ability to measure concentrations and follow nucleotide tracers accurately in a very dilute environment provides a unique opportunity to address questions on microbial community metabolism, nutrient dynamics and energy flux.

Adenosine Triphosphate↗

Terminal reactions in the anaerobic digestion of animal waste.

An anaerobic mesophilic digestor was operated using beef cattle waste (diluted to 5.75% volatile solids) as substrate; retention time was 10 days with daily batch feed. Volatile solids destruction was 36%. Daily gas production rate was 1.8 liters of gas (standard temperature and pressure) per liter of digestor contents (0.99 liters of CH(4) per liter of digestor contents). Acetate turnover was measured, and it was calculated that 68% of the CH(4) was derived from the methyl group of acetate. When the methanogenic substrates acetic acid or H(2)/CO(2) were added to the digestor on a continuous basis, the microflora were able to adapt and convert them to terminal products while continuing to degrade animal waste to the same extent as without additions. The methanogenic substrates were added at a rate at least 1.5 times the microbial production rate which was measured in the absence of added substrates. Added acetate was converted directly to CH(4) by acetoclastic methanogens; H(2) addition greatly stimulated acetate production in the digestor. A method is described for the measurement of acetate turnover in batch-fed digestors.

Journal Article↗

Contrasting patterns of soil N-cycling in model ecosystems of Fennoscandian boreal forests.

The low plant productivity of boreal forests in general has been attributed to low soil N supply and low temperatures. Exceptionally high productivity occurs in toe-slope positions, and has been ascribed to influx of N from surrounding areas and higher rates of soil N turnover in situ. Despite large apparent natural variations in forest productivity, rates of gross soil N mineralization and gross nitrification have never been compared in Fennoscandian boreal forests of contrasting productivity. We report contrasting patterns of soil N turnover in three model ecosystems, representing the range in soil C-to-N ratios (19-41) in Fennoscandian boreal forests and differences in forest productivity by a factor close to 3. Gross N mineralization was seven times higher when soil, microbial, and plant C-to-N ratios were the lowest compared to the highest. This process, nitrification and potential denitrification correlated with inorganic, total and microbial biomass N, but not microbial C. There was a constant ratio between soil and microbial C-to-N ratio of 3.7+/-0.2, across wide ratios of soil C-to-N and fungi-to-bacteria. Soil N-cycling should be controlled by the supplies of C and N to the microbes. In accordance with plant allocation theory, we discuss the possibility that the high fungal biomass at high soil C-to-N ratio reflects a particularly high supply of plant photosynthates, substrates of high-quality C, to mycorrhizal fungi. Methods to study soil N turnover and N retention should be developed to take into account the impact of mycorrhizal fungi on soil N-cycling.

Bacteria↗

Generation of long-lived B cells in germ-free mice.

In the present study we have addressed the question of whether the composition of the peripheral B cell pool is similar in mice raised under conventional, specific pathogen-free or germ-free breeding conditions. For this purpose, the representation of various B lineage subsets was quantitated by flow cytometry and the lifespan of B cells analyzed by labeling dividing cells with the thymidine analogue 5-bromo-2'-deoxyuridine in vivo. The results indicate that except for an increased fraction of CD45R (B220)dull B lineage cells in the bone marrow and a marginally faster turnover of splenic B cells in germ-free compared to conventional mice, there is no obvious difference in the representation and turnover of B cells in the different kinds of mice. The data indicate that a stable pool of peripheral B cells is generated even in the absence of microbial stimulation.

Animals↗

Microbial fermentation in certain mammals.

The fermentation in the caecum and large intestine of ruminants is negligible compared with that in the rumen. In small ruminants the rate per unit contents is faster than in large ones, due to faster turnover. The cellulolytic bacteria of several ruminants are similar but differ in nutritional requirements.

Animals↗