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Effects of acetate on facultative autotrophy in Chlamydomonas reinhardtii assessed by photosynthetic measurements and stable isotope analyses.

The green alga Chlamydomonas reinhardtii can grow photoautotrophically utilizing CO(2), heterotrophically utilizing acetate, and mixotrophically utilizing both carbon sources. Growth of cells in increasing concentrations of acetate plus 5% CO(2) in liquid culture progressively reduced photosynthetic CO(2) fixation and net O(2) evolution without effects on respiration, photosystem II efficiency (as measured by chlorophyll fluorescence), or growth. Using the technique of on-line oxygen isotope ratio mass spectrometry, we found that mixotrophic growth in acetate is not associated with activation of the cyanide-insensitive alternative oxidase pathway. The fraction of carbon biomass resulting from photosynthesis, determined by stable carbon isotope ratio mass spectrometry, declined dramatically (about 50%) in cells grown in acetate with saturating light and CO(2). Under these conditions, photosynthetic CO(2) fixation and O(2) evolution were also reduced by about 50%. Some growth conditions (e.g. limiting light, high acetate, solid medium in air) virtually abolished photosynthetic carbon gain. These effects of acetate were exacerbated in mutants with slowed electron transfer through the D1 reaction center protein of photosystem II or impaired chloroplast protein synthesis. Therefore, in mixotrophically grown cells of C. reinhardtii, interpretations of the effects of environmental or genetic manipulations of photosynthesis are likely to be confounded by acetate in the medium.

Acetates↗

Purification and properties of acetyl-CoA synthetase (ADP-forming), an archaeal enzyme of acetate formation and ATP synthesis, from the hyperthermophile Pyrococcus furiosus.

Acetyl-CoA synthetase (ADP-forming) is an enzyme in Archaea that catalyzes the formation of acetate from acetyl-CoA and couples this reaction with the synthesis of ATP from ADP and Pi (acetyl-CoA + ADP + Pi --> acetate + ATP + CoA) [Schifer, T., Selig, M. & Schonheit, P. (1993) Arch. Microbiol. 159, 72-83]. The enzyme from the anaerobic hyperthermophile Pyrococcus furiosus was purified 96-fold with a yield of 20% to apparent electrophoretic homogeneity. The oxygen-stable enzyme had an apparent molecular mass of 145 kDa and was composed of two subunits with apparent molecular masses of 47 kDa and 25 kDa, indicating an alpha2beta2 structure. The N-terminal amino acid sequences of both subunits were determined; they do not show significant identity to other proteins in databases. The purified enzyme catalyzed the reversible conversion of acetyl-CoA, ADP and Pi to acetate, ATP and CoA. The apparent Vmax value in the direction of acetate formation was 18 U/mg (55 degrees C), the apparent Km values for acetyl-CoA, ADP and Pi were 17 microM, 60 microM and 200 microM, respectively. ADP and Pi could not be replaced by AMP and PPi, defining the enzyme as an ADP-forming rather than an AMP-forming acetyl-CoA synthetase. The apparent Vmax value in the direction of acetyl-CoA formation was about 40 U/mg (55 degrees C), and the apparent Km values for acetate, ATP and CoA were 660 microM, 80 microM and 30 microM, respectively. The purified enzyme was not specific for acetyl-CoA or acetate, in addition to acetyl-CoA (100%), the enzyme accepts propionyl-CoA (110%) and butyryl-CoA (92%), and in addition to acetate (100%), the enzyme accepts propionate (100%), butyrate (92%), isobutyrate (79%), valerate (36%) and isovalerate (34%), indicating that the enzyme functions as an acyl-CoA synthetase (ADP-forming) with a broad substrate spectrum. Succinate, phenylacetate and indoleacetate did not serve as substrates for the enzyme (<3%). In addition to ADP (100%), GDP (220%) and IDP (250%) were used, and in addition to ATP (100%), GTP (210%) and ITP (320%) were used. Pyrimidine nucleotides were not accepted. The enzyme was dependent on Mg2+, which could be partly substituted by Mn2+ and Co2+. The pH optimum was pH 7. The enzyme has a temperature optimum at 90 degrees C, which is in accordance with its physiological function under hyperthermophilic conditions. The enzyme was stabilized against heat inactivation by salts. In the presence of KCI (1 M), which was most effective, the enzyme did not loose activity after 2 h incubation at 100 degrees C.

Acetic Acid↗

Identification of acetate-utilizing Bacteria and Archaea in methanogenic profundal sediments of Lake Kinneret (Israel) by stable isotope probing of rRNA.

Acetate is an important intermediate in the decomposition of organic matter in anoxic freshwater sediments. Here, we identified distinct microorganisms active in its oxidation and transformation to methane in the anoxic methanogenic layers of Lake Kinneret (Israel) profundal sediment by rRNA-based stable isotope probing (RNA-SIP). After 18 days of incubation with amended [U-(13)C]acetate we found that archaeal 16S rRNA was (13)C-labelled to a far greater extent than bacterial rRNA. We identified acetoclastic methanogens related to Methanosaeta concilii as being most active in the degradation and assimilation of acetate. Oxidation of the acetate-methyl group played only a minor role, but nevertheless 'heavy'(13)C-labelled bacterial rRNA templates were identified. 'Heavy' bacteria were mainly affiliated with the Betaproteobacteria (mostly Rhodocyclales and Nitrosomonadales), the Nitrospira phylum (related to 'Magnetobacterium bavaricum' and Thermodesulfovibrio yellowstonii), and also with the candidate phylum 'Endomicrobia'. However, the mode of energy gain that allowed for the assimilation of (13)C-acetate by these bacterial groups remains unknown. It may have involved syntrophic oxidation of acetate, reduction of chlorinated compounds, reduction of humic substances, fermentation of organic compounds, or even predation of (13)C-labelled Methanosaeta spp. In summary, this SIP experiment shows that acetate carbon was predominantly consumed by acetoclastic methanogens in profundal Lake Kinneret sediment, while it was also utilized by a small and heterogeneous community of bacteria.

Acetates↗

One-year acarbose treatment raises fasting serum acetate in diabetic patients.

alpha-Glucosidase inhibitors such as acarbose improve blood glucose control in diabetes by delaying or reducing carbohydrate absorption. The fermentation of malabsorbed carbohydrate in the colon is associated with the production of gas, leading to flatulence, and short chain fatty acids such as acetate, which may have systemic effects. To see if acarbose raised fasting serum acetate in diabetic patients, we studied 85 subjects selected from the 267 who had completed a 1-year, double-blind, placebo-controlled, parallel design study of the effects of acarbose in the treatment of diabetes. At baseline, there was no significant difference between the 44 subjects subsequently randomized to placebo and the 41 randomized to acarbose, respectively, in fasting serum acetate (80 +/- 5 vs 71 +/- 4 mumoll-1) or glycosylated haemoglobin (HbA1C; 7.2 +/- 0.3 vs 7.4 +/- 0.3%). Compared to placebo, acarbose treatment significantly increased fasting serum acetate by 11 +/- 4 vs 2 +/- 3 mumoll-1 (p < 0.02) and reduced HbA1C by -0.59 +/- 0.16 vs -0.13 +/- 0.20% (p < 0.02). Acarbose treatment had no significant effect on serum cholesterol or non-esterified fatty acids, but was associated with a significant increase in flatulence. There was no relationship between changes in serum acetate and changes in HbA1C, serum cholesterol or symptoms. We conclude, in subjects with diabetes who tolerate therapy for a 1-year period, that acarbose treatment increases serum acetate. The magnitude of change in acetate was unrelated to side-effects or changes in blood glucose control or serum lipids.

Acarbose↗

Endometrial resection follow up: late onset of pain and the effect of depot medroxyprogesterone acetate.

OBJECTIVE: To observe longer term (9 to 18 months) follow up of women after a transcervical resection of the endometrium (TCRE) and the effect of post-operative medroxyprogesterone acetate on the results. DESIGN: An observational study. SETTING: A district public hospital and a nearby private hospital in Sydney, Australia. SUBJECTS: Sixty-one women who underwent TCRE from January to December 1991 were contacted 9 to 18 months after the procedure. They were questioned about symptoms and levels of satisfaction at six months, 12 months and at the time of interview, 9-18 months after the procedure. The 27 women treated from 1 January to 31 August 1991 were given medroxyprogesterone acetate 150 mg at the time of surgery. From 1 September to 31 December 1991 no medroxyprogesterone acetate was given (32 women). Two women underwent immediate hysterectomy, and are included as unsuccessful TCREs but are excluded from description of effects of medroxyprogesterone acetate on the results of TCRE. RESULTS: Late onset, defined as after 12 months, of pain with or without bleeding occurred in 7 out of 52 women (13.5%). Overall, 49 out of 61 women (80.3%) were satisfied with the operation at the time of interview, 9 to 18 months post-operatively. Success rates, measured by satisfaction, were 89% (24/27) in the medroxyprogesterone acetate group and 75% (24/32) in the no medroxyprogesterone acetate group. CONCLUSION: Follow up after endometrial resection revealed that a definite subgroup of women develop late onset of pain with or without bleeding. Results at four to six months do not necessarily correlate with longer term outcomes. This needs to be investigated with larger, long term follow up studies, as does the apparently beneficial effects of medroxyprogesterone acetate on the long term results of TCRE.

Adult↗

Treatment of hyperphosphatemia in hemodialysis patients: The Calcium Acetate Renagel Evaluation (CARE Study).

BACKGROUND: Hyperphosphatemia underlies development of hyperparathyroidism, osteodystrophy, extraosseous calcification, and is associated with increased mortality in hemodialysis patients. METHODS: To determine whether calcium acetate or sevelamer hydrochloride best achieves recently recommended treatment goals of phosphorus </=5.5 mg/dL and Ca x P product </=55 mg(2)/dL(2), we conducted an 8-week randomized, double-blind study in 100 hemodialysis patients. RESULTS: Comparisons of time-averaged concentrations (weeks 1 to 8) demonstrated that calcium acetate recipients had lower serum phosphorus (1.08 mg/dL difference, P= 0.0006), higher serum calcium (0.63 mg/dL difference, P < 0.0001), and lower Ca x P (6.1 mg(2)/dL(2) difference, P= 0.022) than sevelamer recipients. At each week, calcium acetate recipients were 20% to 24% more likely to attain goal phosphorus [odds ratio (OR) 2.37, 95% CI 1.28-4.37, P= 0.0058], and 15% to 20% more likely to attain goal Ca x P (OR 2.16, 95% CI 1.20-3.86, P= 0.0097). Transient hypercalcemia occurred in 8 of 48 (16.7%) calcium acetate recipients, all of whom received concomitant intravenous vitamin D. By regression analysis hypercalcemia was more likely with calcium acetate (OR 6.1, 95% CI 2.8-13.3, P < 0.0001). Week 8 intact PTH levels were not significantly different. Serum bicarbonate levels were significantly lower with sevelamer hydrochloride treatment (P < 0.0001). CONCLUSION: Calcium acetate controls serum phosphorus and calcium-phosphate product more effectively than sevelamer hydrochloride. Cost-benefit analysis indicates that in the absence of hypercalcemia, calcium acetate should remain the treatment of choice for hyperphosphatemia in hemodialysis patients.

Acetates↗

Role of acetaldehyde and acetate in the development of ethanol-induced cardiac lipidosis, studied in isolated perfused rat hearts.

Isolated perfused rat hearts were used to study the effects of ethanol, acetaldehyde, and acetate on the cellular redox state and fatty acid metabolism in the myocardium. Ethanol had negligible effects on the cellular redox state but at high concentrations depressed the contractile activity and thereby secondarily the oxygen consumption. Acetaldehyde in concentrations below 50 microM had negligible effects on the redox state of the mitochondrial free NAD+/NADH couple, as studied by surface fluorometry of flavins and nicotinamide nucleotides. A reduction of NAD+ was observed with concentrations between 50 and 500 microM, while in the range of 0.5-1 mM the effect was biphasic, i.e., an initial reduction was followed by oxidation concomitantly with an increase in heart rate and peak systolic pressure. Acetate in millimolar concentrations caused in the coronary flow. A mitochondrial acetaldehyde dehydrogenase was revealed in the myocardium, having an apparent Km of 1.1 microM for acetaldehyde. Acetaldehyde in 50-microM concentration had no major effects on the uptake, oxidation, or lipid incorporation of oleate in the myocardium. Acetate in concentrations less than 2 mM did not affect the uptake of oleate into the myocardium, but did inhibit is oxidation and enhance its incorporation into tissue lipids in a dose-dependent manner. 2 mM acetate caused a 91% increase in oleate incorporation into tissue lipids over 30 min. The data can be interpreted as showing that acetaldehyde and acetate, the metabolites of ethanol, have metabolic effects on the myocardium, but only those of acetate are significant in concentrations encountered during ethanol oxidation in vivo. It is probable that acetate is involved in the development of ethanol-induced myocardial lipidosis, inhibiting the oxidation of fatty acids, and channelling them into the esterification pathway.

Acetaldehyde↗

Hog1p mitogen-activated protein kinase determines acetic acid resistance in Saccharomyces cerevisiae.

When glucose-repressed, Saccharomyces cerevisiae cannot use acetic acid as a carbon source and is inhibited in growth by high levels of this compound, especially at low pH. Cultures exposed to a 100 mM acetate stress activate both the Hog1p and Slt2p stress-activated MAP kinases. Nevertheless, only active Hog1p, not Slt2p, is needed for the acquisition of acetate resistance. Hog1p undergoes more rapid activation by acetate in pH 4.5, than in pH 6.8 cultures, an indication that the acid may have to enter the cells in order to generate the Hog1p activatory signal. Acetate activation of Hog1p is absent in the ssk1Delta and pbs2Delta mutants, but is present in sho1Delta and ste11Delta, showing that it involves the Sln1p branch of the high-osmolarity glycerol (HOG) pathway signaling to Pbs2p. In low-pH (pH 4.5) cultures, the acetate-activated Hog1p, although conferring acetate resistance, does not generate the GPD1 gene or intracellular glycerol inductions that are hallmarks of activation of the HOG pathway by hyperosmotic stress.

Acetic Acid↗

Acetate production from hydrogen and [13C]carbon dioxide by the microflora of human feces.

Fecal suspensions from humans were incubated with 13CO2 and H2. The suspensions were from subjects who harbored 10(8) and 10(10) methanogens per g (dry weight) of feces, respectively, and from a subject who did not harbor methanogens. Quantitative nuclear magnetic resonance spectroscopy showed that acetate labeled in both the methyl and carboxyl groups was formed by suspensions from the subject without methanogens and the subject with the lower concentrations of methanogens. The amounts of labeled acetate formed were in agreement with the amounts expected based on measurements of H2 utilization. No labeled acetate was formed by suspensions from the subject with the higher concentrations of methanogens, and essentially all of the H2 used was accounted for by CH4 production. Suspensions from the subject with lower concentrations of methanogens produced both methane and acetate from H2 and CO2. The results indicate that reduction of CO2 to acetate may be a major pathway for microbial production of acetate in the human colon except when very high concentrations of methanogens (ca. 10(10) per g [dry weight] of feces) are present. Double-labeled acetate was also formed from H2 and 13CO2 by fecal suspensions from nonmethanogenic and moderately methanogenic rats.

Acetates↗

DNA microarray analyses of the long-term adaptive response of Escherichia coli to acetate and propionate.

In its natural environment, Escherichia coli is exposed to short-chain fatty acids, such as acetic acid or propionic acid, which can be utilized as carbon sources but which inhibit growth at higher concentrations. DNA microarray experiments revealed expression changes during exponential growth on complex medium due to the presence of sodium acetate or sodium propionate at a neutral external pH. The adaptive responses to acetate and propionate were similar and involved genes in three categories. First, the RNA levels for chemotaxis and flagellum genes increased. Accordingly, the expression of chromosomal fliC'-'lacZ and flhDC'-'lacZ fusions and swimming motility increased after adaptation to acetate or propionate. Second, the expression of many genes that are involved in the uptake and utilization of carbon sources decreased, indicating some kind of catabolite repression by acetate and propionate. Third, the expression of some genes of the general stress response increased, but the increases were more pronounced after short-term exposure for this response than for the adaptive response. Adaptation to propionate but not to acetate involved increased expression of threonine and isoleucine biosynthetic genes. The gene expression changes after adaptation to acetate or propionate were not caused solely by uncoupling or osmotic effects but represented specific characteristics of the long-term response of E. coli to either compound.

Acetates↗

Investigation of an acetate-fed denitrifying microbial community by stable isotope probing, full-cycle rRNA analysis, and fluorescent in situ hybridization-microautoradiography.

The acetate-utilizing microbial consortium in a full-scale activated sludge process was investigated without prior enrichment using stable isotope probing (SIP). [13C]acetate was used in SIP to label the DNA of the denitrifiers. The [13C]DNA fraction that was extracted was subjected to a full-cycle rRNA analysis. The dominant 16S rRNA gene phylotypes in the 13C library were closely related to the bacterial families Comamonadaceae and Rhodocyclaceae in the class Betaproteobacteria. Seven oligonucleotide probes for use in fluorescent in situ hybridization (FISH) were designed to specifically target these clones. Application of these probes to the sludge of a continuously fed denitrifying sequencing batch reactor (CFDSBR) operated for 16 days revealed that there was a significant positive correlation between the CFDSBR denitrification rate and the relative abundance of all probe-targeted bacteria in the CFDSBR community. FISH-microautoradiography demonstrated that the DEN581 and DEN124 probe-targeted cells that dominated the CFDSBR were capable of taking up [14C]acetate under anoxic conditions. Initially, DEN444 and DEN1454 probe-targeted bacteria also dominated the CFDSBR biomass, but eventually DEN581 and DEN124 probe-targeted bacteria were the dominant bacterial groups. All probe-targeted bacteria assessed in this study were denitrifiers capable of utilizing acetate as a source of carbon. The rapid increase in the number of organisms positively correlated with the immediate increase in denitrification rates observed by plant operators when acetate is used as an external source of carbon to enhance denitrification. We suggest that the impact of bacteria on activated sludge subjected to intermittent acetate supplementation should be assessed prior to the widespread use of acetate in the wastewater industry to enhance denitrification.

Acetates↗

Fermentation of glucose, fructose, and xylose by Clostridium thermoaceticum: effect of metals on growth yield, enzymes, and the synthesis of acetate from CO 2 .

Clostridium thermoaceticum ferments xylose, fructose, and glucose with acetate as the only product. In fermentations with mixtures of the sugars, xylose is first fermented, then fructose, and last, glucose. Fructose inhibits the fermentation of glucose, and this inhibition appears to be due to a repression of the synthesis of an enzyme needed for glucose utilization. Addition of metals to the culture medium increases the cell yield drastically from about 7 to 18 g per liter, and Y(glucose) values between 40 and 50 are obtained. According to the postulated pathways of the fermentation of glucose and synthesis of acetate from CO(2) by C. thermoaceticum, 3 mol of ATP are available as energy for growth. Thus a Y(adenosine 5'-triphosphate) of 13 to 16 is obtained. Because the normal Y(ATP) value is 10.5, this could mean that an additional source of ATP is available by an unknown mechanism. The addition of metals also increases the nicotinamide adenine dinucleotide phosphate-dependent formate dehydrogenase activity, the overall reaction ((14)CO(2) --> acetate), and the incorporation of the methyl group of 5-methyltetrahydrofolate into acetate. These reactions are catalyzed very efficiently by cells harvested in early growth, whereas cells obtained at the end of a fermentation have very low formate dehydrogenase activity and capacity to incorporate CO(2) into acetate. The following enzymes involved in the synthesis of acetate from CO(2) and in the metabolism of pyruvate are present in extracts of C. thermoaceticum: 10-formyltetrahydrofolate synthetase, 5,10-methenyltetrahydrofolate cyclohydrolase, 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methylenetetrahydrofolate reductase, phosphate acetyltransferase, and acetate kinase. These enzymes are not or are very little affected by the addition of metals to the growth medium. The amount of corrinoids in cells from early growth is low, whereas it is high in cells harvested late in growth. The opposite is found for the activity of delta-aminolevulinate dehydratase, which is high at the beginning of growth and low at the end.

Acetates↗

Properties of acetate kinase isozymes and a branched-chain fatty acid kinase from a spirochete.

Spirochete MA-2, which is anaerobic, ferments glucose, forming acetate as a major product. The spirochete also ferments (but does not utilize as growth substrates) small amounts of l-leucine, l-isoleucine, and l-valine, forming the branched-chain fatty acids isovalerate, 2-methylbutyrate, and isobutyrate, respectively, as end products. Energy generated through the fermentation of these amino acids is utilized to prolong cell survival under conditions of growth substrate starvation. A branched-chain fatty acid kinase and two acetate kinase isozymes were resolved from spirochete MA-2 cell extracts. Kinase activity was followed by measuring the formation of acyl phosphate from fatty acid and ATP. The branched-chain fatty acid kinase was active with isobutyrate, 2-methylbutyrate, isovalerate, butyrate, valerate, or propionate as a substrate but not with acetate as a substrate. The acetate kinase isozymes were active with acetate and propionate as substrates but not with longer-chain fatty acids as substrates. The acetate kinase isozymes and the branched-chain fatty acid kinase differed in nucleoside triphosphate and cation specificities. Each acetate kinase isozyme had an apparent molecular weight of approximately 125,000, whereas the branched-chain fatty acid kinase had a molecular weight of approximately 76,000. These results show that spirochete MA-2 synthesizes a branched-chain fatty acid kinase specific for leucine, isoleucine, and valine fermentation. It is likely that a phosphate branched-chain amino acids is also synthesized by spirochete MA-2. Thus, in spirochete MA-2, physiological mechanisms have evolved which serve specifically to generate maintenance energy from branched-chain amino acids.

Acetate Kinase↗

Protein content and enzyme activities in methanol- and acetate-grown Methanosarcina thermophila.

The cell extract protein content of acetate- and methanol-grown Methanosarcina thermophila TM-1 was examined by two-dimensional polyacrylamide gel electrophoresis. More than 100 mutually exclusive spots were present in acetate- and methanol-grown cells. Spots corresponding to acetate kinase, phosphotransacetylase, and the five subunits of the carbon monoxide dehydrogenase complex were identified in acetate-grown cells. Activities of formylmethanofuran dehydrogenase, formylmethanofuran:tetrahydromethanopterin formyltransferase, 5,10-methenyltetrahydromethanopterin cyclohydrolase, methylene tetrahydromethanopterin:coenzyme F420 oxidoreductase, formate dehydrogenase, and carbonic anhydrase were examined in acetate- and methanol-grown Methanosarcina thermophila. Levels of formyltransferase in either acetate- or methanol-grown Methanosarcina thermophila were approximately half the levels detected in H2-CO2-grown Methanobacterium thermoautotrophicum. All other enzyme activities were significantly lower in acetate- and methanol-grown Methanosarcina thermophila.

Acetates↗

Identification of RamA, a novel LuxR-type transcriptional regulator of genes involved in acetate metabolism of Corynebacterium glutamicum.

In Corynebacterium glutamicum, the acetate-activating enzymes phosphotransacetylase and acetate kinase and the glyoxylate cycle enzymes isocitrate lyase and malate synthase are coordinately up-regulated in the presence of acetate in the growth medium. This regulation is due to transcriptional control of the respective pta-ack operon and the aceA and aceB genes, brought about at least partly by the action of the negative transcriptional regulator RamB. Using cell extracts of C. glutamicum and employing DNA affinity chromatography, mass spectrometry, and peptide mass fingerprinting, we identified a LuxR-type transcriptional regulator, designated RamA, which binds to the pta-ack and aceA/aceB promoter regions. Inactivation of the ramA gene in the genome of C. glutamicum resulted in mutant RG2. This mutant was unable to grow on acetate as the sole carbon and energy source and, in comparison to the wild type of C. glutamicum, showed very low specific activities of phosphotransacetylase, acetate kinase, isocitrate lyase, and malate synthase, irrespective of the presence of acetate in the medium. Comparative transcriptional cat fusion experiments revealed that this deregulation takes place at the level of transcription. By electrophoretic mobility shift analysis, purified His-tagged RamA protein was shown to bind specifically to the pta-ack and the aceA/aceB promoter regions, and deletion and mutation studies revealed in both regions two binding motifs each consisting of tandem A/C/TG4-6T/C or AC4-5A/G/T stretches separated by four or five arbitrary nucleotides. Our data indicate that RamA represents a novel LuxR-type transcriptional activator of genes involved in acetate metabolism of C. glutamicum.

Acetates↗

Effect of lead acetate on the susceptibility of rats to bacterial endotoxins.

Selye, H. (Université de Montréal, Montreal, Canada), B. Tuchweber, and L. Bertók. Effect of lead acetate on susceptibility of rats to bacterial endotoxins. J. Bacteriol. 91:884-890. 1966.-A single, normally well-tolerated, intravenous injection of lead acetate increases the sensitivity of the rat to the endotoxins of various gram-negative bacteria about 100,000 times above normal. Under the conditions of these experiments, the mortality and organ changes normally produced by the intravenous injection of 100 mug of Escherichia coli endotoxin were essentially the same as those obtained by use of 1 nanogram in lead-sensitized rats. The sensitizing effect of lead acetate for E. coli endotoxin is greatest when the two agents are given simultaneously. However, considerable sensitization is still detectable when endotoxin is injected up to 1 hr before or 7 hr after sensitization with lead. No sensitization was noted when the endotoxin was administered 24 hr before or after lead acetate. Under our experimental conditions, the minimal dose of lead acetate which could still induce significant sensitization to E. coli endotoxin was 1 mg per 100 g of body weight. Although lead acetate induces a high degree of susceptibility to various endotoxins, other reticuloendothelial blocking agents did not acquire unusual toxicity after pretreatment with lead. Finally, none of the other metals or reticuloendothelial blocking agents tested could duplicate the pronounced decrease in endotoxin resistance induced by lead acetate.

Acetates↗

Treatment of plantar fasciitis by LowDye taping and iontophoresis: short term results of a double blinded, randomised, placebo controlled clinical trial of dexamethasone and acetic acid.

OBJECTIVES: To determine if, in the short term, acetic acid and dexamethasone iontophoresis combined with LowDye (low-Dye) taping are effective in treating the symptoms of plantar fasciitis. METHODS: A double blinded, randomised, placebo controlled trial of 31 patients with medial calcaneal origin plantar fasciitis recruited from three sports medicine clinics. All subjects received six treatments of iontophoresis to the site of maximum tenderness on the plantar aspect of the foot over a period of two weeks, continuous LowDye taping during this time, and instructions on stretching exercises for the gastrocnemius/soleus. They received 0.4% dexamethasone, placebo (0.9% NaCl), or 5% acetic acid. Stiffness and pain were recorded at the initial session, the end of six treatments, and the follow up at four weeks. RESULTS: Data for 42 feet from 31 subjects were used in the study. After the treatment phase, all groups showed significant improvements in morning pain, average pain, and morning stiffness. However for morning pain, the acetic acid/taping group showed a significantly greater improvement than the dexamethasone/taping intervention. At the follow up, the treatment effect of acetic acid/taping and dexamethasone/taping remained significant for symptoms of pain. In contrast, only acetic acid maintained treatment effect for stiffness symptoms compared with placebo (p = 0.031) and dexamethasone. CONCLUSIONS: Six treatments of acetic acid iontophoresis combined with taping gave greater relief from stiffness symptoms than, and equivalent relief from pain symptoms to, treatment with dexamethasone/taping. For the best clinical results at four weeks, taping combined with acetic acid is the preferred treatment option compared with taping combined with dexamethasone or saline iontophoresis.

Acetic Acid↗

Acetate absorption in the normal and secreting rat jejunum.

Acetate absorption was studied in rat jejunum using steady state perfusion in vivo. Absorption conformed to apparent saturation kinetics and was similar in magnitude to glucose absorption. When compared with normal saline, acetate perfusion was associated with luminal alkalinisation. There was no difference in total CO2 secretion when similar rates of acetate and glucose absorption were compared, suggesting that total CO2 secretion was the result of mucosal metabolism. Absorption of acetate and propionate were mutually inhibitory. Acetate absorption was also inhibited by Tris-Hepes pH 7.0. When the gut was pretreated with cholera toxin to induce a secretory state, acetate absorption was reduced by 41.9%. This effect could be reproduced if similar water secretion was osmotically induced by the addition of mannitol. These data suggest that acetate is absorbed, at least, partially by non-ionic diffusion in the rat jejunum and that its absorption is reduced in the secreting intestine by solvent drag.

Acetates↗