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Acetate-mediated effects of ethanol.

Ethanol has been shown to increase markedly portal blood flow, primarily by increasing intestinal blood flow. This effect of ethanol is reproduced by acetate, infused at rates equivalent to those leading to endogenous acetate production following ethanol administration. The physiological mediator, adenosine, is also known to increase markedly intestinal and portal tributary blood flow. We have shown that adenosine receptor blockade with 8-phenyltheophylline completely abolishes the effects of ethanol, acetate, and adenosine on intestinal and portal blood flow, suggesting that increases in adenosine tone may constitute a common mechanism mediating the actions of both ethanol and acetate on the splanchnic vasculature. Studies are also presented that show that acetate administration has marked effects on central nervous system function. On two tests, motor coordination and anesthetic potency, both ethanol and acetate showed similar effects. The effects of acetate were fully abolished by 8-phenyltheophylline. The effects of ethanol were partially blocked by 8-phenyltheophylline, with a greater effect of this blocker being seen at low doses of alcohol. Whereas ethanol at low doses increased locomotor activity in mice, acetate markedly reduced it. The effect of acetate on locomotion was fully reversed by the adenosine receptor blocker 8-phenyltheophylline, whereas the activating effect of ethanol on locomotion was markedly enhanced by this blocker. These data suggest that the actions of ethanol on locomotor activity normally result from the combination of a direct stimulatory effect of ethanol per se and an inhibitory effect of acetate, produced endogenously from ethanol. When the latter effect of acetate is abolished by adenosine receptor blockade, the activating effect of ethanol is fully expressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗

Shigella flexneri inhibition by acetic acid.

The degree of Shigella flexneri inhibition by acetic acid in a chemically defined medium was dependent upon the concentration of undissociated acetic acid in the medium. Under the conditions of the experiments, the critical concentration of undissociated acetic acid that completely inhibited S. flexneri multiplication was approximately 0.0018 M. Adjustment of the medium from pH 6.0 to 7.0 after incubation, which reduced the concentration of undissociated acid 10-fold, completely reversed inhibition, and S. flexneri attained a viable population equivalent to its population in medium without acetic acid. The effects of acetic acid on cellular processes were also studied. The acid interfered with the intracellular accumulation of glucose and glutamic acid but did not interfere with the accumulation of phosphate. The glucose analogue 3-o-methyl-D-glucose, which is taken up by S. flexneri but not metabolized, was used to determine if inhibition resulted from interference with permeation or interference with intracellular accumulation through inhibition of glucose metabolism. Acetic acid did not interfere with the uptake of the glucose analogue by S. flexneri, indicating that inhibition probably involves interference with metabolism. Further evidence for this conclusion was obtained from respiration studies with cell-free extracts in the presence and absence of acetic acid. Inhibition of oxygen uptake by acetic acid in the absence of a permeability barrier suggested a metabolic block rather than interference with permeation. The inhibition of oxygen uptake by cell-free extracts occurred at both pH 6.0 and 7.0, indicating that the degree of dissociation of the acid is unimportant regarding interference with metabolism by intracellular material. The degree of dissociation is important, however, regarding uptake of acetic acid by S. flexneri. Whole cells were more permeable to the undissociated form of acetic acid than to the dissociated form. The data indicate that acetic acid, when taken up by S. flexneri, interferes with the metabolism of glucose by the cells.

Acetates↗

Citric acid cycle in the hyperthermophilic archaeon Pyrobaculum islandicum grown autotrophically, heterotrophically, and mixotrophically with acetate.

The hyperthermophilic archaeon Pyrobaculum islandicum uses the citric acid cycle in the oxidative and reductive directions for heterotrophic and autotrophic growth, respectively, but the control of carbon flow is poorly understood. P. islandicum was grown at 95 degrees C autotrophically, heterotrophically, and mixotrophically with acetate, H2, and small amounts of yeast extract and with thiosulfate as the terminal electron acceptor. The autotrophic growth rates and maximum concentrations of cells were significantly lower than those in other media. The growth rates on H2 and 0.001% yeast extract with and without 0.05% acetate were the same, but the maximum concentration of cells was fourfold higher with acetate. There was no growth with acetate if 0.001% yeast extract was not present, and addition of H2 to acetate-containing medium greatly increased the growth rates and maximum concentrations of cells. P. islandicum cultures assimilated 14C-labeled acetate in the presence of H2 and yeast extract with an efficiency of 55%. The activities of 11 of 19 enzymes involved in the central metabolism of P. islandicum were regulated under the three different growth conditions. Pyruvate synthase and acetate:coenzyme A (CoA) ligase (ADP-forming) activities were detected only in heterotrophically grown cultures. Citrate synthase activity decreased in autotrophic and acetate-containing cultures compared to the activity in heterotrophic cultures. Acetylated citrate lyase, acetate:CoA ligase (AMP forming), and phosphoenolpyruvate carboxylase activities increased in autotrophic and acetate-containing cultures. Citrate lyase activity was higher than ATP citrate synthase activity in autotrophic cultures. These data suggest that citrate lyase and AMP-forming acetate:CoA ligase, but not ATP citrate synthase, work opposite citrate synthase to control the direction of carbon flow in the citric acid cycle.

Acetates↗

Acetate causes endothelium-independent increases in cyclic AMP in rat caudal artery.

The mechanism of the vasorelaxant action of acetate is unknown. Because cyclic nucleotides have been linked to vasorelaxation in vascular smooth muscle, we studied the effects of acetate on tissue adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) levels in rat caudal artery. Acetate (4 mM) induced an increase in tissue cAMP levels (control: 5.1 +/- 0.67, acetate: 7.1 +/- 0.97 pmol/mg protein, P less than 0.05), with the increase noted as early as 15-30 s after acetate exposure, and peaking at 60 s. The time course of the cAMP response was compatible with the vasorelaxant effect of acetate against an arginine vasopressin (AVP, 2 X 10(-9) M) contraction. Both the increase in cAMP and the vasorelaxant effect were completely blocked by 10(-3) M 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Acetate increased cAMP levels in 3-isobutyl-1-methylxanthine (IBMX)-treated tissue with an effective concentration producing 50% of the maximum response (EC50) of 1.5 mM, similar to the relaxant EC50 (without IBMX) of 2.2 mM against an AVP contraction. In other experiments, the effect of acetate on cAMP was shown to be independent of endothelium. In contrast, acetate had no effect on tissue cGMP levels, whether the endothelium was present or absent. The results suggest that acetate causes an increase in tissue cAMP levels that is not dependent on presence of a functioning endothelium. The changes in cAMP may be contributory to the vasorelaxant effect of acetate in the caudal artery.

1-Methyl-3-isobutylxanthine↗

Delineation of myocardial oxygen utilization with carbon-11-labeled acetate.

Although positron-emission tomography (PET) with labeled fatty acid delineates infarct size and permits qualitative assessment of fatty acid utilization, quantification of oxidative metabolism is limited by complex alterations in the pattern of utilization of fatty acid during ischemia and reperfusion. Because metabolism of acetate by myocardium is less complex than that of glucose or palmitate, we characterized kinetics of utilization of radiolabeled acetate in 37 isolated rabbit hearts perfused with modified Krebs-Henseleit buffer and performed a pilot tomographic study in man. Results of initial experiments with carbon-14-labeled acetate (14C-acetate) indicated that the steady-state extraction fraction of acetate averaged 61.5 +/- 4.0% in control hearts (n = 4), 93.6 +/- 0.9% in hearts rendered ischemic (n = 4), and 54.8 +/- 4.0% in hearts reperfused after 60 min of ischemia (n = 3). Oxidation of 14C-acetate, assessed from the rate of efflux of 14CO2 in the venous effluent, correlated closely with the rate of oxygen consumption under diverse metabolic conditions (r = .97, p less than .001). In addition, no significant differences were observed between rates of efflux of total 14C in all chemical species (reflecting total clearance of tracer from myocardium) and efflux of 14CO2. Clearance of 11C-acetate, measured externally with gamma probes in normal and ischemic myocardium, correlated closely with clearance of 14C-acetate measured directly in the effluent (r = .99, p less than .001) and with overall myocardial oxygen consumption (r = .95, p less than .001). Accumulation and clearance of 11C-acetate from human myocardium with PET demonstrated kinetics comparable to those seen with radiolabeled acetate in vitro. Thus externally detectable clearance of 11C-acetate provides a quantitative index of myocardial oxidative metabolism despite variation in the patterns of intermediary metabolism that confounds interpretation of results with conventionally used tracers such as glucose and fatty acid.

Acetates↗

Biodegradation of cellulose acetate by Neisseria sicca.

Bacteria capable of assimilating cellulose acetate, strains SB and SC, were isolated from soil on a medium containing cellulose acetate as a carbon source, and identified as Neisseria sicca. Both strains degraded cellulose acetate membrane filters (degree of substitution, DS, mixture of 2.8 and 2.0) and textiles (DS, 2.34) in a medium containing cellulose acetate (DS, 2.34) or its oligomer, but were not able to degrade these materials in a medium containing cellobiose octaacetate. Biodegradation of cellulose acetate (DS, 1.81 and 2.34) on the basis of biochemical oxygen demand reached 51 and 40% in the culture of N. sicca SB and 60 and 45% in the culture of N. sicca SC within 20 days. A decrease in the acetyl content of degraded cellulose acetate films and powder was confirmed by infrared and nuclear magnetic resonance analyses. After 10-day cultivation of N. sicca SB and SC, the number-average molecular weight of residual cellulose acetate decreased by 9 and 5%, respectively. Activities of enzymes that released acetic acid and produced reducing sugars from cellulose acetate were mainly present in the culture supernatant. Reactivity of enzymes for cellulose acetate (DS, 1.81) was higher than that for cellulose acetate (DS, 2.34).

Acetic Acid↗

Megestrol acetate treatment of growth failure in children infected with human immunodeficiency virus.

OBJECTIVE: To evaluate the effect of megestrol acetate on weight gain and linear growth in human immunodeficiency virus-infected children with growth failure. METHODS: All human immunodeficiency virus-infected children with growth failure treated with megestrol acetate at our institution were evaluated retrospectively. Weight, height, and weight:height ratio were documented from 6 months before initiation of megestrol acetate until 6 months after treatment was discontinued. Measurements were corrected for age and sex by conversion to z-scores. Incremental growth was determined before, during, and after treatment. The potential effects of CD4+ T-lymphocyte count and percentage, antiretroviral therapy, and intercurrent illnesses on growth were evaluated. RESULTS: Nineteen patients were treated with a total of 27 courses of megestrol acetate. The median duration of therapy was 7 months (range, 3 to 11 months), and the median megestrol acetate dose was 7.91 mg/kg/day (range, 4.06 to 8.56 mg/kg/day). From 6 months and 3 months before treatment to the onset of therapy, median changes in weight z-scores were -.27 and -.15, respectively. During megestrol acetate treatment, median changes in weight z-scores were +.29 after 1 month of therapy, +.40 after 3 months, and +.57 after 6 months. After megestrol acetate therapy was discontinued, poor weight gain and weight loss resumed. Median 6-month growth velocities for weight were less than the 10th percentile before megestrol acetate, greater than the 97th percentile during treatment, and less than the 3rd percentile after treatment was discontinued. Megestrol acetate therapy was not associated with changes in linear growth. Antiretroviral therapy, CD4+ T-lymphocyte count or percentage, or intercurrent illnesses were not associated with statistically significant differences in response to megestrol acetate therapy. CONCLUSIONS: Megestrol acetate treatment of growth failure in pediatric human immunodeficiency virus disease is associated with weight gain, without affecting linear growth.

Adolescent↗

Regional blood flow redistribution due to acetate.

There is little information about the effects of acetate on regional blood flow in unanesthetized animals. Isosmolal sodium acetate or saline was infused at a rate of 250 mumol/kg.min into conscious rats such that, in the acetate group, plasma acetate levels averaged 2.06 +/- 0.23 mM. Sequential injections of tracer-tagged microspheres were used to determine the effect of acetate infusion on cardiac output, total peripheral vascular resistance, and various organ blood flow rates. At this infusion level, acetate had no discernible effect on either central hemodynamics or arterial blood gases. However, there was marked alteration of regional organ perfusion. After 5 min of infusion, acetate (relative to control) increased blood flow markedly to the splanchnic bed (+40 +/- 6.1%), including all individual splanchnic organs except for the stomach. Acetate also increased blood flow to the heart (+33 +/- 5.2%) and kidneys (+29 +/- 5.4%); all P < 0.05. Acetate had no specific effect on total cerebral blood flow or on regional brain circulations. Acetate had no effect on flow to skeletal muscle (-30 +/- 11%; P = not significant) or fat (-5 +/- 6.3%; P = 0.097), although flow to muscle tended to decrease. These data suggest that low plasma levels of acetate, which do not alter total peripheral resistance, cause a marked redistribution of blood flow to the splanchnic organs and to the kidneys. Brain blood flow is unaffected.

Acetates↗

Determinants of the acetate recovery factor: implications for estimation of [13C]substrate oxidation.

When using (13)C or (14)C tracers to study substrate metabolism, an acetate correction factor should be applied to correct for loss of label in the exchange pathways of the tricarboxylic acid cycle. We have shown recently that the [(13)C]acetate recovery factor has a high inter-individual variability and should therefore be determined in every subject. In the present study we examined the factors that might explain some of the variability between subjects in acetate recovery factor. Data were pooled from four different studies with identical protocols, in which the acetate recovery factor was measured, prior to an intervention, to correct plasma fatty acid oxidation rates. Acetate recovery was measured after 2 h of [1, 2-(13)C]acetate infusion at rest followed by 1 h of cycling exercise at 40-50% of maximal oxygen uptake. Inter-individual variance in acetate recovery was 12.0% at rest and 16.1% during exercise. Stepwise regression revealed that, at rest, 37.1% of the acetate recovery could be accounted for by basal metabolic rate adjusted for fat-free mass, percentage body fat and respiratory quotient (RQ). During exercise, 69.1% of the variance in acetate recovery could be accounted for by energy expenditure adjusted for fat-free mass, % body fat and RQ. In conclusion, we show that the acetate recovery factor has a high inter-individual variability, both at rest and during exercise, which can partly be accounted for by metabolic rate, RQ and % body fat. These data indicate that the acetate recovery factor needs to be determined in every subject, under similar conditions as used for the tracer-derived determination of substrate oxidation. Failure to do this might result in large under- or over-estimation of plasma substrate oxidation, and hence to artificial differences between groups.

Acetic Acid↗

[On-line hemodiafiltration without acetate].

PURPOSE: The suitably filtered dialysate which is currently reinfused during on-line hemodiafiltration (HDF-OL) contains bicarbonate and small doses of acetate. The trend of acetataemia During "forced" convective treatments has never been studied. The gain in acetate secondary to the considerable quantities of fluids infused might have clinical significance in relation to the well-known side effects of this anion. METHODS: In this pilot study 12 patients underwent HDF-OL with reinfusion in predilution of 40 L of substitution fluids containing or not 3 mmol/L of acetate. Apart from this variable, all the other treatment parameters were the same in both procedures. The treatments were carried out in two short consecutive intervals in a random sequence. RESULTS: During HDF-OL the use of dialysate containing small doses of acetate is associated with levels of acetataemia 5-6 times higher compared to the basal. HDF-OL without acetate cancels out this increase. The acetate gained by the patients is significant, on average 75 mmol, and accounts for over 1/3 of the global base gain. Consequently, the bicarbonataemia levels at the end of treatment are significantly higher in HDF-OL with acetate than in the treatment without. Two hours after the end of the treatments the IL-6 levels tend to grow in both methods, but numerically less in HDF-OL without acetate; the difference verges on meaningfulness. CONCLUSIONS: The acetate gain is significant during forced convective treatments carried out with standard dialysate. This acetate gain can trigger cytokinin activation. These events are cancelled out by eliminating the acetate from the dialysate. The absence of this anion will be compensated with appropriate increases in the concentration of bicarbonate in the dialysis fluid.

Acetates↗

Effects of acetate during regular hemodialysis.

The utilization of acetate and its effects on acid-base balance and on free fatty acid metabolism were investigated during regular hemodialysis (HD). Fourteen patients with chronic renal failure were studied during two successive dialysis treatments for which either acetate or bicarbonate were used as a buffer anion in the dialysate. In the acetate studies the mean plasma acetate concentration in the arterial line rose from 0.16 mM to 4.67 mM, while it rose from 0.17 mM to 0.62 mM during bicarbonate dialysis. There was a linear relationship between acetate utilization and the acetate concentration in the venous line. The increase of the blood pH during bicarbonate HD was due to an immediate increase of HCO3, whereas acetate caused a smaller HCO3 rise and a pronounced fall of the pCO2. The heart rate was higher during acetate than during bicarbonate HD. During both types of dialysis there was a twofold rise of total FFA as well as the individual fatty acids palmitate, palmitoleate, oleate, stearate and linoleate which was of similar magnitude when acetate or bicarbonate were used. The postulated antilipolytic effect of the short-chain fatty acid acetate could not be demonstrated under the circumstances of routine hemodialysis. Pre-dialysis dopamine was elevated in 7 of the 11 patients and remained high during both types of HD; other hormones were normal during acetate and bicarbonate HD.

Acetates↗

Production of endogenous acetate by the liver in lactating ewes.

The production of endogenous acetate by the liver has been investigated in lactating ewes using animals with indwelling arterial, and portal and hepatic venous cannulae. The capacity of the liver to produce acetate from acetyl-CoA in vitro has also been examined using homogenates prepared from liver biopsy samples. Mean arterial, portal and hepatic venous blood acetate concentrations in four ewes at 4 weeks lactation were 0.40, 1.00 and 1.46 mM respectively. The mean exogenous and endogenous acetate production rates were 56 and 54 mmol/h respectively, giving a total of 110 MMOL/h. The mean portal-hepatic venous difference in free fatty acid concentration was 81 muM. Converting this uptake of free fatty acids by the liver (based on palmitate as a standard) to 2-carbon equivalents, the acetate produced accounted for 70% of the fatty acids taken up. The correlation coefficient (r2) between uptake of free fatty acids and production of acetate by the liver was 0.83 (P less than 0.01). Calculation of the net acetate production in vivo gave a mean value for the production of acetate of 0.75 nmol/min. Calculation of the in vitro enzymic capacity of the liver to produce acetate from acetyl-CoA gave a mean of 0.94 mmol/min. These results indicate that enzymic production of acetate from acetyl-CoA, via carnitine acetyltransferase and acetylcarnitine hydrolase (see Costa and Snoswell 1975a), can adequately account for the substantial production of acetate by the liver in lactating ewes.

Acetates↗

Starch acetate microparticles for drug delivery into retinal pigment epithelium-in vitro study.

Starch acetates are novel biodegradable polymers which undergo slower degradation and swelling than native starch. Retinal pigment epithelium (RPE) is an important target tissue in ocular treatment. The cellular uptake of starch acetate microparticles and degradation of starch acetate by cultured human RPE-cell line (D407) was examined. Calcein-containing starch acetate microparticles were prepared by a modified water-in-oil-in-water double-emulsion technique. The cellular uptake of the starch acetate microparticles was analysed using flow cytometry and confocal microscopy. Degradation of starch acetate films by the homogenate of lysed RPE cells was determined by gel permeation chromatography. The effect of the microparticles on RPE cell viability was determined by the MTT colorimetric assay. The mean diameter (D50%) of microparticles was 11 microm. During 3-h incubation in RPE-cell culture, 8.1 +/- 0.8% of D407 cells took up starch acetate microparticles. Confocal microscopy confirmed the internalisation of microparticles. Incubation of the starch acetate film in the RPE-cell homogenate considerably decreased the molecular weight of starch acetate in the film during 24 h. The viability of cultured RPE cells was at least 82% after 24-h incubation with the microparticles. The present results show that the starch acetate microparticles are taken up by the RPE cells and the polymer can be degraded by the enzymes in these cells. Starch acetate microparticles may be suitable for drug delivery to the RPE.

Cell Line↗

Caspofungin acetate: an antifungal agent.

The pharmacology, bioavailability and pharmacokinetics, clinical efficacy, and adverse effects of caspofungin acetate are reviewed. Caspofungin acetate is an echinocandin with fungicidal activity against a wide range of pathogens, including Candida spp., Aspergillus spp., and Histoplasma spp. It is active against fluconazole-resistant and fluconazole-susceptible strains of Candida albicans. Caspofungin acetate irreversibly inhibits the enzyme 1,3-beta-D-glucan synthase, preventing the formation of glucan polymers and disrupting the integrity of the fungal cell wall. Caspofungin acetate has an elimination half-life of 9-10 hours and is suitable for once-daily regimens. Data from animal and human studies demonstrate that the drug is 80-96% protein bound. Less than 3% of the dose is eliminated unchanged in the urine, and the proposed route of elimination is hepatic. In a trial of 128 patients with Candida esophagitis, clinical response rates were higher with caspofungin acetate 50 or 70 mg/day (85%) than with amphotericin B 0.5 mg/kg/day (67%). Most enrolled patients had HIV infection, and almost half had CD4+ lymphocyte counts of less than 50 cells/microL in another study, 56 immunocompromised patients with aspergillosis were treated with one 70-mg dose of caspofungin acetate, then 50 mg once a day. All patients had refractory invasive aspergillosis or were intolerant of amphotericin B, liposomal amphotericin B, or azole therapy. In patients who received at least one dose of caspofungin acetate, a favorable response was reported in 41%. In 128 patients who received either caspofungin acetate or amphotericin B, fewer caspofungin acetate recipients (1.4%) had elevated serum creatinine levels and discontinued therapy because of adverse effects (4%) than amphotericin B recipients (15% and 22%, respectively). The manufacturer's recommended dose for infections caused by Candida or Aspergillus spp. has not been determined. Caspofungin acetate appears to be fungicidal, with a wide spectrum of antifungal activity and a good safety profile. The lack of adequate efficacy and safety data in humans makes a recommendation to add this drug to the formulary premature. Pending advanced clinical trials and cost information, caspofungin acetate may be a reasonable addition to the formulary, particularly in hospitals with large immunocompromised patient populations.

Adult↗

Isolation of a Strain of Clostridium thermoaceticum Capable of Growth and Acetic Acid Production at pH 4.5.

Using a series of pH controlled batch fermentations operated in a fed-batch mode and adaptation and selection techniques where pH and acetic acid provided the selective pressures, we isolated a culture of Clostridium thermoaceticum that can grow and produce acetic acid at pH 4.5. At pH 4.5 the fastest mass doubling time was 36 h, and the highest acetic acid concentration reached was 4.5 g/liter. Generally, as the pH was decreased from 6.0 and the initial acetic acid concentration increased, the mass doubling time increased, and the final acetic acid concentration decreased. These observations can be explained in terms of inhibition by the free acetic acid concentration at a given pH, relative to the total acetic acid concentration (free acid plus acetate ion). We have thus reached one of the criteria determined by us to be required for an economically viable fermentation acetic acid process, i.e., pH 4.5. A second requirement for a mass doubling time of about 7 h (0.1/h dilution rate) can probably be reached by selection in continuous culture. The final requirement for an acetic acid concentration of 50 g/liter will be the most difficult to achieve in view of the organism's sensitivity to low concentrations of free acetic acid.

Journal Article↗

Effects of environmental parameters on the formation and turnover of acetate by forest soils.

The capacity to form acetate from endogenous matter was a common property of diverse forest soils when incubated under anaerobic conditions. At 15 to 20(deg)C, acetate synthesis occurred without appreciable delay when forest soils were incubated as buffered suspensions or in microcosms at various percentages of their maximum water holding capacity. Rates for acetate formation with soil suspensions ranged from 35 to 220 (mu)g of acetate per g (dry weight) of soil per 24 h, and maximal acetate concentrations obtained in soil suspensions were two- to threefold greater than those obtained with soil microcosms at the average water holding capacity of the soil. Cellobiose degradation in soil suspensions yielded H(inf2) as a transient product. Under anaerobic conditions, supplemental H(inf2) and CO(inf2) were directed towards the acetogenic synthesis of acetate, and enrichments yielded a syringate-H(inf2)-consuming acetogenic consortium. At in situ temperatures, acetate was a relatively stable anaerobic end product; however, extended incubation periods induced acetoclastic methanogenesis and sulfate reduction. Higher mesophilic and thermophilic temperatures greatly enhanced the capacity of soils to form methane. Although methanogenic and sulfate-reducing activities under in situ-relevant conditions were negligible, these findings nonetheless demonstrated the occurrence of methanogens and sulfate-reducing bacteria in these aerated terrestrial soils. In contrast to the protracted stability of acetate under anaerobic conditions at 15 to 20(deg)C with unsupplemented soils, acetate formed by forest soils was rapidly consumed in the presence of oxygen and nitrate, and substrate-product stoichiometries indicated that acetate turnover was coupled to oxygen-dependent respiration and denitrification. The collective results suggest that acetate formed under anaerobic conditions might constitute a trophic link between anaerobic and aerobic processes in forest soils.

Journal Article↗

Megestrol acetate therapy in geriatric patients: case reviews and associated deep vein thrombosis.

OBJECTIVE: To provide a brief review of the literature discussing treatment of unplanned weight loss in geriatric patients, focusing on megestrol acetate and to report two cases of deep vein thrombosis (DVT) associated with megestrol acetate therapy in geriatric nursing facility residents. DATA SOURCES: Biomedical literature accessed through MEDLINE and PubMed (1990-2003); product manufacturer information. DISCUSSION: Unplanned weight loss, a common problem among frail geriatric nursing facility residents, is associated with increased morbidity and mortality. Once reversible causes of weight loss are identified and addressed, dietary changes, including the addition of nutritional supplements, may be of benefit. In some cases, medications are prescribed. Megestrol acetate oral suspension is approved by the Food and Drug Administration for the treatment of anorexia, cachexia, or unexplained significant weight loss in patients with AIDS. Megestrol acetate tablets are FDA-approved for palliative treatment of advanced breast or endometrial cancer. In recent years, several published prospective and retrospective reports have described the use of megestrol acetate for unplanned weight loss in geriatric patients. While clinical efficacy trials reported diarrhea, impotence, and rash as the most commonly occurring adverse events, post-marketing reports have included deep vein thrombosis and pulmonary embolism. DVP has occurred in geriatric patients. CASE SUMMARIES: Case #1: An 86-year-old female with Alzheimer's disease and decreased oral intake was prescribed megestrol acetate suspension 400 mg po bid after a 30-day weight loss of 4.8 kg. Ten days later she developed DVT. Megestrol acetate was discontinued, and she was hospitalized and treated, recovering successfully. Case #2: An 85-year old female with Alzheimer's disease who had stopped eating was prescribed megestrol acetate tablets 40 mg po bid. Four months later she developed DVT. Megestrol acetate was discontinued and she was hospitalized and treated, recovering successfully. CONCLUSION: Thromboembolic events are potential adverse events associated with megestrol acetate therapy. Caution should be observed in using megestrol acetate in geriatric patients, especially nursing facility residents who often have impaired mobility.

Journal Article↗

The possible role of acetate in exercise hyperemia in dog skeletal muscle.

The possible role of acetate in the genesis of exercise hyperemia was studied in five series of dogs. Intraarterial infusion of an isomotic solution of sodium acetate at 0.76 ml/min in the dog forelimb decreased the resistance to flow through skeletal muscle by 48%, primarily by decreasing resistance to flow through small vessels. Skin lymph flow and lymph protein concentration were unaffected. The hindlimb of the conscious dog took up acetate at rest (A-V difference, + 58.3 +/- 19.6 nmoles/ml) and put out acetate during treadmill exercise (A-V difference, -105.6 +/- 20.12 nmoles/ml); femoral venous blood acetate concentration increased by 145 nmoles/ml (control 195 nmoles/ml). In the gracilis muscle of the anesthetized dog, simulated exercise at 0.5, 1.0 or 2.0 Hz increased acetate tissue content (72, 248 and 442 nmoles/g, respectively), output (18,899, and 1,830 nmoles/100 g/min, respectively) and venous concentration (82, 49 and 39 nmoles/ml, respectively) and changes in tissue acetate content correlated with changes in vascular resistance r = 0.75, P less than 0.001. Intraarterial infusion of an isosmotic solution of sodium acetate in the quiescent gracilis muscle perfused at constant flow produced a significant (6%) decrease in resistance when arterial blood acetate was increased by a calculated 96 nmoles/ml. These studies suggest that acetate might be included among those metabolites that contribute to exercise hyperemia.U

Acetates↗