SEARCH · PubMed Health

Results for “Acetates”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources

PubMed1995

Short chain fatty acid absorption from the human distal colon: interactions between acetate, propionate and calcium.

OBJECTIVE: Our purpose was to conduct a preliminary study to see if propionate and calcium affected acetate absorption, and acetate and calcium affected propionate absorption from the human distal colon. METHODOLOGY: We studied six healthy subjects on eight occasions in randomized order after overnight fasts. Test solutions (300 ml) were infused into the rectum, retained for 30 minutes, and then the infusion fluid was collected for analysis. The infusion solutions contained combinations of sodium acetate (56.25 mmol/L), sodium propionate (18.75 mmol/L) and calcium chloride (50 mmol/L) plus polyethylene glycol (PEG) as an unabsorbable marker. RESULTS: The reduction in the acetate:PEG concentration ratio over 30 minutes after acetate alone, 4.1 +/- 4.2, was significantly less than after acetate plus propionate, 40.2 +/- 11.9, and acetate plus calcium, 34.0 +/- 8.9 (p < 0.05). However, the change in acetate:PEG ratio when acetate, propionate and calcium were all infused together, 13.2 +/- 4.6, was no different from acetate alone. The reduction in the propionate:PEG concentration ratio after propionate alone was 15.7 +/- 3.3, and this was not significantly affected by adding acetate and calcium either alone or together. CONCLUSIONS: We conclude that the absorption of acetate in the rectum and distal colon of humans may be influenced by the presence of calcium and propionate. More detailed kinetic studies are required to confirm these results and characterize the transport mechanisms involved.

Acetates↗

PubMed1975

The metabolism of acetate in the perfused hind-quarter of the rat.

The elimination kinetics of acetate, the main end product of ethanol metabolism in the liver and the influence of acetate oxidation on the redox- and energy state of the isolated perfused hind-quarter of the rat were studied. The rate of acetate uptake increased with increasing initial concentration of acetate in the perfusion medium, suggesting that the plasma level of free acetate may be one factor in the regulation of acetate uptake in the skeletal muscle. Addition of acetate as a single dose did not affect the net production of lactate or the uptake of glucose. In continuous infusion experiments at a constant concentration of 2 mM of acetate in the medium, the lactate/pyruvate ratio was unaffected in the medium and in the muscle tissue. Addition of acetate did not affect the oxygen uptake. Experiments with 14-C-acetate showed that about 50% of added radioactivity was found in form of 14-CO2 accounting for 25 to 45% of the oxidative metabolism in the muscle tissue. It was calculated that about 25% of the acetate produced in the liver during ethanol oxidation can be consumed in the resting, perfused hind-quarter of the rat. The tissue content of high-energy phosphate compounds was not significantly affected by acetate.

Acetates↗

PubMed1976

Acetate as a metabolic substrate in the fetal lamb.

Fetal acetate metabolsim was studied in chronically catheterized fetal lambs of 110-141 days' gestation. Acetate concentration was measured enzymatically in whole blood drawn simultaneously from maternal and fetal pre- and postplacental vessels. The oxygen content of the fetal blood samples was also measured. Fetal umbilical venous acetate concentration was found to be proportional to the maternal arterial acetate concentration and had a mean value of 0.366 mM. Fetal blood acetate increased significantly, by a mean of 0.081 mM, during circulation through the placenta. This increase was proportional to both the maternal acetate concentration and the concentration gradient of acetate across the placenta. The mean maternal arterial acetate concentration was 1.153 mM. Maternal blood lost significant amounts of acetate, 0.112 mM, during circulation through the uterus and appeared to be the source of the acetate being gained by the fetus. It is estimated that a total of 23 mmol of acetate/kg of fetal weight is being taken up by the fetus each day, providing it with 0.560 g of carbon/kg. Comparisons of acetate uptake with fetal oxygen uptake indicate 10% of the daily fetal oxygen consumption would be required to completely oxidize the acetate being gained by the fetus.

Acetates↗

PubMed1978

Metabolic control of the circulation. Effects of acetate and pyruvate.

Chloralose-anesthetized dogs were infused intravenously with either Tris-acetate or Tris-pyruvate at 0.0375, 0.075, and 0.15 mmol/kg per min successively, each for 20 min. Acetate infusion increased cardiac output, left ventricular dP/dt and dP/dt/P, and coronary blood flow, while pyruvate infusion did not. Infusions of either substance increased arterial blood and skeletal muscle concentrations of citrate and malate, but only acetate infusion increased the tissue AMP content and decreased the ATP:AMP ratio. The increase in cardiac output produced by acetate was accompanied by an increase in total body oxygen consumption and a decrease in the difference between arterial and mixed venous blood oxygen. Myocardial oxygen consumption increased during acetate infusion, but the decrease in myocardial oxygen extraction and the increase in coronary sinus blood oxygen saturation suggest that an active coronary vasodilation which was not a result of the increased cardiac work, occurred. The concentration of hypoxanthine in the coronary sinus and the content of myocardial adenosine increased, which suggests that the increase in coronary blood flow was caused by the vasodilator action of adenosine released from the myocardium, and that adenosine production is not necessarily tied to PO(2). These systemic and coronary hemodynamic changes also occurred when acetate (0.075 mmol/kg per min) was infused into conscious dogs. Acetate infusion also increased blood flow to the gastrointestinal tract, kidneys, intercostal muscle, and diaphragm. These changes were not affected by propranolol pretreatment, but were abolished by pretreatment with fluoroacetate which reduced acetate oxidation. These results suggest that the circulatory stimulation produced by acetate was not caused by increases in tricarboxylic acid cycle intermediates. Instead, it was probably related to the increased cleavage of ATP to AMP that accompanies activation of acetate to acetyl CoA, and was not mediated via beta-adrenergic receptors. It is speculated that hemodynamic changes may occur in patients who undergo hemodialysis with acetate-containing dialysate. Hemodynamic changes of ethanol may also be brought about by acetate, which is one of the intermediates that accumulates during ethanol metabolism.

Acetates↗

PubMed1975

Androgenic properties and adrenal depressant activity of megestrol acetate observed in castrated male rats.

Megestrol acetate (17alpha-acetoxy-6-dehydro-6-methylprogesterone), a synthetic steroid with high progestational activity, is used in oral contraceptives but also in the treatment of prostatic diseases in man. To investigate whether megestrol acetate has any androgenic properties the growth of the ventral and dorsolateral prostate, the coagulating glands and the seminal vesicles was studied morphologically in castrated rats treated with megestrol acetate and in non-treated castrated rats. The effect of megestrol acetate on the body weight, the levator ani muscle and the adrenals was also studied. Megestrol acetate was administered in daily doses of 0.02 mg, 0.2 mg, 2.0 mg or 20.0 mg for a period of 21 days. Megestrol acetate in the two higher doses retarded growth and gave a low weight for the levator ani muscle at autopsy indicating an anti-anabolic or catabolic action of megestrol acetate in high doses. Megestrol acetate in daily doses of 0.2, 2.0 and 20.0 mg caused an involution of the adrenal glands. After the two higher doses the weight of the adrenals amounted to only about a third of that of the untreated rats. Megestrol acetate in the lower doses had no demonstrable effect on the growth of the accessory reproductive glands. After the two higher doses of megestrol acetate some growth of the dorsal part of the dorsolateral prostate and of the coagulating glands was observed. Only the seminal vesicles exhibited complete morphological criteria of an androgenic stimulation and then only after the largest dose of megestrol acetate. The investigation shows that megesterol acetate has weak androgenic properties which are apparent at a dose per kg body weight approximately 200 times greater than that used in the treatment of prostatic diseases in man.

Acetates↗

PubMed2002

Glatiramer acetate: a review of its use in relapsing-remitting multiple sclerosis.

UNLABELLED: Glatiramer acetate is a synthetic copolymer composed of a random mixture of four amino acids that modifies the immune response that results in the CNS inflammation, demyelination and axonal loss characteristic of relapsing-remitting multiple sclerosis (RRMS). In three randomised, double-blind trials in patients with RRMS, subcutaneous glatiramer acetate 20 mg/day was significantly more effective than placebo for the primary outcome measure of each trial (mean relapse rate, proportion of relapse-free patients and number of gadolinium-enhancing lesions on magnetic resonance imaging [MRI] scans). The mean relapse rate was significantly reduced at endpoint (approximately one-third less) in the two larger trials (the US pivotal trial [primary endpoint] and the European/Canadian study [tertiary endpoint]) in patients receiving glatiramer acetate compared with those receiving placebo. The rate was 78% less for glatiramer acetate than placebo patients in the pilot trial that investigated a slightly different patient population. Glatiramer acetate significantly decreased disease activity and burden of disease, as assessed in the European/Canadian study using a range of MRI measures. Patients with RRMS treated with glatiramer acetate in the US trial were significantly more likely to experience improved disability (whereas placebo recipients were more likely to experience worsening disability) and their overall disability status was significantly improved compared with placebo recipients. Data from the active-treatment extension of the US trial suggest that glatiramer acetate has sustained clinical benefits up to 8 years. Glatiramer acetate was generally well tolerated; the most commonly reported treatment-related adverse events were localised injection-site reactions and transient post-injection systemic reactions. Both reactions were generally mild and self limiting but were responsible for the majority of withdrawals from treatment (up to 6.5 and 3.5%, respectively). Glatiramer acetate is not associated with the influenza-like syndrome or neutralising antibodies that are reported in patients treated with interferon-beta for RRMS. The cost effectiveness of glatiramer acetate has yet to be definitively determined as assessment of available data is confounded by very different models, data sources and assumptions. CONCLUSION: Glatiramer acetate has shown efficacy in well controlled clinical trials in patients with RRMS; it reduces relapse rate and decreases MRI-assessed disease activity and burden. It is generally well tolerated and is not associated with the influenza-like symptoms and formation of neutralising antibodies seen with the interferons-beta. Based on available data and current management guidelines, glatiramer acetate is a valuable first-line treatment option for patients with RRMS.

Adjuvants, Immunologic↗

PubMed2003

Spotlight on glatiramer acetate in relapsing-remitting multiple sclerosis.

Glatiramer acetate (Copaxone) is a synthetic copolymer composed of a random mixture of four amino acids that modifies the immune response that results in the CNS inflammation, demyelination and axonal loss characteristic of relapsing-remitting multiple sclerosis (RRMS). In three randomised, double-blind trials in patients with RRMS, subcutaneous glatiramer acetate 20 mg/day was significantly more effective than placebo for the primary outcome measure of each trial (mean relapse rate, proportion of relapse-free patients and number of gadolinium-enhancing lesions on magnetic resonance imaging [MRI] scans). The mean relapse rate was significantly reduced at endpoint (approximately one-third less) in the two larger trials (the US pivotal trial [primary endpoint] and the European/Canadian study [tertiary endpoint]) in patients receiving glatiramer acetate compared with those receiving placebo. The rate was 78% less for glatiramer acetate than placebo patients in the pilot trial that investigated a slightly different patient population. Glatiramer acetate significantly decreased disease activity and burden of disease, as assessed in the European/Canadian study using a range of MRI measures. Patients with RRMS treated with glatiramer acetate in the US trial were significantly more likely to experience improved disability (whereas placebo recipients were more likely to experience worsening disability) and their overall disability status was significantly improved compared with placebo recipients. Data from the active-treatment extension of the US trial suggest that glatiramer acetate has sustained clinical benefits up to 8 years. Glatiramer acetate was generally well tolerated; the most commonly reported treatment-related adverse events were localised injection-site reactions and transient post-injection systemic reactions. Both reactions were generally mild and self limiting but were responsible for the majority of withdrawals from treatment (up to 6.5% and 3.5%, respectively). Glatiramer acetate is not associated with the influenza-like syndrome or neutralising antibodies that are reported in patients treated with interferon-beta for RRMS. The cost effectiveness of glatiramer acetate has yet to be definitively determined as assessment of available data is confounded by very different models, data sources and assumptions. In conclusion, glatiramer acetate has shown efficacy in well controlled clinical trials in patients with RRMS; it reduces relapse rate and decreases MRI-assessed disease activity and burden. It is generally well tolerated and is not associated with the influenza-like symptoms and formation of neutralising antibodies seen with the interferons-beta. Based on available data and current management guidelines, glatiramer acetate is a valuable first-line treatment option for patients with RRMS.

Adjuvants, Immunologic↗

PubMed2000

Michaelis-Menten elimination kinetics of acetate during ethanol oxidation.

BACKGROUND: The redistribution of acetate cannot be explained using a linear kinetic model. We studied the pharmacokinetics of acetate during ethanol oxidation in the rabbit. METHODS: An ethanol saline solution (0.5, 1.5, and 2.5 g/kg) was injected bolus intravenously. We measured blood ethanol, acetaldehyde, and acetate concentrations by using head-space gas chromatography. RESULTS: Blood acetate concentration changed in three phases: an ascending, a plateau, and a declining phase. The first-order rate constant of the declining phase was smaller than that of the ascending phase and decreased dose dependently. Statistical moment analysis of the blood acetate profiles showed that the normalized area under the curve (AUC/Dose) and the mean residence time (MRT) increased with increasing dose amount. These increases suggest a capacity-limited elimination of acetate. We attempted simultaneous multiline fitting, using the three blood acetate disappearance curves, to determine the pharmacokinetic model. Consequently, the blood acetate profile was best described by a Michaelis-Menten elimination kinetic model. The Vmax and Km values of acetate elimination were 40.80 +/- 14.10 mM/hr and 0.47 +/- 0.19 mM, respectively. The fraction of a dose of ethanol converted to acetate (f(AcA)) was calculated to be 0.54. The estimated values are average parameter values of three different doses. Fitted curves suggest smaller f(AcA) at a low dose and larger f(AcA) at a higher dose, which indicate increases of accumulation and redistribution of acetate at higher doses. CONCLUSIONS: Acetate elimination during ethanol oxidation obeys capacity-limited kinetics.

Acetaldehyde↗

PubMed1979

Measurement of acetate in human blood by gas chromatography: effects of sample preparation, feeding, and various diseases.

We measured acetate concentrations in whole blood, serum, and plasma by a modification of a previously described method involving vacuum distillation and gas chromatography. The mean acetate concentration of fresh venous plasma from 27 normal subjects was 51 +/- 5 mumol/L (95% confidence limits ranged from 0 to 103 mumol/L). The acetate concentrations of serum and plasma incubated for 2 h at either 4 degrees C or 27 degrees C were the same. The acetate concentration of whole blood incubated at 27 degrees C was significantly greater than that of blood incubated at 4 degrees C. This change may have resulted from the production of acetate by erythrocytes or from the hydrolysis of acetate esters. Storage of plasma at -20 degrees C for 24 h significantly increased acetate concentrations from 26 +/- 6 mumol/L to 63 +/- 4 mumol/L. After the subjects consumed a standard breakfast, venous plasma acetate concentrations increased from 58 to 97 mumol/L at 30 min. Acetate concentrations in arterial plasma exceeded those in venous plasma. Plasma acetate concentrations were not significantly altered in patients with malignancy or diabetes mellitus, but severe liver disease and severe acidosis were both associated with increased acetate concentrations. These preliminary observations suggest that plasma acetate concentrations may be altered in several disease states.

Acetates↗

PubMed1983

Acetate and energy metabolism during hemodialysis.

The oxidation of acetate infused in acetate infused in large quantities during acetate dialysis should provide considerable energy for the hemodialysis patient. Previous attempts to measure acetate oxidation rate and thus energy yield by measuring bicarbonate generation rate are flawed because bicarbonate generation occurs by equimolar proton consumption when acetate is activated to acetyl Co-A but before acetyl Co-A has entered the Krebs cycle. Besides the Krebs cycle, acetyl Co-A could enter many other nonoxidative pathways. By using the primed continuous infusion radioisotope (1-14C acetate) dilution technique of Steele, in conjunction with indirect calorimetry, we obtained direct measurements of acetate turnover and immediate oxidation rates and energy yield in 7 stable hemodialysis patients. Commercial dialysate contained glucose (12.4 mmoles/liter), acetate (38 mmoles/liter), plus routine electrolytes. Acetate turnover was 57.2 +/- 2.9 mumoles/min X kg. Of the acetate entering the body, 31.6 +/- 3.8 mumoles/min X kg were immediately oxidized to carbon dioxide and water, which accounted for 54.4 +/- 5.2% of the turnover rate. The amount that entered the blood was 869 mmoles, and 472 mmoles (54.4%) were oxidized; 138 mmoles (15.8%) made up the steady-state pool, and 258 mmoles were directed into nonoxidative pathways (29.7%). During dialysis, 40.3 +/- 4.8% of the carbon dioxide output or metabolic rate was accounted for by acetate oxidation. Thus, acetate emerged as the major contributor to energy production, supplying up to 65% of the total caloric needs during dialysis. The RQ calculated from the lung carbon dioxide excretion was 0.74 +/- 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

PubMed1994

Fetal hemoglobin induction by acetate, a product of butyrate catabolism.

Butyrate induces fetal hemoglobin (HbF) synthesis in cultures of erythroid progenitors, in primates, and in man. The mechanism by which this compound stimulates gamma-globin synthesis is unknown. In the course of butyrate catabolism, beta oxidation by mitochondrial enzymes results in the formation of two acetate molecules from each molecule of butyrate. Studies were performed to determine whether acetate itself induces HbF synthesis. In erythroid burst-forming unit (BFU-E) cultures from normal persons, and individuals with sickle cell disease and umbilical-cord blood, dose-dependent increases in gamma-globin protein and gamma mRNA were consistently observed in response to increasing acetate concentrations. In BFU-E cultures from normal adults and patients with sickle cell disease, the ratio of gamma/gamma + beta mRNA increased twofold to fivefold in response to acetate, whereas the percentage of BFU-E progeny staining with an anti-gamma monoclonal antibody (MoAb) increased approximately twofold. Acetate-induced increases in gamma-gene expression were also noted in the progeny of umbilical cord blood BFU-E, although the magnitude of change in response to acetate was less because of a higher baseline of gamma-chain production. The effect of acetate on HbF induction in vivo was evaluated using transgenic mouse and primate models. A transgenic mouse bearing a 2.5-kb mu locus control region (mu LCR) cassette linked to a 3.3-kb A gamma gene displayed a near twofold increase in gamma mRNA during a 10-day infusion of sodium acetate at a dose of 1.5 g/kg/d. Sodium acetate administration in baboons, in doses ranging from 1.5 to 6 g/kg/d by continuous intravenous infusion, also resulted in the stimulation of gamma-globin synthesis, with the percentage of HbF-containing reticulocytes (F reticulocytes) approaching 30%. Surprisingly, a dose-response effect of acetate on HbF induction was not observed in the baboons, and HbF induction was not sustained with prolonged acetate administration. These results suggest that both two-carbon fatty acids (acetate) and four-carbon fatty acids (butyrate) stimulate synthesis of HbF in vivo.

Acetates↗

PubMed1986

Isolation and characterization of ack and pta mutations in Azotobacter vinelandii affecting acetate-glucose diauxie.

Azotobacter vinelandii mutants defective for acetate utilization that were resistant to fluoroacetate (FA) were isolated. FA-resistant mutant AM6 failed to transport [14C]acetate and lacked enzymatic activity for both acetate kinase and phosphotransacetylase. Growth of wild-type A. vinelandii was sensitive to 10 mM glycine; however, all FA-resistant strains were resistant to glycine toxicity. Isolated mutants that were spontaneously resistant to glycine were also resistant to FA and lacked both acetate kinase and phosphotransacetylase activity. The glycine-resistant mutant AM3, unlike mutant AM6, was capable of growth on acetate. The mutant strain AM6 was unable to growth under acetate-glucose diauxie conditions. Glucose utilization in this mutant, unlike that in wild-type A. vinelandii, was permanently arrested in the presence of acetate. Revertants of strain AM6 were selected on plates with acetate or acetate-glucose. Two classes of revertants were isolated. Class I revertant mutants AM31 and AM35 were positive for both acetate kinase and phosphotransacetylase activities. These revertants were also sensitive to both FA and glycine. Class II revertant strains AM32 and AM34 still lacked acetate kinase and phophotransacetylase activity. Both of these revertants remained resistant to FA and glycine.

Acetate Kinase↗

PubMed2004

Applicability of CoA/acetyl-CoA manipulation system to enhance isoamyl acetate production in Escherichia coli.

Coenzyme A (CoA) and its thioester derivatives are important precursor molecules for many industrially useful compounds such as esters, PHBs, lycopene and polyketides. Previously, in our lab we could increase the intracellular levels of CoA and acetyl-Coenzyme A (acetyl-CoA) by overexpressing one of the upstream rate-controlling enzymes pantothenate kinase with a concomitant supplementation of the precursor pantothenic acid to the cell culture medium. In this study, we showed that the CoA/acetyl-CoA manipulation system could be used to increase the productivity of industrially useful compounds derived from acetyl-CoA. We chose the production of isoamyl acetate as a model system. Isoamyl acetate is an important flavor component of sake yeast and holds a great commercial value. Alcohol acetyl transferase (AAT) condenses isoamyl alcohol and acetyl-CoA to produce isoamyl acetate. The gene ATF2, coding for this AAT was cloned and expressed in Escherichia coli. This genetic engineered E. coli produces isoamyl acetate, an ester, from intracellular acetyl-CoA when isoamyl alcohol is added externally to the cell culture medium. In the current study, we showed that in a strain bearing ATF2 gene, an increase in intracellular CoA/acetyl-CoA by overexpressing panK leads to an increase in isoamyl acetate production. Additionally, the cofactor manipulation technique was combined with more traditional approach of competing pathway deletions to further increase isoamyl acetate production. The acetate production pathway competes with isoamyl acetate production for the common intracellular metabolite acetyl-CoA. Earlier we have shown that acetate pathway deletion (ackA-pta) increases isoamyl acetate production. The acetate production pathway was inactivated under elevated CoA/acetyl-CoA conditions, which lead to a further increase in isoamyl acetate production.

Acetyl Coenzyme A↗

PubMed2005

[Actions of a 19-norprogesterone derivative on mammary gland: nomegestrol acetate].

UNLABELLED: As the biological effects of progestins vary according to their molecular structure, it becomes essential to differentiate the various types of progestins, particularly with regard to the breast. OBJECTIVE: The purpose of this review was to gather published data on the effects of a 19-norprogesterone derivative, nomegestrol acetate, on the breast. Materials and methods. All experimental and clinical published studies reporting data in the literature on nomegestrol acetate and breast were reviewed. RESULTS: In experiments on steroid receptors, it was shown that nomegestrol acetate presents a high binding specificity and affinity for progesterone receptors, notably in normal and cancerous human breast tissues. It sharply inhibits synthesis of progesterone receptors in hormone-dependent T-47D human breast cancer cells grown in an estrogenic culture medium, thereby demonstrating its strong progestational activity. On the other hand, it does not bind to estrogen receptors and lacks any estrogenic potential, confirmed by the lack of induction of alkaline phosphatase activity of endometrial Ishikawa cells. Estrogen-induced synthesis of estrogen receptors is also inhibited by nomegestrol acetate, a major determinant of its strong intrinsic anti-estrogenic activity. Unlike androgenic progestins (e.g. 19-nortestosterone derivatives and medroxyprogesterone acetate) which may act indirectly on the breast by inducing modifications of sex hormone binding globulin (SHBG) and insulin-like growth factor-I (IGF-I), nomegestrol acetate is devoid of any androgenic activity. In studies carried out on the effects of progestins on enzyme activities involved in estradiol (E2) formation in breast tissue, nomegestrol acetate can control E2 levels in breast cancer tissue in vitro: it inhibits estrone sulfatase activity that converts estrone sulfate (E1S) to estrone (E1) and inhibits 17beta-hydroxysteroid dehydrogenase type 1 activity that converts E1 to E2, resulting in blockade of E2 bioformation in MCF-7 and T-47D human breast cancer cells. It also stimulates sulfotransferase activity and subsequently the transformation of non conjugated estrogens E1 and E2 into biologically inactive estrogen sulfates. In vitro studies on cell proliferation have demonstrated that nomegestrol acetate, on the one hand, is unable to stimulate proliferation of MCF-7 cells cultured in a medium devoid of estrogens and, on the other hand, can exert antiproliferative effects on T-47D cells grown in an estrogenic environment. Furthermore, studies on mammary apoptosis have shown that the withdrawal of nomegestrol acetate induces apoptosis peak of normal human breast epithelial cells in vitro and in vivo. In clinical trials carried out with premenopausal women, nomegestrol acetate administered in antigonadotropic sequence has demonstrated its efficacy in the treatment of cyclical mastodynia and early onset benign breast diseases. With postmenopausal hormone replacement therapy (HRT) combining estrogen and nomegestrol acetate, clinical trial results showed low incidence of mastodynia while under treatment as well as moderate increase in mammographic density, particularly with continuous combined regimens, however rapidly reversed by a short-term suspension of HRT. Noclinical data with this progestagen is available on breast cancer risk. CONCLUSION: In addition to efficacy on mastodynia, in vitro and in vivo study results support the good tolerance of nomegestrol acetate on breast, in the short and medium term.

Apoptosis↗

PubMed2004

Unexpected highly chemoselective deprotection of the acetals from aldehydes and not ketones: TESOTf-2,6-lutidine combination.

Acetal functions are recognized as good protecting groups of carbonyl groups. Although many deprotecting methods of acetals to carbonyl functions have already been developed, there is no methodology which can deprotect acetals in the presence of ketals because the usual acidic or radical reactions occur more easily via the more stable cationic or radical intermediates from the ketals. On the other hand, this new method can proceed in a reverse manner to that described in previous reports. That is, the method can deprotect aliphatic acetals in the presence of ketals. The reaction condition is common for silylation, i.e., the TESOTf-2,6-lutidine combinations. Although the TMSOTf-2,6-lutidine combination can also deprotect acetals, it lacks chemoselectivity in deprotection of the acetals from aldehydes and ketones. The treatment of acetals with TESOTf and 2,6-lutidine in CH2Cl2 followed by a H2O workup gave the corresponding aldehydes. Of course, the compounds, which have both acetal and hydroxyl functions afforded the compounds obtained by the usual silylation of an alcohol and deprotection of an acetal without any problem. However, deprotection of the ketals from ketones was not observed during the conversion reaction of acetals from aldehydes. This chemoselectivity was confirmed in the reactions of the compounds that have the acetal and ketal in the same molecule. In both cases, the acetal functions were deprotected to give aldehydes with intact ketals. Furthermore, under the conditions described here, many functional groups such as methoxy, acetoxy, allyl alcohol, and silyloxy ether are intact. This method is very mild and available for many compounds.

Journal Article↗

PubMed2005

Validation of human physiologically based pharmacokinetic model for vinyl acetate against human nasal dosimetry data.

Vinyl acetate has been shown to induce nasal lesions in rodents in inhalation bioassays. A physiologically based pharmacokinetic (PBPK) model for vinyl acetate has been used in human risk assessment, but previous in vivo validation was conducted only in rats. Controlled human exposures to vinyl acetate were conducted to provide validation data for the application of the model in humans. Five volunteers were exposed to 1, 5, and 10 ppm 13C1,13C2 vinyl acetate via inhalation. A probe inserted into the nasopharyngeal region sampled both 13C1,13C2 vinyl acetate and the major metabolite 13C1,13C2 acetaldehyde during rest and light exercise. Nasopharyngeal air concentrations were analyzed in real time by ion trap mass spectrometry (MS/MS). Experimental concentrations of both vinyl acetate and acetaldehyde were then compared to predicted concentrations calculated from the previously published human model. Model predictions of vinyl acetate nasal extraction compared favorably with measured values of vinyl acetate, as did predictions of nasopharyngeal acetaldehyde when compared to measured acetaldehyde. The results showed that the current PBPK model structure and parameterization are appropriate for vinyl acetate. These analyses were conducted from 1 to 10 ppm vinyl acetate, a range relevant to workplace exposure standards but which would not be expected to saturate vinyl acetate metabolism. Risk assessment based on this model further concluded that 24 h per day exposures up to 1 ppm do not present concern regarding cancer or non-cancer toxicity. Validation of the vinyl acetate human PBPK model provides support for these conclusions.

Adolescent↗

PubMed1981

Anaerobic Degradation of Lactate by Syntrophic Associations of Methanosarcina barkeri and Desulfovibrio Species and Effect of H(2) on Acetate Degradation.

When grown in the absence of added sulfate, cocultures of Desulfovibrio desulfuricans or Desulfovibrio vulgaris with Methanobrevibacter smithii (Methanobacterium ruminantium), which uses H(2) and CO(2) for methanogenesis, degraded lactate, with the production of acetate and CH(4). When D. desulfuricans or D. vulgaris was grown in the absence of added sulfate in coculture with Methanosarcina barkeri (type strain), which uses both H(2)-CO(2) and acetate for methanogenesis, lactate was stoichiometrically degraded to CH(4) and presumably to CO(2). During the first 12 days of incubation of the D. desulfuricans-M. barkeri coculture, lactate was completely degraded, with almost stoichiometric production of acetate and CH(4). Later, acetate was degraded to CH(4) and presumably to CO(2). In experiments in which 20 mM acetate and 0 to 20 mM lactate were added to D. desulfuricans-M. barkeri cocultures, no detectable degradation of acetate occurred until the lactate was catabolized. The ultimate rate of acetate utilization for methanogenesis was greater for those cocultures receiving the highest levels of lactate. A small amount of H(2) was detected in cocultures which contained D. desulfuricans and M. barkeri until after all lactate was degraded. The addition of H(2), but not of lactate, to the growth medium inhibited acetate degradation by pure cultures of M. barkeri. Pure cultures of M. barkeri produced CH(4) from acetate at a rate equivalent to that observed for cocultures containing M. barkeri. Inocula of M. barkeri grown with H(2)-CO(2) as the methanogenic substrate produced CH(4) from acetate at a rate equivalent to that observed for acetate-grown inocula when grown in a rumen fluid-vitamin-based medium but not when grown in a yeast extract-based medium. The results suggest that H(2) produced by the Desulfovibrio species during growth with lactate inhibited acetate degradation by M. barkeri.

Journal Article↗

PubMed1984

Elucidation of Growth Inhibition and Acetic Acid Production by Clostridium thermoaceticum.

The production of acetic acid by Clostridium thermoaceticum was studied by using batch fermentations. In a pH-controlled fermentation with sodium hydroxide (pH 6.9), this organism was able to produce 56 g of acetic acid per liter. On the other hand, when the pH was not controlled and was decreased during fermentation to 5.4, the maximum attainable acetic acid concentration was only 15.3 g/liter. To obtain a better understanding of the end product inhibition, various salts were tested to determine their effect on the growth rate of C. thermoaceticum. An inverse linear relationship between the growth rate and the final cell concentration to the sodium acetate concentration was found. By using different concentrations of externally added sodium salts, the relative growth inhibition caused by the anion was found to be in the order of acetate > chloride > sulfate. Various externally added cations of acetate were also examined with respect to their inhibitory effects on growth. The relative magnitude of inhibition on the growth rate was found to be ammonium > potassium > sodium. The combined results have shown that the undissociated acetic acid was much more inhibitory than the ionized acetate ion. Complete growth inhibition resulted when the undissociated acetic acid concentration was between 0.04 and 0.05 M and when the ionized acetate concentration was 0.8 M. Therefore, at low pH (below 6.0), undissociated acetic acid is responsible for growth inhibition, and at high pH (above 6.0), ionized acetate ion is responsible for growth inhibition.

Journal Article↗