Investigation of the Potential Energy Surface for the First Step in the Alkaline Hydrolysis of Methyl Acetate

The potential energy surface for the first step of the alkaline hydrolysis of methyl acetate was explored by a variety of methods. The conformational search routine within SPARTAN was used to determine the lowest energy am1 and pm3 structures for the anionic tetrahedral intermediate. Ab initio single point and geometry optimization calculations were performed to determine the lowest energy conformer, and the linear synchronous transition (lst) method was used to provide an initial structure for transition state optimization. Transition states were obtained at the am1, pm3, 3-21G, and 3-21 + G levels of theory. These transition states were compared with the anionic tetrahedral intermediates to examine the assumption that the intermediate is a good model for the transition state. In addition, the Cramer/Truhlar sm3 solvation model was used at the semiempirical level to compare gas phase and aqueous alkaline hydrolysis of methyl acetate.

Inflammatory myopathy and severe rhabdomyolysis induced by leuprolide acetate therapy for prostate cancer: a case report

Introduction Leuprolide acetate is a synthetic analog of gonadotropin-releasing hormone used for the treatment of prostate cancer. Its side effects are hot flashes, nausea, and fatigue. We report a case of a patient with proximal inflammatory myopathy accompanied by severe rhabdomyolysis and renal failure following the second application of leuprolide acetate. Drug withdrawal and steroid therapy resulted in remission within six weeks of the diagnosis. To the best of our knowledge, our case report describes the second case of leuprolide acetate-induced inflammatory myopathy and the first case of severe leuprolide acetate-induced rhabdomyolysis and renal failure in the literature. Case presentation A 64-year-old Swiss Caucasian man was admitted to the hospital because of progressive proximal muscle weakness, dyspnea, and oliguria. He had been treated twice with leuprolide acetate in monthly doses. We performed a muscle biopsy, which excluded other causes of myopathy. The patient's renal failure and rhabdomyolysis were treated with rehydration and steroid therapy. Conclusion The aim of our case report is to highlight the rare but severe side effects associated with leuprolide acetate therapy used to treat patients with inflammatory myopathy: severe rhabdomyolysis and renal failure.

Effects of lactate and acetate on the determination of serum ethyl glucuronide by CZE

The analysis of ethyl glucuronide (EtG), a marker of recent alcohol consumption, in serum with an optimized CZE assay is reported. The method uses a 0.1-mm id fused-silica capillary of 50 cm effective length that is coated with linear polyacrylamide, a pH 4.4 nicotinic acid/epsilon-aminocaproic acid (EACA) BGE, reversed polarity and indirect analyte detection. The assay is based on a 1:1 dilution of serum with deionized water and has LODs for EtG, lactate and acetate of 3.8 x 10(-7) M, 2.60 x 10(-6 )M and 2.18 x 10(-6 )M, respectively. Separation of EtG from endogenous macro- and microcomponents (anionic serum components of high and low concentration, respectively) and its quantification are shown to be possible for a wide range of lactate (stacker) and acetate (destacker) concentrations, macrocomponents that have an impact on the CZE behavior of EtG and that change after intake of ethanol. The assay has been successfully applied to the analysis of EtG, lactate and acetate in (i) sera of volunteers that ingested known amounts of alcohol and (ii) samples of patients that were classified (teetotalers and social drinkers vs. alcohol abusers) via analysis of carbohydrate-deficient transferrin.

First clinical experience with anecortave acetate (Retaane)

BACKGROUND: Anecortave acetate is an angiostatic cortisene which is injected as a posterior juxtascleral depot and has been shown to be effective in the treatment of exudative age-related macular degeneration (AMD). The compound is not yet approved in Switzerland but can be used as "compassionate use" in individual cases. PATIENTS AND METHODS: An uncontrolled case series with standardised documentation of ETDRS visual acuity, near acuity, need for magnification and fluorescein angiography was performed. RESULTS: 22 eyes of 19 patients (8 male, 11 female, average age 78.8 years) were treated with a posterior juxtascleral depot injection (PJD) of 15 mg anecortave acetate. The mean change in visual acuity after 3 months in eyes treated with anecortave acetate was -2.6 ETDRS letters corresponding to 0.52 Snellen lines. 3/20 eyes gained more than 1 line. 11/20 eyes showed stable visual acuity (+/- 1 Snellen line, +/- 5 ETDRS letters). 5/20 eyes developed moderate vision loss (one to two Snellen lines, 6-10 ETDRS letters). 1/20 lost 18 ETDRS letters (> 3 Snellen lines). There were no moderate or severe adverse events. CONCLUSIONS: A PJD of 15 mg anecortave acetate is safe and well tolerated. In eyes with occult CNV without recent progression or with residual neovascular activity after photodynamic therapy anecortave acetate may be an alternative therapeutic option before considering intravitreal anti-VEGF agents due to the much less invasive character and lower risk profile.

Expansion of mortar bars in the presence of potassium acetate deicer

Carboxylate-based deicing and anti-icing chemicals became widely used in the mid 1990s, replacing more environmentally burdensome chemicals. Within a few years of their adoption, distress of portland cement concrete runways was reported by a few airports using the new chemicals. Distress manifested characteristics identical to that of alkali silica reactivity (ASR), but onset occurred early in the pavement’s operating life and with pavements thought to contain innocuous aggregate. The carboxylate-based deicing chemicals were suspected of exacerbating ASR-like expansion. Innocuous, moderately, and highly reactive aggregates were tested using modified ASTM C1260 and ASTM C1567 procedures with soak solutions containing deicer solutions and sodium hydroxide or potassium hydroxide. ASR-like expansion is exacerbated in the presence of potassium acetate. The expansion rate produced by a given aggregate is also a function of the alkali hydroxide used. Petrographic analyses were performed on thin sections prepared from mortar bars used in the experiments. Expansion occurred via two mechanisms; rupture of aggregate grains and expansion of paste.

Citrate- vs. acetate-based dialysate in bicarbonate haemodialysis: consequences on haemodynamics, coagulation, acid-base status, and electrolytes

BACKGROUND: A concentrate for bicarbonate haemodialysis acidified with citrate instead of acetate has been marketed in recent years. The small amount of citrate used (one-fifth of the concentration adopted in regional anticoagulation) protects against intradialyser clotting while minimally affecting the calcium concentration. The aim of this study was to compare the impact of citrate- and acetate-based dialysates on systemic haemodynamics, coagulation, acid-base status, calcium balance and dialysis efficiency. METHODS: In 25 patients who underwent a total of 375 dialysis sessions, an acetate dialysate (A) was compared with a citrate dialysate with (C+) or without (C) calcium supplementation (0.25 mmol/L) in a randomised single-blind cross-over study. Systemic haemodynamics were evaluated using pulse-wave analysis. Coagulation, acid-base status, calcium balance and dialysis efficiency were assessed using standard biochemical markers. RESULTS: Patients receiving the citrate dialysate had significantly lower systolic blood pressure (BP) (-4.3 mmHg, p < 0.01) and peripheral resistances (PR) (-51 dyne.sec.cm-5, p < 0.001) while stroke volume was not increased. In hypertensive patients there was a substantial reduction in BP (-7.8 mmHg, p < 0.01). With the C+ dialysate the BP gap was less pronounced but the reduction in PR was even greater (-226 dyne.sec.cm-5, p < 0.001). Analyses of the fluctuations in PR and of subjective tolerance suggested improved haemodynamic stability with the citrate dialysate. Furthermore, an increase in pre-dialysis bicarbonate and a decrease in pre-dialysis BUN, post-dialysis phosphate and ionised calcium were noted. Systemic coagulation activation was not influenced by citrate. CONCLUSION: The positive impact on dialysis efficiency, acid-base status and haemodynamics, as well as the subjective tolerance, together indicate that citrate dialysate can significantly contribute to improving haemodialysis in selected patients.

Selective removal of anomeric O-acetate groups in carbohydrates using HCl04-Si02-tr

A convenient methodology has been developed for the selective removal of the anomeric acyl group of carbohydrate derivatives using HCI04-Si02 under acidic reaction conditions. Anomeric benzoyl groups can also be removed selectively following similar reaction conditions. The yields were excellent in all cases.

Fatty acylated proteins and the protein kinase C signaling pathway

Numerous proteins in intracellular signaling pathways are known to be covalently modified by long chain fatty acids. The objective of this project was to identify potentially novel components of the protein kinase C signaling pathway by virtue of their fatty acylation. A 64 kDa palmitoylated protein (p64) was identified that became deacylated following stimulation of quiescent cells with serum, FGF, or PDBu, suggesting that stimulus-dependent deacylation might alter interactions between p64 and other membrane/cytoskeletal components. A myristoylated protein of 68 kDa observed during these studies was identified as the "80K" PKC substrate. This protein was acylated cotranslationally with myristate through an amide linkage. The majority of the 80K protein was tightly associated with the plasma membrane, with approximately 20% in the cytosol. Although phosphorylation of the membrane-bound and soluble forms of the protein was increased 6-fold in response to PDBu, no changes in the subcellular distribution or myristoylation of the protein were observed. A cDNA encoding the murine form of this protein was cloned, and its deduced amino acid sequence revealed the presence of an N-terminal myristoylation consensus and five potential sites for phosphorylation by PKC. A mutant in which the N-terminal glycine residue was changed to alanine was no longer a substrate for NMT and consequently lost its membrane-binding potential. However, its ability to be phosphorylated in response to purified growth factors and phorbol esters was unimpaired. These results indicate that the myristoylated N-terminus of the 80K protein is required for its association with the plasma membrane, and that the cytoplasmic form of the protein can be phosphorylated independently of the membrane-bound form. Mutants of PKC were constructed in which the regulatory domain was removed and replaced by the N-terminus of the 80K or Al proteins. Unexpectedly, both the myristoylated and nonmyristoylated fusion proteins were tightly associated with the nuclear envelope. Further deletion analyses mapped nuclear targeting signals to the hinge region and a portion of the catalytic domain of PKC, explaining the ability of PKC to be translocated to the nucleus in response to certain stimuli. ^

Recurrent Nicolau syndrome associated with subcutaneous glatiramer acetate injection--a case report.

BACKGROUND Glatiramer acetate is worldwide used as first line treatment in relapsing remitting multiple sclerosis. Local skin reactions associated with glatiramer acetate are common, however, only isolated cases of severe local injection site reactions known as Nicolau Syndrome have been reported so far. CASE PRESENTATION We describe the case of a recurrent Nicolau Syndrome occurred during longstanding glatiramer acetate treatment in a woman with multiple sclerosis. The haemorrhagic patch necrotized and was treated locally as a deep second degree burn with excision of dead skin tissue and was healed. Treatment with glatiramer acetate was definitely suspended. CONCLUSIONS GA injections can be complicated by isolated or recurrent Nicolau Syndrome, a potentially life-threatening condition of which neurologists should be aware.

Acetate metabolism and the control of environmental pH in Candida albicans and Saccharomyces cerevisiae

Candida albicans is the most common opportunistic fungal pathogen of humans. The balance between commensal and pathogenic C. albicans is maintained largely by phagocytes of the innate immune system. Analysis of transcriptional changes after macrophage phagocytosis indicates the C. albicans response is broadly similar to starvation, including up-regulation of alternate carbon metabolism. Systems known and suspected to be part of acetate/acetyl-CoA metabolism were also up-regulated, importantly the ACH and ACS genes, which manage acetate/acetyl-CoA interconversion, and the nine-member ATO gene family, thought to participate in transmembrane acetate transport and also linked to the process of environmental alkalinization. ^ Studies into the roles of Ach, Acs1 and Acs2 function in alternate carbon metabolism revealed a substantial role for Acs2 and lesser, but distinct roles, for Ach and Acs1. Deletion mutants were made in C. albicans and were phenotypically evaluated both in vitro and in vivo. Loss of Ach function resulted in mild growth defects on ethanol and acetate and no significant attenuation in virulence in a disseminated mouse model of infection. While loss of Acs1 did not produce any significant phenotypes, loss of Acs2 greatly impaired growth on multiple carbon sources, including glucose, ethanol and acetate. We also concluded that ACS1 and ACS2 likely comprise an essential gene pair. Expression analyses indicated that ACS2 is the predominant form under most growth conditions. ^ ATO gene function had been linked to the process of environmental alkalinization, an ammonium-mediated phenomenon described here first in C. albicans. During growth in glucose-poor, amino acid-rich conditions C. albicans can rapidly change its extracellular pH. This process was glucose-repressible and was accompanied by hyphal formation and changes in colony morphology. We showed that introduction of the ATO1G53D point mutant to C. albicans blocked alkalinization, as did over-expression of C. albicans ATO2, the only C. albicans ATO gene to lack the conserved N-terminal domain. A screen for alkalinization-deficient mutants revealed that ACH1 is essential for alkalinization. However, addition of acetate to the media restored alkalinization to the ach1 mutant. We proposed a model of ATO function in which Atos regulated the cellular co-export of ammonium and acetate. ^

Methane concentration and porewater acetate of sediment cores from the IODP Expedition 301 Site U1301

In deep subsurface sediments of the Juan de Fuca Ridge Flank, porewater acetate that is depleted in 13C relative to sedimentary organic matter indicates an acetogenic component to total acetate production. Thermodynamic calculations indicate common fermentation products or lignin monomers as potential substrates for acetogenesis. The classic autotrophic reaction may contribute as well, provided that dihydrogen (H2) concentrations are not drawn down to the thermodynamic thresholds of the energetically more favorable processes of sulfate reduction and methanogenesis. A high diversity of novel formyl tetrahydrofolate synthetase (fhs) genes throughout the upper half of the sediment column indicates the genetic potential for acetogenesis. Our results suggest that a substantial fraction of the acetate produced in marine sediment porewaters may derive from acetogenesis, in addition to the conventionally invoked sources fermentation and sulfate reduction.

Pore water acetate and hydrogen, helium and methane gas concentrations in ODP Leg 204 sediments

Acetate and hydrogen concentrations in pore fluids were measured in samples taken at seven sites from southern Hydrate Ridge (SHR) offshore Oregon, USA. Acetate concentrations ranged from 3.17 to 2515 µM. The maximum acetate concentrations occurred at Site 1251, which was drilled on a slope basin to the east of SHR at depths just above the bottom-simulating reflector (BSR) that marks the boundary of gas hydrate stability. Acetate maxima and localized high acetate concentrations occurred at the BSR at all sites and frequently corresponded with areas of gas hydrate accumulation, suggesting an empirical relationship. Acetate concentrations were typically at a minimum near the seafloor and above the sulfate/methane interface, where sulfate-reducing bacteria may consume acetate. Hydrogen concentrations in pressure core samples ranged from 16.45 to 1036 parts per million by volume (ppmv). In some cases, hydrogen and acetate concentrations were elevated concurrently, suggesting a positive correlation. However, sampling of hydrogen was limited in comparison to acetate, so any relationships between the two analytes, if present, were difficult to discern.

Biogeochemistry and microbiology of groundwater during acetate and bicarbonate amendment to an alluvial aquifer

These data are from a field experiment conducted in a shallow alluvial aquifer along the Colorado River in Rifle, Colorado, USA. In this experiment, bicarbonate-promoted uranium desorption and acetate amendment were combined and compared to an acetate amendment-only experiment in the same experimental plot. Data include names and location data for boreholes, geochemical data for all the boreholes between June 1, 2010 and January 1, 2011, microarray data provided as signal to noise ratio (SNR) for individual microarray probes, microarray data provided as signal to noise ratio (SNR) by Genus.