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Decreased expression of decay-accelerating factor on endothelial cells of immune complex-mediated vasculitic skin lesions.

Endothelial cells may be damaged directly by the membrane attack complex of complement in immune complex vasculitis of the skin. However, for endothelial cell membrane injury to occur, normal regulatory mechanisms must fail. One of the main complement regulatory proteins of endothelial cells is decay-accelerating factor, a surface protein which interferes with either the classical or alternative pathway C3 and C5 convertases. We have investigated the expression of decay-accelerating factor in 4 patients with histologically proven cutaneous immune complex vasculitis, using an immuno-electronmicroscopic technique. We demonstrated that endothelial cells of upper dermal vessels in vasculitic lesions were almost completely devoid of decay-accelerating factor. By contrast, the expression of this protein on endothelial cells in uninvolved skin of the patients was the same as in skin of healthy volunteers. As yet, the mechanism responsible for depletion of decay-accelerating factor is not clear. Absence of decay-accelerating factor may follow enzymatic release from the phosphatidylinositol anchor, proteolytic stripping from the cell membrane or a down-regulation of decay-accelerating factor synthesis. Regardless of mechanism, endothelial cell injury or death could serve a phlogistic function to facilitate complement-mediated destruction of endothelial cells for removal and repair.

Adolescent↗

Acceleration of functional reentry by rapid pacing in anisotropic cardiac monolayers: formation of multi-wave functional reentries.

OBJECTIVE: Attempts to cardiovert tachycardia by rapid point pacing can sometimes result in transient or stable increase of the heart rate (acceleration), changed ECG morphology, and/or fibrillation. The goal of this study was to investigate the effect of rapid pacing on the dynamics of functional reentry in monolayer cultures of cardiac cells. METHODS: Fully confluent, uniformly anisotropic monolayers of neonatal rat ventricular myocytes were prepared using methods of microabrasion. Cells were paced by a point electrode at rest and during functional reentry, and membrane voltages were optically mapped. RESULTS: Point pacing readily induced single loop anisotropic functional reentry with monomorphic optical pseudo-ECG (pECG) and average rotation period of 193+/-52 ms (n=71 monolayers). Attempts to cardiovert reentry by rapid pacing at rates 10-50% faster than the reentry rate were successful in 57/71 monolayers. In 14/71 monolayers, the number of rotating waves was stably increased by 1 to 4, yielding a 10-70% acceleration of pECG rate and change to a different monomorphic or polymorphic pECG. The resulting multi-wave functional reentries were classified based on the number and direction of their rotating waves. The higher the number of waves in the multi-wave reentry, the more accelerated was the rate of cell firing in the monolayer. Importantly, stable acceleration was only inducible in monolayers with relatively deep and broad conduction velocity restitution relationships. Reapplication of point pacing further accelerated, decelerated, or eventually terminated the reentrant activity. CONCLUSIONS: These results suggest that stable multiplication of rotating waves in conjunction with a deep and broad conduction velocity restitution relationship is a possible mechanism for stable acceleration of functional reentry by rapid pacing.

Animals↗

Fractal analysis of acceleration signals from patients with CPPD, rheumatoid arthritis, and spondyloarthroparthy of the finger joint.

Arthritis is one of the leading causes of disability and affects a major segment of the population. Consequently, accurate diagnosis of arthritis is important. Arthritis due to calcium pyrophosphate deposition disease (CPPD), rheumatoid arthritis, and spondyloarthropathy, induce complex changes in the cartilage and the articular surface. The fractal dimension provides a measure of the complexity of a signal. Recently, we have developed non-invasive acceleration measurements to characterize the arthritic patients. The question remains if the fractal dimension of the acceleration signal is different for different arthritis conditions. The purpose of this study was to distinguish between different types of arthritis of the finger joint using the fractal dimension of the acceleration signal obtained from the finger joint of the arthritic patients. Acceleration signals were obtained from the finger joint of arthritis patients with rheumatoid arthritis, spondyloarthropathy, and calcium pyrophosphate deposition disease of the finger joint. ANOVA results showed that there were significant differences between the fractal dimension of acceleration signals from patients having calcium pyrophosphate deposition disease and rheumatoid arthritis and spondyloarthropathy. Fractal dimension of acceleration signals, in concert with other clinical symptoms, can be used to classify different types of arthritis.

Arthritis, Rheumatoid↗

Acceleration of 3D, nonlinear warping using standard video graphics hardware: implementation and initial validation.

Thin Plate Spline (TPS) transformations are used in many medical imaging algorithms, but are time-prohibitive for iterative or interactive use. We have utilized current generation consumer 3D graphics cards to accelerate the application of the TPS nonlinear transformation by combining hardware accelerated 3D textures, vertex shaders and trilinear interpolation. Our hardware accelerated algorithm warped a 512x512x173 Computed Tomography (CT) dataset in 2.3 s, and the same study, scaled to 256x256x173, in 0.5 s, using a set of 92 landmarks. An accelerated software implementation of the TPS transformation warped the 512x512x173 study in 32.9 s and the 256x256x173 study in 9.5 s. Subtracted images were used for qualitative analysis of the warp and the Mutual Information (MI) and Sum of Absolute Difference (SAD) similarity metrics were used to quantitatively compare the output of the hardware accelerated algorithm to that of the software algorithm. The hardware accelerated algorithm provided a 7-65 times performance increase when compared to the software algorithm, and produced output of comparable quality (MI > 300 and SAD < 1.75%).

Algorithms↗

A randomised trial of accelerated radiotherapy for localised invasive bladder cancer.

BACKGROUND AND PURPOSE: To evaluate the efficacy and toxicity of an accelerated fractionation regimen to treat localised muscle invasive bladder cancer. PATIENTS AND METHODS: A prospective randomised trial was undertaken in 229 patients randomised between 1988 and 1998 comparing accelerated fractionation (AF) to a dose of 60.8 Gy in 32 fractions over 26 days with conventional fractionation (CF) treating to 64 Gy in 32 fractions over 45 days. Accelerated fractionation was delivered using two fractions per day with a 6h gap between fractions and with the first daily fraction size being 1.8 Gy and the second daily fraction size being 2.0 Gy. There was a 1 week treatment gap after the first 12 fractions. Conventional fractionation was one fraction per day, 5 days per week. Eligible patients had clinical stage T2 or T3, N0 or N1, M0 transitional cell carcinoma. The primary endpoint of the trial was local control and the trial was powered to detect a 20% difference (alpha 0.05, power 90%). Secondary endpoints were toxicity and survival. RESULTS: In the initial phase of the trial, randomisation was unequal such that in total 129 patients were randomised to accelerated fractionation and 100 to conventional fractionation. Acute toxicity was evaluable in 121 patients treated with AF and 96 patients treated with CF. RTOG grade 2 or 3 bowel toxicity was noted in 44% of AF patients compared to 26% of CF patients (P trend =0.001). Acute grade 2 or 3 bladder toxicity was seen in 35% of AF patients compared to 36% of CF patients (P=0.99). Late radiation toxicity was evaluated in patients surviving free from local recurrence at 2 years post treatment. Late radiation toxicity equivalent to RTOG grade 2 or more had occurred in 44% (95% CI 34-55%) of AF patients and in 38% (95% CI 26-49%) of CF patients (logrank over 5 years follow-up P=0.23). There was no significant difference in analysis of time to loss of local tumour control comparing the two treatment arms; local recurrence was recorded in 29 of the 100 patients treated with CF and in 41 of 129 patients treated with AF (logrank P=0.86). There was also no significant difference between the treatment arms comparing disease-free survival and overall survival. The overall survival figures at 3 years were for AF 54% (95% CI 45-63%) and for CF 47% (95% CI 36-57%). By 5 years the overall survival was 37% for AF and 40% for CF. There were two treatment related deaths, both on the AF arm of the trial. CONCLUSIONS: This accelerated fractionation schedule did not improve on the efficacy of conventional fractionation for patients with T2 and T3 bladder cancer and accelerated fractionation was associated with increased acute bowel reactions.

Adult↗

Pharmacokinetic, pharmacodynamic, and safety evaluation of an accelerated dose titration regimen of sotalol in healthy middle-aged subjects.

BACKGROUND: Current labeling recommends that therapy with sotalol be initiated in a monitored setting at 80 mg every 12 hours for 2 to 3 days, followed by 120 to 160 mg every 12 hours for at least 2 days before safety and efficacy can be ascertained and patients discharged. An accelerated titration regimen that shortens hospital stay without compromising patient safety would improve the usefulness of the drug. Although such regimens have been used by clinicians, they have not been formally evaluated. METHODS: Healthy, middle-aged sedentary men and women received sotalol in a double-blind, two-way crossover study with a 2-week washout phase to evaluate an accelerated titration regimen--placebo every 6 hours for four doses, followed by 80 mg sotalol every 6 hours for four doses, then 160 mg sotalol every 12 hours for nine doses--and compare it with the standard titration--placebo alternating with 80 mg sotalol every 6 hours for eight doses, followed by 160 mg sotalol every 12 hours for nine doses. QT intervals, RR intervals, and sotalol concentrations in plasma were measured at specific times throughout the study and during washout in a similar fashion for both regimens. RESULTS: Thirty-four subjects completed both regimens. The target prolongation of QTc (90% of the value achieved at steady state) was achieved 22 1/2 hours sooner with the accelerated titration regimen (P = .0003). There were no cardiovascular adverse events during either loading phase. At no time during the accelerated titration regimen did the sotalol concentrations in plasma or the QTc or RR interval prolongation exceed the values eventually achieved at steady state. The relationship between sotalol concentration and QTc was linear and independent of the regimen. CONCLUSION: The accelerated titration regimen for sotalol can shorten the time to attain the dosage usually required to effectively control arrhythmias, without excessive QT prolongation and the associated increased risk of torsades de pointes. The hospital stay of patients in whom antiarrhythmic therapy with sotalol is initiated can be shortened by 1 day if this accelerated titration regimen is used.

Adrenergic beta-Antagonists↗

Acceleration perception and spatial distortion in a left unilateral neglect patient.

To explain relative leftward overextension in a line extension task by left unilateral neglect subjects, Bisiach et al. (1998) suggested that the representation of space is distorted--i.e., dilated towards the left side. If perception of the velocity of a moving stimulus is due to a calculation of the distance covered per unit time in representational space, then a stimulus with uniform linear motion should be perceived as decelerating when moving leftwards in the visual field of a subject with left unilateral neglect. We investigated the perception of acceleration in a patient with left unilateral neglect and spatial distortion (revealed as relative left overextension in a line extension task) using a task in which the stimuli were right and left moving targets with variable acceleration. The patient's ability to perceive acceleration was much lower (higher acceleration threshold) for leftward movements than rightward movements. Fourteen months later unilateral neglect had improved, and the relative left overextension and decreasing acceleration threshold for leftward movements were reduced. By contrast, alterations in the perception of acceleration for leftward movements were not found in a patient with left unilateral neglect and left underextension and in a patient with right brain damage and left hemianopia. These findings in one patient with left spatial unilateral neglect and a relative left overextension in a line extension task are consistent with the hypothesis that representational space is distorted, with a disproportionate leftward expansion, that affects perception of movement.

Aged↗

Marginal gap of crowns made with a phosphate-bonded investment and accelerated casting method.

STATEMENT OF PROBLEM: Numerous materials and methods have been used for complete crown fabrication. Conventional investing and casting procedures for phosphate-bonded investments require a 2- to 4-hour process before completion. Accelerated laboratory techniques have been used, but may not result in castings with equal marginal accuracy. PURPOSE: This study measured the marginal gap and determined the clinical acceptability of single castings invested in a phosphate-bonded investment with the use of conventional and accelerated methods. MATERIAL AND METHODS: Forty-four individual stone casts were poured from impressions made from a master die. Conventional and accelerated methods of investing and casting were followed in the fabrication of 44 single-unit castings. Twenty-two casts were used in each of the 2 groups. Each casting and its respective stone die were examined with a microscope at 4 predetermined sites. Perpendicular and 25-degree tilted measurements of marginal gap were documented for each. Evidence of marginal gap was then evaluated by t test. RESULTS: Measurements recorded on the perpendicular and on a 25-degree tilt showed no statistically significant difference between conventional and accelerated groups. All gap measurements except one were within the range of clinical acceptability. The measurements revealed that conventional and accelerated perpendicular gap means were 13.2 and 13.6 microm, respectively, and the average tilted gap means were 31.6 and 32.2 microm, respectively. CONCLUSIONS: A phosphate-bonded investment (Ceramigold) selected for an accelerated casting technique produced single castings within 30 minutes with marginal gaps comparable to those found that used conventional methods.

Crowns↗

Acceleration of fibrinolysis by high-frequency ultrasound: the contribution of acoustic streaming and temperature rise.

High-frequency ultrasound has been shown to accelerate enzymatic fibrinolysis. One of the supposed mechanisms of this effect is the enhancement of mass transport by acoustic streaming, i.e., ultrasound-induced macroscopic flow around the clot. In this study, which is aimed at further elucidating the mechanisms of the acceleration of fibrinolysis by ultrasound, we investigated whether ultrasound would accelerate fibrinolysis if the flow around the thrombus is already present, as may occur in vivo. The effect of the ultrasound-induced temperature rise was also studied. In a model of a plasma clot submerged in plasma, containing tissue-type plasminogen activator, mild stirring of the outer plasma producing a shear rate of 40 seconds(-1) at the surface of the clot resulted in a two-fold acceleration of lysis. A similar effect was obtained with ultrasound (1 MHz, 2 W/cm(2)). Furthermore, if ultrasound was applied together with stirring, only 30% acceleration by ultrasound was documented, fully attributable to the concomitant temperature rise. In a model with tissue-type plasminogen activator incorporated throughout a plasma clot, the effect of ultrasound (two-fold shortening of lysis time) was fully attributable to the concomitant temperature rise of a few degrees. We concluded that the acceleration of enzymatic plasma clot lysis by high-frequency ultrasound in the models we used can be largely explained by a combination of the effects of heating and acoustic streaming, equivalent to mild stirring. The thermal effects can hardly be utilized in vivo due to the danger of tissue overheat. The therapeutic advantage of transcutaneous high-frequency ultrasound as an adjunct to thrombolytic therapy may appear limited to the situations where there is no flow in the direct environment of the thrombus.

Acoustics↗

A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003.

PURPOSE: The optimal fractionation schedule for radiotherapy of head and neck cancer has been controversial. The objective of this randomized trial was to test the efficacy of hyperfractionation and two types of accelerated fractionation individually against standard fractionation. METHODS AND MATERIALS: Patients with locally advanced head and neck cancer were randomly assigned to receive radiotherapy delivered with: 1) standard fractionation at 2 Gy/fraction/day, 5 days/week, to 70 Gy/35 fractions/7 weeks; 2) hyperfractionation at 1. 2 Gy/fraction, twice daily, 5 days/week to 81.6 Gy/68 fractions/7 weeks; 3) accelerated fractionation with split at 1.6 Gy/fraction, twice daily, 5 days/week, to 67.2 Gy/42 fractions/6 weeks including a 2-week rest after 38.4 Gy; or 4) accelerated fractionation with concomitant boost at 1.8 Gy/fraction/day, 5 days/week and 1.5 Gy/fraction/day to a boost field as a second daily treatment for the last 12 treatment days to 72 Gy/42 fractions/6 weeks. Of the 1113 patients entered, 1073 patients were analyzable for outcome. The median follow-up was 23 months for all analyzable patients and 41.2 months for patients alive. RESULTS: Patients treated with hyperfractionation and accelerated fractionation with concomitant boost had significantly better local-regional control (p = 0.045 and p = 0.050 respectively) than those treated with standard fractionation. There was also a trend toward improved disease-free survival (p = 0.067 and p = 0.054 respectively) although the difference in overall survival was not significant. Patients treated with accelerated fractionation with split had similar outcome to those treated with standard fractionation. All three altered fractionation groups had significantly greater acute side effects compared to standard fractionation. However, there was no significant increase of late effects. CONCLUSIONS: Hyperfractionation and accelerated fractionation with concomitant boost are more efficacious than standard fractionation for locally advanced head and neck cancer. Acute but not late effects are also increased.

Adult↗

Phase III trial of accelerated hyperfractionation with or without difluromethylornithine (DFMO) versus standard fractionated radiotherapy with or without DFMO for newly diagnosed patients with glioblastoma multiforme.

PURPOSE: To report the results of a prospective Phase III trial for patients with newly diagnosed glioblastoma multiforme (GBM), treated with either accelerated hyperfractionated irradiation with or without difluromethylornithine (DFMO) or standard fractionated irradiation with or without DFMO. METHODS AND MATERIALS: Adult patients with newly diagnosed GBM were registered and randomized following surgery to one of 4 treatment arms: Arm A, accelerated hyperfractionation alone using 2 fractions a day of 1.6 Gy to a total dose of 70.4 Gy in 44 fractions; Arm B, accelerated hyperfractionation as above plus DFMO 1.8 gm/m2 by mouth every 8 h beginning one week before radiation until the last fraction was given; Arm C, single-fraction irradiation of 1.8 Gy/day to 59.4 Gy; Arm D, single-fraction irradiation as in Arm C plus DFMO given as in Arm B. Patients were followed for progression-free survival (PFS) and overall survival (OS), as well as for toxicity. Eligibility required histologically proven GBM, age > or =18, Karnofsky performance status (KPS) > or =60, and no prior chemotherapy or radiotherapy. Adjuvant chemotherapy was not used in this protocol. RESULTS: A total of 231 eligible patients were enrolled. There were 95 men and 136 women with a median age of 57 years, and median KPS of 90. Extent of resection was total in 23, subtotal in 152, and biopsy only in 56 patients. The 4 arms were balanced with respect to age, KPS, and extent of resection. Times to event measurements are from date of diagnosis. Median OS and PFS were 40 and 19 weeks for Arm A; 42 and 22 weeks for Arm B; 37 and 16 weeks for Arm C; and 44 and 19 weeks for Arm D (p = 0.48 for survival; p = 0.32 for PFS). Comparison of the 2 arms treated with DFMO to the 2 arms without DFMO revealed no difference in OS (37 weeks vs. 42 weeks, p = 0.12) or PFS and thus no benefit to the use of DFMO. Comparison of the 2 standard fractionation arms to the 2 accelerated hyperfractionation arms also resulted in no difference in OS (42 weeks vs. 41 weeks, p = 0.75) or PFS, showing no benefit to accelerated hyperfractionated irradiation. CONCLUSION: In this prospective Phase III study, no survival or PFS benefit was seen with accelerated hyperfractionated irradiation to 70.4 Gy, nor was any benefit seen with DFMO as a radiosensitizer. Standard fractionated irradiation to 59.4 Gy remains the treatment of choice for newly diagnosed patients with glioblastoma multiforme.

Adult↗

Modifying radical radiotherapy in high grade gliomas; shortening the treatment time through acceleration.

PURPOSE: To evaluate the efficacy and toxicity of accelerated radiotherapy in patients with primary high grade glioma, where acceleration is used as a means of delivering a shortened course of radical radiotherapy. PATIENTS AND METHODS: Two-hundred and eleven patients with primary high grade glioma were treated at the Royal Marsden NHS Trust between 1987 and 1997 with accelerated radiotherapy (55 Gy in 34 fractions twice daily), to planning target volume (PTV) defined as enhancing tumour and a 3 cm margin. All had histologically confirmed high grade glioma (53 anaplastic astrocytoma, 137 glioblastoma multiforme, 4 gliosarcoma, 5 gemistocytic astrocytoma, 12 high grade astrocytoma not otherwise specified). The mean Karnofsky performance status (KPS) was 90 and median age was 54 years (range 19-77). RESULTS: Of 211 patients entered, 201 were able to complete radiotherapy; 39 patients (19%) had deterioration in KPS during radiotherapy and this was transient in 11. Median survival of 211 patients was 10 months with 1 year, 2 year, and 3 year survival probabilities of 38%, 14%, and 8% respectively. Age and extent of excision were independent prognostic factors for survival. Previous comparison to matched cohort receiving 60 Gy in 30 daily fractions did not demonstrate significant survival difference. CONCLUSION: Accelerated radiotherapy is a feasible treatment approach for patients with high grade glioma. The survival and functional outcome are comparable to conventional radiotherapy and the treatment is without serious acute toxicity. While acceleration of conventional dose irradiation could be tested in randomised studies, it is unlikely this approach would result in a clinically meaningful survival benefit. Accelerated radiotherapy therefore remains one of the ways of delivering radical irradiation in patients with high grade glioma. However, it adds complexity to what is a palliative treatment regimen and the rationale and advisability should be re-examined, particularly in terms of impact on quality of life, true patient preference, and health economic considerations.

Adult↗

In vitro study of the mechanisms of senescence acceleration.

Accelerated senescence can be considered to be an aging process that occurs after development and maturity and is characterized by a higher rate of increase in the degree of senescence than seen in the "normal senescence process." We devised culture methods to determine precise population doublings in cultured fibroblast-like cell lines and subsequently compared the aging process, in vitro, in cell lines established from either accelerated senescence-prone or- resistant strains of mice to obtain evidence of accelerated aging. Fibroblast-like cell lines were established from the dorsal dermis of the newborn accelerated senescence-prone mice of the SAMP11 strain and from accelerated senescence-resistant mice of the SAMR1 strain. All cell lines from both strains showed senescence as evidenced by a crisis in growth; then were immortalized. However, in cell lines from the SAMP11 strain, this growth crisis occurred more rapidly and at earlier population doubling levels than in cell lines from the SAMR1 strain. The methods and materials should aid in the elucidation of mechanisms linked to accelerated senescence in mice.

Aging↗

Ventricular excitation maps using tissue Doppler acceleration imaging: potential clinical application.

OBJECTIVES: The purpose of this study is to validate the use of tissue Doppler acceleration imaging (TDAI) for evaluation of the onset of ventricular contraction in humans. BACKGROUND: Tissue Doppler acceleration imaging can display the distribution, direction and value of ventricular acceleration responses to myocardial contraction and electrical excitation. METHODS: Twenty normal volunteers underwent TDAI testing to determine the normal onset of ventricular acceleration. Two patients with paroxysmal supraventricular tachycardia and 30 patients with permanent pacemakers underwent introduction of esophageal and right ventricular pacing electrodes, respectively, and were studied to visualize the onset of pacer-induced ventricular acceleration. Eight patients with dual atrioventricular (AV) node and 20 patients with Wolff-Parkinson-White (WPW) syndrome underwent TDAI testing to localize the abnormal onset of ventricular acceleration, and the results were compared with those of intracardiac electrophysiology (ICEP) tests. RESULTS: The normal onset and the onset of dual AV node were localized at the upper interventricular septum (IVS) under the right coronary cusp within 25 ms before the beginning of the R wave in the electrocardiogram (ECG). In all patients in the pacing group, the location and timing of the onset conformed to the positions and timing of electrodes (100%). In patients with WPW syndrome, abnormal onset was localized to portions of the ventricular wall other than the upper IVS at the delta wave or within 25 ms after the delta wave in the ECG. The agreement was 90% (18 of 20) between the abnormal onset and the position of the accessory pathways determined by ICEP testing. CONCLUSIONS: These results suggest that TDAI is a useful noninvasive method that frequently is successful in visualizing the intramural site of origin of ventricular mechanical contraction.

Adolescent↗

Cyclopiazonic acid induces accelerated progress of meiosis in pig oocytes.

In mammalian oocytes, calcium plays an important role in the regulation of meiotic maturation. In our study, we used the mycotoxin cyclopiazonic acid (CPA), an inhibitor of calcium-dependent ATPases, to mobilise intracellular calcium deposits during in vitro maturation of pig oocytes. The CPA treatment of maturing oocytes significantly accelerated the progress of their maturation. Oocytes entered the CPA-sensitive period after 21 h of in vitro culture. A very short (5 min) exposure to CPA (100 mM) is sufficient to accelerate maturation and it seems that accelerated maturation can be triggered by a transient elevation of intracellular calcium levels. The effect of CPA is not mediated through the cumulus cells, because maturation is accelerated by CPA treatment even in oocytes devoid of cumulus cells. Culture of oocytes with the calcium channel blocker verapamil (concentrations ranging from 0.01 to 0.04 mM) blocked the progress of oocyte maturation beyond the stage of metaphase I. This block can be overcome by the mobilisation of intracellular calcium deposits after CPA treatment (100 nM). The microinjection of heparin (20 pl, 0.1 mg/ml), the inhibitor of inositol triphosphate receptors, before CPA treatment prevented the acceleration of oocyte maturation. This indicates that CPA mobilises the release of calcium deposits through inositol trisphosphate receptors. On the other hand, the microinjection of procaine (20 pl, 200 nM) or the microinjection of ruthenium red (20 pl, 50 mM), both inhibitors of ryanodine receptors, did not prevent accelerated maturation in CPA-treated oocytes. If present in pig oocytes, ryanodine receptors evidently play no part in the liberation of calcium from intracellular stores after CPA treatment.

Animals↗

Accelerators increase permeability of cuticles for the lipophilic solutes metribuzin and iprovalicarb but not for hydrophilic methyl glucose.

Effects of diethylsuberate (DESU), tributyl phosphate (TBP), and monodisperse ethoxylated alcohols (EAs) on rate constants of penetration (k) of model solutes across astomatous cuticular membranes isolated from Madagascar ivy (Stephanotis floribunda) and pear (Pyrus communis) leaves were studied. Model solutes (selected on the basis of their octanol/water partition coefficients, K(ow)) were iprovalicarb (log K(ow) = 3.18), metribuzin (log K(ow) = 1.60), and methyl glucose (MG) (log K(ow) = -3.0). K(ow) varied by more than 6 orders of magnitude. Accelerators had wax/water partition coefficients (log K(ww)) ranging from 1.75 (DESU) to 4.32 (C(12)E(2)), and their equilibrium concentrations in Stephanotis wax varied from 0 to about 160 g kg(-)(1). Accelerators increase solute mobility in cuticles by increasing fluidity of cutin and waxes. This effect was quantified by plotting log k versus the accelerator concentration in wax. With the lipophilic solutes metribuzin and iprovalicarb, these plots were linear. Slopes of these plots characterize the intrinsic activities of the accelerators, and they decreased in the order DESU (0.029) > TBP (0.015) > EAs (0.01). Using these intrinsic activities, the effects of accelerators on rate constants of penetration can be calculated for any accelerator concentration in wax. For instance, at 50 g kg(-)(1), rate constants for lipophilic solutes increased by factors of 28 (DESU), 5.6 (TBP), and 3.2 (C(12)E(n)()), respectively. Permeability of cuticles for the hydrophilic MG was not increased by DESU, TBP, C(12)E(2), and C(12)E(4), while C(12)E(6) and C(12)E(8) increased it. Small hydrophilic solutes such as MG can access aqueous pores in cuticles, and this pathway is not affected by changes in fluidity of amorphous waxes. After rate constants of penetration of ionic CaCl(2) were compared with those for nonionic MG, it was concluded that 60% of the MG diffused across aqueous pores, while 40% used an alternative pathway. Because the solubility of MG in wax is extremely low, it is unlikely that MG diffused along the lipophilic pathway used by metribuzin and iprovalicarb. This agrees with the observation that DESU and TBP had no effect on rate constants for MG. An alternative pathway of unknown properties is suggested. It is speculated that C(12)E(6) and C(12)E(8) sorbed in cuticles might have generated a polar pathway for MG.

3-O-Methylglucose↗

Metal- and Ligand-Accelerated Catalysis of the Baylis-Hillman Reaction.

The Baylis-Hillman reaction, the coupling of an unsaturated carbonyl compound/nitrile with aldehydes, is a valuable reaction but is limited in its practicality by poor reaction rates. We have endeavored to accelerate the reaction using Lewis acids and found that while conventional Lewis acids gave reduced rates group III, and lanthanide triflates (5 mol %) gave increased rates. The optimum metal salts were La(OTf)(3) and Sm(OTf)(3), which gave rate accelerations (k(rel)) of approximately 4.7 and 4.9, respectively, in reactions between tert-butyl acrylate and benzaldehyde when using stoichiometric amounts of DABCO. At low loadings of DABCO (up to 10 mol %), no reaction occurred due to association of DABCO with the metal. Use of additional ligands to displace the DABCO from the metal was studied, and the rate of reaction was found to increase further in most cases. Of the ligands tested, at 5 mol %, (+)-binol gave one of the largest rate accelerations (3.4-fold) and was studied in more detail. It was found that reactions occurred even at low DABCO concentration so that here the Lewis base and Lewis acid were able to promote the reaction without interference from each other. While the (+)-binol (and other chiral ligands) failed to provide any significant asymmetric induction, a substantial nonlinear effect was observed with binol. Thus, use of racemic binol gave no effect on the rate. In seeking to maximize the rate attainable, more soluble (liquid) ligands were studied. Diethyl tartrate and triethanolamine gave rate enhancements of 5.2x and 3.5x at 50 mol %, respectively, versus 1.5x and 2.3x at 5 mol %. The best protocol was to use 100 mol % DABCO, 50 mol % triethanolamine, and 5 mol % La(OTf)(3). This gave overall rate accelerations of between 23-fold and 40-fold depending on the acrylate and approximately 5-fold for acrylonitrile. A simple acid wash removed the reagents, leaving the product in the organic phase. While triethanolamine accelerated the reaction without the lanthanum triflate (18-22-fold at 80 mol %), the reaction in the presence of the metal salt was faster. The system was tested synthetically on various substrates and found to give good rate accelerations with both activated (benzaldehyde and p-nitrobenzaldehyde) and less activated aldehydes (anisaldehyde and cyclohexanecarboxaldehyde) with acrylates. The limited amount of dimerized acrylate in the latter reactions is noteworthy and should extend the range of substrates that can be made by the Baylis-Hillman reaction using our optimum conditions.

Journal Article↗

A detailed analysis of the mechanisms controlling the acceleration of 2,4-DCP monooxygenation in the two-tank suspended growth process.

The mechanisms underlying the observed acceleration of monooxygenation reactions in two-tank accelerator/aerator suspended growth system are evaluated in detail. The accelerator tank is characterized by a very high electron flow through reduced nicotinamide adenine dinucleotide (NADH + H+), particularly when the retention-time ratio is small. Only a small fraction of the electron flow was diverted to oxygenation reactions, and the major sinks of NADH + H+ were respiration and biomass synthesis. The main producer of NADH + H+ is oxidation of acetate, a rapidly degraded electron-donor substrate. The half-maximum-rate concentration for oxygen used in respiration was 0.03 mg/L, while the half-maximum-rate concentration for oxygen used as a cosubstrate in monooxygenation was 0.18 mg/L. Thus, monooxygenations were more sensitive to oxygen limitation than was respiration. The NADH + H+ concentration had a direct effect on the monooxygenation kinetics. The rate coefficients for both monooxygenation reactions were directly proportional to the specific growth rate in the accelerator, which supports that the accelerator tank caused an up-regulation of the monooxygenase content. Because the rate coefficients in the aerator tank were much larger than in the one-tank system, even though the specific growth rates were nearly the same, monooxygenases may have carried over from the accelerator tank to the aerator tank. Its higher concentration of 2,4-dichlorophenol (2,4-DCP) and the higher specific growth rate were the main reasons why the accelerator had faster kinetics for 2,4-DCP utilization than did the aerator tank. The apparently higher levels of monooxygenase in both tanks of the two-tank system also appears be a primary reason why its performance was substantially superior to that of the one-tank system in terms of 2,4-DCP removal.

Biodegradation, Environmental↗