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Refractory peritoneal carcinomatosis is a common terminal feature of epithelial ovarian cancer (EOC). Previous reports have suggested that immunotherapy is a promising therapeutic strategy for EOC. Interleukin (IL)‑33 is a member of the IL‑1 superfamily of cytokines. The role of IL‑33 in tissue inflammation and promoting type 2 immune responses has been established, and recently, there is accumulating evidence to suggest the involvement of IL‑33 in carcinogenesis. In this study, we focused on the association between the tumor expression of IL‑33 and ovarian peritoneal carcinomatosis. We used an immunosufficient murine model of peritoneal carcinomatosis and human EOC samples. The overexpression of IL‑33 in the ID8 mouse EOC cell line tumors significantly prolonged the survival of immunocompetent mice in the peritoneal carcinomatosis setting, but not in the subcutaneous model. In addition, the silencing of IL‑33 in ID8‑T6 cells (subclone with high dissemination potential) significantly shortened the survival of the tumor‑bearing mice. This was likely due to the intratumoral accumulation of CD8+ and CD4+ T cells, and a decrease in CD11b+Gr1+ cells. Furthermore, IL‑33 induced the intraperitoneal microenvironment favoring tumor elimination through the inhibition of differentiation into CD11b+Gr1+ cells. On the whole, the findings of this study suggest IL‑33 to be a cytokine that reflects antitumor peritoneal conditions. Further investigation of the antitumorigenic role of IL‑33 may aid in the development of more effective therapeutic approaches for the treatment of EOC with peritoneal carcinomatosis.

Postsynaptic density (PSD)-95, the most abundant postsynaptic scaffolding protein, plays a pivotal role in synapse development and function. Continuous palmitoylation cycles on PSD-95 are essential for its synaptic clustering and regulation of AMPA receptor function. However, molecular mechanisms for palmitate cycling on PSD-95 remain incompletely understood, as PSD-95 depalmitoylating enzymes remain unknown. Here, we isolated 38 mouse or rat serine hydrolases and found that a subset specifically depalmitoylated PSD-95 in heterologous cells. These enzymes showed distinct substrate specificity. α/β-Hydrolase domain-containing protein 17 members (ABHD17A, 17B, and 17C), showing the strongest depalmitoylating activity to PSD-95, showed different localization from other candidates in rat hippocampal neurons, and were distributed to recycling endosomes, the dendritic plasma membrane, and the synaptic fraction. Expression of ABHD17 in neurons selectively reduced PSD-95 palmitoylation and synaptic clustering of PSD-95 and AMPA receptors. Furthermore, taking advantage of the acyl-PEGyl exchange gel shift (APEGS) method, we quantitatively monitored the palmitoylation stoichiometry and the depalmitoylation kinetics of representative synaptic proteins, PSD-95, GluA1, GluN2A, mGluR5, Gαq, and HRas. Unexpectedly, palmitate on all of them did not turn over in neurons. Uniquely, most of the PSD-95 population underwent rapid palmitoylation cycles, and palmitate cycling on PSD-95 decelerated accompanied by its increased stoichiometry as synapses developed, probably contributing to postsynaptic receptor consolidation. Finally, inhibition of ABHD17 expression dramatically delayed the kinetics of PSD-95 depalmitoylation. This study suggests that local palmitoylation machinery composed of synaptic DHHC palmitoylating enzymes and ABHD17 finely controls the amount of synaptic PSD-95 and synaptic function. SIGNIFICANCE STATEMENT Protein palmitoylation, the most common lipid modification, dynamically regulates neuronal protein localization and function. Its unique reversibility is conferred by DHHC-type palmitoyl acyl transferases (palmitoylating enzymes) and still controversial palmitoyl-protein thioesterases (depalmitoylating enzymes). Here, we identified the membrane-anchored serine hydrolases, ABHD17A, 17B, and 17C, as the physiological PSD-95 depalmitoylating enzymes that regulate PSD-95 palmitoylation cycles in neurons. This study describes the first direct evidence for the neuronal depalmitoylating enzyme and provides a new aspect of the dynamic regulatory mechanisms of synaptic development and synaptic plasticity. In addition, our established APEGS assay, which provides unbiased and quantitative information about the palmitoylation state and dynamics, revealed the distinct regulatory mechanisms for synaptic palmitoylation.

Two new compounds, 10-dehydroxymelleolide D (1) and 13-hydroxymelleolide K (2), along with seven known compounds, 5'-O-methylmelledonal (3), melleolide D (4), 13-hydroxydihydromelleolide (5), melleolide (6), armillarinin (7), armillaridin (8), and armillarikin (9), were isolated from the culture broth of Armillaria sp. Their structures were determined by spectroscopic data analysis. All the compounds inhibited plant growth of lettuce. Melleolide (6) and armillarikin (9) inhibited mycelial growth of Coprinopsis cinerea and/or Flammulina velutipes.

Five novel compounds (1–3, 5, and 6), and two known ones (4 and 7) were isolated from the culture broth of Agrocybe praecox. Their structures were determined by the interpretation of spectroscopic data. Compounds 1–4 inhibited hypocotyl growth of lettuce, and 1, 3, and 4 inhibited the root growth.

Safer heparin-neutralizing agents are currently required to replace protamine, the use of which causes adverse effects such as anaphylaxia. Low-molecular-weight (LMW) heparin mimetics that potentiate antithrombin III (AT) action are also valuable as anti-thrombotics. This paper describes a high-throughput assay for both heparin-neutralizing agents and LMW heparin mimetics without the use of blood preparations. The assay is based on turbidimetric measurement of a solution of collagen, heparin, and a test compound. Native collagen molecules spontaneously form insoluble fibrils when transferred to a physiological buffer, and this process is inhibited by heparin. In the presence of a heparin-neutralizing agent or an LMW heparin mimetic, the inhibitory effect of heparin is canceled and turbidity increase is retrieved. We demonstrated that this assay is effective in detecting potential agents with high reliability (Z' factor=0.9). The screening of a chemical library (34400 compounds) was further performed in a 384-well format, and led to the identification of a novel heparin-neutralizing agent. Since this assay protocol is feasible for an automated high-throughput screening (HTS) system, it could enhance the lead seeking process for drugs related to heparin/heparan sulfate (HS) functions.

Five novel compounds, applanatines A–E (1–5), and a known one (6) were isolated from the culture broth of Ganoderma applanatum. Their structures including the relative configurations were determined by the interpretation of spectroscopic data. Compounds 3 and 4 suppressed the growth of Fusobacterium nucleatum, that is, a prominent member of the oral microflora implicated in periodontitis.

Precise regulation of protein assembly at specialized membrane domains is essential for diverse cellular functions including synaptic transmission. However, it is incompletely understood how protein clustering at the plasma membrane is initiated, maintained and controlled. Protein palmitoylation, a common post-translational modification, regulates protein targeting to the plasma membrane. Such modified proteins are enriched in these specialized membrane domains. In this review, we focus on palmitoylation of PSD-95, which is a major postsynaptic scaffolding protein and makes discrete postsynaptic nanodomains in a palmitoylation-dependent manner and discuss a determinant role of local palmitoylation cycles in creating highly localized hotspots at the membrane where specific proteins concentrate to organize functional domains.

Using Cacao husk, a by-product of chocolate production, as a substitute for sawdust in Hericium erinaceum cultivation was investigated.1 By replacing sawdust with Cacao husks, a substitution ratio of 25% or less is useful as a substrate.2 It was analyzed, the proximate composition ; total dietary fiber, minerals, free monosaccharide, free disaccharide and free sugar alcohol in fruit body cultivated in the substrate substituted at 0, 50 and to 100%. The proximate composition, total dietary fiber and mineral content showed the same readings regardless of all the substrates. The total monosaccharide and total disaccharide content became higher as the substitutive ratio of cacao husk increased. On the other hand, the total sugar alcohol content decreased.

Three novel compounds were isolated from the culture broth of Armillaria sp. Their structures were elucidated mainly by spectroscopic data analyses. All the compounds regulated hypocotyl and root growth of lettuce.

Laser frequency stabilization is essential for interferometric gravitational-wave detectors to attain their target sensitivity. We have designed a multistage laser frequency stabilization system which has been applied in the development of the TAMA 300 gravitational-wave detector in Japan. The control topology consisting of two cascaded loops were employed to secure high feedback gain and reliable detector operation and thus allow the best frequency stability and uninterrupted long-term observation. We achieved simultaneously a frequency stability of 5 × 10^(−5) Hz/√HZ , and a common-mode rejection ratio (which reduces the coupling of frequency noise to spurious signals in the detector) of 37 dB. The developed system enabled us to operate TAMA 300 with sufficient sensitivity and stability that it had the potential to register gravitational-wave events. The system was confirmed to be suitable for a gravitational-wave detector from the observation run of TAMA 300.

The chronological lifespan (CLS) of the budding yeast Saccharomyces cerevisiae is a model for the aging of post-mitotic cells in higher eukaryotes. In this study, we found that the sesquiterpene aryl ester melleolide expands the CLS of budding yeast. In contrast, melleolide compromised the CLS of the fission yeast Schizosaccharomyces pombe. This indicates that melleolide might have a potential anti-aging activity against some types of cell, and that it might be useful as a selective anti-fungal drug.

Three novel lettuce hypocotyl and root growth regulating compounds, armillariols A (I), B (II), and C (III), are isolated from the culture broth of Armillaria sp.

TAMA300, an interferometric gravitational-wave detector with 300-m baseline length, has been developed and operated with sufficient sensitivity to detect gravitational-wave events within our galaxy and sufficient stability for observations; the interferometer was operated for over 10 hours stably and continuously. With a strain-equivalent noise level of $h\sim 5 \times 10^{-21} /\sqrt{\rm Hz}$, a signal-to-noise ratio (SNR) of 30 is expected for gravitational waves generated by a coalescence of 1.4 $M_\odot$-1.4 $M_\odot$ binary neutron stars at 10 kpc distance. %In addition, almost all noise sources which limit the sensitivity and which %disturb the stable operation have been identified. We evaluated the stability of the detector sensitivity with a 2-week data-taking run, collecting 160 hours of data to be analyzed in the search for gravitational waves., 5 pages, 4 figures

Four compounds were isolated from scrap cultivation beds of the mushroom, Hericium erinaceum. Compounds 1–4 were identified as methyl 4-hydroxy-3-(3-methylbutanoyl) benzoate, 2-chloro-1,3-dimethoxy-5-methylbenzene, methyl 4-chloro-3,5-dimethoxybenzoate, and 4-chloro-3,5-dimethoxybenzaldehyde by an interpretation of the NMR and MS data, respectively. This is the first reported isolation of 1 from a natural source. All the compounds showed protective activity against endoplasmic reticulum stress-dependent cell death.

We have developed Vacuum Electroslag Remelting process (VSR) by ourselves. This process is ESR process under vacuum or low pressure. This process has many strong points as compared with VAR and ESR process. Especially on this process, it is possible to attain ultra low oxygen content by controlling the interaction of air and molten slag.Using this process, we have succeeded in producing the stainless steel ingot, oxygen content of which was less than 10ppm and inclusion number of which was very low.

Pigment epithelium-derived factor (PEDF) is a collagen-binding protein that is abundantly distributed in various tissues, including the eye. It exhibits various biological functions, such as anti-angiogenic, neurotrophic, and neuroprotective activities. PEDF also interacts with extracellular matrix components such as collagen, heparan sulfate proteoglycans (HSPGs), and hyaluronan. The collagen-binding property has been elucidated to be important for the anti-angiogenic activity in vivo (Hosomichi, J., Yasui, N., Koide, T., Soma, K., and Morita, I. (2005) Biochem. Biophys. Res. Commun. 335, 756–761). Here, we investigated the collagen recognition mechanism by PEDF. We first narrowed down candidate PEDF-binding sequences by taking advantage of previously reported structural requirements in collagen. Subsequent searches for PEDF-binding sequences employing synthetic collagen-like peptides resulted in the identification of one of the critical binding sites for PEDF, human α1(I)(929–938) (IKGHRGFSGL). Further analysis revealed that the collagen recognition by PEDF is sequence- and conformation-specific, and the high affinity binding motif is KGXRGFXGL in the triple helix. The PEDF-binding motif significantly overlapped with the heparin/HSPG-binding motif, KGHRG(F/Y). The interaction of PEDF with collagen I was specifically competed with by heparin but not by chondroitin sulfate-C or hyaluronan. The binding sequences for PEDF and heparin/HSPG also overlapped with the covalent cross-linking sites between collagen molecules. These findings imply a functional relationship between PEDF and HSPGs during angiogenesis, and the interaction of these molecules is regulated by collagen modifications.

Three new compounds, 3-hydroxyhericenone F (1), hericenone I (2), and hericenone J (3), were isolated from the mushroom Hericium erinaceum. The structures of 1-3 were determined by the interpretation of spectral data. Compound 1 showed the protective activity against endoplasmic reticulum (ER) stress-dependent Neuro2a cell death, however, compounds 2 and 3 did not.

The effect of dietary eritadenine on the plasma homocysteine concentration was investigated in methionine-induced hyperhomocysteinemic rats. The rats were fed on the control or eritadenine-supplemented (50 mg/kg) diet for 10 d. The animals were then injected with saline or methionine at a level of 100 or 300 mg/kg of body weight, and sacrificed 2 h or a more appropriate time after injection. The methionine injection increased the post-2 h concentration of plasma homocysteine in a dose-dependent manner in the control rats, this increase being significantly suppressed in the eritadenine-fed rats. This effect persisted up to 8 h after the methionine injection. The hepatic concentrations of S-adenosylmethionine and S-adenosylhomocysteine were increased by eritadenine, whereas the hepatic homocysteine concentration was inversely decreased. The cystathionine beta-synthase activity in the liver was increased by eritadenine. It is suggested from these results that eritadenine might suppress the methionine-induced increase in plasma homocysteine concentration by dual mechanisms: slowing the homocysteine production from S-adenosylhomocysteine and increasing the removal of homocysteine due to the enhanced activity of cystathionine beta-synthase.

BACKGROUND: Few epidemiologic studies have examined the association between the rate of eating and obesity. In this study, we cross-sectionally examined the association of the self-reported rate of eating with current Body Mass Index (BMI), and BMI-change from 20 years of age to the current age.METHODS: Subjects were 3737 male (mean age ± standard deviation and mean BMI ± standard deviation: 48.2 ± 7.1 years and 23.3 ± 2.7 kg/m2) and 1005 female (46.3 ± 7.0 years and 21.8 ± 2.8 kg/m2) Japanese civil servants. We measured self-reported categorical rate of eating, current BMI, BMI at age 20, and BMI-change from age 20. Energy intake was assessed over a 1-month period with a brief-type diet history questionnaire.RESULTS: The multiple regression analysis in which the current BMI was regressed by categorical rate of eating, energy intake, age, and lifestyle factors showed that current BMI steadily increased by -0.99, -0.67, 0.81, and 1.47 kg/m2 along with the progress of categorical rate of eating from the 'medium' group to 'very slow', 'relatively slow', 'relatively fast', and 'very fast' groups, respectively, in men. In women, the corresponding values were -1.06, -0.35, 0.50, and 1.34 kg/m2. When the BMI increment from age 20 to current age was regressed in the same manner, the increment was -0.63, -0.34, 0.57, and 1.05 kg/m2 in men and -0.71, -0.32, 0.34, and 1.14 kg/m2 in women, respectively. Additionally, both BMI at age 20 and current height were positively associated with rate of eating.CONCLUSIONS: Our results among middle-aged men and women suggest that eating fast would lead to obesity.J Epidemiol 2006; 16: 117-124.

We analyzed 6 hours of data from the TAMA300 detector by matched filtering, searching for gravitational waves from inspiraling compact binaries. We incorporated a two-step hierarchical search strategy in matched filtering. We obtained an upper limit of 0.59/hour (C.L.=90%) on the event rate of inspirals of compact binaries with mass between 0.3M_solar and 10M_solar and with signal-to-noise ratio greater than 7.2. The distance of 1.4M_solar (0.5M_solar) binaries which produce the signal-to-noise ratio 7.2 was estimated to be 6.2kpc (2.9kpc) when the position of the source on the sky and the inclination angle of the binaries were optimal., Comment: 5 pages, 4 figures. To appear Phsical Review D

Effects of the optical isomers of propranolol on blood pressure in the rat, and in the spinal rat during adrenaline infusion were studied to investigate the mechanism of the pressor action of propranolol. Both isomers of propranolol produced a sustained pressor action in the rat and in the spinal rat infused with adrenaline. The magnitude of the pressor action produced by the d- and 1-propranolol was proportional to their beta-adrenoceptor blocking activities in the heart as was reported by several investigators. It is concluded that the pressor action of propranolol is due to the blockade of the beta-adrenoceptors mediating vasodilation in the skeletal muscle vascular beds.

Recent clinical studies have suggested an association of tolbutamide (TB) therapy with an increased incidence of cardiovascular deaths. In this study, the effects of a newly synthetized hypoglycemic agent, gliclazide (GC), on the cardiovascular system were investigated, and compared with those of TB. Results are as follows: GC was found to be about ten times as active as TB in decreasing blood glucose in rabbits. GC and TB produced a dose-dependent increase in blood pressure and little change in heart rate in rats and rabbits. In driven left rat and rabbit atria, these agents produced a positive inotropic effect. The positive inotropic effects of these drugs were not altered by pretreatment with propranolol, or theophylline. These agents produced little change in the rate in spontaneous beating rat, rabbit and guinea pig atria. Higher doses produced a slightly negative chronotropic response. Neither agent potentiated the intropic effects of isoproterenol on the rabbit and guinea pig left atria. In isolated perfused working rabbit hearts, these compounds produced a slight decrease in coronary flow. It is concluded that GC and TB possess positive inotropic effects on isolated atria, and these effects are not mediated either through adrenergic mechanisms or the cyclic AMP system.

We previously reported that the pressor action of propranolol was observed in the rat anesthetized with urethane. In the present study, rats, anesthetized with pentobarbitone or ether, treated with curare or unanesthetized, were used to investigate the influence of anesthetics on the blood pressure response to propranolol. Propranolol always produced a pressor response under these experimental conditions as well as urethane anesthesia. But under pentobarbitone anesthesia, the magnitude of the pressor action was significantly lower than that obtained under the other experimental conditions. It is concluded that the choice of urethane as the anesthetic does not create a situation irrelevant to that found with other anesthetics and that the cardiovascular responses of rat to propranolol are unique when compared to other species.

We showed in previous studies that pro pranolol produced a pressor action in the rat, and that this action was also observed in the spinal rat infused with adrenaline, noradrenaline and a mixture of isoproterenol and vasopressin, but not with vasopression alone. The action was also observed in the guinea pig infused with adrenergic beta-stimulants. In the present work, conditions in the peripheral vessels in which propranolol observed in the spinal rat infused with a mixture of various doses of isoproterenol and vasopressin. The effect of propranolol on the blood pressure in guinea pigs and rabbits with a reduced vasoconstrictive tone in the peripheral vascular beds with alpha-blockade was studied. Propranolol produced a pressor action in the spinal rat infused with a mixture of isoproterenol and vasopressin, and the magnitude of the rise depended on the mixing rate of the doses of these two drugs. The drug also produced a sustained rise in blood pressure in guinea pigs and rabbits treated with alpha-blockers. Thus, it is concluded that propranolol produces a marked pressor action when peripheral vessels are maintained in conditions with an appropriate constrictive and beta-adrenoceptive vasodilator tone.

The actions of bradykinin and the influences of several drugs on them were investigated on the isolated spontaneous beating and electrically driven atria of guinea pigs.Results : (1) Bradykinin produced an increase of heart rate and myocardial contractile force. These actions were dose dependent. 2) The positive chronotropic and inotropic actions of bradykinin were not influenced by reserpinization or by administering α- and β-adrenergic blocking agents. Therefore, bradykinin was considered to possess a direc cardiac stimulating action. 3) Homochlorcyclizine, pyridinolcarbamate and diphenhydramine depressed the positive chronotropic action significantly, but did not affect the positive inotropic action of bradykinin. 4) Histamine did not relate to the cardiac action of bradykinin.

In the intact rabbit, 0.1 μg of bradykinin administered into the saphenous vein caused a constriction of both artery and vein and a decrease of venous flow in the ear with a depression of blood pressure. In these experiments the vasoconstriction following bradykinin may have had a variety of causes other than direct action. 0.1 μg of bradykinin administered into the central artery of the ear caused a vasodilatation and an increase of venous flow.In the isolated rabbit ear preparations and guinea pig hindguarters, the perfusion pressure influenced venous outflow responses to bradykinin. Venous outflow was also influenced by the concentrations of bradykinin. Lower concentrations of bradykinin and higher perfusion pressure induced an increase in outflow and higher concentrations of bradykinin and lower perfusion pressure induced a decrease. The arterio-dilatation and venoconstriction were observed in isolated rabbit ear.The direct action of bradykinin on the vessels is considered to be arterio-dilatation and venoconstriction. However, in certain preparations and under certain circumstances, bradykinin causes diverse action on the vessels. It is suggested that in the experiments in which the direct action is not observed, this action may be latent.

The action of ATP, phosphocreatine (PHC) and their related compounds was investigated on the perfused isolated hearts of mammalia and amphibia. Result : ATP and ADP increased the amplitude of mammalian and amphibian heart contraction after a temporary decrease and greatly increased the rate of coronary flow of the mammalian heart, while PHC showed no increase in the rate of mammalian coronary flow, but it increased the amplitude of both hearts' contraction with no temporary decrease followed.

Effects of practolol, alprenolol and pindolol on blood pressure in the rat were studied. Also effects of these three beta-blocking agents on blood pressure and heart rate in spinal rats during adrenaline infusion were studied and compared with those of propranolol. The beta-blocking agents produced a sustained pressor action in the rat, and in the spinal rat infused with adrenaline. The magnitude of the pressor action induced by the beta-blockers was in the following order: pindolol larger than or equal to propranolol larger than or equal to alprenolol greater than practolol. Minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline were in the following order; practolol greater than alprenolol larger than or equal to propranolol larger than or equal to pindolol. The magnitude of the pressor action produced by the same dose of these beta-blockers and minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline seemed to be roughly proportional to their beta-receptor blocking activities. It was concluded that the minimum doses of these beta-blockers required to cause a pressor action and the magnitude of the pressor action induced by the beta-blockers in the spinal rat infused with adrenaline could be used to compare their beta-blocking activities and that practolol, a cardioselective beta-blocker, seems to block not only cardiac beta-receptor but to some extent also peripheral vascular beta-receptors.

In a previous experiment, the pressor action of propranolol was observed in the spinal rat in which the β-receptor vascular tone was induced by infusions of β-adrenergic stimulating agents. This pressor action is considered to be due to the blockade of the β-adrenoceptive vasodilator tone provided by β-stimulants in the peripheral vessel. In this experiment, the pressor action of propranolol was used to investigate the mechanism of the vasodilator action of some vasodilators. Nylidrin, isoxsuprine, bamethan, acetylcholine and papaverine were used as vasodilators. Propranolol produced a pressor action in the spinal rat during infusions of the mixture of nylidrin, isoxsuprine or bamethan and vasopressin, but not during infusions of the mixture of papaverine or acetylcholine and vasopressin. This observation suggests that nylidrin, isoxsuprine and bamethan caused vasodilation through stimulation of β-vascular receptors. This method could be used to ascertian the role of β-receptor activation as a mechanism for the vasodilator action of some drugs.

THE 16-acetyl derivative of digitalinum has been prefaced as follows. Digitalinum verum hexaacetate was obtained by the usual reaction of digitalinum verum with acetic anhydride in pyridine solution; this hexaacetate, using snail enzyme1, was partially deacetylated by potassium hydrogen carbonate to digitalinum verum diacetate, m.p. 181°–184°, (α)D–24.0° (CH3OH). The substance was separated by partition chromatography from the reaction mixtures, but it could not be induced to crystallize. The existence of acetoxyl group on carbon atom 16 of this glycoside has been confirmed by the facts that on treatment with alumina it affords a hydrogenated derivative, and that the molecular rotation difference between digitalinum verum and this compound is similar to the difference between gitoxigenin and oleandrigenin. Evidence is also given by the fact that it is hydrolysed into oleandrigenin on Mannich hydrolysis at low temperature (0°–5°).

Digitalinum verum is a cardiac glycoside which was discovered at first by Kiliani (1) in digitalis seeds. Its pharmacological action was inves.igated by Fromherz (2), Chen (3) and one of the authors (4). Rec intly Okano et al. (5) produced 16-acetyl digitalinum verum (16AD) by partial acetylation of digitalinum verum (Fig. 1). This glycoside is highly soluble in water though parent compound, digitalinum verum is not. We used various animals to study the pharmacological action of this substance, and found that it was a much more potent and rapid ac ing compound than its parent.