Physostigmine (Phs) is a reversible inhibitor of acetylcholinesterase (AChE) that penetrates the blood-brain barrier (BBB) and could be used to protect the central nervous system (CNS) against the effects of nerve agents. For prophylactic effectiveness, long, steady, and adequate inhibition of AChE activity by Phs is needed to broadly protect against the CNS effects of nerve agents. Here, we evaluated the efficacy of transdermal patches containing Phs and procyclidine (PC) as prophylactic agents. Patches (25 cm(2)) containing 4.4smg Phs and 17.8smg PC had a protective ratio of approximately 78.6-fold in rhesus monkeys challenged with VX nerve agent and given an antidote. Physiologically based pharmacokinetic model in conjunction with an indirect pharmacodynamic (PBPK/PD) was developed for Phs and scaled to rhesus monkeys. The model was able to reproduce the concentration profile and inhibitory effect on AChE of Phs in monkeys, as evidenced by correlation coefficients of 0.994 and 0.992 for 25 cm(2) and 49 cm(2) patches, respectively (i.e., kinetic data), and 0.989 and 0.968 for 25 cm(2) and 49 cm(2) patches, respectively (i.e., dynamic data). By extending the monkey PBPK/ PD model to humans, the effective human dose was predicted to be five applications of a 25 cm(2) patch (i.e., 22smg Phs), and two applications of a 49scm(2) patch (i.e., 17.4smg Phs). Therefore, given that patch application of Phs in rhesus monkeys has a prolonged effect (namely, AChE inhibition of 19.6% for the 25 cm(2) patch and 23.0% for the 49 cm(2) patch) for up to 216sh, patch formulation of Phs may provide similar protection against nerve agent intoxication in humans.
BACKGROUND: Bradysia procera, a ginseng stem fungus gnat, is one of the most serious insect pests of Korea ginseng (Panax ginseng), causing significant damage to plant growth. The goal of this study was to determine the toxicity and mechanism of action of phenylpropanoids (trans-anethole and estragole) isolated from the methanol extract and hydrodistillate of Illicium verum fruit against third-instar larvae and eggs of B. procera. RESULTS: The filter-paper mortality bioassay revealed that estragole (LC50, 4.68 g/cm(2) ) has a significant fumigant effect, followed by trans-anethole (LC50, 43.92 g/cm(2) ). However, estragole had the lowest toxic effect when compared to commercially available insecticides. After 7 days, estragole and trans-anethole at 75 g/cm(2) inhibited egg hatchability by up to 97 and 93%, respectively. At 0.09 g/cm(2) , insecticides had an inhibitory effect on egg-hatching ability ranging from 88 to 94%. Furthermore, in both closed and open containers, these active constituents were able to consistently induce vapor-phased toxicity. Both estragole and trans-anethole have the ability to inhibit acetylcholinesterase, which is involved in neurotransmitter function. However, the active constituent estragole from I. verum fruit acted as a potent acetylcholinesterase (AChE) inhibitor and had a slightly lower effect on cyclic AMP than octopamine alone. CONCLUSION: This finding suggests that estragole may influence B. procera neurotransmitter function via both the AChE and octopaminergic receptors. More research is needed to demonstrate the potential applications of I. verum fruit-derived products as potential larvicides and ovicides for B. procera population control.
Title: Synthesis and biological evaluation of 1,2,4-triazolidine-3-thiones as potent acetylcholinesterase inhibitors: in vitro and in silico analysis through kinetics, chemoinformatics and computational approaches Mahajan PG, Dige NC, Vanjare BD, Raza H, Hassan M, Seo SY, Kim CH, Lee KH Ref: Mol Divers, 24:1185, 2020 : PubMed
We have designed and synthesized a novel acidic ionic liquid and explored its catalytic efficiency for the synthesis of 1,2,4-triazolidine-3-thione derivatives. A simple reaction between aldehydes and thiosemicarbazide for short time in 60:40 v/v water/ethanol at room temperature offers target 1,2,4-triazolidine-3-thione derivatives. The formation of target compounds is confirmed by NMR, IR and ESI-MS analysis. Pleasingly, synthesized compounds show noteworthy acetylcholinesterase (AChE) inhibitory activity with much lower IC(50) values 0.0269 +/- 0.0021-1.1725 +/- 0.0112 microM than standard Neostigmine methylsulphate. In addition, synthesized 1,2,4-triazolidine-3-thiones exhibits significant free radical scavenging activity as compared to standard vitamin C. The studies on validation of Lipinski's rule through chemoinformatics properties and molecular docking analysis are in support of in vitro analysis. Therefore, overall present study illustrates synthesis of some new 1,2,4-triazolidines-3-thiones which can serve as a template for drug designing such as AChE inhibitors. Herein, we proposed ionic liquid-catalyzed ease of synthetic approach for medicinally important 1,2,4-triazolidine-3-thiones and their bio-evaluations.
BACKGROUND: The efficacy of acetylcholinesterase inhibitors and memantine in the symptomatic treatment of Alzheimer's disease is well-established. Randomised trials have shown them to be associated with a reduction in the rate of cognitive decline. AIMS: To investigate the real-world effectiveness of acetylcholinesterase inhibitors and memantine for dementia-causing diseases in the largest UK observational secondary care service data-set to date. METHOD: We extracted mentions of relevant medications and cognitive testing (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores) from de-identified patient records from two National Health Service (NHS) trusts. The 10-year changes in cognitive performance were modelled using a combination of generalised additive and linear mixed-effects modelling. RESULTS: The initial decline in MMSE and MoCA scores occurs approximately 2 years before medication is initiated. Medication prescription stabilises cognitive performance for the ensuing 2-5 months. The effect is boosted in more cognitively impaired cases at the point of medication prescription and attenuated in those taking antipsychotics. Importantly, patients who are switched between agents at least once do not experience any beneficial cognitive effect from pharmacological treatment. CONCLUSIONS: This study presents one of the largest real-world examination of the efficacy of acetylcholinesterase inhibitors and memantine for symptomatic treatment of dementia. We found evidence that 68% of individuals respond to treatment with a period of cognitive stabilisation before continuing their decline at the pre-treatment rate.
Title: Facile Synthesis, Crystal Structure, DFT Calculation and Biological Activities of 4-(2-fluorophenyl)-3-(3-methoxybenzyl)-1H-1,2,4-triazol-5 (4H)-one (5) Saleem M, Rafiq M, Jeong YK, Cho DW, Kim CH, Seo SY, Choi CS, Hong SK, Lee KH Ref: Med Chem, 14:451, 2018 : PubMed
BACKGROUND: In the past few decades, design, synthesis, and characterization of novel heterocyclic compounds with auspicious biological profile received the considerable attention of the scientific community. Among them, the small and simple organic molecular backbone like triazole moiety have a broad spectrum of applications in the medicinal as well as diagnostic areas. OBJECTIVE: The objective of present study was synthesis, characterization, and exploration of biological profile of 4-(2-fluorophenyl)-3-(3-methoxybenzyl)-1H-1,2,4-triazole-5(4H)-one (5). The tautomeric interconversion of the molecule was observed by the single crystal XRD and DFT analysis. METHODS: N-(2-fluorophenyl)-2-[2-(3-methoxyphenyl)acetyl]hydrazine carboxamide (4) was synthesized by the condensation of 2-(3-methoxyphenyl)acetohydrazide (3) with 1-fluoro-2- isocyanatobenzene. The dehydrocyclization of compound (4) yielded target compound (5) by refluxing in 2 N aqueous sodium hydroxide solutions. The target molecule was characterized by FTIR, 1H NMR, 13C NMR, single crystal X-ray diffraction analysis and DFT calculation. The enzymatic assay measurements were carried out by using a microplate reader (OPTI Max, Tunable Microplate Reader; Wavelength range: 340-850 nm; for 96-well plates) while DFT calculation was performed by Gaussian 09 package. RESULTS: The XRD result and DFT calculations showed that molecule 5 predominantly exists in thione conformation and crystallized in the triclinic system of P-1 space group. Furthermore, for the practical applicability of synthesized compound 5, the in vitro acetylcholinesterase as well as alpha-glucosidase inhibition activities were performed and found moderate enzyme inhibition potential comparable with that of reference inhibitors. CONCLUSION: This study might be helpful for future design and development of potent enzyme inhibitor to control Alzheimer's as well as diabetic disease. The DFT and single crystal XRD analysis data might be helpful for understanding the mechanism of drug binding and its mode of action.
Upregulation of beta2 subunit-containing (beta2*) nicotinic acetylcholine receptors (nAChRs) is implicated in several aspects of nicotine addiction, and menthol cigarette smokers tend to upregulate beta2* nAChRs more than nonmenthol cigarette smokers. We investigated the effect of long-term menthol alone on midbrain neurons containing nAChRs. In midbrain dopaminergic (DA) neurons from mice containing fluorescent nAChR subunits, menthol alone increased the number of alpha4 and alpha6 nAChR subunits, but this upregulation did not occur in midbrain GABAergic neurons. Thus, chronic menthol produces a cell-type-selective upregulation of alpha4* nAChRs, complementing that of chronic nicotine alone, which upregulates alpha4 subunit-containing (alpha4*) nAChRs in GABAergic but not DA neurons. In mouse brain slices and cultured midbrain neurons, menthol reduced DA neuron firing frequency and altered DA neuron excitability following nAChR activation. Furthermore, menthol exposure before nicotine abolished nicotine reward-related behavior in mice. In neuroblastoma cells transfected with fluorescent nAChR subunits, exposure to 500 nm menthol alone also increased nAChR number and favored the formation of (alpha4)3(beta2)2 nAChRs; this contrasts with the action of nicotine itself, which favors (alpha4)2(beta2)3 nAChRs. Menthol alone also increases the number of alpha6beta2 receptors that exclude the beta3 subunit. Thus, menthol stabilizes lower-sensitivity alpha4* and alpha6 subunit-containing nAChRs, possibly by acting as a chemical chaperone. The abolition of nicotine reward-related behavior may be mediated through menthol's ability to stabilize lower-sensitivity nAChRs and alter DA neuron excitability. We conclude that menthol is more than a tobacco flavorant: administered alone chronically, it alters midbrain DA neurons of the nicotine reward-related pathway.
Title: Lipase-catalyzed in-situ biosynthesis of glycerol-free biodiesel from heterotrophic microalgae, Aurantiochytrium sp. KRS101 biomass Kim KH, Lee OK, Kim CH, Seo JW, Oh BR, Lee EY Ref: Bioresour Technol, 211:472, 2016 : PubMed
Heterotrophic microalgae, Aurantiochytrium sp. KRS101 had a large amount of lipid (56.8% total lipids). The cells in the culture medium were easily ruptured due to thin cell wall of Aurantiochytrium sp., which facilitated in-situ fatty acid methyl esters (FAMEs) production directly from biomass. The harvested biomass had a high content of free fatty acids (FFAs), which was advantageous for glycerol-free FAMEs production. FAMEs were directly produced from Aurantiochytrium sp. KRS101 biomass (48.4% saponifiable lipids) using Novozyme 435-catalyzed in-situ esterification in dimethyl carbonate (DMC). DMC was used as a lipid extraction reagent, acyl acceptor and reaction medium. A 433.09mg FAMEs/g biomass was obtained with 89.5% conversion under the optimal condition: DMC to biomass ratio of 5:1 (v/w) and enzyme to biomass ratio of 30% (w/w) at 50 degrees C for 12h. Glycerol could not be detected in the produced FAMEs.
Retrospective epidemiological studies show an inverse correlation between susceptibility to Parkinson's disease and a person's history of tobacco use. Animal model studies suggest nicotine as a neuroprotective agent and nicotinic acetylcholine (ACh) receptors (nAChRs) as targets for neuroprotection, but the underlying neuroprotective mechanism(s) are unknown. We cultured mouse ventral midbrain neurons for 3 weeks. Ten to 20% of neurons were dopaminergic (DA), revealed by tyrosine hydroxylase (TH) immunoreactivity. We evoked mild endoplasmic reticulum (ER) stress with tunicamycin (Tu), producing modest increases in the level of nuclear ATF6, phosphorylated eukaryotic initiation factor 2alpha, nuclear XBP1, and the downstream proapoptotic effector nuclear C/EBP homologous protein. We incubated cultures for 2 weeks with 200 nm nicotine, the approximate steady-state concentration between cigarette smoking or vaping, or during nicotine patch use. Nicotine incubation suppressed Tu-induced ER stress and the unfolded protein response (UPR). Study of mice with fluorescent nAChR subunits showed that the cultured TH+ neurons displayed alpha4, alpha6, and beta3 nAChR subunit expression and ACh-evoked currents. Gene expression profile in cultures from TH-eGFP mice showed that the TH+ neurons also express several other genes associated with DA release. Nicotine also upregulated ACh-induced currents in DA neurons by approximately 2.5-fold. Thus, nicotine, at a concentration too low to activate an appreciable fraction of plasma membrane nAChRs, induces two sequelae of pharmacological chaperoning in the ER: UPR suppression and nAChR upregulation. Therefore, one mechanism of neuroprotection by nicotine is pharmacological chaperoning, leading to UPR suppression. Measuring this pathway may help in assessing neuroprotection. SIGNIFICANCE STATEMENT: Parkinson's disease (PD) cannot yet be cured or prevented. However, many retrospective epidemiological studies reveal that PD is diagnosed less frequently in tobacco users. Existing programs attempting to develop nicotinic drugs that might exert this apparent neuroprotective effect are asking whether agonists, antagonists, partial agonists, or channel blockers show the most promise. The underlying logic resembles the previous development of varenicline for smoking cessation. We studied whether, and how, nicotine produces neuroprotective effects in cultured dopaminergic neurons, an experimentally tractable, mechanistically revealing neuronal system. We show that nicotine, operating via nicotinic receptors, does protect these neurons against endoplasmic reticulum stress. However, the mechanism is probably "inside-out": pharmacological chaperoning in the endoplasmic reticulum. This cellular-level insight could help to guide neuroprotective strategies.
RATIONALE: Continuous performance tests (CPTs) are widely used to assess attentional processes in a variety of disorders including Alzheimer's disease and schizophrenia. Common human CPTs require discrimination of sequentially presented, visually patterned 'target' and 'non-target' stimuli at a single location. OBJECTIVES: The aims of this study were to evaluate the performance of three popular mouse strains on a novel rodent touchscreen test (rCPT) designed to be analogous to common human CPT variants and to investigate the effects of donepezil, a cholinesterase inhibitor and putative cognitive enhancer. METHODS: C57BL/6J, DBA/2J and CD1 mice (n = 15-16/strain) were trained to baseline performance using four rCPT training stages. Then, probe tests assessed the effects of parameter changes on task performance: stimulus size, duration, contrast, probability, inter-trial interval or inclusion of flanker distractors. rCPT performance was also evaluated following acute administration of donepezil (0-3 mg/kg, i.p.). RESULTS: C57BL/6J and DBA/2J mice showed similar acquisition rates and final baseline performance following rCPT training. On probe tests, rCPT performance of both strains was sensitive to alteration of visual and/or attentional demands (stimulus size, duration, contrast, rate, flanker distraction). Relative to C57BL/6J, DBA/2J mice exhibited (1) decreasing sensitivity (d') across the 45-min session, (2) reduced performance on probes where the appearance of stimuli or adjacent areas were changed (size, contrast, flanking distractors) and (3) larger dose- and stimulus duration-dependent changes in performance following donepezil administration. In contrast, CD1 mice failed to acquire rCPT (stage 3) and pairwise visual discrimination tasks. CONCLUSIONS: rCPT is a potentially useful translational tool for assessing attention in mice and for detecting the effects of nootropic drugs.
Considerable attention has recently been paid to the N-Myc downstream-regulated gene (NDRG) family because of its potential as a tumor suppressor in many human cancers. Primary amino acid sequence information suggests that the NDRG family proteins may belong to the alpha/beta-hydrolase (ABH) superfamily; however, their functional role has not yet been determined. Here, we present the crystal structures of the human and mouse NDRG2 proteins determined at 2.0 and 1.7 A resolution, respectively. Both NDRG2 proteins show remarkable structural similarity to the ABH superfamily, despite limited sequence similarity. Structural analysis suggests that NDRG2 is a nonenzymatic member of the ABH superfamily, because it lacks the catalytic signature residues and has an occluded substrate-binding site. Several conserved structural features suggest NDRG may be involved in molecular interactions. Mutagenesis data based on the structural analysis support a crucial role for helix alpha6 in the suppression of TCF/beta-catenin signaling in the tumorigenesis of human colorectal cancer, via a molecular interaction.
Title: Identification of male specimens of the Culex pipiens complex (Diptera: Culicidae) in the hybrid zone using morphology and molecular techniques Sanogo YO, Kim CH, Lampman R, Halvorsen JG, Gad AM, Novak RJ Ref: Journal of Medical Entomology, 45:203, 2008 : PubMed
The identification of the members of the Culex pipiens L. complex in arbovirus surveillance programs relies heavily on the use of morphology. In this work, we studied Cx. pipiens complex male mosquitoes collected from nine different locations, from northern, southern, and the hybrid zone sites in North America; Cairo, Egypt; and Nairobi, Kenya. Specimens were identified using DV/D ratio and also using amplification of the acetylcholinesterase (ACE.2) gene by both conventional and real-time polymerase chain reaction, and examination of the CQ11 locus. Consistent with previous findings, the morphological and molecular identifications did not always agree, particularly in regions of extensive introgression. There was an increased frequency of hybrid forms in late summer and early fall in Champaign Co., IL, that is north of the previously described Cx. pipiens complex hybrid zone. This represents an expansion of the North American hybrid zone. The biological and epidemiological relevance of the high degree of introgression and the late season increase in the proportion of intermediate forms is discussed.
Title: A real-time TaqMan polymerase chain reaction for the identification of Culex vectors of West Nile and Saint Louis encephalitis viruses in North America Sanogo YO, Kim CH, Lampman R, Novak RJ Ref: American Journal of Tropical Medicine & Hygiene, 77:58, 2007 : PubMed
In North America, West Nile and St. Louis encephalitis viruses have been detected in a wide range of vector species, but the majority of isolations continue to be from pools of mixed mosquitoes in the Culex subgenus Culex. Unfortunately, the morphologic identification of these important disease vectors is often difficult, particularly in regions of sympatry. We developed a sensitive real-time TaqMan polymerase chain reaction assay that allows reliable identification of Culex mosquitoes including Culex pipiens pipiens, Cx. p. quinquefasciatus, Cx. restuans, Cx. salinarius, Cx. nigripalpus, and Cx. tarsalis. Primers and fluorogenic probes specific to each species were designed based on sequences of the acetylcholinesterase gene (Ace2). Both immature and adult mosquitoes were successfully identified as individuals and as mixed species pools. This identification technique provides the basis for a rapid, sensitive, and high-throughput method for expounding the species-specific contribution of vectors to various phases of arbovirus transmission.
Title: Pharmacological characterization of orally active cholinesterase inhibitory activity of Prunus persica L. Batsch in rats Suh SJ, Koo BS, Jin UH, Hwang MJ, Lee IS, Kim CH Ref: Journal of Molecular Neuroscience, 29:101, 2006 : PubMed
Prunus persica L. Batsch water extract (PPE) is a potent acetylcholinesterase (AChE) inhibitor screened for the treatment of Alzheimer's disease. The effects of oral administration of the PPE were examined with comparison of those of selective butyrylcholinesterase inhibitors of 9-amino-1,2,3,4-tetrahydroacridine hydrochloride (tacrine) and tetraidopropylpyrophosphoramide (iso-OMPA) and a selective AChE inhibitor, donepezil, on the cholinesterase activity in the brain and plasma of rats. After the sequential solvent fractionation of the methanol extract of P. persica L. Batsch, the highest inhibitory fraction was that of chloroform (75%). The concentration that was required for 50% enzyme inhibition (IC(50) value) was 5.6 microg/mL for the chloroform fraction. Oral administration of PPE or tacrine caused a dose-dependent inhibition of brain and plasma cholinesterase activities. The ID(50) values of these compounds for brain cholinesterase activity were 2.7 g/kg and 8.9 mg/kg, respectively. On the other hand, the ID(50) values for plasma cholinesterase activity were 18.6 g/kg and 27.5 mg/kg, respectively. Thus, the ratios of the ID(50) (plasma < brain) were 6.0 and 3.1, respectively. These results suggest that orally administered PPE satisfactorily penetrates into the brain and inhibits cholinesterase there and that PPE is a potent inhibitor of brain cholinesterase in comparison with plasma cholinesterase in vivo.
The rumen represents the first section of a ruminant animal's stomach, where feed is collected and mixed with microorganisms for initial digestion. The major gas produced in the rumen is CO(2) (65.5 mol%), yet the metabolic characteristics of capnophilic (CO(2)-loving) microorganisms are not well understood. Here we report the 2,314,078 base pair genome sequence of Mannheimia succiniciproducens MBEL55E, a recently isolated capnophilic Gram-negative bacterium from bovine rumen, and analyze its genome contents and metabolic characteristics. The metabolism of M. succiniciproducens was found to be well adapted to the oxygen-free rumen by using fumarate as a major electron acceptor. Genome-scale metabolic flux analysis indicated that CO(2) is important for the carboxylation of phosphoenolpyruvate to oxaloacetate, which is converted to succinic acid by the reductive tricarboxylic acid cycle and menaquinone systems. This characteristic metabolism allows highly efficient production of succinic acid, an important four-carbon industrial chemical.
Title: A water extract of Curcuma longa L. (Zingiberaceae) rescues PC12 cell death caused by pyrogallol or hypoxia/reoxygenation and attenuates hydrogen peroxide induced injury in PC12 cells Koo BS, Lee WC, Chung KH, Ko JH, Kim CH Ref: Life Sciences, 75:2363, 2004 : PubMed
A number of studies indicate that free radicals are involved in the neurodegeneration in Alzheimer's disease (AD). The role of superoxide anion (O2*-) in neuronal cell injury induced by reactive oxygen species (ROS) was examined in PC12 cells using pyrogallol (1,2,3-benzenetrior), a donor to release O2*-. Pyrogallol induced PC12 cell death at concentrations, which evidently increased intracellular O2*-, as assessed by O2*- sensitive fluorescent precursor hydroethidine (HEt). A water extract of Curcuma longa L. (Zingiberaceae) (CLE), having O2*- scavenging activity rescued PC12 cells from pyrogallol-induced cell death. Hypoxia/reoxygenation injury of PC12 cells was also blocked by CLE. The present study was also conducted to examine the effect of CLE on H2O2 -induced toxicity in rat pheochromocytoma line PC12 by measuring cell lesion, level of lipid peroxidation and antioxidant enzyme activities. Following a 30 min exposure of the cells to H2O2 (150 microM), a marked decrease in cell survival, activities of glutathione peroxidase and catalase as well as increased production of malondialdehyde (MDA) were found. Pretreatment of the cells with CLE (0.5-10 microg/ml) prior to H2O2 exposure significantly elevated the cell survival, antioxidant enzyme activities and decreased the level of MDA. The above-mentioned neuroprotective effects are also observed with tacrine (THA, 1 microM), suggesting that the neuroprotective effects of cholinesterase inhibitor might partly contribute to the clinical efficacy in AD treatment. Further understanding of the underlying mechanism of the protective effects of these radical scavengers reducing intracellular O2*- on neuronal cell death may lead to development of new therapeutic treatments for hypoxic/ischemic brain injury.
Title: Comparative effect of Prunus persica L. BATSCH-water extract and tacrine (9-amino-1,2,3,4-tetrahydroacridine hydrochloride) on concentration of extracellular acetylcholine in the rat hippocampus Kim YK, Koo BS, Gong DJ, Lee YC, Ko JH, Kim CH Ref: J Ethnopharmacol, 87:149, 2003 : PubMed
Prunus persica L. BATSCH seed-water extract (PPE) has been used in the treatment of the degenerative disorders, such as hypermenorrhea and dysmenorrhea, in Taiwan, China, Japan and Korea. In this study, the effects of oral administration of PPE on the extracellular acetylcholine concentration in the hippocampus of rats were evaluated, and compared to that of tacrine (9-amino-1,2,3,4-tetrahydroacridine hydrochloride), a well-known and centrally acting acetylcholinesterase (AChE) inhibitor, which had been developed for the treatment of Alzheimer's disease. We measured the inhibition of brain AChE. PPE at 2.5g/kg and tacrine at 5mg/kg showed significant effects for more than 6h. At these doses, the maximum increases were observed at about 1.5h after administration of PPE, and at about 2h with tacrine, and were 454 and 412% of the pre-level, respectively. The results suggest that oral administration of PPE and tacrine increases acetylcholine concentration in the synaptic cleft of the hippocampus mostly through AChE inhibition, and that PPE has a potent and long-lasting effect on the central cholinergic system.
Title: Pyridostigmine cotreatment for controlled ovarian hyperstimulation in low responders undergoing in vitro fertilization-embryo transfer Kim CH, Chae HD, Chang YS Ref: Fertil Steril, 71:652, 1999 : PubMed
OBJECTIVE To investigate the effect of pyridostigmine, an acetylcholinesterase inhibitor, as cotreatment for controlled ovarian hyperstimulation (COH) in low responders.
DESIGN:
Randomized, double-blind, placebo-controlled study.
SETTING:
A reproductive medicine unit in a university hospital.
PATIENT(S):
Seventy infertile women with a history of low ovarian response to COH using a GnRH agonist as part of a long stimulation protocol in previous IVF-ET cycles.
INTERVENTION(S):
Sixty milligrams of pyridostigmine or placebo was administered orally twice daily from the first day of COH until the day of hCG injection in patients undergoing IVF-ET cycles.
MAIN OUTCOME MEASURE(S):
In vitro fertilization results, pregnancy outcome, and serum and intrafollicular concentrations of GH and insulin-like growth factor-1.
RESULT(S):
Pyridostigmine cotreatment was associated with significant decreases in the amount of gonadotropins and the duration of stimulation required. The clinical pregnancy rate was higher in the pyridostigmine group, but this difference was not statistically significant (25.7% vs. 11.4%). The serum GH level on the day of hCG injection was significantly higher in the pyridostigmine group than in the placebo group. Follicular fluid concentrations of GH and insulin-like growth factor-1 were significantly higher in the pyridostigmine group.
CONCLUSION(S):
This study suggests that pyridostigmine cotreatment for COH could affect the serum and intrafollicular GH and insulin-like growth factor-1 concentrations and, hence, improve the ovarian response to COH and the results of IVF in low responders undergoing IVF-ET.
Title: [The nervous system of Fibricola seoulensis by acetylcholinesterase histochemistry]. [Korean] Cheon EW, Kim CH Ref: Korean Journal of Parasitology, 31:321, 1993 : PubMed
F. seoulensis were obtained from artificially infected albino rats at 3, 4, 5, 6, 7 days after infection. The worms and metacercariae were washed in physiological saline solution, and fixed with 10% neutral formalin. The acetylcholinesterase (AchE) stained by enzyme histochemistry using acetylthiocholine iodide as substrate. Eserine, iso-OMPA and BW284C51 were used as inhibitors of AchE. The nervous system consists of three pairs longitudinal nerve trunks interconnected with excretory plexus in posterior half, and pharynx and oral sucker in anterior half of metacercariae and adults. The longitudinal nerve trunks are interconnected with transverse commissures and numerous circular commissures. Considerable numbers of circular commissures are interconnected with longitudinal nerve trunks lying on the surface of the worms. At each stage of juvenile worms, AchE and nonspecific cholinesterase activities were observed in the oral sucker, ventral sucker, pharynx and nerve system. Isozymes of AchE in F. seoulensis were separated into the two bands, 69 kDa and 132 kDa. The major band was 69 kDa.
