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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetaldehyde, the first product of ethanol metabolism, has previously been shown to form potentially harmful adducts with various proteins. The aim of this study was to investigate whether acetaldehyde--either exogenous or metabolically derived--binds to gastric mucosal proteins. Homogenized rat gastric mucosa was incubated with various concentrations of radiolabeled acetaldehyde or ethanol for different time periods. Acetaldehyde-protein adducts were determined by a liquid scintillation counter. In addition, mucosa was incubated with nonlabeled ethanol, and the acetaldehyde formed was measured by using headspace gas chromatography. Incubation of gastric mucosa with (14C)-acetaldehyde led to a concentration- and time-dependent radiolabeling of mucosal proteins. Formation of acetaldehyde adducts occurred relatively rapidly within 30 minutes and even at low acetaldehyde levels (5 micromol/L). Stable adducts represented 77% +/- 5% (mean +/- SEM) of the total adducts formed. In the presence of ethanol, acetaldehyde production and adduct formation took place in a concentration- and time-dependent manner. 4-Methylpyrazole and sodium azide inhibited acetaldehyde production to 7% +/- 1% of control and decreased the amount of acetaldehyde adducts to 55% +/- 8%. Enhanced acetaldehyde formation (to 420% +/- 50%) was clearly reflected in increased adduct formation (550% +/- 110%). In conclusion, both exogenous and endogenous acetaldehyde binds to gastric mucosal proteins in vitro. Gastric mucosal acetaldehyde production and the consequent adduct formation could be a pathogenetic factor behind ethanol-associated gastric injury.
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PMID:Binding of acetaldehyde to rat gastric mucosa during ethanol oxidation. 917 29

Non-coating fixation methods, in particular the tannic acid/arginine/osmium tetroxide procedure, are employed for a number of reasons on the guinea-pig organ of Corti hair cell stereocilia glycocalyx and the imprints of the stereocilia at the bottom side of the tectorial membrane, and on the rat and cat intestinal epithelial microvilli glycocalyx and mucus-producing goblet cells. These methods are used firstly to confirm that non-coating prepared specimens can be embedded for TEM observation at 60-100 kV without loss of detail information, and these images can be compared with cryo-FE-SEM images of the same structure/tissue. Secondly, they show that specimens treated according non-coating techniques become optimally preserved and electrically conductive, so that no external conductive coating is required. In this way a comparison of images of subsequent fresh fracture faces is possible without a decrease in information on detail, which otherwise could happen after subsequent coating layers required after standard fixation. Thirdly, they show that non-coating methods can be used quite well with low accelerating voltages because the osmium-tannic acid complex in the specimen surface produces a large number of backscattered and secondary electrons in the surface layer, showing in particular surface phenomena. Fourthly, they show that with an optimal non-coating preservation, in combination with a well-balanced pre-fixation mixture, preparation artefacts due to extraction and even dehydration and drying are minimized. This is compared with images of the organ of Corti hair cells treated with a so-called three-aldehyde pre-fixation mixture, which causes disrupted stereocilia to cling onto the bottom side of the tectorial membrane.
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PMID:Non-coating fixation techniques or redundancy of conductive coating, low kV FE-SEM operation and combined SEM/TEM of biological tissues. 1004 19

Alcohol abuse is commonly associated with reduced bone mass and osteoporosis as a consequence of both systemic and direct cellular effects. To clarify some of the pathways by which alcohol exerts its actions directly on bone cells, we investigated the formation of early osteoblast progenitors (colony-forming units for fibroblasts; CFU-F) in long-term murine and human bone marrow cultures exposed to ethanol and to its main metabolite, acetaldehyde. In murine bone marrow cultures, obtained from Swiss female mice, ethanol inhibited CFU-F formation (maximal reduction +/- SEM: 50 +/- 2%; p < 0.01) at concentrations ranging from 0.04% to 0.6% that are similar to those reached in vivo in alcoholics. Acetaldehyde strongly reduced CFU-F formation at concentrations of 0.004% and 0.02%, and completely abolished it at the dose of 0.06%. Similarly, ethanol (at concentrations > or =0.02%) and acetaldehyde (from 0.004% to 0.06%) significantly decreased the number of CFU-F in human bone marrow cultures; the mean reduction observed with ethanol was 63 +/- 12% (p < 0.05), whereas acetaldehyde completely prevented CFU-F formation at the concentration of 0.06%. These in vitro observations were confirmed by the in vivo findings that the CFU-F formation in bone marrow cultures from nine young, chronic, noncirrhotic alcoholics was significantly reduced (70 +/- 15%), compared with seven age-matched normal subjects (p < 0.01). In addition, acetaldehyde inhibited cell proliferation in human osteoblastic cells (MG-63 and HOBIT cell lines), whereas ethanol reduced proliferation only in MG-63 cells. Our results indicate that ethanol and acetaldehyde may directly inhibit the osteoblastogenic potential of the bone marrow, and this effect may contribute to the decreased bone formation observed in alcoholics.
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PMID:Ethanol and acetaldehyde inhibit the formation of early osteoblast progenitors in murine and human bone marrow cultures. 1006 72

Bronchial responsiveness to acetaldehyde, a main factor in alcohol-induced bronchoconstriction, and methacholine were compared between 10 subjects with alcohol-induced bronchoconstriction and 16 asthmatic subjects without alcohol sensitivity. In the alcohol-sensitive group, the geometric mean (geometric SEM (GSEM)) of the provocative concentration of methacholine (PC20,meth) and acetaldehyde (PC20,acet) causing a 20% fall in forced expiratory volume in one second were 0.947 mg x mL(-1) (GSEM 0.139) and 21.0 mg x mL(-1) (GSEM 0.112), respectively, which were not significantly different from those in the nonalcohol-sensitive group, which were 0.634 mg x mL(-1) (GSEM 0.115) and 31.7 mg x mL(-1) (GSEM 0.077), respectively. The ratio of airway responsiveness to acetaldehyde relative to methacholine (log PC20,acet/PC20,meth) was 1.345+/-0.093 (mean+/-SEM) in the alcohol-sensitive group, which was significantly different from the value of 1.699+/-0.059 in the nonalcohol-sensitive group (p=0.0025). A significant correlation was observed between PC20,meth and PC20,acet in both the alcohol-sensitive group (r=-0.742, p=0.0115) and nonsensitive group (r=0.882, p<0.0001). In conclusion, the airways of asthmatic subjects with alcohol-induced bronchoconstriction have a selective hyperresponsiveness to acetaldehyde.
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PMID:Increased airway responsiveness to acetaldehyde in asthmatic subjects with alcohol-induced bronchoconstriction. 1048 23

Described is the first catalytic, asymmetric synthesis of (-)-podophyllotoxin and its C(2)-epimer, (-)-picropodophyllin. Asymmetry is achieved via the enzymatic desymmetrization of advanced meso diacetate 20, through PPL-mediated ester hydrolysis. A second key feature of the synthesis is the strategically late introduction of the highly oxygenated natural ring E through an arylcopper species. The successful implementation of this approach augers well for the introduction of other functionalized rings E for future SAR work. The synthesis begins from piperonal, which is fashioned into isobenzofuran (IBF) precursor 14 in three steps (bromination, acetalization, and halogen-metal exchange/hydroxymethylation). Interestingly, treatment of 14 with HOAc in commerical dimethyl maleate (contains 5% dimethyl fumarate) leads to a nearly equimolar mixture of fumarate- (15) and maleate-IBF Diels-Alder adducts (16 and 17), indicating that IBF 11 reacts about 15 times faster with dimethyl fumarate than with dimethyl maleate. With scrupulously pure dimethyl maleate a 2.8:1 endo:exo mixture of maleate DA adducts is still obtained. On the other hand, the desired meso diester 16 is obtained pure and in nearly quantitative yield by employing neat dimethyl acetylene dicarboxylate as the dienophile, followed by catalytic hydrogenation. Reduction (LiAlH(4)) of 16 provides meso diol 19, which is then treated with Ac(2)O, BzCl, and PhCH(2)COCl to provide the corresponding meso diesters, 20-22. Screening of these meso benzoxabicyclo[2.2.1]heptyl substrate candidates across a battery of acyl transfer enzymes leads to an optimized match of diacetate 20 with PPL. Even on 10-20 g scales, asymmetry is efficiently introduced here, yielding the key chiral intermediate, monoacetate 25 (66% isolated yield, 83% corrected yield, 95% ee). Protecting group manipulation and oxidation (Swern) provide aldehyde 27b, which undergoes efficient retro-Michael ring opening to produce dihydronaphthalene 30, in which the C(3) and C(4) stereocenters are properly set. Following several unsuccessful approaches to the intramolecular delivery of ring E (via Claisen rearrangement, Heck-type cyclization, or radical cyclization), a highly diastereoselective, intermolecular conjugate addition of the arylcopper reagent derived from (3,4,5-trimethoxy)phenylmagnesium bromide and CuCN to acyl oxazolidinone 50 was developed (85% yield, only the required alpha-stereochemistry at C(1) is observed). The conjugate addition product is converted to (-)-picropodophyllin in two steps (lactonization, SEM deprotection) or to (-)-podophyllotoxin, in three steps, through the introduction of a C(2)-epimerization step, under Kende conditions, prior to the final conjugate addition.
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PMID:Enzyme-assisted asymmetric total synthesis of (-)-podophyllotoxin and (-)-picropodophyllin. 1081 19

The membrane system of the rat parietal cells in the resting state and after stimulation with tetragastrin (gastrin) was examined by ultra-high-resolution scanning electron microscopy after removal of the cytoplasmic matrix by the aldehyde-osmium-DMSO-osmium procedure. The intracellular canaliculus was lined with numerous microvilli. Viewed from the cytoplasmic side, the intracellular canaliculi appeared as an arborized system of cactus-like structures with numerous holes about 100 nm in diameter corresponding to the basal openings of the microvilli. The intracellular canaliculi were more developed after gastrin stimulation than in the resting state. In resting cells, most of the tubulovesicles were isolated, 100-200 nm in diameter, spherical or tubular in shape. After gastrin stimulation, these structures were interconnected by slender tubules of about 30 nm in diameter forming together tubulovesicular network. Stereo SEM views clearly demonstrated that the tubulovesicular network was connected with the intracellular canaliculus by the slender connecting tubulus. The increase in the canalicular membrane area and the depletion of tubulovesicles is explained by the transfer of the tubulovesicular membrane to the intracellular canaliculus. In the resting parietal cell, the microvilli are slender and their interior is packed with microfilaments. After gastrin stimulation, the microvilli are swollen and their interior is edematous. These morphological changes seem to indicate the accumulation of fluid in the microvilli after gastrin stimulation.
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PMID:Ultra-high-resolution scanning electron microscopic studies on the membrane system of the rat parietal cells after tetragastrin stimulation. 1132 16

A total synthesis of the pseudopterolides, kallolide A (36) and kallolide A acetate (35), has been achieved. The racemic forms were prepared from the syn adduct 20 of furan 13 and stannane 17 (BF(3).OEt(2)-promoted addition) via the 15-membered propargylic allylic ether 25. [2,3]Wittig ring contraction led to the cis, anti, cis product 26. Alcohol 26 was transformed to butenolide 34 with net retention of configuration by Pd(PPh(3))(4)-catalyzed carbonylation of the mesylate 27 and ensuing AgNO(3)-catalyzed cyclization of the derived allenic acid 29. Solvolysis of the SEM ether (at C2) 34 in acetic acid or aqueous t-BuOH afforded racemic kallolide A acetate (35) and kallolide A (36), respectively, with inversion of stereochemistry by an S(N)1 process. Key elements of stereocontrol, including the steric outcome of the [2,3]Wittig ring contraction, the allenic ester isomerization, and the solvolysis reactions, were predicted from molecular mechanics calculations. The C8 and C2 epimers 45 and 46 of the cis, anti, cis kallolide A SEM ether precursor 34 were also prepared. The synthetic route originated from the anti adduct 19 of aldehyde 13 and the allylic chloride 16 and CuCl (cat), HSiCl(3), and i-Pr(2)NEt. Adduct 19 was subjected to the same sequence as the syn counterpart 20 to produce the trans, anti, cis [2,3]Wittig ring contraction product 42. The derived allenoate 44 afforded a 1:1 mixture of butenolides 45 and 46 upon sequential treatment with TBAF and AgNO(3). Finally, the natural enantiomer (+)-36 of kallolide A was synthesized from the enantioenriched syn adduct (+)-20, prepared by addition of allylic stannane 17 to aldehyde 13 promoted by a modified chiral acyloxyborane Lewis acid.
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PMID:Stereoselective Total Synthesis of the Pseudopterolide Kallolide A. 1167

High alcohol intake is an independent risk factor for upper gastrointestinal (GI)-tract cancers. There is increasing evidence that acetaldehyde, the first metabolite of ethanol, might be responsible for ethanol-associated carcinogenesis. Especially among Asian heavy drinkers with the ALDH2-deficiency gene, i.e., a genetic inability to remove acetaldehyde, the risk of digestive tract cancers is markedly increased. Local acetaldehyde production from ethanol either by oral microbes, mucosal cells or salivary glands is a plausible carcinogenic agent in the saliva. The aim of our study was to examine whether is it possible to bind carcinogenic acetaldehyde from saliva with L-cysteine, which is slowly released from a special buccal tablet. Nine healthy male volunteers took part in our study, and each subject served as his own control. A placebo or L-cysteine-containing tablet was fastened under the upper lip. Thereafter the volunteers ingested 0.8 g/kg of body weight of 10% (v/v) ethanol, and saliva samples were collected at 20 min intervals for 320 min. Salivary acetaldehyde and ethanol levels were analysed by headspace gas chromatography. The mean reduction of acetaldehyde concentration of the saliva with the L-cysteine tablet compared to placebo was 59% (CL(95%) 43%, 76%). Area under the curve (AUC(0-320min)) with the L-cysteine and placebo tablet were 54.3 +/- 11 microM x hr and 162 +/- 34.2 microM x hr (mean +/- SEM), respectively (p = 0.003). After alcohol intake, up to two-thirds of carcinogenic acetaldehyde can be removed from saliva with a slow-releasing buccal L-cysteine drug formulation. Thus, a buccal cysteine tablet could potentially be used to prevent upper GI-tract cancers, especially among high-risk individuals.
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PMID:Removal of acetaldehyde from saliva by a slow-release buccal tablet of L-cysteine. 1177 89

Specific effects of the cytotoxic secondary lipid oxidation product, 4-hydroxynonenal (10(-8)-10(-4) M), on intact sheets of rat jejunum were measured as changes in short circuit current (delta(I)sc) following cumulative addition to either the mucosal or serosal side, using the analogous aldehyde, nonenal, as reference. 4-Hydroxynonenal stimulated I(sc) from the serosal side (maximal delta(I)sc = 27.2 +/- 3.5 microA/cm2, mean +/- SEM, N = 32) while nonenal stimulated I(sc) primarily from the mucosal side (maximal delta(I)sc = 16.2 +/- 3.4 microA/cm2, N = 20). Inhibition by 100 microM bumetanide (4-hydroxynonenal: 88.9 +/- 3.0%, N = 6, p < 0.05, nonenal: 69.3 +/- 2.9%, N = 6, P < 0.05) indicated chloride secretion. Nonenal-induced delta(I)sc was inhibited (72.5 +/- 1.2%, N = 8, P < 0.05) by a combination of nordihydroguaiaretic acid (100 microM) and piroxicam (10 microM), while 4-hydroxynonenal-induced delta(I)sc, was abolished by piroxicam (N = 8, P < 0.001) and inhibited by 1 microM tetrodotoxin (69.8 +/- 9.7%, N = 6, P < 0.001). These data indicate that 4-hydroxynonenal stimulates chloride secretion mediated by prostaglandins and the enteric nervous system. The site of action (serosal) being opposite to the reference aldehyde.
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PMID:Oxidant-stimulated chloride secretion in rat jejunum in vitro is mediated by eicosanoids. 1275 76

Antigen-sampling M cells are found in the follicle-associated epithelium above organized lymphoid tissue in many mucosae. They play a key role in initiating the mucosal immune response and act as a site of entry for opportunistic pathogens. This study investigates the presence of M cells in the Guinea pig conjunctiva. Maackia amurensis leukoagglutinin I and II (MAL-I and MAL-II) were identified as potential conjunctival M cell markers based on a screening of 12 lectins and 5 carbohydrate epitope antibodies on aldehyde-fixed follicles. Biotinylated or fluorescein-conjugated MAL-I was then instilled into conjunctival sacs in vivo for 15-60 min. Specimens were assessed by epi-fluorescence stereomicroscopy, confocal scanning laser microscopy and transmission and scanning electron microscopy (TEM and SEM). Selective labelling of a subset of epithelial cells overlying lymphoid follicles was observed following in vivo exposure to MAL-I. MAL-I labelling was restricted to cells with sparse, irregular microvilli. Cells preferentially labelled with MAL-I were found to internalize the lectin during a 60 min in vivo exposure. MAL-I was transcytosed to basolateral membranes of cells filled with intracellular vesicles during a 45 min in vivo incubation. This study demonstrates that the Guinea pig conjunctiva contains a cell with morphological and functional characteristics of antigen-sampling M cells.
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PMID:Conjunctival M cells selectively bind and translocate Maackia amurensis leukoagglutinin. 1578 Dec 82


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