Formaldehvde and Dhenol exposure during an anatom; dissecdon course: a Dossible source of IgE-mediated sensitizkion?

The sensitizing potency of formaldehyde and phenol exposure during 4 weeks of an anatomy dissection course was assessed in 45 medical students. Specific IgE against formaldehyde by RAST and by ELISA and specific IgE against phenol by ELISA were assessed before and after the course. At the start of the course. symptoms, type I allergy, respiratory diseases, and smoking habits were noted. At the end of the course, only symptoms experienced during the dissection lessons were assessed. Indoor formaldehyde levels were measured continuously. The mean indoor formaldehyde level was 0.124±0.05 ppm, with a minimum of 0.059 ppm and a maximum of 0.219 ppm. Specific IgE against formaldehyde or phenol was found in none of the subjects at the beginning of the course, and no student showed specific IgE against formaldehyde or phenol after the course. Assessment of primarily irritant symptoms during the lessons revealed itch and paraesthesia of hands in 33/45 students (P<0.00005), headache in 15/45 students, burning eyes in 13/45 students (P<0.02), dizziness in 8/45 students (P<0.008), sneezing in 4/45 students, epistaxis in 2/45 students, and shortness of breath in 1/45 students. According to our data, l-month exposure to formaldehyde and phenol during an anatomy dissection course does not induce specific IgE against formaldehyde or phenol.     

Condensation polymerization of triphenylamine with carbonyl compounds

Triphenylamine (TPA) was reacted with carbonyl compounds such as formaldehyde, butyraldehyde, benzaldehyde, and acetone in the presence of an acid catalyst. ¹H and ¹³C NMR spectra revealed that the carbonyl compounds react only at the p-position of TPA. The reactivity of formaldehyde with TPA is lower than that with phenol. If equal molar amounts of formaldehyde are reacted, however, TPA condensation proceeds to high molecular weight polymers, while phenol provides only low molecular weight compounds (up to 1 000). TPA-aldehyde polymers have glass transition temperatures in the range of 135 – 176°C. These polymers show good solubility and sufficient stability after film formation.     

Preservation of neural tissue with a formaldehyde‐free phenol‐based embalming protocol

The adverse effects formaldehyde fixation has on tissues both gross anatomically and histologically are well documented. Consequently, researchers are seeking alternative embalming techniques that better preserve in vivo characteristics of tissues. Phenol‐based embalming is one method that has shown promise in its ability to adequately preserve the in vivo qualities of tissues through preliminary explorations at the gross anatomical level. The literature on phenol‐based embalming is currently scarce, especially with regard to its effects on tissues at the microscopic level. For the current study we aimed to document the histologic effects of a formaldehyde‐free phenol‐based embalming solution on neural tissue, with the hope of providing novel insight into the effects of soft‐embalming on tissues at the microscopic level. Cerebral and cerebellar tissue obtained from porcine brains was fixed in phenol‐ and formaldehyde‐based fixatives; the latter served as a control. Fixed samples were processed for histological analysis. The phenol‐based embalming solution provided excellent preservation of the cerebral and cerebellar tissue morphology. Of note was the decrease in separation artifact seen in both tissue types relative to the control tissue, as well as anomalous circular artifacts in the white matter. The results of this study indicate that the phenol‐based embalming solution preserves neural tissue at the histological level, perhaps superiorly in many aspects when compared to the formaldehyde‐fixed samples. Further investigations of both gross anatomy and histology are recommended on the basis of these promising new findings to determine its potential utilities within research and education. Clin. Anat. 32:224–230, 2019. © 2018 Wiley Periodicals, Inc.     

Studies on formaldehyde resins, 19. General base catalysis in hydroxymethylation of melamine with formaldehyde

Hydroxymethylation of melamine with formaldehyde to form N-(hydroxymethyl)melamine (2,4-diamino-6-hydroxymethylamino-1,3,5-triazine) was investigated kinetically by the use of hydrogen phosphate/phosphate buffers in aqueous media at pH 11 ? 12. This reaction was found to follow a general base catalysis which results from the kinetic investigation, showing that the reaction takes place by a concerted mechanism involving base, melamine, and formaldehyde. This mechanism differs from that of the base catalyzed hydroxymethylation of phenol or benzamide with formaldehyde, because the acidic phenol and benzamide easily form their conjugate bases by addition of the basic catalyst in a preceding equilibrium step.     

Photo-oxydation de résines phénoliques

Analytical and kinetic aspects of photo-oxidation in the solid state of phenolic resins (phenolformaldehyde polycondensates) are described. On the basis of Fourier-transform infrared analysis it should be noted that resins contain, in addition to methylene-bridged structures, ether linkages (? CH₂? O? CH₂) between aromatic structures. Photochemistry of the phenolic resins involves two primary processes. Photolysis of the phenolic groups leads to the formation of quinone methide structures and photo-oxidation of the dimethylene ether linkages to hydroperoxy groups which are photo- and thermo-unstable. These hydroperoxy groups are converted into ester and formate groups.     

Exposure to formaldehyde and phenol during an anatomy dissecting course: sensitizing potency of formaldehyde in medical students

BACKGROUND: The sensitizing potency of formaldehyde and phenol during anatomy dissecting was investigated. The objective was to determine whether exposure induces specific IgE or IgG against formaldehyde-albumin or phenol-albumin. METHODS: In 27 medical students, specific IgE against formaldehyde-albumin by RAST plus ELISA and specific IgE against phenol-albumin by ELISA were assessed. In addition, specific IgG against formaldehyde-albumin was assessed in 23 students. Symptoms before and during dissecting were assessed, and indoor formaldehyde and phenol were measured. RESULTS: Mean indoor formaldehyde was 0.265 +/- 0.07 mg/m3, and mean indoor phenol was 4.65 +/- 2.96 mg/m3. Specific IgE/IgG against formaldehyde-albumin was not found at the beginning. Four students developed specific IgE against formaldehyde-albumin (RAST classes of > or =2.0), and all four also had specific IgE in the ELISA, but IgG against formaldehyde-albumin was not found. Specific IgE against phenol-albumin was not seen. Itch and paresthesia of the hands (P<0.00001), dizziness (P<0.008), burning eyes (P<0.01), headache, sneezing, epistaxis, gingival bleeding, oral or pharyngeal itch, and shortness of breath were experienced. CONCLUSIONS: Formaldehyde exposure during dissecting may induce specific IgE, but not IgG, against formaldehyde-albumin. Sensitization did not correlate with symptoms.     

Influence of cytochrome c-deficiency on the energy conservation of whole cells of Acetobacter methanolicus sp. MB 58

The ability of A. methanolicus sp. MB 58 and of a cytochrome c-deficient mutant (A. methanolicus sp. MB 58105) to synthesize ATP by the oxidation of methanol, ethanol, glucose, formate and formaldehyde was investigated. It was found out that cells of the wild type were energized and that cells of the mutant were not energized by the oxidation of ethanol. The energization of cells by the oxidation of glucose, formate and formaldehyde is obviously not influenced by the cytochrome c defect. The results point to a coupling of the alcohol dehydrogenase at cytochrome c, as already postulated in a previous paper for the alcohol and the methanol dehydrogenases of A. methanolicus sp. MB 70. The dehydrogenases responsible for the oxidation of glucose and formate should be coupled to other cytochromes of the respiratory chain. Evidence for the coupling of the formaldehyde dehydrogenase could not be obtained, because it was not possible to differentiate between cytochrome-dependent oxidation of formaldehyde and the NAD⁺-dependent oxidations after fixation of formaldehyde.     

Darstellung von Austauschern mit Kryptanden als Ankergruppen

Four exchangers ( 8, 9, 16, and 17 ) with cryptate forming anchor-groups were prepared and their properties were studied. They were synthesized by the reaction of the cryptate formers 6 and 7 with chloromethylated polystyrene or by condensation of the cryptate formers 14 and 15 with formaldehyde or with formaldehyde/phenol. The exchangers were found to be very resistant towards heat and chemical attack. Their capacities for alkali salts amount to 1,0–1,3 mmol per gram of the air-dried resin.     

Some physical and chemical properties of Bhanja virus

Bhanja virus is acid-labile, relatively thermostable, resistant to trypsin and heparin; a complete inactivation was achieved with chloramine B or formaldehyde, while phenol was ineffective, and UV radiation only partially effective.     

Method for inactivating and fixing unstained smear preparations of mycobacterium tuberculosis for improved laboratory safety

The inactivation of smears that contain Mycobacterium tuberculosis for microscopy before removal of the material from a biosafety cabinet is an important safety factor in preventing the potential transmission of tuberculosis to laboratory workers. The fixing and inactivating properties of heat flaming, 70% ethanol, and 1, 3, and 5% phenol in ethanol for smears containing M. tuberculosis were investigated. Heat flaming failed to inactivate the smear material, whereas 5% phenol in ethanol successfully fixed and inactivated all smears containing M. tuberculosis both from concentrated sputum samples and from culture material.     

Non-covalent nano-adducts of co-poly(ester amide) and poly(ethylene glycol): preparation, characterization and model drug-release studies

Biodegradable, biocompatible poly(ester amide)s (co-PEAs), composed of amino acids, fatty diols and carboxylic acids, have been synthesized. To improve the performance of co-PEAs in Federal Drug Administration-approved solvents such as water and ethanol, these polymers were complexed with poly(ethylene glycol) (PEG) of 10 kDa molecular mass have been prepared by solution blending. The non-covalent adducts were purified by precipitation into hexanes. Co-PEAs are soluble in organic solvents but are insoluble in water and ethanol; however, the co-PEA/PEG (0.8:1, w/w) adducts are soluble in ethanol and slightly soluble in water. 2D-NOESY NMR spectroscopy suggests that the non-covalent adducts are held together by multiple non-covalent interactions between the -CH2- groups of the two polymers (co-PEA and PEG). Differential scanning calorimetry studies indicate that the two polymers are interacting in the non-covalent adducts; the thermal properties of the adducts are different from those of the pure polymers. The solid-state adduct structures have been determined by atomic force microscopy (AFM). By one sample preparation method, nanoscale pancake-like structures were observed with an average diameter of 260 nm and an average height of 16 nm. Films of co-PEAs and (co-PEA)/PEG adducts containing Rhodamine B Base (RhBB), a model hydrophobic drug, were prepared. From the adduct/RhBB film containing 3% RhBB, 20% of the total RhBB was released within the first 2 h. Film and adduct composition may be varied to obtain different release profiles. The studies reported here demonstrate that non-covalent conjugation is a relatively easy and effective approach in developing new materials for application as biomaterials.     

Influences of DNA isolation and RNA contamination on carcinogen-DNA adduct analysis by 32P-postlabeling

³²P-Postlabeling is a widely applied assay for the analysis of carcinogen-DNA adducts. Optimization of most steps in this assay has been given attention, but influences of DNA isolation and DNA purity on adduct quantitation have not been investigated systematically. In this study, DNA was isolated from human lymphocytes exposed to benzo[a]pyrene (B[a]P, 10 μM) for 18 hr and from liver of rats i.p.-treated with B[a]P (10 mg/kg body weight) using two different DNA isolation methods: a phenol-extraction and a salting-out procedure. Subsequently, DNA was analysed by nuclease P1 (NP1) or butanol-enriched ³²P-postlabeling. Influences of RNA contamination were studied by labeling RNA isolated from in vitro exposed lymphocytes. In the in vitro experiment, DNA adduct levels were significantly higher using the salting-out procedure (63.2 ± 13.7 adducts per 10⁸ nucleotides, n = 9) as compared with the phenol-extraction (14.3 ± 0.8). RNA was ∼4 times less efficiently labeled as compared to DNA. Nonetheless, RNA contamination of DNA samples may result in an overestimation of DNA adduct levels when butanol enrichment is used, because RNA adduct levels seemed to be substantially higher than DNA adduct levels in the same cells. DNA adduct analysis by nuclease P1 enrichment is probably less affected, since RNA adducts appeared to be NP1 sensitive. In vivo, three different adducts were found by NP1 enriched ³²P-postlabeling in the liver of B[a]P-exposed rats. Again, DNA adduct levels were significantly higher using salting out as compared to phenol extraction for the adduct which comigrated with the BPDE-DNA adduct standard (adduct 1) and an unknown adduct (adduct 2). However, the results were the opposite for another B[a]P-derived DNA adduct (adduct 3). Our results suggest that differences in DNA isolation procedures as well as RNA contamination influence quantitative DNA adduct analysis by ³²P-postlabeling. Environ. Mol. Mutagen. 32: 344–350, 1998 © 1998 Wiley-Liss, Inc.     

Enhancement of radiation sensitivity in lung cancer cells by celastrol is mediated by inhibition of Hsp90

The radiosensitizing activity of celastrol, a quinone methide triterpene was examined. We found that celastrol treatment of the NCI-H460 lung cancer cell line increased radiation-induced cell killing. The increased radiosensitivity was correlated with decreased levels of Hsp90 clients, such as EGFR, ErbB2 and survivin as well as with increased p53 expression. Celastrol inhibited the ATP-binding activity of Hsp90. Furthermore, celastrol treatment dissociated an Hsp90 client protein, EGFR, and this in turn resulted in degradation of the client protein. These results were not observed with another structurally similar triterpenoid, 6β-acetonyl-22β-hydroxytingenol (TG), suggesting that a specific structural feature of the triterpenoid is required for radiosensitization. Moreover celastrol treatment increased p53 levels by phosphorylating Ser15 and Ser20 residues as well as by inhibiting its proteasomal degradation. Celastrol may be considered an effective radiosensitizer acting as an inhibitor of Hsp90 and a p53 activator. The two activities could be applicable to a broad range of cancer cells with either wild-type or mutant p53 because either activity could be effective for the enhancement of radiation cell killing. Further analysis with other triterpenoids should identify the functional moiety of the structure and additional candidates for effective radiosensitizers, which can be used in combined radiotherapy.     

The effect of ethanol-induced CYP2E1 on proteasome activity: the role of 4-hydroxynonenal

Previous studies have shown that the induction of P450 cytochrome 2E1 (CYP2E1) is associated with the loss of proteasomal activities. To correlate the loss of proteasomal activity with CYP2E1 induction, ethanol was fed intragastrically for 1, 3, 7, and 15 days. The maximum induction of CYP2E1 (3.5-fold) occurred after 15 days of ethanol feeding. However, there was no significant decrease in the 26 S chymotrypsin-like and trypsin-like activity over this period of time. When ethanol was given to rats for 1 month, CYP2E1 was significantly induced, and the proteasomal activity was significantly decreased. These results indicate that proteasomal activity was not directly affected by ethanol or CYP2E1 induction. Since 4-hydroxynonenal (4-HNE) concentration was significantly increased at 1 month of ethanol feeding, it was suspected that 4-HNE adduct formation with proteasome subunits could be the mechanism of proteasome inhibition. Using an antibody to 4-HNE adducted proteins in Western blot analysis of the 26 S proteasome fraction isolated from the liver of alcohol fed rats, one extra band appeared around 44 kDa. When the antibody to an ATPase Rpt4 was used to stain the stripped membrane, the same band that was detected with the 4-HNE antibody was detected with the Rpt4 antibody. An adduct of 4-HNE formed with the Rpt4 subunit of 26 S could impede the association of 19 S and 20 S and thus account for the observed decrease of proteasomal activity.     

Synthesis of 3′,5′-bis(morpholinomethyl)-4′-hydroxy- and 3′,5′-bis(4-methyl-1-piperazinylmethyl)-4′-hydroxymethacrylanilide. Copolymerization and metal ion binding properties of monomers and copolymers

4′-Hydroxymethacrylanilide was modified by Mannich reaction with morpholine/formaldehyde and 1-methyl-piperazine/formaldehyde, respectively. The interaction of the resulting monomers 3 and 4 and their corresponding copolymers with acrylamide ( 5 and 6 ) with Cu^{2 +} ions was studied by photometric methods. Incorporation of the aminomethylated phenol derivatives 3 and 4 in an acrylamide-methylene diacrylamide network system was performed to yield a product which selectively adsorbs Cu²⁺ in the presence of Ni²⁺, Co²⁺, Cd²⁺ and Ca²⁺ ions.     

Phenol degradation by Acinetobacter calcoaceticus NCIB 8250

Acinetobacter calcoaceticus NCIB 8250 utilizes phenol as sole source of carbon and energy via an ortho-cleavage pathway. The presence of ethanol in mixed substrate cultivations repressed the utilization of phenol. In fed batch cultivation the phenol tolerance was increased at least 2-fold. Maximum degradation rates of 150 Mg phenol/(l h) and 280 mg phenol/(g h). respectively were observed. Phenol hydroxylase is induced by its substrate and in parallel the catechol-l,2-dioxygenase is detectable. The presence of active phenol hydroxylase is strongly connected with the phenol degradation. Using a spectrophotometric enzyme assay the partially purified phenol hydroxylase was characterized with respect to kinetic parameters. The apparent K_m values for phenol, FAD and NADPH were estimated to be 147 μm, 35 μm and 416 UM, respectively. Both FAD and NADPH were essential for maximum activity of the cytoplasmically localized enzyme. No substrate inhibition of phenol hydroxylase by phenol was observed up to 0.8 mM. The pH and temperature optima were pH 7.8 and 33°C, respectively. The partially purified enzyme showed a broad substrate specificity. It hydroxylated the three isomeric cresols, chlorophenols and methylated chlorophenols. Pyrogallol, 3,4-dihydroxy-L-phenylalanine and resorcinol were oxygenated with higher rates than phenol. With the exception of phenol all other enzyme substrates tested did not serve as growth substrates.     

Kinetics and mechanism of the alkali-catalysed addition of formaldehyde to phenol and substituted phenols

In view of the differences in the positional reactivities, reported by different authors, in phenol and methylol phenols, an exhaustive kinetic study using quantitative paper chromatography has been carried out not only on phenol and methylol phenols but also on phenols with methyl group and chlorine atom substituents. The o-position is less reactive than the p-position in phenol and substituted phenols for the addition of formaldehyde in the presence of alkali catalyst, with a correspondingly higher activation energy. The effect of the methylol group appears to be intermediate between the activating effect of the electron repelling methyl group and the deactivating effect of the electron attracting chlorine atom. But the marked activating effect of the methyl and methylol group in the o-position is tried to be accounted for by intra-molecular hydrogen bonding. The activating effect of chlorine atom in the o-position is explained in terms of the electron repulsion between chlorine atom and the phenoxide anion. The few characteristic differences in the positional reactivities observed in the results of earlier workers are not found in the results obtained in the present investigation.     

Darstellung und spektroskopische analyse von oligo{[4-(1,1,3,3-tetramethylbutyl) (bzw. 4-octyl)-2-hydroxy-1,3-phenylen]methylen}en und ihrer Ausgangsverbindungen

4-(1,1,3,3-Tetramethylbutyl)phenol and 4-octylphenol, obtained by Fries rearrangement of the corresponding phenyl carboxylates and subsequent reduction of the carbonyl group, were monobrominated in ortho-position and hydroxymethylated with formaldehyde. Originating from these compounds, six 2,2′-methylenediphenol ( 2a–f ) as well as seven 2,6-bis(2-hydroxybenzyl)phenol derivatives ( 3a–g ) were prepared, which have methyl, 1,1,3,3-tetramethylbutyl, and octyl substituents in various ratios in para-position to the phenolic hydroxy groups. The IR- and ¹H-NMR-spectroscopical analyses confirmed the assumed structures of the synthesized oligo-nuclear phenolic compounds.     

Unifying mechanism for toxicity and addiction by abused drugs: electron transfer and reactive oxygen species

Abused drugs are of grave concern throughout the world for a variety of reasons. Although impressive advances have been made, there are many unknown mechanistic aspects. This report presents a novel hypothesis based on a unifying theme for action of the major classes of abused drugs, in addition to commonly abused therapeutic drugs. The approach is based on electron transfer (ET), reactive oxygen species (ROS), and oxidative stress (OS). It is significant that physiologically active substances generally incorporate ET functionalities, either per se, or more usually in their metabolites. In order to achieve ET in vivo, the reduction potential must be more positive than -0.5 V, which is the case for metabolites of abused drugs, except for special cases. Since the ET process is catalytic, only small quantities of agent are needed for generation of large amounts of ROS during redox cycyling. Bioaction with cellular materials could entail ET alone or participation of ROS. In the abused category, among the main classes of ET functionalities are quinones and iminiums, with alpha-dicarbonyl and nitroxyl radical being rarer. Nicotine yields nicotine iminium, myosmine iminium, and DNA base iminium via alkylation by a metabolic nitrosamine. In the case of alcohol, diacetyl (an alpha-dicarbonyl) is formed, which can lead to conjugated imine (or iminium) by condensation with pri-amine of protein. Phencyclidine is unusual since the iminium product is non-conjugated. However, data indicate that the conformation present at the binding site can accommodate delocalization of the derived radical. For cocaine, various metabolites may play a role: iminium, nitroxyl radical, nitrosonium and formaldehyde. Dealkylation of the ether moiety of ecstasy provides a catechol function capable of redox cycling with the o-quinone partner. Amphetamine and methamphetamine also appear to function by way of the catechol route, as well as morphine and heroin. Tetrahydrocannabinol produces an epoxide, a functionality capable of DNA base alkylation accompanied by ROS. LSD undergoes oxidation to a phenol which may be a quinone precursor. Therapeutic drugs display the indicated metabolic relationships: benzodiazepines, iminium; phenytoin, quinone; phenobarbital, catechol; aspirin, catechol and hydroquinone; acetaminophen, iminoquinone. Extensive evidence exists for formation of ROS, organ injury by OS, depletion of AOs, and protection by AOs for the various drugs. There is also discussion of computational approaches, addiction mechanism and prevention, and health promotion.