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Research has been conducted on the thermal or photochemical ethyl diazoacetate reaction with benzene to produce the isomeric cycloheptatrienes mixture. The details of this reaction are discussed.

The article discusses a study to evaluate the acute lung toxicity in rats of intratracheally instilled TiO2 particles that were substantially encapsulated with pyrogenically deposited, amorphous silica. It aims to determine if Pigment A TiO2 particles impart significant toxicity in the lungs of rats and how its activity compares with other reference particulate materials. It suggests that the inhalation of Pigment A TiO2 particles have a low risk potential for producing detrimental pulmonary health effects.

This article focuses on the influence of exchange rate changes on prices. The main proposition of the Scandinavian theory that was set out in this article has for the most part been verified. Under the fixed exchange rates relative prices were stable, and changes in the exchange rate generated offsetting movements in the domestic currency prices of exports. The evidence is less conclusive on the transmission of price changes in domestic currency terms from export prices to wholesale prices. It has in the past been possible for a devaluation to bring about a permanent increase either in wages or in profits in the exporting sector.

The aim of these studies is to develop a respiratory allergy model in Brown Norway (BN) rats using ovalbumin (Ova) as the antigenic stimulus. Specifically, we are interested in studying the mechanisms underlying the development of pulmonary T helper type 2 (Th2) responses following Ova sensitization and inhalation challenge. We have previously reported on the development of an active pulmonary inflammatory response characterized by the presence of eosinophils and measurement of serum immunoglobulin E levels in Ova-sensitized but not in alum-treated, Ova-challenged or sham control rats. In the current study, we have used cDNA microarray technology to assess the gene expression in tracheobronchial, mesenteric and submaxillary lymph nodes, as well as in pulmonary cells and tissues of Ova-sensitized, alum-sensitized or sham control BN rats. Preliminary cDNA microarray results of lung tissue from BN rats exposed to ova-ova (Ova-sensitized, Ova-challenged) 4 or 24 h after ova challenge did not show up-regulation (relative to sham controls) of mRNA for interleukin-4 (IL-4) or IL-5 but did show up-regulation of eotaxin (4 h), intercellular adhesion molecules (ICAM) and vascular cell adhesion molecules (VCAMs), which are likely to be prerequisites for eosinophilic pulmonary inflammatory responses measured at 24 and 48 h post Ova inhalation exposure. In addition, reverse transcriptase-polymerase chain reaction analysis of lung tissue from BN rats exposed to ova-ova 4 and 24 h after challenge demonstrated up-regulation of mRNA for IL-10 (Th2 response). Studies are ongoing to identify the time course and anatomic location of Th2 responses related to the development of Ova-induced respiratory allergy responses in BN rats. [ABSTRACT FROM AUTHOR]

The aims of this study were to assess in rats, using a well-developed, short-term pulmonary bioassay, the acute pulmonary toxicity of intratracheally instilled triethoxyoctylsilane (OTES)-coated (i.e. hydrophobic) pigment-grade TiO2 particles relative to uncoated, hydrophilic TiO2 particle control samples and to bridge the results of these instillation studies with data previously generated from inhalation studies with uncoated, pigment-grade TiO2 particles, using these uncoated pigment-grade TiO2 particles as the inhalation/instillation bridge material. Rats were intratracheally instilled with 2 or 10 mg/kg of the following TiO2 particle types: TiO2 with OTES, TiO2 with Tween 80, or TiO2 with OTES and Tween 80. Saline-instilled rats served as controls. The lungs of sham and exposed rats were evaluated by bronchoalveolar lavage and histopathology at 24 h, 1 week, 1 month and 3 months post-exposure. The results demonstrated that only the high dose (10 mg/kg) pigment-grade TiO2 particles and those with Tween 80 produced a transient pulmonary inflammatory response, and this reached control levels within 1 month post-exposure. We conclude that the OTES coating on the pigment-grade TiO2 particle does not cause significant pulmonary toxicity. [ABSTRACT FROM AUTHOR]

Four groups of 48 male rats each were exposed, nose-only, 6 h/day, 5 days/week, for a total of 4 weeks (i.e. 20 exposures) to aerosols of Nylon respirable-sized, fiber-shaped particulates (RFPs) at concentrations of 0, 4, 15 and 57 f/cm³ (ratio of RFPs:particles = 1:10-20). The samples containing Nylon RFPs were prepared using flock rotary cutters followed by vigorous opening procedures. Following 4 week exposures, the lungs of sham and Nylon-exposed rats were evaluated at 1 day, 1 week, as well as 1, 3, 6 and 12 months after exposure. At each of the post-exposure time points, the lungs of rats were either lavaged (for 3 months after exposure) or infusion fixed for cell proliferation, histopathology and fiber clearance/retention studies. This report contains data obtained during a 6 month post-exposure period. Preliminary results show that the retained mean lung burdens at 1 day after exposure were 1.75 × 107 (high level), 3.4 × 106 (mid level) and 4.8 × 105 (low level) RFPs/lung. Mean lengths and diameters of the Nylon aerosol were 9.8 and 1.6 µm, respectively. There were no significant increases in lung weights or indications of pulmonary inflammation in Nylon-exposed animals versus controls--based on cell differentials, bronchoalveolar lavage (BAL) fluid analyses and chemotaxis activity. More than 90% of the alveolar macrophages recovered by BAL (high level) contained Nylon RFPs or particles within their cytoplasm. Interim histopathological analyses have thus far revealed no adverse lower pulmonary or upper respiratory effects. [ABSTRACT FROM AUTHOR]

These studies were designed to investigate mechanisms through which inhaled p-aramid respirable- sized fiber-shaped particulates (RFP) are biodegraded in the lungs of exposed rats and hamsters. We have postulated that lung fluids coat/activate inhaled p-aramid RFP which deposit in the lung and promote enzymatic attack and consequent shortening. Aliquots of p-aramid or cellulose (biopersistent control) RFP were instilled into the lungs of rats and the lungs digested 24 h later using two different (KOH or enzymatic) digestion methods. For in vitro studies the two RFP types were incubated with lavage fluid and processed via simulated digestion; in addition, rat lung epithelial cells, macrophages or co-cultures were incubated with p-aramid and digested 1, 24 or 168 h post-exposure. In vivo the enzyme but not the KOH digestion method resulted in shortening of p-aramid but not cellulose RFP recovered from rat lungs. The results of in vitro studies showed that mean lengths of p-aramid RFP incubated with saline and processed by either digestion method were not found to be altered. Indeed, only the preparation of p-aramid RFP that had been incubated with BAL fluid and processed with the enzyme solution resulted in cleavage of p-aramid RFP. In contrast to the in vitro acellular studies with p-aramid RFP, the combination of BAL fluid incubation and enzyme digestion method had no measurable effect on shortening of cellulose RFP, indicating that the results with p-aramid were specific. In vitro cellular studies demonstrated a shortening of p-aramid RFP in exposed macrophages and co-cultures but not in lung epithelial cells 24 h and 1 week post-exposure. These findings demonstrate that lung fluids coat and activate the p-aramid RFP as a prerequisite for cleavage and describe a likely mechanism for the biodegradability of inhaled p-aramid RFP in the lungs of exposed animals. [ABSTRACT FROM AUTHOR]

The aims of this study were to assess in rats, using a well-developed, short-term pulmonary bioassay, the acute pulmonary toxicity of intratracheally instilled triethoxyoctylsilane (OTES)-coated (i.e. hydrophobic) pigment-grade TiO2 particles relative to uncoated, hydrophilic TiO2 particle control samples and to bridge the results of these instillation studies with data previously generated from inhalation studies with uncoated, pigment-grade TiO2 particles, using these uncoated pigment-grade TiO2 particles as the inhalation/instillation bridge material. Rats were intratracheally instilled with 2 or 10 mg/kg of the following TiO2 particle types: TiO2 with OTES, TiO2 with Tween 80, or TiO2 with OTES and Tween 80. Saline-instilled rats served as controls. The lungs of sham and exposed rats were evaluated by bronchoalveolar lavage and histopathology at 24 h, 1 week, 1 month and 3 months post-exposure. The results demonstrated that only the high dose (10 mg/kg) pigment-grade TiO2 particles and those with Tween 80 produced a transient pulmonary inflammatory response, and this reached control levels within 1 month post-exposure. We conclude that the OTES coating on the pigment-grade TiO2 particle does not cause significant pulmonary toxicity. [ABSTRACT FROM AUTHOR]

Background: The large extracellular matrix protein SVEP1 mediates cell adhesion via integrin α9β1. Recent studies have identified an association between a missense variant in SVEP1 and increased risk of coronary artery disease (CAD) in humans and in mice Svep1 deficiency alters the development of atherosclerotic plaques. However how SVEP1 functionally contributes to CAD pathogenesis is not fully understood. Monocyte recruitment and differentiation to macrophages is a key step in the development of atherosclerosis. Here, we investigated the requirement for SVEP1 in this process., Methods: SVEP1 expression was measured during monocyte-macrophage differentiation in primary monocytes and THP-1 human monocytic cells. SVEP1 knockout THP-1 cell lines and the dual integrin α4β1/α9β1 inhibitor, BOP, were utilised to investigate the effect of these proteins in THP-1 cell adhesion, migration and cell spreading assays. Subsequent activation of downstream integrin signalling intermediaries was quantified by western blotting., Results: SVEP1 gene expression increases in monocyte to macrophage differentiation in human primary monocytes and THP-1 cells. Using two SVEP1 knockout THP-1 cells we observed reduction in monocyte adhesion, migration, and cell spreading compared to control cells. Similar results were found with integrin α4β1/α9β1 inhibition. We demonstrate reduced activity of Rho and Rac1 in SVEP1 knockout THP-1 cells., Conclusions: SVEP1 regulates monocyte recruitment and differentiation phenotypes through an integrin α4β1/α9β1 dependent mechanism., General Significance: These results describe a novel role for SVEP1 in monocyte behaviour relevant to CAD pathophysiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate the acute lung toxicity in rats of intratracheally instilled TiO2 particles that have been substantially encapsulated with pyrogenically deposited, amorphous silica. Groups of rats were intratracheally instilled either with doses of 1 or 5 mg/kg of hydrophilic Pigment A TiO2 particles or doses of 1 or 5 mg/kg of the following control or particle-types: 1) R-100 TiO2 particles (hydrophilic in nature); 2) quartz particles, 3) carbonyl iron particles. Phosphate-buffered saline (PBS) instilled rats served as additional controls. Following exposures, the lungs of PBS and particle-exposed rats were evaluated for bronchoalveolar lavage (BAL) fluid inflammatory markers, cell proliferation, and by histopathology at post-instillation time points of 24 hrs, 1 week, 1 month and 3 months. The bronchoalveolar lavage results demonstrated that lung exposures to quartz particles, at both concentrations but particularly at the higher dose, produced significant increases vs. controls in pulmonary inflammation and cytotoxicity indices. Exposures to Pigment A or R-100 TiO2 particles produced transient inflammatory and cell injury effects at 24 hours postexposure (pe), but these effects were not sustained when compared to quartz-related effects. Exposures to carbonyl iron particles or PBS resulted only in minor, short-term and reversible lung inflammation, likely related to the effects of the instillation procedure. Histopathological analyses of lung tissues revealed that pulmonary exposures to Pigment A TiO2 particles produced minor inflammation at 24 hours postexposure and these effects were not significantly different from exposures to R-100 or carbonyl iron particles. Pigment A-exposed lung tissue sections appeared normal at 1 and 3 months postexposure. In contrast, pulmonary exposures to quartz particles in rats produced a dose-dependent lung inflammatory response characterized by neutrophils and foamy (lipid-containing) alveolar macrophage accumulation as well as evidence of early lung tissue thickening consistent with the development of pulmonary fibrosis. Based on our results, we conclude the following: 1) Pulmonary instillation exposures to Pigment A TiO2 particles at 5 mg/kg produced a transient lung inflammatory response which was not different from the lung response to R-100 TiO2 particles or carbonyl iron particles; 2) the response to Pigment A was substantially less active in terms of inflammation, cytotoxicity, and fibrogenic effects than the positive control particle-type, quartz particles. Thus, based on the findings of this study, we would expect that inhaled Pigment A TiO2 particles would have a low risk potential for producing adverse pulmonary health effects.

Man-made organic fibers (MMOFs) have been manufactured for over 50 years. Until recently, there have been few concerns raised regarding the safety of organic fiber dusts. This is due, in large part, to the perception that the dimensions of most, if not all, of these products were too large to be inhaled into the distal lungs of workers, i.e., were considered to be nonrespirable. A brief review of some of the issues related to organic fiber toxicology is presented herein. Some of the organic fiber-types used in commerce are identified and some fundamental tenets of fiber toxicology are discussed. In addition, the European Union, in their recent consideration for banning chrysotile asbestos fibers, evaluated some organic fiber substitutes and compared them to the hazards of asbestos. A brief review of their conclusions is described below. Finally, the results of some recent studies assessing the mechanisms of biodegradability of para-aramid respirable-sized, fiber-shaped particulates (RFP) are presented. Para-aramid (p-aramid) RFP are the most extensively-studied respirable organic fiber-type and RFP is the new term which describes respirable-sized organic fibers (ECETOC, 1996) (1). The results of these studies provide clues regarding the mechanism(s) of p-aramid RFP shortening in the lungs of exposed animals, and may be relevant for humans.

A variable-temperature (1)H- and (13)C-NMR study revealed a conformational equilibrium for 1,3,3,5,7,7-hexamethyl-1,5-diazacyclooctane (4) having DeltaG() = 8.8 +/- 0.6 kcal/mol at 184 K. This activation barrier connects a major and a minor form of 4. Molecular mechanics calculations on 4 led to the conclusion that the major form is a set of twist-chair-chairs interconverting rapidly via the chair-chair and that the minor form is most likely a set of twist-boat-boats interconverting rapidly via the boat-boat. The proximity of the two nitrogen lone pairs in the major form of 4 made plausible the expectation that 4, as well as a related diamine with apposed nitrogens, 3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane (3), might bind a Lewis acid, namely BH(3), using both lone pairs simultaneously and equally. This proved not to be the case: for 3 only the bis-BH(3) adduct was found and for 4 the mono-BH(3) adduct utilized only one nitrogen lone pair. The structure of the bis-BH(3) adduct of 4 (12) was determined by X-ray crystallography to be a twist-boat-boat with BH(3)s cis. Molecular mechanics calculations on 12 were consistent with the solid state conformation found.

A random copolymer, poly(CA), containing approximately equal amounts of cytidine (C) and adenosine (A), when incubated with a mixture of guanosine-5'-phosphoro-(2-methylimidazole) (2-MeImpG) and uridine-5'-phosphoro-(2-methylimidazole) (2-MeImpU), facilitates the incorporation of uridine (U) into oligomeric products with low efficiency. If 2-aminoadenosine (aA) is substituted for adenosine in the template, U is incorporated into the products with much higher efficiency. Random copolymers of C and U act as templates for the efficient synthesis of oligomers from 2-MeImpG and 2-MeImpA only if the concentration of substrates is relatively high (0.1 M). The substitution of 2-MeImpA permits the reaction to occur with much lower substrate concentrations. This effect is most prominent for template containing large amounts of U.

The 31mer 5'-TCA ACG CTA GAA TTC GGA TCC ATC GCT TGG T, the complementary 33mer 5'-CCA AGC GAT GGA TCC GAA TTC TAG CGT TGA GAT, the 40mer 5'-GGC CAG GAT GGT GAA GAA TTC GAT CCG GTA CGT AGC TAA G, and the complementary 42mer 5'-TAC TTA GCT ACG TAC CGG ATC GAA TTC TTC ACC ATC CTG GCC were synthesized and their reactivity towards EcoRI was studied. It was found that the 31mer and the 40mer were cleaved at a comparable rate to the 31mer-33mer hybrid and the 40mer-42mer hybrid, respectively. The rate of cleavage of the 33mer and the 42mer was an order of magnitude lower. To rule out possible intermolecular duplex formation, the 33mer was immobilized on cellulose by ligation and labeled with alpha 32P-dCTP using Klenow fragment of E. coli DNA polymerase. EcoRI cleaved this immobilized oligomer into specific fragments.

The template-directed oligomerization of activated derivatives of 2-aminoadenylic acid (paA) on polyuridylic acid (poly(U)) in aqueous buffers was studied. The reaction differs from that of adenylic acid (pA) under identical conditions, in that only di- and tri-nucleotides are observed as substantial products rather than a longer sequence of oligomers. The reaction of paA also differs from that of pA in that it does not require Mg++, and is less susceptible to increased temperature. The relevance of these observations to the chemical evolution of polynucleotide replication is discussed. Improved syntheses of paA and its diphosphate are reported.

This paper reports details of the synthesis of oligodeoxynucleotides containing the modified base 5-methyl-N4,N4-ethanocytosine (Ce). The 9-fluorenylmethoxycarbonyl group is used as a protecting group for the exocyclic amines of dA and dC. This group can be removed rapidly under very mild conditions. Oligomers containing the Ce base form a cross-link when hybridized to their complementary deoxyoligonucleotides. Some of the scope and limitations of these cross-link forming oligonucleotides are reported.

In order to gain more understanding about the mode of action of DNA polymerase, eight related partially self-complementary "hairpin" shaped oligodeoxynucleotides were prepared. Four of the oligomers contained either 1-beta-D-arabinofuranosyluracil (ara-U) or 1-beta-D-2'deoxyxylofuranosylthymine (dxT) nucleoside analogs at their 3' termini. We investigated the ability of the oligomers to prime DNA synthesis in relationship to the stability of the hybridized region, the nature of the sugar terminus and the DNA polymerase used (reverse transcriptase, or polymerase alpha). The results are discussed in relation to the mode of action of some nucleoside analog inhibitors of DNA polymerase. An understanding of the mechanism of DNA polymerase action was used to design template-primer analogs as polymerase inhibitors. Two of the oligodeoxynucleotide analogs prepared were found to be potent inhibitors of polymerase alpha.