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The Tennessee Bureau of Investigation (TBI) serves all 95 counties of Tennessee, but the data included in this article are primarily focused in Upper East and East Tennessee (the parts of the state included in the eastern time zone). The forensic chemistry (seized drug) unit of the TBI began reporting nitazene analogues in late 2019. The primary analogues found in forensic chemistry cases were isotonitazene and metonitazene. After discussion and review of reporting statistics, the forensic toxicology unit began to monitor for these compounds in toxicology samples by using ion characteristics with the nitazene analogues. Between March 2021 and December 2023, TBI toxicology received 49,639 cases statewide. Of those, 20,105 (40.5%) received toxicology testing. Approximately 95% of TBI toxicology cases are related to Driving Under the Influence (DUI)/motor vehicle-related incidents. Fatal overdoses and cases from the medical examiner office comprise <5% of TBI toxicology caseload. The toxicology section utilizes the SCIEX 3200 Qtrap with a SCIEX Exion LC AC autosampler system to monitor multiple reaction monitoring transition of nitazene analogues. The ion monitoring for two nitazene analogues, isotonitazene and metonitazene, started in March 2021. Ion monitoring should not be construed as a confirmed result but rather as an indication that a drug may be present. A comparison of this data from the forensic toxicology and forensic chemistry units revealed the rise of new drugs that required a more in-depth review to understand the magnitude and scope. This article is also intended to encourage collaboration between forensic toxicology and forensic chemistry (seized drug) units., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background: The European baseline series (EBS) of contact allergens is subject to change. An allergen is considered for inclusion when routine patch testing of patients with suspected contact dermatitis results in ≥0.5% prevalence rate., Objectives: We aimed to determine the frequency of sensitizations to 30 EBS allergens and 10 locally added allergens. Additionally, we assessed the strength and evolution of reactions to all tested allergens and co-reactivity of additional allergens., Methods: Patch testing with our baseline series of 40 allergens was done in 748 consecutive adults. Tests were applied to the upper back and removed by patients after 48 h. Readings were done on Day 3 (D3) and D6 or D7 (D6/7). Positive reactions fulfilled the criteria of at least one plus (+) reaction. A retrospective analysis was done., Results: Eight allergens not listed in the EBS had ≥0.5% prevalence rate (i.e., cocamidopropyl betaine, thiomersal, disperse blue mix 106/124, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, propylene glycol, Compositae mix II and dexamethasone-21-phosphate), and 16.6% of positive reactions would have been missed without D6/7 readings., Conclusion: We propose further studies to evaluate whether cocamidopropyl betaine, disperse blue mix 106/124, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea and Compositae mix II need to be added to the EBS., (© 2022 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

A rod-shaped, Gram-negative staining strain, FBM22 T , was isolated from a microbial fermentation bed substrate from a pig farm. Its colonies appeared yellow and were 0.5-1.2 mm in diameter. Cells were 0.3-0.5 μm wide, 0.5-0.83 μm long. Optimal growth occurred at 30 °C and pH 7.0-8.0; NaCl was not required for growth. The strain performed denitrification and nitrate reduction functions. And it could produce catalase. FBM22-1 T utilized the following organic substrates for growth: tyrosine, glutamic acid, D-glucose, and galactose. The novel isolate could degrade 2-nitropropane as carbon and nitrogen source. The dominant respiratory quinone was Q-10. The major polar lipids were diphosphatidylglycerol, phosphatidylcholine and phosphatidylethanolamine. C 18:1 ω7c, C 16:1 ω7c and/ or C 16:1 ω6c, and C 14:0 2-OH were the major (≥ 8%) fatty acids. The G+C content was 56.8 mol%. FBM22 T was found to be a member of the genus Sphingopyxis in the family Sphingomonadaceae of the class Alphaproteobacteria. It had the highest sequence similarity with the type strains Sphingopyxis terrae subsp. ummariensis UI2 T (96.47%) and Sphingopyxis terrae subsp. terrae NBRC 15098 T (96.40%). Furthermore, FBM22 T had 18.7% and 18.4% relatedness (based on digital DNA-DNA hybridization) with its two relatives (S. terrae subsp. ummariensis UI2 T and S. terrae subsp. terrae NBRC 15098 T ). The morphological, physiological, and genotypic differences identified in this study support the classification of FBM22 T as a novel species within the genus Sphingopyxis, for which the name Sphingopyxis yananensis sp. nov. is proposed. The type strain is FBM22 T (= KCTC 82290 T  = CCTC AB2020286 T )., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Scatter plot analyses for 14,169 phenylethanes of the substructure C β -C α H 2 -Ph with three open coordination positions at C β and 150,568 phenylethanes of C β -C α HX-Ph with an additional open coordination position X at C α have been performed, based on searches in the Cambridge Structural Database. The correlation of rotation angle ψ = C β -C α -C i -C o with a pyramidalization angle θ = C o -C o' -C i -C α in a 360° rotation about the bond C α -C i reveals a sinusoidal pattern with three maxima and minima, whereas the correlation of rotation angle ψ with bond angle ω = C β -C α -C i and bond length d = C β -C α results in sinusoidal patterns with two maxima and minima. A total of 3993 nitro derivatives of the substructure C β -C α HX-NO 2 confirm the results and show that atoms C i /C o /C o' in the phenyl compounds can be replaced by atoms N/O/O' without any change in the two- and threefold patterns. In 15,295 methyl acetates of the substructure C β -C α HX-C'(═O)OMe, pyramidalization of the group C α C'(═O)OMe results in a chiral flat tetrahedron with four different corners. ( R θ )/( S θ ) selectivity in the configuration of the tetrahedron is induced by the bonds C α -C β , C α -H, and C α -X, emanating from the tetrahedral center C α . It is surprising that bonds as different as C α -C β , C α -H, and C α -X (X = H, C, N, O, S, etc.) give almost the same induction intensities.

Geometries of nitromethane homodimers have been revisited using ab initio and density functional methodologies, following their formation within cryogenic matrices, confirmed using infrared spectroscopy. In contrast to the claim that the intermolecular interactions are due to dispersion forces or very weak hydrogen bonds, in the present work, concrete evidence for the prevalence of O═N...O pnicogen bonding has been presented. The pnicogen bonds have been found to be primarily responsible for the characteristic geometry of a homodimer. The formation of a nitromethane dimer with pnicogen bonding stabilization is evidenced using matrix isolation infrared spectroscopy with Ne and Ar matrices and computations. The interactions within homodimers have been characterized using quantum theory of atoms in molecules, natural bond orbital, energy decomposition, electrostatic potential mapping, and noncovalent interaction analyses. The larger intermolecular separations in liquid nitromethane indicated by previous molecular dynamics-based studies alongside the supposed invariance of infrared spectra in the gas phase and liquid phase could have led to the assumption of a lack of intermolecular interactions. However, the prevalence of hydrogen and pnicogen bonds across these larger than usual separations is affirmed by the geometries presented here.

Route design and proof of concept synthesis was conducted on a synthetically challenging atropisomeric KRAS G12C inhibitor to support clinical API manufacture. Improvements to the synthesis of a chiral piperazine fragment gave reduced step count and streamlined protecting group strategy via the formation and methanol ring opening of an N -carboxy-anhydride (NCA). The complex atropisomeric nitroquinoline was accessed via an early stage salt-resolution followed by a formal two-part nitromethane-carbonylation, avoiding a high temperature Gould-Jacobs cyclization that previously led to atropisomer racemization. The substrate scope of the formal nitromethane-carbonylation strategy was further explored for a range of ortho -substituted bromo/iodo unprotected anilines.

A novel N,N-dibenzyl diaminomethylenemalononitrile organocatalyst efficiently promoted asymmetric Henry reactions of trifluoromethyl enones with nitromethane, affording corresponding highly functionalized products in high yields with excellent enantioselectivities (up to 90% ee). This study is the first to report the successful example of the asymmetric 1,2-additions of nitromethane to trifluoromethyl enones., (© 2021 Wiley-VCH GmbH.)

Objective: To investigate the efficacy of Fig fruit powder and olive on hepatic, renal and splenic injury induced by 2-nitropropane (2-NP) in mice, especially if they were used in combination., Methods: A total of 40 adult BALB/c male mice weighting 25-30 g/each. Mice were categorized into five groups (8 each). Group 1 as negative control. Group 2 as positive control group intraperitoneally injected with 2-NP (100 mg/kg b. w.) 3 times/weekly for eight weeks. Group 3 injected with 2-NP and were orally supplemented with Fig (300 mg/kg). Group 4 injected with 2-NP and were orally supplemented with olive (100 mg/kg). Group 5 injected with 2-NP and were orally supplemented with mixture of Fig and olive (3:1 respectively)., Results: Histopathological observation of liver in mice treated with 2-NP showed cellular degeneration, pyknosis, and congestion of the portal vein. In kidney there were disorganization of the cortical tissues, cellular necrosis and plenty of inflammatory lymphocytic aggregation. Significant elevations in liver function parameters (alanine aminotransferase and aspartate aminotransferase), mRNA expression levels of tumor necrosis factor-α, nicotinamide adenine dinucleotide phosphate oxidase and cyclooxygenase were detected as anti-inflammatory markers and 5-lipoxygenase, interleukin-1α and interleukin-6 as inflammatory biomarkers for liver and spleen, also significant elevations was detected in lipid peroxidation levels. The levels of antioxidants, glutathione, glutathione peroxidase, catalase and superoxide dismutase were significantly decreased., Conclusion: our findings indicated that Fig fruit powder and olive protected against hepatic, renal and splenic injury induced with 2-NP in mice, especially if they were used in combination.

Adding aluminum hydride (AlH 3 ) into energetic materials (EMs) can improve their combustion and energy performance effectively. However, the potential mechanism of AlH 3 on EMs is still unclear. Based on the ReaxFF-lg method, the thermal decomposition of nitromethane/nano-aluminum hydride (NM/nano-AlH 3 ) composites were studied. The addition of AlH 3 reduces the energy barrier and increases the energy release during the decomposition of NM, accelerates the decomposition of NM. The main way of AlH 3 oxidation involves the capture of O atoms from NM. The results show that AlH 3 content and passivated layer affect the oxidation and hydrogen release of AlH 3 . The explosion of small particle size AlH 3 leads to rapid oxidation and hydrogen release. The oxidation of large particle size AlH 3 is dominated by the inward and outward diffusion of O and Al atoms. The products of NM/nano-AlH 3 composites are H 2 O, CO 2 , N 2 gases, and Al clusters. This work is expected to guide the application of AlH 3 in EMs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Adding amines to liquid nitromethane (NM) is known to lower the threshold for the shock-to-detonation transition because amines catalyze proton transfer reactions that are the initial steps in the energy release process. We studied NM with 1 wt % ethylenediamine (NM/EDA) with 4 ns input shocks using time and space resolved diagnostics: photon Doppler velocimetry (PDV), optical pyrometry, and nanosecond video imaging. The 4 ns shocks are fast enough to time-resolve the reaction kinetics and the shock-to-detonation transition. We find that it is possible to shock ignite the NM/EDA without producing a detonation, so there is more to amine sensitization of the shock-to-detonation process than simply lowering the barrier to initial reactions. We find that although 1 wt % EDA has little effect on the ambient properties of NM, it dramatically alters the Hugoniot. The shock speed in NM/EDA is reduced, indicating that shocked NM/EDA is significantly more compressible than NM. Higher compressibility is associated with greater adiabatic heating, so EDA both lowers the barrier to proton transfer reactions and increases shock energy absorption. To explain the enhanced compressibility, we propose that shocking NM/EDA produces a reactive flow that has a much higher ionic strength than in NM. The sudden transformation from a molecular liquid to an ionic liquid with stronger intermolecular interactions is responsible for enhanced compressibility and shock heating.

Ozonation is widely used in wastewater reclamation treatment trains, either for micropollutant control or as a disinfectant and preoxidant in certain reuse processes. We recently found that ozonation of secondary effluent produces nitromethane, which can be efficiently transformed to genotoxic halonitromethanes by chlorination. In this work, the fate of nitromethane through water reuse treatment trains was characterized by analyzing samples from five reuse operations employing ozone. Nitromethane was poorly (<50%) rejected by reserve osmosis (RO), not removed by, and in some cases, increased by ultraviolet/advanced oxidation processes (UV/AOP). Sufficient nitromethane remained after advanced treatment that when chlorine was added to mimic secondary disinfection, halonitromethane formation was consistently observed. In contrast, biological activated carbon removed most (>75%) nitromethane. Bench-scale experiments were conducted to verify low removal by RO in clean systems and with wastewater effluent and to quantify the kinetics of direct and indirect photolysis of nitromethane in UV/AOP. An explanation for increasing nitromethane concentration during AOP is proposed. These results indicate that nitromethane presents a unique hazard to direct potable reuse systems, due to its ubiquitous formation during wastewater ozonation, poor removal by RO and UV/AOP, and facile conversion into genotoxic halonitromethanes upon chlorine addition.

The current article was designed to assess the role of chitosan nanoparticles (CNPs) in the management of hepatic injury induced by the hepatocarcinogen 2-nitropropane (2-NP). Rats were divided into three groups. The first group served as a control, the second group was injected with 2-NP, while the third group was treated with CNPs 1 h before 2-NP injection every other day for 4 weeks. The 2-NP injection upregulated serum AST and ALT activities, as well as hepatic TNF- α, IL-6, and MDA levels and the expression of vascular endothelial growth factor (VEGF) and caspase-3, whereas GSH contents and SOD activity were decreased. Immunohistochemistry investigations revealed that the hepatic protein expression of collagen I, inducible nitric oxide synthetase, proliferating cell nuclear antigen, cluster of differentiation, and p53 were upregulated. hematoxylin and eosin (H&E) and Masson's trichrome stains supported the previous parameters, and CNPs ameliorated most of the previous biochemical parameters. CNPs achieved promising results in the limitation of 2-NP hepatotoxicity.

Diesel engines are playing a vital responsibility in the field of automobile, agriculture, construction, and power generation. In the present world, much research is going on in the field of renewable energy to replace conventional sources of energy. But it is not very easy to replace diesel engines with other sources due to the better power output and reliability. The emissions from CI engines are very harmful for human health and for the environment. The major emissions are smoke and NOx which need to be controlled in an effective manner. In this work, direct injection variable compression ratio CI engine was used in experimental investigations for determining the combustion characteristics for D-MXEE-NM blends at different compression ratios. By performance analysis and exhaust emission of engine at peak load, D-MXEE5-NM2.5 (diesel 92.5%, 2-methoxyethyl ether 5%, and nitromethane 2.5%) blend was identified as best blend among all tested fuel blends and pure diesel at normal compression ratio (17.5). Further, all considered fuels with different CR values at peak load were ranked by Entropy-VIKOR method. From the analysis, D-MXEE5-NM2.5 at CR 19.5 was found as best fuel blend (ranked first) among all fuel blends and different compression ratios considered with same experimental conditions. By comparison of best fuel blend D-MXEE5-NM2.5 (at advanced compression ratio 19.5) with diesel (at standard CR 17.5), emission decline (HC 66.66%, CO 70.00%, and smoke 16.09%) and performance improvement (decrement in BSFC 7.07% and increment in BTE 4.41%) were obtained significantly at peak load. However, negligible increment in NOx (3.58%) was observed.

Potable reuse of wastewater is expanding, and ozonation for water reuse is becoming more common, either as a preoxidant before membranes or as part of ozone/biological activated carbon (O 3 /BAC) systems. However, previous research has demonstrated that ozone drastically increases the formation potential of genotoxic halonitromethanes (HNMs), including during O 3 /BAC. Chloropicrin, the most common HNM, is synthesized by chlorinating nitromethane, suggesting that nitromethane may be the immediate precursor of chloropicrin, although nitromethane is unlikely to occur naturally in wastewater. We hypothesized that wastewater ozonation forms nitromethane, which would be the key intermediate toward HNMs. Ozonation of wastewater effluent was shown to form abundant nitromethane, which explained the majority (in one case, all) of subsequent chloropicrin formation. Next, we investigated a suspected category of nitromethane precursor: stimulant drugs, such as ephedrine and methamphetamine, and certain antidepressants. These drugs all feature N -methylamine functional groups, and certain N -alkylamines have been shown to produce primary nitroalkanes upon ozonation. Ozonation of N -methylamine drugs ubiquitously formed nitromethane, typically at >50% yield. Subsequent chlorination converted nitromethane to chloropicrin. The reaction mechanism was investigated to understand the variation in nitromethane yield between different precursors. These results suggest that nitromethane fate during reuse and nitromethane control should be investigated.

Sphingolipids have been considered for many years only as structural components of membranes. It is now acknowledged that they are also involved in controlling cellular processes such as proliferation.The present work was designed to find the anticancer activity of the crab Dromia dehanni hemolymph in in-vivo and in vitro with special reference to the anticancer compound sphingolipids isolation and characterization. The active fraction of the purified hemolymph was subjected to NMR and ESI-MS/MS analysis. The ESI-MS/MS spectrum exhibited intense signals for sodiated molecular ions [M + Na] + of sphingomyelins (SM) identified as N-2-O-Acetyl-12 pentadecenoyl sphingosine phosphorylcholine, N-9-eicosenoyl- sphinganine phosphocholine and the corresponding dehydro sphingomyelin, N-9-eicosenoyl- dehydro- sphinganine phosphocholine along with the ions at m/z 147, 184 characteristic of phosphocholine. The present study revealed D. dehaani might be a great source for the novel anti-cancer compounds which can be used for human benefits., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nitromethane is a known toxicant and suspected human carcinogen. Exposure to nitromethane in a representative sample of the civilian, noninstitutionalized population in the United States ≥12 years old was assessed using 2007-2012 National Health and Nutritional Examination Survey (NHANES) data. Nitromethane was detected in all 8000 human blood samples collected, of which 6730 were used for analyses reported here. Sample-weighted median blood nitromethane was higher among exclusive combusted tobacco users (exclusive smokers; 774 ng/L) than nonusers of tobacco products (625 ng/L). In stratified sample-weighted regression analysis, smoking 0.5 pack of cigarettes per day was associated with a statistically significant increase in blood nitromethane by 150 ng/L, and secondhand smoke exposure (serum cotinine >0.05 ng/mL and <10 ng/mL) was statistically significant with a 31.1 ng/L increase in blood nitromethane. Certain dietary sources were associated with small but statistically significant increases in blood nitromethane. At median consumption levels, blood nitromethane was associated with an increase of 7.55 ng/L (meat/poultry), 9.32 ng/L (grain products), and 14.5 ng/L (vegetables). This is the first assessment of the magnitude and relative source apportionment of nitromethane exposure in the U.S. population.

In this study it is demonstrated that human odor collected from items recovered at a post-blast scene can be evaluated using human scent specific canine teams to locate and identify individuals who have been in contact with the improvised explosive device (IED) components and/or the delivery vehicle. The purpose of the experiments presented here was to document human scent survivability in both peroxide-based explosions as well as simulated roadside IEDs utilizing double-blind field trials. Human odor was collected from post-blast device and vehicle components. Human scent specific canine teams were then deployed at the blast scene and in locations removed from the blast scene to validate that human odor remains in sufficient quantities for reliable canine detection and identification. Human scent specific canines have shown the ability to identify individuals who have been in contact with IEDs using post-blast debris with an average success from site response of 82.2% verifying that this technology has great potential in criminal, investigative, and military applications., ((c) 2010 Elsevier Ireland Ltd. All rights reserved.)

2-Nitropropane (2-NP), a widely used industrial solvent, is carcinogenic to rats. To clarify the mechanism of carcinogenesis by 2-NP, we investigated DNA damage by 2-NP metabolites, N-isopropylhydroxylamine (IPHA) and hydroxylamine-O-sulfonic acid (HAS), using 32P-5'-end-labelled DNA fragments obtained from genes that are relevant to human cancer. In the presence of Fe(III) EDTA, both IPHA and HAS caused DNA damage at every nucleotide position without marked site preference. The damage was inhibited by free hydroxyl radical (-*OH) scavengers, catalase and deferoxamine mesilate, an iron chelating agent. These results suggest that the DNA damage was caused by -*OH generated via H(2)O(2) by both IPHA and HAS. In contrast, in the presence of Cu(II), IPHA frequently caused DNA damage at thymine. The Cu(II)-mediated DNA damage caused by IPHA was inhibited by catalase, methional and bathocuproine, a Cu(I)-specific chelator, suggesting the involvement of H(2)O(2) and Cu(I). These results suggest that the DNA damage induced by IPHA in the presence of Cu(II) was caused by a reactive oxygen species like the Cu(I)-hydroperoxo complex. On the other hand, HAS most frequently induced DNA damage at 5'-TG-3', 5'-GG-3' and 5'-GGG-3' sequences. Catalase and methional only partly inhibited the Cu(II)-mediated DNA damage caused by HAS, suggesting that the reactive oxygen species and another reactive species participate in this process. Formation of 8-oxodG by IPHA or HAS increased in the presence of metal ions. This study suggests that metal-mediated DNA damage caused by 2-NP metabolites plays an important role in the mutagenicity and the carcinogenicity of 2-NP.

Paired, boneless pork loin muscles were obtained from 76 market hogs to evaluate tenderness, meat quality characteristics, sensory attributes, and microbial characterization of pork muscle exposed to the Hydrodyne Process (H) compared with untreated control (C) loin. A subset of 16 paired loins was randomly selected for use in sensory evaluation and microbial characterization. Loins were vacuum packaged and immersed in a heat shrink tank prior to the H treatment. The Hydrodyne treatment exposed the loin to the pressure equivalent of a 150-g explosive, generating a pressure distribution of approximately 703 kg/cm2 at the surface of the samples. Meat quality assessments taken following treatment included subjective color, firmness/wetness, marbling scores (1 to 5 scale), Minolta reflectance and color readings, drip loss, and lipid content. The P-value for statistical significance for main effects and interactions was set at <.05 in all analyses. Administration of H resulted in a 17% improvement in Warner-Bratzler shear force (2.69 vs. 3.24 kg), with the shear force similar at two end-point cooking times (11 and 16 min) corresponding to approximately 75 and 83 degrees C, respectively. No differences between H and C were observed for color score, firmness score, Minolta L, Minolta Y, or drip loss on uncooked samples. The H loins had lower marbling scores (P<.05) and intramuscular lipid (P<.05) content than the paired C loin. Sensory evaluation on the randomly selected (n = 16) paired loins samples showed no improvement in Warner-Bratzler shear force. Sensory panelists were also unable to detect a difference between H and C loins for both initial and sustained tenderness scores. No differences between H and C loins were found for pork flavor, off-flavor, cohesiveness, or number of chews before swallowing, but H loins had a significantly lower juiciness score and more cooking loss than C loins. Microbial analysis results showed no differences in coliform bacteria counts, aerobic plate counts, and no detectable levels of Escherichia coli bacteria in any loins. The findings support the ability of the Hydrodyne procedure to improve tenderness without impacting other muscle quality attributes of pork.

Applicability of the nitromethane selective quenching rule for discriminating between alternant vs. nonalternant polycyclic aromatic hydrocarbons (PAHs) is examined for 18 representative PAH solutes dissolved in micellar cetyltrimethylammonium chloride (CTACl), micellar dodecyltrimethylammonium bromide (DTAB), micellar Brij-35 and micellar sodium octanoate (SO) solvent media. Experimental results show that nitromethane quenched fluorescence emission of only the 10 alternant PAHs in the two cationic (CTACl and DTAB) and nonionic Brij-35 surfactant solvent media as expected. Emission intensities of nonalternant PAHs, except for the few exceptions noted previously, were unaffected by nitromethane addition. Unexpected quenching behavior was observed, however, in the case of nonalternant PAHs dissolved in micellar sodium octanoate solvent media. Nitromethane quenched fluorescence emission of all nonalternant PAHs studied in the SO solvent media, which is contrary to the selective quenching rule.

To test whether carotenoids can modulate the initiation of liver preneoplasia by diethylnitrosamine (DEN) or by 2-nitropropane (2-NP) in a sequential protocol of hepatocarcinogenesis, male weanling rats were fed for three or four weeks (respectively) diets containing beta-carotene, canthaxanthin, astaxanthin, or lycopene (300 mg/kg diet) or an excess of vitamin A (15,000 retinol equivalents/kg diet) or were treated intraperitoneally with 3-methylcholanthrene. During this period, all rats were injected intraperitoneally with the initiator carcinogen, either 2-NP (6 times at 100 mg/kg body wt) or DEN (once at 100 mg/kg body wt). Three weeks after the termination of carotenoid or vitamin A feeding, the rats received 50 ppm of 2-acetylaminofluorene in their diet for a two-week period, in the middle of which they were subjected to two-thirds partial hepatectomy, and were sacrificed one week later. gamma-Glutamyl transpeptidase- and placental glutathione S-transferase-positive foci were detected in frozen-cut liver sections by histochemical and histoimmunochemical techniques, respectively. None of the treatments tested had any influence on the number and size of preneoplastic liver foci induced by 2-NP, despite a significant incorporation and persistence in the liver of the carotenoids, except astaxanthin, and of supplemental vitamin A. Feeding the rats lycopene significantly decreased the size of gamma-glutamyl transpeptidase- and glutathione S-transferase-positive foci induced by DEN (by 64% and 65%, respectively), as well as the fraction of liver volume occupied by foci (by 84% and 79%, respectively), but did not significantly reduce their number. The other carotenoids, including beta-carotene, exerted no significant effects on DEN-induced preneoplasias. Lycopene does not appear to act through its antioxidant properties, but rather through its modulating effect on the liver enzyme activating DEN, cytochrome P-450 2E1.

No-carrier-added racemic [11C]metaraminol was prepared by a selective condensation of [11C]nitroethane with 3-hydroxy-benzaldehyde using tetrabutylammonium fluoride in tetrahydrofuran (THF) as a catalyst, followed by a reduction with Raney nickel in formic acid. [11C]Metaraminol was produced in 30 to 45% decay-corrected yield from [11C]nitroethane (13 to 20% decay corrected from [11C]CO2) within 45 to 55 min total synthesis time. Reversed phase high-performance liquid chromatography (HPLC) was used for the separation of the racemic erythro- and threo-forms of [11C]metaraminol. The radiochemical purity was higher than 98%, and the specific radioactivity at the end of synthesis was 500 to 800 Ci/mmol (18 to 30 GBq/mumol). Positron emission tomography (PET) examination of racemic erythro-[11C]metaraminol in a Cynomolgus monkey showed a high uptake of radioactivity in the heart. Following pretreatment with the selective norepinephrine reuptake inhibitor desipramine, the radioactivity uptake in the myocardium was markedly reduced (80%), demonstrating the specificity of erythro-[11C]metaraminol for the norepinephrine reuptake system of the heart. Pretreatment with desipramine had no effect on radioactivity in lung. The metabolism was rapid for [11C]metaraminol. The amounts of the total radioactivity representing [11C]metaraminol in plasma, determined by HPLC, were 14% at 6 min and 8% at 34 min. The high specific uptake of racemic erythro-[11C]metaraminol indicates that enantiomerically pure (R,S)-[11C]metaraminol has potential for detailed mapping of the sympathetic innervation of the human myocardium.

Spontaneous and hepatocarcinogen (2-nitropropane, 2-NP)-induced levels of 8-hydroxy-2'-deoxyguanosine (oh8dG) in the nuclear DNA of regenerating liver [24, 48, 72 h and 7 days after partial hepatectomy (PH)] of male Sprague-Dawley rats were analysed for the verification of a hypothesis that the high susceptibility of proliferating hepatocytes to DNA damage is related to the well-known high susceptibility to carcinogens after PH. Interestingly, the spontaneous level of nuclear oh8dG in regenerating liver was significantly decreased (P < 0.01) at 48 h after PH (1.05 +/- 0.31 oh8dG/10(5)dG) compared with the level in normal rats (1.90 +/- 0.41). 2-NP induced an oh8dG level of 4.49 +/- 0.86 in nuclear DNA of rat liver without PH. However, in rats administered 2-NP (injections were performed 6 h before each sacrifice) after PH, the oh8dG level was significantly higher at 24 h (5.45 +/- 1.41, P < 0.05), 48 h (5.85 +/- 0.88, P < 0.01) and 72 h (5.67 +/- 1.07, P < 0.05) after PH than those with 2-NP exposure alone. Therefore, it is suggested that nuclear DNA in proliferating hepatocytes is in a stage susceptible to exogenous attack by 2-NP, and consequently this phenomenon might be related to the induction of hepatocarcinogenesis after PH.

A method for the preparation of [1-11C]D-glucose (III) and [1-11C] D-mannose (IV) from [11C] nitromethane is described. [11C]Nitromethane was produced using the on-line method from [11C]methyl iodide. The condensation of no-carrier-added or carrier-added [11C]nitromethane with D-arabinose to form the intermediate epimeric [1-11C]D-nitro alcohols (I and II) was investigated under various conditions. Compounds I and II were converted to III and IV by the classical Nef reaction with IV as the major product [(IV)/(III) = 3/1-4/1]. The isolated radiochemical yield of III and IV was 25-30% (based on [11C]nitromethane and decay-corrected) and 14-17% (EOB) with a total synthesis time of 50 min, including HPLC-purification. Compounds III and IV were isolated using semi-preparative HPLC and the radiochemical purity was greater than 97%. In a typical run, 1.5-2.0 mCi of III and 6-8 mCi of IV could be isolated (starting from 70-90 mCi [11C]nitromethane).

The odor threshold of 2-nitropropane (2-NP) has been characterized as not capable of providing warning that air concentrations possibly exceed acceptable guidelines. However, recent testing indicates that the odor threshold is significantly lower than previously thought. In particular, the odor threshold has been indicated by this study to be below the current TLV for 2-NP.

The synthesis and characterization of the anomeric pairs of the per-O-acetylaldohexopyranosyl cyanides of D-galactose, L-fucose, D-glucose, and D-mannose, as well as of 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl cyanide, are described. Cyanation of the readily available, per-O-acetylaldohexopyranosyl bromides with mercuric cyanide in nitromethane, and subsequent purification, gave the corresponding, crystalline glycosyl cyanides with a high degree of 1,2-trans stereoselectivity. Thus, per-O-acetylated aldohexopyranosyl cyanides of the 1,2-trans configuration were obtained in yields ranging from 20 to 79%, whereas the corresponding 1,2-cis anomers were obtained in yields of less than or equal to 8.4%, the ratios of the 1,2-trans:1,2-cis anomers so prepared being greater than or equal to 8.5:1. The principal by-products of these irreversible, cyanation reactions were the per-O-acetylated 1,2-O-[1-(exo- and endo-cyano)ethylidene]aldohexopyranoses, obtained in yields of up to 40%. The structural assignments of the per-O-acetylaldohexopyranosyl cyanides were unequivocally established by elemental analysis, chemical transformation, vibrational spectroscopy, and 13C- and 1H-nuclear magnetic resonance spectroscopy. Correlations between the physical properties and the anomeric configurations of these C-aldohexopyranosyl compounds are described.

Nitroparaffins act on the guinea-pig ileum by several mechanisms. They produce contraction partly by ganglionic stimulation and partly by direct liberation of transmitter from the nerve endings. They also inhibit the response to acetylcholine and nicotine, but interfere less with the action of histamine, serotonin or bradykinin. The two opposite effects of the nitro compounds are independent of each other. Within the homologous series of normal nitroparaffins, the excitatory action diminishes and the inhibitory effect increases with the lengthening of the carbon chain.